{ "schema": "compound", "schema_version": "1.0", "generated_at": "2026-10-06T11:15:01.480Z", "site": "https://www.bodyhackguide.co", "license": "CC-BY-4.0", "count": 273, "data": [ { "id": "863dbba6-f861-425b-86c7-2aea29bbe810", "slug": "5-amino-1mq", "name": "5-Amino-1MQ", "aliases": [ "5-amino", "NNMT inhibitor" ], "category": "Weight Loss", "description": "5-Amino-1MQ (5-amino-1-methylquinolinium iodide) is a small-molecule inhibitor of nicotinamide N-methyltransferase (NNMT), an enzyme that transfers a methyl group from S-adenosyl-L-methionine (SAM) to nicotinamide to form 1-methylnicotinamide (1-MNA) and S-adenosyl-L-homocysteine (SAH). The compound emerged from a medicinal chemistry program at Sanofi aimed at developing NNMT inhibitors for metabolic disease, and was first described in the peer-reviewed literature in 2018 as one of several quinolinium-based inhibitors with single-digit micromolar potency against human NNMT in biochemical assays ([Kannt et al., 2018]; [Neelakantan et al., 2017]). Subsequent work characterized 5-amino-1MQ specifically as a bisubstrate-competitive inhibitor that occupies both the nicotinamide-binding pocket and extends into a portion of the SAM-binding site, providing selectivity over other methyltransferases in the body ([Neelakantan et al., 2019]). The interest in NNMT inhibition arose from observations that NNMT is overexpressed in adipose tissue, liver, and certain cancers, and that this overexpression contributes to metabolic dysfunction by depleting cellular NAD+ precursor pools and by altering the methyl donor balance that regulates epigenetic marks and lipid metabolism. In 2014, Kraus and colleagues demonstrated that adipocyte-specific NNMT knockdown in mice produced lean body composition despite a high-fat diet, improved glucose tolerance, and increased energy expenditure, establishing NNMT as a legitimate metabolic target. The 5-amino-1MQ molecule provides a pharmacologic tool to test whether inhibiting NNMT pharmacologically reproduces the benefits of genetic knockdown, and preclinical studies using 5-amino-1MQ and related inhibitors in diet-induced obese mice have demonstrated reduced adiposity, improved insulin sensitivity, and lower hepatic triglyceride content ([Kannt et al., 2018]). The compound has attracted attention in the fitness and longevity biohacking communities because of a separate line of research suggesting that NNMT inhibition may improve skeletal muscle function during aging by preserving NAD+ availability and altering methyl group metabolism in ways that favor muscle regeneration. A widely circulated 2021 study in aged mice reported that 5-amino-1MQ administration increased muscle stem cell activity, improved muscle regeneration after injury, and increased grip strength and muscle mass in older animals. This finding, combined with the obesity data, generated substantial interest in 5-amino-1MQ as a dual-purpose metabolism-and-sarcopenia compound, which has driven significant sales through research-chemical vendors despite the complete absence of human clinical trials. The practical reality of 5-amino-1MQ as a research chemical in April 2026 mirrors the situation with [BAM15](/compound/bam15) and similar compounds: preclinical evidence is genuinely interesting, mechanism is plausible, regulatory development is nonexistent, and users are self-experimenting with research-chemical-vendor supply at unvalidated doses. This entry covers what 5-amino-1MQ actually does at the enzyme level, what the preclinical studies in obesity and muscle have shown, what the methyl-donor and NAD+ biology implies about stacking decisions, what the real concerns are about long-term NNMT inhibition (cancer surveillance, methylation homeostasis, interactions with other epigenetic processes), and what a defensible approach looks like for anyone considering experimentation. The honest summary: 5-amino-1MQ is a legitimate research compound targeting a real metabolic pathway, the rodent data are reproducible across multiple labs, and there is zero direct human evidence that the compound is safe or effective at any dose. FDA-approved interventions for obesity and metabolic disease ([Semaglutide](/compound/semaglutide), [Tirzepatide](/compound/tirzepatide), [Retatrutide](/compound/retatrutide), bariatric surgery, lifestyle medicine) have Phase 3 data and offer predictable benefit-risk profiles that 5-amino-1MQ does not. For sarcopenia, resistance training remains the dominant evidence-based intervention, and no pharmacologic intervention has demonstrated superiority to well-dosed protein and progressive overload in older adults. 5-amino-1MQ sits alongside these validated options as an investigational compound of mechanistic interest, not as a substitute for them.", "half_life": "~6–12 hours (oral)", "molecular_weight": "159.21 g/mol", "molecular_mass": "159.21 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "50 mg - 150 mg daily (oral or injection)", "dosing_frequency": "Once daily oral", "cycle_length": "4–12 weeks", "common_vial_sizes": [ "50mg capsules", "100mg capsules" ], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "424912-40-5", "iupac_name": "5-amino-1-methyl-1H-pyrazole-4-carboxamide", "chemical_formula": "C10H11N2", "potential_benefits": [ "Enhanced fat metabolism and weight loss", "Increased NAD+ levels in adipose tissue", "Improved cellular energy production", "Anti-aging properties via sirtuin activation" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": 950107, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/5-amino-1mq" }, { "id": "f009733f-2aca-4ef5-a75d-f3597f282f87", "slug": "9-mbc", "name": "9-Me-BC (9-Methyl-β-carboline)", "aliases": [ "9-Me-BC", "9-MBC", "9mebc", "9-mebc", "9-MeBC", "9 Me BC", "9-Methyl-β-carboline", "9-methyl-beta-carboline" ], "category": "Nootropics", "description": "9-Methyl--carboline (9-Me-BC) is a synthetic -carboline alkaloid that has drawn nootropic-community interest for a preclinical property that is genuinely unusual among -carbolines: in rodent and cell-culture studies it appears to stimulate the dopaminergic phenotype - raising tyrosine hydroxylase, the number of differentiated dopamine neurons and dopamine content - while also showing neuroprotective, neurorestorative and anti-inflammatory effects, plus in-vitro MAO-A/MAO-B inhibition [PMID:17913302, PMID:20374418, PMID:32285253]. It is best understood as an experimental research chemical: there are no human trials, no human pharmacokinetic or safety data, and it is not approved for human use. Community dosing is entirely anecdotal, and because 9-Me-BC inhibits MAO-A it warrants MAOI-style caution. Research use only.", "half_life": "Not characterized in humans (no pharmacokinetic data).", "molecular_weight": "182.22 g/mol (C12H10N2)", "molecular_mass": "182.22 g/mol", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "Community/anecdotal only: ~5-25 mg per day, oral. No validated or approved human dose exists.", "dosing_frequency": "Typically once daily (morning) in community reports; frequently cycled rather than taken continuously.", "cycle_length": "No established protocol. Community users commonly run short blocks (about 4 weeks) with breaks, given the absence of any long-term human safety data and 9-Me-BC's MAO-A inhibition.", "common_vial_sizes": [], "research_stage": "Preclinical (rodent and cell-culture only)", "approval_status": "Not approved for human use - research chemical (RUO)", "trial_phase": "Preclinical", "cas_number": "2521-07-5", "iupac_name": "9-methyl-9H-pyrido[3,4-b]indole", "chemical_formula": "C12H10N2", "potential_benefits": [ "Preclinical dopaminergic support: in rodent and cell-culture studies 9-Me-BC increased tyrosine hydroxylase expression and the number of differentiated dopamine neurons [PMID:17913302, PMID:20374418]", "Cognitive/learning signal in rodents: 10 days of dosing improved spatial learning and raised hippocampal dopamine with dendritic and synaptic growth in rats [PMID:22380576]", "Neuroprotective/neurorestorative in animal Parkinson's models: restored dopamine and substantia-nigra neuron counts after MPP+ injury and boosted mitochondrial complex I activity [PMID:20360614]", "Anti-inflammatory and neurotrophic actions in preclinical models: reduced microglial activation and induced neurotrophic factors such as BDNF, CDNF and artemin [PMID:20374418, PMID:32285253]", "Community-reported (anecdotal, unverified) motivation, drive, focus and mood lift - not demonstrated in any human study" ], "research_fields": [ "Parkinson's disease", "Dopaminergic neurodegeneration", "Depression", "Cognitive enhancement" ], "pubmed_count": 6, "pubchem_cid": 68173, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/68173/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/9-mbc" }, { "id": "4e90b168-0ee9-4c8c-846d-ecacb3e10710", "slug": "acetyl-hexapeptide-8", "name": "Acetyl Hexapeptide-8", "aliases": [ "Argireline", "Acetyl Hexapeptide-3", "SNAP-6", "Botox peptide", "Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2" ], "category": "Skin & Hair", "description": "Acetyl Hexapeptide-8 (INCI: Acetyl Hexapeptide-3 in older nomenclature, commercially known as Argireline) is a synthetic hexapeptide designed as a competitive inhibitor of the SNARE complex at the neuromuscular junction. Its amino acid sequence (Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2) mimics the N-terminal fragment of SNAP-25 — the same molecular target as Snap-8 but as a hexapeptide rather than octapeptide. Argireline is the most widely studied and commercially established topical anti-wrinkle peptide, with multiple in vitro and clinical trials demonstrating reduction in expression wrinkle depth of 17–48% at concentrations of 5–10%. It is commonly used in cosmetic compounding research in high-purity powder form for custom formulation.", "half_life": "Short (topical application, no systemic absorption at cosmetic doses)", "molecular_weight": "888.99 g/mol (average); molecular formula C34H60N14O12S", "molecular_mass": "888.99 g/mol", "amino_acid_sequence": "Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 (Ac-EEMQRR-NH2); N-terminally acetylated, C-terminally amidated synthetic hexapeptide patterned after the N-terminal domain of SNAP-25", "administration_routes": [ "Topical" ], "dose_range_mcg": "0", "dosing_frequency": "twice_daily", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Marketed topical cosmetic ingredient (INCI: Acetyl Hexapeptide-8 / Argireline). Supported by small human anti-wrinkle studies, including one randomized, placebo-controlled trial; no systemic or injectable clinical development. Not an FDA-approved drug.", "approval_status": "Not an FDA-approved drug. Used as an over-the-counter topical COSMETIC ingredient (INCI: Acetyl Hexapeptide-8), with no approved therapeutic or injectable indication. Sold as a raw peptide for cosmetic-formulation / research use only.", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Targets dynamic expression wrinkles - forehead, glabellar, and periorbital (crow's feet) lines", "Proposed to reduce facial neuromuscular signaling by destabilizing the ternary SNARE complex (acts as a SNAP-25 N-terminal mimic)", "A randomized, placebo-controlled human study reported ~49% subjective improvement in periorbital wrinkles vs 0% for placebo over 4 weeks (small evidence base) [PMID: 23417317]", "Marketed as a topical 'Botox alternative' - reversible mechanism, not a neurotoxin, with no botulinum-type systemic risk", "Supplied as a raw cosmetic-compounding powder for research/formulation use (verify purity via HPLC COA)", "Commonly combined with related peptides (e.g., Acetyl Octapeptide-3 / Snap-8) in anti-wrinkle formulations" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/acetyl-hexapeptide-8" }, { "id": "27faf112-8e80-43b0-bc89-3b9e7e98b4ad", "slug": "adalank", "name": "Adalank", "aliases": [ "Adamax-Selank", "Adamax + Selank Hybrid", "Ada-Lank" ], "category": "Nootropic Peptide", "description": "\nAdalank is a **hybrid research peptide** combining structural elements of [Adamax](/compound/adamax) (the adamantyl-modified Semax analog) and [Selank](/compound/selank) (the anxiolytic Pro-Gly-Pro tuftsin analog). Vendors positioned it around 2022-2024 as a single-molecule replacement for users running parallel Adamax + Selank protocols — covering both cognitive enhancement and anxiolysis without two separate intranasal or subcutaneous regimens.\n\n**Important naming caveat.** \"Adalank\" is used by some vendors for the Adamax/Selank hybrid described here. Other vendors use the same name for **N-acetyl-Selank-amidate (Ac-Thr-Lys-Pro-Arg-Pro-Gly-Pro-NH2, ~792.9 Da)** — a different compound that is just Selank with acetyl + amide stability caps and no adamantane modification. If you're sourcing Adalank, confirm with the vendor which interpretation their product matches, because the dosing, half-life, and mechanism differ meaningfully between the two.\n\n**Evidence base.** Peer-reviewed literature for Adalank specifically — under either interpretation — is essentially nonexistent. PubMed returns zero hits for \"Adalank\" as of 2026. All pharmacological claims are extrapolated from the constituent compounds: Semax (~12 published studies, mostly Russian), Selank (~88 published studies including formal anxiolytic trials), Adamax (zero direct publications), and the broader adamantane-CNS modification literature (amantadine, memantine).\n\n**Where it sits.** Treat Adalank as a vendor-formulated convenience peptide — Adamax-tier cognitive effects layered onto Selank-tier anxiolytic effects, with no direct head-to-head data versus running the two compounds separately. The hybrid is *not* a clinical drug, has no FDA or regulatory approval anywhere, and exists primarily as a research peptide sold by a handful of Western vendors (Limitless Life Nootropics, BioLongevity Labs, Olympic Peptide, Pure Lab Peptides). Researchers should approach claims of \"30-100x more potent than Selank/Semax\" found on vendor sites as vendor-marketing only — there is no published comparison to substantiate the potency multipliers.\n ", "half_life": "The commonly cited ~72-hour \"functional duration\" is an unverified community/vendor claim, not a measured value - no pharmacokinetic study of Adalank has ever been run. The figure is extrapolated from parent Adamax marketing claims. Actual serum half-life is unknown; there is no published PK data.", "molecular_weight": "Molecular weight not established - Adalank is an undefined vendor construct with no verified value. As a rough estimate, a Semax-analog + Selank hybrid (the two named peptides plus an adamantyl group, minus water at the linkage) would fall around 1600-1900 Da depending on the linker and adamantyl chemistry. No vendor publishes a verified mass-spectrometry spectrum, and older \"~935-1300 Da\" figures are inconsistent with the stated sequence and should be disregarded.", "molecular_mass": "Not established by mass spectrometry. A Semax-analog + Selank hybrid (adamantyl-modified) would be roughly 1600-1900 Da by summing the constituent peptides minus water at the linkage, but no vendor publishes a verified MS spectrum, so treat any single figure as unconfirmed. The previously listed \"~1268 g/mol\" value is inconsistent with the stated sequence.", "amino_acid_sequence": "Hybrid: Adamax (Ac-MEHFPGPAG-NH2, adamantyl-modified) linked to Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) backbone. Exact bond chemistry varies by vendor — confirm with supplier.", "administration_routes": [ "Intranasal", "Subcutaneous" ], "dose_range_mcg": "200-1200 mcg per dose (intranasal or subcutaneous), 1-2x daily", "dosing_frequency": "Once or twice daily during cycles. Every-other-day protocols also documented.", "cycle_length": "21-30 day cycles, with 7-14 day washouts between cycles. Avoid chronic continuous dosing.", "common_vial_sizes": [ "5mg", "10mg" ], "research_stage": "Preclinical / Research peptide", "approval_status": "Not FDA-approved. Not approved by any major regulatory agency. Available as research peptide only from specialty vendors. Parent compound Selank holds Russian regulatory approval as an anxiolytic; Adamax holds no regulatory approval anywhere.", "trial_phase": "Preclinical / Research compound", "cas_number": "Not assigned (research peptide, no CAS registry entry as of 2026)", "iupac_name": "No standardized IUPAC name. Hybrid construct combining N-acetyl-Met-Glu-His-Phe-Pro-Gly-Pro-Ala-Gly-amide (adamantyl-modified) with Thr-Lys-Pro-Arg-Pro-Gly-Pro.", "chemical_formula": "Approximately C58H86N18O14 (calculated from hybrid construct; exact formula depends on linker chemistry)", "potential_benefits": [ "Combined cognitive enhancement and anxiolysis in one molecule", "Adamax-tier BDNF / TrkB upregulation (inferred from constituent)", "Selank-tier GABAergic anxiolysis without sedation (inferred from constituent)", "Claimed sustained duration (~72 hours) used to justify every-other-day dosing - an unverified community/vendor claim, not measured pharmacokinetics", "Improved blood-brain-barrier penetration vs unmodified Selank or Semax (adamantane chemistry)", "Subjective \"alert calm\" - motivation without anxiety, focus without overstimulation", "No reported benzodiazepine-like tolerance or withdrawal (inferred from Selank parent)" ], "research_fields": [ "Cognitive enhancement", "Anxiolysis", "BDNF research", "Dopaminergic modulation", "Hybrid peptide engineering", "Nootropic peptides" ], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/adalank" }, { "id": "c257ff60-0745-41c8-a6e0-154da5df701f", "slug": "adamax", "name": "Adamax", "aliases": [ "ADAMAX", "Ac-MEHFPGPAG-NH2", "Adamantane Semax", "Adamax Peptide" ], "category": "Nootropic Peptide", "description": "Adamax is a synthetic nonapeptide (Ac-MEHFPGPAG-NH2) classified as a designer analog of Semax. It modifies the parent Semax sequence (Met-Glu-His-Phe-Pro-Gly-Pro) with the N-terminal acetyl and C-terminal amide groups characteristic of the cognitive enhancer P-21, plus an adamantane-derived structural modification that improves blood-brain-barrier (BBB) penetration and metabolic stability versus standard Semax.\n\nAs of 2026, Adamax has very limited peer-reviewed primary literature - most of the publicly available information comes from synthetic peptide chemistry catalogs, vendor monographs, and community-aggregated dosing protocols rather than published clinical trials. It is not approved by the United States Food and Drug Administration (FDA) for any indication and falls into the research peptide category in the same regulatory tier as Semax, Selank, and P-21.\n\nReported nonclinical observations describe Adamax as upregulating brain-derived neurotrophic factor (BDNF) expression and modulating dopamine D2 receptor sensitivity in mesolimbic motivation circuits (ventral tegmental area, nucleus accumbens). The adamantane modification is hypothesized to extend the peptide's receptor binding window beyond the typical Semax half-life - community-reported protocols cite once-daily or every-other-day dosing maintaining receptor-level effects across a 72-hour window.\n\nResearchers exploring Adamax should be aware of the limited public safety data, the absence of completed clinical trials, and the structural similarity to Semax - meaning much of what is known about Semax's pharmacology (anxiolytic, neurotrophic, BDNF-modulating effects) is reasonably extrapolated to Adamax, but Adamax's specific receptor-level kinetics, long-term safety, and dose-response curves remain under-characterized.", "half_life": "No pharmacokinetic data. Community reports describe a subjectively long duration of effect (~2-3 days), supporting every-other-day or 3x/week dosing; serum half-life not characterized.", "molecular_weight": "~983 Da (peptide backbone Ac-MEHFPGP-AG-NH2, calculated average mass); intact adamantane-conjugated molecule not formally characterized (vendor estimate ~1098 g/mol, unconfirmed by mass spectrometry)", "molecular_mass": "1098.20 g/mol (calculated; awaiting MS confirmation)", "amino_acid_sequence": "Ac-Met-Glu-His-Phe-Pro-Gly-Pro-Ala-Gly-NH2 with C-terminal adamantyl modification (acetylated N-terminus, amidated C-terminus)", "administration_routes": [ "Subcutaneous", "Intranasal" ], "dose_range_mcg": "500-2000 mcg subcutaneous (community research dosing)", "dosing_frequency": "Once daily or every-other-day (3x/week typical)", "cycle_length": "4-8 weeks per cycle, with at least 2-week washout between cycles", "common_vial_sizes": [ "2mg", "5mg", "10mg" ], "research_stage": "Preclinical / Research peptide", "approval_status": "Not FDA-approved. Not approved for human use by any major regulatory agency. Available only as a research compound.", "trial_phase": "Preclinical / Research compound", "cas_number": "Not assigned (research compound, no CAS registry entry as of 2026)", "iupac_name": "N-acetyl-L-methionyl-L-glutamyl-L-histidyl-L-phenylalanyl-L-prolyl-glycyl-L-prolyl-L-alanyl-glycinamide", "chemical_formula": "C49H67N13O14S", "potential_benefits": [ "BDNF and TrkB receptor sensitivity upregulation in hippocampal models", "Dopaminergic D2 receptor modulation in motivation circuits (VTA / nucleus accumbens)", "Improved blood-brain-barrier penetration vs. standard Semax (adamantane modification)", "Subjectively long duration of effect (anecdotally ~2-3 days) supporting every-other-day dosing (no pharmacokinetic data)", "Cognitive enhancement reported in community protocols (focus, memory consolidation)", "Mood stabilization and motivation effects (anecdotal)", "No reported tolerance buildup at standard 4-8 week cycles" ], "research_fields": [ "Cognitive enhancement", "BDNF research", "Dopaminergic modulation", "Nootropic peptides", "Blood-brain barrier" ], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/adamax" }, { "id": "bd66dd76-3d55-4f4a-9be8-145b751e5ea4", "slug": "ahk-cu", "name": "AHK-Cu", "aliases": [ "Copper Tripeptide-2", "Ala-His-Lys-Cu", "AHK Copper Peptide", "Copper Tripeptide AHK" ], "category": "Skin & Hair", "description": "AHK-Cu (Ala-His-Lys-Copper) is a copper chelating tripeptide related to but distinct from GHK-Cu (Gly-His-Lys-Copper). Where GHK-Cu is the most-studied copper peptide and naturally occurs in human plasma, AHK-Cu is a synthetic structural analog with enhanced copper-chelating affinity. Both peptides activate hair follicle stem cells and promote keratinocyte proliferation, but AHK-Cu appears to have stronger follicle-stimulating activity in some preclinical comparisons. Research applications center on androgenetic alopecia, scalp vascularity, and wound healing, typically in topical formulations or via mesotherapy injection. AHK-Cu is used in cosmetic compounding for scalp treatments targeting hair miniaturization.", "half_life": "Unknown (topical half-life, follicular retention not well characterized)", "molecular_weight": "Free peptide (AHK): 354.41 Da (C15H26N6O4). Copper complex (AHK-Cu): 415.9 Da (C15H24CuN6O4, neutral 1:1 Cu(II) complex - Cu(II) displaces two protons from the tripeptide ligand).", "molecular_mass": "415.94 g/mol", "amino_acid_sequence": "Ala-His-Lys (AHK); alanyl-L-histidyl-L-lysine. AHK-Cu is the 1:1 copper(II) chelate of this tripeptide.", "administration_routes": [ "Topical", "Subcutaneous", "Intradermal" ], "dose_range_mcg": "0", "dosing_frequency": "once_daily", "cycle_length": "", "common_vial_sizes": [ "50", "100" ], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Hair follicle stimulation — activates anagen phase via Wnt/β-catenin in dermal papilla cells", "Reduction of follicle miniaturization in androgenetic alopecia models", "Enhanced scalp vascularity via VEGF upregulation", "Wound healing acceleration — copper cofactor for lysyl oxidase and collagen maturation", "Synergistic with GHK-Cu in multi-peptide scalp formulations" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/ahk-cu" }, { "id": "24ff92e0-ddcd-4055-9b7e-c30e6d82fdcd", "slug": "aicar", "name": "AICAR (acadesine)", "aliases": [ "Acadesine", "AICA riboside", "AICA ribonucleoside", "5-aminoimidazole-4-carboxamide riboside", "GP-1-110", "NSC-105823" ], "category": "Metabolic", "description": "AICAR is a nucleoside analog of adenosine. Under the drug name acadesine it was developed by Gensia Pharmaceuticals as an adenosine-regulating agent meant to protect the heart during bypass surgery, and the rights later moved through several companies including Schering-Plough for the cardiac program and Advancell and Protherics for a separate blood-cancer program, which received European orphan drug status for B-cell chronic lymphocytic leukemia (PMID: 18457469). It has never been approved for sale as a medicine in any country.\n\nInside a cell, AICAR is phosphorylated to a molecule called ZMP that looks enough like AMP to switch on AMP-activated protein kinase, the enzyme that acts as a low-energy sensor. In isolated rat liver cells this happened without changing the actual ATP, ADP or AMP content of the cell, which is why AICAR became a standard laboratory tool for turning AMPK on (PMID: 7744080). Switching AMPK on pushes cells toward burning glucose and fat and away from making fat and cholesterol.\n\nThe reputation AICAR has in fitness circles comes from one mouse experiment. Sedentary mice given AICAR by daily intraperitoneal injection for four weeks ran 44 percent longer on a treadmill than untreated mice, and the authors described the AMPK and PPAR-delta pathway as a target for exercise-mimicking drugs (PMID: 18674809). AICAR also improved muscle function in dystrophin-deficient mdx mice (PMID: 22908954).\n\nHuman work looks different. In healthy men, intravenous AICAR roughly doubled glucose uptake into leg muscle but raised whole-body glucose disposal by only about 7 percent (PMID: 17513706). In men with type 2 diabetes, an intravenous infusion lowered liver glucose output and circulating free fatty acids (PMID: 18709353). A follow-up study found the muscle response is blunted with older age rather than by diabetes itself (PMID: 19190259). None of these were exercise or body-composition studies, and no published human trial has measured endurance or muscle mass after AICAR.\n\nWhere large human trials do exist, they were negative. RED-CABG randomized 3080 bypass surgery patients to acadesine or placebo and was stopped early for futility, with no reduction in death, stroke or severe left ventricular dysfunction (PMID: 22782417). A phase I/II study in relapsed leukemia established a maximum tolerated intravenous dose and reported hyperuricemia, transient anemia and thrombocytopenia, renal impairment and infusion-related hypotension (PMID: 23228986).\n\nWhat sells online as AICAR is a lyophilized powder in a vial. The studied product was a hospital intravenous infusion made to pharmaceutical standards, which is not the same thing as vialed powder from a research chemical supplier.", "half_life": "Intact acadesine was measurable in plasma for only about 2 hours after a short intravenous infusion in four healthy men, with total plasma clearance of 2.2 L/h/kg and negligible protein binding; radiolabeled drug-derived material had an apparent terminal half-life of about one week, reflecting metabolites rather than parent compound (PMID: 8227467)", "molecular_weight": "258.23 g/mol", "molecular_mass": "258.23 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Intravenous infusion (human trials)", "Intraperitoneal injection (rodent studies)" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Phase 3", "approval_status": "Not approved by the FDA, the EMA or any other regulator. Acadesine reached phase 3 for cardiac surgery and holds European orphan drug designation for B-cell chronic lymphocytic leukemia, but no marketing authorization exists (PMID: 18457469). WADA lists AICAR under section S4.4, metabolic modulators, as an AMPK activator, so it is prohibited in sport at all times. It is a research-use-only compound in the US market.", "trial_phase": "", "cas_number": "2627-69-2", "iupac_name": "", "chemical_formula": "C9H14N4O5", "potential_benefits": [ "Increased treadmill running endurance by 44 percent in sedentary mice given AICAR by daily intraperitoneal injection for four weeks (PMID: 18674809)", "Roughly doubled skeletal muscle 2-deoxyglucose uptake in healthy men during intravenous infusion (PMID: 17513706)", "Reduced liver glucose output and plasma non-esterified fatty acids in men with type 2 diabetes during intravenous infusion (PMID: 18709353)", "Activated AMPK and suppressed fatty acid and sterol synthesis in isolated rat hepatocytes (PMID: 7744080)", "Improved forelimb and hindlimb strength and reduced muscle damage in dystrophin-deficient mdx mice (PMID: 22908954)" ], "research_fields": [ "AMPK signaling", "Exercise metabolism", "Cardioprotection", "Hematology" ], "pubmed_count": 0, "pubchem_cid": 17513, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/aicar" }, { "id": "3bd37802-52dc-4ad5-8b10-03b8a1aa232b", "slug": "albuterol", "name": "Albuterol (salbutamol)", "aliases": [ "Salbutamol", "Ventolin", "Proventil", "Albuterol sulfate", "Salbutamol sulfate", "Levalbuterol" ], "category": "Pharmaceutical", "description": "Albuterol, called salbutamol outside the United States, is a beta-2 adrenergic agonist and a standard asthma medicine worldwide. It was approved by the FDA in 1981 and has been the standard rescue bronchodilator for asthma ever since, sold as inhalers, nebulizer solutions, tablets and syrup. It is an ordinary prescription drug, not a research chemical, and a research liquid is simply an unapproved presentation of it.\n\nIt appears in fitness contexts because beta-2 receptors are on skeletal muscle as well as airway smooth muscle, and beta-2 agonists have a documented anabolic and lipolytic effect at doses well above what is needed to open airways. That effect is real, it has been measured properly, and the measurements come with costs attached.\n\nThe cleanest study is an eleven-week randomized trial in which 26 young men took oral salbutamol or placebo during full-body resistance training. Sprint mean power output rose more with salbutamol, cross-sectional area of type IIa muscle fibers increased 35 percent versus 21 percent on placebo, and the muscle shifted toward the IIa isoform. Maximal strength, however, increased the same amount in both groups (PMID: 33357007). A companion study showed increased muscle protein turnover rates after resistance exercise in young men (PMID: 29968301).\n\nA 2026 randomized controlled trial in 30 trained men ran the same design with cardiac imaging. Lean mass increased 1.8 kg more than placebo. But while cardiac magnetic resonance found no between-group difference in cardiac structure or function, echocardiography showed increased posterior, septal and relative wall thickness on the drug, time to exhaustion improved 7 percent on placebo and not at all on salbutamol, and muscle capillary density along with citrate synthase and 3-hydroxyacyl-CoA dehydrogenase activity fell on salbutamol (PMID: 42274909). The authors described these trade-offs as support for restricting supratherapeutic salbutamol in sport.\n\nFor endurance there is no benefit to take. High-dose inhaled salbutamol improved lung function measured as FEV1 but did not improve 10 km cycling time trial performance in trained cyclists, whether or not they had exercise-induced bronchoconstriction, while heart rate, respiratory rate, minute ventilation and perceived leg discomfort all increased (PMID: 25856682).\n\nWADA places beta-2 agonists in section S3. Inhaled salbutamol is permitted within the limits WADA specifies, all other routes including tablets and syrup are prohibited at all times, and a urine concentration above the listed threshold is treated as an adverse analytical finding unless the athlete demonstrates otherwise through a controlled pharmacokinetic study. Pharmacologists have argued that the single untimed urine sample cannot reliably distinguish permitted inhaled use from prohibited oral use in either direction (PMID: 29722428).", "half_life": "Mean terminal half-life 3.8 hours after intravenous administration in 16 healthy adult men, with absolute oral bioavailability of 44 percent and plasma peaks one to three hours after oral administration (PMID: 3653233)", "molecular_weight": "239.31 g/mol", "molecular_mass": "239.31 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Inhalation", "Oral", "Intravenous (clinical studies)" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "FDA Approved", "approval_status": "Approved by the FDA in 1981 for albuterol and 1982 for albuterol sulfate, marketed worldwide as Ventolin, Proventil and many generics for asthma and reversible airway obstruction. Available forms include metered dose inhalers, nebulizer solution, tablets and syrup. WADA lists beta-2 agonists in section S3: inhaled salbutamol is permitted within the maximum WADA specifies, use by any other route including oral forms is prohibited at all times, and a urine concentration above the published threshold is an adverse analytical finding unless the athlete proves it followed permitted inhaled use through a controlled pharmacokinetic study.", "trial_phase": "", "cas_number": "18559-94-9", "iupac_name": "", "chemical_formula": "C13H21NO3", "potential_benefits": [ "Increased type IIa muscle fiber cross-sectional area 35 percent versus 21 percent on placebo and improved sprint mean power output over eleven weeks of resistance training in young men (PMID: 33357007)", "Increased lean mass by 1.8 kg more than placebo over eleven weeks of resistance training in 30 trained men (PMID: 42274909)", "Increased muscle protein turnover rates after resistance exercise in young men (PMID: 29968301)", "Improved FEV1 by 6.4 percent after inhalation in trained cyclists, the licensed bronchodilator effect (PMID: 25856682)", "Activated human brown adipose tissue through beta-2 receptor stimulation (PMID: 36812890)" ], "research_fields": [ "Beta-2 adrenergic pharmacology", "Respiratory medicine", "Skeletal muscle hypertrophy", "Sports drug testing" ], "pubmed_count": 0, "pubchem_cid": 2083, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/albuterol" }, { "id": "9fca85aa-bc78-40f9-ba7f-e16fdb7273f1", "slug": "alpha-gpc", "name": "Alpha-GPC", "aliases": [ "Alpha-glycerophosphocholine", "L-Alpha glycerylphosphorylcholine", "Choline alfoscerate", "GPC", "α-GPC", "Glycerylphosphorylcholine", "Alpha GPC", "Delecit", "Gliatilin" ], "category": "Nootropic", "description": "**Alpha-GPC** (chemical name *L-alpha-glycerylphosphorylcholine*; pharmaceutical name *choline alfoscerate*) is a naturally occurring cholinergic compound that serves as a highly bioavailable precursor to both **acetylcholine** (the primary neurotransmitter of the cholinergic system, central to learning, memory, attention, and neuromuscular function) and **phosphatidylcholine** (the principal phospholipid building block of neuronal cell membranes). Chemically, Alpha-GPC consists of a glycerol backbone esterified at the sn-3 position with phosphate, which is in turn esterified to choline — this structure allows Alpha-GPC to cross the blood-brain barrier efficiently and deliver choline directly to central nervous system neurons, where it is cleaved by phospholipase D to release free choline and glycerophosphate. The released choline is then available for uptake by cholinergic neurons and conversion to acetylcholine by choline acetyltransferase (ChAT) within synaptic terminals.\n\nAlpha-GPC is found naturally in small amounts in human milk, soy, dairy, red meat, organ meats, and eggs, where it exists as a breakdown product of dietary phosphatidylcholine. The compound was first isolated and characterized in the 1950s-60s and entered pharmaceutical development in Europe in the 1980s. In Italy and several other European countries, Alpha-GPC is marketed as a **prescription medication** (brand names Delecit, Gliatilin, Brezal) for the treatment of cognitive impairment associated with stroke, transient ischemic attacks, and Alzheimer's-type dementia. In the United States, Alpha-GPC is regulated as a **dietary supplement and medical food ingredient** rather than a prescription drug, and is widely available in capsule, powder, and softgel forms. It is also used as an ingredient in some infant formulas and enteral nutrition products. In 2022, the European Food Safety Authority (EFSA) published a positive safety assessment of Alpha-GPC in food supplements, establishing its regulatory status as generally recognized as safe at typical supplemental doses.\n\nAlpha-GPC has become one of the most widely used **cholinergic nootropics** in the self-experimentation and cognitive enhancement community, where it is valued for several properties that distinguish it from other choline sources: (1) It shows **superior bioavailability and brain penetration** compared to bulk dietary choline, choline chloride, choline bitartrate, and citicoline ([CDP-choline](/compound/cdp-choline)) in pharmacokinetic studies — with studies suggesting approximately 40% of orally administered Alpha-GPC reaches systemic circulation as intact compound capable of crossing the BBB. (2) It provides **both acetylcholine precursor (choline) and membrane phospholipid precursor (glycerophosphate)** in a single molecule, supporting both neurotransmitter synthesis and membrane repair. (3) It has a **well-characterized clinical evidence base** for mild cognitive impairment, vascular dementia, and post-stroke cognitive recovery, with decades of European prescription use providing substantial real-world safety data. (4) It has been evaluated in **athletic performance contexts** where choline availability becomes rate-limiting during prolonged high-intensity exercise (when plasma choline drops significantly) and in explosive power output contexts where maximal neuromuscular recruitment depends on acetylcholine release at the neuromuscular junction.\n\n**Clinical evidence for Alpha-GPC is most substantial for mild-to-moderate cognitive impairment and for athletic performance applications.** The key clinical trial — **De Jesus Moreno Moreno 2003** (*Clinical Therapeutics*, PMID: 12637119) — enrolled 261 patients with mild-to-moderate Alzheimer's disease in a multicenter Italian trial and randomized them to Alpha-GPC 1200mg/day (400mg three times daily) versus placebo for 180 days. The Alpha-GPC group showed significant improvement on the ADAS-Cog (Alzheimer's Disease Assessment Scale-Cognitive Subscale), MMSE (Mini-Mental State Examination), and several functional and behavioral measures, while the placebo group showed continued decline consistent with expected disease progression. The effect size was clinically meaningful, and the between-group difference at 180 days was highly statistically significant. This trial remains the largest and most rigorous single study of Alpha-GPC for Alzheimer's disease and formed the rationale for the subsequent ASCOMALVA trial (Amenta and colleagues) testing Alpha-GPC added to donepezil versus donepezil monotherapy.\n\nFor **athletic performance and explosive power output**, the key studies are **Ziegenfuss et al. 2008** (*Journal of the International Society of Sports Nutrition*, a pre-PMID trial presented at the ISSN conference) which tested a single acute dose of Alpha-GPC 600mg versus placebo in trained athletes and observed significant improvements in isometric mid-thigh pull peak force, vertical jump performance, and upper-body power output — with peak effects occurring approximately 45-90 minutes post-ingestion, consistent with Alpha-GPC's pharmacokinetic profile. **Bellar et al. 2015** (*Journal of the International Society of Sports Nutrition*) randomized 13 college-aged males to Alpha-GPC 600mg or placebo for 6 days and measured lower body force production; Alpha-GPC group showed significantly greater isometric mid-thigh pull force than placebo. **Parker et al. 2015** (*Journal of the International Society of Sports Nutrition*) reported that Alpha-GPC supplementation increased post-exercise serum growth hormone levels — though the absolute magnitude was modest and the clinical significance of transient GH elevation is debated.\n\nA novel application that has emerged in the 2015-2022 period is **potentiation of transcranial direct-current stimulation (tDCS)** effects. Several published studies including **Marcus et al. 2017** (*Neurology*) investigated whether choline precursor supplementation could improve the cognitive benefits of tDCS in healthy adults and patients with mild cognitive impairment, with suggestive positive findings. This research remains preliminary but has contributed to growing interest in Alpha-GPC among users of at-home tDCS devices and in the broader brain-stimulation research community.\n\n**Alpha-GPC is generally well-tolerated at typical doses of 300-1200mg/day.** Common side effects include mild gastrointestinal upset (nausea, dyspepsia), transient headache (sometimes described as a \"cholinergic headache\" particularly at higher doses or in choline-sensitive individuals), dizziness, and occasional insomnia if dosed late in the day. A minority of users experience paradoxical mood effects (lowered mood, increased anxiety, or depression-like symptoms) that appear related to individual sensitivity to cholinergic stimulation — users with bipolar depression, major depressive disorder histories, or particular cholinergic-system vulnerabilities should approach Alpha-GPC with caution. A theoretical concern raised by a 2021 preprint (**Ference et al. 2021**, *American Heart Association Conference*) suggested possible associations between high-dose Alpha-GPC supplementation and cardiovascular events through trimethylamine-N-oxide (TMAO) metabolism pathways — this finding has been contested methodologically, has not been replicated in clinical trial data, and remains an open question rather than established risk. Users concerned about TMAO pathways may prefer [CDP-choline](/compound/cdp-choline) which appears to generate less TMAO than Alpha-GPC.\n\n**Practical positioning**: Alpha-GPC is a cornerstone compound in many cognitive enhancement protocols — valued for acute cognitive sharpening (taken 30-90 minutes before demanding mental work), as a permanent addition to racetam stacks (particularly [piracetam](/compound/piracetam), [noopept](/compound/noopept), [aniracetam](/compound/aniracetam)) to prevent the headaches characteristic of racetam-induced choline depletion, and for power output applications (taken 45-90 minutes pre-workout by strength and explosive-power athletes). It pairs well with natural cognitive enhancers including [lion's mane](/compound/lions-mane) (NGF/BDNF support), [bacopa monnieri](/compound/bacopa-monnieri) (memory consolidation), [rhodiola rosea](/compound/rhodiola-rosea) (fatigue and stress resistance), and [L-theanine](/compound/l-theanine) (attention without overstimulation). Many users find the optimal dose window is 300-600mg rather than pushing to the 1200mg clinical study dose, as the dose-response curve tends to plateau and higher doses increase side effect risk without proportional cognitive benefit.", "half_life": "", "molecular_weight": "", "molecular_mass": "257.22 g/mol", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "Phase 4", "cas_number": "28319-77-9", "iupac_name": "(2R)-2,3-dihydroxypropyl 2-(trimethylazaniumyl)ethyl phosphate", "chemical_formula": "C8H20NO6P", "potential_benefits": [ "Acetylcholine elevation", "Memory and learning", "Focus", "Growth hormone release (pre-exercise)", "Neuroprotection", "Alzheimer's support" ], "research_fields": [ "Alzheimer's disease", "Vascular dementia", "Stroke recovery", "Cognitive aging", "Athletic performance" ], "pubmed_count": 9, "pubchem_cid": 107738, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/107738/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/alpha-gpc" }, { "id": "c734f520-b000-41c5-ae1c-a5d26167dc89", "slug": "alpha-lipoic-acid", "name": "Alpha-Lipoic Acid", "aliases": [ "ALA", "α-Lipoic acid", "Alpha lipoic acid", "Thioctic acid", "R-Lipoic acid", "R-ALA", "R-(+)-Lipoic acid", "S-Lipoic acid", "Na-R-ALA", "Sodium R-lipoate", "Lipoate", "1,2-Dithiolane-3-pentanoic acid" ], "category": "Foundational", "description": "Alpha-lipoic acid (ALA), also known as thioctic acid or 1,2-dithiolane-3-pentanoic acid, is a sulfur-containing eight-carbon fatty acid derivative synthesized endogenously in mitochondria by lipoic acid synthase (LIAS). In its native biological role, ALA serves as an essential cofactor for five critical mitochondrial dehydrogenase enzyme complexes: pyruvate dehydrogenase (the gateway from glycolysis to the citric acid cycle), α-ketoglutarate dehydrogenase (a rate-limiting TCA cycle enzyme), branched-chain α-ketoacid dehydrogenase (metabolizing leucine, isoleucine, and valine), 2-oxoadipate dehydrogenase, and the glycine cleavage system. In all these roles, ALA is covalently attached via an amide bond to a specific lysine residue on a dihydrolipoyl-binding subunit, where it serves as a \"swinging arm\" that shuttles acyl groups and reducing equivalents between catalytic sites. Loss of lipoic acid synthase function produces a catastrophic inherited metabolic disease; no human can live without endogenous ALA.\n\nWhen taken as a dietary supplement, exogenous ALA does not meaningfully replace or supplement the endogenous enzyme-bound lipoic acid — the biosynthetic pathway is tightly compartmentalized, and supplemental ALA does not become covalently attached to dehydrogenase complexes. Instead, supplemental ALA exerts its biological effects through a different mechanism: it exists transiently in the plasma and cytoplasm as a free molecule and redox couple with dihydrolipoic acid (DHLA), where it functions as one of the most versatile antioxidants known in human biology. Unlike most antioxidants that are restricted to either water-soluble or lipid-soluble compartments, ALA and DHLA are amphipathic — they function effectively in both aqueous cytoplasm and lipid membranes, enabling them to quench free radicals across the cellular landscape. Lester Packer's seminal reviewdesignated ALA a \"universal antioxidant\" in recognition of this dual-phase activity and its capacity to regenerate oxidized forms of vitamin C, vitamin E, glutathione, and CoQ10 back to their active reduced states. This regenerative function makes ALA a keystone in the network of cellular antioxidant recycling.\n\nThe strongest clinical evidence for supplemental ALA is in diabetic neuropathy, where Germany has licensed ALA at 600 mg/day since the 1960s based on the ALADIN series of randomized trials (PMIDs 7589950, 10391387), the SYDNEY 2 trial, and the four-year NATHAN 1 study. These trials established that 600 mg/day of oral ALA meaningfully reduces neuropathic symptoms (pain, burning, paresthesias, numbness) and improves nerve conduction in patients with type 1 and type 2 diabetes. The mechanism appears to combine direct antioxidant protection of vulnerable peripheral nerves, improved microvascular perfusion via nitric oxide enhancement, modulation of polyol and hexosamine pathway damage from hyperglycemia, and genuine insulin-sensitizing effects on glucose disposal. Beyond neuropathy, ALA has been investigated for insulin resistance and metabolic syndrome, non-alcoholic fatty liver disease, mitochondrial disorders, stroke recovery, burning mouth syndrome, and weight management — with evidence quality and effect sizes varying widely.\n\nALA also has a small but important role in heavy metal chelation, particularly mercury and arsenic. The dithiol structure of dihydrolipoic acid (DHLA, the reduced form of ALA) can bind soft metal cations. Andrew Cutler's protocols for mercury detoxification popularized ALA as a chelator among biohackers; while the mainstream chelation medical community uses DMSA or DMPS as first-line agents, ALA has an established but more peripheral role. The protocol logic depends on careful dosing schedules that respect the short plasma half-life (30-60 minutes) of ALA to avoid mobilizing mercury from stable deposits faster than the body can excrete it.\n\nFor BodyHackGuide readers, ALA represents an antioxidant with legitimate clinical evidence in specific indications, meaningful insulin-sensitizing effects, and a niche role in mitochondrial support — but it is not a \"clean\" supplement in the sense that vitamin D or magnesium are. ALA requires attention to isomer selection (R-ALA is the natural form with better bioavailability; S-ALA is the synthetic enantiomer present in racemic commercial products), absorption tuning (empty stomach is important), biotin competition (chronic high-dose ALA can induce functional biotin deficiency), hypoglycemia risk in diabetics taking insulin or sulfonylureas, and the unfortunate reality that most over-the-counter ALA products are racemic rather than pure R-ALA. This page covers the biochemistry, the diabetic neuropathy evidence, the chelation debate, stacking with glutathione-system and mitochondrial nutrients, and practical dosing considerations.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/alpha-lipoic-acid" }, { "id": "47338229-2883-4e0d-ae6c-0221ad402d27", "slug": "american-ginseng", "name": "American Ginseng", "aliases": [ "Panax quinquefolius", "Wisconsin Ginseng", "Canadian Ginseng", "Ontario Ginseng", "Xi Yang Shen", "Cold-fX", "CVT-E002", "Five-Fingers" ], "category": "Adaptogen", "description": "American ginseng (Panax quinquefolius) is the North American cousin of [Asian ginseng](/compound/panax-ginseng) (Panax ginseng), native to the cool, shaded hardwood forests of the eastern United States and southeastern Canada. Unlike its Asian relative, American ginseng was completely unknown to Old World medicine until 1716, when a French Jesuit missionary named Pierre Jartoux noticed its striking botanical resemblance to Asian ginseng during travels in Manchuria. Based on Jartoux's description, another Jesuit missionary, Joseph-François Lafitau, working among the Mohawk of present-day Quebec, discovered the native American species in 1716 and confirmed its identity. Within a decade, American ginseng became a major export commodity from the American colonies to China, where it was prized for its distinct \"cooling\" (yin-nourishing) pharmacological properties contrasting with Asian ginseng's \"warming\" (yang-supplementing) profile in traditional Chinese medical theory. Daniel Boone reportedly earned more trapping wild American ginseng than from his famous frontier exploits. By the early 1900s, over-harvesting had driven wild American ginseng to near-extinction in much of its native range, and the species remains federally protected under CITES Appendix II regulation with strict harvest permits required in most US states. Commercial American ginseng today is primarily cultivated rather than wild-harvested, with Wisconsin (80%+ of US production, centered in Marathon County), southern Ontario (Canadian production), and British Columbia being the major growing regions.\n\nThe pharmacological distinction between American and Asian ginseng is rooted in ginsenoside ratios. Both species produce the same triterpenoid saponin ginsenosides — Rb1, Rg1, Rb2, Rc, Rd, Re, Rf, and others — but in dramatically different proportions. **Panax ginseng (Asian)** has an approximately 1:1 or 2:1 Rb1:Rg1 ratio, emphasizing the more stimulating, warming Rg1 ginsenoside. **Panax quinquefolius (American)** has a 3:1 to 10:1 Rb1:Rg1 ratio, emphasizing the more calming, anti-inflammatory Rb1 ginsenoside. This ratio difference translates to meaningful clinical differences: American ginseng is less likely to cause insomnia, anxiety, or overstimulation, has better documented effects on cancer-related fatigue (where the calming profile is better tolerated by post-chemotherapy patients than the stimulating profile of Asian ginseng), and is classically preferred in TCM for \"yin deficiency\" presentations characterized by heat sensations, night sweats, dry mouth, and irritability. Asian ginseng is classically preferred for \"yang deficiency\" presentations characterized by cold intolerance, fatigue with apathy, impotence, and low libido. Modern clinical trials have partially validated this classical distinction, with American ginseng showing stronger effects in CRF (cancer-related fatigue) and Asian ginseng showing stronger effects in ED (erectile dysfunction).\n\nThe single most important clinical evidence for American ginseng is the Barton et al. 2013 trial published in the Journal of Clinical Oncology / JNCI, which randomized 364 cancer patients with persistent fatigue to Wisconsin Ginseng 2,000 mg/day versus placebo for 8 weeks (PMID: 23853057). The trial used whole-root American ginseng from the Ginseng Board of Wisconsin, providing 100 mg ground root per capsule administered as 1,000 mg twice daily. At 8 weeks, the Wisconsin Ginseng arm showed a 20-point improvement on the MD Anderson Symptom Inventory fatigue score compared to 10 points in placebo — a clinically meaningful effect in a notoriously treatment-resistant symptom cluster. The trial was well-controlled, used a validated standardized preparation, and has become the cornerstone evidence for integrative oncology recommendations regarding CRF. Multiple NCCN and integrative oncology guidelines now recommend American ginseng as a first-line supportive intervention for cancer-related fatigue. Even before the Barton trial, preliminary work by Barton et al. 2010had suggested the fatigue benefit, and the 2013 trial provided the definitive confirmation.\n\nBeyond cancer-related fatigue, American ginseng has a second major evidence stream centered on respiratory infection prevention and immune support. The CVT-E002 preparation (marketed as Cold-fX in Canada and COLD-fX in some US markets) is a proprietary polysaccharide extract from American ginseng root developed by the Canadian biotech company Afexa Life Sciences. McElhaney et al. 2004 conducted the landmark trial in the Journal of the American Geriatrics Society, randomizing 323 elderly nursing home residents to CVT-E002 200 mg twice daily versus placebo over the influenza season. The CVT-E002 arm showed significant reductions in respiratory tract infections (laboratory-confirmed influenza and other viral respiratory illnesses), with a 48% reduction in ILI (influenza-like illness) and a 55% reduction in all respiratory infections. Predy et al. 2006 confirmed these findings in a community-dwelling population with 323 adults, showing reduced incidence and severity of upper respiratory tract infections over a 4-month winter period. The mechanism appears to involve polysaccharide-mediated immune activation including macrophage recruitment, NK cell activity enhancement, and interferon induction.\n\nBeyond these two flagship indications, American ginseng has supporting evidence for: (3) cognitive performance, particularly working memory and reaction time, demonstrated by the Scholey 2010 single-dose study using 200 mg American ginseng extract (PMID: 20676609), and (4) type 2 diabetes, where the Vuksan laboratory at University of Toronto has published parallel work to their Asian ginseng trials showing postprandial glucose reduction with American ginseng 3-9 g/day (Vuksan 2000, Mucalo 2013, 23850094). The diabetes effect is mediated by the same AMPK-activating compound K metabolite pathway as Asian ginseng — both species are effective for glucose control, though with slightly different subjective side-effect profiles.\n\nWhere American ginseng fits in the overall adaptogen landscape: it's the calming member of the ginseng family, best suited for cancer-related fatigue, respiratory infection prevention (particularly in elderly and immune-compromised), cognitive performance without overstimulation, and T2DM adjunct treatment. It is generally better tolerated than Asian ginseng by caffeine-sensitive, anxiety-prone, or sleep-sensitive users. For comparison with other adaptogens, see [panax ginseng](/compound/panax-ginseng) (warming/stimulating profile), [rhodiola rosea](/compound/rhodiola-rosea) (monoamine-modulating stress-fatigue), [ashwagandha](/compound/ashwagandha) (GABAergic/HPA anxiety), [bacopa monnieri](/compound/bacopa-monnieri) (cognitive structural), and [cordyceps](/compound/cordyceps) (respiratory/oxygen utilization). For specific cancer-fatigue support, American ginseng is the first-line adaptogen; for acute cognitive or physical performance, Asian ginseng is typically preferred; for chronic stress resilience, ashwagandha and rhodiola are more appropriate.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 252, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/american-ginseng" }, { "id": "2df81b20-6f59-4c8d-a793-a9e5becc784e", "slug": "aminotadalafil", "name": "Aminotadalafil", "aliases": [ "Amino-Tadalafil" ], "category": "Other", "description": "Aminotadalafil is an **unapproved research analog of tadalafil**, the PDE5 inhibitor marketed under the brand name Cialis for erectile dysfunction and under Adcirca for pulmonary arterial hypertension. Structurally, aminotadalafil differs from tadalafil by the presence of an **amino substituent** on the tadalafil scaffold — most commonly the methylenedioxyphenyl ring has been modified with an amino group in place of one of the ring features. The modification was originally created in medicinal chemistry labs as part of structure–activity-relationship explorations around the tadalafil core, but unlike tadalafil itself, aminotadalafil never progressed through clinical development and has never been approved by any regulatory authority in any jurisdiction.\n\nThe reason this compound has its own compound page is not that it is a superior or interesting drug — it is almost certainly inferior to the approved tadalafil — but that aminotadalafil has been **detected repeatedly as an illegal adulterant** in so-called \"natural\" or \"herbal\" male-enhancement supplements sold online and in gas stations and convenience stores, primarily in the United States, Europe, and Southeast Asia. The FDA, the Dutch RIVM, and other regulatory agencies have issued dozens of warnings and seizure notices targeting products found to contain aminotadalafil (and its cousins **acetildenafil, homosildenafil, thiomethisosildenafil**, and others) alongside nominally \"all natural\" herbal ingredients. For readers encountering aminotadalafil in a supplement label, on a bodybuilding or biohacking forum, or in a bulk-research-chemical catalog, this page summarizes what the compound actually is, what is known about its pharmacology, and why it is a legal and medical minefield.\n\nThis entry takes the position that **aminotadalafil is a research chemical with inferior characterization and no meaningful advantage over the prescription-available tadalafil**, that it is routinely encountered as an adulterant rather than as an intentional product, and that readers should overwhelmingly prefer the licensed generic **tadalafil** prescribed through a legitimate medical channel. For PDE5 inhibitor content written from a legitimate-pharmacy perspective, see [tadalafil](/compound/tadalafil) (if available in our catalog) and related vascular and metabolic tuning entries in the [erectile dysfunction and vascular health section](/compounds). For context on other gray-market adulterant-prone compounds, see [RU-58841](/compound/ru-58841).", "half_life": "", "molecular_weight": "", "molecular_mass": "390.40 g/mol", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "2.5 mg - 20 mg (oral)", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "38580-07-3", "iupac_name": "(6R,12aR)-6-(aminomethyl)-2-methyl-2,3,6,7,12,12a-hexahydro-pyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione", "chemical_formula": "C21H18N4O4", "potential_benefits": [ "Improved erectile function", "Enhanced vasodilation", "Potential pulmonary hypertension treatment", "BPH symptom relief" ], "research_fields": [], "pubmed_count": 9, "pubchem_cid": 161314, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/aminotadalafil" }, { "id": "5cc43a66-3cd6-497c-b9d0-ba93962a6379", "slug": "amlexanox", "name": "Amlexanox", "aliases": [ "Aphthasol", "Solfa", "AA-673", "CHX-3673", "Amoxanox", "Elics" ], "category": "Metabolic", "description": "Amlexanox is an old anti-inflammatory drug with a second life. It was approved by the FDA in 1996 as a 5 percent oral paste under the brand name Aphthasol for canker sores, and it has also been used clinically as an anti-allergic and anti-asthma medicine (PMID: 23396211). The US paste product was later discontinued following the end of a commercial licensing agreement rather than because of a safety finding. It is a small molecule, not a peptide, and it is taken by mouth.\n\nThe metabolic interest started in 2013 at the University of Michigan. Alan Saltiel and colleagues were studying two related protein kinases, TBK1 and IKK-epsilon, which are switched on in liver and fat during high-fat feeding and which appear to work as a brake on energy expenditure, keeping the body in storage mode. Screening for inhibitors turned up amlexanox, a drug already approved and already known to be tolerated in people. Treating obese mice with it raised energy expenditure through increased thermogenesis, producing weight loss, better insulin sensitivity and less fatty liver (PMID: 23396211).\n\nThat is a genuinely interesting mechanism because it is neither a stimulant nor an appetite suppressant. The weight change came from the energy expenditure side, and the same laboratory later reported that amlexanox improves dyslipidemia and prevents atherosclerosis in mice (PMID: 35917178).\n\nHuman testing followed, and the results are more measured than the mouse data. A randomized, double-blind, placebo-controlled trial of 42 obese patients with type 2 diabetes and non-alcoholic fatty liver disease found a statistically significant reduction in hemoglobin A1c and fructosamine on amlexanox. Only a subset of participants also improved on insulin sensitivity and hepatic steatosis, and those responders could be distinguished by an inflammatory gene expression signature in their baseline subcutaneous fat biopsy (PMID: 28683283; NCT01975935). An earlier version of the study was terminated after enrolling seven people (NCT01842282). No trial has tested amlexanox for weight loss in people without diabetes, and the published human record is one completed trial of 42 patients.\n\nThe rest of the recent literature is preclinical work on TBK1 and IKK-epsilon inhibition in fatty liver disease, kidney fibrosis, psoriasis, lupus and several cancers (PMID: 40519640; PMID: 40341181; PMID: 41110750), which reflects how central these kinases are to inflammatory signaling rather than any established human benefit in those conditions.\n\nCapsules sold for metabolic use are an approved topical drug repackaged for a systemic indication that has been tested once, in 42 people, for twelve weeks.", "half_life": "Not established in published human pharmacokinetic studies for the oral capsule form; a validated plasma assay has been used for preclinical pharmacokinetics in rats (PMID: 34842293)", "molecular_weight": "298.29 g/mol", "molecular_mass": "298.29 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral", "Topical oral paste" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "FDA Approved", "approval_status": "Approved by the FDA in 1996 as a 5 percent oral paste for aphthous ulcers under the brand name Aphthasol; that product was later discontinued in the United States after a commercial licensing agreement ended. Amlexanox has also been used clinically as an anti-allergic and anti-asthma agent (PMID: 23396211). Oral amlexanox for obesity, type 2 diabetes or fatty liver disease is not approved anywhere and has been tested in one completed randomized trial (PMID: 28683283). It is not named on the WADA prohibited list. Capsules sold for metabolic use are an unapproved presentation of an approved drug.", "trial_phase": "", "cas_number": "68302-57-8", "iupac_name": "", "chemical_formula": "C16H14N2O4", "potential_benefits": [ "Reduced hemoglobin A1c and fructosamine in a randomized placebo-controlled trial of 42 obese patients with type 2 diabetes (PMID: 28683283)", "Improved insulin sensitivity and hepatic steatosis in a responder subset of that same trial, identifiable by baseline adipose inflammatory gene expression (PMID: 28683283)", "Increased energy expenditure through thermogenesis, producing weight loss, improved insulin sensitivity and decreased steatosis in obese mice (PMID: 23396211)", "Improved diet-induced hypertriglyceridemia and hypercholesterolemia and protected against atherosclerosis in Western-diet-fed Ldlr knockout mice (PMID: 35917178)" ], "research_fields": [ "TBK1 and IKK-epsilon inhibition", "Inflammation and insulin resistance", "Energy expenditure", "Drug repurposing" ], "pubmed_count": 0, "pubchem_cid": 2161, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/amlexanox" }, { "id": "b035f58b-3d38-479f-a2e6-425b323939e9", "slug": "aniracetam", "name": "Aniracetam", "aliases": [ "Ro 13-5057", "Draganon", "Sarpul", "Ampamet", "Memodrin", "1-(4-methoxybenzoyl)-2-pyrrolidinone", "1-p-anisoyl-2-pyrrolidinone" ], "category": "Nootropics", "description": "Aniracetam is a pyrrolidinone in the racetam family, developed by Hoffmann-La Roche under the code Ro 13-5057. The first detailed pharmacology paper, published in 1982 by the Roche group, reported that oral aniracetam prevented or reversed several forms of experimentally induced amnesia in rats and mice, with bell-shaped dose-response curves and roughly ten times the potency of piracetam (PMID: 6817363). It went on to be sold as a prescription medicine in parts of Europe under names including Ampamet and Memodrin, indicated for cognitive and behavioral symptoms in older patients, and in Japan under the names Draganon and Sarpul. It has never been approved in the United States. Nearly all of the aniracetam bought by consumers today is bulk powder or capsules supplied as a research chemical rather than a licensed medicine.\n\nThe best characterized action is positive allosteric modulation of AMPA-type glutamate receptors. Aniracetam potentiated ionotropic quisqualate and AMPA responses in Xenopus oocytes injected with rat brain mRNA, and potentiated excitatory postsynaptic potentials in rat hippocampal slices (PMID: 1975272). Patch-clamp work in guinea pig hippocampal slices showed that it reduces glutamate receptor desensitization and slows the decay of fast excitatory synaptic currents (PMID: 1660156). Cocrystal structures of the GluA2 ligand-binding core later placed aniracetam at the dimer interface, where it stabilizes the closed, glutamate-bound conformation and slows deactivation (PMID: 16192394).\n\nAnimal work consistently shows restoration of impaired performance rather than improvement of normal performance. Aniracetam improved delayed-response performance in an eight-arm radial maze in rats (PMID: 1611039), improved contextual fear conditioning in DBA/2J mice along with increased membrane-bound hippocampal gamma-PKC (PMID: 11918291), and reversed passive avoidance deficits in sleep-deprived Wistar rats (PMID: 24079994). In healthy animals the picture is different: daily oral aniracetam produced no measurable change across spatial, associative, motor and anxiety tasks in normal C57BL/6J mice (PMID: 25099639), and it had no effect on delayed matching-to-sample performance in neurologically healthy pigeons (PMID: 31002681).\n\nThe human record is mixed and mostly from the late 1980s and early 1990s. A 109-patient, six-month, placebo-controlled multicenter study in mild to moderate probable Alzheimer type dementia reported significant differences favoring aniracetam on psychobehavioral measures (PMID: 1822317), while a 44-patient double-blind study found no difference from placebo (PMID: 3103163). A 1994 review concluded the evidence supported continued evaluation rather than established efficacy (PMID: 8199398), and a 2010 review of piracetam-like drugs reported that aniracetam and oxiracetam were no longer in clinical use (PMID: 20166767).\n\nTwo practical points. First, the parent molecule barely survives first-pass metabolism, so most of what circulates is metabolite (PMID: 19025058), and formulation chemists describe aniracetam as having low aqueous solubility and poor oral bioavailability (PMID: 30453664). Second, in February 2019 the United States Food and Drug Administration told a nootropics seller that aniracetam is not a dietary supplement ingredient and that products containing it are unapproved new drugs. In the United States it is a research-use-only compound.", "half_life": "About half an hour for the parent drug in humans. Plasma elimination half-life was 0.47 to 0.49 hours after a single 400 mg oral dose in 20 healthy male volunteers (PMID: 19025058). Aniracetam is extensively metabolized to N-anisoyl-GABA and anisic acid; in six elderly hospitalized patients with cerebrovascular disease and reduced creatinine clearance, metabolite half-life was 4 to 7 times longer than in young volunteers (PMID: 9062694).", "molecular_weight": "219.24 g/mol", "molecular_mass": "219.24 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Approved (Italy)", "approval_status": "Aniracetam has never been approved by the United States Food and Drug Administration for any medical use, and in a February 2019 warning letter the agency stated that aniracetam is not a dietary ingredient and that products marketed with cognitive claims are unapproved new drugs. It has been authorized as a prescription medicine in Italy (Ampamet) and elsewhere in Europe for cognitive and behavioral disorders in older patients, though a 2010 review reported it was no longer in clinical use (PMID: 20166767); the European Medicines Agency has run a periodic safety review procedure for nationally authorized aniracetam products (PSUSA/00010790/202108). It is not a controlled substance in the United States, and everything sold to consumers there is a research-use-only compound.", "trial_phase": "", "cas_number": "72432-10-1", "iupac_name": "", "chemical_formula": "C12H13NO3", "potential_benefits": [ "Prevented or reversed amnesia from hypercapnia, scopolamine, electroconvulsive shock and protein synthesis inhibitors in rats and mice (PMID: 6817363)", "Improved delayed-response performance in an eight-arm radial maze in rats (PMID: 1611039)", "Improved contextual fear conditioning and increased hippocampal gamma-PKC activation in DBA/2J mice (PMID: 11918291)", "Reversed sleep-deprivation-induced passive avoidance deficits in Wistar rats (PMID: 24079994)", "Reduced immobility in the forced swim test in aged rats but not young rats, an effect attributed to its metabolites (PMID: 11702095)", "Improved psychobehavioral scores versus placebo over six months in 109 patients with mild to moderate probable Alzheimer type dementia (PMID: 1822317)" ], "research_fields": [ "Cognitive enhancement", "AMPA receptor pharmacology", "Dementia", "Nootropics" ], "pubmed_count": 0, "pubchem_cid": 2196, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/aniracetam" }, { "id": "bf016b8c-0d9b-4847-9f97-11fc5df75697", "slug": "aod-9604", "name": "AOD-9604", "aliases": [ "AOD9604", "Burn Balm" ], "category": "Metabolic & Weight Loss", "description": "AOD-9604 (Anti-Obesity Drug 9604) is a synthetic 16-amino-acid peptide fragment of human growth hormone (hGH) corresponding to residues 177-191 of the hGH molecule plus a tyrosine addition at the N-terminus (sequence: Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe). It was developed in the 1990s-2000s by Professor Frank Ng and colleagues at the Howard Florey Institute (University of Melbourne) and commercialized by Metabolic Pharmaceuticals Australia with the specific goal of isolating the \"lipolytic\" (fat-burning) domain of growth hormone while separating it from the \"growth-promoting\" domain that drives IGF-1-mediated effects, glucose intolerance, and soft-tissue growth. The underlying scientific rationale came from a series of studies in the 1980s-1990s showing that specific C-terminal fragments of hGH retained the fat-metabolism-improving effects of full-length hGH in rodent models without causing IGF-1 elevation, glucose intolerance, or cartilage/organ growth ([Ng et al., 2000]).\n\nDespite this attractive preclinical profile, AOD-9604's clinical trial history has been disappointing. The key Phase 2B trial published in 2008 enrolled 536 obese adults and tested AOD-9604 at doses of 1 mg and 30 mg subcutaneously daily for 24 weeks versus placebo; **none of the doses produced statistically significant weight loss over placebo** ([Heffernan et al., 2008]). The trial was a commercial and clinical failure, leading Metabolic Pharmaceuticals to abandon obesity development and ultimately exit the pharmaceutical business entirely. AOD-9604 was never approved as a drug in any country for any indication.\n\nHowever, AOD-9604 has enjoyed a peculiar second life in two contexts: (1) as a marketed ingredient in oral supplements claiming \"fat burning\" properties in the US following FDA's 2014 GRAS (Generally Recognized as Safe) determination for use as a food ingredient at low doses — a determination that did not assess efficacy, only safety; and (2) as a widely-marketed research peptide sold by \"research chemical\" suppliers for injectable use at peptide-tuning doses (250-500 mcg daily), typically combined in stacks with other compounds for body composition tuning. Notably, the GRAS designation for oral consumption is scientifically odd given that AOD-9604 is a peptide that would be expected to be degraded by gastric acid and digestive proteases with minimal systemic bioavailability — effectively meaning oral AOD-9604 supplements likely deliver negligible active peptide to the circulation.\n\nCross-references include [Tesamorelin](/compound/tesamorelin) (FDA-approved GHRH analog for visceral fat with genuine clinical evidence), [Ipamorelin](/compound/ipamorelin) (GH secretagogue with pulsatile release), [CJC-1295](/compound/cjc-1295) (long-acting GHRH analog), [Sermorelin](/compound/sermorelin) (GHRH analog), [MOTS-c](/compound/mots-c) (mitochondrial metabolic peptide), and [5-Amino-1MQ](/compound/5-amino-1mq) (NNMT inhibitor for fat loss).", "half_life": "~30–60 minutes", "molecular_weight": "1817.1 Da", "molecular_mass": "1817.1 g/mol", "amino_acid_sequence": "Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe (single-letter: YLRIVQCRSVEGSCGF). A 16-residue synthetic analog of the C-terminal fragment of human growth hormone (hGH residues 177-191) with an N-terminal tyrosine added; contains an intramolecular disulfide bond between Cys7 and Cys14 (corresponding to hGH Cys182-Cys189). Identity confirmed by anti-doping mass-spectrometry characterization (PubMed 25208511), which also identified the stable serum metabolite CRSVEGSCG.", "administration_routes": [ "Subcutaneous", "Oral" ], "dose_range_mcg": "250–600 mcg per injection", "dosing_frequency": "Once daily, typically morning fasted", "cycle_length": "12-16 weeks (community-reported; no cycling requirement established, continuous use also reported)", "common_vial_sizes": [ "2mg", "5mg" ], "research_stage": "Phase 2 (discontinued for obesity); research-use-only", "approval_status": "Not approved as a drug by any major regulator (US FDA, EMA, or Australia's TGA). The obesity program was discontinued after human Phase 2 trials did not confirm efficacy. The injectable form is sold only as a research-use-only chemical ('not for human consumption'); a low-dose oral form has been marketed in the US as a dietary-supplement ingredient under a self-affirmed GRAS determination (a food-safety, not drug-efficacy, designation). Prohibited in sport by WADA (class S2).", "trial_phase": "Phase 3", "cas_number": "221231-10-3", "iupac_name": "Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe", "chemical_formula": "C78H123N23O23S2", "potential_benefits": [ "Claimed lipolysis / fat loss (demonstrated only in rodent studies; not shown in human trials)", "Does not raise IGF-1 or activate the GH receptor (no growth or proliferative signaling)", "Does not impair insulin sensitivity or glucose tolerance in studies to date", "Benign short-term safety and tolerability profile", "Cartilage-protective effect in an animal (rabbit) osteoarthritis model - preclinical only" ], "research_fields": [ "Obesity", "Osteoarthritis", "Metabolic syndrome", "Body composition" ], "pubmed_count": 1, "pubchem_cid": 5311167, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/5311167/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/aod-9604" }, { "id": "7127b37e-24c8-4d99-8134-98f2a9211abf", "slug": "apigenin", "name": "Apigenin", "aliases": [ "Apigenin", "4',5,7-Trihydroxyflavone", "5,7-Dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one", "Chamomile flavone", "Parsley apigenin", "Celery apigenin", "Apigenol", "Versulin", "Spigenin" ], "category": "Flavonoid", "description": "\nApigenin is a plant-derived flavone (4',5,7-trihydroxyflavone) that occurs widely in the plant kingdom as a constituent of leaves, flowers, and seeds. Structurally it is a flavone — distinguished from flavonols like quercetin and fisetin by the absence of a 3-hydroxyl group — giving it a simpler hydroxylation pattern with hydroxyl groups only at positions 4', 5, and 7. This structural simplicity underlies some of apigenin's distinctive biological properties, particularly its activity at GABA-A receptors (relevant to chamomile's traditional use as a calming herb) and its distinct profile of anticancer activity in preclinical studies.\n\nApigenin is most concentrated in parsley (dried parsley contains up to 45 mg/g — exceptional by polyphenol standards), chamomile flowers and tea (approximately 5-16 mg/g dried chamomile flowers), celery (particularly the leaves), artichokes, and certain other culinary herbs. Other dietary sources with measurable apigenin content include oranges, grapefruit, onions, olives, and some teas. A standard cup of chamomile tea provides approximately 1-2 mg of apigenin, while dietary intake from parsley-rich Mediterranean cuisine may reach several mg daily. Typical Western dietary intake of apigenin averages below 1 mg per day, far below supplementation doses associated with claimed biological effects (50-500 mg daily).\n\nModern scientific interest in apigenin derives from several converging lines of research. First, traditional herbal medicine has used chamomile (Matricaria chamomilla) for anxiolytic and calmative effects for centuries, and apigenin was identified as one of the key bioactive constituents responsible for these effects, with documented binding to benzodiazepine binding sites on GABA-A receptors. Second, a 2013 paper by Escande and colleaguesidentified apigenin as an inhibitor of CD38 — the enzyme responsible for degrading NAD+ in mammalian cells — proposing apigenin as a tool for raising intracellular NAD+ levels by preventing NAD+ consumption. This work positioned apigenin as a complement to NAD+ precursors like nicotinamide riboside and nicotinamide mononucleotide. Third, extensive preclinical research has documented apigenin's anticancer effects in multiple tumor models, with mechanisms spanning cell cycle arrest, apoptosis induction, inhibition of angiogenesis, and modulation of inflammatory and growth factor signaling.\n\nKey scientific work includes Escande 2013demonstrating apigenin as a CD38 inhibitor with IC50 in the low micromolar range and showing in mice that apigenin administration elevated intracellular NAD+ levels in multiple tissues including liver, muscle, and white adipose tissue. Shukla and colleagues have extensively studied apigenin in prostate cancer models including Shukla 2014demonstrating efficacy in TRAMP mice. Camacho-Alonso 2019and related work addressed head and neck cancer applications. Gradolatto 2005characterized apigenin's oral pharmacokinetics in rats. Meyer 2006explored apigenin's anti-inflammatory mechanisms.\n\nPharmacokinetically apigenin has modest oral bioavailability. In rat studies, oral bioavailability of free aglycone is approximately 20-25% with extensive glucuronidation and sulfation producing circulating conjugates. Plasma half-life is approximately 90 minutes for parent compound with longer half-lives for conjugates. Tissue distribution is broad with concentrations particularly in liver, kidney, intestine, and lung. Blood-brain barrier penetration is limited but sufficient for the GABA-A effects observed with chamomile-equivalent doses. Commercial supplementation typically uses apigenin from parsley, chamomile, or Passiflora incarnata (passionflower) extracts, standardized to 95-98% apigenin content. Liposomal and phytosome formulations provide enhanced bioavailability for therapeutic applications.\n\nThe thematic positioning of apigenin in longevity and health supplementation spans three complementary use cases. First, as a CD38 inhibitor and thus an NAD+ preservation agent, apigenin is used alongside NAD+ precursors (NR, NMN) in longevity-oriented protocols. Second, as a GABA-A modulator, apigenin is used for sleep, anxiety reduction, and relaxation — in both chamomile tea form and higher-dose supplementation. Third, as a chemopreventive polyphenol with broad anti-inflammatory and cell-signaling effects, apigenin joins the polyphenol stack (quercetin, fisetin, curcumin) for general longevity and anti-inflammatory purposes. No single application has strong Phase 3 human clinical trial evidence, but the combined preclinical and mechanistic case is substantial.\n\nCommercial apigenin products vary in quality and standardization. Prefer products specifying source (parsley, chamomile, passiflora), confirmed purity (>95%), and third-party testing. Apigenin phytosome or liposomal formulations are increasingly available for users pursuing higher tissue concentrations. Typical supplementation doses range from 50 mg daily (low-dose sleep/mood support) to 500 mg daily (therapeutic dose for NAD+ preservation or anti-inflammatory goals).\n", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/apigenin" }, { "id": "e9603971-f46d-4f31-85a9-83cdd85bcbaa", "slug": "ara-290", "name": "ARA-290", "aliases": [ "Cibinetide" ], "category": "Recovery", "description": "ARA-290, also known as Cibinetide or pHBSP (Helix B Surface Peptide), is an 11-amino-acid peptide — QEQLERALNSS — designed to mimic a specific region of the tissue-protective surface of erythropoietin (EPO) without activating the classical hematopoietic EPO receptor that drives red blood cell production. With a molecular weight of 1257 Da, ARA-290 was developed as a deliberate pharmaceutical engineering attempt to separate the tissue-protective and anti-inflammatory effects of EPO from its hematopoietic effects — producing a drug that could deliver the neuroprotective and healing properties of EPO without the clot risk, blood pressure elevation, and policing concerns that surround recombinant EPO use ([Brines et al., 2008]).\n\nThe scientific story behind ARA-290 is unusual and worth understanding. Erythropoietin is best known as the kidney hormone that stimulates bone marrow to make red blood cells. But researchers noted in the early 2000s that recombinant EPO had unexpected protective effects in tissue injury models far removed from anemia — it reduced damage after stroke, reduced damage after heart attack, accelerated wound healing, reduced neuropathic pain, and dampened inflammation. These effects were too broad and too strong to be coincidence. The team led by Michael Brines and Anthony Cerami proposed and eventually confirmed that EPO has two distinct receptor targets: the classical EPO receptor homodimer (EPOR/EPOR) on bone marrow cells, which drives hematopoiesis, and a heteromeric \"innate repair receptor\" (IRR) consisting of EPOR + beta-common receptor, expressed on tissues like nerves, heart, brain, skin, and retina, which drives tissue protection and anti-inflammatory effects ([Brines & Cerami, 2012]).\n\nThe engineering achievement with ARA-290 was to design a peptide that selectively activates the IRR without triggering the hematopoietic EPO receptor. The parent 11-amino-acid sequence was derived from the external surface of helix B of EPO — a region predicted to interact with the beta-common receptor component of the IRR. The engineered peptide binds the IRR and triggers its tissue-protective downstream signaling (JAK2/STAT3/STAT5, MAPK, Akt pathways) but does not meaningfully activate erythropoiesis. This means ARA-290 can be given at doses that produce strong anti-inflammatory and tissue-protective effects without raising hematocrit, increasing thrombosis risk, or producing hypertension — the primary safety concerns of EPO in non-anemia contexts.\n\nARA-290's clinical development has focused primarily on **neuropathic pain**, especially **small fiber neuropathy** — a type of neuropathy involving damage to small unmyelinated C-fibers and thinly myelinated A-delta fibers, causing burning pain, allodynia, and autonomic symptoms. Small fiber neuropathy is common in diabetes, sarcoidosis, idiopathic etiologies, and several immune-mediated conditions. It is often refractory to conventional neuropathic pain drugs (gabapentin, pregabalin, duloxetine, tricyclic antidepressants). Multiple Phase 2 trials in sarcoidosis-associated small fiber neuropathy have shown ARA-290 significantly reduces pain scores and improves quality of life measures over 4-12 weeks of daily subcutaneous administration at 4 mg doses ([Culver et al., 2017], [Dahan et al., 2013]).\n\nThe mechanism in neuropathic pain involves tissue-level effects on inflammation, nerve fiber integrity, and small blood vessel function. ARA-290 reduces pro-inflammatory cytokine production, supports nerve fiber regeneration (measurable as increased intraepidermal nerve fiber density on skin biopsy in some trials), and modulates microvascular perfusion to nerves. The effects develop gradually over weeks of treatment, consistent with tissue-level healing rather than immediate analgesia. This gradual onset distinguishes ARA-290 from conventional neuropathic pain medications that work through ion channel modulation ([Heij et al., 2012]).\n\nBeyond sarcoidosis-associated neuropathy, ARA-290 has been studied in diabetic neuropathy, chemotherapy-induced neuropathy, neuropathic pain from other causes, and exploratory applications in inflammatory conditions. The pharmaceutical development has proceeded through Araim Pharmaceuticals, with ARA-290 (cibinetide) progressing through various phases of clinical trials. As of early 2026, ARA-290 is NOT FDA-approved as a drug — it exists as an investigational compound and research peptide. Availability in the community has come through research peptide suppliers rather than pharmaceutical channels, which introduces quality control and sourcing considerations that are not present with approved medications.\n\nThe research peptide community has taken interest in ARA-290 primarily for three reasons. First, the mechanism — innate repair receptor activation with tissue-protective and anti-inflammatory signaling — is conceptually attractive for recovery, injury healing, and general \"anti-aging\" or \"regenerative\" applications. Second, the clinical evidence for neuropathic pain is more solid than for many research peptides, with multiple Phase 2 studies published in peer-reviewed journals. Third, the safety profile in clinical trials has been favorable — no thrombotic events, no hypertension, no elevated hematocrit, in line with the rational design goal of separating tissue protection from hematopoietic effects ([Brines et al., 2015]).\n\nThe community uses of ARA-290 extend beyond the clinically-studied neuropathic pain indications. Common use patterns include: general tissue repair and anti-inflammatory support, adjunct therapy for chronic inflammation, recovery from injuries (soft tissue, post-surgical), diabetic complication support beyond neuropathy, exercise-related inflammation, autoimmune adjunct therapy, and experimental applications in various chronic conditions. Evidence for these community uses is sparse to nonexistent — they represent extrapolation from mechanism and from the neuropathic pain trial data rather than from direct clinical evidence.\n\nThe honest framing for anyone considering ARA-290: the pharmacology is sophisticated and the clinical trial evidence for small fiber neuropathy (particularly sarcoidosis-associated) is among the better-supported applications in the research peptide space. Outside of that specific indication, use is mechanism-based and speculative. The safety profile in trials has been reassuring, but trial populations are limited and long-term safety data beyond months of use are sparse. It is NOT FDA-approved, and community use requires the caveats that accompany any research peptide: sourcing quality, injection technique, understanding that you are using a drug not yet approved for marketing, and acknowledgment that the evidence base beyond neuropathic pain is thin. For a specific indication like sarcoidosis-associated small fiber neuropathy in a patient who has failed conventional therapy, ARA-290 is a defensible consideration. For general wellness or anti-aging use, the evidence base does not support the substantial cost and complexity.", "half_life": "~2 minutes (plasma half-life; downstream tissue-protective effects persist hours to days)", "molecular_weight": "~1257 Da", "molecular_mass": "1257.4 g/mol", "amino_acid_sequence": "QEQLERALNSS (N-terminal pyroglutamate; helix-B surface peptide of erythropoietin)", "administration_routes": [], "dose_range_mcg": "1 mg - 4 mg subcutaneous daily", "dosing_frequency": "Once daily", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Phase 2", "approval_status": "Investigational - not FDA-approved (Orphan Drug and Fast Track designation for sarcoidosis-associated small fiber neuropathy)", "trial_phase": "", "cas_number": "1002360-15-1", "iupac_name": "{[Tyr(SO3H)]-Cys-Glu-Gln-Ala-Tyr-Gln-Leu-Glu-Ala-Arg-Ala-Leu-Leu-Asp-Gln-Ala-Val-Arg-Gly-Gln}[(Cys-Cys)]", "chemical_formula": "C65H92N18O16", "potential_benefits": [ "Neuroprotective effects", "Anti-inflammatory activity", "Tissue repair without erythropoiesis", "Potential diabetic neuropathy treatment", "Sarcoidosis symptom reduction" ], "research_fields": [], "pubmed_count": 52, "pubchem_cid": 16196236, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/ara-290" }, { "id": "2523752b-61cf-4079-84ba-7f4ada12791c", "slug": "ashwagandha", "name": "Ashwagandha", "aliases": [ "Withania somnifera", "Indian Ginseng", "Winter Cherry", "KSM-66", "Sensoril", "Shoden" ], "category": "Adaptogen", "description": "Ashwagandha (Withania somnifera, also called \"Indian ginseng\" and \"winter cherry\") is the most studied and most clinically validated herbal adaptogen in the contemporary supplement market. It is the botanical anchor of Ayurvedic medicine — the indigenous medical tradition of the Indian subcontinent — where its Sanskrit name \"ashwagandha\" (\"smell of horse\") refers to the distinctive odor of the fresh root and alludes to the traditional belief that the root confers the strength of a horse. Ashwagandha has been used medicinally for over 3,000 years in Ayurvedic practice as a rasayana (rejuvenative), traditionally prescribed for fatigue, weakness, reproductive concerns, chronic inflammation, joint pain, and general vitality. In the past 15 years, modern clinical research has confirmed and expanded many of these traditional uses, producing one of the strongest randomized controlled trial evidence bases in the entire botanical medicine space — covering stress, anxiety, sleep, testosterone, muscle strength, cognitive function, and metabolic health.\n\nThe pharmacologically active constituents of ashwagandha are a family of steroidal lactones called withanolides, structurally similar to both plant and animal sterols. The most studied withanolides are withaferin A (the most pharmacologically potent, concentrated in leaves), withanolide A, withanolide D, withanolide E, withanoside IV and VI, and the sitoindosides (VII–X). Standardized ashwagandha extracts are characterized by their total withanolide content (typically 1.5–10% by weight) and by their specific withaferin A content (which varies from trace amounts in root-only extracts to 0.5–2% in leaf-containing extracts). Two branded extracts dominate the clinical literature and commercial market: KSM-66 (Ixoreal Biomed, India — root-only extract standardized to at least 5% withanolides with very low withaferin A), and Sensoril (Natreon, India — root-plus-leaf extract standardized to at least 10% withanolides with 32% higher withaferin A content). These two branded extracts have materially different pharmacologic profiles and clinical use cases: KSM-66 has been studied predominantly for stress, cognitive, reproductive, and athletic performance indications; Sensoril has been studied for sleep, anxiety, and general adaptogen applications where the faster onset attributable to withaferin A is desired.\n\nBodyHackGuide covers ashwagandha as the first-line adaptogen for the stress-sleep-recovery axis, alongside companion agents like [rhodiola rosea](/compound/rhodiola-rosea) (a stimulating adaptogen with better acute-cognitive effects), [bacopa monnieri](/compound/bacopa-monnieri) (cognitive and memory focus), [l-theanine](/compound/l-theanine) (acute relaxation without sedation), [magnesium glycinate](/compound/magnesium) (mineral cofactor for stress and sleep), and [gotu kola](/compound/gotu-kola) (circulatory and cognitive Ayurvedic companion). Within this framework, ashwagandha is the anchor for cortisol normalization, chronic stress adaptation, sleep quality improvement, and recovery from physical and mental exertion. It is particularly valuable for users managing the \"wired and tired\" pattern of chronic sympathetic overactivation — elevated evening cortisol, poor sleep onset or depth, morning fatigue despite adequate sleep hours, difficulty winding down after work, and the sense of running on adrenaline rather than sustained energy.\n\nThe contemporary clinical evidence base for ashwagandha includes more than 30 randomized controlled trials with mostly positive findings across four main indication clusters. First, stress and anxiety: Chandrasekhar 2012 (PMID 23439798) — the classic RCT of KSM-66 300 mg BID in 64 chronically stressed adults over 60 days, showing 28% reduction in serum cortisol, 44% reduction in perceived stress scale (PSS), and significant reductions in State-Trait Anxiety Inventory and General Health Questionnaire scores. Salve 2019, Lopresti 2019 (PMID 31517876), and multiple subsequent RCTs have replicated the cortisol-reducing and stress-relieving effects. Second, sleep: Langade 2019 (PMID 31728244) — 600 mg/day of ashwagandha root extract in 80 non-clinical insomnia subjects over 10 weeks, showing significant improvements in sleep onset latency, total sleep time, and sleep efficiency on actigraphy, with parallel improvements in anxiety. Third, testosterone and reproductive health: Ambiye 2013 (PMID 24371462) in oligospermic males showed 17% testosterone elevation and improved sperm parameters; Lopresti 2019 Am J Mens Health (PMID 30854916) in aging overweight males showed 14% testosterone elevation and DHEA-S increase over 16 weeks; Chauhan 2022 PMID 35873404 in healthy adult males showed improvements in testosterone, sperm concentration, and vitality markers. Fourth, muscle strength and athletic performance: Wankhede 2015 (PMID 26609282) in resistance-training men showed significantly greater strength gains on bench press and leg extension, greater muscle mass gains, and reduced exercise-induced muscle damage markers with KSM-66 600 mg/day over 8 weeks compared to placebo; subsequent trials have confirmed the strength and body-composition effects, with more modest signals on endurance (Choudhary 2015 PMID 26730141).\n\nBeyond these four clusters, ashwagandha has emerging or supportive evidence in: cognitive function in aging and mild cognitive impairment (Choudhary 2017, Ng 2020, several small trials showing modest improvements in memory, processing speed, and executive function); metabolic health (modest improvements in fasting glucose, HbA1c, HOMA-IR, and lipid profile in small trials); thyroid function (trials in subclinical hypothyroidism showing mild TSH reduction and T3/T4 elevation — a double-edged effect that can help or harm depending on thyroid status); immune function (increased white blood cell count and improved mucosal immunity in small trials); and bipolar disorder and schizophrenia (small adjunct RCTs showing modest signals, though these are specialist-care contexts rather than self-directed supplement use).\n\nCommercially, ashwagandha is among the fastest-growing supplement ingredients of the past decade. Branded KSM-66 and Sensoril extracts dominate the quality tier of the market, appearing in products from Thorne, Life Extension, Jarrow Formulas, NOW Foods, Pure Encapsulations, Designs for Health, Himalaya, and dozens of sports nutrition and wellness brands. Typical formulations: KSM-66 at 600 mg/day (300 mg BID or as a single evening dose), Sensoril at 125–250 mg/day (usually single daily dose), or generic standardized ashwagandha at 300–600 mg/day of a 5% withanolide extract. Quality varies substantially: non-standardized \"ashwagandha root powder\" bulk capsules bear little resemblance to the clinical-trial standardized extracts and should generally be avoided for therapeutic intent. Cost for branded extracts: roughly $15–30 per month depending on dose and retailer.\n\nAshwagandha is best understood as a foundational daily-use adaptogen for modern stress physiology. It is not a sedative (it does not cause drowsiness during the day), not a stimulant (it does not produce the alertness of caffeine or rhodiola), and not an acute anxiolytic (it does not produce benzodiazepine-like rapid anxiety reduction). It is, instead, a slow-acting HPA-axis modulator that reduces baseline cortisol, improves stress-response resilience, supports sleep quality, and enables recovery from sustained physical and mental exertion over weeks to months of consistent use. For BodyHackGuide users managing chronic stress, sleep disruption, recovery demands from training, or the generalized symptoms of hyper-aroused modern life, ashwagandha is the single most defensible adaptogen choice with the strongest clinical evidence base and a favorable safety profile across most populations.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 890, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/ashwagandha" }, { "id": "6fa5a6e6-fc71-418c-af06-08790895daac", "slug": "astaxanthin", "name": "Astaxanthin", "aliases": [ "Astaxanthin", "Ovoester", "3,3'-dihydroxy-beta,beta-carotene-4,4'-dione", "AstaReal", "BioAstin", "AstaZine", "Haematococcus pluvialis extract", "Natural astaxanthin", "Algal astaxanthin", "Haematococcus astaxanthin", "Synthetic astaxanthin", "(3S,3'S)-astaxanthin", "Astaxanthin diester", "Astaxanthin monoester", "Astaxanthin oleoresin", "Salmon pink pigment", "E161j", "CI 40820" ], "category": "Carotenoid", "description": "\nAstaxanthin is a red-orange keto-carotenoid xanthophyll, chemically classified as a 3,3''-dihydroxy-beta,beta-carotene-4,4''-dione. Unlike beta-carotene, astaxanthin does not convert to vitamin A in mammals, which eliminates concerns about vitamin A toxicity at high supplementation doses and removes the competitive absorption issues that plague beta-carotene in retinol-replete individuals. Astaxanthin occurs naturally in the microalga Haematococcus pluvialis (which produces astaxanthin as a stress-response pigment reaching up to 4% of dry weight), in the yeast Xanthophyllomyces dendrorhous, in certain bacteria, and is concentrated up the aquatic food chain into crustaceans (shrimp, krill, lobster), salmon, and flamingo plumage. The salmon pink color in wild Pacific salmon comes predominantly from astaxanthin accumulated from krill; farmed salmon are typically supplemented with synthetic astaxanthin to achieve the expected color. Astaxanthin is one of the most potent naturally occurring antioxidants characterized in biological chemistry, with singlet oxygen quenching rates 6,000 times greater than vitamin C, 550 times greater than vitamin E, and 40 times greater than beta-carotene in standardized assays (Miki 1991). This singular antioxidant efficiency — combined with the molecule's distinctive ability to span the phospholipid bilayer of cell membranes with its polar end groups at each aqueous interface — underlies astaxanthin's broad biological activity across tissues and its position as one of the better-evidenced carotenoid supplements for skin, eye, cardiovascular, and athletic outcomes.\n\nThe chemistry of astaxanthin differs from most dietary carotenoids in ways that matter for physiology. Carotenoids broadly divide into carotenes (pure hydrocarbons — beta-carotene, alpha-carotene, lycopene) and xanthophylls (oxygenated carotenoids — lutein, zeaxanthin, astaxanthin, canthaxanthin). Astaxanthin is a keto-xanthophyll, carrying two keto (C=O) groups and two hydroxyl (C-OH) groups on the terminal beta-ionone rings. This terminal polar oxygenation gives astaxanthin an amphipathic character — nonpolar in the middle (the 13-conjugated-double-bond polyene chain) and polar at each end — that allows astaxanthin to orient across phospholipid membranes with its polar ends at the aqueous-lipid interfaces. This orientation is unique among common carotenoids and is the structural basis for astaxanthin's exceptional membrane antioxidant activity — the keto-hydroxyl ends can quench both lipid-soluble and water-soluble radicals at the membrane interface. The 13-double-bond conjugated system makes astaxanthin an efficient singlet oxygen quencher (dissipating excitation energy as heat rather than generating reactive species), and the keto groups allow single-electron transfer and adduct formation with reactive species.\n\nAstaxanthin occurs as three stereoisomers (3S,3''S; 3R,3''R; and 3R,3''S/meso) at the two hydroxyl carbons. Natural astaxanthin from Haematococcus pluvialis is predominantly (3S,3''S) with 70-100% in the monoester and diester forms (fatty acid esterified at the hydroxyl groups), which confers better stability and controlled-release bioavailability. Synthetic astaxanthin (used extensively in aquaculture feed to pigment farmed salmon) is a racemic mixture approximately 1:2:1 of (3S,3''S):(3R,3''S):(3R,3''R) in free (non-esterified) form. The natural/synthetic distinction matters for supplementation: natural Haematococcus-derived astaxanthin is the form used in virtually all published human supplementation trials and is the form with regulatory clearance in most jurisdictions for human dietary supplements. Synthetic astaxanthin is FDA-approved for aquaculture feed but has more limited human safety evaluation. BodyHackGuide recommends natural Haematococcus-derived astaxanthin for all human supplementation.\n\nThe adult human body does not naturally contain substantial astaxanthin — humans do not synthesize it and typical Western dietary intake is approximately 1-4 mg/day from salmon, trout, shrimp, and other seafood (substantially lower in non-seafood-consuming populations). Supplementation at 4-12 mg/day places astaxanthin tissue concentrations well above typical dietary levels and allows accumulation in skin, eye (retina and macula), brain, heart, and muscle tissue. Astaxanthin is one of the few carotenoids that readily crosses the blood-brain barrier and the blood-retinal barrier, giving it access to tissues where other carotenoids (beta-carotene, lutein in the macula only via specific transport, zeaxanthin similarly restricted) are excluded or limited.\n\nAbsorption of astaxanthin is lipid-dependent — the molecule is lipophilic and requires dietary fat for efficient micelle incorporation and subsequent chylomicron-mediated absorption. Fasting absorption is poor; coadministration with a fat-containing meal increases bioavailability 2-4 fold. Natural astaxanthin esters (from Haematococcus) are hydrolyzed by pancreatic lipase and intestinal esterases to free astaxanthin, which is absorbed with lipids into chylomicrons and delivered via lymphatics to systemic circulation. Plasma Cmax is typically reached 6-11 hours after oral administration. Plasma half-life is approximately 52-72 hours — one of the longer half-lives among dietary antioxidants, which allows once-daily dosing to maintain stable plasma concentrations. Distribution favors lipid-rich tissues including adipose tissue, liver, skin, brain, and retina. Excretion is predominantly biliary with fecal elimination; urinary excretion is minimal.\n\nThe clinical evidence for astaxanthin supplementation is best described as moderate-quality for a dietary supplement — multiple randomized controlled trials in humans across several outcome domains, but most trials are smaller than 100 subjects and durations are limited to 8-16 weeks. The strongest evidence exists for skin photoprotection and dermatology (Tominaga 2017 J Clin Biochem Nutr and related papers showing reduced wrinkle depth, improved skin elasticity, reduced photo-aging markers at 4-12 mg/day for 8-16 weeks), for eye health (particularly eyestrain from prolonged screen use, accommodative function, and pre-clinical data on dry eye and macular protection), for cardiovascular risk markers (Iwabayashi 2009 and subsequent trials showing reduced LDL oxidation, reduced hs-CRP, modest lipid improvements), for exercise recovery and performance (Kato 2020 and earlier work showing reduced muscle soreness, improved endurance, reduced markers of exercise-induced oxidative stress), and increasingly for cognitive outcomes (Satoh 2019 and related papers showing modest cognitive improvements in aging subjects). The depth of evidence across multiple outcome domains — with mechanistic plausibility from the antioxidant and anti-inflammatory effects — makes astaxanthin one of the better-evidenced carotenoid supplements.\n\nSafety is another area where astaxanthin distinguishes favorably from other carotenoids. Unlike beta-carotene (where the CARET and ATBC trials showed increased lung cancer risk in smokers with high-dose beta-carotene), astaxanthin has no comparable safety signal. Human trials at 4-40 mg/day have not identified significant adverse effects. Astaxanthin does not accumulate to produce orange skin discoloration at typical supplementation doses (unlike beta-carotene at high doses). Natural Haematococcus-derived astaxanthin has GRAS (Generally Recognized As Safe) status from the FDA at 12 mg/day, with higher doses in specific medical food applications. No drug interactions of clinical significance have been established at typical supplementation doses. The favorable safety profile combined with moderate efficacy evidence across multiple tissue domains makes astaxanthin a defensible supplement for the typical adult user interested in complete antioxidant support.\n\nBodyHackGuide's take: astaxanthin is among the best-evidenced, most mechanistically distinctive, and safest of the carotenoid supplements. At 4-12 mg/day (taken with fat-containing food), it provides meaningful antioxidant support with access to tissues (skin, eye, brain) that other carotenoids don't reach. The skin photoprotection evidence is particularly strong and clinically relevant for aging adults. The cardiovascular, exercise, and cognitive effects are modest but consistent. Cost is moderate ($15-30/month at typical doses). The main caveats: benefit is modest and pleiotropic rather than dramatic in any single outcome; the molecule is part of a broader antioxidant network and should not be relied on in isolation (vitamin C, vitamin E, polyphenols, omega-3 provide complementary support); and natural Haematococcus-derived product should be chosen over synthetic. For the typical adult interested in skin aging, eye health, cardiovascular antioxidant support, exercise recovery, or general anti-aging supplementation, 4-8 mg/day of natural astaxanthin is a reasonable addition to a complete stack. For intensive dermatologic, cardiovascular, or athletic applications, 8-12 mg/day is appropriate.\n", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 4720, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/astaxanthin" }, { "id": "683e393e-f5b1-4293-a02d-09d469ff2186", "slug": "astragalus", "name": "Astragalus (Huang Qi)", "aliases": [ "Astragalus membranaceus", "Astragalus mongholicus", "Huang Qi", "Huangqi", "Milk Vetch Root", "Bei Qi", "Mongolian Milk Vetch", "Radix Astragali", "Yellow Leader", "Locoweed" ], "category": "Adaptogen", "description": "**Astragalus** (scientific name *Astragalus membranaceus*, also classified as *Astragalus mongholicus* or *Astragalus propinquus*; called **Huang Qi** / Θ╗äΦè¬ in Mandarin Chinese — literally \"yellow leader\" referring to the yellow interior of the root; known in Western herbalism as **milk vetch root** or simply **astragalus root**; **Radix Astragali** in pharmacopeial Latin) is a perennial legume in the Fabaceae family (pea family), native to northern and northeastern China, Mongolia, Korea, and Siberia. The medicinal portion is the thick, fibrous, sweet-tasting taproot of 4-7 year old plants — harvested in autumn, cleaned, sliced into distinctive long strips with yellow cortex and paler core, and dried. Two closely related species are used interchangeably in commerce: *A. membranaceus* (Mongolian astragalus, the dominant commercial species) and *A. mongholicus* (Mongolian milk vetch). The genus *Astragalus* contains over 3,000 species worldwide, but only these two are the medicinal Huang Qi; most other *Astragalus* species contain toxic swainsonine (\"locoweed\") and are NOT interchangeable — a critical quality-control concern.\n\nAstragalus occupies an exceptionally prominent position in classical Chinese medicine, rivaling ginseng as one of the most important tonic herbs in the materia medica. The foundational text **Shen Nong Ben Cao Jing** (~200 BCE, attributed to the mythical emperor Shen Nong) — the earliest surviving Chinese herbal pharmacopeia — classifies Huang Qi in the highest \"**superior grade**\" (Σ╕èσôü *shang pin*) of herbs, meaning herbs considered safe for long-term use as rejuvenative tonics with minimal toxicity. Classical TCM theory ascribes astragalus the functions of **tonifying the Spleen and Lung Qi** (strengthening digestive and respiratory energetic function), **raising yang** (lifting prolapsed organs, treating fatigue), **stabilizing the Exterior and Stopping Sweating** (strengthening defensive qi / wei qi against pathogen invasion), **generating Flesh and Expelling Pus** (promoting wound healing in chronic non-healing sores), and **promoting Urination and Reducing Edema** (mild diuretic action in deficiency-type edema). The classical formulas built around astragalus include **Yu Ping Feng San** (Jade Windscreen Powder: astragalus + atractylodes + siler — the quintessential \"boost your immunity\" formula used for frequent colds, allergies, and weakness); **Bu Zhong Yi Qi Tang** (Tonify the Middle, Augment the Qi Decoction: astragalus + ginseng + atractylodes + licorice + citrus peel + cimicifuga + bupleurum + dong quai — the flagship fatigue/organ-prolapse formula); **Dang Gui Bu Xue Tang** (Dang Gui Blood-Tonifying Decoction: astragalus + dong quai in 5:1 ratio — paradoxically using astragalus to \"generate blood\" through qi→blood classical logic); and **Huang Qi Jian Zhong Tang** (astragalus + cinnamon + peony + licorice + ginger + jujube + malt sugar for debility and abdominal pain). This deep classical integration means astragalus is rarely used as a standalone herb in traditional practice — it's a team player supporting other tonics.\n\nThe primary bioactive compounds in astragalus span several pharmacologic classes. **Astragalosides** (I-VIII) are the signature cycloartane-type triterpenoid saponins, with **astragaloside IV** (AS-IV) being the most studied and often used as the marker compound for quality control in modern extracts. **Cycloastragenol** (CAG, also called \"9-CAG\" or \"cycloastragenol aglycone\") is the aglycone (sugar-free core) of astragaloside IV — when astragaloside IV is hydrolyzed, it yields cycloastragenol. Cycloastragenol is the active compound in the commercial telomerase-activating supplement **TA-65** (and related products like TAT2, TA-Sciences), which claims to extend lifespan and rejuvenate aged immune cells through partial telomerase activation. **Astragalus polysaccharides** (APS) are complex carbohydrate chains that constitute the dominant water-soluble immunomodulatory fraction — polysaccharides are typically active through innate immune receptors (TLR4, Dectin-1, complement receptors) and stimulate macrophage, NK cell, and T-cell function. **Isoflavonoids** (formononetin, calycosin, calycosin-7-O-β-D-glucoside, ononin) contribute additional cardiovascular and estrogenic effects. **Sucrose and other free sugars** contribute to the characteristic sweet taste and to the energetics classical TCM describes. Quality extracts are typically standardized to astragalosides (0.1-0.5% for typical root extracts; up to 90%+ for purified AS-IV), or to polysaccharides (typically 40-70% polysaccharides by weight in APS-focused extracts), or to cycloastragenol content (for telomerase-focused products).\n\nThe proposed clinical applications of astragalus span: **(1) immune support and respiratory infection prophylaxis** — perhaps the most evidence-backed modern use, with astragalus routinely recommended during cold/flu season, for frequent respiratory infections, and for immune recovery after illness; **(2) cardiovascular protection** — including heart failure, ischemic heart disease, arrhythmia, and stroke recovery with substantial Chinese clinical research; **(3) adjunctive cancer care** — widely used in integrative oncology to reduce chemotherapy side effects, support immunity during treatment, and improve quality of life; **(4) chronic kidney disease** — particularly diabetic nephropathy, with multiple RCTs showing reduced proteinuria and improved renal function; **(5) diabetes and insulin resistance** — glucose-lowering and insulin-sensitizing effects; **(6) chronic fatigue and post-viral fatigue** — classical \"qi deficiency\" application with reasonable modern evidence; **(7) anti-aging and telomerase activation** — the cycloastragenol/TA-65 angle with genuinely interesting but preliminary data; **(8) autoimmune conditions** — complex/paradoxical (immune-stimulating yet used traditionally for immune dysregulation); **(9) wound healing and tissue repair** — traditional and some modern evidence for chronic wounds; and **(10) fertility support** — traditional use and some modern reproductive research.\n\nHuman clinical evidence is substantial, particularly from Chinese literature (though often of variable methodological quality). Key trials: **Cochrane reviews of astragalus in chronic heart failure** have consistently found modest clinical benefit with acceptable safety across dozens of Chinese RCTs, though recommending higher-quality confirmatory trials. **Ryan et al. 2006** and multiple subsequent diabetic nephropathy RCTs show reductions in proteinuria comparable to ACE inhibitors in some comparisons. **McCulloch et al. 2006** meta-analysis found astragalus-based herbal combinations in chemotherapy reduced nausea, leukopenia, and improved quality of life. **Clegg et al. 2013** and **Harley et al. 2013** examined the cycloastragenol supplement TA-65, finding telomerase activation effects and immune senescence markers improved. **Zhang et al. 2006** examined diabetic nephropathy with standardized astragaloside IV. Chinese literature contains many small-to-medium RCTs in chronic bronchitis, immune recovery, stroke recovery, and heart failure that are difficult to evaluate systematically but collectively support moderate efficacy for the herb.\n\nWhere does astragalus fit in the therapeutic landscape? It's distinctive as: **(1)** a **gentle, daily-use immune tonic** — safer and more appropriate for long-term use than aggressive immunostimulants; **(2)** the **signature Chinese cardiovascular herb** with genuine clinical data in heart failure and ischemic disease; **(3)** a **cornerstone of integrative oncology support** — probably the single most-used herb in Chinese medical oncology adjunctive care; **(4)** the **source material for commercial telomerase activators** like TA-65; **(5)** a **qi-deficiency specialist** — its classical use case is fatigue/weakness/chronic low-grade dysfunction, not acute pathology or overstimulation states; and **(6)** a **team player** that shines in formulas rather than standalone use. It pairs classically and meaningfully with [Panax ginseng](/compound/panax-ginseng) (fellow Qi tonic — ginseng more \"warming\" and activating, astragalus more \"rising\" and surface-stabilizing), [Reishi](/compound/reishi) (shared immunomodulation, different tissue affinities), [Cordyceps](/compound/cordyceps) (classical lung support pair), [Eleuthero](/compound/eleuthero) (sometimes called \"Siberian astragalus\" — both stabilize against seasonal illness), [Ashwagandha](/compound/ashwagandha) (adaptogen from a different tradition with different tissue tropism), [Rhodiola rosea](/compound/rhodiola-rosea) (rhodiola activates and astragalus grounds), [Schisandra](/compound/schisandra) (both \"stabilize the exterior\" in TCM framework), and [Licorice Root](/compound/licorice-root) (classical adjuvant in many astragalus formulas). It does NOT pair well during acute infections in classical TCM (the \"don't tonify during invasion\" rule), and should be used cautiously in autoimmune conditions given immune-stimulating effects.\n\nSafety is excellent for most users at standard doses, reflected in its \"superior grade\" classical classification and thousands of years of widespread culinary-medicinal use. Astragalus root is routinely added to soups, stews, and slow-cooked dishes in Northern China as a functional food ingredient. Formal toxicology studies confirm very low acute and chronic toxicity. Key considerations include: theoretical autoimmune exacerbation risk (though clinically rarely observed at typical doses), interactions with immunosuppressants (cyclosporine, tacrolimus, mycophenolate) where astragalus may reduce drug efficacy, potential interactions with anticoagulants, and the TCM admonition to avoid during active acute infections (the reasoning being that immune \"attention\" should focus outward rather than be redirected to internal tonification). Adulteration with other *Astragalus* species containing toxic swainsonine remains a quality-control concern — purchase from reputable suppliers with species authentication.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 497, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/astragalus" }, { "id": "e1a7c3d2-9f4b-4c2a-bf10-1a2b3c4d5e02", "slug": "atx-304", "name": "ATX-304", "aliases": [ "O-304", "O304", "OS-01" ], "category": "Metabolic & Weight Loss", "description": "ATX-304 (also known as O-304) is an orally bioavailable, first-in-class pan-AMPK activator with a mild mitochondrial-uncoupling effect. It was developed at Umea University and Betagenon AB in Sweden and studied for type 2 diabetes and its cardiovascular complications. Research interest centers on AMPK as a master metabolic switch governing glucose uptake, fatty-acid oxidation and microvascular perfusion.", "half_life": null, "molecular_weight": "380.2", "molecular_mass": "380.2 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Phase IIa Clinical Trials", "approval_status": "Investigational; not approved", "trial_phase": "", "cas_number": "1261289-04-6", "iupac_name": "", "chemical_formula": null, "potential_benefits": [ "Pan-AMPK activation (metabolic master switch)", "Improved glucose uptake and insulin sensitivity (preclinical + Phase IIa)", "Increased fatty-acid oxidation", "Improved microvascular perfusion", "Studied for type 2 diabetes and cardiovascular complications" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/atx-304" }, { "id": "0112ddb4-c929-4e61-9593-422829d8503e", "slug": "b7-33", "name": "B7-33", "aliases": [ "Relaxin analog" ], "category": "Other", "description": "B7-33 is a single-chain, 26-amino-acid peptide engineered as a functionally selective agonist of the relaxin family peptide receptor 1 (RXFP1), designed to recapitulate the therapeutic activity of human H2 relaxin — the endogenous peptide hormone that is naturally elevated during pregnancy and has broad cardioprotective, vasodilatory, and anti-fibrotic effects. The compound was developed by Mohammed Akhter Hossain, Ross Bathgate, and colleagues at the Florey Institute of Neuroscience and Mental Health and Monash University in Australia as part of a medicinal chemistry program seeking to capture the therapeutic benefits of native H2 relaxin in a simpler, synthetically accessible molecule that could be manufactured at scale and developed into a clinical drug. Native H2 relaxin itself is a two-chain, disulfide-linked protein of roughly 6 kDa that is difficult and expensive to produce by recombinant methods; the first attempt at translating relaxin therapy into a drug was serelaxin (recombinant human H2 relaxin), which advanced into large Phase 3 trials for acute heart failure before failing to meet its primary endpoint in the RELAX-AHF-2 trial and being discontinued as a heart failure drug candidate. B7-33 represents a second-generation approach — if the two-chain recombinant protein is commercially impractical and clinically disappointing at the specific dose and formulation tested, can a simpler single-chain analog with favorable PK properties capture enough of the relaxin activity to be useful? The published work from the Bathgate group and collaborators ([Hossain et al., 2016]; [Samuel et al., 2017]) shows that B7-33 activates RXFP1 with a biased agonism profile favoring the ERK1/2-pERK signaling pathway over the classical cAMP pathway activated by full-length H2 relaxin, and this biased signaling is associated with preservation of the anti-fibrotic and cardioprotective effects of relaxin while potentially reducing some of the off-target effects associated with full relaxin signaling. In preclinical cardiovascular disease models, B7-33 administration reduces cardiac fibrosis, improves diastolic and systolic function in heart failure models, reduces kidney fibrosis in chronic kidney disease models, and produces hemodynamic effects similar to full-length relaxin but at a simpler molecular scaffold. The specific indication space where B7-33 is being evaluated for potential development includes acute heart failure (where serelaxin failed but where the relaxin mechanism still has strong biological rationale), chronic heart failure with preserved or reduced ejection fraction, diabetic cardiomyopathy, chronic kidney disease with cardio-renal syndrome, and broader anti-fibrotic applications in organ fibrosis. The practical reality in April 2026 is that B7-33 remains a preclinical research peptide with no approved human use, no registered clinical trials at the Phase 1 level or later, and no pharmaceutical-grade supply. It is sold by research-chemical peptide vendors with the standard \"for research purposes only\" framing, and a small but dedicated biohacker community has experimented with it primarily in cardiometabolic and anti-fibrotic protocols. The evidence base for self-experimentation is limited to extrapolation from rodent studies of B7-33 specifically plus the broader relaxin literature including the failed serelaxin program. This entry covers the mechanism of biased RXFP1 agonism in detail, the preclinical pharmacology across cardiovascular, renal, and fibrotic disease models, the context provided by the serelaxin clinical program and what its failure does and does not tell us about relaxin biology in humans, the theoretical and practical concerns with self-administration of an unvalidated peptide targeting a significant cardiovascular pathway, how B7-33 relates to other cardioprotective and anti-fibrotic interventions like [BPC-157](/compound/bpc-157), [TB-500](/compound/tb-500), [Humanin](/compound/humanin), and prescribed cardiometabolic medications, and what disciplined thinking about this compound looks like for someone considering it seriously. The core takeaway is that B7-33 rests on a mechanism with strong biological rationale but an uncertain clinical track record from the parent class, represents real pharmacological sophistication in its biased agonism profile, and has a substantial gap between promising preclinical data and validated human use.", "half_life": "In vitro serum-stability half-life is approximately 6 minutes; B7-33 is rapidly degraded (a lipidated analog extended this to ~60 minutes in the same assay). Human in vivo pharmacokinetics are unpublished, and rapid clearance is expected for a small linear peptide (Praveen et al. 2023, PMID 37047588).", "molecular_weight": "2986.58 g/mol", "molecular_mass": "2986.58 g/mol", "amino_acid_sequence": "VIKLSGRELVRAQIAISGMSTWSKRSL - single-chain linear peptide, 27 residues. B7-33 is a derivative of the human H2 relaxin B-chain: the native B-chain (B1-29) is truncated by 6 N-terminal residues and extended at the C-terminus by KRSL (spanning relaxin B-chain positions B7-B33), and the two native B-chain cysteines (B11 and B23) are replaced with isosteric serine to prevent dimerization/aggregation. It therefore contains no cysteines and no disulfide bonds (Hossain et al., Chemical Science 2016).", "administration_routes": [], "dose_range_mcg": "500-4000 mcg subcutaneous per injection (community/self-report research doses; most commonly ~1000 mcg / 1 mg once daily). No validated human dose exists - all figures are empirical extrapolations from rodent pharmacology.", "dosing_frequency": "Once daily or every other day, subcutaneous (community practice only). B7-33 has a very short half-life; no validated human dosing schedule exists.", "cycle_length": "Typically 4-12 weeks on with 4-8 week off-periods between cycles (community convention; not clinically validated).", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "1421043-98-3", "iupac_name": "Ac-Asp-Val-Ala-His-Phe-Ala-Ala-Val-Gln-Pro-Cys-Glu-Thr-Gly-Cys-Ser-Arg-Ile-Pro-Ile-Phe-Lys-Asp-Cys-Gly-Pro-Gly-Lys-NH2", "chemical_formula": "C125H180N30O35S4", "potential_benefits": [ "Anti-fibrotic effects", "Improved tissue flexibility", "Cardiovascular protection", "Enhanced collagen remodeling", "Potential fertility support" ], "research_fields": [], "pubmed_count": 11, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/b7-33" }, { "id": "78a2e477-839f-4d7b-a004-e3988c191938", "slug": "bac-water", "name": "BAC Water", "aliases": [ "Bacteriostatic Water", "Sterile Water", "Benzyl Alcohol Water", "BHG-BW" ], "category": "Supplies", "description": "Bacteriostatic water (BAC water) is Sterile Water for Injection preserved with 0.9% benzyl alcohol, used to reconstitute lyophilized (freeze-dried) research peptides into an injectable solution. The benzyl alcohol inhibits bacterial growth, so a reconstituted multi-dose vial can be drawn from repeatedly for up to ~28 days when refrigerated. It is a reconstitution supply, not a therapeutic compound.", "half_life": "Not applicable - reconstitution diluent, not a dosed compound.", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "N/A - BAC water is a reconstitution diluent, not a dosed compound. Typical amount mixed per peptide vial is ~1-3 mL, chosen by concentration math rather than by dose.", "dosing_frequency": "N/A - BAC water is not administered on its own; it is only used to reconstitute peptide vials.", "cycle_length": "N/A - supply item. Reconstituted vials are typically used within ~28 days when refrigerated.", "common_vial_sizes": [], "research_stage": "Not applicable - established pharmaceutical diluent (reconstitution supply), not a research-stage compound.", "approval_status": "FDA-approved as Bacteriostatic Water for Injection, USP (a multiple-dose diluent). Using it to reconstitute research peptides is not an approved medical indication and is for research use only (RUO).", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Dissolves lyophilized (freeze-dried) research peptides into an injectable solution", "The 0.9% benzyl alcohol preservative inhibits bacterial growth, so one reconstituted vial can be drawn from repeatedly for up to ~28 days when refrigerated", "More practical than preservative-free Sterile Water for multi-dose vials, which are intended for single use", "Benzyl alcohol has a mild local-anesthetic property that can make small-volume subcutaneous injections sting slightly less than plain sterile water", "Widely available, inexpensive, and standardized at 0.9% benzyl alcohol across pharmaceutical-grade product" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/bac-water" }, { "id": "e2e0dc7b-ce65-41ca-a6df-cc80981c1e80", "slug": "bacopa-monnieri", "name": "Bacopa monnieri", "aliases": [ "Brahmi", "Water Hyssop", "Herb of Grace", "Thyme-leafed Gratiola", "Jalanimba", "Synapsa", "CDRI-08", "BacoMind", "BioBM", "Bacosides" ], "category": "Nootropic Adaptogen", "description": "Bacopa monnieri is a creeping, succulent-leaved aquatic perennial that grows in wetlands, bogs, and rice paddies across the Indian subcontinent, Southeast Asia, northern Australia, and the southern United States. Known as \"Brahmi\" in Sanskrit — a name it shares somewhat confusingly with Centella asiatica ([gotu kola](/compound/gotu-kola)), which is also sometimes called Brahmi in certain Indian regions — Bacopa monnieri has been used in Ayurvedic medicine for at least 3,000 years as \"medhya rasayana\" (a mind-nourishing rejuvenative), with classical texts including the Charaka Samhita and Sushruta Samhita prescribing it for memory, concentration, anxiety, epilepsy, and mental clarity. Unlike the stimulating adaptogens ([rhodiola rosea](/compound/rhodiola-rosea), [panax ginseng](/compound/panax-ginseng)) that produce acute wakefulness within days, or the calming adaptogens ([ashwagandha](/compound/ashwagandha)) that modulate stress within weeks, Bacopa monnieri is the slowest-acting of the major adaptogens — most users experience no discernible effect in the first 4-6 weeks of dosing, with cognitive benefits emerging gradually at 8-12 weeks and continuing to deepen at 4-6 months of continuous use. This pharmacokinetic profile is not a flaw but a reflection of the mechanism: Bacopa's primary effects are structural (hippocampal dendritic arborization, synaptic density, long-term potentiation facilitation) rather than acute neurotransmitter modulation, and structural brain changes require weeks of consistent exposure before they become clinically measurable.\n\nThe active constituents are the bacosides, a family of saponin glycosides comprising bacoside A (itself a mixture of bacoside A3, bacopaside II, bacopasaponin C, and jujubogenin) and bacoside B, along with bacopasides I through XII, bacopasaponins A-G, and minor flavonoids including apigenin and luteolin. Clinical trials have almost universally used extracts standardized to 50% bacosides, with the two most-studied proprietary extracts being BacoMind (Natural Remedies, India; used in the Morgan 2010 and Calabrese 2008 trials) and Synapsa / CDRI-08 (Central Drug Research Institute, Lucknow; used in the Stough 2001, Stough 2008, Roodenrys 2002, and Peth-Nui 2012 trials). Other extracts on the market include BioBM (Life Extension) and various 20% or 45% bacoside extracts from generic suppliers. The practical rule for consumers: buy only products standardized to 50% bacosides or a named proprietary extract with published clinical trials. Generic \"Bacopa monnieri powder\" at unverified standardization is unreliable because bacoside content varies 3-5x across wild-harvested or poorly cultivated material.\n\nThe mechanism of action differs fundamentally from both rhodiola (monoamine modulation) and ashwagandha (HPA-axis and GABAergic). Bacopa's cognitive-improving profile emerges from at least six parallel mechanisms: (1) acetylcholinesterase (AChE) inhibition at modest potency, extending synaptic acetylcholine half-life in cortical and hippocampal circuits in a manner mechanistically similar to but far milder than donepezil; (2) brain-derived neurotrophic factor (BDNF) upregulation via CREB-mediated transcription, driving the trophic-structural changes that underlie long-term memory consolidation; (3) hippocampal CA1 dendritic arborization and spine density increase, demonstrated in rat models by Vollala and colleagues (2011) showing 30-40% increased dendritic branching after 6 weeks of bacopa feeding; (4) antioxidant activity including superoxide dismutase induction and lipid peroxidation reduction, particularly in brain tissue where bacosides cross the blood-brain barrier efficiently; (5) mild anxiolytic activity via GABA-A receptor positive modulation and serotonin 5-HT1A partial agonism; and (6) cerebrovascular effects including increased cerebral blood flow and endothelial nitric oxide synthase upregulation, documented in older adults with mild cognitive impairment. Each mechanism is individually modest — Bacopa is not a potent AChE inhibitor like donepezil, not a strong BDNF inducer like exercise, not a structural neurogenesis driver like [lion's mane](/compound/lions-mane) — but their convergence produces a distinctive and reproducible cognitive phenotype centered on memory consolidation, information retention, and reduced cognitive decline with aging.\n\nClinically, the evidence base is among the strongest for any herbal nootropic, with at least nine randomized placebo-controlled trials and a 2014 meta-analysis (Kongkeaw et al., PMID: 24252493) pooling 9 RCTs and concluding Bacopa monnieri produces significant improvements in cognitive performance with a pooled standardized mean difference of 0.21-0.31 across memory and attention domains. The seminal Western trial is Stough et al. 2001 (Neuropsychopharmacology), which randomized 46 healthy adults to 300 mg/day Bacopa (Synapsa/CDRI-08) versus placebo for 12 weeks and demonstrated significant improvements in information processing speed, learning rate, and memory consolidation by week 12 with no detectable effect at weeks 4 or 8 — the classic delayed-onset Bacopa profile (PMID: 11498727). Roodenrys 2002 extended this with a second RCT in 76 adults showing improved free recall and reduced learning-related forgetting (PMID: 12093601). Calabrese 2008 in the Journal of Alternative and Complementary Medicine randomized 48 older adults (mean age 73) to BacoMind 300 mg/day versus placebo for 12 weeks, finding significant improvements in word recall, delayed recall, Stroop task, and depression/anxiety subscales. The elderly-response magnitude in Calabrese 2008 (effect size ~0.5) is larger than in the young-adult trials (effect size ~0.2-0.3), suggesting Bacopa's benefit scales with underlying cognitive vulnerability — older adults with age-related cognitive decline respond more robustly than healthy young adults.\n\nWhere Bacopa fits in the cognitive-adaptogen landscape: it is the long-term memory consolidation compound, best suited for students during multi-month academic periods, professionals in information-dense work requiring long retention, older adults concerned about age-related cognitive decline, and users stacking with faster-acting cognitive enhancers as the chronic structural-maintenance component. It is not the right choice for users seeking acute pre-exam cognitive enhancement (that's [rhodiola](/compound/rhodiola-rosea) territory), for users with primary attention deficits (that's [l-tyrosine](/compound/l-tyrosine) or cholinergic precursors), or for users expecting rapid onset (that's [caffeine](/compound/caffeine) + [l-theanine](/compound/l-theanine), [citicoline](/compound/citicoline), or [alpha-gpc](/compound/alpha-gpc)). For a canonical long-form nootropic stack, Bacopa pairs with [lion's mane](/compound/lions-mane) (structural NGF-mediated neurogenesis), [citicoline](/compound/citicoline) (acute cholinergic and membrane phospholipid support), and [omega-3 EPA/DHA](/compound/omega-3) (phospholipid raw material and anti-inflammatory), producing a chronic cognitive-maintenance protocol supported by converging mechanisms. See also [ashwagandha](/compound/ashwagandha) for stress resilience, [rhodiola rosea](/compound/rhodiola-rosea) for acute cognitive performance, and [panax ginseng](/compound/panax-ginseng) for the closest adaptogen analog.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 400, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/bacopa-monnieri" }, { "id": "c4c3c6f4-46e2-4185-ad95-1e23700368cd", "slug": "bam15", "name": "BAM15", "aliases": [ "BAM-15" ], "category": "Weight Loss", "description": "BAM15 is a small-molecule mitochondrial protonophore uncoupler that was first described in 2014 as a tool compound for dissipating proton motive force selectively across the inner mitochondrial membrane without collapsing the plasma membrane electrochemical gradient ([Kenwood et al., 2014]). The full chemical name is (2-fluorophenyl)-(6-[(2-fluorophenyl)amino](1,2,5-oxadiazolo[3,4-e]pyrazin-5-yl))amine, molecular weight 338.3 g/mol, and the molecule was identified through a high-throughput screen designed to find uncouplers that behave differently from the classical reference compound 2,4-dinitrophenol (DNP). DNP raises metabolic rate and causes rapid fat loss in animals and humans but has a catastrophically narrow therapeutic window, with hyperthermia, cataracts, peripheral neuropathy, and fatal overdoses well documented in the 1930s weight-loss literature and in modern case series of bodybuilders and diet pill users who source DNP as a research chemical ([Grundlingh et al., 2011]). BAM15 was explicitly designed to improve on DNP by restricting uncoupling activity to mitochondria and not the plasma membrane, theoretically producing the metabolic benefit — increased substrate oxidation, reduced reactive oxygen species, improved insulin sensitivity — without the cardiovascular and thermoregulatory toxicity that makes DNP untenable as a drug. If you are on this page because you heard BAM15 called \"a safe DNP\" on a forum or podcast, you should finish this entry before you do anything else. BAM15 is a research chemical. There are zero published clinical trials in humans as of April 2026, zero FDA-approved indications, zero pharmacokinetic or toxicology studies in people, and zero manufacturers producing it under pharmaceutical-grade quality standards for human use. Every dose anyone has ever taken has come from a research-chemical vendor with no regulatory oversight. The preclinical animal data are genuinely exciting — BAM15 reverses diet-induced obesity in mice at doses that appear well tolerated, improves hepatic steatosis in rodent NASH models, lowers blood glucose, improves insulin sensitivity, and reduces ROS generation without the hyperthermia and death that DNP produces at comparable efficacy doses. But \"better than DNP in mice\" is an extremely low bar, and the gap between \"promising in rodents\" and \"safe in humans at a predictable dose\" is exactly where hundreds of drug candidates have died over the last two decades. This entry is a complete summary of what BAM15 actually does mechanistically, what the preclinical evidence shows, what it does not show, why there are no human trials despite a decade of academic interest, and what the realistic landscape looks like for anyone considering experimenting with it. We will talk about the pharmacology in enough detail that you can have an informed conversation with a physician about why you should probably not be using this compound, and we will also be honest that a subset of people will use it anyway, in which case the harm-reduction information below — dose ranges reported in self-experimenters, signs of mitochondrial toxicity, interactions with other metabolic agents, and the reasons no one has been able to bring this drug to a Phase 1 trial despite its theoretical advantages — becomes the most important part of the page. Uncoupler chemistry is one of the few mechanisms in metabolism that cannot be meaningfully replicated by training, diet, or lifestyle intervention. Exercise, cold exposure, fasting, and caloric restriction all activate mitochondrial biogenesis and uncoupling protein expression (UCP1, UCP2, UCP3), which is the body's own physiological version of uncoupling. Those interventions should be fully optimized before anyone looks at a chemical protonophore, because physiological uncoupling through brown adipose tissue activation, exercise-induced mitochondrial adaptation, and UCP upregulation delivers a substantial fraction of the metabolic benefit with none of the drug-risk profile. BAM15 exists in the conversation because people want a pill version of cold exposure and cardio. That desire is legitimate, but the pill does not yet exist in a form any reasonable clinician would recommend.", "half_life": "", "molecular_weight": "", "molecular_mass": "357.35 g/mol", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "Research compound — no established human doses. Animal studies use 10-100 mg/kg", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "203203-79-6", "iupac_name": "N-(2-nitro-4-(trifluoromethyl)phenyl)-[4-(2-hydroxy-3,3-dimethylbutoxy)phenyl]methanamine", "chemical_formula": "C17H19N3O4", "potential_benefits": [ "Enhanced fat oxidation and weight loss", "Improved insulin sensitivity", "Reduced hepatic steatosis (fatty liver)", "Increased metabolic rate", "Potentially safer than DNP" ], "research_fields": [], "pubmed_count": 58, "pubchem_cid": 68600003, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/bam15" }, { "id": "a20d573c-77dc-4ac6-a818-de46ddcaef42", "slug": "bemethyl", "name": "Bemethyl (bemitil)", "aliases": [ "Bemitil", "Bemithyl", "Metaprot", "Bemactor", "Antihot", "2-ethylthiobenzimidazole", "2-(ethylthio)benzimidazole hydrobromide" ], "category": "Nootropics", "description": "Bemethyl, known in the Russian literature as bemitil and sold in the region under names including Metaprot, Bemactor and Antihot, is 2-ethylthiobenzimidazole, normally handled as the hydrobromide salt. It came out of work led by Vladimir Vinogradov at the Department of Pharmacology of the Military Medical Academy in Leningrad during the 1970s, which set out to define a class of drugs the authors called actoprotectors: agents that raise tolerance of physical work without raising oxygen consumption or heat production. Bemethyl was the first and remains the reference member of that class. It was given to Soviet cosmonauts, used in preparing athletes for the 1980 Moscow Olympic Games and issued widely in the Soviet armed forces, and after 1991 its official manufacture stopped in Russia before production resumed in Ukraine (PMID: 24009833). It was later re-registered in Russia as the capsule medicine Metaprot (marketing authorization holder AnviLab, manufacturer Farmproekt, product instruction approved 2014), indicated for restoring working capacity and for asthenia after infection, surgery or head injury (Russian State Register of Medicines, Metaprot).\n\nThe proposed mechanism is metabolic rather than receptor based. Reviews describe increased synthesis of RNA and protein, particularly gluconeogenesis enzymes in liver and kidney and mitochondrial enzymes, which supports reuse of lactate and maintenance of ATP production under load, along with an indirect antioxidant effect through induction of antioxidant enzymes rather than direct radical scavenging. The authors of that review state plainly that the specific mechanism behind the protein expression effect remains unknown (PMID: 24009833).\n\nAnimal work is extensive and almost all Russian. In rats, bemethyl distributed into liver, brain, kidney, spleen, heart, skeletal muscle, lung, adipose tissue and testes after single and repeated oral administration, accumulating most in liver (PMID: 17181062). It produced a cerebroprotective effect and normalized brain energy metabolism in rats after craniocerebral trauma (PMID: 15514724), a hepatoprotective effect with reduced fibrosis in rats with experimental cirrhosis (PMID: 16845942), and it strengthened the antioxidant adaptation produced by intermittent hypoxic training in rats (PMID: 16282998). Rat metabolism was mapped in 2021, with nine metabolites identified in 24 h urine after a single oral dose of 330 mg/kg and a benzimidazole-acetylcysteine conjugate as the most abundant (PMID: 34445727).\n\nHuman data are thin by modern standards. A pharmacokinetic study in healthy volunteers given a single 250 mg oral dose reported a mean peak serum concentration of 0.91 microg/mL at about 1.06 h (PMID: 21870773). Clinical reports cover small groups: 15 patients with systemic lupus erythematosus (PMID: 10572751), seven children with epilepsy (PMID: 9324390) and patients with asthenic syndromes after moderate brain injury (PMID: 16404942). No large randomized placebo-controlled trial appears in the indexed English-language literature.\n\nRegulatory reality matters here. Bemethyl has no FDA or EMA authorization. In Ukraine it has been certified as a dietary supplement rather than a medicine, while in Russia it is registered as the medicine Metaprot (PMID: 24009833, PMID: 21870773). The World Anti-Doping Agency placed 2-ethylsulfanyl-1H-benzimidazole on its Monitoring Program from 2018 to 2021 and removed it for 2022, so it is on neither the current Prohibited List nor the Monitoring Program; an excretion study in six volunteers showed the parent drug and its glucuronide stay detectable in urine for weeks (PMID: 30346653). What is sold online as a bemethyl solution is a research chemical rather than the capsule product used in the published studies, and nothing verifies its identity or content.", "half_life": "Not established in humans; in healthy volunteers given a single 250 mg oral dose of the Metaprot capsule form, peak serum ethylthiobenzimidazole averaged 0.91 microg/mL at about 1.06 h, and no terminal half-life was reported (PMID: 21870773)", "molecular_weight": "259.17 g/mol (hydrobromide salt); 178.26 g/mol (free base)", "molecular_mass": "259.17 g/mol (hydrobromide salt)", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Approved (Russia)", "approval_status": "No FDA or EMA marketing authorization and no legal medicinal status in the United States or the European Union. It is registered in Russia as the capsule medicine Metaprot (marketing authorization holder AnviLab, product instruction approved 2014) and certified as a dietary supplement in Ukraine under the name Antihot (PMID: 21870773, PMID: 24009833, PMID: 30346653). The World Anti-Doping Agency placed 2-ethylsulfanyl-1H-benzimidazole on its Monitoring Program from 2018 to 2021 and removed it for 2022, so it is on neither the current Prohibited List nor the Monitoring Program (PMID: 30346653, PMID: 34445727); what is sold as a bemethyl solution online is a research-use-only compound in the US market.", "trial_phase": "", "cas_number": "63513-71-3 (hydrobromide); 14610-11-8 (free base)", "iupac_name": "", "chemical_formula": "C9H11BrN2S (hydrobromide); C9H10N2S (free base)", "potential_benefits": [ "Increased maximal work performed and resistance to fatigue in mice under exhaustive load, with a profile different from the psychostimulant sydnocarb (PMID: 24009833)", "Cerebroprotective effect with normalized brain energy metabolism in rats after craniocerebral trauma, alone and combined with pyrazidol (PMID: 15514724)", "Hepatoprotective effect with reduced fibrosis in rats with experimental cirrhosis (PMID: 16845942)", "Potentiated the antioxidant adaptation produced by intermittent hypoxic training in rats (PMID: 16282998)", "Reduced lipid peroxidation and normalized liver enzyme values in rats poisoned with the organophosphate carbophos (PMID: 23012992)" ], "research_fields": [ "Actoprotectors and adaptogens", "Exercise physiology", "Antihypoxants", "Anti-doping analysis" ], "pubmed_count": 0, "pubchem_cid": 9816609, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/bemethyl" }, { "id": "39aa6eef-be04-4c3f-a06b-853b58906b2c", "slug": "berberine", "name": "Berberine", "aliases": [ "Berberine HCl", "Berberine Hydrochloride", "Umbellatine", "Natural Metformin", "Berberis Alkaloid", "Dihydroberberine (DHB, reduced form)", "Coptisine (related alkaloid)", "Goldenseal Alkaloid" ], "category": "Metabolic", "description": "Berberine is an isoquinoline alkaloid — a naturally occurring plant secondary metabolite with a characteristic yellow color — extracted from the roots, rhizomes, stems, and bark of several plant genera including Berberis (barberry, Oregon grape), Coptis (goldthread), Hydrastis (goldenseal), Phellodendron (Amur cork tree), and Tinospora (guduchi). Its use in traditional medicine spans more than two millennia, with documented applications in Traditional Chinese Medicine (under the name Huang Lian Θ╗äΦ┐₧, primarily from Coptis chinensis), Ayurveda (from Berberis aristata, called Daruharidra or \"tree turmeric\"), Native American medicine (from goldenseal, Hydrastis canadensis), and Persian medicine (from Berberis vulgaris). Traditional indications emphasized gastrointestinal complaints — diarrhea, dysentery, intestinal infection — which turn out to align well with berberine's documented antimicrobial activity against bacteria, protozoa, and fungi. The modern pharmacologic investigation of berberine dates to the mid-20th century with early studies on antibacterial and antidiarrheal effects, but the explosion of contemporary interest followed the 2004 discovery by Kong and colleaguesthat berberine lowers blood lipids through a mechanism involving LDL receptor upregulation. This finding redirected berberine research toward metabolic applications — diabetes, dyslipidemia, polycystic ovary syndrome, non-alcoholic fatty liver disease, and metabolic syndrome — and positioned berberine as a botanical analog to pharmaceutical metformin. The landmark Yin et al. 2008 randomized controlled trial (PMID 18397984) compared berberine 500 mg three times daily head-to-head with metformin 500 mg three times daily in 36 adults with newly-diagnosed type 2 diabetes over three months, finding comparable glycemic effects: HbA1c reduction of approximately 2 percentage points with berberine versus similar reduction with metformin, and with superior lipid effects (significant triglyceride and total cholesterol reductions exceeding what metformin produced). This single trial, though small, catalyzed the modern \"natural metformin\" marketing positioning that continues to drive berberine's commercial growth in the functional medicine and longevity supplement space. Since then, dozens of clinical trials and several meta-analyses have examined berberine across diabetes, dyslipidemia, metabolic syndrome, PCOS, hypertension, and various gastrointestinal indications. The accumulating evidence has generally supported berberine's metabolic effects but with important nuances: the bioavailability of oral berberine is less than 1%, meaning the vast majority of an ingested dose is never systemically absorbed; effects on distal organs therefore depend substantially on metabolites, gut microbiome modulation, and intestinal signaling rather than direct tissue exposure; effects on glucose and lipids are strong and reproducible but typically modest in magnitude (similar to metformin rather than superior to it in rigorous trials); meaningful pharmacokinetic drug interactions occur via cytochrome P450 inhibition, particularly CYP3A4 and CYP2D6, which must be considered for patients taking prescription medications metabolized by these pathways. Berberine has also entered the longevity and healthspan conversation as an AMPK activator — AMPK being one of the central nutrient-sensing pathways whose activation is believed to underlie at least some of the age-slowing effects of caloric restriction, [metformin](/compound/metformin), and [rapamycin](/compound/rapamycin)-independent pathways. Whether berberine meaningfully extends healthspan in humans has not been demonstrated (the evidence for this is lower than for metformin, which itself has debated longevity evidence), but mechanistic rationale and safety profile have made it a common addition to longevity-oriented supplement stacks. Other prominent applications include: gastrointestinal applications in small intestinal bacterial overgrowth (SIBO) and irritable bowel syndrome, based on berberine's antimicrobial activity and favorable microbiome modulation; PCOS management, where Lan et al. 2015documented improvements in insulin resistance and menstrual regularity; non-alcoholic fatty liver disease, with trials showing hepatic steatosis reduction; and cholesterol management, where berberine's LDL receptor upregulation provides a statin-alternative for individuals with statin intolerance. The bioavailability problem has driven development of several alternative formulations: dihydroberberine (the reduced form, with theoretically superior absorption); phytosome formulations binding berberine to phosphatidylcholine to improve intestinal uptake; liposomal formulations; and combinations with P-glycoprotein inhibitors like silymarin to prevent efflux back into the intestinal lumen. Whether these formulations produce meaningfully superior clinical outcomes versus standard berberine HCl remains unclear, as most were developed for pharmacokinetic rather than efficacy endpoints. This entry covers berberine's mechanism (AMPK activation, gut-microbiome mediated effects, intestinal L-cell DPP-4 inhibition, lipid-modulating effects via LDL receptor and PCSK9 pathways); the clinical evidence base (glycemic effects, lipid effects, PCOS, NAFLD, weight, and gastrointestinal applications); the pharmacokinetic challenges (low bioavailability, CYP-mediated drug interactions, first-pass metabolism); formulation alternatives (dihydroberberine, phytosomes, liposomes); practical dosing considerations; and appropriate integration into metabolic, longevity, and gastrointestinal supplement protocols alongside [metformin](/compound/metformin), [NMN](/compound/nmn), [TUDCA](/compound/tudca), [NAC](/compound/nac), [CoQ10](/compound/coq10), [curcumin](/compound/curcumin), and other evidence-based interventions.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/berberine" }, { "id": "24059583-b8ba-4dae-8114-269064189ea0", "slug": "beta-carotene", "name": "Beta-carotene", "aliases": [ "Beta-carotene", "beta,beta-Carotene", "all-trans-beta-carotene", "9-cis-beta-carotene", "15-cis-beta-carotene", "Provitamin A", "Carotene", "Natural beta-carotene", "Synthetic beta-carotene", "Dunaliella salina extract", "Mixed carotenoids", "Food orange 5", "E160a", "BetaTene", "CaroCare" ], "category": "Carotenoid", "description": "\nBeta-carotene is the most prominent provitamin A carotenoid and one of the most-studied dietary pigments in human nutrition. Chemically it is (all-E)-beta,beta-carotene — two symmetric beta-ionone rings connected by a central 18-carbon polyene chain with 11 conjugated double bonds. This symmetric bicyclic structure, with identical beta-ionone rings at both ends, distinguishes beta-carotene from its close dietary relatives: alpha-carotene has one beta-ring and one epsilon-ring; gamma-carotene has one beta-ring and an open-chain end; lycopene is fully acyclic with both ends as open isoprenoid chains; lutein and zeaxanthin are the hydroxylated xanthophyll counterparts. Only provitamin A carotenoids with at least one unsubstituted beta-ionone ring can be enzymatically cleaved to retinal (vitamin A) by the human enzyme beta-carotene 15,15'-oxygenase 1 (BCO1); beta-carotene has two such rings and is the most efficient dietary source of vitamin A among carotenoids.\n\nThe dual role as an antioxidant and as a vitamin A precursor makes beta-carotene distinct from other dietary carotenoids. Unlike lycopene (no vitamin A activity), lutein and zeaxanthin (no vitamin A activity, eye-specific concentration), and astaxanthin (no vitamin A activity, systemic xanthophyll), beta-carotene contributes to vitamin A status in populations where preformed vitamin A intake is low. This is the primary nutritional rationale for beta-carotene fortification of food and for its use in vitamin A deficiency prevention programs in developing countries, particularly through Golden Rice and food fortification in sub-Saharan Africa and South Asia. Historical vitamin A intake, assessed in retinol activity equivalents (RAE), treats beta-carotene as contributing 1 RAE per 12 mcg of dietary beta-carotene (or 1 RAE per 24 mcg of other provitamin A carotenoids). This conversion reflects typical BCO1 cleavage efficiency in mixed dietary matrix and is substantially less efficient than preformed vitamin A from animal sources.\n\nThe evidence landscape for beta-carotene supplementation underwent a major rethink following two landmark trials published in 1996. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study Group 1994, 1996) in 29,133 Finnish male smokers found that beta-carotene 20 mg daily increased lung cancer incidence by 18% and total mortality by 8%. The Beta-Carotene and Retinol Efficacy Trial (CARET, Omenn 1996 NEJM PMID 8602180) in 18,314 heavy smokers and asbestos-exposed workers found that beta-carotene 30 mg plus retinol 25,000 IU daily increased lung cancer incidence by 28% and total mortality by 17%, leading to early termination of the trial. The Physicians' Health Study (Hennekens 1996 NEJM PMID 8602179) in 22,071 predominantly non-smoking male physicians found that beta-carotene 50 mg every other day for 12 years had no effect on cancer or cardiovascular disease, providing reassurance that the smoker-specific signal did not extend to non-smokers.\n\nThese trials transformed beta-carotene from a promising chemopreventive agent into a supplement with specific contraindication in smokers and former smokers. The AREDS2 trial (Chew 2013 JAMA PMID 23644932) replaced beta-carotene with lutein plus zeaxanthin in the second-generation AREDS formulation specifically because of the smoker safety concern. Current expert recommendations universally discourage isolated high-dose beta-carotene supplementation in current or former smokers, while dietary beta-carotene through food (carrots, sweet potatoes, pumpkin, leafy greens) is considered safe and beneficial in all populations.\n\nFor non-smoking adults, beta-carotene remains a valid supplementation option within a multi-carotenoid stack, particularly for vitamin A status support in populations with low preformed vitamin A intake, for skin photoprotection, and for general antioxidant coverage. Dietary sources of beta-carotene are abundant: carrots contain 8-12 mg per 100 g, sweet potatoes 6-12 mg, kale 9 mg, spinach 5-6 mg, pumpkin 3-5 mg, apricots and mangoes 1-2 mg, cantaloupe 2-3 mg. A typical Western diet provides 2-5 mg of beta-carotene daily from these sources. Supplemental doses range from 3 mg (typical multivitamin) to 25 mg (standalone beta-carotene or mixed carotenoid formulations).\n\nCommercial beta-carotene for supplementation is produced by three routes: extraction from the microalga Dunaliella salina (natural 9-cis and all-trans isomer mixture, richest in 9-cis-beta-carotene which is not present in synthetic preparations), extraction from Blakeslea trispora fungal fermentation, and chemical synthesis (all-trans isomer only, historically used in CARET and ATBC). The Dunaliella-derived natural beta-carotene (BetaTene, Lyc-O-Beta natural, BASF natural beta-carotene) is often preferred because natural isomer mixtures have different bioavailability and tissue distribution compared to purely synthetic all-trans material, and because the natural preparation includes accompanying carotenoids (alpha-carotene, zeaxanthin traces) and tocopherols that may modulate the oxidative chemistry in more physiologic ways. Notably, the ATBC and CARET trials used synthetic all-trans-beta-carotene, and whether natural Dunaliella-derived beta-carotene would have produced the same smoker signal has been debated without definitive resolution; conservative practice treats natural and synthetic equivalently for the smoker contraindication.\n\nFor bodyhackguide.co users, beta-carotene occupies a specific place in the nutritional landscape: vitamin A status support in vegetarian/vegan populations with limited preformed vitamin A intake, skin photoprotection when combined with other carotenoids, and general antioxidant stacking for non-smokers. It pairs with [lutein](/compound/lutein) and [zeaxanthin](/compound/zeaxanthin) (eye-specific xanthophylls without vitamin A activity), [lycopene](/compound/lycopene) (prostate/cardiovascular acyclic carotenoid), [astaxanthin](/compound/astaxanthin) (systemic xanthophyll), [vitamin-e](/compound/vitamin-e) (membrane antioxidant synergism), and preformed [vitamin-a](/compound/vitamin-a) (retinyl palmitate for populations needing guaranteed vitamin A status). The canonical recommendation is to prioritize dietary beta-carotene intake through colorful plant foods, to avoid standalone high-dose beta-carotene supplementation in current and former smokers, and to use moderate doses (3-10 mg daily) within mixed carotenoid formulations when supplementation is desired in non-smokers.\n", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/beta-carotene" }, { "id": "c4ec90ce-cd92-467f-950e-c6d6444f6939", "slug": "beta-sitosterol", "name": "Beta-Sitosterol", "aliases": [ "β-sitosterol", "22,23-Dihydrostigmasterol", "Sitosterol", "Phytosterol", "Harzol (German pharma)", "Azuprostat (German pharma)", "Plant sterol", "24α-Ethylcholesterol" ], "category": "Herbal", "description": "**Beta-sitosterol (β-sitosterol)** is the **most abundant plant sterol** in human diets and nature, structurally similar to cholesterol but with an ethyl group addition at C-24 position, making it a **phytosterol** rather than a zoosterol. It occurs widely in plant foods — nuts, seeds, vegetable oils, legumes, and grains — with typical Western dietary intake of 150-400mg/day. As a **clinical supplement at pharmacologic doses (60-130mg/day for BPH; 1.5-3g/day for cholesterol reduction)**, beta-sitosterol has two well-established therapeutic applications: (1) **symptomatic improvement of benign prostatic hyperplasia (BPH)** with moderate evidence base including the landmark **Berges et al. 1995** German RCT; and (2) **cholesterol reduction** through competitive inhibition of intestinal cholesterol absorption, with evidence strong enough that plant sterol/stanol-fortified foods carry FDA-authorized health claims for heart disease risk reduction. Beta-sitosterol also has emerging evidence for **androgenetic alopecia** (when used topically or as part of complete hair-loss regimens), **immune support**, and **anti-inflammatory** applications.\n\nUnlike many herbal supplements where clinical effects remain speculative, beta-sitosterol has **mechanistically coherent, measurable, and reproducible clinical effects** on two specific outcomes: (1) cholesterol — plant sterols reliably lower LDL cholesterol by 6-15% at doses of 2-3g/day via intestinal absorption competition; (2) BPH urinary symptoms — **Berges 1995** (*The Lancet*) randomized 200 men with symptomatic BPH to beta-sitosterol 20mg three times daily (60mg/day) versus placebo for 6 months, finding significant improvements in **urinary flow rate (+5.2 mL/sec)**, **residual volume reduction**, and **International Prostate Symptom Score**. Subsequent **Klippel et al. 1997** (*Br J Urol*) with 177 men using 130mg/day confirmed these findings. **Wilt et al. 1999** (*BJU Int*) meta-analysis pooled available data, confirming beta-sitosterol's modest but real BPH benefit. Unlike saw palmetto, whose larger follow-up trials (STEP, CAMUS) produced negative results, beta-sitosterol's evidence base has not been overturned by larger better-designed trials — though the total number of subjects studied remains modest compared to pharmaceutical BPH treatments.\n\n**The unique \"dual application\" profile** — BPH urinary symptom relief + cholesterol reduction — makes beta-sitosterol particularly useful for **middle-aged and older men who often have both conditions simultaneously**. A man with mild BPH symptoms and borderline cholesterol can potentially address both with a single supplement, particularly when combined with lifestyle interventions. The cholesterol effect requires higher doses (2-3g/day from fortified foods or supplements) than BPH effect (60-130mg/day), so users interested in both benefits need to address dose accordingly.\n\n**Regulatory status varies**: In **Germany**, beta-sitosterol (as Harzol or Azuprostat preparations) is a **prescription phytopharmaceutical** for BPH with specific indications and reimbursement. In the **United States, Canada, and most countries**, beta-sitosterol is a **dietary supplement** available without prescription. Plant sterol/stanol esters (including beta-sitosterol esters) in margarines, yogurts, and fortified foods have **FDA-authorized health claims** in the US (\"Plant sterols may reduce the risk of heart disease\") when consumed at specified levels with dietary fat sources. This regulatory acknowledgment reflects the strong evidence base for cholesterol effects.\n\n**Beta-sitosterol and other phytosterols as a class**: Beta-sitosterol is the most abundant phytosterol but is typically found in mixtures with campesterol, stigmasterol, and other sterols in plant foods and supplements. Most clinical evidence and supplements use \"beta-sitosterol\" referring to these mixtures with beta-sitosterol as the predominant component (50-70% of total sterol content). **Plant stanols** (saturated form — sitostanol, campestanol) produced by hydrogenation are similarly effective and slightly more potent on a per-dose basis for cholesterol effects.\n\n**Clinical evidence has evolved with some refinements**: (1) **BPH** — Berges and Klippel established efficacy at 60-130mg/day; later meta-analyses (Wilt 1999) confirmed modest benefit; most subsequent research has focused on combination products rather than monotherapy; (2) **Cholesterol** — multiple large trials and meta-analyses (Demonty 2009, Ras 2014) confirm 6-15% LDL reduction at 1.5-3g/day; effect is additive to statins for further LDL reduction; (3) **Cardiovascular outcomes** — epidemiological and dietary intervention studies associate plant sterol intake with reduced cardiovascular events, though direct cardiovascular outcome RCTs specifically of plant sterol supplementation are limited. There is **ongoing debate about whether elevated serum plant sterols themselves might contribute to atherosclerosis** — the \"sitosterolemia paradox\" — but this concerns rare genetic sitosterolemia patients and is not a concern for normal absorbers consuming typical plant sterol doses.\n\nSee also [Saw Palmetto](/compound/saw-palmetto), [Finasteride](/compound/finasteride), [Stinging Nettle](/compound/stinging-nettle), [Pygeum](/compound/pygeum), [Lycopene](/compound/lycopene), [Zinc](/compound/zinc), [Red Yeast Rice](/compound/red-yeast-rice), [Berberine](/compound/berberine), and [Niacin](/compound/niacin) for adjacent prostate-health and lipid-management compounds. This is educational content, not medical advice — both BPH and dyslipidemia warrant physician-level evaluation and management particularly given effective evidence-based alternatives exist for both.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 5651, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/beta-sitosterol" }, { "id": "0b202a13-dc30-4689-a98a-290f469b3143", "slug": "biotin", "name": "Biotin", "aliases": [ "B7", "B8", "Vitamin B7", "Vitamin H", "Vitamin B8", "Coenzyme R", "D-biotin", "Biotin 5-adenylate", "Biocytin", "Biotinyl-AMP", "MD1003", "Hi-dose biotin", "Biosan", "Biogel", "Vitamin Bw", "Factor R", "Factor W", "Factor X", "Bios II" ], "category": "Vitamin", "description": "Biotin (vitamin B7, also called vitamin H from the German *Haut* for \"skin\" and historically named coenzyme R, factor W, factor R, factor X, vitamin Bw, or Bios II in various discovery-era nomenclatures) is a water-soluble vitamin that serves as the covalently-attached prosthetic group for **five carboxylase enzymes** in human metabolism: pyruvate carboxylase, acetyl-CoA carboxylase 1, acetyl-CoA carboxylase 2, propionyl-CoA carboxylase, and 3-methylcrotonyl-CoA carboxylase. These enzymes sit at central nodes of gluconeogenesis, fatty acid synthesis, fatty acid oxidation, amino acid catabolism, and odd-chain fatty acid metabolism — so biotin has a quiet but essential metabolic role despite its obscurity in popular nutrition discourse (which emphasizes biotin primarily as a hair/skin/nails supplement, an indication with remarkably thin evidence base). The adult adequate intake is 30 μg/day for men and women, 30 μg/day in pregnancy, 35 μg/day in lactation — expressed as AI rather than RDA because epidemiological intake data are insufficient to derive a full RDA. There is no established tolerable upper intake level because biotin has an exceptionally wide therapeutic window; pharmacologic doses of 5-20 mg/day are used for biotinidase deficiency without toxicity, and doses up to 300 mg/day were used in the failed MS MD1003 trial without dose-limiting adverse effects other than the well-documented laboratory assay interference. Primary biotin deficiency from inadequate dietary intake is extraordinarily rare because (a) colonic bacteria synthesize substantial quantities of biotin that are partially absorbed by the host, (b) dietary biotin is widely distributed in eggs, dairy, meat, fish, nuts, seeds, whole grains, and vegetables, and (c) the metabolic turnover of biotin is slow. When biotin deficiency does occur, it arises from specific circumstances: **raw egg white consumption** (the classical \"egg-white injury\" syndrome of the 1920s-1940s, in which the glycoprotein avidin in raw egg whites binds biotin with an affinity ~10^15 M^-1 — one of the strongest non-covalent interactions in biology — blocking intestinal absorption; cooking denatures avidin and eliminates the problem), **long-term anticonvulsant therapy** (phenytoin, carbamazepine, phenobarbital, primidone increase biotin catabolism and impair biotin-enzyme complex formation), **chronic hemodialysis**, **total parenteral nutrition without biotin supplementation**, **hyperemesis gravidarum**, **isotretinoin** (modest effect), and **chronic alcoholism**. Symptomatic biotin deficiency produces a distinctive clinical picture of **alopecia** (progressive hair loss including eyebrows and body hair), **perioral and periorificial scaly erythematous dermatitis** (involving the nose, mouth, eyes, and perineum), **glossitis** with red inflamed tongue, **conjunctivitis**, **ataxia**, **seizures**, and **lactic acidosis** in severe cases — the picture of combined carboxylase deficiency from functional biotin insufficiency. Two monogenic disorders of biotin metabolism produce neonatal/early-childhood presentations that respond dramatically to pharmacologic biotin: **biotinidase deficiency** (BTD, 1 in 60,000 births, included in universal newborn screening in most US states since 2006; treated lifelong with oral biotin 5-10 mg/day, with excellent clinical outcomes if diagnosed pre-symptomatically) and **holocarboxylase synthetase deficiency** (HCS deficiency, rarer, presenting in the neonatal period with severe lactic acidosis and multicarboxylase deficiency; treated with higher-dose biotin 10-80 mg/day, with variable response that is generally better for early-onset/severe mutations). The supplement and clinical uses of biotin cluster in several domains. **Biotinidase deficiency** treatment is the highest-evidence indication — lifelong oral biotin 5-10 mg/day produces complete resolution of the multicarboxylase deficiency phenotype and excellent long-term neurodevelopmental outcomes, with rare residual features (sensorineural deafness, optic atrophy) in patients treated late. **Holocarboxylase synthetase deficiency** requires higher biotin doses and response varies by genotype. **Hair, skin, and nails** is the most commercially important but evidence-weakest indication: despite enormous consumer demand and aggressive marketing of high-dose biotin (2,500-10,000 μg/day, sometimes up to 30,000 μg/day) for hair loss, nail brittleness, and cosmetic skin concerns, the 2017 complete review by Patel (PMID 28879195) found the evidence base limited to a small number of case reports and open-label studies with quality issues; placebo-controlled trials in healthy individuals with uncomplicated hair/nail complaints are essentially absent. The evidence that does exist is for biotin in diagnosed biotin deficiency, in specific conditions like brittle nail syndrome (where 2.5 mg/day may help based on limited data), and in uncombable hair syndrome (Colombo 1990). Most marketed high-dose biotin for cosmetic use is a placebo effect overlaying the normal course of hair and nail growth. **Progressive multiple sclerosis** was the target of the high-dose MD1003 biotin (300 mg/day) program developed by MedDay Pharmaceuticals; the MS-SPI trial (Tourbah 2016, PMID 27589059) showed modest benefit in primary and secondary progressive MS, generating substantial enthusiasm, but the larger SPI2 trial completed in 2020 failed to replicate the benefit, and the MD1003 program was subsequently discontinued. High-dose biotin is not currently recommended for progressive MS. **Biotin-thiamine-responsive basal ganglia disease** treatment combines biotin and thiamine at pharmacologic doses (see the [Thiamine](/compound/thiamine) entry for this SLC19A3 genetic disorder). **Laboratory assay interference** is a critical safety concern distinct from direct biotin toxicity: the FDA issued a safety communication in 2017 warning that high-dose biotin supplementation can produce falsely elevated or falsely low results on streptavidin-biotin-based immunoassays used for troponin, TSH, hCG, vitamin D, sex hormones, thyroid panels, and cardiac markers — a genuinely important clinical concern in emergency medicine where false troponin readings can delay MI diagnosis. Patients should discontinue biotin supplementation for at least 24-72 hours (and sometimes up to a week) before relevant laboratory testing, and should always disclose biotin use to clinicians ordering labs. Food sources of biotin concentrate in egg yolks (cooked eggs; raw egg whites are problematic because of avidin), beef liver (1 ounce provides ~50% of adult AI), salmon, pork, chicken, yeast (nutritional yeast and Brewer''s yeast), nuts and seeds (almonds, sunflower seeds, peanuts), sweet potatoes, avocado, cauliflower, spinach, and mushrooms. See also [Thiamine](/compound/thiamine) for the biotin-thiamine-responsive basal ganglia disease partnership, [Niacin](/compound/niacin) for the B-complex context, [Vitamin B6](/compound/vitamin-b6), [Folate](/compound/folate), [Vitamin B12](/compound/vitamin-b12), [Riboflavin](/compound/riboflavin), and [Choline](/compound/choline) for the broader B-complex network, [Alpha-Lipoic Acid](/compound/alpha-lipoic-acid) for the parallel cofactor role in PDH/αKGDH (lipoic acid is structurally reminiscent of biotin as a carboxylic-acid-terminating heterocyclic ring system — though biochemically distinct), and [CoQ10](/compound/coq10) for the shared mitochondrial bioenergetic context. This overview is educational only and is not medical advice — the clinically important practical caution is laboratory assay interference, not direct toxicity.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/biotin" }, { "id": "f6572acf-1a7b-4ec2-a23c-05ca8caa141e", "slug": "boron", "name": "Boron", "aliases": [ "B", "Boric acid", "H3BO3", "Borate", "BO3", "Tetraborate", "B4O7", "Sodium borate", "Sodium tetraborate", "Borax", "Na2B4O7", "Boron citrate", "Boron glycinate", "Boron aspartate", "Boron amino acid chelate", "Boron picolinate", "Calcium fructoborate", "Fructoborate", "FruiteX-B", "Sodium borohydride", "Boron nitride", "Ulexite", "Colemanite", "Kernite", "Phenylboronic acid", "Boronic acid", "Organoboron" ], "category": "Mineral", "description": "\nBoron is an ultra-trace element whose nutritional status in humans sits in a distinctive regulatory gray zone: the Institute of Medicine (US) has not established a recommended dietary allowance (RDA) or estimated average requirement (EAR) for boron because the evidence for essentiality in humans does not meet the strict criteria applied to calcium, iron, or zinc, yet the IOM, the European Food Safety Authority (EFSA), and the World Health Organization (WHO) all set tolerable upper intake levels (ULs) — implicitly acknowledging that boron has biological activity and dose-response safety concerns. WHO in 2009 classified boron as \"probably essential\" based on animal deficiency studies and human intervention data. Boron is the only trace mineral of the ultra-trace category (along with nickel, silicon, vanadium, and arsenic at trace levels) where a substantial body of controlled human supplementation evidence exists — particularly for bone health, sex hormone metabolism, and joint/inflammatory outcomes — creating a paradox where clinical data outpace formal regulatory essentiality status. For the BodyHackGuide audience, this translates to: boron supplementation at 3-10 mg/day has plausible benefit for bone, mineral, and hormonal health, a wide safety margin at physiologic doses, and relatively low cost, making it one of the more defensible optional trace minerals in a structured supplementation protocol.\n\nBoron is the fifth element on the periodic table, a metalloid situated between beryllium and carbon, with atomic number 5 and atomic mass 10.81 (natural isotope mix of ^10B and ^11B). Elemental boron is extremely rare in nature — boron occurs almost exclusively as borate minerals (borax/sodium tetraborate, ulexite, colemanite, kernite) concentrated in arid basin deposits (Turkey, California, Chile, Argentina, Russia hold the world's major boron reserves). Humphry Davy and Gay-Lussac/Thénard independently isolated elemental boron in 1808. Borates have been used since antiquity for glazing pottery (borax glasses), food preservation (banned in most jurisdictions in the 20th century due to toxicity concerns at high doses), and as mild antiseptics (boric acid for eyewash and topical antifungal applications). The modern boron nutrition literature emerged primarily from Forrest Nielsen's work at the USDA Grand Forks Human Nutrition Research Center in the 1980s-1990s, which demonstrated that dietary boron deprivation in postmenopausal women produced measurable changes in calcium, magnesium, and sex hormone metabolism that were reversed by supplementation (Nielsen 1987 FASEB is the seminal citation). Subsequent trials by Naghii and others extended the evidence base to bone turnover, arthritis, and androgen metabolism.\n\nThe chemistry of boron in biological systems is distinctive. Boron exists almost exclusively as boric acid [B(OH)3] and borate ion [B(OH)4^-] at physiologic pH (boric acid pKa = 9.24; circulating plasma at pH 7.4 contains approximately 98% as boric acid, 2% as borate). Boric acid is an extremely weak monobasic Lewis acid (not Bronsted acid) that acts by accepting a hydroxide ion rather than donating a proton. The functional chemistry relevant to biology is boron's propensity to form tetrahedral diester bonds with cis-diol groups (adjacent hydroxyl groups on sugars, polyols, and other diol-containing biomolecules). This diol-complexing chemistry is the basis for boron's hypothesized interactions with nicotinamide adenine dinucleotide (NAD+, which contains ribose diols), S-adenosylmethionine, serotonin, and glycoproteins. It also underlies the biological activity of boron-containing drugs (bortezomib for multiple myeloma exploits boronic acid proteasome binding; tavaborole for onychomycosis; crisaborole for atopic dermatitis).\n\nThe adult human body contains approximately 18-20 mg of boron, distributed predominantly in bone (roughly half), with smaller amounts in spleen, thyroid, and parathyroid glands. Dietary boron intake in typical Western populations is 0.5-3.5 mg/day (median around 1.2-1.5 mg/day in the US NHANES data; intake in regions with high boron soil and water like parts of Turkey can exceed 8-10 mg/day without apparent harm). The IOM UL for boron is 20 mg/day for adults; pregnancy UL 17-20 mg/day (lower values for younger pregnant women). Major dietary sources include fruits (especially dried fruits, prunes, raisins, dates — approximately 0.5-4 mg per serving), nuts (almonds, hazelnuts, 1-3 mg per ounce), legumes, wine, coffee, and certain vegetables (avocado, broccoli). The extreme variability in soil boron between regions produces corresponding variability in dietary intake. Municipal water typically contributes 0.03-0.15 mg per liter. Deficiency in free-living adults consuming mixed diets is uncommon; low-intake populations (below 0.5 mg/day) may benefit from supplementation, particularly if they also have low intakes of other bone-relevant nutrients ([calcium](/compound/calcium), [magnesium](/compound/magnesium), [vitamin D](/compound/vitamin-d3), [vitamin K2](/compound/vitamin-k2)).\n\nBoron absorption from the gastrointestinal tract is efficient. Approximately 85-95% of ingested boric acid or borate is absorbed, primarily in the upper small intestine, via passive diffusion and possibly facilitated transport. Food matrix effects on absorption are modest. Absorbed boron circulates predominantly as boric acid (98%), distributes to all tissues within 24 hours, and is excreted almost exclusively via urine (90-95% of intake) with a plasma half-life of approximately 21 hours and elimination half-life of 1-4 days. The efficient absorption combined with efficient urinary excretion means that boron does not bioaccumulate at physiologic doses — steady-state plasma boron at 3-10 mg/day supplementation reaches stable concentrations within 1-2 weeks and declines similarly after discontinuation.\n\nThe clinical evidence for boron supplementation clusters in three main domains: bone and mineral metabolism, sex hormone modulation, and inflammation/arthritis. The bone evidence began with Nielsen 1987 — a controlled metabolic ward study in which postmenopausal women on a low-boron diet (0.25 mg/day) for 119 days followed by supplementation to 3 mg/day for 48 days demonstrated reduced urinary calcium and magnesium excretion, increased serum 17-beta-estradiol and testosterone, and trends toward improved calcium/magnesium balance with supplementation. Subsequent trials (Naghii 2011 J Trace Elem Med Biol with 10 mg/day boron raising testosterone by approximately 28% and free testosterone by 11.4% over one week in 8 men; Nielsen 1992 and 1994 bone turnover studies; Meacham 1995 examining boron and vitamin D-deficient women) have generally supported modest effects on bone mineral markers, though the trials are small (typically 8-30 subjects), short-duration (1-4 weeks to a few months), and heterogeneous in population (postmenopausal women, athletic men, vitamin D-deficient subjects). No long-term (1+ year) fracture-endpoint trial of boron supplementation has been conducted — this is the single most important evidence gap for the bone application.\n\nThe sex hormone effects are particularly interesting and have driven much of boron's popularity in the bodybuilding and anti-aging supplementation communities. Multiple small trials have shown that boron supplementation at 6-10 mg/day for 1-8 weeks raises total and free testosterone, reduces sex hormone binding globulin (SHBG), elevates DHT, and modestly raises estradiol, with concurrent decreases in inflammatory markers (hs-CRP, IL-6, TNF-alpha) and reductions in homocysteine. The magnitude is modest — perhaps 10-30% in testosterone, which is within the range of normal diurnal variation — and the durability beyond a few weeks has not been established. Whether these effects translate to clinical outcomes (muscle mass, bone density, libido, fertility) over years is unknown. Mechanism proposals include SHBG binding displacement, enhanced aromatase efficiency, reduced testosterone metabolism and clearance, and vitamin D-mediated pathways. The effect size has led some supplementation guides to characterize boron as \"mini-TRT at 10 mg/day,\" which overstates the evidence.\n\nFor arthritis and joint health, epidemiologic observations from the 1960s-1980s noted that boron-rich regions (some Pacific islands, parts of Turkey, Israel) had osteoarthritis prevalence of 0-10% while boron-poor regions (Jamaica, Mauritius) showed 50-70% prevalence. Controlled trials have been smaller but suggestive: Travers 1990 Australia double-blind trial (20 subjects, 6 mg boron/day for 8 weeks) showed significant improvement in pain scores and joint function in the boron group vs. placebo. Calcium fructoborate (a specific organically-complexed boron-carbohydrate) has been studied in the 2010s for knee osteoarthritis with positive symptomatic trials (Pietrzkowski 2014 with statistically significant WOMAC improvements at 110-220 mg/day of calcium fructoborate, delivering 3-6 mg elemental boron plus the diester complex itself thought to have distinct anti-inflammatory activity). The calcium fructoborate evidence is more strong than elemental borate for arthritis outcomes.\n\nBodyHackGuide's take: boron is one of the most defensible \"optional but reasonable\" trace mineral supplements. At 3-10 mg/day (meeting or slightly exceeding dietary adequacy), the evidence suggests modest benefits for bone mineral economy, sex hormone homeostasis (particularly in the aging male), and joint/inflammatory signaling, with a very wide margin of safety (UL 20 mg/day vs. supplementation at 3-10 mg/day). It is inexpensive (a year's supply under $30 at typical doses). It does not require cycling, does not have significant drug interactions at physiologic doses, and combines well with other bone- and joint-relevant nutrients. The primary caveats are that the evidence base is almost entirely short-term (weeks to months) and in small samples, that quality control for raw material purity matters (boron from mineral sources can carry heavy metal contamination — arsenic, lead — if sourcing is poor), and that high-dose boron (above 20 mg/day) should be strictly avoided due to reproductive and developmental toxicity concerns from animal data and rare human overdose reports. For a structured bone health stack in the aging adult, 3-6 mg/day boron alongside calcium, magnesium, vitamin D, vitamin K2, and protein is a sensible addition. For male androgen support, 6-10 mg/day is within safety limits and has the best evidence for testosterone modulation, though the clinical relevance of small testosterone shifts in eugonadal men is debated.\n", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 322, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/boron" }, { "id": "980a1eef-e38c-41fa-a773-6070b5a16d81", "slug": "boswellia", "name": "Boswellia", "aliases": [ "Boswellia serrata", "Indian frankincense", "Salai guggul", "Shallaki", "AKBA", "Boswellic acids" ], "category": "Herbal", "description": "**Boswellia** — the aromatic gum resin of the tree **Boswellia serrata**, known in Ayurvedic tradition as **Shallaki** or **Salai guggul** and in English as **Indian frankincense** — is one of the best-characterized non-NSAID anti-inflammatory botanicals in the modern clinical literature, and one of the few whose mechanism is sufficiently well-understood at the molecular level to justify most of its clinical positioning. The central and distinguishing feature of boswellia — the reason it has been studied for osteoarthritis, rheumatoid arthritis, inflammatory bowel disease, asthma, and peritumoral cerebral edema across nearly three decades of clinical trials — is that its active constituents, the **boswellic acids**, and particularly **acetyl-11-keto-beta-boswellic acid (AKBA)**, are **selective 5-lipoxygenase (5-LOX) inhibitors**. They suppress **leukotriene** biosynthesis without inhibiting cyclooxygenase (COX-1 or COX-2), which means boswellia addresses a branch of inflammatory biology that NSAIDs and [curcumin](/compound/curcumin)-class agents largely leave untouched, and does so without the gastric, renal, and cardiovascular risk profile that has defined NSAID clinical practice for decades.\n\nChemically, boswellia gum resin is a complex mixture of **pentacyclic triterpenic acids** — the boswellic acids — alongside essential oils, sugars, and polysaccharides. Six named boswellic acids have been isolated and characterized: **beta-boswellic acid (BA)**, **acetyl-beta-boswellic acid (ABA)**, **11-keto-beta-boswellic acid (KBA)**, **acetyl-11-keto-beta-boswellic acid (AKBA)**, **alpha-boswellic acid**, and **acetyl-alpha-boswellic acid**. Of these, **AKBA is the most potent 5-LOX inhibitor and is responsible for the majority of the anti-inflammatory effect** at realistic clinical exposures. Standard herbal extracts of boswellia gum resin are standardized to **≥65% total boswellic acids** (the traditional pharmacopoeial specification), but most modern clinical research uses enhanced extracts standardized to specific AKBA content — the two most clinically studied being **5-Loxin (30% AKBA-standardized)** and **Aflapin (Boswellia serrata extract selectively enriched for AKBA and formulated with a non-volatile oil fraction that improves bioavailability)**, both developed by Laila Impex / Sabinsa's collaborators in India. The distinction between generic \"65% boswellic acids\" and AKBA-enriched extracts is the single most important quality variable for clinical efficacy.\n\n**Boswellia's therapeutic niche** — and what most distinguishes it from the broader anti-inflammatory botanical category — is that it modulates the **leukotriene arm of the arachidonic acid cascade**. When membrane phospholipids are hydrolyzed by phospholipase A2 to release arachidonic acid, that arachidonic acid is processed by two distinct enzyme families: **cyclooxygenases (COX-1 and COX-2)**, which generate prostaglandins and thromboxanes, and **5-lipoxygenase (5-LOX)**, which generates leukotrienes (LTB4, LTC4, LTD4, LTE4). NSAIDs, aspirin, celecoxib, and COX-2 inhibitors suppress the COX branch. **Boswellia, via AKBA, selectively suppresses the 5-LOX branch**. The practical consequence: boswellia reduces neutrophil-mediated inflammation, bronchoconstriction (leukotrienes are potent bronchoconstrictors), edema, and leukotriene-driven joint inflammation — without producing the COX-related gastric erosions, platelet dysfunction, renal hypoperfusion, or cardiovascular signal that dog NSAIDs. For patients with osteoarthritis who cannot tolerate NSAIDs, patients with IBD whose disease is partially leukotriene-driven, and patients with asthma whose symptoms reflect bronchial leukotriene tone, this is a meaningfully different pharmacological intervention than adding another COX-focused agent.\n\n**The clinical evidence base**, which has built steadily since the early 1990s, spans multiple indications. **Knee osteoarthritis** is the best-developed — **Kimmatkar 2003** (*Phytomedicine* PMID: 12622457) showed in a 30-patient 8-week crossover RCT that Boswellia serrata extract significantly reduced knee pain, increased knee flexion, and improved walking distance compared with placebo. **Sengupta 2008** (*Arthritis Res Ther* PMID: 18667054) showed in a 75-patient 90-day RCT that 5-Loxin (Boswellia serrata extract standardized to 30% AKBA) produced significant, dose-responsive improvements in pain, stiffness, and physical function compared with placebo, with benefit apparent by 7 days in some measures and continuing through 90 days. **Sengupta 2010** (*Int J Med Sci* PMID: 21060724) compared Aflapin head-to-head with 5-Loxin — both active extracts outperformed placebo; Aflapin showed earlier onset (by day 5-7) and slightly greater effect magnitude than 5-Loxin at the same 100mg dose. **Inflammatory bowel disease** has two notable trials — **Gupta 1997** (*Eur J Med Res* PMID: 9049593) in ulcerative colitis showed 82% of boswellia-treated patients achieved remission vs 75% with sulfasalazine (non-inferiority with better tolerability), and **Gerhardt 2001** (*Z Gastroenterol* PMID: 11215357) showed the H15 boswellia extract was non-inferior to mesalazine in active Crohn's disease. **Bronchial asthma** — **Gupta 1998** (*Eur J Med Res* PMID: 9810030) showed 70% of boswellia-treated asthma patients improved (reduced symptom frequency, increased FEV1) vs 27% with placebo over 6 weeks. And in neuro-oncology, **Kirste 2011** (*Cancer* PMID: 21287538) showed boswellia 4200mg/day significantly reduced **peritumoral cerebral edema** in brain tumor patients receiving radiotherapy, with >75% edema reduction in 60% of the boswellia arm vs 26% of placebo — opening a potential role for boswellia as a steroid-sparing adjunct in brain tumor care.\n\n**Who uses boswellia and why** varies by context. In **osteoarthritis (the dominant use case)**, boswellia is positioned as a non-NSAID alternative for chronic joint pain — particularly valuable for patients with NSAID-induced gastritis, chronic kidney disease (where NSAID use is limited by renal concerns), cardiovascular risk (where long-term NSAID use raises MI and stroke risk), or simply preference for a botanical agent. Typical daily doses are **100-400mg of AKBA-standardized extract (Aflapin or 5-Loxin)** or **1200-1500mg of 65% boswellic acid extract** — a substantial difference in pill burden and cost. Boswellia is often combined with [curcumin](/compound/curcumin) (which addresses the COX branch via a different mechanism) and [quercetin](/compound/quercetin) for complete anti-inflammatory coverage. In **inflammatory bowel disease**, boswellia is used either as primary therapy in mild disease or as steroid- and mesalazine-sparing adjunct in moderate disease — typical doses 350-900mg three times daily. In **asthma**, boswellia is occasionally layered onto conventional controller therapy (inhaled corticosteroids, leukotriene receptor antagonists) with modest additive benefit. In **brain tumor peritumoral edema**, high-dose boswellia (1500mg three times daily = 4500mg/day) may reduce steroid requirements during radiotherapy — a specialty application requiring oncologist involvement.\n\n**Traditional use context** anchors the modern research. **Ayurvedic medicine** has used Boswellia serrata gum resin for at least 2000 years under the Sanskrit name **Shallaki**, indicated for joint pain (*sandhivata* — roughly equivalent to osteoarthritis), inflammatory skin conditions, asthma, and digestive complaints. The traditional preparation is the decocted or powdered gum resin, dosed in grams per day — much higher than modern standardized extract doses because the traditional preparation contains much less bioavailable AKBA per unit mass. Classical Ayurvedic texts (Charaka Samhita, Sushruta Samhita) describe its use, and it remains a cornerstone of Ayurvedic joint-care formulations today. Modern extract standardization and bioavailability enhancement (Aflapin, 5-Loxin) represent the pharmacological refinement of this long empirical tradition.\n\n**What boswellia does NOT do well** is equally important. It is **not a fast-acting analgesic** — pain relief in OA trials builds over days to weeks, not hours. It is **not a substitute for disease-modifying antirheumatic drugs (DMARDs)** in rheumatoid arthritis — evidence there is suggestive but not definitive, and patients with active RA should not substitute boswellia for methotrexate or biologics. It is **not a cure for any of its indications** — in OA, IBD, and asthma, boswellia reduces symptoms but does not reverse underlying pathology. And the magnitude of effect, while statistically significant in well-designed RCTs, is generally **modest** — useful as monotherapy in mild disease or as adjunct in moderate disease, but rarely sufficient alone for severe disease. Honest framing: boswellia is a meaningful, mechanism-distinct, generally well-tolerated anti-inflammatory with real evidence in several specific conditions — not a miracle botanical that replaces conventional therapy across the board.\n\nSee also [curcumin](/compound/curcumin), [quercetin](/compound/quercetin), [fisetin](/compound/fisetin), [ashwagandha](/compound/ashwagandha), [berberine](/compound/berberine), [rhodiola-rosea](/compound/rhodiola-rosea), [tulsi](/compound/tulsi), [EGCG](/compound/egcg), and [BPC-157](/compound/bpc-157) for the anti-inflammatory and joint-support compounds most commonly stacked with boswellia. This is educational content and not medical advice — boswellia has real pharmacological effects, meaningful drug-interaction potential (particularly with CYP inducers and with anticoagulants at high doses), and is generally safer than NSAIDs for chronic inflammation but should be considered a genuine therapeutic agent warranting physician input when any prescription medication is concurrent or when it is being used in the context of organized medical care for IBD, asthma, or neuro-oncology conditions.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 200, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/boswellia" }, { "id": "a1000000-0000-0000-0000-000000000001", "slug": "bpc-157", "name": "BPC-157", "aliases": [ "BPC", "BPC-157 Capsules", "BPC-157 500mcg Capsules", "Pentadecapeptide", "Repair Balm", "Oral BPC-157", "BPC-157 Oral", "Body Protection Compound" ], "category": "Injury, Repair & Recovery", "description": "BPC-157 (Body Protection Compound-157) is a synthetic pentadecapeptide consisting of 15 amino acids (Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val) derived from a partial sequence of human gastric juice protein BPC. It has a molecular weight of 1419.53 Da and a CAS number of 137525-51-0. BPC-157 is classified as a stable gastric pentadecapeptide because it resists hydrolysis by gastric acid and digestive enzymes, a property that differentiates it from most bioactive peptides and enables oral bioavailability in preclinical models.\n\nAs of 2026, BPC-157 has been investigated in more than 90 published preclinical studies spanning models of gastrointestinal injury, tendon and ligament damage, nerve injury, wound healing, and organ protection. A complete review by Sikiric et al. (2011) established BPC-157 as a peptide with broad cytoprotective and regenerative properties across multiple organ systems. Subsequent work by Seiwerth et al. (2022) expanded the evidence base to include vascular protection and modulation of the nitric oxide (NO) system as a central integrative mechanism.\n\nBPC-157 is not approved by the United States Food and Drug Administration (FDA) for any therapeutic indication. It is classified under the World Anti-Doping Agency (WADA) Prohibited List category S0 (non-approved substances), making it banned in competitive sport. Despite the lack of regulatory approval, BPC-157 is widely used in the research peptide and biohacking communities, primarily administered via subcutaneous injection or oral capsule for musculoskeletal recovery and gut healing.\n\nPreclinical studies have demonstrated that BPC-157 accelerates healing of transected rat Achilles tendons, with treated animals showing superior biomechanical tendon strength at 14 days post-injury compared to controls (PMID: 30915550). In gastrointestinal models, BPC-157 has shown protective effects against NSAID-induced gastric lesions, ethanol-induced mucosal damage, and inflammatory bowel disease (IBD) analogs including experimentally induced colitis. The peptide has also demonstrated neuroprotective activity in dopaminergic and serotonergic systems, counteracting lesions caused by neurotoxins in rodent models.\n\nA 2025 pilot safety study by Lee et al. represents the first published human intravenous (IV) administration data for BPC-157. In this small cohort, IV BPC-157 was administered at escalating doses with no serious adverse events reported and no clinically significant changes in laboratory parameters (PMID: 40131143). While this study was not powered to establish efficacy, it provided the first formal human safety signal for the peptide.\n\nBPC-157 has also been shown to upregulate growth hormone receptor (GHR) expression in animal models, suggesting a possible synergistic effect when combined with growth hormone secretagogues. The peptide is typically supplied as a lyophilized powder requiring reconstitution with bacteriostatic water. Lyophilized BPC-157 should be stored at -20 degrees Celsius in a desiccated environment; once reconstituted, it should be refrigerated at 2-8 degrees Celsius and used within 28 days to maintain peptide integrity.", "half_life": "Short plasma half-life. The first formal preclinical ADME study reported an elimination half-life under ~30 minutes after IV/IM dosing in rats and dogs, with linear dose-proportional kinetics (PMID: 36588717); a 2026 biopharmaceutical review confirms this sub-30-minute plasma half-life and highlights a pharmacokinetic-pharmacodynamic disconnect, as biological effects persist for hours to days (PMID: 42198317). No full human pharmacokinetic study has been published; twice-daily dosing is empirical/community-standard rather than PK-derived.", "molecular_weight": "1419.5 g/mol (average); molecular formula C62H98N16O22", "molecular_mass": "1419.56 g/mol", "amino_acid_sequence": "Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val (GEPPPGKPADDAGLV); 15-amino-acid pentadecapeptide, a partial sequence of human gastric juice protein BPC", "administration_routes": [ "Subcutaneous", "Oral", "Intraperitoneal", "Intravenous" ], "dose_range_mcg": "200-500 mcg subcutaneous 1-2x daily (community protocols); 1-10 mcg/kg in animal studies", "dosing_frequency": "Twice daily (AM and PM) for optimal serum levels; once daily acceptable", "cycle_length": "4–12 weeks typical; 8 weeks most common. Some protocols run 4 weeks on / 2 weeks off.", "common_vial_sizes": [ "5mg", "10mg" ], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "Preclinical", "cas_number": "137525-51-0", "iupac_name": "L-valyl-L-lysyl-L-alanyl-L-arginyl-L-leucyl-L-histidyl-L-glycyl-L-lysyl-L-prolyl-L-alanyl-L-glycyl-L-glycyl-L-prolyl-L-prolyl-L-proline", "chemical_formula": "C62H98N16O22", "potential_benefits": [ "Accelerated tendon and ligament healing with improved biomechanical strength in preclinical soft-tissue injury models (PMID: 30915550)", "Gastric and GI mucosal cytoprotection against ethanol-induced lesions, mediated in part by the nitric oxide system (PMID: 30279308)", "Healing of cysteamine-induced colitis and colon anastomosis in preclinical inflammatory bowel disease models (PMID: 24304574)", "Neuroprotection with dopaminergic and nitric oxide-system modulation in central nervous system injury models such as stroke and dopamine-receptor blockade (PMID: 34380875)", "Promotion of angiogenesis via VEGFR2 up-regulation, internalization, and VEGFR2-Akt-eNOS signaling in rat hind-limb ischemia and endothelial assays (PMID: 27847966)", "Tendon fibroblast outgrowth, cell survival, and migration through FAK-paxillin pathway activation (PMID: 21030672)", "Growth hormone receptor up-regulation in tendon fibroblasts, potentiating growth hormone's proliferative effect (PMID: 25415472)", "Nitric oxide-system interaction with endothelium protection, angiogenesis, and EGR-1-mediated growth-factor and collagen expression (PMID: 22300085)" ], "research_fields": [ "Wound healing", "Gastric ulcers", "Tendinopathy", "Neuroprotection", "IBD" ], "pubmed_count": 214, "pubchem_cid": 9941957, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/9941957/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/bpc-157" }, { "id": "7e4e41c7-be02-4940-b1d4-d490eed90f0b", "slug": "bpc-tb-blend", "name": "BPC-157/TB-500 Blend", "aliases": [ "BPC/TB Blend", "BPC TB Stack" ], "category": "Recovery", "description": "Combined healing peptide blend", "half_life": "BPC-157: short - under ~30 min in animal PK studies (rats/dogs); no human PK data. TB-500 (thymosin beta-4): active fragment ~30 min, though tissue effects are prolonged.", "molecular_weight": "BPC-157: ~1419.5 g/mol (average; molecular formula C62H98N16O22). TB-500 (thymosin beta-4): ~4963 Da (full 43-residue peptide).", "molecular_mass": "BPC-157: 1419.56 g/mol; TB-500 (thymosin beta-4): 4963.5 g/mol", "amino_acid_sequence": "BPC-157: Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val (GEPPPGKPADDAGLV); 15-amino-acid partial sequence of human gastric juice protein BPC. TB-500 (thymosin beta-4): SDKPDMAEIEKFDKSKLKKTETQEKNPLPSKETIEQEKQAGES (43-amino-acid peptide; the actin-binding motif LKKTETQ corresponds to residues 17-23).", "administration_routes": [ "Subcutaneous", "Intramuscular" ], "dose_range_mcg": "Dosed per component (a fixed daily blend over-doses TB-500 - see notes). BPC-157: 250-500 mcg once daily SUBQ. TB-500 (thymosin beta-4): 2-2.5 mg twice weekly during a 4-6 week loading phase, then 2-2.5 mg once weekly for maintenance (~5 mg/week during loading). If a pre-blended fixed-ratio daily vial is used, its TB-500 fraction should be ~250-350 mcg per injection so the weekly TB-500 total stays near ~5 mg.", "dosing_frequency": "BPC-157: once daily SUBQ. TB-500: twice weekly during the loading phase, then maintenance ~2-3x/week or once weekly for TB-500 as needed.", "cycle_length": "BPC-157: 4-6 weeks (may be extended). TB-500: 4-6 week loading phase, then maintenance ~2-3x/week or once weekly for TB-500 as needed.", "common_vial_sizes": [ "5mg", "10mg" ], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "Blend", "potential_benefits": [ "Accelerated tissue healing (preclinical/anecdotal)", "Reduced recovery time", "Anti-inflammatory support", "Complementary repair mechanisms: angiogenesis (BPC-157) plus actin-regulated cell migration (TB-500)" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/bpc-tb-blend" }, { "id": "9817ab25-fa96-441a-8a21-19d901d4186c", "slug": "bromantane", "name": "Bromantane", "aliases": [], "category": "Nootropics", "description": "Bromantane is an atypical psychostimulant and anxiolytic developed in the 1980s at the Zakusov Institute of Pharmacology of the Russian Academy of Medical Sciences, originally created as an adaptogen for Soviet military and elite athletic use and later approved in Russia for the treatment of neurasthenic and asthenic disorders under the trade name Ladasten. Chemically it is N-(2-adamantyl)-N-(para-bromophenyl)amine, an adamantane derivative structurally related to amantadine and memantine but pharmacologically distinct from both. What makes Bromantane unusual and clinically interesting is that it acts simultaneously as a mild dopamine reuptake inhibitor and as an activator of tyrosine hydroxylase and aromatic L-amino acid decarboxylase gene expression in mesolimbic and mesocortical dopamine neurons, producing a gentle upregulation of endogenous dopamine synthesis rather than the forceful synaptic dopamine release characteristic of amphetamines or methylphenidate; alongside this dopaminergic effect it promotes neurosteroid synthesis particularly of allopregnanolone and related GABA-A positive modulators, which is thought to underlie its anxiolytic rather than anxiogenic profile and distinguishes it from conventional stimulants that typically produce dose-dependent anxiety. The clinical positioning in Russia has been for neurasthenia, asthenic depression, chronic fatigue states, post-infectious fatigue, and adaptation support during physical and cognitive stress, with multiple placebo-controlled and active-comparator trials published in Russian and occasionally English literature reporting benefits across fatigue, attention, mood, and sleep quality scales at daily doses typically in the 50-100 mg range for 2-6 week courses. Outside Russia Bromantane has never been approved for clinical use, is not controlled under most Western drug schedules because it predates modern scheduling and does not fit amphetamine or modafinil frameworks cleanly, and circulates primarily as a research chemical or grey-market nootropic with substantial user interest in biohacker communities. Its anti-doping status is important for athletes: WADA added Bromantane to the prohibited list in 1996 following the Atlanta Olympics when several Russian athletes tested positive, and it remains on the WADA S6 stimulants list; competitive athletes should absolutely avoid it regardless of the legal status in their jurisdiction. For a BodyHackGuide reader the honest framing is that Bromantane has a legitimate and interesting pharmacological profile, modest but real Russian clinical evidence for asthenic syndromes, a safety profile that appears favourable compared to classical stimulants in available data, and significant practical limitations around sourcing, anti-doping concerns, and absence of Western replication. Evidence-graded alternatives for fatigue, attention, and mood that a reader should consider alongside or instead of Bromantane include modafinil and armodafinil for wakefulness and attention (prescription in most jurisdictions), methylphenidate and amphetamine formulations for diagnosed ADHD under specialist care, SSRIs and SNRIs for depression and anxiety with comorbid fatigue, structured exercise and cardiorespiratory fitness development, sleep disorder workup and treatment where indicated, and addressing iron deficiency, vitamin D insufficiency, thyroid dysfunction, sleep apnoea, and depression as common reversible causes of chronic fatigue. Internal cross-links include [noopept](/compound/noopept), [selank](/compound/selank), [semax](/compound/semax), [bpc-157](/compound/bpc-157), [modafinil](/compound/modafinil), [methylene-blue](/compound/methylene-blue), [nad](/compound/nad), and [sulbutiamine](/compound/sulbutiamine) where those entries exist.", "half_life": "", "molecular_weight": "", "molecular_mass": "322.25 g/mol", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "Russia Approved", "cas_number": "87913-26-6", "iupac_name": "N-(2-adamantyl)-N-(4-bromophenyl)amine", "chemical_formula": "C16H20BrN", "potential_benefits": [ "Motivation and drive", "Anxiety reduction", "Physical stamina", "Crash-free stimulation", "Dopamine synthesis upregulation", "Mood enhancement" ], "research_fields": [ "Asthenia", "ADHD", "Anxiety", "Athletic performance", "Dopaminergic enhancement" ], "pubmed_count": 34, "pubchem_cid": 2450, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/2450/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/bromantane" }, { "id": "e4a2e1eb-00cb-4de6-ab62-ee537d5ad5d9", "slug": "bronchogen", "name": "Bronchogen", "aliases": [ "Bronch peptide" ], "category": "Recovery", "description": "\nBronchogen is a short synthetic peptide developed in Russia by Vladimir Khavinson and his collaborators at the St. Petersburg Institute of Bioregulation and Gerontology, positioned as a \"bronchial bioregulator\" intended to support respiratory epithelium and ciliated-airway function in chronic obstructive pulmonary disease (COPD), chronic bronchitis, and age-related decline of mucociliary clearance. It is usually described in Khavinson-family publications as the tetrapeptide Ala-Glu-Asp-Pro (AEDP), sometimes written H-Ala-Glu-Asp-Pro-OH or A-E-D-P. It sits alongside [Pinealon](/compound/pinealon), [Thymogen](/compound/thymogen), [Vilon](/compound/vilon), [Epitalon](/compound/epithalon), and [Livagen](/compound/livagen) within the Khavinson short-peptide bioregulator family, and it is the defined-sequence counterpart to a polypeptide preparation called Chonluten that is prepared from bovine bronchial mucosa — a relationship that mirrors the Thymogen/Thymalin and Livagen/Stamakort pattern throughout the bioregulator programme.\n\nOutside Russia and a small handful of former-Soviet pharmacology journals, Bronchogen is **not a registered drug, not an FDA- or EMA-reviewed supplement, and not a member of the WADA Prohibited List**. There are no phase II or phase III randomised trials indexed in PubMed or ClinicalTrials.gov, and the peptide does not appear in GOLD, ERS, or NICE guidelines for COPD or chronic bronchitis. The published Russian work — most of it authored or co-authored by Khavinson and colleagues, with occasional collaborators in Almaty and Minsk — comprises *in vitro* cell-culture experiments in bronchial epithelial cells, small rodent studies of induced lung injury, and a handful of uncontrolled observational case series in elderly patients with chronic respiratory disease ([Khavinson et al., 2011]; [Chalisova et al., 2015]; [Kuznik et al., 2011]).\n\nThe central claim made for Bronchogen is the standard Khavinson short-peptide model applied to the bronchial epithelium: passive membrane permeation, nuclear import, and sequence-selective chromatin modulation that preferentially up-regulates genes associated with epithelial regeneration, mucociliary function, and surfactant production. The specific-tissue selectivity claim — that AEDP targets bronchial rather than hepatic or pineal tissue — is not supported by structural biology or by modern biodistribution studies, and rests on extrapolation from the aggregate Khavinson framework. The hypothesis is internally consistent within the Khavinson programme; it is also substantially less validated than the pharmacology of even moderately well-studied respiratory drugs.\n\nBodyHackGuide covers Bronchogen because it is sold online in post-Soviet supplement channels (typically as 20 mg oral capsules containing an undisclosed quantity of actual peptide) and because it shows up in longevity-stack discussions where the speaker frames it as a respiratory-support bioregulator alongside proven interventions. We describe what is known, what is claimed, and what is missing — and we steer readers who want evidence-graded respiratory support toward interventions with substantial replication: smoking cessation, pulmonary rehabilitation, inhaled bronchodilators and corticosteroids for obstructive disease, GLP-1 agonist-mediated weight loss for obesity-related restrictive disease, and, where specifically indicated, biologics such as benralizumab, mepolizumab, or dupilumab. Bronchogen is a plausible hypothesis. It is not, in 2026, an evidence-graded respiratory therapy.\n", "half_life": "Not established (no published human pharmacokinetic data; rapid enzymatic hydrolysis within minutes is expected for a tetrapeptide of this class)", "molecular_weight": "446.45 g/mol", "molecular_mass": "446.45 g/mol", "amino_acid_sequence": "Ala-Glu-Asp-Leu (AEDL)", "administration_routes": [], "dose_range_mcg": "20 mg oral capsule once daily, 10-day cycles", "dosing_frequency": "Once daily", "cycle_length": "10 days on, 60-90 days washout", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Not approved (investigational; marketed only in Russia and post-Soviet markets, no FDA/EMA registration)", "trial_phase": "", "cas_number": "90203-90-0", "iupac_name": "L-Alanyl-L-glutamyl-L-aspartyl-L-leucine", "chemical_formula": "Ala-Glu-Asp-Leu", "potential_benefits": [ "Respiratory tissue repair", "Improved bronchial function", "Support for chronic respiratory conditions", "Mucosal membrane normalization" ], "research_fields": [], "pubmed_count": 7, "pubchem_cid": 16765792, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/bronchogen" }, { "id": "98b588e8-f091-493c-970c-bda8e0212367", "slug": "caffeine", "name": "Caffeine", "aliases": [ "1,3,7-trimethylxanthine", "Methyltheobromine", "Trimethylxanthine", "Theine", "Guaranine", "Mateine", "Caffeine anhydrous", "Caffeine citrate" ], "category": "Nootropic", "description": "**Caffeine** (1,3,7-trimethylxanthine) is a **natural methylxanthine alkaloid** found in the seeds, fruits, leaves, and bark of over 60 plant species — most notably **Coffea** (coffee), **Camellia sinensis** (tea), **Theobroma cacao** (cacao), **Paullinia cupana** (guaraná), **Ilex paraguariensis** (yerba mate), and **Cola acuminata** (kola nut). It is the **world's most widely consumed psychoactive substance**, with an estimated 80-90% of the global adult population consuming caffeine regularly — primarily through coffee, tea, cocoa, soft drinks, and energy drinks. Caffeine is the reference compound in pharmacology for **adenosine receptor antagonism** and one of the most comprehensively studied drugs in human history, with over 50,000 published studies covering its pharmacokinetics, pharmacodynamics, cognitive effects, cardiovascular impact, exercise performance, sleep effects, metabolic effects, addiction profile, and clinical applications.\n\n**Pharmacologically, caffeine is a non-selective adenosine receptor antagonist** — it binds and blocks adenosine A1, A2A, A2B, and A3 receptors throughout the body, with particularly important effects in the central nervous system (A1 and A2A antagonism in striatum, cortex, and sleep-regulating nuclei), heart (A1 antagonism contributing to mild tachycardia), adipose tissue (A1 antagonism promoting lipolysis), and airways (A2B antagonism contributing to mild bronchodilation). Adenosine is an endogenous signaling molecule that accumulates during wakefulness and neural activity, promoting sleepiness and reducing arousal through these receptor systems — **caffeine works by blocking adenosine's sleep-promoting and fatigue-signaling effects**, producing the familiar alerting, arousal, and performance-improving effects. Beyond adenosine receptor antagonism, caffeine at higher doses (typically >500mg) has additional pharmacologic actions: phosphodiesterase inhibition (modest), intracellular calcium mobilization via ryanodine receptors, and GABA-A receptor modulation — but these higher-dose mechanisms are not primary at typical consumption levels.\n\n**Caffeine pharmacokinetics are remarkably variable between individuals**, primarily reflecting genetic variation in the hepatic cytochrome P450 enzyme **CYP1A2**, which metabolizes ~95% of ingested caffeine. The **CYP1A2*1F polymorphism (rs762551)** divides the population into \"fast metabolizers\" (AA genotype, ~40% of caffeine more rapidly cleared) and \"slow metabolizers\" (CC genotype, substantially slower clearance), with heterozygotes (AC) intermediate. This genetic variation produces notable differences in **plasma half-life**: 3-5 hours in fast metabolizers, 5-8 hours in intermediates, and **up to 10-15 hours in slow metabolizers**. The same 200mg caffeine dose can produce very different durations of effect — and very different sleep impacts from afternoon coffee — depending on CYP1A2 genotype. Additional modulators: **oral contraceptives reduce caffeine clearance by ~40%** (effectively doubling half-life), **pregnancy reduces clearance by 50-60% in third trimester**, **smoking induces CYP1A2 and increases clearance by 30-50%** (so smokers often report paradoxically shorter caffeine effects), **liver disease prolongs half-life**, and various medications (fluvoxamine, ciprofloxacin, cimetidine) inhibit CYP1A2 and prolong caffeine effects substantially. Understanding one's own caffeine pharmacokinetics — through genetic testing, self-observation of sleep effects from afternoon caffeine, and awareness of life-stage changes — is key to optimal caffeine use.\n\n**Clinical applications and evidence base span notable breadth**: (1) **Cognitive performance and alertness** — caffeine 40-200mg reliably improves reaction time, sustained attention, vigilance, and cognitive performance under fatigue (**Smith 2002** meta-analysis, **Lorist & Tops 2003**). (2) **Exercise performance** — caffeine 3-6 mg/kg ingested ~60 minutes before exercise reliably improves endurance performance by 2-5% (**Grgic et al. 2020** umbrella review), improves muscular endurance and some aspects of power output, and is classified by WADA as **monitored but not banned** at current consumption levels (though it was banned 1984-2004). (3) **Headache treatment** — caffeine potentiates analgesic effects of acetaminophen and aspirin (the basis for combinations like Excedrin); is first-line for post-dural puncture headache at IV doses; and improves many tension and migraine headaches. (4) **Neonatal apnea of prematurity** — IV caffeine citrate is standard-of-care treatment, with the landmark **CAP trial (Schmidt 2006, 2012)** establishing long-term developmental benefits. (5) **Asthma and respiratory conditions** — caffeine has mild bronchodilator effects; not a replacement for β2-agonists but some supplementary role. (6) **Weight management** — caffeine modestly increases energy expenditure and fat oxidation, though weight loss effects of caffeine alone are clinically modest. (7) **Parkinson disease prevention** — strong epidemiological evidence (Ross 2000, Palacios 2012) that lifetime coffee/caffeine consumption is associated with reduced Parkinson disease risk. (8) **Type 2 diabetes prevention** — strong epidemiology (van Dam 2002, 2006) associating coffee consumption with reduced diabetes risk (effect may involve components beyond caffeine). (9) **Hepatoprotection** — coffee/caffeine consumption associated with reduced liver cirrhosis, reduced hepatocellular carcinoma, reduced NAFLD progression.\n\n**Caffeine is simultaneously one of the safest and most problematic drugs in common use.** Safe at typical consumption levels (≤400mg/day for most adults per EFSA/FDA), it produces **tolerance, dependence, and withdrawal syndrome** with regular use — the characteristic \"caffeine withdrawal headache,\" fatigue, and reduced cognitive performance on cessation are well-documented (**Juliano & Griffiths 2004** meta-analysis established caffeine withdrawal as a clinically-defined syndrome with DSM-5 inclusion). Tolerance to many caffeine effects develops over 1-2 weeks of regular use, though tolerance is incomplete and most chronic users still derive significant alertness and performance benefits. At high doses (>500mg), caffeine produces anxiety, tachycardia, tremor, insomnia, and GI distress; at very high doses (>5-10g), caffeine is potentially lethal — **fatal caffeine toxicity** has occurred primarily from concentrated caffeine powder overdoses (FDA-issued warnings 2014) or severe energy drink overconsumption combined with pre-existing cardiac conditions. Individual sensitivity varies enormously; some individuals experience significant anxiety at 50mg while others tolerate 400mg without obvious effects.\n\nSee also [L-Theanine](/compound/l-theanine), [Adenosine](/compound/adenosine), [Theacrine](/compound/theacrine), [Yerba Mate](/compound/yerba-mate), [Green Tea Extract](/compound/green-tea-extract), [Alpha-GPC](/compound/alpha-gpc), [CDP-Choline](/compound/cdp-choline), and [Tyrosine](/compound/tyrosine) for adjacent nootropic, alertness, and attention-support compounds. This is educational content, not medical advice — caffeine use intersects with many health conditions, medications, and life stages (pregnancy, certain cardiovascular conditions, anxiety disorders, sleep disorders) where individualized guidance matters.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 4235, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/caffeine" }, { "id": "6ad9cf5a-0938-429a-ad44-ac4db136d852", "slug": "cag", "name": "CAG", "aliases": [ "CAG peptide", "Collagen-derived peptide", "Gly-Hyp-Pro related peptide" ], "category": "Recovery", "description": "CAG is not a standardized research-peptide designation. The letters are sometimes used loosely for collagen- or cartilage-related short sequences (for example the tripeptide Cys-Ala-Gly), but no single, vendor-sold research compound is reliably identified by \"CAG,\" and no peer-reviewed pharmacology exists under that name. If you are looking for a defined cartilage-targeting peptide, see Cartalax (the Ala-Glu-Asp-Leu / AEDL Khavinson bioregulator).", "half_life": "Unknown", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [ "Subcutaneous", "Intraarticular" ], "dose_range_mcg": "0", "dosing_frequency": "once_daily", "cycle_length": "", "common_vial_sizes": [ "5", "10" ], "research_stage": "Not a defined single compound", "approval_status": "Not applicable - ambiguous designation, not a characterized compound", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "\"CAG\" has no verified, standardized peptide identity - no specific benefits can be honestly attributed to it. See Cartalax, GHK-Cu, BPC-157, or TB-500 for defined compounds." ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/cag" }, { "id": "d10a3443-1d6a-4bb3-bd8d-4cff02cc733c", "slug": "cagrilintide", "name": "Cagrilintide", "aliases": [ "NN9838" ], "category": "Metabolic & Weight Loss", "description": "Cagrilintide (also known as AM833, development code NN9838) is a long-acting amylin analog developed by Novo Nordisk as a next-generation weight-management therapy, designed to be co-administered with the GLP-1 receptor agonist semaglutide in a fixed-ratio combination known as CagriSema. It represents the first clinically successful revival of amylin pharmacology since pramlintide (Symlin) was approved in 2005 for type 1 and type 2 diabetes — a product that never achieved commercial success largely because of its inconvenient three-times-daily subcutaneous dosing schedule and its narrow label. Cagrilintide solves the pharmacokinetic problem: through acylation with a fatty acid chain (in a strategy similar to Novo Nordisk's use of the same chemistry in semaglutide and insulin degludec), cagrilintide binds reversibly to albumin, extending its half-life from native amylin's 13 minutes to approximately 159 hours (6-7 days), enabling once-weekly subcutaneous injection ([Enebo et al., 2021]).\n\nAmylin itself is a 37-amino-acid peptide hormone co-secreted with insulin by pancreatic beta cells in response to nutrient ingestion, at roughly 1-5% the molar ratio of insulin. It was discovered in 1987 by Per Westermark and colleagues as the principal constituent of pancreatic amyloid deposits in type 2 diabetes (hence the name amylin — from amyloid). The mature hormone contains a disulfide bond between cysteine-2 and cysteine-7 and a C-terminal amide essential for bioactivity, giving it a cyclic head and a linear tail. Native amylin is aggregation-prone and forms the same toxic oligomers and fibrils implicated in beta-cell failure, which is why all clinical amylin analogs (pramlintide, cagrilintide, amycretin) have substituted key amyloidogenic residues (typically proline substitutions at positions 25, 28, 29) to block the fibrillation pathway while preserving receptor binding.\n\nIn the Phase 2 randomized trial of cagrilintide monotherapy at 4.5 mg weekly in adults with obesity, mean weight loss at 26 weeks was approximately 10.8% versus 3.0% with placebo and 9.0% with liraglutide 3.0 mg daily ([Lau et al., 2021]). More importantly, the CagriSema Phase 2 combination trial — cagrilintide 2.4 mg + semaglutide 2.4 mg weekly — produced 15.6% placebo-adjusted weight loss at 32 weeks, substantially greater than either component alone and comparable to tirzepatide and retatrutide results, generating intense pharma-industry and investor interest ([Enebo et al., 2021]). The Phase 3 REDEFINE program (REDEFINE 1, 2, 3, 4) has enrolled over 6,000 participants, with REDEFINE 1 (adults with obesity, no diabetes) and REDEFINE 2 (type 2 diabetes) reading out weight loss endpoints of 22.7% at 68 weeks in the landmark cohort, positioning CagriSema to compete with tirzepatide (Zepbound/Mounjaro) and the emerging triple agonist retatrutide as the next-generation incretin-amylin combination therapy. Cross-references include [Semaglutide](/compound/semaglutide) (the GLP-1 component of CagriSema), [Tirzepatide](/compound/tirzepatide) (the leading dual GLP-1/GIP competitor), [Retatrutide](/compound/retatrutide) (triple agonist in development), [Mazdutide](/compound/mazdutide) (GLP-1/glucagon dual agonist from Innovent), and [Orforglipron](/compound/orforglipron) (oral non-peptide GLP-1 agonist).", "half_life": "~159 hours (approximately 7 days)", "molecular_weight": "", "molecular_mass": "4246.7 g/mol", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "Once weekly", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Phase 3", "approval_status": "Investigational (not FDA-approved)", "trial_phase": "Phase 3", "cas_number": "2172366-25-3", "iupac_name": "Amylin analog with N-terminal fatty acid acylation (proprietary)", "chemical_formula": "C195H286N46O60", "potential_benefits": [ "Weight loss", "Appetite suppression (via different pathway than GLP-1)", "Glucagon suppression", "Complementary to GLP-1 agonists" ], "research_fields": [ "Obesity", "Type 2 diabetes", "Metabolic syndrome" ], "pubmed_count": 46, "pubchem_cid": 0, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/cagrilintide" }, { "id": "4e7efe95-329a-4e6c-be85-7d78be7d7834", "slug": "calcium", "name": "Calcium", "aliases": [ "Ca", "Ca2+", "Calcium ion", "Elemental calcium", "Calcium carbonate", "CaCO3", "Tums", "Oyster shell calcium", "Calcium citrate", "Calcium citrate malate", "Calcium bisglycinate", "Calcium chelate", "Calcium lactate", "Calcium gluconate", "Calcium hydroxyapatite", "Microcrystalline hydroxyapatite", "MCHC", "Calcium phosphate", "Tricalcium phosphate", "Dicalcium phosphate", "Calcium malate", "Calcium orotate", "Calcium aspartate", "Calcium ascorbate", "Coral calcium", "Dolomite", "Bone meal calcium" ], "category": "Mineral", "description": "\nCalcium is the most abundant mineral in the human body — roughly 1,000 to 1,500 grams in a 70 kg adult, with 99% sequestered in the skeleton and teeth as crystalline hydroxyapatite [Ca10(PO4)6(OH)2], and the remaining 1% distributed across extracellular fluid, intracellular cytoplasm, mitochondria, and the endoplasmic/sarcoplasmic reticulum. That small 1% operates one of biology's most exquisitely regulated signaling systems: extracellular calcium is maintained at 1.10-1.35 mmol/L (total) and 1.10-1.30 mmol/L (ionized) with homeostatic precision rivaling blood glucose and pH, while intracellular cytosolic free calcium rests at roughly 50-100 nmol/L — a 10,000-fold concentration gradient across the plasma membrane that allows transient calcium influxes to function as universal signaling events. Muscle contraction, neurotransmitter release, hormone secretion, fertilization, enzyme activation, gene transcription, apoptosis — calcium signaling sits at the heart of all of them. Humphry Davy isolated elemental calcium metal in 1808 by electrolysis of lime (CaO); the dietary essentiality of calcium for bone formation was recognized in the 19th century; and the modern era of calcium biology dates from Sydney Ringer's 1883 discovery that frog hearts required calcium in perfusate to contract, opening a century of work culminating in the Nobel Prize-winning calcium channel and calcium-sensing receptor characterizations.\n\nThe adult RDA for calcium is 1,000 mg/day for most adults and 1,200 mg/day for women over 50 and all adults over 70, with tolerable upper intake level set at 2,500 mg/day for adults 19-50 and 2,000 mg/day for those over 50. Children require 700-1,300 mg/day depending on age. Pregnancy and lactation maintain the adult RDA because calcium economy shifts (increased intestinal absorption offsets fetal and breast-milk demand). The average US diet provides 900-1,100 mg/day from dairy (major contributor), tofu made with calcium sulfate, leafy greens (with varying bioavailability — spinach has high oxalate and poor absorption while kale, bok choy, and collards are well-absorbed), fortified foods (plant milks, juices, cereals), fish with edible bones (sardines, canned salmon), almonds, and fortified breakfast cereals. Calcium supplementation is one of the most common supplement uses worldwide, particularly in postmenopausal women for osteoporosis prevention — but its evidence base is substantially more nuanced than the marketing suggests.\n\nCalcium absorption occurs primarily in the small intestine via two mechanisms. Active transcellular uptake in the duodenum and proximal jejunum is vitamin D-dependent: calcitriol (1,25-dihydroxyvitamin D3) upregulates TRPV6 (the apical calcium channel), calbindin-D9k (cytosolic calcium buffer/shuttle), and PMCA1b (basolateral calcium ATPase extrusion pump), enabling calcium uptake against its electrochemical gradient. This system saturates at intake approaching 200-300 mg per meal and is rate-limited by vitamin D adequacy and calbindin expression. Passive paracellular absorption across the jejunum and ileum handles the majority of calcium absorbed at higher intakes, operating by diffusion through tight junctions driven by luminal calcium concentration. The net absorption fraction is 25-35% from dairy in adults, up to 50-60% in infants and growing children, 10-15% from vegetables with significant oxalate content, 45-60% from bok choy and kale, and 20-45% from supplement forms depending on gastric acid and meal context. Calcium absorption declines with age (reduced vitamin D and mucosal responsiveness) and is impaired by achlorhydria, proton pump inhibitor therapy, and severe gastric resection.\n\nOnce absorbed, calcium circulates in plasma in three pools: ionized (free Ca2+, ~50%, the biologically active species), protein-bound (primarily to albumin, ~40%, with smaller amounts bound to globulins), and complexed with small molecules (citrate, phosphate, sulfate, ~10%). Ionized calcium is the regulated species; total calcium measurements must be interpreted in the context of albumin level (correction formula: corrected Ca = measured Ca + 0.02 × [4.0 - albumin g/dL] in SI units) or ionized calcium can be measured directly. Serum calcium is maintained within a narrow range by an integrated hormonal system: parathyroid hormone (PTH, secreted by chief cells when calcium-sensing receptor [CaSR] detects falling ionized calcium) increases bone resorption, enhances renal calcium reabsorption, and stimulates renal 1α-hydroxylase (CYP27B1) to produce calcitriol; calcitriol increases intestinal calcium absorption and potentiates PTH effects on bone; calcitonin (from thyroid C cells) modestly inhibits osteoclast activity in response to high calcium; and FGF23 (fibroblast growth factor 23, from osteocytes) regulates phosphate and suppresses calcitriol.\n\nThe bone biology story is extensively integrated with [vitamin D3](/compound/vitamin-d3) and [vitamin K2](/compound/vitamin-k2). Osteoblasts secrete osteoid — a collagen-rich matrix that mineralizes through hydroxyapatite deposition. Osteoblasts also produce osteocalcin and matrix Gla protein (MGP), both vitamin K-dependent γ-carboxylated proteins that regulate mineralization; osteocalcin promotes hydroxyapatite formation in bone matrix, while MGP (expressed in arterial walls) inhibits vascular calcification. This dual system — vitamin K driving calcium deposition where it should go (bone) and inhibiting deposition where it should not go (arteries) — is why the current biohacker consensus around \"calcium paradox\" argues for K2-MK7 co-supplementation with calcium to direct calcium away from vascular plaque. Osteoclasts resorb bone through H+ secretion creating an acidic resorption lacuna that dissolves hydroxyapatite, combined with collagenase release to degrade the organic matrix. The balance between osteoblast-mediated formation and osteoclast-mediated resorption is regulated by the RANK/RANKL/OPG axis (osteoblasts express RANKL, osteoclasts express RANK, and osteoprotegerin OPG is a decoy receptor inhibiting RANKL); estrogen loss at menopause shifts this balance toward resorption, and the resulting bone loss is the foundation of postmenopausal osteoporosis — and the rationale for calcium supplementation in this population.\n\nThe Women's Health Initiative (WHI) calcium + vitamin D trial (Jackson 2006 NEJM) is the largest randomized controlled trial of calcium supplementation in postmenopausal women — 36,282 women randomized to calcium carbonate 1,000 mg/day + vitamin D3 400 IU/day vs. placebo, 7 years of follow-up. The trial showed a small 1% improvement in hip bone density and a 12% reduction in hip fracture in the active arm, but this was not statistically significant in the primary intention-to-treat analysis. In a per-protocol analysis among adherent women (>80% compliance), hip fracture was reduced 29%, reaching significance. A more concerning signal emerged: a 17% increased incidence of kidney stones in the supplementation arm (confirmed signal). Subsequent Bolland meta-analyses (2008, 2010, 2011, culminating in BMJ 2011) reported that calcium supplementation (with or without vitamin D) was associated with approximately 25-30% increased myocardial infarction risk in older adults, a finding that generated substantial controversy. Re-analyses, particularly of WHI by Prentice 2013, disputed the cardiovascular signal, and more recent large-scale data (EPIC-Heidelberg, UK Biobank analyses) have produced mixed findings. The current pragmatic consensus: prefer dietary calcium whenever possible, keep supplementation to 500-600 mg/day when needed (taken in divided doses), combine with vitamin D and K2, and focus supplementation on women with documented low dietary intake or established osteoporosis rather than blanket use in everyone over 50.\n\nColorectal cancer is another positive but modest signal. The Calcium Polyp Prevention Study (Baron 1999 NEJM, PMID 9887161) randomized 930 patients with prior colorectal adenoma to calcium carbonate 1,200 mg/day vs. placebo for 4 years; the active arm showed a 19% reduction in recurrent adenoma (RR 0.81, 95% CI 0.67-0.99). Subsequent European calcium supplementation trials have shown similar modest benefit, though the effect disappears when supplementation stops. Dietary calcium intake inversely correlates with colorectal cancer risk in large cohort studies (WCRF 2018 continuous update). Dosing for prevention is typically 1,200 mg/day from food and supplements combined.\n\nBlood pressure. The DASH diet trial (Appel 1997 NEJM, PMID 9099655) provided evidence that dietary patterns high in calcium (from low-fat dairy), potassium, and magnesium, combined with reduced sodium, reduce systolic blood pressure by 5-11 mmHg. Isolated calcium supplementation has shown smaller, less consistent effects on blood pressure (1-2 mmHg reductions in meta-analyses); the DASH pattern is more effective than calcium pills.\n\nPreeclampsia prevention. Calcium supplementation 1-2 g/day in pregnancy has been studied for preeclampsia prevention. Meta-analyses (Hofmeyr Cochrane 2018, PMID 30277579) indicate a 55% reduction in preeclampsia in low-calcium-intake populations (pooled benefit from 13 trials), leading to WHO recommendation for calcium supplementation during pregnancy in populations with low dietary calcium. In well-nourished populations, benefit is marginal.\n\nKidney stones paradox. High dietary calcium reduces stone risk (via intestinal oxalate binding preventing oxalate absorption); high supplemental calcium, particularly when taken between meals, increases stone risk (elevated urinary calcium without intestinal oxalate binding). Curhan 1997 (NEJM) established this dietary/supplement distinction. Recommendations for stone formers: calcium from food with meals is protective, supplements taken between meals are risky. Calcium citrate is generally preferred over calcium carbonate in stone formers because citrate itself is an inhibitor of stone formation.\n\nBodyHackGuide's take: calcium is essential and highly regulated, but the modern public-health narrative of \"calcium supplement = bone health\" overreaches the evidence. Dietary calcium from dairy, fortified plant milks, tofu, leafy greens, sardines, almonds, and calcium-fortified foods should be the primary strategy; a Mediterranean-style diet usually delivers 800-1,200 mg/day without effort. Supplementation at 500-600 mg/day (in divided doses, with meals, preferably calcium citrate for PPI users and stone formers, carbonate for others) is reasonable for documented low intake or established osteoporosis. Combine with [vitamin D3](/compound/vitamin-d3) 2,000-4,000 IU/day, [vitamin K2](/compound/vitamin-k2) MK-7 100-180 μg/day, [magnesium](/compound/magnesium) 300-400 mg/day, and adequate protein intake. Weight-bearing exercise and resistance training do more for bone than calcium supplementation alone. Avoid high-dose (>1,500 mg/day supplemental) calcium given cardiovascular signal concerns, stone risk, and the declining evidence for incremental bone benefit.\n", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 1288, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/calcium" }, { "id": "3ae8d52b-2bc1-4048-9ce2-73a8e3a20c55", "slug": "cardarine", "name": "Cardarine (GW501516)", "aliases": [ "GW501516", "GW-501516", "GW1516", "GSK-516", "Endurobol", "Cardarin" ], "category": "Metabolic", "description": "Cardarine is the market name for GW501516, a synthetic agonist of the nuclear receptor PPAR-delta developed by GlaxoSmithKline as a treatment for low HDL cholesterol and the lipid problems that travel with metabolic syndrome. It is not a SARM and has nothing to do with androgen receptors, despite being sold alongside them. Company trials reached phase 2 and the program ended there. GW501516 has never been approved by any regulator.\n\nPPAR-delta is a transcription factor found in muscle, fat and liver that controls the genes for burning fat. Turning it on shifts cells toward using fatty acids for fuel instead of carbohydrate. In human skeletal muscle cells, GW501516 increased fat oxidation and raised expression of CPT1, CD36 and ABCA1 (PMID: 17110604).\n\nThe endurance reputation is built on rodent work. In mice, a PPAR-delta agonist combined with exercise training increased oxidative muscle fibers and running endurance beyond training alone, and the same paper coined the phrase exercise mimetic (PMID: 18674809). Mice treated with GW501516 also showed improved muscle function in a muscular dystrophy model (PMID: 22908954). No human trial has ever measured endurance, VO2max or time to exhaustion on this drug.\n\nWhat the human trials did measure was blood lipids. In healthy volunteers dosed for two weeks, HDL cholesterol rose in both treatment groups while it fell on placebo, and clearance of fat after a meal improved (PMID: 17110604). In 268 people with low HDL, twelve weeks of treatment raised HDL by up to 16.9 percent and lowered triglycerides by 16.9 percent, apolipoprotein B by 14.9 percent and LDL cholesterol by 7.3 percent (PMID: 22814748). Two weeks in moderately overweight men lowered triglycerides by 30 percent and liver fat by 20 percent (PMID: 18024853), and a crossover study in dyslipidemic men with central obesity mapped the lipoprotein kinetics behind those changes (PMID: 21816786).\n\nThe cancer question is the reason this compound is not on pharmacy shelves. In Apc(min) mice, which are prone to intestinal polyps, GW501516 significantly increased both the number and the size of polyps, with a fivefold rise in polyps larger than 2 mm (PMID: 14758356). A later mouse study found that the same agonist accelerated colorectal tumorigenesis while a PPAR-delta antagonist suppressed it (PMID: 30679176). Reviewing that work, researchers warned in print that PPAR-delta agonists then in development for dyslipidemia and obesity might raise tumor risk in humans (PMID: 15539957).\n\nGW1516 was added to the WADA prohibited list in January 2009 and its urinary metabolites were characterized for routine doping control (PMID: 19946680). When 44 internet products sold as SARMs were analyzed, GW501516 was among the unapproved drugs found in products that did not declare it (PMID: 29183075).", "half_life": "Not reported in the published human trials; the phase 1 and phase 2 studies described lipid outcomes over two to twelve weeks of oral dosing without publishing a terminal half-life (PMID: 17110604; PMID: 22814748)", "molecular_weight": "453.51 g/mol", "molecular_mass": "453.51 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Discontinued", "approval_status": "Never approved by the FDA, the EMA or any other regulator, and the clinical program stopped after phase 2 studies in dyslipidemia. WADA prohibits GW1516 at all times under section S4.4, metabolic modulators, as a PPAR-delta agonist; it was added to the list in January 2009 and doping control assays for its urinary metabolites are in routine use (PMID: 19946680). It is a research-use-only compound in the US market with no legal human use.", "trial_phase": "", "cas_number": "317318-70-0", "iupac_name": "", "chemical_formula": "C21H18F3NO3S2", "potential_benefits": [ "Raised HDL cholesterol by up to 16.9 percent and lowered triglycerides by 16.9 percent over twelve weeks in 268 adults with low HDL cholesterol (PMID: 22814748)", "Lowered fasting triglycerides by 30 percent and liver fat content by 20 percent over two weeks in moderately overweight men (PMID: 18024853)", "Increased HDL cholesterol and improved post-meal fat clearance over two weeks in healthy sedentary volunteers (PMID: 17110604)", "Increased oxidative muscle fibers and treadmill running endurance when combined with training in mice (PMID: 18674809)", "Increased fatty acid oxidation and CPT1, CD36 and ABCA1 expression in cultured human skeletal muscle cells (PMID: 17110604)" ], "research_fields": [ "PPAR-delta signaling", "Lipid metabolism", "Exercise mimetics", "Sports drug testing" ], "pubmed_count": 0, "pubchem_cid": 9803963, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/cardarine" }, { "id": "e27fd253-23f8-4ca7-aef2-ad6d5c638b3b", "slug": "cardiogen", "name": "Cardiogen", "aliases": [ "Cardiac peptide" ], "category": "Recovery", "description": "\nCardiogen is a short synthetic peptide developed in Russia by Vladimir Khavinson and his collaborators at the St. Petersburg Institute of Bioregulation and Gerontology, positioned as a \"myocardial bioregulator\" intended to support cardiomyocyte function, vascular endothelium, and cardiac tissue resilience in age-related cardiovascular decline, post-infarction recovery, and chronic heart failure. It is usually described in Khavinson-family publications as the tetrapeptide Ala-Glu-Asp-Arg (AEDR), sometimes rendered H-Ala-Glu-Asp-Arg-OH or A-E-D-R, and sits alongside [Pinealon](/compound/pinealon), [Thymogen](/compound/thymogen), [Vilon](/compound/vilon), [Epitalon](/compound/epithalon), [Livagen](/compound/livagen), and [Bronchogen](/compound/bronchogen) within the Khavinson short-peptide bioregulator family. Cardiogen is the synthetic defined-sequence counterpart to a polypeptide product called Chelohart (or Korteksin for the brain-targeted version), which is prepared from bovine cardiac tissue extract — mirroring the extract-plus-defined-sequence pattern Khavinson's group applies across the bioregulator programme.\n\nOutside Russia, Cardiogen is **not registered as a drug, not reviewed by FDA, EMA, or PMDA, and not listed on WADA's Prohibited List** — though the WADA S0 catch-all for \"non-approved substances\" arguably covers any unregistered peptide for competitive athletes. There are no phase II or phase III randomised trials indexed in PubMed or ClinicalTrials.gov, and Cardiogen does not appear in ACC/AHA, ESC, or NICE guidelines for ischaemic heart disease, heart failure, or cardiac aging. The published Russian work comprises *in vitro* cardiomyocyte culture experiments, small rodent studies of induced cardiac injury, and uncontrolled observational case series in elderly patients with chronic cardiovascular disease ([Khavinson et al., 2011]; [Chalisova et al., 2014]; [Anisimov et al., 2010]).\n\nThe central claim for Cardiogen is the standard Khavinson short-peptide model applied to cardiac tissue: passive membrane permeation through the cardiomyocyte sarcolemma, nuclear import, and sequence-selective chromatin modulation producing preferential up-regulation of cardiomyocyte-survival, mitochondrial-biogenesis, and regeneration programmes. Tissue-specific targeting toward the heart — rather than liver, brain, or thymus — is asserted but not supported by structural biology, modern biodistribution, or contemporary transcriptomic characterisation of cardiac tissue after AEDR exposure. The hypothesis is internally consistent within the Khavinson framework; it is substantially less validated than the pharmacology of even modestly-studied cardiac therapies.\n\nBodyHackGuide covers Cardiogen because it is sold online in post-Soviet supplement channels (typically 20 mg oral capsules containing an undisclosed amount of actual peptide) and appears frequently in longevity-stack discussions framed as a cardiac-support bioregulator. We describe what is known, what is claimed, and what is missing — and we steer readers seeking evidence-graded cardiovascular protection toward interventions with overwhelming replication: blood-pressure control, LDL-cholesterol reduction via statins and PCSK9 inhibitors, SGLT2 inhibitors for heart failure and diabetic cardiomyopathy, GLP-1 agonists for cardiometabolic risk, anticoagulation where indicated, and aerobic exercise as the single most important lifestyle variable in cardiac aging. Cardiogen is a plausible hypothesis. It is not, in 2026, a cardiovascular therapy.\n", "half_life": "Not characterized in humans. As a short linear tetrapeptide (Ala-Glu-Asp-Arg), Cardiogen is expected to undergo rapid enzymatic hydrolysis to its constituent amino acids; no validated modern pharmacokinetic half-life has been published.", "molecular_weight": "489.5 g/mol (C18H31N7O9, tetrapeptide Ala-Glu-Asp-Arg)", "molecular_mass": "489.5 g/mol", "amino_acid_sequence": "Ala-Glu-Asp-Arg (AEDR)", "administration_routes": [], "dose_range_mcg": "20 mg oral once daily x10 days, or 2-5 mg SC daily x10 days; 60-90 day washout", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "70381-80-5", "iupac_name": "L-Alanyl-L-glutamyl-L-aspartyl-glycine", "chemical_formula": "Ala-Glu-Asp-Gly", "potential_benefits": [ "Cardiovascular tissue support", "Cardiac muscle repair", "Improved heart function markers", "Anti-aging effects on heart tissue" ], "research_fields": [], "pubmed_count": 9, "pubchem_cid": 16117367, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/cardiogen" }, { "id": "e4f40cc6-bff0-4595-b3a0-c645720900d3", "slug": "cartalax", "name": "Cartalax", "aliases": [ "AED" ], "category": "Recovery", "description": "\nCartalax is a short synthetic peptide developed in Russia by Vladimir Khavinson and colleagues at the St. Petersburg Institute of Bioregulation and Gerontology, positioned as a \"cartilage bioregulator\" intended to support chondrocyte function, cartilage matrix synthesis, and joint tissue resilience in age-related osteoarthritis, post-traumatic joint disease, and intervertebral disc degeneration. It is usually described in Khavinson-family publications as the tetrapeptide Ala-Glu-Asp-Leu (AEDL), sometimes written H-Ala-Glu-Asp-Leu-OH or A-E-D-L, though the literature also references slight sequence variants in early publications. Cartalax sits alongside [Pinealon](/compound/pinealon), [Thymogen](/compound/thymogen), [Vilon](/compound/vilon), [Epitalon](/compound/epithalon), [Livagen](/compound/livagen), [Bronchogen](/compound/bronchogen), and [Cardiogen](/compound/cardiogen) within the Khavinson short-peptide bioregulator family, and is the defined-sequence counterpart to a polypeptide preparation called Sygumir (in some marketing) or cartilage-derived polypeptide complexes from Khavinson's original extract programme.\n\nOutside Russia, Cartalax is **not registered as a drug, not reviewed by FDA, EMA, or PMDA, and not in any WADA category** — though the WADA S0 non-approved substances clause arguably applies for competitive athletes. There are no phase II or phase III RCTs in PubMed or ClinicalTrials.gov, and Cartalax does not appear in OARSI, ACR, or EULAR osteoarthritis guidelines. Published Russian work comprises *in vitro* chondrocyte culture studies, rodent osteoarthritis model experiments, and small uncontrolled observational series in elderly patients with knee, hip, and spinal osteoarthritis ([Khavinson et al., 2011]; [Chalisova et al., 2014]; [Anisimov et al., 2010]).\n\nThe central claim for Cartalax is the standard Khavinson short-peptide model applied to cartilage tissue: passive membrane permeation into chondrocytes, nuclear import, sequence-selective chromatin modulation, and preferential upregulation of chondrocyte survival, matrix synthesis (type II collagen, aggrecan, hyaluronic acid), and anti-catabolic programmes (downregulation of MMPs, ADAMTS). The tissue-specificity claim — that AEDL selectively targets cartilage rather than other connective tissue — is asserted but not supported by modern biodistribution, structural biology, or transcriptomics. The hypothesis is internally consistent within the Khavinson programme; it is substantially less validated than the pharmacology of evidence-graded osteoarthritis therapy.\n\nBodyHackGuide covers Cartalax because it is sold online in post-Soviet supplement channels (typically 20 mg oral capsules) and appears in longevity-stack discussions alongside joint-support adjuncts. We describe what is known, what is claimed, and what is missing — and we steer readers seeking evidence-graded joint and cartilage support toward interventions with better replication: weight management (single most impactful intervention for knee OA), structured exercise and physical therapy, NSAIDs where appropriate for symptomatic relief, intraarticular corticosteroid or hyaluronic acid injection, topical NSAIDs, [Curcumin](/compound/curcumin) and [Boswellia](/compound/boswellia) for modest anti-inflammatory benefit, collagen peptides and undenatured type II collagen (UC-II) with mixed but some positive evidence, [BPC-157](/compound/bpc-157) and [TB-500](/compound/tb-500) as experimental peptide options with more mechanism data than Cartalax, and surgical intervention (arthroscopy, joint replacement) where indicated. Cartalax is a plausible hypothesis. It is not, in 2026, an evidence-graded cartilage therapy.\n", "half_life": "No published human or animal pharmacokinetic data for Cartalax. As a small (~446.5 Da) tetrapeptide, rapid plasma hydrolysis (on the order of minutes) is expected, consistent with other Khavinson short peptides, but this has not been directly measured.", "molecular_weight": "446.5 Da (C18H30N4O9)", "molecular_mass": "446.5 g/mol", "amino_acid_sequence": "Ala-Glu-Asp-Leu (AEDL)", "administration_routes": [], "dose_range_mcg": "20 mg oral/sublingual once daily for 10 days; 60-90 day washout", "dosing_frequency": "Once daily", "cycle_length": "10 days per cycle; 60-90 day washout", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "L-Alanyl-L-glutamyl-L-aspartyl-L-serine", "chemical_formula": "Ala-Glu-Asp-Ser", "potential_benefits": [ "Joint and cartilage repair support", "Connective tissue maintenance", "Anti-aging effects on musculoskeletal system", "Improved joint mobility" ], "research_fields": [], "pubmed_count": 6, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/cartalax" }, { "id": "27c76818-e38e-4864-a206-df8114957891", "slug": "cdp-choline", "name": "CDP-Choline", "aliases": [ "Citicoline", "Cytidine 5'-diphosphocholine", "Cytidine diphosphate-choline", "Cognizin", "Ceraxon", "Somazina", "Somazon", "NeurAxon", "CDPC" ], "category": "Nootropic", "description": "**CDP-choline** (cytidine 5'-diphosphocholine, pharmaceutical name **citicoline**) is a naturally occurring intracellular intermediate in the **Kennedy pathway** for phosphatidylcholine synthesis — the primary biochemical route by which all nucleated cells produce the dominant membrane phospholipid. Structurally, CDP-choline consists of **cytidine** (a pyrimidine nucleoside) linked via a diphosphate bridge to **choline**. When administered orally, CDP-choline is rapidly hydrolyzed in the gastrointestinal tract to its two constituent components — **cytidine** and **choline** — both of which are independently absorbed, cross the blood-brain barrier via their respective transporters, and are subsequently reassembled intracellularly into CDP-choline within neurons and other tissues. The intact CDP-choline molecule itself has negligible bioavailability after oral dosing; the therapeutic activity of oral citicoline comes from the combined delivery of its two metabolic building blocks, each of which supports distinct downstream neurochemical functions.\n\nCDP-choline was first developed as a pharmaceutical agent in Japan in the late 1970s-1980s (brand names **Nicholin**, subsequently **Cognizin** for the proprietary Kyowa Hakko fermentation-produced form) and in Europe (brand names **Ceraxon**, **Somazina**, **Somazon**) as a treatment for **ischemic stroke recovery**, **traumatic brain injury**, **vascular dementia**, and **age-associated cognitive decline**. In these regions it remains a **prescription medication** available in oral, intramuscular, and intravenous formulations. In the **United States**, CDP-choline is regulated as a **dietary supplement and medical food ingredient** rather than a prescription drug, and the proprietary **Cognizin** form (a stabilized pharmaceutical-grade citicoline) is widely used in cognitive-enhancement supplements, often at doses of 250-500mg per capsule.\n\nIn the cognitive-enhancement and nootropics community, CDP-choline occupies a distinctive niche alongside [Alpha-GPC](/compound/alpha-gpc), the other premium cholinergic precursor. Users often approach the two as complementary rather than competitive: **Alpha-GPC** provides highly bioavailable choline with superior acute CNS penetration (favored for acute pre-workout, pre-task, and short-term cognitive applications); **CDP-choline** provides choline plus **cytidine** (converted to uridine in humans), with the cytidine/uridine component offering independent benefits for neuronal membrane synthesis, synaptic function, and dopamine signaling beyond what Alpha-GPC provides (favored for long-term cognitive support, daily-use nootropic stacking, and applications where the uridine pathway is specifically relevant). CDP-choline also generates **less trimethylamine-N-oxide (TMAO)** than Alpha-GPC — a potentially important consideration for users concerned about the TMAO-cardiovascular hypothesis.\n\n**The clinical evidence base for CDP-choline is more extensive than for any other cholinergic precursor**, with decades of prescription use in Europe and Asia providing substantial real-world safety data and a strong body of randomized trial data across multiple indications. The single largest trial — **ICTUS (International Citicoline Trial on acUte Stroke), Dávalos et al. 2012** (*Lancet*) — randomized 2,298 patients with moderate-to-severe acute ischemic stroke to citicoline 2,000mg/day versus placebo for 6 weeks. The primary outcome (global recovery at 90 days) did not reach statistical significance (odds ratio 1.03, 95% CI 0.86-1.25), ending a 20-year period during which citicoline had been a standard European post-stroke treatment. The ICTUS result ended formal stroke indication for citicoline in many regulatory settings. However, secondary analyses and meta-analyses including Cochrane reviews have continued to identify possible subgroup benefits and modest effects in milder strokes, TBI, and age-related cognitive decline.\n\nFor **age-associated cognitive impairment and vascular dementia**, the **Fioravanti & Yanagi 2005 Cochrane review**and its 2020 update included multiple randomized trials totaling hundreds of patients and concluded that citicoline produced modest improvements in memory, attention, and global cognitive performance in elderly patients with cognitive deficits — with effect sizes smaller than prescription cholinesterase inhibitors but with a more favorable side-effect profile. For **cognitive enhancement in healthy adults**, the **Silveri et al. 2008** studyused magnetic resonance spectroscopy to document that 6 weeks of citicoline 500mg or 2,000mg produced measurable increases in frontal-lobe phosphatidylcholine, phosphocreatine, and ATP levels — providing mechanistic support for claimed cognitive-enhancement effects. **McGlade et al. 2012**randomized 60 adolescent females to citicoline 250mg, 500mg, or placebo for 28 days and observed dose-dependent improvements on attentional tasks (Ruff 2 & 7 Test) and reduced impulsivity on the Conners' Continuous Performance Test II.\n\nFor **traumatic brain injury**, the **COBRIT trial (Zafonte et al. 2012)** in *JAMA*randomized 1,213 TBI patients to citicoline 2,000mg/day or placebo for 90 days and found no significant benefit on global functional or cognitive recovery — another large negative trial that further limited formal indications. Subsequent analysis of subgroups, however, has continued to support possible benefit in milder TBI, children, and populations different from the COBRIT enrollment.\n\nFor **ADHD**, small trials have suggested cognitive improvements in attention and processing speed. For **Parkinson's disease adjunctive use**, citicoline has been explored based on its dopamine-precursor-sparing and neuroprotective properties; evidence is preliminary. For **amblyopia and glaucoma**, citicoline has been studied in European ophthalmology with some positive findings for visual evoked potentials and retinal ganglion cell function, and oral citicoline has become an accepted adjunct in some ophthalmology practices for these conditions.\n\nCDP-choline has an **exceptionally favorable safety profile** — multiple decades of European prescription use and extensive global supplement use have documented a very low rate of serious adverse events, minimal drug interactions, and good tolerability at doses up to 2,000mg/day. The most common side effects are mild gastrointestinal complaints and occasional headache; serious adverse events are rare. Unlike [Alpha-GPC](/compound/alpha-gpc), CDP-choline has not been significantly associated with the 2021 cardiovascular/TMAO concerns, as less of the choline component is converted to TMA by gut bacteria in most studies.\n\nSee also [Alpha-GPC](/compound/alpha-gpc), [Uridine Monophosphate](/compound/uridine-monophosphate), [Omega-3 fatty acids](/compound/omega-3-fatty-acids), [Piracetam](/compound/piracetam), [Noopept](/compound/noopept), [Aniracetam](/compound/aniracetam), [Lion's Mane](/compound/lions-mane), [Bacopa Monnieri](/compound/bacopa-monnieri), [Phosphatidylserine](/compound/phosphatidylserine), [Caffeine](/compound/caffeine), and [L-theanine](/compound/l-theanine) for adjacent cognitive-support compounds and stacking context. This overview is educational only and is not medical advice.", "half_life": "", "molecular_weight": "", "molecular_mass": "488.32 g/mol", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "Phase 4", "cas_number": "987-78-0", "iupac_name": "[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl (3-trimethylaminopropyl) hydrogen phosphate", "chemical_formula": "C14H26N4O11P2", "potential_benefits": [ "Acetylcholine support", "Dopamine D2 upregulation (via uridine)", "Focus and attention", "Memory", "Neuroprotection", "Stroke recovery" ], "research_fields": [ "Stroke", "Vascular cognitive impairment", "Alzheimer's disease", "ADHD", "Glaucoma" ], "pubmed_count": 56, "pubchem_cid": 13804, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/13804/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/cdp-choline" }, { "id": "b29ef108-0e90-4d7a-b6cf-c6f158574c89", "slug": "cerebrolysin", "name": "Cerebrolysin", "aliases": [ "Cerebrolysin", "Cere", "EVER NEURO 215", "Cerebrolyzin" ], "category": "Nootropic Peptide", "description": "Cerebrolysin is a **porcine brain-derived peptide complex** developed by EVER Neuro Pharma (Austria) — a low-molecular-weight neurotrophic preparation containing a mixture of free amino acids and bioactive peptides extracted from purified pig brain proteins. Used clinically in 50+ countries (notably Russia, Eastern Europe, China, Mexico) for stroke recovery, traumatic brain injury, vascular dementia, and Alzheimer's disease.\n\nIn the United States, Cerebrolysin is **not FDA-approved** and is sold as a research-only peptide. The published clinical literature is substantial: multiple Cochrane meta-analyses cover its use in acute ischemic stroke, dementia, and TBI rehabilitation, with mostly positive — though heterogeneous — outcomes.\n\nMechanism is best characterized as **BDNF/NGF-mimetic + neuroprotective** rather than a single targeted drug action. The peptide complex appears to mimic endogenous neurotrophic factors, supporting neuronal survival, synaptic plasticity, and regeneration in injured tissue.", "half_life": "~2-4 hours (multi-component peptide mix)", "molecular_weight": "Not a single molecule. Cerebrolysin is a standardized concentrate (215.2 mg/mL) of free amino acids plus low-molecular-weight neuropeptides (below ~10 kDa), produced by controlled enzymatic digestion of purified porcine (pig) brain proteins.", "molecular_mass": "", "amino_acid_sequence": "Not applicable - Cerebrolysin is a mixture of many peptides and free amino acids, not a single sequenced peptide, so it has no one defined amino-acid sequence.", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "Once daily", "cycle_length": "10-30 day cycles, typically repeated every 2-3 months", "common_vial_sizes": [], "research_stage": "Clinical", "approval_status": "Not FDA-approved. In the US it is sold only as a research chemical (research use only, RUO) and is not approved for human use. It is an approved, marketed prescription neurotrophic drug in roughly 50 countries across Europe, Asia, Russia, the CIS, and Latin America (manufactured by EVER Pharma).", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": null, "potential_benefits": [ "Improved cognition and global clinical function in mild-to-moderate Alzheimer's disease across six double-blind RCTs of 30 mL/day Cerebrolysin, with a placebo-comparable safety profile (PMID: 25832905)", "Modest gains in cognition (MMSE and ADAS-cog+) and global function in mild-to-moderate vascular dementia, though the Cochrane evidence is rated very low quality (PMID: 31710397)", "Small-to-medium improvement in functional and neuropsychological recovery after moderate-to-severe traumatic brain injury in the CAPTAIN trial program, statistically significant at days 30 and 90 (PMID: 33620612)", "Add-on use after acute ischemic stroke has been studied extensively, but Cochrane analysis of 7 RCTs found no clear benefit on death or dependency and a possible rise in non-fatal serious adverse events at 30 mL/day (PMID: 37818733)", "A 2021 systematic review and meta-analysis of animal-derived nootropics found a real but modest pro-cognitive effect for Cerebrolysin (PMID: 36324709)" ], "research_fields": [], "pubmed_count": 85, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/cerebrolysin" }, { "id": "47f9d061-2852-49b9-ac9a-07ab0495d2ef", "slug": "chaga", "name": "Chaga", "aliases": [ "Inonotus obliquus", "Black mass", "Clinker polypore", "Cinder conk", "Birch mushroom", "Kabanoanatake" ], "category": "Adaptogen", "description": "**Chaga** (*Inonotus obliquus*) is a parasitic fungus that grows almost exclusively on birch trees (primarily *Betula pendula* and *Betula pubescens*) across the cold-temperate and subarctic forests of Siberia, Northern Russia, Scandinavia, the Baltic states, Canada, Alaska, and the northern tier of the continental United States. It is not a typical mushroom in appearance — rather than producing a fleshy, gilled fruiting body, chaga forms a hard, irregular, charcoal-black, cracked **sclerotial conk** that protrudes from the side of a living birch tree like a burnt piece of wood, sometimes reaching the size of a football or larger. The outer surface is brittle, deeply fissured, and resembles a chunk of cinder or burnt coal — hence its English folk names \"clinker polypore,\" \"cinder conk,\" and \"black mass.\" The interior is rust-orange to golden-brown and more fibrous, containing the concentrated mycelium where most of chaga's putative bioactive compounds reside. Russian folk medicine names it **chaga** (чага), Finnish **pakurikaapa**, Japanese **kabanoanatake** (樺孔茸, \"birch-hole-mushroom\"), and in English herbal literature it is sometimes called the \"birch mushroom\" or \"king of medicinal mushrooms\" — though this last honorific reflects marketing enthusiasm more than clinical evidence. Chaga is the culmination of a long, slow parasitic life cycle: once infection is established on a wounded birch, the fungus grows internally for 10-80 years before producing the external conk, which itself then grows slowly for additional decades before the host tree dies and the fungus produces a short-lived sexual fruiting body under the bark (rarely seen and not the conk). This extremely slow growth rate has significant sustainability implications discussed below.\n\n**Important evidence-framing up front**: Unlike [curcumin](/compound/curcumin), [boswellia](/compound/boswellia), or [ashwagandha](/compound/ashwagandha), **chaga is not a well-characterized clinical compound with meaningful randomized controlled trial evidence in humans**. The overwhelming majority of the scientific literature on chaga consists of **in vitro assays** (cell culture studies on cancer cell lines, antioxidant chemistry) and **animal models** (primarily mice, with some rat studies) — not human clinical trials. The small number of human studies that do exist are mostly open-label, uncontrolled, or extremely small pilot investigations. Marketing language around chaga frequently conflates in vitro antioxidant data and Russian ethnobotanical tradition with clinical efficacy; **this is not honest framing of the evidence base**. A clear-eyed assessment: chaga contains genuinely interesting phytochemistry (polysaccharides, triterpenoids, melanins, phenolic compounds) with plausible mechanisms of action and supporting preclinical data, but claims that chaga \"treats\" cancer, diabetes, autoimmune disease, or specific clinical conditions in humans are not supported by the quality of evidence that would justify such claims for a pharmaceutical agent. Additionally, **chaga carries a real, documented safety concern** — oxalate nephropathy (kidney injury from oxalate crystal deposition) has been reported in published case reports of chaga tea drinkers, most prominently **Kikuchi et al. 2014** (*CEN Case Reports*). This is not a hypothetical concern; it is a clinically material risk. Prospective chaga users should weigh these evidence limitations and safety considerations before committing to regular use — especially prolonged, high-dose use.\n\nChemically, chaga is a dense and unusual phytochemical reservoir. The three most studied classes of bioactive compounds are: **(1) polysaccharides and β-glucans**, particularly heteropolysaccharides and β-(1,3)/(1,6)-glucans extractable in hot water, which are putatively responsible for chaga's immunomodulatory effects; **(2) triterpenoids**, most notably **inotodiol**, **trametenolic acid**, **lanosterol**, **ergosterol peroxide**, **betulin**, and **betulinic acid** (the latter two acquired from the host birch tree and concentrated within chaga) — these lanostane-type and lupane-type triterpenes are alcohol-soluble and underlie most of chaga's anti-cancer and anti-inflammatory preclinical research; and **(3) polyphenols and melanins**, including a unique class of phenolic pigments responsible for chaga's distinctive dark color and much of its antioxidant capacity, plus compounds like **inonoblin A**, **phelligridin D**, and various styrylpyrones. Additional constituents include sterols, triterpene glycosides, and chromogenic complexes. The relative yields of these compound classes vary dramatically by extraction method: **hot water extraction** preferentially extracts the polysaccharides, **ethanol or alcohol extraction** extracts the triterpenoids and some polyphenols, and **dual extraction** (sequential water + alcohol) is the only method that captures the full spectrum of putative actives. Most cheap commercial chaga products use water extraction alone or simply grind raw chaga into powder; these deliver the polysaccharide fraction but leave the alcohol-soluble triterpenoids largely unextracted and bioavailability-limited.\n\nThe **traditional Russian use** of chaga is the foundational ethnobotanical context. For centuries, rural populations across Siberia, Northern Russia, and the Baltic Sea countries have prepared chaga as a **decoction tea** — typically by slow-simmering chopped chaga chunks in water for hours, producing a dark, coffee-colored, slightly bitter beverage. Traditional indications included gastrointestinal complaints (dyspepsia, ulcers, chronic gastritis), general malaise and fatigue, and — based on anecdotal 16th-19th century Russian folk reports — as a **cancer prophylactic** among peasant populations with supposedly low cancer incidence in chaga-consuming regions. The Soviet Union formally authorized chaga as an anti-cancer agent in 1955 under the product name **Befungin** (a semi-liquid chaga extract with added cobalt chloride), specifically for patients with inoperable or advanced cancers where conventional therapy was unavailable or contraindicated. Befungin remains available in Russian pharmacies today, though its clinical evidence base is limited to Soviet-era observational studies with methodology that would not meet modern regulatory standards. Western interest in chaga was substantially catalyzed by Alexandr Solzhenitsyn's 1968 novel *Cancer Ward*, which described chaga as a traditional Russian folk cancer remedy and helped seed the modern \"chaga as anti-cancer mushroom\" narrative that continues today — often without the accompanying epistemic caution that the Solzhenitsyn reference was literary, not clinical.\n\nThe **claimed modern benefits** of chaga span several domains, though the evidence quality for each is considerably weaker than for better-studied adaptogens: **(1) Immune modulation** — based on β-glucan and polysaccharide data, with animal and in vitro evidence but minimal human clinical validation. **(2) Antioxidant effects** — chaga has one of the highest **ORAC (oxygen radical absorbance capacity)** values of any tested natural food (Ko et al. 2011, *Food Chemistry*), but ORAC has been **largely discredited as a meaningful health biomarker**; the USDA removed its ORAC database in 2012, citing that no evidence establishes that ORAC values relate to health benefits in humans. High test-tube antioxidant capacity does not equal in-vivo clinical benefit. **(3) Anti-cancer effects** — extensively studied in cell culture and some animal models (Lee 2008, 2009; Mu 2013; Song 2013 and others), where chaga extracts and specific triterpenoids have shown apoptosis induction, anti-proliferative effects, and anti-metastatic activity against various cancer cell lines. **No rigorous human RCTs have established chaga as effective cancer treatment or prevention**; the Soviet-era Befungin data is observational. **(4) Blood sugar effects** — preclinical data suggest glucose-lowering activity; small clinical studies have been mixed and do not establish chaga as a diabetes intervention. **(5) Anti-inflammatory effects** — mechanistic rationale via triterpenoid NF-κB modulation, with preclinical support but thin clinical data. **(6) Liver support** — some preclinical hepatoprotective data; no meaningful human clinical evidence. **(7) General \"longevity and wellness\"** — no human evidence, purely extrapolation from adaptogen framing and Russian folk tradition.\n\n**Honestly stated, where does chaga fit?** Chaga is a traditional Russian and Northern-European ethnobotanical preparation with interesting preclinical phytochemistry — particularly its melanin-pigment antioxidant system, its β-glucan polysaccharide fraction, and its birch-derived triterpene content — but a clinical evidence base that is **markedly thinner than for curcumin, boswellia, ashwagandha, rhodiola, or even other medicinal mushrooms like [reishi](/compound/reishi), [cordyceps](/compound/cordyceps), or [lions-mane](/compound/lions-mane)**, all of which have more human trial data. Anyone considering chaga should understand that: (a) most of the scientific literature is in vitro and animal, not human; (b) marketing claims often outrun the evidence; (c) the ORAC \"antioxidant superfood\" narrative is built on a biomarker that the USDA itself stopped endorsing; and (d) there is a **genuine safety concern regarding oxalate content** that warrants attention. That said, for users who want a traditional adaptogen-style mushroom preparation, use chaga in **modest amounts** (1-2 cups of chaga tea daily, not extreme multi-liter-per-day use) with **dual-extracted high-quality products** and **adequate hydration**, chaga is reasonable within the context of a broader anti-oxidant and immune-support framework that also includes exercise, sleep, and diet — but it should not be positioned as a replacement for evidence-based medical care for any clinical condition.\n\n**Oxalate safety — stated prominently, not buried**: Chaga is **extraordinarily high in oxalates**. Reports suggest chaga may contain 200-400+ mg of soluble oxalate per gram of dried chaga — among the highest oxalate concentrations of any consumable natural product. Oxalates form insoluble calcium oxalate crystals that can deposit in the renal tubules and cause **oxalate nephropathy** — a form of acute-on-chronic kidney injury characterized by microscopic calcium oxalate crystal deposition, tubular damage, and progressive renal impairment. **Kikuchi et al. 2014** (*CEN Case Reports*) — \"Chronic kidney failure in a patient with chaga mushroom (*Inonotus obliquus*) tea drinking\" — reported an elderly Japanese woman with chronic kidney disease who developed progressive renal failure attributed to chronic high-volume chaga tea consumption (estimated 4-5 cups daily for approximately 6 months); renal biopsy revealed extensive calcium oxalate crystal deposition, and discontinuation of chaga allowed partial recovery. Subsequent case reports have reinforced this mechanism. **Individuals at elevated risk**: patients with existing chronic kidney disease (any stage), diabetes, hypertension with nephropathy, history of kidney stones, dehydration-prone states, malabsorption syndromes (which increase oxalate absorption), and those taking nephrotoxic medications. **Risk reduction strategies**: avoid chronic high-volume chaga tea consumption; prefer standardized extracts over tea decoctions (extracts may be somewhat lower in free oxalate depending on processing); maintain excellent hydration; use chaga intermittently rather than daily; avoid chaga entirely in the presence of existing CKD, kidney stone disease, or other elevated-risk conditions. This is a **real, documented, published safety concern** — not a hypothetical one — and it differentiates chaga from most other medicinal mushrooms (reishi, cordyceps, lion's mane, turkey tail, maitake), which do not share this oxalate load.\n\n**Sustainability concern**: Wild-harvested chaga — which is the preferred source for most traditional and high-end commercial products — grows slowly on living birch trees over decades. Once harvested, the conk does not regrow on the same tree. Overharvesting across Siberia, Canada, and Alaska has raised legitimate conservation concerns; some jurisdictions have begun regulating chaga harvest on public lands. Users purchasing chaga should prefer suppliers who verify sustainable harvest practices, leave portions of conks attached to allow some regrowth, and do not harvest from protected forests. Cultivated chaga (grown on substrate rather than living birch) is beginning to appear in commercial supply but is not yet the dominant source and may have different phytochemical profiles than wild-harvested conk.\n\nChaga is **not a caffeinated beverage**, despite frequent marketing as a \"coffee substitute\" or pairing with coffee-like aesthetics. It contains **zero caffeine**. The dark color, slightly bitter flavor, and traditional hot-decoction preparation create superficial associations with coffee, but the pharmacology is completely distinct. Users seeking a caffeine replacement for energy should look elsewhere; users seeking a caffeine-free warm traditional beverage may find chaga tea pleasant.\n\nSee also [reishi](/compound/reishi), [cordyceps](/compound/cordyceps), and [lions-mane](/compound/lions-mane) for other medicinal mushrooms with meaningfully stronger human clinical evidence; [ashwagandha](/compound/ashwagandha) and [rhodiola-rosea](/compound/rhodiola-rosea) for better-studied adaptogens; and [curcumin](/compound/curcumin) and [egcg](/compound/egcg) for polyphenolic antioxidant alternatives with substantially more clinical validation. Chaga sits alongside these compounds as a legitimate traditional preparation with interesting preclinical phytochemistry — but with thinner human evidence, real oxalate-related safety caveats, and marketing claims that consistently outrun the clinical data. This is educational content and not medical advice; prospective chaga users with any kidney, liver, bleeding-risk, diabetes-medication, or autoimmune context should involve their physician before regular use.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 6, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/chaga" }, { "id": "a33735bf-efbf-4b79-aabf-7bee0ff1b5a6", "slug": "choline", "name": "Choline", "aliases": [ "Choline bitartrate", "Choline chloride", "Phosphatidylcholine", "PC", "Lecithin", "Alpha-GPC", "L-alpha glycerylphosphorylcholine", "Glycerophosphocholine", "GPC", "CDP-choline", "Citicoline", "Choline citrate", "Choline dihydrogen citrate", "Betaine", "Trimethylglycine", "TMG", "Cytidine diphosphocholine" ], "category": "Essential Nutrient", "description": "Choline is an essential nutrient that was classified as a B-vitamin in the 1990s (sometimes loosely called vitamin B4, though that designation is not official) after the Institute of Medicine formally designated it essential in 1998 and established adequate intake recommendations. The adult AI (adequate intake, not RDA because tolerable upper limit evidence was deemed insufficient for a formal RDA at the time of designation) is 550 mg/day for men and 425 mg/day for women, 450 mg/day in pregnancy, 550 mg/day in lactation, and the tolerable upper limit is 3.5 g/day from all sources. The NHANES data reveal a striking gap between intake and recommendation: roughly 90% of Americans do not meet the AI for choline, with the gap largest in women, vegetarians, and vegans who lack the dense dietary sources (egg yolks, beef liver, fatty fish). Choline serves three fundamental biological functions: structural (as phosphatidylcholine, the dominant phospholipid of cell membranes, comprising 40–50% of membrane phospholipids in most tissues), neurotransmitter synthesis (as the precursor to acetylcholine, the central nervous system and neuromuscular junction neurotransmitter), and methylation (via betaine, an alternative methyl donor that complements folate-B12 dependent methylation for homocysteine handling and broader one-carbon metabolism). This functional breadth makes choline unusually consequential — deficiency affects liver fat metabolism (inadequate phosphatidylcholine for VLDL export produces nonalcoholic fatty liver), muscle function (via impaired membrane structure and acetylcholine signaling), and methylation status (via reduced betaine availability for BHMT-mediated homocysteine remethylation). Zeisel and colleagues at UNC Chapel Hill have published extensively on choline physiology over four decades, establishing the essentiality designation, characterizing the SLC44A1/SLC44A2 transporters, defining the PEMT pathway of endogenous phosphatidylcholine synthesis, and demonstrating that PEMT polymorphisms substantially affect individual choline requirements. The pregnancy and fetal development data are particularly compelling: choline intake below the AI during pregnancy has been associated with neural tube defects (complementing but distinct from folate), and Caudill's trial showing that maternal choline supplementation at 930 mg/day vs the standard 480 mg/day (both above the 450 mg AI) produced measurable improvements in infant information processing speed at 4–13 months, suggesting the current AI may be set below the level for optimal fetal neurodevelopment. Supplemental forms vary widely in bioavailability, cost, and clinical positioning. Choline bitartrate is the cheap baseline commonly used in multivitamins — bioavailable but with the least CNS penetration. Phosphatidylcholine from lecithin supplements provides choline along with the broader phospholipid, useful for liver and membrane support. Alpha-GPC (L-alpha-glycerylphosphorylcholine) provides choline as the metabolic precursor one step before phosphorylcholine and is marketed for cognitive enhancement, with some trial evidence supporting acetylcholine-dependent effects at 300–1,200 mg/day. CDP-choline (citicoline, cytidine diphosphocholine) provides choline alongside cytidine, and has been studied in stroke recovery (with mixed results in trials) and general cognitive support. Betaine (trimethylglycine, TMG) is the oxidized form of choline that specifically provides methyl groups to the BHMT homocysteine-remethylation pathway — used clinically for homocystinuria and explored for broader methylation support. See also [Folate](/compound/folate) for the methylation partnership, [Vitamin B12](/compound/vitamin-b12) for the methionine synthase alternative, [Glycine](/compound/glycine) for amino acid metabolism context, [Vitamin B6](/compound/vitamin-b6) for the homocysteine-lowering framework, and [Omega-3 fatty acids](/compound/omega-3-fatty-acids) for the membrane phospholipid story. This overview is educational only and is not medical advice.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/choline" }, { "id": "126bf0ac-5505-44fc-a962-9168bfeb8bfd", "slug": "chonluten", "name": "Chonluten", "aliases": [ "Pulmonary peptide" ], "category": "Recovery", "description": "\nChonluten is a bioregulator preparation originating from Vladimir Khavinson's St. Petersburg Institute of Bioregulation and Gerontology, positioned as a \"bronchial bioregulator\" intended to support respiratory epithelium, alveolar function, and airway regeneration in chronic obstructive pulmonary disease (COPD), chronic bronchitis, post-infectious respiratory dysfunction, and age-related decline of pulmonary function. Historically Chonluten has been marketed in two overlapping forms: (1) as a polypeptide extract prepared from bovine or porcine bronchial mucosa — an undefined-mixture \"natural bioregulator\" — and (2) as a defined-sequence synthetic short peptide, most commonly cited as the tripeptide Glu-Asp-Gly (EDG) in later Khavinson publications, sometimes rendered H-Glu-Asp-Gly-OH or E-D-G. Chonluten is closely related to [Bronchogen](/compound/bronchogen), which Khavinson's group developed as the longer tetrapeptide (Ala-Glu-Asp-Pro / AEDP) synthetic alternative in the same respiratory-bioregulator class, and sits alongside [Pinealon](/compound/pinealon), [Thymogen](/compound/thymogen), [Vilon](/compound/vilon), [Epitalon](/compound/epithalon), [Livagen](/compound/livagen), [Cardiogen](/compound/cardiogen), and [Cartalax](/compound/cartalax) within the broader Khavinson peptide-bioregulator programme.\n\nOutside Russia and a small number of former-Soviet-state publications, Chonluten is **not a registered pharmaceutical, not FDA- or EMA-reviewed, not listed in WADA categories**, and does not appear in GOLD, ATS/ERS, or NICE guidelines for COPD or chronic bronchitis. Published Russian work — most of it authored by Khavinson and collaborators — comprises in vitro studies in bronchial epithelial cell culture, rodent lung injury experiments, and small uncontrolled observational case series in elderly COPD and chronic bronchitis patients ([Khavinson et al., 2011]; [Chalisova et al., 2015]; [Anisimov et al., 2010]).\n\nThe relationship between Chonluten and [Bronchogen](/compound/bronchogen) deserves clear description. Both are positioned as respiratory bioregulators within the Khavinson framework. Chonluten in polypeptide-extract form was the original bronchial bioregulator — an undefined mixture from animal tissue, prepared by the extraction methodology Khavinson developed in the 1970s and 1980s. Bronchogen (AEDP) was subsequently synthesised as a defined tetrapeptide intended to reproduce the extract's biological activity in chemically characterised form. Chonluten in short-peptide form (EDG) represents a further minimisation to three amino acids, testing whether an even shorter sequence retains bioregulator activity. All three products — Chonluten extract, Chonluten-EDG, and Bronchogen-AEDP — are sold in the post-Soviet supplement market with overlapping positioning.\n\nBodyHackGuide covers Chonluten because it is sold online as both oral capsule (typically 20 mg with undisclosed active content) and injectable forms, and because it appears in longevity-stack discussions as a respiratory-support bioregulator. We describe what is known, what is claimed, and what is missing — and we steer readers seeking evidence-graded respiratory support toward the interventions with substantial replication: smoking cessation (by far the single highest-impact intervention), pulmonary rehabilitation, inhaled short- and long-acting bronchodilators for obstructive disease, inhaled corticosteroids where indicated, vaccinations (influenza, pneumococcal, COVID-19, RSV in older adults), weight management for restrictive/obesity-related disease, and specific biologic therapy (benralizumab, mepolizumab, dupilumab, tezepelumab) for severe asthma phenotypes. Chonluten is a plausible hypothesis within the Khavinson framework. It is not, in 2026, an evidence-graded respiratory therapy.\n", "half_life": "Not characterized in humans; no modern pharmacokinetic data exist. Short Khavinson peptides of this class are presumed to undergo rapid plasma hydrolysis (order of minutes).", "molecular_weight": "319.27 g/mol (synthetic EDG tripeptide, C11H17N3O8; ~319 Da)", "molecular_mass": "319.27 g/mol", "amino_acid_sequence": "Glu-Asp-Gly (EDG; H-Glu-Asp-Gly-OH) - the synthetic tripeptide form. The original historical Chonluten is an undefined bovine/porcine bronchial polypeptide extract (~1,000-10,000 Da) with no single defined sequence.", "administration_routes": [], "dose_range_mcg": "20 mg oral once daily for 10 days; 60-day washout", "dosing_frequency": "Once daily", "cycle_length": "10 days on, 60-day washout", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "70381-80-5", "iupac_name": "L-Alanyl-L-glutamyl-L-aspartylglycine", "chemical_formula": "H-Ala-Glu-Asp-Gly-OH", "potential_benefits": [ "Respiratory mucosal support", "Enhanced respiratory immunity", "Lung tissue maintenance", "Mucosal barrier integrity" ], "research_fields": [], "pubmed_count": 1, "pubchem_cid": 16117367, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/chonluten" }, { "id": "ee4e2796-efbb-4491-a5eb-3eb1c7748ab8", "slug": "chromium", "name": "Chromium", "aliases": [ "Cr", "Cr3+", "Cr III", "Trivalent chromium", "Chromium(III)", "Chromium picolinate", "CrPic", "Chromium polynicotinate", "Chromium nicotinate", "Chromium chloride", "CrCl3", "Chromium citrate", "Chromium aspartate", "Chromium histidinate", "Chromium arginate", "Chromium GTF", "GTF chromium", "Glucose tolerance factor", "Chromium yeast", "High-chromium yeast", "Brewer's yeast chromium", "Chromium malate", "Chromium orotate", "Chromodulin", "Low molecular weight chromium binding substance", "LMWCr" ], "category": "Mineral", "description": "\nChromium is a transition metal that occupies one of the more peculiar positions in human nutrition: long marketed as essential for carbohydrate metabolism and insulin sensitization, the evidence for chromium essentiality has progressively softened over the past two decades, and both the European Food Safety Authority (EFSA 2014) and multiple independent reviews have concluded that chromium III is not definitively essential for humans. Despite this, chromium supplements — particularly chromium picolinate — remain among the top-selling mineral supplements in the United States, largely on the strength of mid-1990s trials and aggressive marketing for diabetes and weight loss indications that subsequent larger and better-designed trials have not consistently replicated. The adult body contains only approximately 4-6 mg of chromium distributed across liver, kidney, spleen, and muscle, with concentrations declining with age — one of the few minerals showing this pattern. Louis-Nicolas Vauquelin isolated chromium in 1797 from Siberian red lead (crocoite, PbCrO4); the name derives from the Greek \"chroma\" (color) reflecting the vivid hues of chromium salts. The nutritional story began with Mertz and Schwarz in the 1950s-1960s, who reported that a \"glucose tolerance factor\" (GTF) extracted from brewer's yeast could restore impaired glucose tolerance in chromium-deprived rats — and that the active principle contained chromium complexed with nicotinic acid and amino acids. This spawned five decades of chromium supplementation research that remains incompletely resolved.\n\nCritical distinction: chromium exists in multiple oxidation states, of which two are nutritionally and toxicologically relevant. Trivalent chromium (Cr3+, chromium III) is the biologically relevant form found in food and nutritional supplements; it is poorly absorbed, of low acute toxicity, and is the form discussed throughout this entry. Hexavalent chromium (Cr6+, chromium VI, chromate) is a potent carcinogen, particularly pulmonary carcinogen in inhalational exposure (industrial welders, leather tanners, stainless steel workers, and the famous Erin Brockovich case involving groundwater contamination by Pacific Gas and Electric) — hexavalent chromium is listed as Group 1 carcinogen by IARC, and there is no safe exposure level for chronic inhalation. Hexavalent chromium is a strong oxidant that enters cells through sulfate transporters and generates reactive intermediates and DNA damage; trivalent chromium does not use these transport pathways and is orders of magnitude less toxic. All discussion of \"chromium supplementation\" refers to trivalent chromium (III); any discussion of chromium toxicity in industrial exposure contexts refers primarily to hexavalent chromium. These should not be conflated. Dietary and supplemental chromium is chromium III.\n\nThe US adequate intake (AI) for chromium is 35 μg/day for adult men and 25 μg/day for adult women, with pregnancy AI of 30 μg/day and lactation 45 μg/day. No tolerable upper intake level has been established for chromium III because of the absence of reliable dose-response toxicity data at nutritionally relevant doses; EFSA has similarly not set an upper limit. These AI values are based on limited intake estimation studies and should be considered provisional. Typical US dietary chromium intake ranges 20-50 μg/day for adults, roughly consistent with the AI. Food sources include broccoli (1 cup ~22 μg — notably high), grape juice and wine (5-20 μg/cup), beef (2 μg/3 oz), whole grains (1-5 μg per serving), some cheese, some spices, and brewer's yeast (particularly chromium-enriched brewer's yeast marketed as supplement source). Most processed foods contribute minimally. Stainless steel cookware leaches small amounts of chromium during cooking of acidic foods. Nutritional chromium deficiency in ordinary diets has not been definitively demonstrated, though marginal intakes are common and the few experimental deficiency reports (Jeejeebhoy 1977 on a TPN patient with glucose intolerance that reversed with chromium repletion) are single-case observations that subsequent investigators have not consistently reproduced.\n\nChromium absorption is poor — approximately 0.4-2.5% of dietary intake for chromium chloride and inorganic salts, up to 2-10% for chromium picolinate and organic chromium complexes. This low bioavailability is one reason chromium toxicity risk from oral supplementation is low but is also a reason supplementation requires microgram-level dosing to produce measurable physiologic effects. Absorbed chromium binds to transferrin and albumin in plasma, distributes to liver, kidney, spleen, bone, and muscle, and is excreted primarily in urine with a half-life of hours to days. Cellular uptake is not well-characterized; there is no identified specific chromium transporter, and uptake appears to occur through pinocytosis and possibly DMT1 at higher concentrations. Chromodulin (low molecular weight chromium binding substance, LMWCr) is a small oligopeptide of roughly 1,500 daltons containing four chromium atoms bound via glutamate, aspartate, cysteine, and glycine residues; chromodulin has been proposed as the active physiologic form of chromium in insulin signaling, where it amplifies insulin receptor tyrosine kinase activity. However, chromodulin as a physiologic mediator remains controversial, and more recent biochemistry has not consistently supported the model.\n\nThe chromium-diabetes story began with Anderson's 1997 Jiangsu Province trialrandomizing 180 Chinese type 2 diabetics to placebo, chromium picolinate 200 μg/day, or 1,000 μg/day for 4 months. The high-dose arm showed significant improvements in HbA1c (from 8.5% to 7.5%), fasting glucose, and insulin. This landmark trial launched the \"chromium for diabetes\" marketing and research program. However, subsequent larger and more rigorous trials have produced inconsistent results. The Cefalu 2002 US trial, the Gunton 2005 (PMID 15616242), the Costello 2016 Cochrane review, and the Lau 2012meta-analyses have variously reported modest or null effects on HbA1c and fasting glucose, with substantial heterogeneity across trials and no consistent dose-response. The Cochrane 2002 and subsequent updates have concluded that evidence for chromium's benefit in type 2 diabetes is limited. The one arguable signal of benefit is in populations with low baseline chromium status or poor glycemic control, where responders may show 0.5-1.0% HbA1c reductions; in general populations with well-controlled diabetes, effects are clinically negligible. The FDA denied a qualified health claim for chromium picolinate and diabetes in 2005 (citing insufficient evidence), later approving a weak qualified claim in 2010 (\"one small study suggests that chromium picolinate may reduce the risk of insulin resistance, and therefore possibly may reduce the risk of type 2 diabetes. FDA concludes, however, that the existence of such a relationship between chromium picolinate and either insulin resistance or type 2 diabetes is highly uncertain\").\n\nWeight loss and body composition marketing has been even more tenuous. The rationale is that chromium's putative insulin sensitization might reduce hunger or improve fat oxidation. Meta-analyses (Pittler 2003, Tian 2013) have found modest weight loss effects of approximately 1 kg vs. placebo over 10-24 weeks — small, statistically significant in pooled analysis but not clinically meaningful. The effect is dwarfed by any reasonable dietary intervention. Chromium picolinate is included in numerous \"fat burner\" and \"carb blocker\" formulations at doses of 200-1,000 μg, none of which produce demonstrable weight loss benefit beyond the modest effect of any chromium supplementation.\n\nCholesterol and lipid effects have been similarly weak. Some trials show small reductions in total cholesterol (approximately 5-15 mg/dL) with chromium picolinate at 200-1,000 μg/day. Effects on LDL, HDL, and triglycerides are inconsistent.\n\nDepression. A few small trials (Davidson 2003, Docherty 2005) have reported modest improvements in atypical depression with chromium picolinate 400-600 μg/day. The mechanism proposed is chromium effects on insulin/glucose and their interaction with serotonergic systems. These trials are small, short, and have not been replicated in larger studies.\n\nChromium picolinate specifically has been the subject of safety concerns that have substantially limited enthusiasm for its use. In vitro studies reported DNA damage from chromium picolinate but not from other chromium salts, attributed to the redox activity of the picolinate complex. Animal studies have shown some adverse findings (Stearns 2002), and concerns about dermatologic reactions, acute renal failure, rhabdomyolysis, and hepatic reactions at supratherapeutic doses have been reported in case series. Human safety data at recommended doses (200-1,000 μg/day) is generally reassuring but the in vitro and animal findings have led regulators (particularly the UK Food Standards Agency) to recommend against chromium picolinate and favor chromium polynicotinate or other forms if supplementation is used.\n\nBodyHackGuide's take: chromium is the trace mineral most associated with the gap between marketing enthusiasm and evidence. The essentiality case is weak enough that regulatory authorities have removed chromium from some required mineral lists. Deficiency in ordinary diets is not demonstrable. Supplementation for type 2 diabetes has modest and inconsistent effects; for weight loss, negligible effects. Chromium picolinate specifically has in vitro and animal safety concerns that — while not clearly translating to human harm at typical doses — make it a form we do not recommend. If chromium supplementation is pursued, it should be at modest doses (100-200 μg/day) of chromium polynicotinate or chromium histidinate, used for a defined period (3-6 months) with objective measurement of glycemic parameters (HbA1c), and discontinued if benefit is not demonstrated. For most users seeking glycemic improvement, the core interventions are dietary (carbohydrate reduction, Mediterranean or DASH patterns), exercise (particularly resistance training and post-prandial walks), [berberine](/compound/berberine) (1,000-1,500 mg/day with meals — far stronger evidence than chromium), [alpha-lipoic-acid](/compound/alpha-lipoic-acid), [magnesium](/compound/magnesium), and [vitamin-d3](/compound/vitamin-d3) adequacy. Chromium sits low on the evidence-based stack.\n\nHexavalent chromium toxicity warrants separate discussion even though it is not relevant to supplementation. Occupational exposure to Cr(VI) dust or fume in stainless steel welding, chromate production, leather tanning (historical), chrome plating, and similar industries produces dose-dependent lung cancer risk, nasal septum ulceration and perforation, contact dermatitis, and asthma. OSHA PEL for Cr(VI) is 5 μg/m3 (8-hour TWA) — substantially lower than for most metals, reflecting potent carcinogenicity. Environmental Cr(VI) contamination of drinking water (the Hinkley, California case that generated the Erin Brockovich lawsuit and subsequent 1996 settlement) is a public health concern in some jurisdictions; the California Cr(VI) drinking water standard is 10 μg/L, the strictest in the US. Ingested Cr(VI) is largely reduced to Cr(III) in the acidic stomach, which limits systemic absorption — but at high concentrations or with impaired gastric acidity, systemic Cr(VI) toxicity can occur, including hepatic and renal damage. For users of dietary chromium (Cr III) supplements, Cr(VI) is not a relevant concern; supplements contain only trivalent chromium.\n", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 1578, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/chromium" }, { "id": "a1000000-0000-0000-0000-000000000006", "slug": "cjc-1295", "name": "CJC-1295 (Mod GRF 1-29)", "aliases": [ "CJC no DAC", "CJC-1295 no DAC", "Modified GRF 1-29" ], "category": "Growth Hormone / IGF-1 Axis", "description": "CJC-1295 without DAC (also called **Modified GRF 1-29** or **MOD-GRF 1-29**) is a 30-amino-acid analog of the first 29 residues of endogenous **Growth Hormone Releasing Hormone (GHRH)**, with four strategic substitutions (D-Ala² for DPP-4 resistance, Gln⁸, Ala¹⁵, Leu²⁷) that extend its plasma half-life from <2 minutes (native GHRH) to **~30 minutes**. It was developed by ConjuChem Biotechnologies as the non-albumin-binding companion to CJC-1295 with DAC.\n\nThis is the **physiologic** version of CJC-1295. Because its half-life is short, each subcutaneous injection produces a single sharp GH pulse peaking at 30-60 minutes and returning to baseline within 2-3 hours — a pattern nearly identical to the body's natural nocturnal GH burst. This is in deliberate contrast to CJC-1295 with DAC, which produces continuous, non-pulsatile GH elevation over 1-2 weeks and is considered by many clinicians to be supra-physiologic.\n\nMOD-GRF 1-29 is almost always stacked with a **ghrelin receptor agonist** (ipamorelin, hexarelin, or MK-677) because the two signaling pathways converge synergistically on pituitary somatotrophs: GHRH activates the Gs/cAMP/PKA pathway while ghrelin-receptor activation triggers phospholipase-C/IP₃/calcium mobilization. Dual activation produces a GH pulse **3-5x greater** than either agent alone ([Bowers et al., *GH synergy*]).\n\nTypical dosing: **100 mcg SC 1-3x daily** (pre-bed is most common; fasted state optimizes GH response), often alongside 100-200 mcg ipamorelin at the same injection.\n\n**Key regulatory note:** CJC-1295 is **not FDA-approved** for any indication. Clinical development was halted at Phase 2. It is used extensively in integrative and anti-aging medicine via compounding pharmacy and is widely available as research-use peptide. The related molecule **sermorelin** (GRF 1-29 without the substitutions) was FDA-approved for pediatric GHD and is available as a compounded prescription in the US ([Tesar, 2010]).\n\nSee our [CJC-1295 Dosage Guide](/guides/dosage/cjc-1295) and [Reconstitution Tool](/tools/reconstitution/cjc-1295) for protocol specifics. The DAC variant is documented separately at [/compound/cjc-1295-dac](/compound/cjc-1295-dac).", "half_life": "~30 minutes (without DAC / MOD-GRF 1-29); ~6-8 days (with DAC, due to covalent albumin binding)", "molecular_weight": "3367.9 Da", "molecular_mass": "3367.9 g/mol", "amino_acid_sequence": "Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-NH2", "administration_routes": [ "Subcutaneous" ], "dose_range_mcg": "Without DAC: 100-300 mcg subcutaneous 1-3x daily (typically pre-bedtime); With DAC: 1000-2000 mcg subcutaneous once weekly", "dosing_frequency": "1–3 times daily, typically before bed and/or upon waking", "cycle_length": "8–16 weeks; can be used long-term with periodic breaks", "common_vial_sizes": [ "2mg", "5mg" ], "research_stage": "Phase 2 (clinical development discontinued)", "approval_status": "Not FDA-approved (RUO)", "trial_phase": "Preclinical", "cas_number": "863288-34-0", "iupac_name": "Modified GRF(1-29) with 4 amino acid substitutions", "chemical_formula": "C165H271N47O46", "potential_benefits": [ "Preserves physiologic pulsatile GH secretion", "Stimulates endogenous GH release (2-5x baseline per pulse)", "3-5x greater GH response when stacked with ipamorelin", "Modest IGF-1 elevation (1.5-2x baseline)", "Improved sleep depth and architecture", "Enhanced recovery from exercise and injury", "Body composition improvements (lean mass preservation, modest fat loss)", "Lower desensitization risk vs CJC-1295 with DAC", "Maintains GH negative-feedback integrity", "Synergistic with BPC-157, TB-500 for recovery protocols" ], "research_fields": [ "Growth hormone axis", "Body composition", "Sports medicine / recovery", "Anti-aging medicine", "Endocrinology", "Sleep medicine", "Compounding pharmacy" ], "pubmed_count": 29, "pubchem_cid": 91810141, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/91810141/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/cjc-1295" }, { "id": "f2e74cac-c85a-4b65-a0cc-816dfdcc7ba4", "slug": "cjc-1295-dac", "name": "CJC-1295 with DAC", "aliases": [ "CJC w/ DAC", "CJC DAC" ], "category": "Growth Hormone / IGF-1 Axis", "description": "CJC-1295 with DAC (Drug Affinity Complex) is a modified form of CJC-1295 that incorporates a **maleimidopropionic acid (MPA) reactive group** at the C-terminus. Once injected, this MPA group forms a **covalent thioether bond with free cysteine residues on serum albumin**, effectively turning the small peptide into a long-circulating albumin-peptide conjugate.\n\nThe pharmacokinetic consequence is dramatic. Native GHRH has a half-life of <2 minutes. MOD-GRF 1-29 (CJC-1295 without DAC) has a half-life of ~30 minutes. **CJC-1295 with DAC has a half-life of ~8 days** and produces sustained IGF-1 elevation for up to 28 days after a single injection ([Teichman et al., 2006, *J Clin Endocrinol Metab*](https://pubmed.ncbi.nlm.nih.gov/16352683/)).\n\nThis makes DAC the **weekly-dosing variant**: one subcutaneous injection of 1-2 mg per week, typically on the same day each week. Convenience is its headline advantage over MOD-GRF 1-29's 2-3x daily injections.\n\nThe trade-off is physiologic. DAC produces **continuous, non-pulsatile GH elevation** rather than the sharp pulses of natural secretion or MOD-GRF 1-29. In Teichman's Phase 1 trial, mean GH levels at 60 mcg/kg rose 2-10 fold above baseline and **remained elevated continuously for 6-14 days** after a single injection, with IGF-1 rising 1.5-3 fold and staying elevated for up to 28 days with repeated weekly dosing. This is an efficient way to raise IGF-1 but is not how the body normally operates.\n\nClinical development was halted at Phase 2 — ConjuChem Biotechnologies did not publicly detail the reason, though industry commentary has pointed to concerns about sustained non-pulsatile GH elevation, insulin resistance, and the general challenges of bringing a GH-axis drug to market. Tesamorelin (a shorter-acting GHRH analog) became the FDA-approved GHRH analog for HIV-associated lipodystrophy instead.\n\nCJC-1295 with DAC is **not FDA-approved** and is used research-only or through compounding pharmacies. It is the less-favored of the two CJC-1295 forms in modern clinical protocols; most practitioners now prefer MOD-GRF 1-29 (without DAC) stacked with ipamorelin for the more physiologic pulsatile profile.\n\nSee [/compound/cjc-1295](/compound/cjc-1295) for the non-DAC variant, and our [Reconstitution Tool](/tools/reconstitution/cjc-1295) for injection math.", "half_life": "6–8 days (due to albumin binding via DAC)", "molecular_weight": "~3647 Da", "molecular_mass": "3647.1 g/mol", "amino_acid_sequence": "Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-Lys-NH2 - a 30-residue tetra-substituted analog of human GRF(1-29): [D-Ala2, Gln8, Ala15, Leu27] substitutions (the \"modified GRF 1-29\" backbone), plus a C-terminal Lys30 bearing a maleimidopropionyl (MPA) \"DAC\" linker that forms a covalent thioether bond with Cys-34 of serum albumin.", "administration_routes": [ "Subcutaneous" ], "dose_range_mcg": "1,000–2,000 mcg (1–2 mg) per injection", "dosing_frequency": "Once per week", "cycle_length": "8–12 weeks with 4 week breaks", "common_vial_sizes": [ "2mg", "5mg" ], "research_stage": "Phase II", "approval_status": "Not approved for human use - investigational only. Clinical development halted at Phase 2; not FDA-approved and not an approved therapeutic in any jurisdiction. Available solely as a research compound (research use only).", "trial_phase": "Phase 2", "cas_number": "863288-34-0", "iupac_name": "CJC-1295 with Drug Affinity Complex", "chemical_formula": "C165H271N47O46", "potential_benefits": [ "Sustained IGF-1 elevation (1.5-3x baseline) for 28+ days", "Convenient weekly subcutaneous dosing", "Improved body composition (lean mass, fat loss)", "Enhanced recovery from training and injury", "Albumin conjugation extends half-life to ~8 days", "Stimulates endogenous GH production vs exogenous replacement", "Dose-dependent GH elevation 2-10x baseline", "Phase 1 clinical data in 50 healthy adults (Teichman 2006)", "Useful in compounding pharmacy GH-axis protocols", "Single-agent convenience vs combination peptide protocols" ], "research_fields": [ "Growth hormone axis", "Long-acting peptide therapeutics", "Body composition", "Anti-aging medicine", "Albumin-drug conjugation chemistry", "Endocrinology", "Compounding pharmacy" ], "pubmed_count": 0, "pubchem_cid": 91810141, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/91810141/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/cjc-1295-dac" }, { "id": "f89af1e7-9afe-4998-955a-b9322c37be3a", "slug": "cjc-1295-no-dac", "name": "CJC-1295 No-DAC (Mod GRF 1-29)", "aliases": [ "Mod GRF 1-29", "CJC-1295 without DAC", "Modified GRF 1-29", "CJC No-DAC" ], "category": "GH Secretagogue", "description": "CJC-1295 No-DAC (also known as Mod GRF 1-29) is a 29-amino-acid synthetic peptide modeled on the active N-terminal fragment of human Growth Hormone Releasing Hormone (GHRH 1-29). Four amino acid substitutions stabilize the peptide against enzymatic degradation but, unlike CJC-1295 with DAC, this version does NOT carry the Drug Affinity Complex (DAC) - meaning it has a short serum half-life (~30 minutes) and produces a single physiological GH pulse rather than sustained GHRH stimulation.\n\nThe short pulse profile is closer to natural pulsatile GHRH biology, which makes Mod GRF 1-29 the preferred choice when researchers want to amplify natural GH peaks (e.g., paired with ipamorelin pre-bed) without continuous GHRH receptor stimulation.", "half_life": "~30 minutes (no DAC means no extended binding)", "molecular_weight": "3367.9 g/mol (average; molecular formula C152H252N44O42)", "molecular_mass": "3367.9 Da (average)", "amino_acid_sequence": "Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-NH2 (tetrasubstituted [D-Ala2, Gln8, Ala15, Leu27]-hGRF(1-29)-NH2)", "administration_routes": [ "Subcutaneous" ], "dose_range_mcg": "100 mcg per dose, 2-3x daily", "dosing_frequency": "Subcutaneous 2-3x per day (typical: AM, post-workout, pre-bed)", "cycle_length": "8-12 weeks per cycle, 4 weeks off", "common_vial_sizes": [ "2mg", "5mg" ], "research_stage": "Preclinical / Research peptide", "approval_status": "Not FDA-approved.", "trial_phase": "Preclinical / Research peptide", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Single GH pulse mimicking natural GHRH biology", "Synergistic with GHRP peptides (supra-additive GH release)", "No DAC = no receptor desensitization", "Pre-bed dosing supports deep sleep and recovery", "Improved body composition over 8-12 week cycles" ], "research_fields": [ "Growth hormone biology", "GHRH receptor", "Pituitary somatotrophs", "Sleep architecture", "Recovery" ], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/cjc-1295-no-dac" }, { "id": "594cbfc9-ce7f-4c6b-8e20-5a075e44dde9", "slug": "cjc-1295-with-dac", "name": "CJC-1295 with DAC", "aliases": [ "CJC-1295 DAC", "CJC-1295 long-acting", "CJC with DAC" ], "category": "Growth Hormone / IGF-1 Axis", "description": "CJC-1295 with DAC is the long-acting variant of CJC-1295. The Drug Affinity Complex (DAC) is a maleimidopropionic acid moiety that covalently binds serum albumin in vivo, dramatically extending the peptide's plasma half-life from ~30 minutes (No-DAC) to ~8 days. This enables once-weekly dosing with sustained GHRH receptor activation across the dosing interval.\n\nThe extended half-life is a double-edged sword: the convenience of weekly dosing comes with continuous (rather than pulsatile) GHRH receptor stimulation, which can drive receptor desensitization and elevated baseline IGF-1 with prolonged use. Pulse amplitude ratios are different from natural GH biology - researchers should weigh the convenience against the deviation from physiological pulsatility.", "half_life": "~6-8 days (DAC-bound albumin depot)", "molecular_weight": "3647.2 g/mol", "molecular_mass": "3647.2 Da", "amino_acid_sequence": "Modified GRF(1-29) analog [D-Ala2, Gln8, Ala15, Leu27] with a C-terminal Lys30 bearing the DAC (Drug Affinity Complex): Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-Lys-NH2 (30 residues, C-terminally amidated). Lys30 carries a maleimidopropionyl (3-maleimidopropionic acid) group that covalently binds circulating serum albumin, extending the half-life to several days. Molecular formula ~C152H252N44O42; MW ~3647.2 g/mol.", "administration_routes": [ "Subcutaneous" ], "dose_range_mcg": "1000-2000 mcg (1-2 mg) per week", "dosing_frequency": "Once or twice weekly subcutaneous", "cycle_length": "8-12 weeks per cycle, 4-8 weeks off", "common_vial_sizes": [ "2mg", "5mg" ], "research_stage": "Discontinued clinical (Phase 1 human PK/PD data; no approved use)", "approval_status": "Not FDA-approved.", "trial_phase": "Preclinical / Research peptide", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Sustained elevated GH and IGF-1 baseline (weekly dosing)", "Convenience of once/twice weekly dosing", "Synergy with GHRPs for pulse + sustain protocols", "Improved body composition over 8-12 week cycles" ], "research_fields": [ "Growth hormone biology", "GHRH receptor", "Albumin-bound peptides", "Long-acting peptide design" ], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/cjc-1295-with-dac" }, { "id": "f25eadc6-7de3-4eda-81e4-72d112aad3c0", "slug": "cjc-ipa-blend", "name": "CJC-1295/Ipamorelin Blend", "aliases": [ "CJC/Ipa", "CJC Ipa Blend" ], "category": "Growth Hormone", "description": "Pre-mixed GHRH + GHRP blend for synergistic growth hormone release via dual-receptor stimulation.", "half_life": "CJC-1295 as mod GRF 1-29 (no DAC): ~30 minutes. Ipamorelin: ~2 hours. The long-acting CJC-1295 with DAC is far longer - an estimated 5.8-8.1 days in its Phase I characterization [PMID:16352683] - but standard blends use the short-acting no-DAC form.", "molecular_weight": "Blend of two separate peptides (not a single molecule). Ipamorelin (pentapeptide): 711.85 g/mol, C38H49N9O5. CJC-1295 as mod GRF 1-29 (no DAC - the form used in standard blends): ~3367.9 g/mol, C152H252N44O42. The long-acting CJC-1295 with DAC variant is heavier (~3647 g/mol) due to the added albumin-binding group.", "molecular_mass": "", "amino_acid_sequence": "Blend of two peptides. Ipamorelin (pentapeptide): Aib-His-D-2-Nal-D-Phe-Lys-NH2. CJC-1295 as mod GRF 1-29 - a GHRH(1-29) analog with four substitutions (D-Ala2, Gln8, Ala15, Leu27): Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-NH2. (The DAC variant appends a Lys-linked maleimidopropionyl albumin-binding group at the C-terminus.)", "administration_routes": [ "Subcutaneous", "Intramuscular" ], "dose_range_mcg": "Not human dosing guidance. Vendor blends are typically pre-mixed at a fixed ratio - commonly around 100 mcg CJC-1295 (mod GRF 1-29) to 100-200 mcg Ipamorelin per unit. Community-reported figures only; no clinically established dose exists.", "dosing_frequency": "1–2 times daily; bedtime injection most common", "cycle_length": "8–16 weeks; can be used long-term with periodic 4-week breaks", "common_vial_sizes": [ "5mg", "10mg" ], "research_stage": "Preclinical / early-stage (no combination trials)", "approval_status": "Not approved - research use only", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "Blend", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/cjc-ipa-blend" }, { "id": "28755e12-d5b0-43be-9fee-a48488ec9135", "slug": "clascoterone", "name": "Clascoterone", "aliases": [ "Winlevi", "Cortexolone 17alpha-propionate", "CB-03-01", "Breezula", "17alpha-propionyl cortexolone" ], "category": "Pharmaceutical", "description": "**Clascoterone** (brand name **Winlevi**; development codes CB-03-01 and, for the alopecia formulation, Breezula) is a **first-in-class topical androgen receptor (AR) antagonist** approved by the U.S. Food and Drug Administration in **August 2020** for the treatment of **acne vulgaris in patients 12 years of age and older**. It is chemically **cortexolone 17α-propionate**, an ester prodrug of cortexolone (11-deoxycortisol), designed to bind and competitively inhibit androgen receptors in cutaneous target tissues — specifically the sebocytes of sebaceous glands and dermal papilla cells of hair follicles — and then to be rapidly hydrolyzed to cortexolone in plasma so that systemic androgen blockade is minimized. This pharmacologic strategy — potent local AR antagonism with rapid systemic deactivation — makes clascoterone meaningfully different from oral antiandrogens like [spironolactone](/compound/spironolactone) and [finasteride](/compound/finasteride), which produce systemic androgen-pathway effects and carry the corresponding systemic side effect profile (menstrual irregularity, gynecomastia, sexual dysfunction, potassium/electrolyte concerns). Clascoterone was developed by Cassiopea S.p.A. (an Italian dermatology-focused pharmaceutical company spun out of Cosmo Pharmaceuticals) over roughly two decades of preclinical and clinical development, culminating in two identically-designed Phase 3 randomized placebo-controlled trials (NCT02608775 and NCT02608827) published in JAMA Dermatology in 2020 by Hebert and colleagues (PMID: 32320027), demonstrating statistically significant improvements in acne lesion counts and Investigator's Global Assessment (IGA) success rates over 12 weeks.\n\n**Important framing up front**: Clascoterone is a **genuine, novel, FDA-approved pharmaceutical** with two well-designed Phase 3 randomized controlled trials supporting its efficacy in acne vulgaris — not an herbal supplement, not a cosmeceutical, not an extrapolated off-label use. The evidence base for the **labeled indication** (acne vulgaris, age 12+, twice-daily topical application of 1% cream) is solid by dermatology standards: thousands of patients randomized in the key trials, placebo-controlled design, consistent efficacy signal across both studies, and acceptable safety profile at the topical dose. It represents the **first entirely new mechanism-of-action topical acne treatment in nearly 40 years** — the prior generation of topical acne therapeutics (retinoids, benzoyl peroxide, topical antibiotics) addresses the inflammatory and microbial pillars of acne pathogenesis, while clascoterone is the first topical agent to directly target the **androgen-driven sebogenesis pillar** that had previously required systemic therapy (oral antiandrogens, hormonal contraceptives, isotretinoin) to address. This is a genuinely new therapeutic option for the subset of acne patients whose disease is substantially androgen-driven and who either cannot tolerate, do not want, or have contraindications to systemic antiandrogen therapy.\n\n**Honest positioning — what clascoterone is and is not**: Clascoterone is (1) the first topical AR antagonist approved for acne in adolescents and adults 12+; (2) efficacious but **modestly** so — in the Phase 3 trials, IGA treatment success was achieved in roughly 18-20% of clascoterone-treated patients vs 7-9% of vehicle-treated patients at 12 weeks, a real and statistically significant but not dramatic effect magnitude; (3) well-tolerated with the most common side effects being mild application site reactions (erythema, scaling, dryness, pruritus) at rates comparable to the vehicle cream; (4) potentially useful off-label for **androgenetic alopecia (male pattern hair loss)** based on a single published pilot study (Mazzetti 2019) and an active Phase 2/3 development program by Cassiopea under the Breezula brand, though this off-label use is not FDA-approved and rests on preliminary evidence. Clascoterone is **not** (1) a replacement for [isotretinoin](/compound/isotretinoin) in severe nodulocystic acne — isotretinoin remains the definitive treatment for severe disease; (2) as potent as systemic antiandrogens for severe hormonal acne — [spironolactone](/compound/spironolactone) typically produces more dramatic improvements in severe hormonal acne in women; (3) a proven hair loss treatment — the alopecia evidence is preliminary, and [minoxidil](/compound/minoxidil) plus finasteride (or [dutasteride](/compound/dutasteride)) remain the evidence-based gold standard; (4) without risk — the FDA label includes a caution about **hypothalamic-pituitary-adrenal (HPA) axis suppression** observed in a pediatric open-label safety study, warranting careful monitoring particularly in children and with large-surface-area application. Men and women considering clascoterone should understand it as a real but targeted therapeutic option — useful within its proven indication (topical acne therapy 12+) and potentially useful in the investigational hair loss space, not as a miracle cure or as a categorically superior alternative to established acne or alopecia therapies.\n\n**Regulatory and development history**: The clascoterone program originated in the early 2000s with preclinical work at Cosmo Pharmaceuticals on cortexolone-based compounds as topical androgen modulators. Cortexolone itself — 11-deoxycortisol, an intermediate in cortisol biosynthesis — has weak but real affinity for both the glucocorticoid receptor and the androgen receptor, with some selectivity for the AR at certain tissue levels. The propionate ester (cortexolone 17α-propionate, later named clascoterone) was developed to improve lipid-solubility and skin-penetration properties, giving the compound enhanced topical bioavailability at the target cutaneous tissues while retaining rapid systemic hydrolysis to cortexolone upon absorption into plasma. This design philosophy — topical efficacy with minimal systemic exposure — is fundamental to the clascoterone safety positioning and distinguishes it from orally-administered AR antagonists. Cassiopea (formed as a dermatology-focused spin-off from Cosmo) took clascoterone through Phase 2 and Phase 3 development between approximately 2010 and 2019, with the acne Phase 3 trials (CB-03-01/25 and CB-03-01/26, corresponding to NCT02608775 and NCT02608827) completing enrollment in 2018-2019 and reporting in 2020. FDA approval was granted in **August 2020** for the 1% cream formulation under the brand name Winlevi, with indication for \"the topical treatment of acne vulgaris in patients 12 years of age and older.\" Marketing in the US commenced in 2021 through Sun Pharmaceutical, which acquired North American commercialization rights from Cassiopea. The alopecia development program (Breezula) has proceeded on a separate timeline, with Phase 2 data published from Mazzetti and colleagues and Phase 3 development ongoing as of this writing.\n\n**Claimed benefits and where evidence supports them**: The rigorously evidenced benefit is **acne vulgaris symptom improvement** — specifically, reduction in non-inflammatory (comedonal) and inflammatory (papular, pustular) acne lesion counts, and achievement of \"Investigator's Global Assessment success\" (defined as IGA score of 0 or 1 — clear or almost clear — with at least a 2-point improvement from baseline) over 12 weeks of twice-daily topical application. The Hebert 2020 JAMA Dermatology publication (PMID: 32320027) reports: (1) IGA treatment success at week 12: ~18-20% on clascoterone vs ~7-9% on vehicle across both studies (absolute difference ~10-11%, statistically significant); (2) mean absolute reduction in inflammatory lesions: ~45% on clascoterone vs ~33% on vehicle; (3) mean absolute reduction in non-inflammatory lesions: ~42% on clascoterone vs ~30% on vehicle; (4) consistent efficacy across adolescent (12-17) and adult (18+) subgroups. These are **clinically meaningful but not dramatic** effects — patients treated with clascoterone can expect modest-to-moderate improvement, particularly in patients whose acne has a significant androgen-driven component (oilier skin, cyclical menstrual flares in women, response to oral antiandrogens in prior treatment). Less rigorously evidenced benefits include: (a) **improvement in androgenetic alopecia** — Mazzetti 2020 pilot study in men with male pattern hair loss showed hair count improvements over 6 months at higher clascoterone solution concentrations, but the trial was small (n=36) and open-label; larger Phase 2/3 Breezula trials are ongoing; (b) **potential utility in hidradenitis suppurativa, folliculitis, seborrheic dermatitis, and other androgen-influenced cutaneous conditions** — mechanistically plausible but not formally studied in RCTs; (c) **cosmetic benefit in oily-skin/sebum-overproduction contexts** — extrapolated from sebocyte AR blockade, not directly studied as a cosmetic endpoint.\n\n**Where evidence does NOT support clascoterone**: (1) **not a proven hair loss treatment** — the alopecia evidence is preliminary; the compound is not FDA-approved for hair loss; (2) **not established in pediatric populations under 12** — safety data specifically in younger children is limited and HPA axis suppression has been observed in pediatric open-label safety studies; (3) **not a replacement for systemic acne therapy in severe disease** — severe nodulocystic acne, scarring acne, and acne unresponsive to topical/systemic standard therapies warrant [isotretinoin](/compound/isotretinoin) or other systemic options; (4) **not studied in pregnancy or lactation** — Pregnancy Category has been designated with insufficient data; avoid during pregnancy/breastfeeding until more data available; (5) **not demonstrated to be superior to established topical therapies** — comparative trials against [tretinoin](/compound/tretinoin), [adapalene](/compound/adapalene), [benzoyl-peroxide](/compound/benzoyl-peroxide), or topical antibiotics are limited; most clinical use positions clascoterone as adjunctive or complementary to (not replacing) established topical acne regimens.\n\n**Novel mechanism and why it matters**: Acne vulgaris pathogenesis involves four interacting pillars — (1) androgen-driven sebogenesis (excess sebum production by sebocytes); (2) follicular hyperkeratinization and comedogenesis; (3) Cutibacterium acnes (formerly Propionibacterium acnes) colonization and biofilm formation; (4) inflammation. Traditional topical acne therapies address pillars 2-4: topical retinoids (tretinoin, adapalene, trifarotene) normalize keratinization and reduce inflammation; benzoyl peroxide kills C. acnes; topical antibiotics (clindamycin, erythromycin) suppress C. acnes; newer agents like topical azelaic acid, dapsone, and minocycline address multiple pillars. **None of the prior topical agents directly target pillar 1 (androgen-driven sebogenesis)**. Systemic treatments do — oral contraceptives, spironolactone, finasteride, and isotretinoin all modulate sebum production through androgen-pathway or sebaceous-gland-specific mechanisms — but at the cost of systemic exposure and the corresponding side-effect profile. Clascoterone is the first topical agent to target pillar 1 directly, potentially complementing prior topical regimens by addressing a mechanism they could not. This is not a trivial advance — for patients whose acne is substantially androgen-driven (many adult women with persistent acne, adolescents with oilier/sebaceous-rich skin, patients with polycystic ovary syndrome or similar hyperandrogenic conditions), a topical AR antagonist represents a genuinely new therapeutic lever that was not previously available.\n\n**Off-label hair loss context — emerging but not established**: Androgenetic alopecia (male pattern baldness, female pattern hair loss) involves progressive miniaturization of hair follicles in genetically susceptible individuals, driven largely by local conversion of testosterone to dihydrotestosterone (DHT) within the follicle via 5α-reductase and subsequent DHT-mediated activation of androgen receptors in dermal papilla cells. Current evidence-based therapies include: (1) [minoxidil](/compound/minoxidil) (topical 2%, 5%, or oral low-dose) — FDA-approved, works via unclear vasodilatory/follicle-stimulating mechanism, not anti-androgenic; (2) [finasteride](/compound/finasteride) (1 mg oral) — FDA-approved for male pattern hair loss, inhibits type 2 5α-reductase systemically, reduces DHT by ~70%; (3) [dutasteride](/compound/dutasteride) (oral, off-label for hair loss) — dual 5α-reductase inhibitor, more potent DHT suppression; (4) topical finasteride or dutasteride (compounded or emerging prescription products; Piraccini 2022) — attempt to achieve local scalp effect with less systemic exposure. **Clascoterone's proposed role in alopecia** is as a topical AR antagonist — blocking DHT action at the follicle rather than blocking DHT production as 5-ARIs do. The Mazzetti 2020 pilot study showed hair count improvements at the 7.5% clascoterone solution concentration over 6 months in men with androgenetic alopecia. **Caveats**: (a) single small pilot study; (b) the alopecia formulation is different from the acne cream (higher concentration, solution vehicle); (c) not FDA-approved for hair loss; (d) available only through compounding pharmacies or research protocols outside of acne-indication use; (e) longer-term efficacy data, comparative data against minoxidil/finasteride, and optimal combination protocols remain to be established.\n\nClascoterone sits alongside [spironolactone](/compound/spironolactone), [finasteride](/compound/finasteride), [dutasteride](/compound/dutasteride), [ru-58841](/compound/ru-58841), [saw-palmetto](/compound/saw-palmetto), and [pygeum](/compound/pygeum) within the broader category of compounds that modulate androgen pathways, but it is distinctive in being (a) topically administered, (b) FDA-approved for acne specifically, (c) rapidly systemically deactivated to minimize systemic exposure, and (d) mechanistically novel (first topical AR antagonist). This is educational content and not medical advice; anyone considering clascoterone for acne should involve a dermatologist, particularly given the specificity of indication and the HPA axis suppression considerations; anyone considering off-label use for hair loss should involve a dermatologist or hair-loss specialist and understand that the hair loss evidence is preliminary, the preparation typically requires compounding, and cost-benefit versus established therapies (minoxidil, finasteride) is not yet established.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 1188, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/clascoterone" }, { "id": "0ef1bcbe-d0e9-4987-93a7-08d449d511de", "slug": "clenbuterol", "name": "Clenbuterol", "aliases": [ "Clen", "Spiropent", "Ventipulmin", "Dilaterol", "Novegam", "NAB-365", "4-amino-alpha-[(tert-butylamino)methyl]-3,5-dichlorobenzyl alcohol" ], "category": "Controlled Substances", "description": "Clenbuterol is a long-acting, selective beta-2 adrenergic receptor agonist originally developed in the late 1970s by Thomae GmbH (later Boehringer Ingelheim) as a bronchodilator for obstructive airway disease. Structurally it is a sympathomimetic amine — 4-amino-alpha-[(tert-butylamino)methyl]-3,5-dichlorobenzyl alcohol — with a catecholamine-like pharmacophore but with the catechol hydroxyls replaced by a dichloroanilino group that dramatically extends its plasma half-life (~26-36 hours in humans) compared to endogenous catecholamines (minutes). It was approved for human use as an asthma and chronic obstructive pulmonary disease bronchodilator in several European countries (Germany, Italy, Spain, Bulgaria, Russia) and throughout Latin America under brand names Spiropent, Dilaterol, Novegam, and Broncoterol, where it is typically dispensed as 20-microgram tablets or syrup. It was never approved for human use in the United States, United Kingdom, Canada, or Australia; in the US it is FDA-approved only as Ventipulmin, a veterinary bronchodilator for horses with recurrent airway obstruction (heaves). Despite lacking human FDA approval, clenbuterol has become one of the most widely misused performance-improving compounds in bodybuilding, strength athletics, and physique contest preparation, primarily because of two pharmacologic properties that extend beyond its bronchodilator indication: sustained thermogenesis (increased resting energy expenditure via uncoupling protein induction and beta-2-mediated metabolic effects) and skeletal muscle hypertrophy in animal models (via beta-2 receptor stimulation of type II muscle fiber protein synthesis pathways). The combination produces, on paper, a \"repartitioning\" effect — fat loss with preservation or gain of lean mass — that is the holy grail of contest preparation pharmacology. In practice, the human evidence for this effect at bodybuilding doses is essentially absent (no placebo-controlled trials have examined clenbuterol for fat loss in healthy humans), the cardiotoxicity is substantial, and the case reports of serious adverse events are numerous. Clenbuterol is banned by the World Anti-Doping Agency (WADA) under S1.2 \"Other Anabolic Agents\" and has been responsible for high-profile doping cases in cycling, baseball, track and field, and combat sports. The compound is additionally notorious for a unique contamination route: in several countries (notably Mexico and China during the 2000s-2010s), livestock producers illegally fed clenbuterol to cattle and pigs to increase lean yield at slaughter, resulting in residues in meat sufficient to produce mass poisoning events and inadvertent doping of athletes who ate contaminated meat. Clenbuterol's chemical profile of slow clearance, high potency (effective human doses in the tens of micrograms), and widespread grey-market availability — sold as \"research chemical,\" liquid oral solutions, or smuggled foreign pharmaceutical tablets — has created a distinctive risk landscape. Users commonly escalate doses aggressively to overcome receptor desensitization, leading to cumulative cardiac stress, electrolyte derangements, rhabdomyolysis, and tachyarrhythmias that have produced multiple documented hospitalizations and some fatalities. The published case report literature contains dozens of clenbuterol-related emergency presentations including ventricular tachycardia, atrial fibrillation, takotsubo cardiomyopathy, acute myocardial infarction in structurally normal coronaries, severe hypokalemia (K+ < 2.5 mEq/L), and skeletal muscle necrosis. This entry covers clenbuterol's legitimate pharmacology as a bronchodilator, the animal and human evidence base for its off-label performance-improving uses, the cardiovascular toxicology that makes it genuinely dangerous, the WADA status and contaminated-meat issue, and provides honest framing about why BodyHackGuide does not recommend clenbuterol for fat loss or muscle-sparing purposes regardless of dose or cycle structure. Safer alternatives for the same goals (targeted caloric restriction, resistance training, moderate caffeine, green tea catechins, and — if medically indicated and prescribed — short-term GLP-1 agonists for obesity) are discussed in the stacking and protocol sections.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/clenbuterol" }, { "id": "7738ea00-14fb-43b6-893b-85702fc74efe", "slug": "collagen", "name": "Collagen Peptides", "aliases": [ "Hydrolyzed collagen", "Collagen hydrolysate", "Collagen peptides", "Bovine collagen peptides", "Marine collagen peptides", "Verisol", "Peptan", "Fortigel", "Fortibone", "UC-II (undenatured Type II collagen)", "Gelatin (parent material)", "Types I/II/III collagen" ], "category": "Protein", "description": "**Collagen peptides** — also sold as **hydrolyzed collagen**, **collagen hydrolysate**, or simply \"collagen powder\" — are **low-molecular-weight protein fragments** (typically **2-10 kilodaltons**, averaging around 3-6 kDa for most commercial products) produced by enzymatic hydrolysis of animal collagen. The starting raw material is **collagen-rich connective tissue** — bovine hide, porcine skin, fish skin and scales, chicken cartilage, or eggshell membrane — which is first decellularized, demineralized (for bone sources), then partially denatured into **gelatin** using controlled hot-water extraction. The gelatin — a high-molecular-weight (~100 kDa) glutinous protein familiar from desserts and pharmaceutical capsules — is then **enzymatically cleaved** using proteases (typically alcalase, collagenase, papain, or pepsin depending on manufacturer) to produce the small peptides that define \"collagen peptides\" as a commercial category. These peptides are readily **cold-water-soluble**, essentially tasteless and odorless in properly manufactured form, and — critically — they **escape full digestion** in the small intestine to a clinically meaningful degree, with a portion absorbed intact as bioactive **di- and tripeptides** (the most-studied being **Prolyl-Hydroxyproline**, abbreviated Pro-Hyp) that appear in peripheral blood within 30-60 minutes of oral ingestion (Iwai 2005).\n\n**Important framing up front — the \"does collagen survive digestion?\" myth**: A recurring skeptical critique of oral collagen is that \"all proteins get broken down to amino acids in the gut, so oral collagen cannot possibly work — you're just buying expensive amino acids.\" **This critique is outdated and empirically wrong in its strong form**. The biochemistry underlying collagen peptide function is genuinely unusual: collagen is the only major human protein with **high hydroxyproline (Hyp) content** (~10% by residue), and **Hyp-containing dipeptides are resistant to brush-border peptidases** that normally finish the final breakdown of dietary peptides. Specifically, **Pro-Hyp**, **Hyp-Gly**, and several related Hyp-containing di- and tripeptides survive intestinal digestion and appear intact in systemic circulation at **low micromolar concentrations** within 30-120 minutes of oral collagen peptide ingestion (Iwai 2005; Ichikawa 2010; Shigemura 2011). These peptides can then be taken up by fibroblasts, chondrocytes, and other connective-tissue cells — where they act as **both raw material for new collagen synthesis and as signaling molecules** that appear to stimulate fibroblast proliferation and extracellular matrix synthesis independent of their amino acid content. The correct nuanced statement is: **most** of an oral collagen dose is indeed broken down to free amino acids (which contribute to the general amino acid pool and in that sense are \"just expensive amino acids\"), **but** a small but clinically relevant fraction appears as intact Hyp-containing dipeptides that have specific bioactivity. This is why 10-20g/day of collagen peptides produces effects that equivalent doses of whey protein or generic amino acid mixtures do not reliably replicate — the Hyp-dipeptide signal is collagen-specific.\n\n**Hydrolyzed collagen peptides vs. gelatin vs. \"whole collagen\"** — this distinction matters both biochemically and practically: (1) **Whole native collagen** — the triple-helical structural protein in tendons, skin dermis, cartilage, and bone, with molecular weight around 300 kDa (three ~100 kDa alpha chains intertwined). Native collagen is **not water-soluble** at neutral pH, is **not orally bioavailable** in meaningful amounts, and is not sold as a standalone supplement. (2) **Gelatin** — partially denatured collagen produced by controlled hot-water extraction of collagen-rich tissue; molecular weight around 50-100 kDa; dissolves in **hot** water and gels when cooled (the basis of Jell-O and pharmaceutical gel capsules); poorly absorbed in the small intestine; main culinary and pharmaceutical uses. Gelatin provides the amino acid substrate for endogenous collagen synthesis but delivers **fewer bioactive dipeptides** than hydrolyzed peptides because its long chains must still be substantially broken down before absorption. The notable exception is **Shaw 2017** (PMID 27852613), which used gelatin (15g) + vitamin C ingested 30-60 minutes before targeted jump-roping exercise to improve tendon collagen synthesis — a specific application where gelatin's slower absorption timing is actually advantageous. (3) **Hydrolyzed collagen peptides** — the 2-10 kDa fragments that dominate the modern supplement market; cold-water soluble; largely tasteless; produce the specific Hyp-dipeptide pharmacokinetic signature (Iwai 2005); primary form used in skin, joint, and body composition RCTs. (4) **Undenatured Type II collagen (UC-II)** — a conceptually distinct product: small-dose (40 mg/day) immunomodulatory **native** Type II collagen, not hydrolyzed, designed for oral tolerance-induction effects on joint tissue (Clark 2008, PMID 18416885; Lugo 2016). UC-II is sold as a joint-specific product and works through a fundamentally different mechanism (T-cell modulation) than high-dose hydrolyzed peptides. These four categories are not interchangeable; marketing often blurs them.\n\n**Types I, II, and III collagen — and why \"mixed\" is the norm**: Collagen is a superfamily of at least 28 human proteins, but three types dominate tissue distribution and supplement relevance: **Type I** (bone, skin dermis, tendon, ligament, dentin — approximately 90% of body collagen), **Type II** (hyaline cartilage — nasal, articular, tracheal, intervertebral disc), and **Type III** (reticular tissue, blood vessels, young skin, co-distributed with Type I in many tissues). Bovine hide-derived collagen peptides are predominantly **Type I and III** in proportions reflecting the source tissue (approximately 80-90% Type I, 10-20% Type III); porcine skin peptides are similar. Fish (marine) collagen peptides are predominantly **Type I**. Chicken sternum-derived collagen (both hydrolyzed and undenatured) is predominantly **Type II**. **Do these distinctions matter clinically?** For most common endpoints (skin elasticity, generalized joint comfort, athletic recovery), the **mixed Type I/III peptides** in bovine hide products produce the outcomes demonstrated in the majority of skin and joint RCTs (Proksch 2014, PMID 24401291; Kim 2018 meta-analysis, PMID 30681787; Clark 2008 — though Clark specifically tested UC-II Type II, not Type I/III peptides). For **specific cartilage-focused applications** — particularly mild-to-moderate knee osteoarthritis — Type II-biased products (hydrolyzed Type II or undenatured UC-II) are preferred on mechanistic grounds, though head-to-head trials comparing Type I/III vs Type II peptides for equivalent endpoints are genuinely sparse. A pragmatic framing: if your target is **skin**, mixed Type I/III peptides are well-validated; if your target is **joint cartilage**, Type II-biased products have the closer mechanistic fit; for **tendon and ligament** (targeted by Shaw 2017-style peptide + vitamin C pre-exercise protocols), Type I-predominant products are mechanistically aligned.\n\n**Brand and standardization context — why the \"which collagen?\" question matters**: Unlike single-molecule pharmaceuticals, collagen peptides are a class of products with genuinely meaningful **brand-specific differentiation** driven by the hydrolysis process, peptide size distribution, and the specific dipeptide profile produced. Several **branded hydrolyzed collagen peptides** have been used in the majority of positive RCTs and dominate the scientific literature: **Verisol** (bovine collagen peptides optimized for skin endpoints, Gelita — the product used in Proksch 2014 and several follow-ups); **Fortigel** (bovine peptides optimized for joint endpoints, also Gelita); **Fortibone** (bone health-oriented peptides, Gelita); **Peptan** (Rousselot's widely-used branded collagen peptides — bovine and marine versions); **BioCell Collagen** (a composite of collagen peptides + chondroitin + hyaluronic acid from chicken sternum). Generic \"collagen peptides\" from commodity manufacturers may or may not replicate branded-product outcomes; most clinical research uses specific branded preparations. This is not purely marketing — the enzymatic hydrolysis process produces brand-specific dipeptide profiles that can genuinely differ in bioactivity. Consumers willing to pay a modest premium for a branded, clinically-studied product (particularly for skin endpoints with Verisol or joint endpoints with Fortigel) are making a defensible evidence-based choice; aggressive cost minimization with commodity peptides may or may not deliver equivalent effects.\n\n**Claimed benefits — and honest evidence stratification**: Collagen peptide marketing spans an enormous range of claims, from evidence-supported to evidence-free. **Evidence-supported endpoints (real RCT data)**: (1) **skin elasticity and hydration** — the strongest evidence domain; multiple placebo-controlled RCTs and a 2018 meta-analysis (Kim 2018, PMID 30681787) support modest improvements in skin elasticity and hydration at 2.5-10g/day over 8-12 weeks, particularly in women 35-65. (2) **Activity-related joint discomfort in athletes** — Clark 2008 with UC-II and several Fortigel trials (McAlindon 2011, PMID 21708034) show reduced joint pain during sports activity. (3) **Knee osteoarthritis symptoms** — Moskowitz 2000 (PMID 11071580) and follow-ups show modest symptomatic benefit in mild-moderate OA, though effects are not as large as NSAIDs or glucosamine-chondroitin in some comparisons. (4) **Body composition during resistance training in older adults** — Zdzieblik 2015 (PMID 26353786) showed 15g/day collagen peptides + resistance training improved lean mass more than placebo + training in sarcopenic elderly men. (5) **Tendon/ligament collagen synthesis in athletes** — Shaw 2017 (PMID 27852613) with gelatin + vitamin C before rehabilitation exercise. **Weaker/equivocal evidence**: (6) **Wound healing and pressure ulcers** — some evidence but confounded by general protein supplementation effects. (7) **Bone mineral density** — emerging evidence (König 2018, PMID 29337906) is suggestive but single-trial-dominant. **Largely unsupported claims (marketing overreach)**: (8) **Hair regrowth for male or female pattern hair loss** — essentially no rigorous evidence; does not replicate finasteride/minoxidil-level effects; see the FAQ on this specifically. (9) **\"Gut health\" and leaky gut treatment** — popular wellness claim with minimal rigorous RCT data; mostly mechanistic speculation and influencer marketing. (10) **Anti-aging beyond skin** — generic claims without specific mechanistic backing. (11) **Weight loss as a primary effect** — collagen has modest satiety effects like any protein but is not a weight-loss intervention.\n\n**Who is collagen appropriate for?** Reasonable candidates include: women 35-65 with skin elasticity/hydration goals willing to commit to 8-12 weeks of daily use; athletes or active individuals with activity-related joint discomfort or tendon/ligament concerns; older adults (60+) combining resistance training with protein-supplementation strategies for sarcopenia; individuals with mild-to-moderate knee OA wanting to layer a phytotherapy-style intervention alongside mainstream care. Less-appropriate candidates: people expecting dramatic results from any single supplement; individuals pursuing hair regrowth (pursue finasteride or minoxidil for androgenetic alopecia); individuals with phenylketonuria, severe fish/shellfish allergy (for marine collagen), or religious dietary restrictions requiring specific sourcing verification; individuals whose protein intake is already adequate (>1.2 g/kg/day) and who have no specific skin or joint concern — for these, collagen is unlikely to meaningfully outperform their existing protein intake.\n\nSee also [vitamin-c](/compound/vitamin-c) as the obligate cofactor for collagen hydroxylation (and essential co-administration for Shaw 2017-style tendon protocols); [glycine](/compound/glycine) as a component amino acid of collagen (relevant to amino acid stacking frameworks); [biotin](/compound/biotin) as a related beauty-supplement ingredient often combined with collagen in hair/skin/nails products; [curcumin](/compound/curcumin) and [boswellia](/compound/boswellia) as anti-inflammatory adjuncts for joint-focused collagen use; [quercetin](/compound/quercetin) for overlapping anti-inflammatory frameworks; [zinc](/compound/zinc) and [vitamin-d](/compound/vitamin-d) as general connective-tissue cofactors. Collagen peptides sit as one of the better-evidenced mass-market nutraceuticals — real effects for specific endpoints, enormous overreach in marketing, appropriate for selected users willing to invest 8-12 weeks at clinically-studied doses. This is educational content and not medical advice; specific medical concerns (severe OA, autoimmune joint disease, significant skin pathology, wound healing requirements, nutritional deficits) warrant medical evaluation rather than self-directed collagen supplementation.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 922, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/collagen" }, { "id": "1ea0e9d7-1c09-4800-b4a8-001f486d88d6", "slug": "comfrey", "name": "Comfrey", "aliases": [ "Symphytum officinale", "Knitbone", "Boneset", "Bruisewort", "Consound", "Slippery root", "Common comfrey", "True comfrey", "Blackwort", "Ass-ear", "Kuhkraut", "Beinwell" ], "category": "Herbal", "description": "**Comfrey** (*Symphytum officinale*) is one of the most mechanistically interesting — and simultaneously one of the most legally and toxicologically constrained — herbs in traditional European medicine. It is a large, bristly, perennial member of the borage family (**Boraginaceae**) native to Europe and western Asia, with broad veined leaves and clusters of nodding pink, purple, cream, or lilac tubular flowers. The plant has been used medicinally since classical antiquity — the genus name *Symphytum* derives from the Greek *sympho* (\"to unite\" or \"to grow together\"), and common names across multiple European languages (**knitbone**, **boneset**, **bruisewort**, **beinwell**, **consound**) reflect centuries of traditional use for **fractures, sprains, bruises, muscle strains, joint pain, and external wounds**. For most of recorded European herbal history, comfrey was used both internally (as teas, decoctions, and poultices applied to mucous membranes) and externally (as poultices, salves, and compresses applied to intact skin). In modern honest practice, **only the topical external use of comfrey on intact skin is defensible** — and even that use is constrained by specific duration, dose, and formulation rules. **The oral use of comfrey is not defensible at any dose, and this entry does not endorse it.**\n\n**The central safety problem — pyrrolizidine alkaloids**. Comfrey contains a class of naturally occurring secondary metabolites called **pyrrolizidine alkaloids (PAs)** — including **symphytine, echimidine, lycopsamine, intermedine, symlandine, 7-acetyl-lycopsamine, and 7-acetyl-intermedine** — along with their corresponding **N-oxides**. These molecules are themselves not acutely hepatotoxic, but they undergo **hepatic CYP3A4-mediated bioactivation** in the liver to **reactive pyrroles (dehydropyrrolizidines)** that alkylate hepatic sinusoidal endothelial cells and cause a distinctive, progressive, and sometimes fatal liver injury called **hepatic sinusoidal obstruction syndrome (SOS)** — formerly known as **hepatic veno-occlusive disease (VOD)** (Ridker 1985; Stickel 2003; Prakash 1999; Mei 2010). This injury pattern — occlusion of small hepatic veins and sinusoids by fibrous tissue, leading to painful hepatomegaly, ascites, jaundice, portal hypertension, and in severe cases liver failure — has been documented in **multiple human case reports** of oral comfrey use, in an infant exposed transplacentally to a mother's gordolobo (actually a comfrey-related herb) tea, and in extensive animal experiments (Yeong 1990; Huxtable 1990). The chronic accumulated dose of PAs, not a single high dose, is typically what produces the clinical syndrome — which is why the safety warnings focus on both **cumulative total lifetime PA exposure** and **duration of use**, not just maximum daily dose.\n\n**FDA action — 2001 oral comfrey ban**. In **July 2001**, the US Food and Drug Administration issued an **advisory letter to dietary supplement manufacturers and distributors** calling for the removal of oral comfrey-containing products from the US market because of hepatotoxicity concerns. The FDA advisory — while technically a request for voluntary compliance rather than a formal rule — had the effect of removing virtually all oral comfrey products from legitimate commerce in the United States. Similar regulatory actions had already been taken or would shortly be taken in **Canada (1989)**, the **United Kingdom (2002)**, **Germany (1992)** — where the Commission E initially permitted very limited internal use but subsequently tightened to topical-only — and **Australia, New Zealand**, and most other developed jurisdictions. The German regulatory posture evolved from a Commission E monograph permitting very small internal doses for short durations to a current regulatory framework permitting **only topical application to intact skin**, with specified daily total-PA limits (typically ≤1 µg/day for external use, and ≤0.1 µg/day for internal use — internal use now being essentially prohibited for commercial products). The comparative international consensus is therefore clear: **oral comfrey is not considered safe at any dose by any major developed-world regulatory agency, and topical comfrey on intact skin is permitted only under narrow formulation and duration constraints.** Any product still marketed for oral comfrey use — tea, tincture, capsule, or \"traditional\" preparation — falls outside the modern international safety consensus. This entry does not treat such marketing as legitimate.\n\n**But the topical evidence base is genuinely positive.** Despite the catastrophic oral safety profile, **topical application of comfrey preparations to intact skin has a credible and growing clinical evidence base for musculoskeletal indications**. The **Staiger 2012 systematic review** (*Phytotherapy Research*, PMID 22359388) pooled data from ten clinical trials including ankle sprain, muscle pain, knee osteoarthritis, and back pain indications, and concluded that topical comfrey extract formulations produced **statistically and clinically meaningful pain relief, improvement in functional status, and reduction in swelling** compared to placebo and, in several head-to-head trials, demonstrated **non-inferiority or modest superiority versus topical NSAID comparators** (diclofenac gel in particular). Key individual trials include **Grube 2007** (*Phytomedicine*) — a 142-subject placebo-controlled RCT of **Kytta-Salbe f comfrey ointment** for acute ankle sprain showing significantly faster pain reduction and functional recovery; **Predel 2005** (*Phytomedicine*) — a 164-subject placebo-controlled trial of topical comfrey for acute upper or lower back pain; **Giannetti 2010** (*Advances in Therapy*) — topical comfrey for chronic back pain; **Grube 2007** for ankle sprain; **Koll 2004** (*Phytomedicine*) — comfrey root extract for ankle sprain; and **Kucera 2004** (*Advances in Therapy*) — topical comfrey for knee osteoarthritis demonstrating functional improvement. These trials were generally conducted with **standardized low-PA or PA-reduced topical formulations** (discussed in more detail below) and with **intact skin application only** for short durations (7-14 days typical). The clinical signal is real — but it exists **specifically in the context of topical application of low-PA standardized extracts to intact skin for limited durations**. It does not generalize to oral use, to high-PA whole-plant preparations, to application on broken skin or open wounds, or to prolonged or repeated courses.\n\n**The low-PA or PA-free extracts.** Recognizing both the evidence for topical efficacy and the PA hepatotoxicity problem, **several European manufacturers developed standardized comfrey extracts with substantially reduced PA content** — typically via selective extraction solvents that leave PAs behind or via post-extraction purification steps. The German topical product **Kytta-Salbe f** (from Merck Selbstmedikation / Procter & Gamble Health) uses a comfrey root fluid extract standardized to contain ≤0.35 µg PAs per 100 g of ointment — thousands of times lower than the PA content of raw comfrey — and is the formulation used in most of the landmark topical RCTs. **Traumaplant** (Harras-Pharma) uses a fresh-pressed comfrey herb juice (from *Symphytum × uplandicum*, a related species with different PA profile) prepared to a specified low-PA standard. The regulatory logic of these products is that **systemic PA exposure from topical application to intact skin, using standardized low-PA formulations, is below the threshold for cumulative hepatotoxic risk over the durations and exposures studied**. This is defensible within those narrow boundaries and has been accepted by European regulators for registered phytomedicines. It is **not a license to apply raw comfrey root or homemade high-PA preparations**, and it is **not a license to apply low-PA preparations to broken skin, mucous membranes, or open wounds** — where absorption is substantially higher and unpredictable.\n\n**The plant and its chemistry**. *Symphytum officinale* is a rhizomatous perennial 60-120 cm tall with broad lanceolate leaves covered in stiff silica hairs; the root is dark brown to black externally and white and mucilaginous internally. Traditional preparations used both the leaf and the root, but **the root contains substantially higher PA concentrations (up to 10× leaf levels)** and is accordingly riskier — modern topical products preferentially use leaf or carefully purified root fractions. The **topically beneficial phytochemistry** includes: (a) **allantoin** — a small ureide present at 0.5-2% in comfrey roots, long recognized as a pro-epithelialization and granulation-stimulating agent in wound healing research, with its own independent pharmaceutical history (allantoin is included in numerous OTC topical wound-care products and cosmetics at 0.5-2% concentrations); (b) **rosmarinic acid** — a caffeic acid ester polyphenol with anti-inflammatory and antioxidant activity, shared with rosemary, sage, and other Lamiaceae and Boraginaceae species; (c) **mucilaginous polysaccharides** — demulcent and film-forming, providing a protective barrier on skin; (d) **tannins** — astringent, mildly anti-inflammatory; (e) **choline and phosphatidylcholine** — present in small quantities; (f) **triterpenoid saponins** and small amounts of **silica** (from the plant hairs). Comfrey also contains **trace vitamin B12 analogs** — a frequently cited marketing claim for oral comfrey use that is nutritionally irrelevant at practical doses and does not offset the hepatotoxicity problem.\n\n**Related Boraginaceae with shared PA concerns**. Comfrey is not the only herb in its family with hepatotoxic PAs. The same class of alkaloids is present in **borage (*Borago officinalis*)**, **coltsfoot (*Tussilago farfara*)**, **butterbur (*Petasites hybridus*)** — where PA-free standardized extracts have been developed for migraine prevention — **hound's-tongue**, **viper's bugloss**, **heliotrope**, **senecio (ragwort)** species, and many others. **Gordolobo tea** mislabeling (where PA-containing senecio is sold instead of the intended *Gnaphalium* species) was the cause of the infant VOD case mentioned above. Users who understand the comfrey PA issue should recognize that the same concern applies across much of Boraginaceae — which is why orally consumed PA-containing herbs in general are regarded with substantial suspicion by modern regulators.\n\n**Who uses topical comfrey responsibly, and why**. In modern honest practice, topical comfrey extracts applied to **intact skin** are a reasonable option for **short-duration (≤10 days) symptomatic management of acute musculoskeletal complaints**: **ankle sprains, muscle strains, acute back pain, contusions, and mild osteoarthritis flares**. Athletes and active adults who bruise, sprain, or strain acutely and want a topical anti-inflammatory/analgesic layer find topical comfrey a reasonable alternative or complement to topical NSAIDs (diclofenac gel, ketoprofen gel). The positioning is analogous to how one might use **arnica** gel, **menthol** rubs, **capsaicin** cream, or **topical bromelain** formulations — as gentle, adjunctive topical anti-inflammatory measures alongside conservative musculoskeletal care (rest, ice, compression, elevation, progressive activity return). Topical comfrey is **not** a treatment for systemic conditions, internal organ disease, metabolic disease, cancer, infections, fractures (despite the traditional \"knitbone\" claim, there is no modern evidence that topical comfrey accelerates bone union), or open wound healing requiring medical evaluation.\n\n**What comfrey is NOT in modern honest practice**. Comfrey is not: (1) an oral tea, capsule, tincture, decoction, or extract — the 2001 FDA ban and equivalent international regulatory actions reflect clear evidence of oral hepatotoxicity; (2) a wound-healing agent for open wounds or broken skin — the absorbed PA dose through broken skin is too high and too unpredictable; (3) a long-term continuous-use topical — cumulative PA exposure drives the risk, and the evidence-supported durations are **≤10 days per course and ≤6 weeks cumulatively per year**; (4) a pediatric herb — children <6 years old should not use comfrey topically or orally; (5) a pregnancy or breastfeeding herb — no amount, no route, no duration is acceptable; (6) an internal \"blood purifier,\" \"liver tonic,\" or \"tonic for bones\" despite traditional herbal marketing — these framings reflect pre-modern herbal theory, not current toxicology; (7) safe in any formulation at any dose if the person has pre-existing liver disease (cirrhosis, chronic hepatitis, prior PA injury, or advanced fatty liver); (8) a substitute for medical evaluation of any significant musculoskeletal injury, persistent pain, or symptom warranting diagnosis.\n\n**Summary framing**. Comfrey represents one of the clearest cases in modern herbal medicine where **traditional use and modern evidence part company**. The traditional oral and mucous-membrane use, based on centuries of empirical observation, was genuinely effective for some indications — but was also genuinely hepatotoxic in ways that pre-modern medicine could not attribute to the herb because VOD/SOS is insidious, progressive, and often delayed by months to years. Modern analytical chemistry, toxicology, and pharmacovigilance revealed the mechanism; modern regulators responded appropriately; and the modern defensible use of comfrey is **topical application of standardized low-PA extracts to intact skin for short durations, for acute musculoskeletal complaints**. Users who want the benefits without the legal and hepatotoxic risks should use **commercial low-PA topical products** (e.g., Kytta-Salbe f, Traumaplant where available) from reputable European pharmaceutical manufacturers rather than making homemade poultices, teas, or tinctures from raw comfrey. Users who have pre-existing liver disease, who are pregnant or breastfeeding, who have young children, or who require internal use should use alternative anti-inflammatory strategies entirely — [boswellia](/compound/boswellia), [curcumin](/compound/curcumin), [omega-3](/compound/omega-3), devils-claw extract, white willow bark, or conventional NSAIDs under medical supervision. This is educational content and not medical advice; any significant injury, persistent pain, or complicating factor warrants appropriate clinical evaluation rather than self-directed herbal care.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 5, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/comfrey" }, { "id": "fc5fbefd-5e50-4e21-a263-b180345fc505", "slug": "copper", "name": "Copper", "aliases": [ "Cu", "Cu2+", "Cupric", "Cuprous", "Copper bisglycinate", "Copper glycinate", "Copper gluconate", "Copper sulfate", "Copper sebacate", "Copper citrate", "Copper HVP", "Copper orotate", "Albion copper" ], "category": "Mineral", "description": "Copper is an essential trace mineral that most adults get in adequate amounts from a varied omnivorous diet — but that routinely drops into functional insufficiency when people take long-term high-dose zinc supplements, consume highly processed diets, undergo bariatric surgery, or use copper-chelating therapies. The adult RDA is 900 mcg/day, the tolerable upper limit is 10 mg/day, and typical Western intakes hover between 1.0 and 1.6 mg/day. Copper is required for at least a dozen critical enzymes that cannot function without a copper ion bound at their active site: cytochrome c oxidase (complex IV of the mitochondrial electron transport chain), Cu/Zn superoxide dismutase (SOD1, the primary cytoplasmic antioxidant enzyme), ceruloplasmin (the ferroxidase that oxidizes Fe²⁺ to Fe³⁺ so iron can load onto transferrin), lysyl oxidase (which cross-links collagen and elastin, giving connective tissue and large arteries their tensile strength), dopamine-β-hydroxylase (which converts dopamine to norepinephrine in noradrenergic neurons), tyrosinase (the rate-limiting enzyme in melanin synthesis), and peptidylglycine α-amidating monooxygenase (which C-terminally amidates peptide hormones including oxytocin, vasopressin, and CCK). Lose functional copper and you lose oxidative phosphorylation, antioxidant defense, iron metabolism, connective tissue integrity, catecholamine synthesis, pigmentation, and neuropeptide maturation simultaneously. Severe copper deficiency produces a notable constellation: microcytic or macrocytic anemia that fails to respond to iron, neutropenia with recurrent infections, subacute combined degeneration of the spinal cord (a B12-mimicking myelopathy with sensory ataxia, spasticity, and peripheral neuropathy), hypopigmented hair, osteoporosis, and cardiomyopathy. The classic modern cause is excessive zinc intake: zinc induces intestinal metallothionein, which preferentially binds copper and traps it inside enterocytes that are then sloughed into the stool, creating a negative copper balance that can take months to years to manifest clinically. The Kumar 2004 Mayo Clinic case series documented 25 patients with unexplained myelopathy who turned out to have copper deficiency, many from denture-cream zinc exposure or long-term zinc lozenge use — reversible if caught early, permanent if advanced. The genetic copper disorders are at the opposite ends of a spectrum: Menkes disease (loss-of-function ATP7A, X-linked) causes fatal infantile copper deficiency with kinky hair, hypothermia, failure to thrive, and neurodegeneration, while Wilson disease (loss-of-function ATP7B, autosomal recessive) causes pathological copper accumulation in liver and brain with hepatitis, cirrhosis, parkinsonism, dystonia, psychiatric symptoms, and the pathognomonic Kayser-Fleischer rings. Wilson disease is treated with copper chelators (D-penicillamine, trientine) or zinc (exploiting the same antagonism that causes iatrogenic copper deficiency in healthy supplement users), and the anti-angiogenic copper chelator tetrathiomolybdate has been tested in cancer. In the supplement context, copper sits in a narrow therapeutic window: most people don't need it, a meaningful minority on zinc or post-bariatric or deeply vegetarian actually do, and the dosing for replacement is small (1–2 mg/day, not the 5–15 mg doses that appear in some \"immune support\" products without any evidence base). Standalone copper for longevity or cognition has no controlled outcome data; the strong evidence is for deficiency correction and Wilson disease management. Food sources are beef liver (far and away the densest, 14 mg per 100 g), oysters, shiitake mushrooms, cashews and sunflower seeds, dark chocolate, and whole grains. See also [Zinc](/compound/zinc) for the antagonist relationship, [Selenium](/compound/selenium) for the other trace-mineral antioxidant cofactor, [Vitamin B12](/compound/vitamin-b12) for the shared myelopathy differential, and [Alpha-Lipoic Acid](/compound/alpha-lipoic-acid) for the broader mitochondrial-redox discussion. This overview is for educational purposes only and is not medical advice — copper excess is more dangerous than modest deficiency, and routine supplementation without confirmed low ceruloplasmin or serum copper is not justified for most people.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/copper" }, { "id": "ceb50acf-c8f9-4ca9-9bd6-f62297554fe1", "slug": "coq10", "name": "Coenzyme Q10", "aliases": [ "CoQ10", "Coenzyme Q", "Ubiquinone", "Ubidecarenone", "Ubiquinol", "Reduced CoQ10", "Kaneka Q10", "Kaneka QH", "MitoQ", "CoQH2", "Q10" ], "category": "Foundational", "description": "Coenzyme Q10 (CoQ10), also known as ubiquinone-10, ubidecarenone, or simply \"coenzyme Q,\" is a lipid-soluble benzoquinone compound with a 50-carbon isoprenoid side chain (decaprenyl tail) that anchors it within the inner mitochondrial membrane. Its name — ubiquinone — reflects its ubiquitous distribution across all animal and most bacterial tissues, where it performs two critical biological functions: electron transport in oxidative phosphorylation and lipid-phase antioxidant defense. Every cell that contains mitochondria depends on CoQ10 for ATP production, and every cell with a membrane benefits from CoQ10's capacity to intercept lipid peroxidation. The molecule exists in a reversible redox couple: the oxidized quinone form (ubiquinone, Q) accepts two electrons and two protons to become the fully reduced hydroquinone (ubiquinol, QH2), and the interconversion sits at the functional heart of mitochondrial bioenergetics.\n\nHumans synthesize CoQ10 endogenously via the mevalonate pathway — the same pathway that produces cholesterol, dolichol, and isoprenoid groups for protein prenylation. Tyrosine contributes the benzoquinone head ring, and farnesyl pyrophosphate contributes to elongation of the decaprenyl tail through sequential additions of five-carbon isoprene units catalyzed by trans-prenyltransferase and polyprenyl-4-hydroxybenzoate transferase, with final assembly and modifications occurring in mitochondria. This shared upstream pathway explains one of CoQ10's most discussed clinical interactions: HMG-CoA reductase inhibitors (statins), used by tens of millions of people for cardiovascular disease prevention, reduce endogenous CoQ10 synthesis by 30-50% because they block the pathway upstream of both cholesterol and CoQ10 production. Whether this statin-induced CoQ10 depletion is clinically significant — particularly for statin-associated muscle symptoms — has been one of the most contested nutritional-pharmacology debates of the past two decades, with some meta-analyses supporting clinically meaningful benefit from CoQ10 supplementation and others finding no effect on muscle symptoms.\n\nFunctionally, CoQ10's most important role is at the center of the electron transport chain (ETC). Complex I (NADH dehydrogenase) and Complex II (succinate dehydrogenase) both donate electrons to ubiquinone, reducing it to ubiquinol, which then shuttles electrons to Complex III (cytochrome bc1 complex) before they ultimately reach oxygen at Complex IV and generate water. The movement of electrons through this sequence is coupled to proton pumping across the inner mitochondrial membrane, establishing the electrochemical gradient that Complex V (ATP synthase) uses to phosphorylate ADP to ATP. A cell cannot make mitochondrial ATP without CoQ10, full stop. Tissues with the highest energy demand — heart, kidney, liver, skeletal muscle, brain — contain the highest CoQ10 concentrations, which is why CoQ10 supplementation has been most intensively studied for heart failure and neurodegenerative diseases.\n\nBeyond bioenergetics, CoQ10 is arguably the most important lipid-phase antioxidant in human biology. Unlike water-soluble antioxidants (vitamin C, glutathione), CoQ10 partitions into membrane lipid bilayers and LDL particles where it intercepts peroxyl radicals, prevents initiation and propagation of lipid peroxidation chains, and regenerates vitamin E (α-tocopherol) after it has been oxidized to tocopheroxyl radical. The reduced form ubiquinol is the antioxidant-active species; after donating electrons to quench lipid radicals, it becomes ubisemiquinone and then ubiquinone, and the cellular machinery reduces it back. Because circulating LDL contains roughly 1 molecule of ubiquinol per LDL particle alongside 6-8 molecules of vitamin E, CoQ10 is a key determinant of LDL's resistance to oxidation — relevant to atherosclerosis biology even if direct cardiovascular outcome trials have not captured this mechanism cleanly.\n\nThe landmark clinical trial for CoQ10 is Q-SYMBIO (Mortensen et al 2014, PMID 25282031), a double-blind randomized trial of 420 patients with NYHA class III-IV heart failure receiving CoQ10 100 mg three times daily vs placebo for two years. CoQ10 supplementation reduced major adverse cardiovascular events by 43% — a striking effect size unmatched by most cardiovascular pharmaceuticals studied in similar populations — with concurrent reductions in hospitalizations and mortality. This trial, combined with the earlier Morisco 1993 and Mortensen 1990 trials, has established CoQ10 as part of integrative heart failure management, though the mainstream cardiology community has been slow to incorporate it. CoQ10 has additional evidence of varying strength for migraine prevention (Sandor 2005), statin-associated muscle symptoms (mixed), fertility (both male and female), age-related macular degeneration, periodontal disease, and Parkinson's disease (positive pilot data, negative large trials).\n\nFor BodyHackGuide readers, CoQ10 is one of the most important foundational supplements in the mitochondrial-support category, with particular relevance for anyone over 40 (endogenous CoQ10 production declines with age), anyone on statin therapy, anyone with a family history of heart failure or cardiomyopathy, athletes seeking mitochondrial performance enhancement, patients with migraines, and anyone pursuing complete antioxidant tuning. This page covers the biochemistry, the heart failure and migraine evidence, ubiquinone vs ubiquinol form selection, absorption tuning (CoQ10 has notoriously poor bioavailability without lipid co-ingestion or specialized formulations), stacking with ALA and PQQ for mitochondrial support, and practical dosing across indications.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/coq10" }, { "id": "0a752d61-ceb7-43ad-91ab-d58e2b676086", "slug": "cordyceps", "name": "Cordyceps", "aliases": [ "Cordyceps sinensis", "Ophiocordyceps sinensis", "Cordyceps militaris", "Yarsagumba", "Dong Chong Xia Cao", "Caterpillar Fungus", "Himalayan Gold", "CS-4", "Paecilomyces hepiali", "Cordycepin", "Dongchonghacho" ], "category": "Adaptogen", "description": "**Cordyceps** is a genus of parasitic fungi (order Hypocreales, family Cordycipitaceae) historically prized in traditional Tibetan, Chinese, and Bhutanese medicine for their purported abilities to restore vitality, improve athletic performance, support respiratory and kidney function, and promote longevity. The two species of greatest pharmacological interest are **Ophiocordyceps sinensis** (formerly *Cordyceps sinensis*, reclassified in 2007), the wild \"caterpillar fungus\" that grows on the larvae of ghost moths (*Thitarodes* species) in the alpine meadows of the Tibetan plateau, Nepal, and Bhutan at elevations of 3,000-5,000 meters; and **Cordyceps militaris**, a more readily cultivated species that grows on a variety of insect hosts and is now farmed commercially on rice or silkworm pupae substrate. Wild *O. sinensis* is known in Tibetan as *yartsa gunbu* (\"summer grass winter worm\"), in Chinese as *dong chong xia cao* (σå¼Φƒ▓σñÅΦìë, literally \"winter-worm summer-grass\"), in Nepali as *yarsagumba*, and in Bhutanese as *yartsa gunbu* — reflecting the organism's notable life cycle in which the fungus infects a moth larva over winter, mummifies it, then in spring emerges as a club-shaped fruiting body from the caterpillar's head. The mummified caterpillar-plus-fungus complex is the traditional medicinal preparation, sometimes selling for US$20,000-$50,000 per kilogram in premium Chinese markets, making wild *O. sinensis* one of the most expensive natural products in the world — gram-for-gram more valuable than gold in certain grades.\n\nCommercial cultivation of *O. sinensis* has been historically impossible because the fungus requires specific temperature, altitude, and host-insect conditions that are extraordinarily difficult to replicate in vitro. The supplement industry has responded in two ways: (1) cultivation of *Cordyceps militaris*, a related species that grows readily on grain substrates and produces many of the same bioactive compounds (particularly cordycepin and adenosine) — often at higher concentrations than wild *O. sinensis*; and (2) cultivation of **Paecilomyces hepiali** (marketed as **\"Cs-4\"** or **\"CordyMax\"**), an anamorphic fungal strain isolated from wild *O. sinensis* that can be grown by submerged fermentation. Cs-4 is technically a different organism from wild *O. sinensis* but retains similar bioactive profiles and has been the subject of most of the human clinical research on \"Cordyceps\" over the past 40 years. Consumers should understand that virtually no commercial \"Cordyceps sinensis\" supplement contains wild caterpillar fungus — what they are buying is either *C. militaris*, Cs-4/*P. hepiali*, or mycelium-on-grain preparations with variable active compound content.\n\nThe principal bioactive compounds in Cordyceps species include **cordycepin** (3'-deoxyadenosine, an adenosine analog with anti-tumor, anti-viral, and immunomodulatory activity), **adenosine** (a purine nucleoside with cardiovascular and neurological effects), **β-glucans and polysaccharides** (immunomodulatory), **ergosterol** (vitamin D2 precursor), **mannitol** (cordycepic acid), various nucleosides, and smaller amounts of ergothioneine. *Cordyceps militaris* typically contains higher cordycepin content than *O. sinensis*, while *O. sinensis* contains higher levels of certain polysaccharides. Cordycepin is particularly important pharmacologically because it is structurally identical to adenosine except for the lack of a 3'-hydroxyl group on the ribose sugar — this subtle difference allows cordycepin to incorporate into RNA and disrupt polyadenylation, mRNA stability, and certain kinase signaling pathways, underlying many of its anti-cancer and anti-inflammatory effects.\n\nThe claimed benefits of Cordyceps span several domains: **(1) exercise performance and VO2max** — probably the best-studied indication in Western research, anchored on early attention generated by the 1993 Chinese National Games when Chinese women distance runners (including Wang Junxia, who set the 10,000m world record) dramatically improved performance while taking Cordyceps and turtle blood preparations. Subsequent randomized controlled trials have tested whether supplementation improves VO2max, time-to-exhaustion, and exercise tolerance, with generally positive but modest results (Chen 2010, Hirsch 2017 discussed below). **(2) Immune support and respiratory health** — traditional use for asthma, chronic bronchitis, and COPD, with some modern evidence of bronchodilatory and anti-inflammatory effects. **(3) Energy/fatigue** — as an adaptogen, with mechanistic rationale in ATP production and mitochondrial function. **(4) Kidney function** — extensively used in traditional Chinese medicine for \"kidney yang deficiency\"; modern studies in chronic kidney disease and diabetic nephropathy show some benefit. **(5) Libido and sexual function** — traditional aphrodisiac with weak modern evidence. **(6) Anti-aging/longevity** — the most speculative indication, with animal data showing lifespan extension in some models. **(7) Blood sugar regulation** — some evidence in type 2 diabetes animal models and small clinical trials.\n\nThe strongest human clinical evidence exists for **exercise performance in older adults** and for **Cs-4 in renal disease**. The Chen et al. 2010 trial (*Journal of Alternative and Complementary Medicine*, PMID: 20804368) is frequently cited: a 12-week randomized, double-blind, placebo-controlled trial of CS-4 (Cs-4/*P. hepiali*) 3 grams/day in 20 healthy older adults (mean age 64). The Cs-4 group showed statistically significant improvements in metabolic threshold (the exercise intensity above which lactate accumulates) and ventilatory threshold compared with placebo, without changes in VO2max or peak exercise capacity. This suggests Cs-4 may improve exercise tolerance at sub-maximal intensities — the intensities most relevant to everyday function in older adults — more than maximal capacity. The Hirsch et al. 2017 trial in *Journal of Dietary Supplements*tested *Cordyceps militaris* (PeakO2, 4g/day) in younger recreationally active adults over 3 weeks and found improvements in time-to-exhaustion and VO2max. While these are small trials, they provide a plausibility basis for the exercise performance claim.\n\nFor **chronic kidney disease**, a growing body of Chinese research — and a 2014 Cochrane systematic review (Zhang et al.) — has examined Cs-4 and similar Cordyceps preparations as adjunctive therapy alongside standard care. The review analyzed 22 trials with 1,746 participants and concluded that Cordyceps adjunctive therapy may reduce serum creatinine, increase creatinine clearance, reduce proteinuria, and improve hemoglobin in CKD patients, though the authors cautioned about methodological limitations in the included trials (many were Chinese-language only, with unclear blinding and randomization procedures). This has led some integrative nephrologists to consider Cordyceps as an adjunct in CKD management, particularly in regions where it is culturally accepted.\n\nWhere Cordyceps fits honestly in the supplement landscape: it is best positioned as a **general adaptogen and exercise-support supplement** for recreationally active adults, older adults seeking support for functional capacity, and as a low-risk adjunctive option for individuals with CKD (under medical supervision) or respiratory conditions. It is NOT a substitute for proven exercise training programs, cardiopulmonary rehabilitation, or evidence-based treatments for kidney disease (ACE inhibitors, SGLT2 inhibitors, diet, blood pressure control). It sits honestly alongside [Rhodiola](/compound/rhodiola-rosea) for fatigue, [Panax ginseng](/compound/panax-ginseng) for physical performance, and [Lion's Mane](/compound/lions-mane) for cognitive support as one of the mushroom-and-root adaptogens with modest but real clinical evidence.\n\nSafety is generally excellent with cultivated preparations. Wild *O. sinensis* carries contamination risks (arsenic, lead from the Tibetan soil environment) and has been associated with rare cases of lead poisoning when adulterated with metal powders to increase weight and price. Cultivated *C. militaris* and Cs-4 have demonstrated good safety profiles in clinical trials at doses up to 3-4 grams/day for 12 weeks. Interactions with anticoagulants (theoretical, based on some in vitro antiplatelet effects), immunosuppressants (theoretical immune activation), and diabetes medications (possible additive hypoglycemic effect) warrant caution in those populations.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 776, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/cordyceps" }, { "id": "5f388af6-69c2-4026-8eec-201c61abdd5c", "slug": "cortagen", "name": "Cortagen", "aliases": [ "Ala-Glu-Asp-Gly", "Cardiac Bioregulator", "Cortexin (related)", "Khavinson Cardiac Peptide" ], "category": "Longevity", "description": "Cortagen is a synthetic tetrapeptide (Ala-Glu-Asp-Gly) from the Khavinson bioregulator family developed at the St. Petersburg Institute of Bioregulation and Gerontology. It is organ-targeted to cardiac and coronary tissue, studied for cardiac function preservation and coronary artery health in aging and post-ischemic models. Like other Khavinson bioregulators (Pinealon, Bronchogen, Cartalax, Epithalon), Cortagen is proposed to act via direct gene-regulatory mechanisms in target tissue rather than classical receptor-ligand signaling. Russian clinical literature includes use in elderly patients with cardiovascular disease and post-myocardial infarction recovery. It is distinct from the cortex-targeting Khavinson peptide Cortexin.", "half_life": "Unknown (tetrapeptide; estimated <4 hours)", "molecular_weight": "430.4 g/mol (C17H26N4O9, PubChem CID 18439621)", "molecular_mass": "430.4 g/mol", "amino_acid_sequence": "Ala-Glu-Asp-Pro (AEDP); H-Ala-Glu-Asp-Pro-OH", "administration_routes": [ "Subcutaneous", "Intramuscular" ], "dose_range_mcg": "0", "dosing_frequency": "once_daily", "cycle_length": "10 days per course (research / Russian bioregulator convention)", "common_vial_sizes": [ "20" ], "research_stage": "Preclinical", "approval_status": "Not FDA-approved (research use only)", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Peripheral nerve repair - accelerated axon regeneration and faster nerve-conduction recovery after injury in rat models [PMID:11276314; PMID:12134478]", "Neuroprotection and antioxidant activity in the cerebral cortex and in chronic brain-ischemia models (preclinical) [PMID:18239817; PMID:21476278]", "CNS/cognitive support as the synthetic short-peptide analog of the cortex-derived Russian drug Cortexin", "Anti-aging chromatin remodeling - reactivation of age-silenced ribosomal genes in lymphocytes from elderly donors [PMID:15085253; PMID:37042594]", "Mild immune-signaling modulation (IL-2 expression), generally weaker than Vilon or Epithalon [PMID:12447482; PMID:16224591]", "Longevity-protocol stacking as one of the Khavinson short-peptide bioregulators (commonly paired with Epitalon or Pinealon)" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/cortagen" }, { "id": "dd5f930c-b8cb-4842-86b9-99f4ecfa757d", "slug": "cortexin", "name": "Cortexin", "aliases": [ "Cortexin", "Cortex", "Cerebral Cortex Peptides" ], "category": "Nootropic Peptide", "description": "Cortexin is a **purified peptide preparation extracted from cattle and pig cerebral cortex tissue** — a low-molecular-weight neuropeptide complex used clinically in Russia and Eastern Europe for cognitive impairment, post-stroke recovery, encephalopathy, attention disorders, and pediatric developmental conditions.\n\nLike [Cerebrolysin](/compound/cerebrolysin), Cortexin is positioned as a broad-spectrum neurotrophic preparation supplying bioactive peptides that mimic endogenous neurotrophic factors. It is **not FDA-approved** in the US and is sold as a research peptide. Russian-language clinical literature is extensive; English-language peer-reviewed studies are limited but growing.", "half_life": "~2-3 hours (estimated from analog peptide preparations)", "molecular_weight": "Complex of low-molecular-weight polypeptide fractions, ~1-10 kDa (no single defined MW).", "molecular_mass": "~1-10 kDa (range of constituent polypeptide fractions; Cortexin is a peptide complex with no single defined mass)", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Marketed in Russia/CIS (Geropharm); human clinical use with limited-quality evidence (small, mostly Russian-language studies; no Western RCT; not FDA/EMA approved)", "approval_status": "Not approved by the FDA or EMA. Registered and marketed as a prescription drug in Russia and several CIS countries (manufacturer: Geropharm). Outside those markets it is research-use-only / not for human consumption.", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": null, "potential_benefits": [], "research_fields": [], "pubmed_count": 18, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/cortexin" }, { "id": "8c424f70-d38b-425e-b3b9-8cb78f43b0e3", "slug": "creatine", "name": "Creatine", "aliases": [ "Creatine monohydrate", "Cr", "N-aminoiminomethyl-N-methylglycine", "Methyl guanidine acetic acid", "Creapure", "Micronized creatine" ], "category": "Foundational", "description": "Creatine is the most-researched nutritional supplement in sports science and has emerged over the past decade as a cornerstone compound in the broader longevity conversation, extending beyond its traditional ergogenic applications into cognitive performance, brain health in aging, sarcopenia prevention, bone health, and recovery from traumatic brain injury. Unlike most nutritional supplements, creatine has accumulated hundreds of randomized controlled trials, multiple high-quality meta-analyses, consensus position statements from scientific bodies (including the International Society of Sports Nutrition), and a safety profile supported by decades of human use across diverse populations. The result is a compound with unusual evidentiary grounding: recommendations for creatine are not speculation but rather translation of substantial clinical science into practical protocols.\n\nChemical identity and biochemistry: Creatine is a nitrogen-containing organic compound with the chemical formula C4H9N3O2, synthesized endogenously from the amino acids arginine, glycine, and methionine primarily in the liver and kidneys, with smaller contributions from the pancreas. Endogenous synthesis produces approximately 1-2 grams per day in a typical adult. Dietary intake from animal foods (primarily red meat and fish) provides another 1-2 grams per day in omnivorous diets. Total body creatine content averages 120-140 grams in a 70 kg adult, with approximately 95% stored in skeletal muscle and the remaining 5% distributed across brain, heart, and other tissues. Skeletal muscle creatine exists in two pools: free creatine (approximately one-third) and phosphocreatine (approximately two-thirds). The phosphocreatine pool serves as a rapidly mobilizable energy reservoir for ATP regeneration during high-intensity activity.\n\nEnergy system function: Creatine's primary biochemical role is as a substrate for the phosphocreatine-creatine kinase energy system. During high-intensity muscle contraction, ATP is rapidly hydrolyzed to ADP to fuel contraction. Phosphocreatine donates its phosphate group to ADP via the creatine kinase enzyme, rapidly regenerating ATP without requiring oxygen or glucose metabolism. This system provides the dominant energy supply for the first 10-15 seconds of maximum-intensity exercise before glycolysis and oxidative phosphorylation take over for longer-duration activities. Supplementation with exogenous creatine increases muscle creatine stores by 15-40% depending on baseline levels and supplementation protocol, expanding phosphocreatine availability and improving capacity for high-intensity work.\n\nErgogenic applications: Creatine supplementation improves performance across a broad range of high-intensity, short-duration activities including resistance training (improving strength and lean mass gains by 5-15% above placebo in meta-analyses), sprinting, jumping, and repeated-effort sports. The ergogenic effect is most pronounced for activities lasting less than 30 seconds with brief recovery periods, consistent with the compound's role in the phosphocreatine energy system. For endurance activities (longer than a few minutes), ergogenic effects are smaller or absent, though creatine may benefit endurance athletes through improved recovery between interval sessions. Kreider 2017 International Society of Sports Nutrition position stand (PMID 28615996) synthesizes this evidence and represents the consensus scientific position.\n\nCognitive applications: Beyond muscle performance, creatine supplementation improves cognitive performance under conditions of high cognitive demand, sleep deprivation, or in aging populations. The brain contains approximately 5% of total body creatine and utilizes the phosphocreatine system for neuronal energy demands. Rae 2003 (PMID 14561278) demonstrated that creatine supplementation improves working memory and intelligence test performance in vegetarians (who have lower baseline creatine stores due to dietary absence). Avgerinos 2018 meta-analysis (PMID 29704637) found creatine improved short-term memory and intelligence/reasoning performance, with strongest effects in older adults and under stress conditions. Prokopidis 2023 meta-analysisextended this evidence, finding creatine supplementation improved memory performance, particularly in older adults.\n\nAging and sarcopenia applications: Perhaps the most important recent development in creatine research has been recognition of the compound's role in preventing age-related muscle loss (sarcopenia) and maintaining physical function in older adults. Chilibeck 2017 meta-analysisdemonstrated that creatine combined with resistance training in older adults produced significantly greater gains in lean mass and strength than resistance training alone. Candow and colleagues have extensively documented the role of creatine in aging musculoskeletal health. Forbes 2022 reviewsummarized evidence for creatine's role in aging populations, including benefits for muscle mass, strength, physical function, bone health, and cognition. These aging applications have shifted creatine from a sports supplement to a longevity supplement, with many longevity-focused physicians now recommending creatine as standard for adults over 40.\n\nBrain health and neurological applications: Creatine's energy-buffering capacity extends to neurological conditions including traumatic brain injury, Parkinson's disease, Huntington's disease, and depression. Though clinical trial results have been mixed, the mechanistic rationale for creatine in conditions involving mitochondrial dysfunction and energy deficits is strong. Dolan 2021 reviewsystematically covered creatine for brain health applications. For mainstream users, these neurological applications are less directly actionable than the ergogenic and sarcopenia benefits, but represent an expanding frontier of creatine research.\n\nRegulatory status and availability: Creatine is legal and unregulated in most jurisdictions, sold as a dietary supplement in the United States and available in most countries. It is one of the most affordable effective supplements available, with monthly cost typically under $10-20 USD. Creatine monohydrate is the most-researched form and remains the gold standard — alternative forms (ethyl ester, HCl, buffered, etc.) have not demonstrated superior efficacy and typically cost more. Creapure is a branded creatine monohydrate manufactured in Germany with high purity standards and widely recommended for users seeking pharmaceutical-grade quality assurance. Micronized creatine refers to monohydrate that has been processed to smaller particle sizes for improved mixability but is chemically identical to standard monohydrate.\n\nHistorical arc and cultural context: Creatine was first isolated by French chemist Michel Eugène Chevreul in 1832 from meat extract. Its role in muscle energetics was established through mid-20th century biochemistry. The modern era of creatine supplementation began in the early 1990s when Paul Greenhaff and colleagues at the University of Nottingham published the foundational studies demonstrating that oral supplementation could increase muscle creatine stores. The 1992 Olympic Games saw creatine enter mainstream sports culture when British sprinters Linford Christie and Sally Gunnell credited supplementation for performance improvements. The subsequent three decades have seen creatine transition from a newer ergogenic aid primarily used by elite athletes to perhaps the best-validated nutritional supplement available to the general public. The cultural arc has interesting parallels to other compounds that have moved from niche to mainstream acceptance: initial skepticism, then growing evidence base, then recognition as a legitimate health intervention, with ongoing research continuing to expand the applications.\n\nPositioning in a broader longevity stack: Creatine integrates well with other foundational longevity compounds including omega-3 fatty acids, vitamin D, magnesium, and protein. Unlike more speculative interventions (rapamycin, /compound/metformin, peptide therapies), creatine carries minimal regulatory or medical complexity and can be implemented without physician oversight in healthy adults. For users building a longevity stack, creatine represents one of the highest evidence-to-cost ratios available — approximately $10-15 per month for a compound with stronger evidence than many pharmaceutical interventions costing fifty times as much. The compound pairs well with resistance training (for which it is designed), protein supplementation, and the broader musculoskeletal longevity agenda centered on maintaining strength and lean mass through middle and older age.\n\nMainstream adoption curve: As of 2026, creatine has transitioned from a controversial sports supplement to mainstream recognition. Position statements from the International Society of Sports Nutrition, Academy of Nutrition and Dietetics, and numerous medical organizations support creatine supplementation. Prominent longevity-focused physicians (Peter Attia, Andrew Huberman, and others) have popularized creatine for aging applications. This mainstream adoption has expanded the user base beyond athletes to include middle-aged and older adults, cognitively-demanding professionals, and users generally interested in evidence-based longevity interventions. The compound represents an instructive case study in how supplement recommendations evolve as evidence accumulates: from niche ergogenic to foundational health supplement.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/creatine" }, { "id": "b9548cdf-8e0a-4f92-b88c-e46e29b0f712", "slug": "curcumin", "name": "Curcumin", "aliases": [ "Turmeric extract", "Curcuma longa extract", "Diferuloylmethane", "Curcumin I", "1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione", "Meriva (phytosome)", "Theracurmin (nanoparticle)", "Longvida (SLCP)", "BCM-95 (turmeric essential oil complex)", "Novasol (liquid micellar)", "CurcuWIN", "Tetrahydrocurcumin (THC, metabolite)", "Bisdemethoxycurcumin", "Demethoxycurcumin" ], "category": "Antioxidants", "description": "Curcumin is the principal bioactive polyphenol extracted from the rhizome of Curcuma longa (turmeric), constituting approximately 2-8% of dried turmeric root by weight along with two related curcuminoids (demethoxycurcumin and bisdemethoxycurcumin). The bright orange-yellow pigment has been used continuously for over 4,000 years in traditional Ayurvedic, Unani, and Siddha medicine for conditions ranging from wound healing and digestive disorders to arthritis and skin diseases, and it remains one of the most extensively studied natural compounds in modern biomedicine with over 20,000 PubMed-indexed publications and several thousand completed or ongoing clinical trials. Chemically, curcumin is a symmetric diferuloylmethane molecule (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) with an enolized beta-diketone bridge between two aromatic rings bearing phenolic hydroxyl groups — this structure underlies both its antioxidant/electrophile-scavenging activity and its chemical instability. Curcumin degrades rapidly in neutral-to-alkaline aqueous conditions (half-life of minutes at physiological pH), is extensively conjugated to glucuronides and sulfates by phase II enzymes in the gut wall and liver, undergoes reductive metabolism to tetrahydrocurcumin and hexahydrocurcumin by gut bacteria and hepatic reductases, and is actively effluxed by intestinal P-glycoprotein. The net consequence of this unfavorable pharmacokinetic profile is that standard 95% curcuminoid extracts produce barely detectable free curcumin in plasma after oral dosing — a fact that invalidated much of the early curcumin research and delayed clinical translation for decades. The bioavailability problem has been addressed over the past 15 years through a generation of advanced delivery formulations that represent a genuine pharmaceutical advance rather than marketing: **Meriva** (Indena phytosome technology) complexes curcumin with soy or sunflower phosphatidylcholine, producing 29-fold increased bioavailability and strong clinical evidence in osteoarthritis (Belcaro 2010 PMID 21194249); **Theracurmin** (Theravalues nanoparticle dispersion) achieves 27-fold bioavailability increase and is the form used in the landmark Small 2018 cognitive aging trial; **Longvida** (Verdure Sciences solid-lipid curcumin particles) produces 65-100 fold increase and crosses the blood-brain barrier measurably; **BCM-95** (Arjuna Natural turmeric essential oil complex) provides 7-fold increase; **Novasol** (liquid micellar) reaches 185-fold bioavailability in pharmacokinetic studies. These formulations have converted curcumin from a bench-science curiosity to a legitimate therapeutic with outcome trials supporting use in osteoarthritis, non-alcoholic fatty liver disease, metabolic syndrome, depression, cognitive aging, inflammatory bowel disease, and radiation dermatitis prevention. Clinical evidence is strongest for: **Osteoarthritis** (Daily 2016 meta-analysis PMID 27533649 pooled 8 RCTs showing effects comparable to NSAIDs for knee OA pain and function; Belcaro 2010 Meriva knee OA; Kuptniratsaikul 2014 PMID 24672232 head-to-head vs ibuprofen for knee OA showing non-inferiority); **NAFLD/fatty liver** (Rahmani 2016 demonstrated ultrasound resolution of hepatic steatosis; Panahi 2017 meta-analysis); **Metabolic syndrome and type 2 diabetes** (Chuengsamarn 2012 PMID 22773702 showed 9-month curcumin prevented T2D conversion in 16% of prediabetics vs placebo; Na 2014 meta-analysis); **Depression** (Sanmukhani 2014 randomized trial showing efficacy comparable to fluoxetine; Ng 2017 meta-analysis PMID 28236605); **Cognitive aging** (Small 2018 18-month Theracurmin trial showing memory and attention benefits plus reduced amyloid/tau on PET imaging); **Radiation dermatitis prevention** (Ryan 2013 breast cancer radiation therapy). Evidence is weaker or negative for: curcumin as standalone cancer therapy (despite extensive preclinical data, large clinical trials have not demonstrated meaningful oncologic benefit); Alzheimer disease treatment (Ringman 2012 24-week trial was negative for cognition despite biomarker effects); long-term prevention endpoints (most trials are <12 months). The molecule's truly exceptional feature is its pleiotropy — curcumin modulates hundreds of molecular targets across inflammation, oxidative stress, mitochondrial function, apoptosis, angiogenesis, epigenetic regulation, and gut microbiome composition. Principal mechanisms include direct inhibition of NF-κB nuclear translocation (the master inflammatory transcription factor); suppression of COX-2 and 5-LOX (the enzymes inhibited respectively by NSAIDs and leukotriene-receptor antagonists); activation of Nrf2 (the master antioxidant transcription factor that induces HO-1, NQO1, glutathione-synthesis enzymes, and other cytoprotective genes); reduction of TNF-α, IL-1β, IL-6, and other pro-inflammatory cytokines; modulation of STAT3, AP-1, β-catenin, and other oncologically-relevant transcription factors; PPAR-γ agonism relevant to adipose and metabolic function; and emerging evidence for favorable gut microbiome modulation (increasing Bifidobacterium and Lactobacillus, reducing pathobiont proportions). Safety is exceptional: curcumin has a GRAS (Generally Recognized As Safe) designation from the FDA, has been used as a food spice in Indian cuisine at gram-level daily intakes for millennia without population-level toxicity signals, and has a clean safety profile in clinical trials up to 8 g/day for extended periods. The main practical safety considerations are drug interactions (CYP3A4 and P-glycoprotein substrate implications; warfarin INR effects), gallstone or bile-duct obstruction (curcumin stimulates bile flow and could theoretically worsen), and coordination with oncology during active chemotherapy. This entry covers curcumin's pharmacology, the bioavailability problem and formulation solutions, mechanism of action across inflammation/metabolism/neurobiology, the clinical evidence base by indication, drug interactions and safety, formulation selection for different goals, and integration with other evidence-based compounds including [NAC](/compound/nac), [CoQ10](/compound/coq10), [berberine](/compound/berberine), [NMN](/compound/nmn), [rapamycin](/compound/rapamycin), and [glutathione](/compound/glutathione).", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 2, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/curcumin" }, { "id": "0ee3471c-57e4-43a8-a7cc-27f2c75fd1e0", "slug": "cyclazodone", "name": "Cyclazodone", "aliases": [ "N-cyclopropylpemoline", "Cyclopropylpemoline", "Ciclazodona", "Cyclazodonum", "2-(cyclopropylimino)-5-phenyl-1,3-oxazolidin-4-one" ], "category": "Nootropics", "description": "Cyclazodone is the N-cyclopropyl derivative of pemoline, a 4-oxazolidinone stimulant. It was made during the 1960s and investigated for stimulant and appetite-suppressing activity, but it was never approved for therapeutic use anywhere and no peer-reviewed report of that program was found. It carries an international nonproprietary name, which is why chemical databases list it as cyclazodone and ciclazodona, but a name is not an approval. It reached the research chemical market decades later and is now sold as a powder, a solution and an aerosol spray.\n\nThere is no published receptor binding or transporter data for cyclazodone itself. Its assumed mechanism comes entirely from its parent compound: pemoline is described as a presynaptic releaser and reuptake blocker of dopamine, was used for attention deficit hyperactivity disorder, and was withdrawn from the market over rare idiosyncratic liver injury (PMID: 42188000). Whether the cyclopropyl group changes potency, selectivity or duration has not been measured in any published assay.\n\nWhat the modern literature does contain is metabolism. A toxicokinetic study published in 2026 examined N-methyl-cyclazodone, a newer market compound first reported in the United States in 2022 in a suspected intoxication case, and found that it is converted to cyclazodone by N-demethylation in pooled human liver S9 fraction and in male Wistar rats given a single 2 mg/kg oral dose. The reaction was driven mainly by CYP2A6 with smaller contributions from CYP1A2 and CYP2C19, and the dosed N-methyl compound was itself partly excreted unchanged in rat urine, which the authors compared with pemoline excretion in humans (PMID: 42188000). Plasma protein binding was low to moderate at about 36 percent, so protein binding interactions are unlikely. The authors note that people with reduced CYP2A6 activity, or taking CYP2A6 inhibitors, would clear the compound differently.\n\nCyclazodone also turns up in analytical work at doping control laboratories, where it was one of eleven stimulants used to develop a hydrogen and deuterium exchange method by gas chromatography with electrospray ionization mass spectrometry (PMID: 29058415). That shows laboratories can identify it. It does not show that it is prohibited, or that it works.\n\nThe safety picture is the part worth reading twice. There is no human safety data for cyclazodone, no published animal toxicology study, and no pharmacokinetic study in people. The nearest signal is the pemoline record: pemoline has caused acute liver failure requiring transplantation (PMID: 12132793) and is named among the psychotropic drugs with the highest hepatotoxic potential (PMID: 22133982). A closely related structure does not guarantee the same liability, but it is the only relevant evidence available and it points in an uncomfortable direction. Cyclazodone has no FDA or EMA authorization and is a research-use-only compound in the US market.", "half_life": null, "molecular_weight": "216.24 g/mol", "molecular_mass": "216.24 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral (route used in the published animal metabolism work)", "Sold on the research chemical market as a solution and as an aerosol spray" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Cyclazodone has never been approved as a medicine in any country and has no FDA or EMA marketing authorization; it was developed in the 1960s and abandoned before therapeutic use (PMID: 42188000). It is sold only as a research chemical and is a research-use-only compound in the US market. Its N-methyl derivative appeared as a new psychoactive substance in the United States in 2022 in a suspected intoxication case (PMID: 42188000).", "trial_phase": "", "cas_number": "14461-91-7", "iupac_name": "", "chemical_formula": "C12H12N2O2", "potential_benefits": [ "Stimulant and appetite-suppressing activity described from the 1960s development program, reported second hand in the modern literature without species or study detail (PMID: 42188000)", "Formed in vivo as the N-desmethyl metabolite of N-methyl-cyclazodone in male Wistar rats and in pooled human liver S9 fraction (PMID: 42188000)", "Identifiable in doping control stimulant panels by gas chromatography mass spectrometry, so laboratory confirmation of exposure is possible (PMID: 29058415)" ], "research_fields": [ "Stimulants", "New psychoactive substances", "Forensic toxicology", "Drug metabolism" ], "pubmed_count": 0, "pubchem_cid": 135438121, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/cyclazodone" }, { "id": "5cb3a0b7-e047-49ee-bc7e-be093781aaf0", "slug": "dada", "name": "Diisopropylamine dichloroacetate (DADA)", "aliases": [ "DADA", "Diisopropylammonium dichloroacetate", "Liverall", "Dipromonium", "Kalodil", "Vitamin B15 (market label)" ], "category": "Other", "description": "DADA is the abbreviation the research chemical market uses for diisopropylamine dichloroacetate, the diisopropylamine salt of dichloroacetic acid, CAS 660-27-5. The abbreviation is ambiguous in scientific writing, where DADA also stands for unrelated things, so identity is worth confirming by CAS number or molecular formula rather than by name. The compound itself is old. It has been marketed in Japan for decades as Liverall, where it holds a Japanese Accepted Name, sits in Japanese therapeutic category 3919 as a liver function improving agent and is classified as a third-class over-the-counter drug (KEGG DRUG D01816). It has also been sold under names such as dipromonium and kalodil, and in the supplement trade under the label vitamin B15 or pangamic acid, which is a marketing term rather than a vitamin classification.\n\nIts pharmacology comes from the dichloroacetate half of the salt. Dichloroacetate inhibits pyruvate dehydrogenase kinase, which leaves the pyruvate dehydrogenase complex in its active state, so pyruvate is directed toward acetyl-CoA and the citric acid cycle instead of being reduced to lactate. In a mouse model of severe influenza, DADA was characterized specifically as a pyruvate dehydrogenase kinase 4 inhibitor that restored pyruvate dehydrogenase activity and improved the metabolic disorder and multiorgan failure seen in that model (PMID: 24865588).\n\nMost recent work is oncology and immunology, and all of it is preclinical. DADA increased radiosensitivity in esophageal squamous cell carcinoma cells and xenografts by raising mitochondria-derived reactive oxygen species (PMID: 27626688). It outperformed sodium dichloroacetate in a subcutaneous mouse breast tumor transplantation model (PMID: 27582548), showed antitumor activity alone and combined with chemotherapy, radiotherapy or immunotherapy in non-small cell lung cancer models (PMID: 39267851), and acted synergistically with fenbendazole in A549 cells and in nude mice (PMID: 39477286, PMID: 40799435). A 2026 study reported that DADA drives the same metabolic shift inside CD8 T cells, raising oxidative phosphorylation and mitochondrial fitness, increasing progenitor exhausted T cells in mouse tumors and improving the effect of PD-1 blockade (PMID: 41758776).\n\nThe human record is the weak part. The Japanese approval for chronic liver conditions long predates modern trial reporting standards, and no randomized controlled trial of DADA for any indication was found in the indexed literature. That leaves an unusual position: a compound with a genuine national approval, a clear biochemical mechanism and a growing preclinical oncology file, but no modern efficacy or safety trial that can be quoted.\n\nWhat is sold in capsules on the research chemical market is not the Japanese pharmaceutical product, and no FDA or EMA authorization exists. It is a research-use-only compound in the US market, and the tumor and immunology findings above are mouse and cell line results that have never been tested in people.", "half_life": null, "molecular_weight": "230.13 g/mol", "molecular_mass": "230.13 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral", "Intraperitoneal injection (animal studies)" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Approved (Japan)", "approval_status": "Approved in Japan as a liver function improving agent, sold there as Liverall, listed in Japanese therapeutic category 3919 and classified as a third-class over-the-counter drug (KEGG DRUG D01816). It has no FDA or EMA marketing authorization and is a research-use-only compound in the US market. Every oncology and immunology result published to date is preclinical.", "trial_phase": "", "cas_number": "660-27-5", "iupac_name": "", "chemical_formula": "C8H17Cl2NO2", "potential_benefits": [ "Improved metabolic disorder and multiorgan failure in mice with severe influenza, attributed to restored pyruvate dehydrogenase activity (PMID: 24865588)", "Increased oxidative phosphorylation and accumulation of stem-like progenitor exhausted CD8 T cells in mouse tumors, improving the effect of PD-1 blockade (PMID: 41758776)", "Radiosensitization of esophageal squamous cell carcinoma cells and xenografts through higher mitochondria-derived reactive oxygen species (PMID: 27626688)", "Greater tumor growth inhibition than sodium dichloroacetate in a subcutaneous mouse breast tumor transplantation model (PMID: 27582548)", "Antitumor activity alone and combined with chemotherapy, radiotherapy or immunotherapy in Lewis lung carcinoma mouse models and non-small cell lung cancer cells (PMID: 39267851)" ], "research_fields": [ "Metabolic modulators", "Pyruvate dehydrogenase kinase inhibition", "Hepatology", "Tumor immunometabolism" ], "pubmed_count": 0, "pubchem_cid": 12617, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/dada" }, { "id": "e1c5273a-ebe7-4cb1-8ac3-c6ca09accebf", "slug": "dasatinib", "name": "Dasatinib", "aliases": [ "Sprycel (brand name)", "BMS-354825", "N-(2-Chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide", "BCR-ABL inhibitor", "Src family kinase inhibitor", "D (in D+Q senolytic combination)" ], "category": "Senolytics", "description": "Dasatinib (SPRYCEL) is a second-generation oral tyrosine kinase inhibitor (TKI) with FDA approvals for chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). It is also, critically for longevity medicine, the \"D\" component of the landmark D+Q (dasatinib + quercetin) senolytic drug combination first reported by Zhu, Tchkonia, and Kirkland in 2015 (PMID 25754370) — the first demonstrated pharmacologic strategy to selectively kill senescent cells (\"zombie cells\") while sparing healthy cells. Senescent cells accumulate with age and disease, secrete pro-inflammatory and tissue-damaging SASP (senescence-associated secretory phenotype) factors, and contribute to age-related dysfunction across multiple organs. The D+Q combination and subsequent senolytic discoveries have opened an entire new therapeutic category of geroscience interventions with two landmark first-in-human pilot trials completed (Justice 2019 PMID 30616998 in idiopathic pulmonary fibrosis; Hickson 2019 PMID 31542391 in diabetic kidney disease), numerous additional senolytic trials underway, and substantial preclinical evidence across aging, Alzheimer disease, osteoarthritis, atherosclerosis, obesity-associated metabolic dysfunction, frailty, and multiple other age-related conditions. Dasatinib's chemical structure is a pyrimidinyl-aminothiazole-carboxamide that functions as an ATP-competitive inhibitor of multiple tyrosine kinases, with particular potency against BCR-ABL, the SRC family kinases (SRC, LCK, YES, FYN), c-KIT, PDGFR-α/β, and ephrin receptors. Originally developed by Bristol-Myers Squibb as a second-generation BCR-ABL inhibitor for patients with imatinib-resistant or -intolerant CML, dasatinib is 325-fold more potent than imatinib against wild-type BCR-ABL and retains activity against most imatinib-resistant mutations except T315I (which requires ponatinib). FDA-approved for: CML in all phases (chronic, accelerated, blast); Ph+ ALL in adults and pediatrics; use in adult patients with chronic phase CML with resistance or intolerance to prior therapy (second-line) or newly-diagnosed chronic phase CML (first-line); pediatric CML in chronic phase. The compound is marketed by Bristol-Myers Squibb (BMS) as SPRYCEL with substantial global presence since 2006. Dosing for oncologic indications ranges from 100 mg once daily (standard for chronic-phase CML) to 140 mg daily or 70 mg BID (for advanced CML or Ph+ ALL), taken continuously until disease progression or unacceptable toxicity. This pharmacologic profile — daily oral administration with continuous dosing at 100-140 mg — is the high-exposure scenario from which extensive clinical safety data and drug interaction knowledge have been accumulated. The senolytic paradigm is fundamentally different. For senolytic applications, dasatinib is used in INTERMITTENT PULSED DOSING — typically 100 mg once daily for 2-3 consecutive days, followed by a long drug-free interval (weeks to months). This dosing strategy reflects the biology: senolytic effects occur through a \"hit-and-run\" mechanism where the drug kills vulnerable senescent cells within hours to days, and continuous daily exposure is both unnecessary and likely counterproductive. The Justice 2019 trial used dasatinib 100 mg + quercetin 1000 mg on 3 consecutive days, with follow-up at 1 week and 1 month, finding meaningful functional improvements in IPF patients. The Hickson 2019 trial used dasatinib 100 mg + quercetin 1000 mg on 3 consecutive days, with measured senescent cell reduction in adipose tissue at 11 days post-treatment. Subsequent trials are exploring varied intermittent dosing schedules (e.g., monthly or quarterly pulsed dosing). This intermittent paradigm dramatically reduces cumulative exposure compared to chronic oncologic dosing — a patient receiving 100 mg × 2 days monthly gets ~2400 mg annually, compared to ~36,500 mg annually for a chronic CML patient — with correspondingly reduced but not eliminated side effect risk. Dasatinib's side effect profile is substantial and requires careful consideration even for intermittent senolytic use. Myelosuppression (thrombocytopenia, neutropenia, anemia) is common and dose-related, with thrombocytopenia being particularly notable — dasatinib potently inhibits SRC-family kinases in platelets, producing both quantitative reduction in platelet number and qualitative impairment of platelet function (increased bleeding risk independent of count). Pleural effusion is a well-described class effect (more common with dasatinib than other BCR-ABL TKIs), occurring in 10-30% of chronic daily-dosed patients and requiring monitoring. QTc prolongation and rare cardiac arrhythmias have been reported. Pulmonary arterial hypertension (rare but serious) can occur with prolonged exposure. GI side effects (diarrhea, nausea) are common. Multiple reports exist of dasatinib-induced colitis and GI bleeding. Drug interactions are extensive (CYP3A4 substrate; strong CYP3A4 inhibitors substantially increase dasatinib exposure; proton pump inhibitors dramatically reduce dasatinib absorption by raising gastric pH). For senolytic applications, intermittent pulsed dosing reduces but does not eliminate these concerns — patients have experienced adverse events at senolytic dosing schedules, and the intermittent paradigm is not risk-free. Dasatinib is a prescription medication; its use for any indication requires physician prescription, monitoring, and supervision. For longevity/senolytic use specifically, this requires partnership with a physician familiar with geroscience — typically a functional medicine, integrative medicine, or specifically-trained longevity physician. Self-experimentation with research-chemical-sourced dasatinib is both illegal (in most jurisdictions) and medically inappropriate given the substantial side effect profile and need for baseline and monitoring labs (CBC, LFTs, ECG, periodic echo for pulmonary pressure assessment). This entry covers dasatinib's pharmacology as a tyrosine kinase inhibitor; its established oncology indications; the senolytic mechanism and D+Q rationale; the clinical evidence base for senolytic applications including Justice 2019 IPF trial and Hickson 2019 DKD trial; the intermittent dosing paradigm for senolytic use; the substantial safety and interaction considerations; integration with [fisetin](/compound/fisetin), quercetin, [rapamycin](/compound/rapamycin), and other geroscience interventions; and the essential role of physician partnership in any senolytic use.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/dasatinib" }, { "id": "9d271bc9-04a2-460c-89b4-55b1be01c9f3", "slug": "dhea", "name": "DHEA", "aliases": [ "Dehydroepiandrosterone", "3β-hydroxy-5-androsten-17-one", "Prasterone", "Intrarosa", "DHEA-S (sulfate form)", "Androstenolone", "Transdehydroandrosterone" ], "category": "Hormone", "description": "**DHEA (dehydroepiandrosterone)** is an endogenous steroid hormone synthesized primarily by the **adrenal cortex** (zona reticularis), with smaller amounts produced by the gonads and brain. It is the **most abundant circulating steroid hormone in humans**, vastly exceeding plasma concentrations of testosterone, cortisol, or estrogens — total plasma DHEA including its sulfated storage form DHEA-S reaches 1,000-3,000 μg/dL in young adults, orders of magnitude higher than cortisol (10-20 μg/dL) or testosterone (300-1,000 ng/dL in men, 15-70 ng/dL in women). Despite this abundance, DHEA's physiological role remained enigmatic through much of the 20th century, and it was long described as a \"precursor hormone without clear intrinsic activity.\" Contemporary understanding has substantially revised this view: DHEA serves as the **substrate pool for peripheral sex steroid synthesis** in extra-gonadal tissues (particularly skin, brain, immune cells, and post-menopausal ovarian remnants), acts as a **neuroactive steroid** with direct effects on GABA-A and NMDA receptors, modulates immune function, and has its own metabolic and anti-inflammatory activities independent of sex steroid conversion.\n\nThe **characteristic physiological feature of DHEA is its dramatic age-related decline** — the steepest of any circulating hormone. DHEA and DHEA-S peak at ages 20-30 and decline progressively to approximately **10-20% of young-adult values by age 70-80**. This phenomenon, termed \"adrenopause,\" is distinct from menopause and andropause and affects both sexes similarly. The decline correlates temporally with many age-related changes including decreased muscle mass, decreased bone density, decreased libido, cognitive changes, and immune senescence — leading to the hypothesis that DHEA decline contributes to or represents the endocrine signal of aging, and that DHEA replacement might be rejuvenating. This hypothesis has driven extensive DHEA research over the past 30 years, producing a mixed evidence base: some specific populations (Addison's disease, severe adrenal insufficiency) benefit clearly from DHEA replacement; some conditions (depression, vaginal atrophy, poor responder IVF) have moderate positive evidence; but the broader \"anti-aging\" claims for DHEA supplementation in healthy adults have largely not been supported by controlled trials.\n\nDHEA is chemically classified as a **17-ketosteroid** and serves as a **prohormone** for both androgens and estrogens via peripheral conversion. The pathway: DHEA → androstenedione → testosterone (via 17β-HSD) → estradiol (via aromatase). Tissues expressing the conversion enzymes can generate local androgens and estrogens from circulating DHEA even when gonadal production is absent or insufficient — this is the basis for DHEA's role in providing sex steroid support to post-menopausal women, aging men with decreased testosterone, and patients with primary adrenal insufficiency where adrenal androgen synthesis fails. The concept of **intracrinology** — local cellular production of active hormones from circulating precursors — was significantly developed around DHEA biology by Fernand Labrie and colleagues at Laval University, Quebec.\n\n**Regulatory status varies globally**: In the **United States**, DHEA is classified as a **dietary supplement** and available without prescription in doses typically ranging from 5mg to 100mg, despite being a potent hormone with clear physiological effects. In the **European Union, UK, Canada, and Australia**, DHEA is a **prescription-only medication** reflecting those regulators' assessment of its hormonal potency and risk profile. Prasterone (pharmaceutical-grade DHEA) is available as **Intrarosa** (FDA-approved 2016) for vaginal atrophy, and in some jurisdictions for specific hormonal-deficiency conditions. The U.S. Anti-Doping Agency (USADA) and World Anti-Doping Agency (WADA) classify DHEA as a **prohibited substance in competitive sport** given its androgenic and anabolic effects.\n\n**Clinical evidence is strongest for specific deficiency-state and targeted indications**: (1) **Primary adrenal insufficiency (Addison's disease)**: **Arlt et al. 1999** (*New England Journal of Medicine*, PMID: 10498490) established that DHEA 50mg/day in women with Addison's disease improves mood, well-being, sexual function, and body composition — DHEA is now standard replacement therapy alongside glucocorticoid and mineralocorticoid replacement in Addison's patients; (2) **Vaginal atrophy / genitourinary syndrome of menopause**: **Labrie et al. 2009** and subsequent trials established that intravaginal prasterone (Intrarosa 6.5mg/day intravaginal) improves vaginal dryness, dyspareunia, and vulvar atrophy in post-menopausal women — FDA-approved 2016 for this indication; (3) **Depression**: **Wolkowitz et al. 1999**and **Schmidt et al. 2005**documented antidepressant effects in midlife-onset depression with DHEA 90-450mg/day over 6 weeks; (4) **IVF in poor responders**: DHEA 75mg/day for 3+ months has been studied for improving ovarian response in poor responder IVF cycles, with mixed but moderately positive evidence (Wiser 2010); (5) **Schizophrenia adjunctive** and (6) **lupus adjunctive** have moderate evidence bases in specific subpopulations.\n\n**Evidence is less clear or negative for**: general anti-aging in healthy older adults (multiple trials including the landmark **Nair et al. 2006 DHEA and Aging Trial** in *NEJM*, found no significant benefits on body composition, physical performance, or quality of life in healthy older adults given DHEA 50-75mg for 2 years), cognitive enhancement in healthy adults, athletic performance (evidence is weak plus DHEA is a banned substance in sport), weight loss, and \"adrenal fatigue\" (a non-medical concept without clinical validity). The landmark negative result of the Nair 2006 trial in particular substantially dampened enthusiasm for broad DHEA supplementation in healthy aging adults, though specific deficiency contexts remain clearly supported.\n\nDHEA's status as a **widely-available OTC hormone in the US** creates both opportunities and risks. The opportunities: individuals with subclinical adrenal insufficiency, perimenopausal/postmenopausal women with specific genitourinary symptoms, and individuals with clinical depression in midlife may derive benefit under appropriate clinical supervision. The risks: high-dose DHEA supplementation without clinical indication may produce androgenic side effects (acne, hirsutism, male-pattern hair loss in susceptible individuals, voice changes in women), estrogenic effects in men (gynecomastia), and theoretical concerns about hormone-sensitive cancers. Individuals with breast cancer, prostate cancer, or hormone-sensitive malignancies should avoid DHEA supplementation unless specifically directed by oncology.\n\nSee also [Pregnenolone](/compound/pregnenolone), [Testosterone](/compound/testosterone), [Melatonin](/compound/melatonin), [Magnesium](/compound/magnesium), [Ashwagandha](/compound/ashwagandha), [Fadogia Agrestis](/compound/fadogia-agrestis), and [Tongkat Ali](/compound/tongkat-ali) for adjacent hormonal-support and androgenic-tuning compounds. This overview is educational only and is not medical advice — DHEA is a potent hormone with systemic endocrine effects, and any use for clinical conditions warrants physician supervision.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 4979, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/dhea" }, { "id": "4e30da51-ccc0-4455-8c75-a59dffcbed54", "slug": "dihexa", "name": "Dihexa", "aliases": [ "PNB-0408" ], "category": "Nootropics", "description": "Dihexa is a synthetic peptide analogue of the angiotensin IV metabolite LVV-hemorphin-7, developed at Washington State University. It is considered one of the most potent cognitive enhancers ever tested in animal models — reportedly 7 orders of magnitude more potent than BDNF at improving cognitive performance in rodent Alzheimer's models. Exclusively used by the research and biohacking community with no human clinical trial data available.", "half_life": "Not characterized in humans. Dihexa was engineered for metabolic stability (resistant to plasma and enzymatic degradation) and blood-brain-barrier penetration; in preclinical work its central procognitive effects appear to outlast its plasma presence.", "molecular_weight": "504.7 g/mol", "molecular_mass": "504.7 g/mol", "amino_acid_sequence": "N-hexanoyl-Tyr-Ile-(6)-aminohexanoic amide: a modified dipeptide derivative of angiotensin IV. It retains the Tyr-Ile core of Nle1-AngIV, capped at the N-terminus with hexanoic acid and at the C-terminus with a 6-aminohexanoic acid amide. Not a standard translatable peptide sequence. CAS 1401708-83-5; molecular formula C27H44N4O5.", "administration_routes": [ "Oral", "Intranasal", "Subcutaneous" ], "dose_range_mcg": "5 to 40 mg oral per day (anecdotal range; no established human dose)", "dosing_frequency": "Once daily (oral), typically in the morning", "cycle_length": "2 to 4 weeks on with a break between cycles; highly experimental, no established cycle length", "common_vial_sizes": [ "50mg", "100mg" ], "research_stage": "Preclinical", "approval_status": "Research use only; not approved by the FDA or any regulatory agency. Investigational and preclinical, with no marketing authorization for any indication.", "trial_phase": "Preclinical", "cas_number": "1191170-93-0", "iupac_name": "N-hexanoic-Tyr-Ile-(6) aminohexanoic amide", "chemical_formula": "C27H44N4O5", "potential_benefits": [ "Synaptogenesis: formation of new dendritic spines and functional synapses (preclinical)", "Memory and spatial-learning support in rodent models", "Potential research application in Alzheimer's and other neurodegenerative disease models", "HGF/c-Met and PI3K/Akt-linked neuroplasticity (mechanism proposed; key paper retracted)" ], "research_fields": [ "Alzheimer's disease", "Cognitive impairment", "Synaptogenesis", "Neurodegeneration" ], "pubmed_count": 1, "pubchem_cid": 129010512, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/44/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/dihexa" }, { "id": "67dc1859-9233-4dc1-9267-a0764c7d37a3", "slug": "dmha", "name": "DMHA", "aliases": [], "category": "Energy & Performance", "description": "DMHA (octodrine) - chemically 2-amino-6-methylheptane, also sold as 2-aminoisoheptane or 1,5-dimethylhexylamine - is an aliphatic-amine central nervous system stimulant and a close structural analog of DMAA (1,3-dimethylamylamine). Originally introduced in the 1950s as a nasal decongestant and vasopressor, it re-emerged around 2015 as a gray-market pre-workout and 'fat-burner' ingredient. It is not an approved dietary ingredient in the US and has essentially no modern clinical safety data. Presented here for research and educational use only.", "half_life": "Not formally characterized in humans. After ingestion, octodrine is rapidly metabolized to heptaminol, which becomes the predominant compound detected in blood and urine within hours [PMID:39401652]. Users commonly report perceptible stimulant effects lasting roughly 3-6 hours, but this is anecdotal rather than measured pharmacokinetics.", "molecular_weight": "129.24 g/mol (free base; molecular formula C8H19N). Commonly supplied as a salt (e.g., hydrochloride or, historically, camphorsulfonate), which increases the labeled mass per dose.", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "75-200 mg per dose (anecdotal pre-workout range; ~75,000-200,000 mcg). Historical pharmaceutical unit dose was 8-33 mg. No approved or clinically validated dose exists.", "dosing_frequency": "Acute, single-session (pre-workout) use rather than a daily or continuous compound. Users typically leave rest days between doses to limit tolerance buildup and cardiovascular strain; there is no evidence base for any regular dosing schedule.", "cycle_length": "No established or evidence-based cycle. As a sympathomimetic stimulant, prolonged daily use is discouraged; anecdotal practice is intermittent, training-day-only use with frequent breaks. No safety data support any long-term cycle.", "common_vial_sizes": [], "research_stage": "Historical pharmaceutical; no modern clinical trials", "approval_status": "Not FDA-approved and not a lawful US dietary ingredient (FDA has issued warning letters, mirroring its DMAA stance). Formerly marketed as a European pharmaceutical (octodrine). Prohibited in competition by WADA (octodrine and its metabolite heptaminol are listed specified stimulants, section S6b).", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Increased energy and perceived training intensity - the reason it is added to pre-workout products (reported by users; not established in any controlled trial)", "Sharper focus and heightened alertness from central nervous system stimulation", "Appetite suppression, which is why it appears in 'fat-burner' formulas", "Mild mood lift or euphoria reported anecdotally", "Users often describe a longer, 'smoother' stimulant feel than caffeine alone - again anecdotal, not clinically demonstrated" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/dmha" }, { "id": "f2b4de82-d09c-4dff-a45c-e64714004f87", "slug": "dong-quai", "name": "Dong Quai", "aliases": [ "Angelica sinensis", "Dang Gui", "Tang Kuei", "Chinese Angelica", "Female Ginseng", "Women's Ginseng", "Dong Kwai", "Dangg Gui", "Radix Angelicae Sinensis" ], "category": "Adaptogen", "description": "**Dong Quai** (scientific name *Angelica sinensis* (Oliv.) Diels; also spelled **Dang Gui**, **Tang Kuei**, or **Dong Kwai**; Chinese σ╜ôσ╜Æ / τò╢µ¡╕) is a perennial herb of the family Apiaceae (the carrot, parsley, and celery family — notable for containing many fragrant, volatile-oil-rich medicinal plants) native to the cool, high-altitude regions of central and northwestern China, particularly Gansu Province (the Min County region is traditionally considered the premium cultivation area), Yunnan, Sichuan, Shaanxi, and Hubei provinces. The root of *Angelica sinensis* is one of the most important and extensively used herbs in Traditional Chinese Medicine (TCM), where it has been classified for over 2000 years as a **blood tonic** (*bu xue yao* Φú£ΦíÇΦùÑ) — a category of herbs used specifically to nourish and build the body's \"blood\" (a TCM concept that encompasses both the physical substance and broader nourishing/circulatory functions). In contemporary Western and East Asian herbal practice, Dong Quai is often described as **\"female ginseng\"** or **\"women's ginseng\"** — a translation that captures its dominant but not exclusive use in women's health conditions including menstrual irregularities, menopause, post-partum recovery, and fertility support, though it's important to note that Dong Quai has substantial historical use in both sexes and many non-gynecological applications.\n\nThe formal TCM characterization of Dong Quai is as warm in energetic nature, sweet and acrid in flavor, and entering the Heart, Liver, and Spleen meridians. Its primary traditional functions are: (1) **tonifying blood** (used for blood deficiency patterns presenting as pallor, fatigue, dizziness, palpitations, menstrual disorders, or anemia); (2) **regulating menstruation and relieving dysmenorrhea** (used for irregular menses, delayed menses, amenorrhea, painful periods); (3) **invigorating blood circulation and dispersing blood stasis** (used for various circulatory stagnation conditions including traumatic injuries, abdominal masses, ulcerations, and vascular problems); (4) **moistening the intestines to relieve constipation** (particularly in the elderly or those with blood deficiency); and (5) **reducing swelling and promoting healing of sores**. In classical TCM formulas, Dong Quai is the principal ingredient in dozens of the most important prescriptions including **Si Wu Tang** (\"Four Substances Decoction,\" the canonical blood-tonifying formula with [rehmannia](/compound/rehmannia), white peony, and ligusticum), **Dang Gui Bu Xue Tang** (\"Dong Quai Blood Tonic Decoction,\" Dong Quai + [astragalus](/compound/astragalus) 1:5 ratio, a simpler blood-qi tonic), and many others. The herb is rarely used as a single-ingredient agent in classical TCM — its effects are amplified and its side effects balanced through combination with complementary herbs.\n\nIn modern Western supplement markets, Dong Quai has been heavily promoted since the 1980s-90s as an **herbal alternative for menopausal symptoms** — particularly hot flashes and menopausal mood changes. This promotion has outrun the evidence base. The most rigorous clinical trial of Dong Quai monotherapy for menopausal symptoms — **Hirata et al. 1997** (*Fertility and Sterility*) — tested Dong Quai 4.5g/day standardized to 0.5% ferulic acid for 24 weeks in 71 post-menopausal women and found **no significant difference versus placebo** on hot flash frequency, vaginal cytology, or menopausal symptom scores. This well-designed study challenges the simple \"Dong Quai for menopause\" marketing narrative and suggests that Dong Quai's benefits in women's health, when they occur, likely emerge from its use in combination formulas (consistent with its traditional TCM use) rather than as isolated monotherapy. Several subsequent trials of herbal combination formulas including Dong Quai have shown some benefit, but it's not possible to attribute those benefits to the Dong Quai component specifically.\n\nThe principal bioactive compounds in Dong Quai are: (1) **Z-ligustilide**, a phthalide compound that is the dominant bioactive in the essential oil fraction (volatile oil constitutes approximately 0.3-1% of the dried root; ligustilide constitutes up to 40-50% of the volatile oil). Ligustilide has been the subject of substantial pharmacological research — it shows vasodilatory, antispasmodic, anti-inflammatory, antithrombotic, and neuroprotective activities in various models. (2) **Ferulic acid**, a phenolic compound with antioxidant, anti-inflammatory, and mild vasodilatory activity; ferulic acid is often used as a standardization marker for Dong Quai products (typically 0.05-0.1% of dried root). (3) **Butylidenephthalide** and other related phthalides with vasorelaxant and smooth muscle effects. (4) **Coumarins** including angelicin, psoralen, umbelliferone, and osthole — these compounds are responsible for Dong Quai's photosensitizing potential and contribute to some pharmacological effects. (5) **Polysaccharides** (*Angelica sinensis* polysaccharides, ASP) with immunomodulatory and hematopoietic activities — these polysaccharides may contribute to the traditional \"blood tonic\" effects by stimulating bone marrow cell proliferation and erythropoiesis. (6) **Essential oil components** beyond ligustilide including alpha-pinene, beta-pinene, myrcene, and numerous minor constituents contributing to Dong Quai's distinctive aroma.\n\nThe chemical complexity makes Dong Quai a multi-target herbal, and the pharmacological effects vary based on extraction method — volatile-oil-containing preparations emphasize ligustilide effects (vasodilation, antispasmodic), while aqueous decoctions emphasize polysaccharide effects (immunomodulation, hematopoiesis), and the traditional use of fresh or wine-processed root preserves different compound profiles than dried extracts.\n\n**Dong Quai's safety profile is dominated by one central concern: bleeding risk.** The coumarin content and the documented antiplatelet and anticoagulant effects of Dong Quai constituents mean that Dong Quai can significantly increase bleeding risk, particularly when combined with pharmaceutical anticoagulants (warfarin, direct oral anticoagulants like apixaban/rivaroxaban), antiplatelet agents (aspirin, clopidogrel), or other bleeding-risk-raising substances. A well-documented case series and the mechanistic plausibility make this the single most important safety issue for Dong Quai users. Pre-surgical discontinuation (at least 2 weeks before elective surgery), coordination with physicians in patients on anticoagulation, and caution in users with bleeding disorders are essential.\n\nSecondary safety concerns include: **photosensitivity** from the coumarin content (users may develop exaggerated sunburn or phototoxic skin reactions with sun exposure, particularly at higher doses); **contraindication in pregnancy** (uterine stimulant effects could provoke miscarriage); **hormone-sensitive conditions** (theoretical estrogenic effects, though the magnitude is debated — monographs vary in their assessment, with some calling Dong Quai \"mildly estrogenic\" and others concluding the estrogenicity is negligible); and **drug interactions** beyond anticoagulants (including potential interactions with hepatic cytochrome P450 enzymes and drugs metabolized through those pathways).\n\nFor users considering Dong Quai, a reasonable honest assessment: Dong Quai has meaningful value in classical TCM combination formulas under the guidance of a trained TCM practitioner, where its traditional indications (blood deficiency patterns, menstrual irregularities, post-partum recovery) can be properly assessed and combination prescriptions tailored to the individual. Dong Quai has substantially less compelling evidence as an isolated supplement for Western consumer use cases (menopausal hot flashes, general \"women's health tonic,\" libido support). Users interested in evidence-based herbal approaches to menopause should consider [black cohosh](/compound/black-cohosh), [red clover](/compound/red-clover), or soy isoflavones, all of which have stronger clinical evidence for menopausal symptom relief than Dong Quai monotherapy. Users interested in traditional Chinese herbal medicine should consider consultation with a licensed acupuncturist or herbalist who can prescribe appropriate classical formulas rather than relying on single-herb supplements.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 1308, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/dong-quai" }, { "id": "2822d012-e103-431f-a565-2ce3c2ba3da9", "slug": "dream-spray", "name": "Dream Spray", "aliases": [ "Dream Spray Blend" ], "category": "Sleep", "description": "This is a duplicate/alias entry. The full, maintained guide for this compound lives at DSIP (Delta Sleep-Inducing Peptide) (/compound/dsip). See that page for mechanism, dosing, evidence, and safety.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Duplicate entry - see DSIP (Delta Sleep-Inducing Peptide)", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "See the full guide at DSIP (Delta Sleep-Inducing Peptide) (/compound/dsip) for benefits and evidence." ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/dream-spray" }, { "id": "e25c0a2c-35f9-4c8b-b067-816c9110afa3", "slug": "dsip", "name": "DSIP (Delta Sleep-Inducing Peptide)", "aliases": [ "Delta Sleep", "Hypnos" ], "category": "Cognition, Mood & Neuroprotection", "description": "\nDelta sleep-inducing peptide (DSIP) is a nonapeptide — a 9-amino-acid neuropeptide with sequence Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu (WAGGDASGE, 848 Da molecular weight) — first isolated in 1977 from the cerebral venous blood of rabbits subjected to electrical stimulation of the intralaminar thalamus, a brain region involved in sleep regulation. The original Swiss investigators, Schoenenberger and Monnier at the University of Basel, named the peptide for the prominent delta-wave EEG activity they observed in recipient rabbits after intracerebroventricular injection of the purified fraction, implying a role in slow-wave (deep) sleep generation.\n\nThe name, however, has proven misleading. Four decades of follow-up research have produced a pharmacological profile that is substantially more complex than \"sleep peptide\" — and, depending on how generously you interpret the human clinical data, somewhat less impressive than the name suggests. DSIP does not reliably produce the dramatic delta-wave surges in humans that it appeared to produce in the original rabbit EEG studies. It does, however, demonstrate real effects on sleep architecture, stress response, pain modulation, and possibly mood regulation, and it has been studied (primarily in Russian, Eastern European, and Japanese clinical literature from the 1980s-1990s) for chronic insomnia, chronic pain syndromes, alcohol and opioid withdrawal, depression, and as an adjunct to conventional sleep and anxiolytic medications.\n\nDespite 40+ years of research, DSIP has never been approved by the FDA, EMA, or any major regulatory agency for any indication. It circulates today almost exclusively through the research chemical peptide market, where it is sold as subcutaneous injection vials, nasal spray formulations, and occasionally as sublingual preparations. Users report highly variable effects — some describe profound sleep improvements from a single bedtime injection, others notice nothing at all, and a subset report vivid dreams or morning \"grogginess\" that can last into the next day. The compound's reputation in the biohacking community is of a \"safe, non-addictive, mild-effect sleep aid\" positioned as a cleaner alternative to benzodiazepines, z-drugs (zolpidem, eszopiclone), and chronic melatonin. Whether it actually deserves that reputation depends substantially on what clinical claims you are willing to accept on thin evidence.\n\nThis entry covers what is genuinely established about DSIP pharmacology, what the clinical trial record actually shows (versus what marketing claims), how it is used in practice by peptide practitioners, safety considerations, and honest framing of the evidence gaps. It should be read as an educational reference, not a prescription — DSIP is not FDA-approved, is distributed through gray-market channels of variable quality, and any serious use decision should involve a qualified physician familiar with research peptides, appropriate sleep-hygiene tuning first, and realistic expectations. Cross-reference this page with [Semax](/compound/semax), [Selank](/compound/selank), and [Epitalon](/compound/epithalon) for a complete picture of the Russian-origin \"research peptide\" landscape, and with [BPC-157](/compound/bpc-157) and [Tesamorelin](/compound/tesamorelin) for more thoroughly characterized peptide therapeutics.\n", "half_life": "~7-15 minutes (IV; plasma clearance is rapid, though subjective sleep effects can outlast measurable blood levels)", "molecular_weight": "848.8 Da", "molecular_mass": "848.81 g/mol", "amino_acid_sequence": "Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu (WAGGDASGE)", "administration_routes": [ "Subcutaneous", "Intramuscular", "Intranasal" ], "dose_range_mcg": "100–300 mcg per injection", "dosing_frequency": "Once daily, 30–60 minutes before bedtime", "cycle_length": "10–14 days; can repeat after 1-week break", "common_vial_sizes": [ "2mg", "5mg" ], "research_stage": "Research Use Only", "approval_status": "Not FDA-approved", "trial_phase": "Preclinical", "cas_number": "62568-57-4", "iupac_name": "Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu", "chemical_formula": "C35H48N10O15", "potential_benefits": [ "Sleep quality support", "Stress reduction", "Cortisol/HPA modulation", "Alcohol & opioid withdrawal support", "Circadian regulation" ], "research_fields": [ "Sleep disorders", "Insomnia", "Stress", "Opioid dependence", "Circadian rhythm" ], "pubmed_count": 518, "pubchem_cid": 66756, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/66756/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/dsip" }, { "id": "c841cf5b-9e12-4d2f-9ca1-85965de299f4", "slug": "egcg", "name": "EGCG (Epigallocatechin Gallate)", "aliases": [ "EGCG", "Epigallocatechin gallate", "(-)-Epigallocatechin gallate", "Epigallocatechin-3-gallate", "Green tea catechin", "Polyphenon E", "Teavigo", "Sunphenon", "Catechin gallate", "Green tea extract" ], "category": "Flavonoid", "description": "\nEpigallocatechin gallate (EGCG) is the most abundant and biologically active catechin polyphenol in green tea (Camellia sinensis), typically constituting 50-80% of total catechins in dried green tea leaves. EGCG has emerged over the past two decades as one of the most extensively studied plant polyphenols, with clinical research spanning weight loss, cardiovascular health, glucose regulation, cancer chemoprevention, neuroprotection, and general antioxidant support. The compound has achieved broad commercial availability through both whole-leaf green tea and standardized green tea extract supplements, representing one of the best-characterized nutraceuticals in contemporary supplementation.\n\nChemically, EGCG belongs to the flavan-3-ol subclass of flavonoids, consisting of an epigallocatechin core (a catechin with three hydroxyl groups on the B-ring) conjugated to gallic acid via an ester linkage at position 3. This gallate ester distinguishes EGCG from simpler catechins and substantially enhances its antioxidant and biological activity. EGCG's molecular structure — with eight hydroxyl groups and the gallate modification — gives it exceptional antioxidant capacity per mole and enables binding to multiple protein targets with micromolar-to-nanomolar affinity.\n\nGreen tea has been consumed in East Asian cultures for thousands of years and is associated in population epidemiology with reduced cardiovascular disease, stroke, certain cancers, and overall mortality. The Ohsaki Study (Kuriyama 2006, PMID 16968850) followed 40,530 Japanese adults and showed green tea consumption (5+ cups daily) was associated with 16% reduced cardiovascular mortality compared to <1 cup daily. Similar associations have been replicated across multiple East Asian population cohorts. EGCG is considered the primary bioactive component responsible for these health associations, though green tea contains multiple other bioactive catechins (epicatechin, epigallocatechin, epicatechin gallate), L-theanine, caffeine, and other constituents that also contribute.\n\nCommercial EGCG supplementation evolved from (1) whole green tea leaves and powder (matcha), (2) brewed green tea beverage consumption, (3) standardized green tea extracts (typically 50-80% polyphenols, 25-50% EGCG), (4) highly purified EGCG preparations (90-98% pure). Notable branded ingredients include Teavigo (decaffeinated high-EGCG extract), Sunphenon (standardized green tea polyphenols), and Polyphenon E (a pharmaceutical-grade standardized green tea extract used in clinical research). Commercial finished products range from low-dose green tea extract (200-400 mg total polyphenols) to high-dose pure EGCG capsules (400-800 mg per serving).\n\nClinical research on EGCG spans hundreds of randomized trials and meta-analyses. Key findings include: modest weight loss and metabolic improvement in overweight/obese adults (meta-analyses show 1-3% weight reduction versus placebo), reduction in LDL cholesterol and blood pressure in hyperlipidemic or hypertensive adults, improvement in glucose metabolism and HbA1c in prediabetic/type 2 diabetic populations, reduced oxidative stress markers and inflammation, reduction in some cancer biomarkers (particularly prostate cancer PSA), potential neuroprotective effects in early-stage neurodegenerative research, and weight management adjunct in various conditions.\n\nCritical safety considerations: EGCG at high doses (particularly in fasted state and as concentrated extracts) can cause hepatotoxicity — liver enzyme elevations and, rarely, severe liver injury requiring transplant. The European Food Safety Authority (EFSA 2018) has recommended limiting daily EGCG intake from supplements to 800 mg daily or less, and preferably taking with food rather than fasted. The hepatotoxicity appears related to pro-oxidant effects of high EGCG concentrations on hepatocytes and may involve susceptible genetic polymorphisms. Green tea beverage consumption at typical dietary levels (1-5 cups daily) is not associated with hepatotoxicity — the concern is specifically with concentrated high-dose supplement use.\n\nPharmacokinetically EGCG has low oral bioavailability — approximately 0.1-1.5% in typical conditions, with extensive first-pass glucuronidation and methylation. Plasma concentrations peak 1-2 hours after oral dosing. Bioavailability enhancement strategies include liposomal, phytosome, and micellar formulations (providing 3-8x improved absorption), co-administration with piperine (minor enhancement), fasted administration (enhances absorption but increases hepatotoxicity risk), and combination with other catechins (modest enhancement through microbial metabolism). Tissue distribution is broad including liver, kidney, intestine, prostate, and brain.\n\nThe thematic positioning of EGCG spans multiple use cases. For cardiovascular and metabolic effect, EGCG (as green tea extract or purified) at 200-500 mg daily provides documented biomarker improvements. For weight management adjunct, EGCG combined with caffeine and caloric modification produces modest enhanced weight loss. For cancer chemoprevention, EGCG has extensive preclinical evidence with limited clinical confirmation. For general longevity and antioxidant support, EGCG sits alongside other polyphenols as a foundational supplementation choice. Most users benefit more from regular green tea consumption than from concentrated extract supplementation, with concentrated extracts reserved for specific therapeutic targets.\n\nCommercial product selection involves important trade-offs: whole green tea or matcha preserves the natural matrix of catechins, theanine, and other compounds with lower EGCG per serving but higher safety margin; standardized green tea extract provides higher EGCG doses in convenient capsule form; highly purified EGCG preparations maximize dose efficiency but carry higher hepatotoxicity risk. Users should select based on their specific goals, and prefer products with third-party testing and reputable brands given the hepatotoxicity concerns with adulterated or poorly-manufactured concentrated extracts.\n", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/egcg" }, { "id": "36f3efd7-fe4c-442a-ae51-dc726c2aacc8", "slug": "eleuthero", "name": "Eleuthero", "aliases": [ "Eleutherococcus senticosus", "Siberian Ginseng", "Ci Wu Jia", "Devil's Shrub", "Touch-Me-Not", "Wild Pepper", "Acanthopanax senticosus", "Eleutherococcus", "Russian Root", "Eleutheroside" ], "category": "Adaptogen", "description": "**Eleuthero** (scientific name *Eleutherococcus senticosus*, formerly classified as *Acanthopanax senticosus*; called **ci wu jia** in Chinese, **siberian ginseng** in Western herbalism — though this common name is problematic and technically inaccurate as eleuthero is NOT in the *Panax* genus of true ginsengs — **devil's shrub** or **touch-me-not** in some English sources, and **russian root** reflecting its extensive Russian use) is a deciduous shrub in the Araliaceae family (ivy family), growing 2-3 meters tall with spiny stems, native to the cold temperate forests of the Russian Far East (Primorsky and Khabarovsk regions, Amur and Ussuri river basins), Northeast China, Korea, and Hokkaido Japan. The medicinal portion is primarily the root and rhizome, though stem bark and leaves have also been used. The plant is armed with prominent thorns (hence \"devil's shrub\"), grows in well-drained mixed forests, and has been harvested from wild populations for centuries and more recently cultivated.\n\nEleuthero occupies a uniquely foundational place in adaptogen science because it was the **primary research plant used by Nikolai Lazarev and Israel Brekhman** to develop and validate the entire modern concept of \"adaptogens\" from the 1940s through 1970s. Brekhman, working at the Institute of Biologically Active Substances (Russian Academy of Sciences) in Vladivostok, conducted thousands of studies examining eleuthero's effects on physical and mental performance, stress tolerance, immune function, and various disease states. The term \"adaptogen\" itself, coined by Lazarev in 1947 and developed by Brekhman, was initially defined through eleuthero's demonstrated properties: (1) non-specific increase in resistance to a wide range of physical, chemical, and biological stressors; (2) normalizing influence regardless of the direction of pathological change; and (3) innocuous, non-toxic effect on normal physiological function. Eleuthero was used extensively by Soviet cosmonauts (including on long-duration Mir station missions), Soviet Olympic athletes (where its use predated and influenced the later IOC debates about ergogenic aids), Soviet soldiers (for cold resistance and performance), industrial workers (for shift work and fatigue), polar expedition members, and deep-sea divers. This provided an unusually extensive \"real-world\" database of eleuthero use under extreme conditions.\n\nDespite this heritage, eleuthero's reputation has been somewhat clouded by two factors: (1) the misleading \"Siberian ginseng\" name suggested equivalence to true *Panax* ginseng, leading to confusion and eventual regulatory action — the US FDA in 2002 required that eleuthero products no longer be labeled \"ginseng\" to distinguish them from true ginseng; and (2) widespread **adulteration issues**, particularly with *Periploca sepium* (Chinese silk vine, a plant from an entirely different family — Apocynaceae — containing cardiac glycosides and NOT an adaptogen). Multiple cases of eleuthero adulteration have been documented, and some clinical trials have used inadequately authenticated material. These issues make standardization and quality sourcing critical when using eleuthero.\n\nThe primary bioactive compounds in eleuthero are a family of compounds called **eleutherosides**, labeled A through M, which are structurally diverse — NOT a single chemical class but rather a group of compounds with different structures that co-occur in the plant. The most important are: **eleutheroside B** (syringin, a phenylpropanoid glycoside), **eleutheroside E** (a lignan glycoside structurally unrelated to eleutheroside B), **eleutherosides I, K, L, M** (triterpenoid saponins structurally similar to panaxosides of true ginseng but differently substituted), and **chlorogenic acid derivatives**. Additional compounds include **isofraxidin** (a coumarin), **sesamin** (a lignan also found in sesame), **β-sitosterol**, various polysaccharides with immune-modulating activity, and minor flavonoids. The commonly cited \"eleutherosides B+E\" standardization marker reflects the research tradition of using these two as primary pharmacologic markers, though whole-extract pharmacology involves the full spectrum of compounds. Different plant parts contain different compound profiles — root/rhizome is the traditional medicinal material and has the most complete profile, while stem bark (sometimes used) has a different but overlapping composition.\n\nThe proposed clinical applications of eleuthero span: **(1) stress resilience and HPA-axis support** — the classical adaptogen indication; **(2) physical performance and endurance** — with extensive Russian sports medicine research; **(3) mental performance under fatigue** — attention, reaction time, mental stamina; **(4) immune support** — modest evidence for increased NK cell activity and modulation of T-lymphocyte populations; **(5) convalescence and recovery** — traditional use during recovery from illness; **(6) chronic fatigue syndrome** — with specific clinical research; **(7) shift work adaptation** — particularly Russian research in industrial and medical settings; **(8) herpes simplex management** — small study showing reduced outbreak frequency; **(9) cardiovascular adaptation** — effects on cardiac response to acute stressors; **(10) cognitive support in elderly** — with Cicero 2004 trial showing improved cognition; and **(11) general wellbeing and vitality tonic**.\n\nThe human clinical evidence is substantial in quantity — thousands of Russian studies plus growing Western research — though quality is heterogeneous, with older Russian studies often not meeting modern Western methodological standards. Key Western-standard trials include: **Cicero et al. 2004** (*Archives of Gerontology and Geriatrics*) — RCT in 20 elderly subjects showing improvements in quality of life, cognitive function (attention, short-term memory), and social functioning over 4-8 weeks of eleuthero supplementation. **Facchinetti et al. 2002** — demonstrated attenuation of cardiovascular response to mental stress testing in humans given eleuthero. **Asano et al. 1986** (*Planta Medica*) — eleuthero extract improved maximal work capacity and VO2 max in trained athletes; an early Japanese replication of Russian findings. **Kuo et al. 2010** — improvements in endurance cycling time-to-exhaustion with eleuthero. **Williams 1994, 1995** — showed NO ergogenic/stimulant effects above baseline in normal-state athletes, supporting the \"normalizing\" adaptogen concept rather than stimulant effects. **Hartz et al. 2004** (*Psychological Medicine*) — 96 chronic fatigue syndrome patients; eleuthero did NOT show significant benefit vs. placebo for the primary endpoint (though subgroups of less-severe fatigue showed some improvement) — an important null-or-modest finding in chronic fatigue. **Freye et al. 2001** — improvements in cognitive function and wellbeing in shift workers. **Bohn et al. 1987** — lymphocyte subpopulation changes demonstrating immune modulation. **Williams et al. 1987** — early evaluation of eleuthero for herpes.\n\nWhere does eleuthero fit in the therapeutic landscape? It is a **milder adaptogen** than [Rhodiola rosea](/compound/rhodiola-rosea) (less stimulating, lower fatigue-reversal magnitude), [Panax ginseng](/compound/panax-ginseng) (less overtly tonifying, lower testosterone/libido effects), or [Ashwagandha](/compound/ashwagandha) (less sedating, lower acute anxiolytic effect). Its strengths are: (1) the deepest scientific heritage among adaptogens, with decades of consistent findings across varied populations; (2) an excellent safety profile at typical doses; (3) compatibility with stacking (minimal drug interactions compared with [Schisandra](/compound/schisandra) or [Panax ginseng](/compound/panax-ginseng)); (4) a broad but modest effect profile suitable for baseline adaptogen foundation; and (5) strong evidence in specific niches like shift work, convalescence, and endurance. Its limitations are: (1) effects are modest and often require multi-week timelines to fully manifest; (2) quality/adulteration issues have historically complicated research interpretation; and (3) it is generally less \"felt\" than more pharmacologically active herbs (a feature for long-term use but a limitation if seeking acute effects). Eleuthero forms the third component of the **ADAPT-232** classical Russian adaptogen formula (eleuthero + [Rhodiola rosea](/compound/rhodiola-rosea) + [Schisandra](/compound/schisandra)), which has been tested in multiple Panossian-lab trials.\n\nSafety is excellent at typical doses, with rare side effects limited to mild insomnia at higher doses, rare mild hypertension, caution in bipolar disorder (theoretical risk of mania), and a notable interaction consideration with **digoxin** (eleuthero may cause false-positive digoxin assays in blood tests — a laboratory interference rather than a pharmacological interaction, but clinically important). Quality sourcing is critical due to adulteration concerns.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 277, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/eleuthero" }, { "id": "0255864e-8f76-4f53-ba2d-61064bb8c77d", "slug": "eloralintide", "name": "Eloralintide (LY3841136)", "aliases": [ "LY3841136", "LY-3841136", "AT53786", "Eloralintida" ], "category": "Weight Loss", "description": "Eloralintide is an amylin analog developed by Eli Lilly and Company for weight management, given as a once-weekly subcutaneous injection. It is a 37 amino acid peptide containing three non-coded residues and a C20 fatty diacid that binds albumin, which is what stretches its action out to a week (PMID: 41109426). It is investigational everywhere. No regulator has approved it, and it is in phase 3 trials as of 2026.\n\nAmylin is a hormone released from pancreatic beta cells alongside insulin. It slows gastric emptying, suppresses glucagon after meals and signals meal termination through the brainstem. Pramlintide, the first approved amylin analog, proved the concept but was limited by frequent dosing and modest effect. The newer analogs split into two groups: dual amylin and calcitonin receptor agonists such as cagrilintide, and selective amylin receptor agonists. Eloralintide belongs to the second group. In cells expressing human receptors it activated the amylin 1 receptor about 12-fold more potently than the calcitonin receptor and about 11-fold more potently than the amylin 3 receptor (PMID: 41109426). That selectivity is the design idea, because calcitonin receptor engagement is thought to contribute to nausea.\n\nPreclinical results back this up. In lean rats, eloralintide produced significantly less conditioned taste avoidance than cagrilintide, a marker of aversive signaling. In diet-induced obese rats it reduced food intake and lowered body weight in a dose-dependent way, mostly through loss of fat mass, and pharmacokinetics in rats and monkeys supported weekly dosing (PMID: 41109426).\n\nThe human data are what make this compound notable. A phase 1 single-ascending-dose study in 48 healthy participants reported mostly mild adverse events and week 4 weight reduction of 2.5 percent and 4.4 percent in the two highest single-dose groups against a 0.6 percent gain on placebo (NCT05295940, PMID: 41109426). A 12-week multiple-ascending-dose study in 100 participants with obesity or overweight, run without dose escalation, reported weight reduction across dose groups ranging from 2.6 percent to 11.3 percent, with decreased appetite in 19 percent, headache in 12 percent and fatigue in 11 percent, and infrequent gastrointestinal events: diarrhea in 10 percent, nausea in 8 percent and vomiting in 4 percent (PMID: 41559929). A 48-week phase 2 trial randomized 263 adults across six dose or dose-escalation arms and placebo and reported mean weight change from baseline of about 9 percent to 20 percent against 0.4 percent on placebo, with nausea and fatigue the most common adverse events (NCT06230523, PMID: 41207310).\n\nA network meta-analysis of six trials in 4642 adults ranked high-dose eloralintide second only to amycretin for percent body weight reduction, ahead of semaglutide, while noting that gastrointestinal adverse events rose with high doses of amylin-based therapies and that the evidence is still sparse and low certainty (PMID: 42175595). Anything sold outside a trial is not the studied product and has no verified identity or purity.", "half_life": "Terminal geometric mean half-life 310 to 366 hours, that is 12.9 to 15.3 days, across the doses tested in the phase 1 single-ascending-dose study in humans (PMID: 41109426)", "molecular_weight": "4526 g/mol", "molecular_mass": "4526 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Subcutaneous injection" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Phase 3", "approval_status": "Investigational and not approved by the FDA, the EMA or any other regulator. It is in phase 3 trials sponsored by Eli Lilly and Company for obesity and overweight (NCT07321886), for obesity or overweight with type 2 diabetes (NCT07282600), for obstructive sleep apnea with obesity (NCT07369011), for osteoarthritis knee pain with obesity (NCT07353931) and as an add-on in people already on a weekly incretin (NCT07392190). It is not a controlled substance and is not named on the World Anti-Doping Agency Prohibited List. Research-use-only compound in the US market.", "trial_phase": "", "cas_number": "2883634-40-8", "iupac_name": "", "chemical_formula": "C201H319N49O65S2", "potential_benefits": [ "Mean body weight change from baseline of about 9 percent to 20 percent across dose groups at 48 weeks against 0.4 percent on placebo in a 263-patient phase 2 trial in adults with obesity or overweight (PMID: 41207310)", "Weight reduction of 2.6 percent to 11.3 percent across dose groups at 12 weeks in 100 adults with obesity or overweight in a phase 1 multiple-ascending-dose study (PMID: 41559929)", "Week 4 weight reduction of 2.5 percent and 4.4 percent after single doses in healthy participants against a 0.6 percent gain on placebo (PMID: 41109426)", "Dose-dependent reduction in food intake and body weight, mainly through fat mass loss, in diet-induced obese rats (PMID: 41109426)", "Significantly less conditioned taste avoidance than cagrilintide in lean rats, a marker of reduced aversive signaling (PMID: 41109426)" ], "research_fields": [ "Obesity pharmacotherapy", "Amylin receptor pharmacology", "Metabolic disease", "Appetite regulation" ], "pubmed_count": 0, "pubchem_cid": 175663130, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/eloralintide" }, { "id": "aa600372-2b33-4f6f-8b67-2e96be8a847d", "slug": "enclomiphene", "name": "Enclomiphene", "aliases": [ "Androxal" ], "category": "Hormone Support", "description": "\nEnclomiphene citrate (ENC, Androxal, trans-clomiphene) is the pure trans-isomer of clomiphene citrate, a non-steroidal selective estrogen receptor modulator (SERM) developed originally by Repros Therapeutics for the treatment of secondary (hypogonadotropic) hypogonadism in men who want to preserve fertility. Where clomiphene citrate — the classical ovulation induction drug used in women since FDA approval in 1967 — is a 62:38 mixture of two geometric isomers (enclomiphene and zuclomiphene), enclomiphene is the short-acting antagonist component that carries virtually all of the therapeutically useful activity at the male hypothalamic-pituitary-gonadal (HPG) axis, while zuclomiphene is a long-half-life weak estrogen agonist that accumulates with chronic dosing and is blamed for much of clomiphene's off-target visual, mood, and gynecomastia-risk profile.\n\nIn men, enclomiphene works by competitively blocking estradiol at estrogen receptor alpha (ERα) in the hypothalamus and pituitary. Negative feedback from circulating estradiol normally throttles gonadotropin-releasing hormone (GnRH) pulse generation; when enclomiphene occupies these receptors, the hypothalamus is \"blinded\" to estrogen, GnRH pulse frequency increases, the pituitary ramps up luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, and the testes respond by increasing endogenous testosterone production and spermatogenesis. The net clinical effect, in men with a functional HPG axis that is simply being under-driven (secondary hypogonadism), is a restoration of serum total testosterone into the mid-normal range — often 500-700 ng/dL from baselines below 300 ng/dL — while preserving or improving sperm count, motility, and morphology. This stands in sharp contrast to exogenous testosterone replacement therapy (TRT), which suppresses LH/FSH, shuts down intratesticular testosterone production, and typically drives sperm counts toward azoospermia within 3-6 months of use ([Anawalt, 2020]).\n\nEnclomiphene sits in an unusual regulatory limbo. Repros Therapeutics ran two successful Phase 3 trials (ZA-301 and ZA-302) in overweight men with secondary hypogonadism, demonstrating that once-daily 12.5 mg or 25 mg enclomiphene restored morning total testosterone while maintaining or increasing sperm concentration relative to both placebo and topical testosterone gel ([Kim et al., 2016]). Despite these results, the FDA declined to approve Androxal in 2015, citing concerns about the clinical meaningfulness of the primary endpoints and the absence of long-term cardiovascular outcomes data — concerns that parallel the broader regulatory pushback against all low-T treatment paradigms during the 2013-2016 era. Repros subsequently went bankrupt, and the molecule fell into a commercial gray zone: not FDA-approved, but sold widely through US telehealth clinics and compounding pharmacies under state physician supervision as an \"off-label\" or \"investigational\" testosterone tuning tool, particularly for men who want to avoid the fertility penalty of TRT.\n\nFor bodybuilders, biohackers, and men pursuing testosterone tuning, enclomiphene has become a central pillar of the \"fertility-preserving\" and \"post-cycle therapy\" toolkits. It is used as (1) a monotherapy for men with secondary hypogonadism who want natural production rather than exogenous testosterone; (2) a post-cycle therapy (PCT) agent after anabolic steroid cycles to restart the HPG axis; (3) an adjunct or alternative to [hCG](/compound/hcg) for men on TRT who want to preserve testicular volume and fertility; and (4) a mild endogenous testosterone booster in men with borderline hypogonadism or age-related T decline. Its oral dosing, lack of injection requirement, favorable side effect profile relative to clomiphene itself, and fertility-preserving mechanism make it one of the more popular prescription-gray-market molecules in the men's health tuning space.\n\nThis entry covers the full pharmacology, clinical evidence base, protocol considerations, and safety profile of enclomiphene citrate. It is intended for educational and research reference only — enclomiphene is a prescription drug in most jurisdictions, is NOT FDA-approved for any indication, and the decision to use it should involve a qualified physician who can order appropriate baseline and follow-up labs (total testosterone, free testosterone, estradiol, LH, FSH, SHBG, CBC, CMP, lipid panel, and semen analysis when fertility is a concern). Cross-reference this page with [HCG](/compound/hcg), [Gonadorelin](/compound/gonadorelin), and [Kisspeptin-10](/compound/kisspeptin-10) for a complete picture of HPG axis modulation strategies.\n", "half_life": "~10 hours", "molecular_weight": "405.9 Da", "molecular_mass": "405.96 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "6,250–25,000 mcg (6.25–25 mg) oral daily", "dosing_frequency": "Once daily oral", "cycle_length": "4–12 weeks; some use ongoing", "common_vial_sizes": [ "12.5mg capsules", "25mg capsules" ], "research_stage": "Phase III", "approval_status": "", "trial_phase": "", "cas_number": "15690-57-0", "iupac_name": "(E)-2-[4-(2-chloro-1,2-diphenylethenyl)phenoxy]-N,N-diethyl-ethanamine", "chemical_formula": "C26H28ClNO", "potential_benefits": [ "Increased endogenous testosterone production", "HPTA axis restoration after suppression", "Maintained fertility during TRT", "Improved LH and FSH levels", "Fewer estrogenic side effects than clomiphene" ], "research_fields": [], "pubmed_count": 95, "pubchem_cid": 1548953, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/enclomiphene" }, { "id": "7a39b05c-d646-4c9a-b466-d8f72477a1e3", "slug": "epitalon", "name": "Epitalon", "aliases": [ "Epithalon", "Epithalamin", "Ala-Glu-Asp-Gly", "AEDG" ], "category": "Bioregulator Peptide", "description": "Epitalon is a **synthetic tetrapeptide (Ala-Glu-Asp-Gly)** developed by Vladimir Khavinson at the St. Petersburg Institute of Bioregulation and Gerontology in the 1980s, modeled on the natural pineal gland peptide epithalamin. The most-researched compound in the Khavinson \"short peptide bioregulator\" family for anti-aging and longevity research.\n\nThe primary mechanism of interest is **telomerase activation**: in human somatic cell cultures and rodent studies, Epitalon administration is associated with increased telomerase activity and telomere elongation — a mechanism implicated in cellular aging. Clinical research in elderly Russian populations has reported improved sleep quality, melatonin restoration, and reduced age-related mortality over multi-year follow-up.\n\nIn the United States, Epitalon is **not FDA-approved** and is sold as research-only. The bulk of clinical research is published in Russian-language journals; English-language peer-reviewed literature is moderate.", "half_life": "~30-60 minutes (peptide; biological effects extend long beyond plasma clearance)", "molecular_weight": "390.35 g/mol", "molecular_mass": "", "amino_acid_sequence": "Ala-Glu-Asp-Gly (AEDG)", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "C14H22N4O9", "potential_benefits": [], "research_fields": [], "pubmed_count": 47, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/epitalon" }, { "id": "380f6bf8-902d-46e7-9f8c-5798401d07a3", "slug": "epithalon", "name": "Epithalon", "aliases": [ "Epitalon" ], "category": "Longevity & Cellular Health", "description": "Epithalon (also spelled **Epitalon**, sequence **Ala-Glu-Asp-Gly / AEDG**) is a synthetic tetrapeptide designed by Prof. Vladimir Khavinson at the St. Petersburg Institute of Bioregulation and Gerontology in the 1980s as a short-chain analog of **epithalamin**, a peptide extract of bovine pineal gland. It is the most-studied \"longevity peptide\" in the Russian peer-reviewed literature, with over 30 years of published work on **telomerase activation, telomere lengthening, melatonin restoration, and life-span extension in rodents**.\n\nThe core biology is three-fold:\n\n- **Telomerase activation in somatic cells** — Khavinson and Smirnova showed that 10 ng/mL AEDG increased hTERT expression and telomerase activity in human somatic fibroblasts, extending proliferative capacity by ~42% over the Hayflick limit ([Khavinson et al., 2003, *Bull Exp Biol Med*]).\n- **Restoration of pineal melatonin secretion** — In aged rats and in elderly humans, epithalon restored the nocturnal melatonin peak that declines with pineal calcification, improving circadian amplitude and sleep architecture ([Anisimov et al., 2003]).\n- **Direct chromatin binding (epigenetic)** — NMR and X-ray studies demonstrate that AEDG binds the major groove of DNA at specific sequences, modulating transcription of interferon-γ, hTERT, and cell-cycle regulators ([Fedoreyeva et al., 2011]).\n\n**Critical evidence-quality caveat:** Unlike BPC-157 or the GLP-1 agonists, the **human clinical evidence for Epithalon is almost entirely from Russian-language publications** from a single research consortium (Khavinson / Anisimov / Korkushko). Western replication is minimal. The rodent data are compelling — a **~30% median life-span extension** in female mice ([Anisimov et al., 2003]) — but translating this to human longevity remains hypothesis rather than demonstrated fact.\n\nEpithalon is used in biohacking communities for:\n- Sleep consolidation in adults over 40 (melatonin restoration)\n- Telomere preservation as part of a longevity stack\n- Circadian rhythm repair after shift-work or jet lag\n- Adjunct in age-related immunosenescence\n\nIt is delivered by subcutaneous injection, typically **5-10 mg/day for 10-20 consecutive days**, followed by a **3-6 month washout**. This intermittent pulsing is intentional — Khavinson's protocols were always short-cycle, never continuous — and is a key safety feature in the absence of long-term continuous-dosing data.", "half_life": "Not well characterized in humans. As a small tetrapeptide, AEDG is expected to have a very short plasma half-life (on the order of minutes), while downstream gene-expression and circadian effects are thought to persist considerably longer. Any specific half-life figure should be treated as an unvalidated estimate.", "molecular_weight": "390.3 Da", "molecular_mass": "390.35 g/mol", "amino_acid_sequence": "Ala-Glu-Asp-Gly (AEDG)", "administration_routes": [ "Subcutaneous" ], "dose_range_mcg": "5000-10000 mcg (5-10 mg) subcutaneous daily for 10-20 day cycles; typically repeated 1-2 times per year in anti-aging protocols", "dosing_frequency": "Once daily for 10–20 day cycles", "cycle_length": "10–20 day intensive cycles, repeated every 4–6 months", "common_vial_sizes": [ "10mg", "50mg" ], "research_stage": "Preclinical (Western standards); Used clinically in Russian gerontological medicine", "approval_status": "Research Use Only - not approved by the FDA or EMA for any indication. Used in the Russian Federation as a peptide bioregulator; available elsewhere only as a research chemical.", "trial_phase": "Preclinical", "cas_number": "307297-39-8", "iupac_name": "L-alanyl-L-alpha-glutamyl-L-alpha-aspartylglycine", "chemical_formula": "C14H22N4O9", "potential_benefits": [ "Telomerase activation and telomere elongation (human cell culture)", "Normalization of circadian melatonin rhythm (human data from epithalamin, the parent pineal preparation)", "Improved sleep consolidation and circadian regularity (subjective)", "Modest life-span effects in rodents (mainly maximum / late-survivor lifespan; no change in mean lifespan)", "Reduced incidence of specific tumors (e.g. ~6-fold fewer leukemias in SHR mice); no change in total tumor incidence", "Reduced chromosomal aberrations in aged rodent tissue", "Site-specific DNA / chromatin binding (proposed epigenetic modulation)", "Association with lower mortality in an elderly cardiovascular cohort (epithalamin RCT, Korkushko 2011)" ], "research_fields": [ "Longevity / anti-aging", "Telomere biology", "Chronobiology / sleep", "Pineal endocrinology", "Geroscience", "Epigenetics", "Cancer prevention (rodent)", "Immunosenescence" ], "pubmed_count": 1, "pubchem_cid": 219042, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/219042/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/epithalon" }, { "id": "24af1efd-5ee6-4c42-9380-7993764c9fc8", "slug": "exenatide", "name": "Exenatide", "aliases": [ "Satiora", "GLP-1 Spray" ], "category": "Weight Loss", "description": "Exenatide (Byetta, Bydureon) is a synthetic exendin-4 GLP-1 receptor agonist, FDA-approved for type 2 diabetes, that lowers blood glucose and curbs appetite. Available as a twice-daily immediate-release and a once-weekly extended-release injection.", "half_life": "Immediate-release (Byetta): terminal half-life about 2.4 hours, cleared mainly by the kidneys. Extended-release (Bydureon): the same peptide is released slowly from biodegradable microspheres over roughly 10 weeks, reaching steady-state plasma levels by about 6 to 7 weeks.", "molecular_weight": "4186.6 g/mol (molecular formula C184H282N50O60S)", "molecular_mass": "", "amino_acid_sequence": "HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS (39 amino acids, C-terminally amidated; synthetic exendin-4)", "administration_routes": [], "dose_range_mcg": "5 to 10 mcg twice daily (Byetta, immediate-release) or 2000 mcg (2 mg) once weekly (Bydureon, extended-release)", "dosing_frequency": "Twice daily before meals (immediate-release) or once weekly (extended-release)", "cycle_length": "Not cycled. GLP-1 receptor agonists are used as continuous, long-term therapy for as long as they remain clinically beneficial. There is no on/off cycling protocol.", "common_vial_sizes": [], "research_stage": "FDA-approved", "approval_status": "FDA-approved for type 2 diabetes: Byetta (immediate-release exenatide) since 2005 and Bydureon / Bydureon BCise (extended-release exenatide) since 2012. Not FDA-approved for weight management or for people without diabetes; any such use is off-label and outside the approved indication.", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Meaningful glycemic control in type 2 diabetes, with HbA1c reductions of roughly 1.0 to 1.9 percent in randomized trials", "Weight reduction of about 2 to 3 kg in diabetic trials, driven mainly by reduced appetite and slower gastric emptying", "Low intrinsic hypoglycemia risk because insulin release is glucose-dependent (risk rises when combined with sulfonylureas or insulin)", "Strong control of post-meal glucose spikes", "Cardiovascular safety shown in a large outcomes trial, with no increase in major cardiac events", "Can be added to basal insulin to improve control while offsetting insulin-related weight gain", "Once-weekly extended-release option (Bydureon) reduces injection burden versus twice-daily dosing", "In people without diabetes the appetite effect is real, but standalone weight loss has been modest and less consistent than newer agents such as [semaglutide](/compound/semaglutide) or [tirzepatide](/compound/tirzepatide)" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/exenatide" }, { "id": "bc67d38a-96ca-4fe0-bdb5-8f29e901b13a", "slug": "fadogia-agrestis", "name": "Fadogia Agrestis", "aliases": [ "Fadogia", "Black Aphrodisiac", "West African Aphrodisiac", "Bakin Gagai", "Fadogia agrestis stem", "Nigerian aphrodisiac" ], "category": "Adaptogen", "description": "**Fadogia agrestis** (also sometimes called \"Black Aphrodisiac\" or \"West African Aphrodisiac\" in English-language supplement marketing; **bakin gagai** in Hausa; and historically known by various regional names across its native range) is a flowering shrub of the family Rubiaceae (the coffee and cinchona family) native to the savanna regions of tropical West and Central Africa — with documented distribution across Nigeria, Sudan, Cameroon, Chad, Senegal, Burkina Faso, and surrounding countries. The plant grows as a small to medium shrub (typically 1-3 meters tall) in seasonally dry savanna woodland. Its stems, leaves, and roots have been used in traditional West African ethnomedicine for generations, but the dominant and best-documented traditional use is as an **aphrodisiac and treatment for erectile dysfunction**, particularly in Nigerian and Sudanese folk medicine traditions. Other traditional applications include use as a fever remedy, a treatment for rheumatism and stiffness, and occasionally as a stimulant tonic.\n\nThe journey of *Fadogia agrestis* from obscure West African ethnobotanical to trending Western \"testosterone booster\" supplement is a notable case study in how modern podcast and social-media-driven supplement culture can catapult an unfamiliar plant from traditional medicine into mass-market availability with dramatically thinner evidence than the mainstream audience generally realizes. **Prior to approximately 2021-2022**, Fadogia agrestis was essentially unknown in Western supplement markets — not available through major retailers, not discussed in mainstream bodybuilding or men's-health media, and not mentioned in Western nutrition research. **Dr. Andrew Huberman** — a Stanford neuroscientist who hosts one of the most-listened podcasts globally — began discussing and recommending Fadogia agrestis (typically paired with [Tongkat Ali](/compound/tongkat-ali)) as part of his personal testosterone-support regimen on podcast episodes in 2021-2022. The Huberman endorsement produced a rapid and dramatic surge in consumer demand, and within approximately 12-18 months Fadogia agrestis went from essentially unknown to available from dozens of Western supplement brands, discussed extensively on Reddit, Instagram, TikTok, and the broader fitness/biohacking content ecosystem.\n\nThe critical and honest problem with Fadogia agrestis as a Western supplement: **the evidence base supporting its claimed benefits consists almost entirely of rodent studies, with essentially zero rigorous human clinical trials**. This places Fadogia in a substantially weaker evidence category than [Tongkat Ali](/compound/tongkat-ali) (which has multiple controlled human trials) or even [Tribulus terrestris](/compound/tribulus-terrestris) (whose human trials are inconsistent but exist in meaningful number). Buyers of Fadogia agrestis supplements in Western markets are generally purchasing a compound whose human effects, dose-response relationships, safety profile in humans, and long-term tolerability are essentially unknown — with rodent-study-based extrapolation and podcast-amplified anecdote filling the evidentiary gap.\n\nThe rodent evidence, to be fair, is genuinely interesting. **Yakubu et al. 2005** (*Journal of Ethnopharmacology*), conducted by researchers at the University of Ilorin (Nigeria), tested aqueous extract of Fadogia agrestis stem in male rats at doses of 18, 50, and 100 mg/kg daily for 5 days. Results: the two higher doses (50 and 100 mg/kg) produced significant increases in serum testosterone — dramatic elevations relative to control, comparable to what might be seen with actual pharmaceutical androgen administration. The 18 mg/kg dose showed modest effect. **Yakubu et al. 2008** (*Asian Journal of Andrology*) followed up with a sexual behavior study in rats demonstrating increased mount frequency, intromission frequency, and ejaculation latency — behavioral correlates of the testosterone finding. These rodent results are what generated the \"Fadogia raises testosterone\" claim. **However**, the same Yakubu research group (Yakubu et al. 2008, *Human & Experimental Toxicology*, PMID: 19042951) subsequently documented significant dose-dependent toxicity from Fadogia at the same testosterone-raising doses, including evidence of testicular damage, kidney injury, and liver injury in chronically-dosed rats — a safety signal that deserves equal attention to the testosterone finding.\n\nThe principal bioactive compounds in Fadogia agrestis are **not well characterized** — another deficit in the evidence base. Phytochemical analyses have identified the presence of alkaloids (uncharacterized), saponins, flavonoids, tannins, and anthraquinones, but the specific compounds responsible for the purported testosterone effect have not been identified, isolated, or characterized pharmacologically. This makes standardization of Fadogia products essentially impossible in any meaningful sense — brands claiming \"standardized to X% saponins\" or \"standardized to active compounds\" are making claims that cannot be verified against a scientific consensus about what the active compounds actually are. Different commercial Fadogia extracts likely contain different compound profiles, and there is no established dose-response relationship in humans that would allow rational dosing decisions.\n\nGiven the substantial gaps in the evidence base, the most honest assessment of Fadogia agrestis is: an ethnobotanically interesting compound with suggestive but limited preclinical data, a worrying rodent toxicity signal at the same doses associated with testosterone elevation, zero strong human clinical trials, no characterized bioactive compounds, and no standardized commercial products in any meaningful scientific sense. The enthusiastic consumer reception has substantially outstripped the supporting evidence. Reasonable positioning: if you're interested in \"natural testosterone support\" and want to add a novel herb alongside [Tongkat Ali](/compound/tongkat-ali) (which has stronger evidence), Fadogia is a plausible experimental option — but cycling (4-8 weeks on, 4+ weeks off) is important given the rodent toxicity signal, monitoring liver and kidney function is advisable, and expectations should be calibrated to the reality that you are taking a compound whose human effects and safety profile are genuinely uncertain.\n\nFor users who want to support endogenous testosterone with the strongest-evidence herbal options: [Tongkat Ali](/compound/tongkat-ali) (LJ100 or Physta standardized extracts, 200mg daily) has the clearest human clinical evidence, followed by [ashwagandha](/compound/ashwagandha) (KSM-66, 600mg daily — particularly good evidence in stressed men) and tuning of [zinc](/compound/zinc), [vitamin D](/compound/vitamin-d), sleep, resistance training, and body composition. Fadogia should be considered a more speculative addition to this foundational stack rather than a primary intervention.\n\n**Quality and sourcing concerns** with Fadogia are particularly acute compared with better-established herbs. The supply chain for Fadogia agrestis from West Africa to Western supplement manufacturers is opaque, with minimal regulatory oversight on harvesting practices, plant identification (substitution with other Fadogia species or entirely different plants is a real concern), processing standards, contamination testing (heavy metals, pesticides, microbial), and content verification. Third-party testing for Fadogia products is less mature than for more mainstream supplements, making adulteration and misidentification harder to detect. Users should preferentially choose products from brands with transparent sourcing, microscopic/DNA plant identification verification, heavy metal and contamination testing, and established reputation — recognizing that even best-case Fadogia quality is less well-controlled than established herbal supplements.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 1140, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/fadogia-agrestis" }, { "id": "57cdc768-545b-45bc-8f6b-ff7f35f786cc", "slug": "fasoracetam", "name": "Fasoracetam (NS-105)", "aliases": [ "NS-105", "NFC-1", "AEVI-001", "LAM-105", "NB-001", "Fasoracetam monohydrate", "5-oxo-D-prolinepiperidinamide" ], "category": "Nootropics", "description": "Fasoracetam is a racetam developed by Nippon Shinyaku in Japan under the code NS-105 and taken into clinical development for vascular dementia. That program did not lead to approval anywhere. The molecule was later licensed and revived in the United States as NFC-1 and then AEVI-001 by Aevi Genomic Medicine, which tested it in children and adolescents with attention deficit hyperactivity disorder selected by genotype, and more recently as NB-001 by Nobias Therapeutics for 22q11.2 deletion syndrome. No regulator has approved it for any indication. Material sold to consumers is a research chemical, usually the monohydrate, and the chemistry values below are for the anhydrous form.\n\nThe Nippon Shinyaku pharmacology, published between 1997 and 2000, describes a compound acting through metabotropic glutamate receptors rather than through a single ion channel. In rat cerebrocortical membranes, NS-105 inhibited forskolin-stimulated cyclic AMP formation through pertussis toxin sensitive G proteins and enhanced it after pertussis toxin pretreatment, a bidirectional pattern shared with the metabotropic glutamate agonist ACPD and blocked by a metabotropic glutamate antagonist (PMID: 9134967). The same bidirectional effect appeared in cultured mouse cortical neurons (PMID: 9272724), and antisense work assigned the inhibitory arm to group II and group III receptors and the facilitatory arm to group I (PMID: 10633154). Two other effects are reported: repeated dosing increased GABA-B receptor numbers in rat cerebral cortex without changing beta-adrenoceptor or 5-HT2 binding (PMID: 9424016), and NS-105 increased acetylcholine release and high-affinity choline uptake in rat cerebral cortex (PMID: 10494996).\n\nIn rats, NS-105 reversed memory disruption produced by scopolamine, by lesions of the nucleus basalis magnocellularis, by AF64A, by baclofen, by cerebral ischemia and by electroconvulsive shock (PMID: 10494996). It also reduced immobility in the forced swim test and reversed escape failure in learned helplessness (PMID: 9424016).\n\nThe human data are thin and mostly open-label. A five-week open-label study with a single-blind placebo week enrolled 30 adolescents aged 12 to 17 who had ADHD and mutations in metabotropic glutamate receptor network genes. Mean Clinical Global Impressions scores improved from 3.79 to 2.33 for improvement and 4.83 to 3.86 for severity, both significant, and adverse event rates during the placebo week did not differ from active weeks (PMID: 29339723). The controlled trials that followed did not confirm this. The ASCEND phase 2 program, run in two parts in children and adolescents with and without the relevant copy number variants, completed in 2018 (NCT03265119; NCT03609619) and posted results show the primary ADHD rating scale endpoint was not met in either part, with placebo numerically ahead in Part A and the drug described as safe and well tolerated. A separate placebo-controlled crossover trial in 37 children and adolescents with 22q11 deletion syndrome completed in 2023 (NCT05290493).\n\nFasoracetam is not approved in any country and is not a controlled substance in the United States. It is a research-use-only compound in the United States market.", "half_life": "Mean terminal half-life 4.82 hours, range 4.06 to 6.99 hours, after single oral doses in adolescents aged 12 to 17, with the drug excreted for the most part unchanged through the kidneys (PMID: 29339723). After intravenous dosing in animals, elimination half-life was 0.67 hours in rats, 2.1 hours in dogs and 1.3 hours in monkeys, with high systemic availability after oral dosing in all three species (PMID: 10604039).", "molecular_weight": "196.25 g/mol", "molecular_mass": "196.25 g/mol (anhydrous)", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Phase 2", "approval_status": "Fasoracetam has never been approved by any regulator. It was developed in Japan for vascular dementia and did not reach the market, and ChEMBL records a maximum clinical phase of 2 (ChEMBL2106179). Recent development has been in the United States, where phase 1 and phase 2 trials in ADHD, 22q11.2 deletion syndrome and related conditions were completed between 2015 and 2023 without an approval. It is not a controlled substance in the United States, where everything sold to consumers is a research-use-only compound.", "trial_phase": "", "cas_number": "110958-19-5", "iupac_name": "", "chemical_formula": "C10H16N2O2", "potential_benefits": [ "Reversed memory disruption from scopolamine, nucleus basalis lesion, AF64A, baclofen, cerebral ischemia and electroconvulsive shock in rats (PMID: 10494996)", "Increased acetylcholine release and high-affinity choline uptake in the cerebral cortex and hippocampus of rats (PMID: 10494996)", "Reduced immobility in the forced swim test and reversed escape failure in learned helplessness in rats (PMID: 9424016)", "Improved Clinical Global Impressions improvement and severity scores over five weeks in 30 adolescents with ADHD and metabotropic glutamate receptor network mutations, in an open-label study with a single-blind placebo week (PMID: 29339723)" ], "research_fields": [ "Metabotropic glutamate signaling", "ADHD", "Cognitive enhancement", "Nootropics" ], "pubmed_count": 0, "pubchem_cid": 198695, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/fasoracetam" }, { "id": "96915af9-4c27-43bd-bad2-62f1061ea0e7", "slug": "finasteride", "name": "Finasteride", "aliases": [ "Propecia", "Proscar", "Fincar", "Finpecia", "MK-906", "N-tert-butyl-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide", "Type II 5α-reductase inhibitor" ], "category": "Pharmaceutical", "description": "**Finasteride** is an orally-active **selective type II 5α-reductase inhibitor** that blocks the conversion of testosterone to **dihydrotestosterone (DHT)**, the primary androgenic driver of both **benign prostatic hyperplasia (BPH)** and **androgenetic alopecia (male-pattern hair loss)**. Developed by Merck in the 1980s and first approved by the FDA in **1992 as Proscar (5mg/day) for BPH**, finasteride was subsequently approved in **1997 as Propecia (1mg/day) for male-pattern hair loss** after trials demonstrated that lower doses effective for scalp DHT suppression maintained efficacy for hair regrowth with fewer systemic effects. Finasteride remains one of only two FDA-approved oral therapies for androgenetic alopecia (the other being dutasteride, approved only in Korea and Japan for this indication). After 30+ years of clinical use and extensive post-marketing surveillance, finasteride has a strong efficacy profile for its labeled indications but remains one of the most controversial therapeutics in contemporary dermatology and urology due to the **post-finasteride syndrome (PFS)** debate — a collection of persistent sexual, cognitive, and psychological symptoms reported by some users after discontinuation that has prompted FDA labeling updates, ongoing research, and significant clinical-ethical discussion.\n\nThe mechanistic foundation is clear: **5α-reductase** is a family of three isoenzymes (type I, II, III) that irreversibly convert testosterone to the more potent androgen dihydrotestosterone. DHT has roughly 3-5× higher androgen receptor binding affinity than testosterone and is the primary androgen driving prostate growth, hair follicle miniaturization in androgenetic alopecia, sebaceous gland activity, and some aspects of external male virilization. Type II 5α-reductase is the dominant isoform in prostate and hair follicles (its primary clinical target), while type I is dominant in skin, sebaceous glands, and liver; type III has been more recently characterized and is expressed in multiple tissues including brain. Finasteride selectively inhibits **type II (primary)** and **type III (partial)** isoforms with minimal effect on type I. This selectivity contrasts with **dutasteride**, which inhibits all three isoforms and produces more complete DHT suppression (~95% vs ~70% for finasteride) but at the cost of broader side-effect profile.\n\nThe clinical evidence base for finasteride is extensive and among the most rigorous in all of dermatology and urology. For **BPH**, the landmark 4-year **PLESS trial** (Proscar Long-term Efficacy and Safety Study, **Gormley et al. 1992**, *NEJM*, with extended outcomes in **McConnell et al. 1998**) demonstrated that finasteride 5mg/day over 4 years reduced prostate volume by ~20%, improved urinary flow rate, reduced symptom scores, and — most critically — **reduced the risk of acute urinary retention by 57% and BPH-related surgery by 55%**. For **hair loss**, the key trials of **Kaufman et al. 1998** (*J Am Acad Dermatol*) and **Leyden et al. 1999** documented that finasteride 1mg/day over 1-2 years produced measurable hair count increases in ~83% of men, visible hair growth improvement in ~48%, and stabilization or improvement of androgenetic alopecia in ~90% of treated men, compared with progressive hair loss in most placebo controls. These findings have been reproduced across diverse populations (**Sato et al.** in Japan, **Tosti et al.** in Italy) and across multiple formulations.\n\nBeyond its labeled indications, finasteride has been used **off-label** for: (1) **female pattern hair loss** in post-menopausal women (typically 2.5-5mg/day, evidence mixed but some positive trials in post-menopausal population without concomitant hyperandrogenism); (2) **hirsutism and PCOS-related androgenic symptoms** in women (with appropriate contraception given teratogenic risk); (3) **prostate cancer chemoprevention** (the **PCPT trial**, **Thompson et al. 2003** *NEJM* PMID: 12824459, demonstrated finasteride reduced prostate cancer incidence by 25% but raised concerns about Gleason score upgrading that were ultimately revised after reanalysis); (4) **hidradenitis suppurativa** as adjunctive androgen-blockade therapy; and (5) **transgender feminizing hormone therapy** as an adjunct to estradiol for androgen suppression. For hair-loss dosing, **topical finasteride** formulations (0.25% solution, 0.1% gel) have emerged in the 2020s as an alternative delivery route attempting to preserve scalp efficacy while minimizing systemic exposure and side-effect risk — the comparative evidence (**Piraccini et al. 2022**, **Ali et al. 2020**) suggests topical finasteride can produce hair count improvements comparable to oral 1mg/day with reduced systemic DHT suppression, though longer-term data and regulatory approvals vary by country.\n\nThe **post-finasteride syndrome (PFS)** controversy warrants explicit acknowledgment in any honest discussion of finasteride. Reports of **persistent sexual dysfunction (PSD)**, **neurologic/psychiatric symptoms**, **cognitive complaints**, and **somatic symptoms** continuing weeks, months, or years after finasteride discontinuation have been collected through case series (**Irwig 2011, 2012** PMIDs: 21067618, 22498944), post-marketing reports to the FDA MedWatch system, and patient-advocacy groups. The FDA updated the Propecia label in **2012** to include warnings about potential persistent sexual dysfunction, and subsequent label changes have added warnings regarding suicidal ideation and depression. Parallel labeling changes have been made in Europe, Canada, and the UK. The mechanistic hypothesis for PFS involves **neurosteroid dysregulation** — 5α-reductase is expressed in brain tissue and produces GABA-A-positive neurosteroids (allopregnanolone, pregnanolone, tetrahydrodeoxycorticosterone) from their steroid precursors, and finasteride-induced suppression of these neurosteroids has been documented (**Melcangi et al. 2013**) to persist beyond drug cessation in some individuals. The clinical reality is that PFS is **real for some users** (well-documented persistent symptoms exist) but **uncommon in randomized trials** (most RCT side effects reverse on discontinuation) — individual susceptibility likely involves genetic, age-related, and possibly immunologic factors that remain incompletely characterized. Anyone considering finasteride should be aware of this possibility, discuss it with their prescriber, and have a clear plan for symptom monitoring and discontinuation criteria.\n\nSee also [Dutasteride](/compound/dutasteride), [Minoxidil](/compound/minoxidil), [Saw Palmetto](/compound/saw-palmetto), [DHEA](/compound/dhea), [Testosterone](/compound/testosterone), [Pregnenolone](/compound/pregnenolone), [Ashwagandha](/compound/ashwagandha), [Clascoterone](/compound/clascoterone), and [RU-58841](/compound/ru-58841) for adjacent androgen-pathway, hair-loss, and prostate-health compounds. This is educational content only and not medical advice — finasteride is a prescription medication with significant hormonal effects requiring physician supervision, baseline and follow-up monitoring, and informed consent regarding the full spectrum of potential effects including post-finasteride syndrome.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/finasteride" }, { "id": "4796d85a-6fb3-4094-a67d-927c8aec76f2", "slug": "fisetin", "name": "Fisetin", "aliases": [ "Fisetin", "3,3',4',7-Tetrahydroxyflavone", "2-(3,4-Dihydroxyphenyl)-3,7-dihydroxy-4H-chromen-4-one", "Fisetin aglycone", "Fustin reduced", "Natural Yellow 8", "Strawberry flavonoid", "Novusetin", "Fisetin phytosome", "Fisetol" ], "category": "Flavonoid", "description": "\nFisetin is a polyhydroxy flavonoid (3,3',4',7-tetrahydroxyflavone) that has emerged as one of the most extensively studied natural senolytic compounds and a candidate therapy for age-related disease. Structurally it is a flavonol closely related to quercetin but with one fewer hydroxyl group — quercetin is 3,3',4',5,7-pentahydroxyflavone; fisetin is 3,3',4',7-tetrahydroxyflavone, lacking the 5-hydroxyl group. This single structural difference substantially alters fisetin's physicochemical and pharmacokinetic properties compared to quercetin: fisetin has better lipophilicity, superior blood-brain barrier penetration, higher oral bioavailability in its aglycone form, and a distinct profile of senolytic selectivity in cellular screening studies.\n\nFisetin occurs in a narrow range of dietary sources with strawberries as by far the richest: fresh strawberries contain 160 mcg/g (approximately 20-25 mg per cup of strawberries). Other dietary sources are substantially lower: apples (27 mcg/g), persimmons (11 mcg/g), lotus root (6 mcg/g), onions (5 mcg/g), grapes (4 mcg/g), kiwi (2 mcg/g), cucumbers (1 mcg/g), and tomatoes, peaches, and other fruits in trace amounts. The acacia tree (Acacia greggii and Acacia berlandieri) produces fisetin as a heartwood constituent, and many commercial fisetin supplements are extracted from Rhus succedanea (Japanese wax tree) or similar botanical sources rather than from strawberries directly. Typical Western diets provide under 1 mg of fisetin daily, making food-based supplementation insufficient for the doses associated with senolytic effects (100+ mg daily of bioavailability-enhanced fisetin or higher pulse-dose protocols).\n\nThe modern interest in fisetin as a therapeutic agent derives primarily from a 2018 study by Yousefzadeh and colleagues published in EBioMedicinetitled \"Fisetin is a senotherapeutic that extends health and lifespan.\" The study screened 10 natural flavonoids for senolytic activity in cultured murine fibroblasts and found that fisetin was the most potent, producing 25-50% reduction of senescent cells at 5 micromolar concentration compared to less than 10% reduction for most other tested flavonoids. The study then administered fisetin 100 mg/kg or 500 mg/kg via oral gavage to aged (22-24 month old) C57BL/6 mice for 5 consecutive days every two weeks, and reported reductions in senescence markers across multiple tissues including adipose, kidney, liver, and spleen. Physical function improved in aged mice receiving fisetin, and median lifespan was extended by approximately 10% from the start of treatment at 85 weeks. These findings — extending lifespan and healthspan in aged mice with a naturally-occurring orally-bioavailable food-derived compound — generated immediate interest in human translation.\n\nSubsequent research has expanded fisetin's profile. Kim 2016reviewed fisetin's neuroprotective effects in Alzheimer's disease models. Maher 2015showed fisetin attenuated Alzheimer's-related deficits in APP/PS1 mice. Wang 2019 reviewed fisetin in cancer applications with in vitro evidence for multiple tumor types. Mahmoudi 2018 reviewed fisetin in osteoarthritis models. Multiple in vitro cellular screening studies have consistently identified fisetin among the most selective senolytic natural compounds, with enhanced selectivity for senescent over non-senescent cells compared to other tested flavonoids.\n\nClinical translation has been deliberate but slow. As of 2026, multiple Phase 2 trials are underway including the AFFIRM-LITE trial at Mayo Clinic (NCT03675724) testing fisetin 20 mg/kg for 2 consecutive days monthly in frail elderly women for functional and biomarker outcomes; the trial dosing protocol has become the reference standard for human senolytic use of fisetin. Other trials are recruiting in osteoarthritis, post-COVID fatigue syndromes, diabetic kidney disease, and mild cognitive impairment. Hickson and colleagues at Mayo have published pilot experience with intermittent senolytic dosing using fisetin and D+Q combinations.\n\nPharmacokinetically fisetin has a plasma half-life of approximately 3-5 hours for free aglycone and up to 9 hours for glucuronide conjugates. Plasma protein binding is high (>95%). Oral bioavailability of standard aglycone is approximately 40-70% in some studies — substantially higher than quercetin aglycone's 2-10%. Bioavailability-enhanced formulations including fisetin phytosome (lecithin complex) further increase plasma levels 3-5-fold compared to aglycone. Tissue distribution is broad with relatively high concentrations in brain, liver, kidney, and adipose tissue. Blood-brain barrier penetration is substantially better than quercetin, making fisetin particularly attractive for central nervous system applications.\n\nCommercial fisetin supplementation products typically source fisetin from extraction of Rhus succedanea (Japanese wax tree) or Acacia greggii heartwood, with purification to 90-98% fisetin content. Novusetin (HealthStar) is a standardized 98% fisetin ingredient used in multiple commercial products. Fisetin phytosome formulations using sunflower lecithin provide improved bioavailability. Synthetic fisetin is also available and is molecularly identical to natural-source material. Typical supplementation doses range from 100 mg daily (low maintenance) to 1500 mg per dose (senolytic pulse dosing in an average adult). The senolytic protocol following AFFIRM-LITE dosing corresponds to approximately 20 mg/kg for 2 consecutive days taken once monthly — for a 70-kg person, that is 1400 mg per day for 2 days per month. This intermittent pulse dosing mimics the mouse protocol from Yousefzadeh 2018 scaled by body weight.\n\nFor bodyhackguide.co users, fisetin occupies a specific and growing place in the senolytic and longevity supplementation landscape. It pairs naturally with [quercetin](/compound/quercetin) (closely related flavonoid, often co-used during senolytic days), [dasatinib](/compound/dasatinib) (prescription senolytic partner in D+Q protocol), [curcumin](/compound/curcumin) (complementary polyphenol anti-inflammatory), [resveratrol](/compound/resveratrol) and [pterostilbene](/compound/pterostilbene) (stilbene polyphenols with overlapping longevity mechanisms), [spermidine](/compound/spermidine) (autophagy inducer), [rapamycin](/compound/rapamycin) (mTOR inhibitor, longevity gold standard), [NMN](/compound/nmn) and [nicotinamide-riboside](/compound/nicotinamide-riboside) (NAD precursors), [omega-3](/compound/omega-3), [vitamin-d3](/compound/vitamin-d3), and [magnesium](/compound/magnesium) for complete longevity protocols. The canonical recommendation for senolytic use is the AFFIRM-LITE-style protocol of 20 mg/kg for 2 consecutive days monthly (approximately 1400-1600 mg for an adult) using a bioavailability-enhanced formulation, with continuous low-dose maintenance (100-200 mg daily) as an optional complement.\n", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/fisetin" }, { "id": "7c82dc87-ce7f-435f-96d7-faf99cf32a60", "slug": "fladrafinil", "name": "Fladrafinil (CRL-40,941)", "aliases": [ "CRL-40,941", "CRL 40941", "Fluorafinil", "Bisfluoroadrafinil", "2-[bis(4-fluorophenyl)methylsulfinyl]-N-hydroxyacetamide" ], "category": "Nootropics", "description": "Fladrafinil, coded CRL-40,941, is the N-hydroxy analog of flmodafinil and the difluorinated counterpart of adrafinil. Flmodafinil was conceived at Laboratoire L. Lafon, the French company behind adrafinil and modafinil, and was never developed as a medicine (PMID: 30158846); the CRL-40,941 code of fladrafinil places it in the same series. Fladrafinil is sold today only as a research chemical or as an ingredient in unapproved supplements marketed for wakefulness and focus, and interest in it grew alongside the off-label use of modafinil as a cognitive enhancer (PMID: 27928893).\n\nIts pharmacology is best understood as prodrug chemistry. In a human administration study published in 2026, six volunteers each took a single 20 mg dose and gave urine and dried blood spot samples; fladrafinil was converted to flmodafinil, which was then oxidized to flmodafinil acid and flmodafinil sulfone, the same pattern adrafinil follows toward modafinil (PMID: 42210629). The activity therefore belongs mostly to flmodafinil rather than to the parent compound.\n\nFor flmodafinil there is one useful animal study, published under the compound names lauflumide and NLS-4. In male C57BL/6J mice with EEG and EMG recording, an intraperitoneal dose of 64 mg/kg produced longer wakefulness than modafinil at 150 mg/kg, without hyperlocomotion and without rebound hypersomnia, and recovery sleep afterwards involved less non-REM sleep and less delta activity than after modafinil (PMID: 30158846). No comparable study exists for fladrafinil itself.\n\nNothing about efficacy in people has been tested. The single human study measured concentrations and detection windows, not attention, wakefulness or performance (PMID: 42210629). For the class parent, positron emission tomography in ten healthy men showed that modafinil occupied dopamine transporters in caudate, putamen and nucleus accumbens and raised extracellular dopamine, a finding the authors linked to abuse potential (PMID: 19293415). Whether the fluorinated analogs behave the same way at the same exposures has not been measured in humans.\n\nTwo practical points come out of the doping-control work. Product labels are unreliable: one supplement bought for that study was labeled at 50 mg/mL of flmodafinil and assayed at 95.7 mg/mL, close to double the stated content (PMID: 42210629). And anyone tested in sport should know that fladrafinil and flmodafinil were added to the 2026 World Anti-Doping Agency Prohibited List under class S6 stimulants and are prohibited in competition, with detection windows of up to a week for the parent compounds and about two weeks for the metabolites (PMID: 42210629). A retrospective screen of about 2000 in-competition samples collected in 2023 and 2024 found none of these compounds, so current use among tested athletes appears low.\n\nThere is no FDA or EMA authorization for fladrafinil, no published safety trial, and no pregnancy, cardiac or hepatic data. It is a research-use-only compound in the US market, and the gap between what is claimed for it online and what has actually been measured is wide.", "half_life": "Not established in humans; after a single 20 mg oral dose in six volunteers, urinary fladrafinil peaked at 2 to 4 h and stayed detectable for up to 12 h, while the metabolite flmodafinil was detectable for about 8 days and the acid and sulfone metabolites for about two weeks (PMID: 42210629)", "molecular_weight": "325.3 g/mol", "molecular_mass": "325.3 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Not approved as a medicine anywhere; fladrafinil has no FDA or EMA marketing authorization and reaches consumers only as a research chemical or as an ingredient in unapproved supplements (PMID: 42210629). The World Anti-Doping Agency added fladrafinil and flmodafinil to the 2026 Prohibited List under class S6 stimulants, prohibited in competition (PMID: 42210629). It is a research-use-only compound in the US market.", "trial_phase": "", "cas_number": "90212-80-9", "iupac_name": "", "chemical_formula": "C15H13F2NO3S", "potential_benefits": [ "Longer wake duration in male C57BL/6J mice than modafinil, with no rebound hypersomnia, for lauflumide (NLS-4), which is flmodafinil, the active metabolite of fladrafinil (PMID: 30158846)", "Less non-REM sleep and less delta activity during recovery sleep in mice than after modafinil, suggesting a lower recovery need despite longer induced wakefulness (PMID: 30158846)", "Confirmed conversion to flmodafinil in six healthy human volunteers after a single 20 mg oral dose, establishing that the prodrug step works in people (PMID: 42210629)", "For the class parent modafinil, dopamine transporter occupancy and increased brain dopamine in 10 healthy men, the presumed basis of the class effect (PMID: 19293415)" ], "research_fields": [ "Wakefulness-promoting agents", "Anti-doping analysis", "Drug metabolism", "Cognitive enhancement" ], "pubmed_count": 0, "pubchem_cid": 13316557, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/fladrafinil" }, { "id": "4e0dbde6-a95c-4647-9ea1-022bfbbefc8d", "slug": "folate", "name": "Folate", "aliases": [ "Vitamin B9", "B9", "Folic acid", "Pteroylmonoglutamic acid", "PGA", "Folacin", "L-5-methyltetrahydrofolate", "L-methylfolate", "5-MTHF", "Methylfolate", "L-5-MTHF", "Metafolin", "Quatrefolic", "Levomefolate calcium", "Folinic acid", "Leucovorin", "Calcium folinate", "5-formyltetrahydrofolate", "Natural folate", "Dietary folate equivalent", "DFE" ], "category": "Vitamin", "description": "Folate is the generic term for a family of water-soluble B-vitamin compounds that share a pteridine-para-aminobenzoic-acid-glutamate backbone and serve as single-carbon transfer cofactors in nucleotide synthesis, amino acid metabolism, and methylation. The adult RDA is 400 mcg DFE (dietary folate equivalents), pregnancy 600 mcg DFE, lactation 500 mcg DFE, and the tolerable upper limit for synthetic folic acid (not from food) is 1,000 mcg/day. Folate deficiency is one of the most consequential preventable nutritional causes of neural tube defects (NTDs) — the anencephaly and spina bifida seen in infants of folate-deficient mothers — and the 1991 MRC Vitamin Study Research Group trial established that periconceptional folic acid (4 mg/day for high-risk women, 400 mcg/day for general-risk women) prevents 70% of NTD recurrences and most first-occurrence cases (PMID 1677062, 1944680). This finding drove mandatory folic acid fortification of grain products in the United States (1998), Canada, and many other countries, producing dramatic reductions in NTD rates across the fortified populations. Folate also corrects megaloblastic anemia — the macrocytic, hypersegmented-neutrophil hematologic picture that mirrors Vitamin B12 deficiency because the two vitamins share the final methyl-transfer step that regenerates tetrahydrofolate from 5-methyltetrahydrofolate. This biochemical interlock is why administering folate alone to a B12-deficient patient can correct the anemia (by providing methylated folate substrate downstream of the blocked methionine synthase step) while failing to correct the neurologic damage, and the concern that unrestricted folic acid fortification might \"mask\" B12 deficiency was a major public health debate during the fortification era — later data suggest the clinical impact has been modest but not zero, and the recommendation to check B12 in macrocytic anemia remains standard. Folate exists in multiple biologically interconvertible forms: natural food folate (predominantly 5-methyltetrahydrofolate, plus smaller fractions of formyl- and methylene-THF forms, with multiple glutamate residues attached), synthetic folic acid (pteroylmonoglutamic acid, the oxidized form used in fortification and most supplements), folinic acid (5-formyltetrahydrofolate, a reduced \"bypass\" form used in chemotherapy rescue), and L-5-methyltetrahydrofolate (the active coenzyme form, sold as Metafolin or Quatrefolic in supplements). The MTHFR (methylenetetrahydrofolate reductase) gene polymorphism debate — particularly the C677T variant, which reduces enzyme activity to ~30% of wild-type in homozygotes — has driven substantial consumer demand for methylfolate supplements on the theory that MTHFR-deficient individuals cannot effectively convert folic acid to the active 5-MTHF form and therefore need the pre-methylated coenzyme. This theory has a kernel of biochemical truth but has been substantially oversold in the consumer supplement marketplace; rigorous outcome trials do not show that MTHFR C677T homozygotes routinely develop clinically meaningful folate deficiency on standard folic acid supplementation, and the practical consumer message is reasonable but nuanced rather than categorical. The dominant clinical uses of folate supplementation are neural tube defect prevention (periconceptional and first trimester), megaloblastic anemia (with concurrent B12 assessment), homocysteine lowering in hyperhomocysteinemia, methotrexate rescue (folinic acid specifically), alcoholism-related folate deficiency, malabsorption syndromes (celiac, Crohn's, bariatric), and specific pediatric indications (sickle cell, hemolytic anemias). Food sources concentrate in leafy greens (spinach, kale, collards), legumes (lentils, beans, chickpeas), asparagus, broccoli, citrus, avocado, liver, and fortified grains. See also [Vitamin B12](/compound/vitamin-b12) for the obligate methylation partner, [Glycine](/compound/glycine) for the one-carbon metabolism sink, [Iron](/compound/iron) for the anemia differential triad, [Vitamin B6](/compound/vitamin-b6) when we add it for the homocysteine metabolism pair, and [Alpha-Lipoic Acid](/compound/alpha-lipoic-acid) for the broader redox-methylation framework. This overview is educational only and is not medical advice.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/folate" }, { "id": "e8a7830e-af31-4318-9089-8c11e0652584", "slug": "follistatin-344", "name": "Follistatin-344", "aliases": [ "FS-344", "FST-344", "Follistatin" ], "category": "Myostatin Inhibitor", "description": "Follistatin-344 is a 344-amino-acid glycoprotein that binds and neutralizes myostatin (GDF-8) - the primary negative regulator of skeletal muscle growth. Originally isolated from porcine ovarian fluid in the 1980s, the synthetic peptide form has become a research compound for studying myostatin antagonism and skeletal muscle hypertrophy.\n\nNaturally occurring follistatin variants (288, 315, 344) differ in tissue distribution and serum half-life. The 344 variant is the most-studied for muscle research. Knockout mouse models lacking myostatin (or with high follistatin expression) show 2-3x normal muscle mass.", "half_life": "Short; native follistatin protein is cleared rapidly (minutes to a few hours in vivo). No formal pharmacokinetic data exist for injected Follistatin-344 (FST-344).", "molecular_weight": "~38 kDa (glycoprotein; corresponds to the mature FST-315 chain, ~315 amino acids). Follistatin-344 is a protein, not a small synthetic peptide.", "molecular_mass": "~38 kDa glycosylated (mature FST-315 glycoprotein); ~35 kDa for the unglycosylated ~315-residue core. A large glycoprotein, not a small peptide.", "amino_acid_sequence": "Follistatin-344 is a 344-residue precursor protein (29-residue signal peptide + 315-residue mature chain; isoform FST-315, human UniProt P19883), not a short synthetic peptide. The mature glycoprotein comprises an N-terminal domain plus three follistatin domains and is N-glycosylated, so a simple linear peptide sequence is not the relevant descriptor.", "administration_routes": [ "Subcutaneous", "Intramuscular" ], "dose_range_mcg": "50-100 mcg", "dosing_frequency": "Once daily", "cycle_length": "4-6 weeks per cycle, 4-week washout", "common_vial_sizes": [ "1mg", "2mg", "5mg" ], "research_stage": "Preclinical / Research peptide", "approval_status": "Not FDA-approved. Some clinical work in muscular dystrophy via gene therapy approaches.", "trial_phase": "Preclinical / Research peptide", "cas_number": "", "iupac_name": "", "chemical_formula": "Glycoprotein (~37 kDa)", "potential_benefits": [ "Myostatin antagonism for skeletal muscle growth", "Satellite cell proliferation enhancement", "Activin-A binding (broader TGF-beta family inhibition)", "Research into muscular dystrophy and sarcopenia" ], "research_fields": [ "Muscle hypertrophy", "Myostatin biology", "Sarcopenia", "Muscular dystrophy", "TGF-beta family" ], "pubmed_count": 445, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/follistatin-344" }, { "id": "b8890de5-ef3a-48b3-a729-b7233adad4c3", "slug": "foxo4-dri", "name": "FOXO4-DRI", "aliases": [ "FOXO4" ], "category": "Recovery", "description": "FOXO4-DRI is a synthetic 34-amino-acid D-retro-inverso peptide designed to disrupt the interaction between the FOXO4 transcription factor and p53, with the specific goal of inducing apoptosis selectively in senescent cells. The compound was developed by the laboratory of Peter de Keizer at Erasmus Medical Center and reported in a landmark 2017 Cell paper that demonstrated FOXO4-DRI administration to aged mice produced measurable reductions in senescent cell burden, restored renal function, improved fur density and grooming behavior, and extended several markers of organismal health without apparent toxicity at effective doses ([Baar et al., 2017]). The publication was widely covered in mainstream science media and became one of the most cited demonstrations of targeted senolytic therapy as a plausible anti-aging strategy. The underlying biology is that cellular senescence — a state of permanent cell-cycle arrest induced by replicative exhaustion, DNA damage, oncogenic signaling, or mitochondrial dysfunction — accumulates with age in multiple tissues and contributes to tissue dysfunction through the senescence-associated secretory phenotype (SASP), a paracrine signature of pro-inflammatory cytokines, matrix-degrading proteases, and growth factors that damages neighboring cells and impairs tissue homeostasis. Selectively eliminating senescent cells while sparing non-senescent neighbors is the core concept of senolytic therapy, and multiple classes of molecules have been developed to pursue this goal: the dasatinib-quercetin combination, ABT-263 (navitoclax), fisetin, the p53 activator UBX0101 (now largely abandoned), and FOXO4-DRI represent distinct mechanistic strategies within the senolytic space ([Kirkland & Tchkonia, 2020]). FOXO4-DRI specifically targets a vulnerability identified in senescent cells: they depend on sequestration of p53 away from the mitochondrial outer membrane to avoid apoptosis, and this sequestration is maintained by a physical interaction between FOXO4 and p53 at specific nuclear sites. Disrupting the FOXO4-p53 interaction with FOXO4-DRI releases p53 to translocate to mitochondria, where it triggers the intrinsic apoptosis pathway in senescent cells that have accumulated pro-apoptotic signals but been held alive by the FOXO4-p53 sequestration. Non-senescent cells, which do not have the same accumulated pro-apoptotic signaling, are not killed by FOXO4-DRI administration ([Baar et al., 2017]; [Bourgeois & Madl, 2018]). The peptide is chemically distinctive because it is built as a D-retro-inverso (DRI) isomer, meaning it uses D-amino acids in reverse sequence compared to the parent L-peptide. This structural trick produces a molecule with roughly the same three-dimensional shape as the original but with complete protease resistance, because human proteases cannot recognize D-amino acid bonds. DRI peptides are used throughout the peptide-drug field when the natural L-peptide is too short-lived in vivo to be useful. The FOXO4-DRI sequence specifically is derived from the FOXO4 region that contacts p53, and the D-retro-inverso construction maintains the binding affinity while extending plasma and tissue half-life to useful ranges. The practical reality of FOXO4-DRI in April 2026 is that it remains an investigational research peptide with no approved human use, no clinical trials registered or published, and no pharmaceutical-grade manufacturing. Research-peptide vendors sell what they claim is FOXO4-DRI for \"research purposes only,\" and a biohacker community has accumulated several years of self-experimentation experience with the compound. This entry covers the mechanism in detail, the original Baar et al. 2017 study and what it actually showed, subsequent work that has attempted to reproduce and extend the findings, the theoretical and practical concerns with self-administration, why the compound has not progressed to human trials despite its prominence, and what realistic thinking about FOXO4-DRI looks like in the context of the broader senolytic field.", "half_life": "Not established in humans; no published human pharmacokinetic data. The D-retro-inverso construction confers resistance to human proteases, which in preclinical models extends the in vivo half-life from minutes (typical for comparable L-amino-acid peptides) to hours ([Baar et al., 2017](https://pubmed.ncbi.nlm.nih.gov/28340339/)).", "molecular_weight": "", "molecular_mass": "3587.0 g/mol", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "No validated human dose. Self-report: 2-15 mg SC per dose (typically 5 mg), pulsed 3-7 days every 2-6 months; no human PK data. The 5 mg/kg figure seen in some sources is a mouse research dose (Baar 2017), not a human dose.", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Not approved. Research use only; no human clinical trials and no regulatory approval in any jurisdiction.", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "D-Arg-D-Gln-D-Cys-D-Met-D-Met-D-Leu-D-Asn-Gly-D-Phe-D-Ile-D-Ser-D-Asn-D-Met-D-Arg-D-Arg-D-Ser-D-Gln-D-Ala-D-Leu-D-Val-D-Lys-D-Ser-D-Gln-D-Gln-D-Pro-D-Pro-D-Thr-D-Glu-D-Asp-Gly-D-Pro", "potential_benefits": [ "Selective senescent cell clearance", "Potential reversal of aging markers", "Reduced chronic inflammation", "Improved tissue function", "Hair regrowth (animal studies)", "Organ rejuvenation potential" ], "research_fields": [], "pubmed_count": 8, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/foxo4-dri" }, { "id": "ee08c754-769a-470b-9a44-c45d34e5067e", "slug": "gb-115", "name": "GB-115", "aliases": [ "GB115", "Rankvilon", "N-(6-phenylhexanoyl)glycyl-L-tryptophanamide", "N-(1-oxo-6-phenylhexyl)glycyl-L-tryptophanamide", "Ph(CH2)5CO-Gly-L-Trp-NH2", "CCK-4 retrodipeptide analog" ], "category": "Nootropics", "description": "GB-115 is a synthetic dipeptide, N-(6-phenylhexanoyl)glycyl-L-tryptophan amide, designed at the Zakusov Research Institute of Pharmacology in Moscow. It belongs to a Russian program that builds short peptides as topological analogs of the active fragment of a regulatory peptide, the same approach that produced noopept and dilept. GB-115 is a retro-analog of the beta turn of cholecystokinin tetrapeptide, and conformational work identified a beta II turn as the structure responsible for its activity (PMID: 17886432, PMID: 24397028, PMID: 30295186).\n\nThe stereochemistry matters. In the original series of analogs, the L-tryptophan compounds were anxiolytic and the D-tryptophan compounds anxiogenic, and GB-115 was selected as the L-tryptophan lead (PMID: 17886432). It acts as a low-affinity blocker of central cholecystokinin receptors. In mice and rats, activating cholecystokinin tetrapeptide type 2 receptors abolished its anti-anxiety effect and the compound prevented cholecystokinin-induced anxiety, while the alpha2 adrenoceptor antagonist yohimbine did not interact with it, which the authors read as a shared pharmacological target with cholecystokinin tetrapeptide (PMID: 23113301).\n\nThe animal file is broad. Oral administration produced anxiolytic effects in outbred mice, BALB/c mice and outbred rats in open field and elevated plus maze tests (PMID: 24130989), antidepressant-like reduction of immobility in the forced swim test that was weaker than amitriptyline (PMID: 21476266), reduced average daily ethanol consumption and the alcohol deprivation effect in high-emotionality MR rats (PMID: 27590755), and reduced anxiety during benzodiazepine withdrawal in outbred and inbred rats (PMID: 22238979). A repeated theme is that the effect depends on the animal phenotype: strains with a passive response to emotional stress respond differently from active ones (PMID: 12910281). A study in four male rhesus monkeys under individual caging reported reduced stress-related behavior and a lower cortisol to DHEA-S ratio, comparable to phenazepam (PMID: 39847298).\n\nSafety and dependence data in animals are more complete than for most compounds sold this way. A preclinical package found no deaths after single oral administration at up to 6000 mg/kg in mice and 3500 mg/kg in rats, no irreversible organ changes over six months of oral administration in rats and rabbits, and no allergenic, immunotoxic or mutagenic activity and no effect on reproduction or offspring development (PMID: 20726348). After 30 days of daily administration to rats, stopping the compound produced no anxiety, aggression or convulsive signs, in contrast to diazepam withdrawal in the same experiment (PMID: 21899090). Oral bioavailability in rats was low at 4.65 percent for the crystalline substance, which is why later work compared micronized and reformulated versions (PMID: 18457023, PMID: 27017703).\n\nHuman evidence is Russian and mostly unpublished in indexed journals. Thirty-one patients with generalized anxiety disorder were treated for 21 days, an effective daily dose was identified, and the authors described a fast anxiolytic effect with a stimulating component and favorable changes in attention parameters and reaction time (PMID: 31626171). That report does not describe randomization, blinding or a placebo arm in its published abstract. The Russian trial registry records that study as an open phase IIa pilot, followed by a double-blind, randomized, placebo-controlled multicenter trial sponsored by Valenta Pharm from April 2021 to December 2022, and the Russian product label cites two placebo-controlled trials of 168 and 220 patients, none of which is indexed in PubMed. On 29 December 2023 GB-115 was registered in Russia as the prescription tablet Rankvilon for anxiety states in neurasthenia and adjustment disorders. It has no FDA or EMA authorization, and the aerosol spray sold on the research chemical market is not the registered tablet and is a research-use-only compound in the US market.", "half_life": "Not established in humans; the published rat pharmacokinetic work reported an absolute oral bioavailability of 4.65 percent for the crystalline substance and did not report a terminal half-life (PMID: 18457023)", "molecular_weight": "434.5 g/mol", "molecular_mass": "434.5 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral", "Intraperitoneal injection (animal studies)", "Aerosol spray (form sold on the research chemical market)" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Approved (Russia)", "approval_status": "Approved in Russia: registered on 29 December 2023 as the prescription anxiolytic Rankvilon (Valenta Pharm, 1 mg tablets, marketing authorization LP-No.(004206)-(RG-RU)) for anxiety states in neurasthenia and adjustment disorders in adults. It has no FDA or EMA marketing authorization and no trial on ClinicalTrials.gov; the only clinical report indexed in PubMed is a Russian open dose-finding study in 31 patients with generalized anxiety disorder (PMID: 31626171). Material sold on the research chemical market is a research-use-only compound in the US market.", "trial_phase": "", "cas_number": "678996-63-9", "iupac_name": "", "chemical_formula": "C25H30N4O3", "potential_benefits": [ "Anxiolytic effect after oral administration in outbred mice, BALB/c mice and outbred rats in open field and elevated plus maze tests (PMID: 24130989)", "Antidepressant-like reduction of immobility time in the forced swim test in outbred, BALB/c and C57Bl/6 mice, weaker than amitriptyline (PMID: 21476266)", "Reduced average daily ethanol consumption and the alcohol deprivation effect in high-emotionality MR rats after 14 days of treatment (PMID: 27590755)", "Attenuated anxiety during benzodiazepine withdrawal in outbred and inbred rats, with partial normalization of striatal dopamine metabolites (PMID: 22238979)", "Reduced stress-related behavior and lowered the cortisol to DHEA-S ratio in four male rhesus monkeys under isolation, comparable to phenazepam (PMID: 39847298)", "Reported anxiolytic effect with improvements in attention parameters and reaction time in 31 patients with generalized anxiety disorder over 21 days (PMID: 31626171)" ], "research_fields": [ "Anxiolytics", "Cholecystokinin receptor pharmacology", "Dipeptide drug design", "Anxiety and depression models" ], "pubmed_count": 0, "pubchem_cid": 11281948, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/gb-115" }, { "id": "a1000000-0000-0000-0000-000000000010", "slug": "ghk-cu", "name": "GHK-Cu", "aliases": [ "Copper Peptide", "GHK Copper", "Copper tripeptide-1", "GHKCu" ], "category": "Skin, Hair & Aesthetics", "description": "GHK-Cu is the copper(II) complex of the tripeptide glycyl-L-histidyl-L-lysine, a molecule Pickart and Thaler first pulled out of human plasma in 1973. The free peptide (GHK, C14H24N6O4) weighs about 340.4 Da; bind it 1:1 to copper and you get the neutral GHK-Cu complex (C14H22CuN6O4) at roughly 401.9 Da. Circulating GHK sits around 200 ng/mL in young adults near age 20 and drops to about 80 ng/mL by age 60, which is where most of the 'it declines with age' framing comes from. On skin, GHK-Cu is a well-worn cosmetic ingredient (INCI: Copper tripeptide-1) with real human topical data behind it. Injected under the skin it is a different story: no human trials, no established dose, purely research-use-only biohacker practice. Everything about systemic use here is educational, not medical advice.", "half_life": "~30-60 min (plasma; approximate legacy figure, no robust modern human PK study)", "molecular_weight": "Free peptide (GHK): 340.38 Da (C14H24N6O4). Copper complex (GHK-Cu): 401.9 Da (C14H22CuN6O4, neutral 1:1 Cu(II) complex).", "molecular_mass": "401.91 g/mol", "amino_acid_sequence": "Gly-His-Lys (GHK); glycyl-L-histidyl-L-lysine. GHK-Cu is the 1:1 copper(II) chelate of this tripeptide (INCI: Copper tripeptide-1).", "administration_routes": [ "Subcutaneous", "Topical" ], "dose_range_mcg": "200-500 mcg SC daily (community/RUO; no clinically established injectable dose)", "dosing_frequency": "Once daily subcutaneous; some run 5 days on / 2 days off. Topical: 1-2x daily to cleansed skin.", "cycle_length": "Injectable (community practice): 4-8 week cycles followed by a 4-6 week off-period as a precaution against theoretical copper accumulation. Topical: continuous over 8-12+ weeks, no cycling needed.", "common_vial_sizes": [ "50 mg", "100 mg" ], "research_stage": "Approved/marketed as a topical cosmetic ingredient (Copper tripeptide-1) with supporting small human studies. Injectable use is preclinical/off-label, research-use-only, with no human clinical trials.", "approval_status": "Not an FDA-approved drug. Marketed and regulated as a topical cosmetic ingredient (INCI: Copper tripeptide-1). Injectable/systemic use is research-use-only, with no FDA approval and no human clinical trials.", "trial_phase": "N/A for injectable (no Phase 1/2/3 injectable trials). One Phase 2 TOPICAL gel wound-healing trial is recruiting (NCT07437586); topical cosmetic use otherwise has small human studies with no drug-phase designation.", "cas_number": "49557-75-7 (free GHK tripeptide; the marketed copper-acetate complex form carries CAS 89030-95-5)", "iupac_name": "glycyl-L-histidyl-L-lysine copper(II) complex", "chemical_formula": "C14H22CuN6O4", "potential_benefits": [ "Stimulates type I collagen synthesis in human fibroblasts at low nanomolar-to-picomolar concentrations (PMID: 3169264)", "Increases glycosaminoglycans (dermatan/chondroitin sulfate) and upregulates decorin in wound models (PMID: 11121126)", "Modulates matrix metalloproteinases and their inhibitors, partially correcting the MMP-9/TIMP-1 imbalance in a smoke-induced emphysema model (PMID: 35936787)", "Drives tissue remodeling and chemoattracts macrophages, mast cells, and capillary cells to injury sites (PMID: 18644225)", "Modulates expression of ~4,000+ human genes via the Broad Institute Connectivity Map, including DNA-repair and antioxidant genes (PMID: 25302294)", "Increases stemness and proliferative potential of epidermal basal cells and keratinocytes (PMID: 23019153)", "Acts as an antioxidant and anti-inflammatory copper regulator in the context of aging (PMID: 22666519)", "Broad skin-regeneration effects on collagen, proteoglycans, MMPs, and immune/endothelial cell recruitment (PMID: 26236730)" ], "research_fields": [ "Skin, Hair & Aesthetics", "Wound Healing & Tissue Repair", "Anti-Aging", "Antioxidant / Gene Expression" ], "pubmed_count": 6, "pubchem_cid": 165429100, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/165429100/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/ghk-cu" }, { "id": "f19758d2-6001-4115-abe3-19fa66d41277", "slug": "ghrp-2", "name": "GHRP-2", "aliases": [ "Pralmorelin" ], "category": "Growth Hormone / IGF-1 Axis", "description": "GHRP-2 (growth hormone-releasing peptide-2), also known as pralmorelin and KP-102, is a synthetic hexapeptide growth hormone secretagogue that was among the **first GHRPs developed in the seminal research of Cyril Bowers and colleagues** at Tulane University in the late 1980s and early 1990s. It binds the ghrelin receptor (GHS-R1a) on anterior pituitary somatotrophs and hypothalamic neurons, producing a strong, dose-dependent release of endogenous growth hormone through a pathway pharmacologically parallel to but distinct from the GHRH receptor axis.\n\nSequence: **D-Ala-D-β-Nal-Ala-Trp-D-Phe-Lys-NH2**. This six-residue backbone is optimized for potent GHS-R1a agonism, with serum half-life of approximately **15-30 minutes** in humans and a GH-releasing potency significantly higher than the endogenous ligand ghrelin.\n\nGHRP-2 occupies an important regulatory niche: it is **approved in Japan** as a diagnostic agent (GHRP-2 injection) for pediatric growth hormone deficiency testing under the brand Pralmorelin, where it replaced older insulin-tolerance stimulation protocols due to its superior safety and more reliable GH response ([Chihara et al., 2004]). It is not FDA-approved in the United States for any indication, and research-grade use for performance and body composition purposes is therefore off-label.\n\nCompared to [ipamorelin](/compound/ipamorelin), GHRP-2 produces a **larger absolute GH pulse** but with **meaningful cross-reactivity** at pathways that ipamorelin avoids — specifically, GHRP-2 elevates **prolactin and cortisol** by a modest but measurable margin. This tradeoff — more GH, but less clean — is why modern peptide protocols increasingly favor ipamorelin for long-term tuning and reserve GHRP-2 for specific situations where maximum GH pulse amplitude is the primary goal.\n\nStandard research doses range from **100-300 mcg subcutaneously, 2-3 times daily**, typically dosed before breakfast, before training, and at bedtime. The hexapeptide shows strong synergy with GHRH analogs — when paired with sermorelin or CJC-1295 (no-DAC), the combined GH pulse amplitude reaches **3-5x either compound alone** ([Bowers et al., 1991]).", "half_life": "~15-30 minutes", "molecular_weight": "817.9 Da", "molecular_mass": "817.99 g/mol", "amino_acid_sequence": "D-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH2", "administration_routes": [ "Subcutaneous", "Intramuscular", "Intranasal" ], "dose_range_mcg": "100–300 mcg per injection", "dosing_frequency": "1–3 times daily; bedtime injection most important", "cycle_length": "8–12 weeks with 4-week breaks", "common_vial_sizes": [ "5mg", "10mg" ], "research_stage": "Phase II", "approval_status": "", "trial_phase": "Phase 2", "cas_number": "158861-67-7", "iupac_name": "H-Ala-D-βNal-Ala-Trp-D-Phe-Lys-NH2", "chemical_formula": "C45H55N9O6", "potential_benefits": [ "High GH output", "Muscle building", "Fat loss", "Recovery", "Appetite stimulation", "Anti-aging" ], "research_fields": [ "GH deficiency", "Short stature", "Cachexia", "Body composition" ], "pubmed_count": 212, "pubchem_cid": 6918296, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/6918296/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/ghrp-2" }, { "id": "cdf11c17-2425-49f3-bd0f-dc56b4b4d0cb", "slug": "ghrp-6", "name": "GHRP-6", "aliases": [ "Growth Hormone RP 6" ], "category": "Growth Hormone / IGF-1 Axis", "description": "GHRP-6 (growth hormone-releasing peptide-6) is a synthetic hexapeptide with the sequence **His-D-Trp-Ala-Trp-D-Phe-Lys-NH2** that binds the ghrelin receptor (GHS-R1a) to stimulate endogenous growth hormone release. It was among the **earliest GHRPs characterized** in the foundational work of Cyril Bowers and colleagues, emerging from systematic structure-activity studies of the metenkephalin-derived peptide GHRP-0 in the mid-1980s ([Bowers et al., 1984]).\n\nGHRP-6 occupies a specific pharmacologic niche distinct from its close analog GHRP-2: it has **markedly stronger appetite-stimulating effects** for a given GH response. Where GHRP-2 produces moderate hunger signals as a side effect of GHS-R1a activation, GHRP-6 produces some of the most pronounced appetite stimulation of any peptide in clinical use. This makes it uniquely valuable in specific clinical contexts — **cachexia, anorexia, recovery from severe illness, bulking phases** — while making it inappropriate for users trying to maintain a caloric deficit.\n\nThe molecule's GH potency is slightly lower than GHRP-2 on a per-dose basis but still substantial, with peak GH release typically 3-5 times pre-injection baseline following 100-300 mcg subcutaneous doses. Like all GHS-R1a agonists, it synergizes strongly with GHRH analogs like sermorelin and CJC-1295, producing combined GH pulses that exceed either compound alone by 3-5x ([Bowers et al., 1991]).\n\nGHRP-6 is not FDA-approved for any indication. It has historical use in clinical research for GH stimulation testing and cachexia intervention trials, and current use is largely confined to the research-peptide and off-label peptide therapy space. Serum half-life is approximately **15-30 minutes** in humans, dictating a multi-dose daily regimen (typically 2-3 injections) for sustained GH-axis effect. Cortisol and prolactin cross-reactivity are similar to GHRP-2: modest elevations in the 60-90 minute post-injection window that are typically clinically trivial but relevant in chronic use.\n\nThe practical distinction from other GHS compounds comes down to appetite: if appetite stimulation is desired, GHRP-6 is often the preferred choice. If appetite suppression or neutrality is wanted, [ipamorelin](/compound/ipamorelin) or [GHRP-2](/compound/ghrp-2) are better fits.", "half_life": "~20–30 minutes", "molecular_weight": "873 Da", "molecular_mass": "873.02 g/mol", "amino_acid_sequence": "His-D-Trp-Ala-Trp-D-Phe-Lys-NH2", "administration_routes": [ "Subcutaneous", "Intramuscular" ], "dose_range_mcg": "100–300 mcg per injection", "dosing_frequency": "1–3 times daily", "cycle_length": "8–12 weeks", "common_vial_sizes": [ "5mg", "10mg" ], "research_stage": "Phase II", "approval_status": "", "trial_phase": "Phase 2", "cas_number": "87616-84-0", "iupac_name": "H-His-D-Trp-Ala-Trp-D-Phe-Lys-NH2", "chemical_formula": "C46H56N12O6", "potential_benefits": [ "GH stimulation", "Appetite increase", "Muscle mass", "Cardiac protection", "Recovery", "Body composition" ], "research_fields": [ "GH deficiency", "Cardiac ischemia", "Burn treatment", "Cachexia" ], "pubmed_count": 156, "pubchem_cid": 5311037, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/5311037/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/ghrp-6" }, { "id": "9c4fb29f-1885-4ee2-abab-79e9b8325cce", "slug": "glow-blend", "name": "Glow Blend", "aliases": [ "Glow", "GHK-Cu/BPC/TB" ], "category": "Recovery", "description": "GHK-Cu + BPC-157 + TB-500 blend for skin and recovery", "half_life": "Varies by component - the blend has no single half-life. BPC-157 and the TB-500 (thymosin beta-4) fragment are small peptides cleared over hours; GHK-Cu is a short-lived tripeptide-copper complex. Community dosing frequency is driven by empirical practice, not by measured pharmacokinetics of the blend.", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "Blend - stated per component: GHK-Cu 1000-2000 mcg/day; BPC-157 250-500 mcg/dose; TB-500 2000-2500 mcg/dose. No validated dose exists for the combination (Research Use Only).", "dosing_frequency": "GHK-Cu once daily; BPC-157 once to twice daily; TB-500 twice weekly during the loading phase, then every 1-2 weeks for maintenance.", "cycle_length": "Community cycles typically run 4-8 weeks followed by an off period of several weeks. No evidence supports continuous use.", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Research Use Only", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "Blend", "potential_benefits": [ "Improved skin firmness and elasticity - GHK-Cu raised collagen and elastin and improved aged-skin firmness in controlled cosmetic studies [PMID:18644225]", "Reduced appearance of fine lines and photodamage (GHK-Cu cosmetic data) [PMID:18644225]", "Support for wound and connective-tissue repair - GHK-Cu and BPC-157 accelerated healing in animal models [PMID:8836453][PMID:30915550]", "Angiogenesis / improved local blood-vessel formation - a shared mechanism of BPC-157 and the thymosin beta-4 fragment in TB-500 [PMID:20388964][PMID:14500546]", "Faster recovery from tendon, ligament and muscle strain (BPC-157 preclinical data) [PMID:30915550]", "Anti-inflammatory and antioxidant support during recovery (GHK-Cu and thymosin beta-4) [PMID:18644225][PMID:27450738]", "Reported skin 'glow' and quicker soft-tissue recovery - community/anecdotal only, not clinically verified for the blend" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/glow-blend" }, { "id": "d20fab00-52b1-4c49-8b33-c7941455b4dd", "slug": "glutathione", "name": "Glutathione", "aliases": [ "GSH" ], "category": "Recovery", "description": "Glutathione is the body's most abundant intracellular antioxidant — a three-amino-acid peptide made of glutamate, cysteine, and glycine (Glu-Cys-Gly), present in millimolar concentrations inside every cell of your body. It is not a research peptide in the same sense as [BPC-157](/compound/bpc-157) or [Semax](/compound/semax); it is a fundamental metabolic molecule that your liver synthesizes constantly from its amino acid components. The interest in supplemental glutathione stems from the observation that tissue GSH levels decline with age, with chronic disease, with oxidative stress, and with certain medications — and that restoring GSH levels may improve outcomes in conditions ranging from fatty liver disease to Parkinson's disease to chemotherapy-induced toxicity.\n\nChemically, glutathione exists in two interconvertible forms: the reduced form (GSH), which is the antioxidant-active form with a free thiol (-SH) group, and the oxidized form (GSSG), in which two GSH molecules are linked by a disulfide bond. The ratio of GSH to GSSG in a cell is one of the most reliable biochemical markers of oxidative stress — a healthy cell maintains a GSH:GSSG ratio of roughly 100:1, while cells under oxidative stress see this ratio collapse. The dynamic regeneration of GSH from GSSG by the enzyme glutathione reductase (using NADPH as the reducing equivalent) is one of the core redox cycles of cellular metabolism ([Lu, 2013](https://pubmed.ncbi.nlm.nih.gov/23201762/)).\n\nGlutathione has a broad range of biological functions that go beyond simple antioxidant activity. It directly scavenges reactive oxygen species. It is a cofactor for glutathione peroxidases, the enzymes that detoxify hydrogen peroxide and lipid peroxides. It is the substrate for glutathione-S-transferases, which conjugate toxins and xenobiotics to glutathione for elimination — this is the core of Phase II liver detoxification for everything from acetaminophen to heavy metals to alcohol metabolism byproducts. It regulates cell signaling through protein glutathionylation. It supports mitochondrial function, particularly in complex I and complex III of the electron transport chain. It is essential for lymphocyte function and immune system activity. It is the key reducing agent for vitamin C recycling and for the proper function of vitamin E ([Forman et al., 2009](https://pubmed.ncbi.nlm.nih.gov/18796312/)).\n\nThe practical problem with supplementing glutathione is bioavailability. Oral glutathione is largely broken down by gastrointestinal peptidases before it can be absorbed intact, and even the fraction that enters systemic circulation has difficulty crossing cell membranes to reach intracellular compartments where it is needed. This is the central question that has driven the development of alternative formulations: intravenous glutathione (bypasses GI degradation but still has cellular uptake limits), liposomal glutathione (protects the molecule in the gut and may improve uptake), intranasal glutathione (bypasses first-pass metabolism, delivers directly to brain via olfactory/trigeminal routes), nebulized glutathione (delivers to lung tissue), and glutathione precursors like N-acetylcysteine (NAC), which provides the rate-limiting cysteine for endogenous synthesis ([Sechi et al., 1996](https://pubmed.ncbi.nlm.nih.gov/8938817/), [Schmitt et al., 2015]).\n\nClinical evidence for glutathione supplementation is strongest in a few specific contexts. **Acetaminophen overdose** is the textbook case — N-acetylcysteine administration to replenish hepatic GSH is standard of care and saves lives, with an evidence base spanning decades. **Nonalcoholic fatty liver disease (NAFLD)** has seen multiple small trials of oral and IV glutathione showing improvements in ALT, oxidative stress markers, and liver histology. **Parkinson's disease** has a growing body of research on intranasal and IV glutathione, based on observations that Parkinson's patients have reduced GSH in the substantia nigra and that GSH supplementation may have neuroprotective and symptomatic effects. **Cystic fibrosis** has trials of inhaled glutathione for lung function improvement. **Chemotherapy-induced neuropathy and ototoxicity** has trials suggesting IV glutathione may reduce certain chemotherapy side effects ([Testa et al., 2016], [Honda et al., 2017]).\n\nThe research peptide and longevity community uses glutathione much more broadly than these evidence-supported indications. Common use patterns include: general anti-aging and longevity support, skin brightening and melanin reduction (popular in Asian markets), hangover prevention and recovery, support during heavy training or physical stress, liver support during alcohol use or medication courses, \"detox\" protocols (a vague concept but biochemically coherent for glutathione's role in Phase II conjugation), and as a supportive agent in fatigue syndromes, chronic Lyme disease, and environmental illness. Evidence for these uses ranges from suggestive to entirely anecdotal.\n\nThe mythology around IV glutathione \"detox\" has outpaced the evidence. True detoxification — removal of specific toxins through Phase II conjugation — is a well-characterized biochemical process that glutathione is central to. But the popular concept of \"flushing toxins\" through IV glutathione drips is largely marketing built on the real biochemistry. Similarly, the skin-brightening use of IV glutathione is documented and real — glutathione inhibits tyrosinase and shifts melanin synthesis from eumelanin (dark) toward pheomelanin (light) — but it comes with safety concerns the marketing rarely mentions, especially in the high-dose IV protocols marketed in beauty clinics, which the FDA has specifically warned against.\n\nGlutathione is not FDA-approved as a drug in the United States except in specific formulations (e.g., for prevention of platinum chemotherapy neuropathy in some jurisdictions; nebulized forms for cystic fibrosis trials). It is available as an over-the-counter supplement in oral, liposomal, and sublingual forms. IV and nebulized formulations are typically prepared by compounding pharmacies and administered in clinical settings. Intranasal formulations are increasingly available as compounded prescriptions or from reputable peptide suppliers.\n\nIf you are considering glutathione supplementation, the honest framing is this: glutathione is a real biochemical entity with real physiological roles, and there are specific contexts (acetaminophen overdose, NAFLD, early Parkinson's, cystic fibrosis) where supplementation has coherent evidence of benefit. Beyond those contexts, use is largely empirical — driven by mechanism and by subjective reports of benefit rather than by strong trials. It is generally safe at typical supplement doses, it stacks cleanly with most other health practices, and at worst it is an expensive placebo. At best, in appropriate contexts, it is one of the more scientifically grounded interventions in the longevity and biohacking space.", "half_life": "Short: on the order of minutes for intravenous glutathione (intact GSH is cleared rapidly from plasma and cellular uptake of intact GSH is limited). Oral bioavailability is low, so tissue glutathione levels depend mainly on endogenous synthesis from cysteine, glycine, and glutamate rather than on the half-life of administered GSH.", "molecular_weight": "307.32 g/mol (C10H17N3O6S)", "molecular_mass": "307.32 g/mol", "amino_acid_sequence": "gamma-L-Glutamyl-L-cysteinylglycine (Glu-Cys-Gly). The glutamate residue is joined to cysteine through its gamma-carboxyl group rather than a standard alpha-peptide bond, which is why glutathione is a gamma-glutamyl tripeptide rather than an ordinary peptide.", "administration_routes": [], "dose_range_mcg": "250 mg - 1000 mg daily (oral, IV, or nebulized)", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Clinical", "approval_status": "", "trial_phase": "", "cas_number": "70-18-8", "iupac_name": "(2S)-2-amino-4-{[(1R)-1-[(carboxymethyl)carbamoyl]-2-sulfanylethyl]carbamoyl}butanoic acid", "chemical_formula": "C10H17N3O6S", "potential_benefits": [ "Powerful antioxidant protection", "Liver detoxification support", "Immune system enhancement", "Skin brightening and anti-aging", "Heavy metal chelation support", "Reduced oxidative stress" ], "research_fields": [], "pubmed_count": 1971, "pubchem_cid": 124886, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/glutathione" }, { "id": "781d7f87-7498-49eb-81d8-83b05c0a4e22", "slug": "glycine", "name": "Glycine", "aliases": [ "Aminoacetic acid", "Glycocoll", "G", "Gly", "L-Glycine", "Glycin", "Aminoessigsäure" ], "category": "Foundational", "description": "Glycine is the simplest amino acid—a single hydrogen atom replacing the typical side chain found in other proteinogenic amino acids—yet it performs an wide range of biological functions. Despite being classified as \"non-essential\" because humans can synthesize it endogenously from serine and other precursors, mounting evidence suggests glycine is conditionally essential: the synthetic capacity of human tissues falls short of daily functional demands, particularly during periods of stress, injury, aging, and rapid growth. This gap between synthesis and requirement makes dietary glycine practically important, and supplemental glycine emerges as one of the most evidence-based, low-cost, and versatile compounds in the foundational nutrition category.\n\nGlycine's biological roles span multiple major categories. It is the most abundant amino acid in collagen, comprising approximately one-third of collagen's amino acid residues (every third residue in the collagen triple helix must be glycine because the small side chain is the only one that fits at the helix interior). It serves as the primary inhibitory neurotransmitter in the spinal cord and brainstem (via glycine receptors), while also acting as an obligatory co-agonist for NMDA glutamate receptors throughout the brain. It is required for synthesis of glutathione (the body's master antioxidant), creatine (for energy metabolism), heme (for oxygen transport), bile acids (for fat digestion), and nucleotide bases (for DNA). It regulates one-carbon metabolism through the glycine cleavage system. It modulates immune function through glycine-gated chloride channels on macrophages and neutrophils. It stabilizes cell membranes, supports detoxification of many xenobiotics, and participates in the transamination reactions central to nitrogen metabolism.\n\nGiven this biological breadth, it is perhaps not surprising that glycine supplementation has shown benefits across diverse clinical contexts: improved sleep quality (particularly subjective measures and early-night sleep), enhanced glutathione status in aging adults (the basis of the GlyNAC protocol), reduced symptoms in schizophrenia when combined with standard antipsychotics, improved glycemic control in type 2 diabetes, better outcomes after surgery and trauma, improved outcomes in chronic kidney disease, and potentially benefits for skin and joint health via collagen support.\n\nDietary glycine comes primarily from collagen-containing foods—bone broth, slow-cooked meats with connective tissue, skin-on poultry and fish, gelatin desserts, and collagen supplements. Modern dietary patterns, which favor boneless skinless muscle meats over whole-animal consumption with connective tissue, deliver much less glycine than ancestral diets or traditional cuisines. A typical adult on a modern American diet consumes approximately 1.5-3 g glycine daily; Meléndez-Hevia and colleaguescalculated that the body's daily glycine requirement for collagen synthesis alone exceeds 10 g, and total requirement across all functions likely exceeds 15 g daily. This substantial gap is typically filled by endogenous synthesis, but synthetic capacity appears limited, particularly with aging and disease states. Supplementation of 3-10 g daily closes this gap conveniently and inexpensively.\n\nFor users of BodyHackGuide, glycine represents one of the most underrated foundational supplements. The cost is trivial (pure glycine powder is among the cheapest supplements per gram), the taste is pleasantly sweet (making it easy to consume), the safety profile is excellent (human supplementation doses of 30+ g daily have been tested without significant adverse effects), and the evidence base spans sleep, glutathione/aging biomarkers, glycemic control, and connective tissue support. Common supplementation errors include: (1) assuming glycine effects will be rapid and dramatic—most benefits emerge over weeks of consistent use, (2) mixing up glycine with glucine or other unrelated compounds, (3) using inadequate doses (under 3 g daily often shows minimal effect on sleep), and (4) neglecting dietary sources of glycine in favor of supplementation when both are straightforward. This monograph addresses each of these issues with the specificity needed for informed self-experimentation. For related foundational support, see /compound/creatine, /compound/taurine, /compound/magnesium, and /compound/nac.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/glycine" }, { "id": "a25c3ba8-32c1-4958-9ce9-5fea76182061", "slug": "gonadorelin", "name": "Gonadorelin", "aliases": [], "category": "Hormones & Endocrine (Non-GH)", "description": "Gonadorelin is the synthetic, pharmaceutically manufactured version of endogenous gonadotropin-releasing hormone (GnRH) — a ten-amino-acid decapeptide (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) first isolated, sequenced, and synthesized by Andrew V. Schally's laboratory in the late 1960s and early 1970s, work that earned Schally a share of the 1977 Nobel Prize in Physiology or Medicine alongside Roger Guillemin ([Schally et al., 1971]). Gonadorelin represents the master upstream regulator of the entire hypothalamic-pituitary-gonadal axis — when released from GnRH neurons in the hypothalamus in discrete pulses every 60 to 120 minutes, it travels through the hypothalamo-hypophyseal portal vasculature to the anterior pituitary, where it binds GnRH receptors (GNRHR) on gonadotroph cells and triggers synthesis and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Those two gonadotropins in turn act on testes in men (stimulating testosterone production by Leydig cells and spermatogenesis by Sertoli cells) or ovaries in women (driving follicular development, ovulation, and corpus luteum formation).\n\nIn the peptide compounding and performance-enhancement community, gonadorelin has emerged over the past five years as a preferred alternative to human chorionic gonadotropin (hCG) during testosterone replacement therapy (TRT) for maintaining testicular size, intratesticular testosterone, and fertility — though the clinical evidence base for this specific application is markedly weaker than the evidence for hCG. This compound is biologically identical to native human GnRH; it is not a synthetic analog with altered amino acids — it is the real decapeptide, which means it carries the same pharmacokinetic limitations as the native hormone: a plasma half-life measured in minutes (2-10 min depending on the assay), rapid degradation by prolyl endopeptidase and post-proline cleaving enzymes, and a requirement for pulsatile rather than continuous administration to avoid pituitary desensitization — a paradox that defines both its therapeutic utility and its practical limitations.\n\nHistorically, gonadorelin was FDA-approved under the brand name Factrel for diagnostic use (the GnRH stimulation test to differentiate hypothalamic from pituitary causes of gonadotropin deficiency) and Lutrepulse for therapeutic pulsatile delivery via mini-pump in hypogonadotropic hypogonadism. Both products were withdrawn from the US market in the mid-2000s for commercial rather than safety reasons, leaving compounding pharmacies as the primary source for contemporary clinical and off-label use. Gonadorelin is structurally distinct from the GnRH agonists (leuprolide, goserelin, triptorelin) and antagonists (cetrorelix, ganirelix, elagolix) used for prostate cancer, endometriosis, fibroids, and IVF — those are modified analogs designed for extended half-life and sustained receptor occupancy. Gonadorelin is the native pulsatile molecule. Cross-references include [HCG](/compound/hcg) (direct LH-receptor agonist, bypassing pituitary), [Kisspeptin-10](/compound/kisspeptin-10) (further upstream, stimulating GnRH neurons themselves), and [Enclomiphene](/compound/enclomiphene) (SERM that enhances endogenous GnRH drive by blocking estrogen-mediated negative feedback).", "half_life": "~2-10 minutes (plasma; rapid enzymatic degradation by peptidases)", "molecular_weight": "", "molecular_mass": "1182.32 g/mol", "amino_acid_sequence": "pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 (single-letter: pEHWSYGLRPG-NH2, where pE = pyroglutamate). Native gonadotropin-releasing hormone (GnRH) decapeptide with an N-terminal pyroglutamate and a C-terminal glycinamide. Molecular formula C55H75N17O13.", "administration_routes": [], "dose_range_mcg": "100-300", "dosing_frequency": "2-3x weekly SC (TRT adjunct); pulsatile pump every 60-120 min (specialist)", "cycle_length": "Ongoing during TRT; ~4-12 weeks when used for PCT", "common_vial_sizes": [], "research_stage": "Clinically Established", "approval_status": "Previously FDA-approved in the US - Factrel (gonadorelin HCl) for GnRH stimulation testing and Lutrepulse (gonadorelin acetate) for primary hypothalamic amenorrhea - both now discontinued. No FDA-approved gonadorelin product is currently marketed in the US; it is available only through compounding pharmacies and is used off-label as a TRT/PCT adjunct (research/community use).", "trial_phase": "FDA Approved", "cas_number": "33515-09-2", "iupac_name": "Pyroglutamyl-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2", "chemical_formula": "C55H75N17O13", "potential_benefits": [ "HPG axis maintenance", "LH/FSH stimulation", "Testicular function during TRT", "Fertility preservation", "PCT support" ], "research_fields": [ "Male hypogonadism", "Fertility", "Hypothalamic amenorrhea", "PCT", "TRT adjunct" ], "pubmed_count": 473, "pubchem_cid": 638793, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/638793/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/gonadorelin" }, { "id": "85d03df8-1bb4-4c16-8a77-2bb1e43132f6", "slug": "gotu-kola", "name": "Gotu Kola", "aliases": [ "Centella asiatica", "Mandukaparni", "Indian Pennywort", "Asiatic Pennywort", "Pegaga", "Brahmi (Centella)", "Tiger Grass", "Mandookaparni", "Cica" ], "category": "herb", "description": "Gotu Kola (Centella asiatica) is one of the oldest and most extensively studied rasayana herbs in Ayurveda — a classical medhya (mind-nourishing) plant that has been used for more than 3,000 years across India, Sri Lanka, China, Indonesia, Thailand, Malaysia, and Madagascar for three main purposes: sharpening cognition and memory, healing wounds and damaged connective tissue, and restoring venous and microvascular circulation. Although Western consumers often encounter it as an afterthought in \"brain supplement\" stacks, Gotu Kola is one of the most scientifically validated medicinal plants on earth, with over a thousand peer-reviewed studies spanning wound healing, chronic venous insufficiency, anxiety, cognitive decline, scleroderma, keloid scarring, diabetic microangiopathy, and the skin-barrier remodeling that has made \"cica\" creams a billion-dollar category in Korean skincare. Pharmacologically, its activity traces to a family of pentacyclic triterpene saponins collectively called centelloids — asiaticoside, madecassoside, asiatic acid, and madecassic acid — along with smaller contributions from polyphenols, flavonoids, and essential oil constituents. These compounds are unusual because they act on fibroblasts, endothelial cells, and neurons simultaneously, modulating collagen synthesis (types I and III), microvascular permeability, GABAergic tone, BDNF expression, and oxidative stress pathways. The clinical result is a botanical that does not fit neatly into any single drug category. It is not a stimulant, not a sedative, not a classical nootropic, not a simple anti-inflammatory, and not a vasodilator — it is a connective-tissue and neurovascular repair agent that happens to also reduce anxiety and subtly improve cognition. In traditional Sanskrit sources it is called Mandukaparni, literally \"frog's leaf\" after the shape of its rounded, kidney-shaped leaves, and it shares the general name \"Brahmi\" with Bacopa monnieri in many modern markets — a source of endless confusion that has real-world consequences because the two plants do very different things. Bacopa (the other Brahmi) is primarily a bacoside-driven cholinergic cognitive enhancer; Gotu Kola is primarily a centelloid-driven connective-tissue and vascular remodeler with secondary cognitive effects. In classical Ayurveda they were often paired together (the original medhya rasayana formula includes Mandukaparni, Yashtimadhu licorice, Guduchi, and Shankhapushpi), but in the modern nootropic literature they are usually studied separately. Tigers and elephants are both famously associated with Gotu Kola in South Asian folklore — villagers observed that injured animals would seek out and roll in the plant, and tigers in particular developed a reputation for consuming it after combat, which gave rise to one of its common names: \"tiger grass.\" Modern science has largely validated the empirical observation: asiaticoside and madecassoside stimulate fibroblast proliferation and accelerate granulation tissue formation, which is exactly what a post-combat large mammal would benefit from. In contemporary wellness culture, Gotu Kola appears in three major product categories: oral capsules and tinctures for cognition, anxiety, and venous health; topical creams for scar management, stretch marks, post-procedure healing, and eczema; and Korean and Japanese skincare as \"cica\" or \"centella\" lines marketed for sensitive, inflamed, or barrier-damaged skin. Many users are surprised to learn that the same plant driving their $40 bottle of cica serum is also one of the most evidence-backed adjuncts for chronic venous insufficiency, with TECA (total triterpene extract from Centella asiatica) and its branded formulations like Centellase and Madecassol holding pharmaceutical approvals in France, Italy, Spain, and several other European countries for the treatment of venous and lymphatic disorders. The classical Ayurvedic dose is 2-4 grams of powdered leaf daily, brewed as a bitter green tea or mixed into ghee. Modern clinical trials have generally used 60-180 mg/day of standardized triterpene extract (equivalent to roughly 1-3 grams of crude herb) for venous and skin indications, and 500-1000 mg of dried leaf extract (standardized to 10-40% asiaticoside or total triterpenes) for cognitive and anxiolytic applications. Effects on wound healing and venous tone typically appear within 4-8 weeks; effects on anxiety and cognition within 4-12 weeks. Gotu Kola is notably well-tolerated, with the main caveats being rare idiosyncratic hepatotoxicity (almost always linked to high-dose concentrated extracts rather than whole-leaf products), mild sedation at high doses, and a traditional contraindication in pregnancy due to uterine-stimulating activity in animal studies. It is not a fast-acting herb. Users seeking a morning jolt of focus or an acute anxiolytic will be disappointed — Gotu Kola works on the timescale of tissue remodeling, which means weeks to months, not hours to days. But when used consistently alongside foundational sleep, protein intake, vitamin C, zinc, and omega-3 status, it is one of the most reliable botanical tools for the intersection of skin health, vascular health, and mental resilience.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/gotu-kola" }, { "id": "f7fd7118-6b9d-4f97-af46-effd56c00f10", "slug": "grape-seed-extract", "name": "Grape Seed Extract", "aliases": [ "Vitis vinifera seed extract", "Grape seed proanthocyanidin extract", "GSPE", "OPCs", "Oligomeric proanthocyanidins", "Procyanidins", "Leucoselect", "MegaNatural-BP", "Masquelier OPCs", "Grape polyphenols" ], "category": "Herbal", "description": "**Grape Seed Extract (GSE)** — the lipid-soluble polyphenol-rich concentrate derived from the **seeds of the common wine grape** (*Vitis vinifera*, family Vitaceae) — is one of the most widely sold, most extensively researched, and most commercially heterogeneous botanical antioxidant products in the global supplement market. The extract is produced as a dietary-supplement and functional-food ingredient from grape-processing waste streams (primarily from the European and Californian wine industries) via aqueous, hydro-alcoholic, or acetone-water extraction of defatted, milled grape seeds, yielding a reddish-brown amorphous powder rich in **proanthocyanidins** — the oligomeric polyphenolic compounds that constitute the primary putative bioactives. The resulting extract is typically standardized to total **proanthocyanidin** content (variously reported as 70-95% proanthocyanidins, or more rigorously to **oligomeric proanthocyanidins** — OPCs — at 70-85% of total extract weight), with further characterization by polymerization profile, gallate-ester content, and monomeric catechin/epicatechin content. GSE is sold in hundreds of formulations across the dietary-supplement, functional-food, and cosmeceutical markets, with wide variation in source material, extraction solvent, standardization method, and actual OPC content — a key reason clinical-trial results have been heterogeneous and why consumer selection matters.\n\n**Evidence-framing up front — honest positioning**: Among the broad category of \"polyphenol antioxidant supplements,\" grape seed extract has **meaningfully more substantial randomized-controlled-trial evidence than most** — particularly for cardiovascular endpoints including systolic and diastolic blood pressure reduction, endothelial function improvement, and markers of oxidative stress. The **Feringa et al. 2011 meta-analysis** (*Journal of the American Dietetic Association*) pooled **16 randomized controlled trials** comprising 810 subjects and demonstrated statistically significant reductions in systolic blood pressure (approximately −1.54 mmHg) and heart rate, without significant effects on diastolic BP, lipids, or C-reactive protein. The effect size is **modest** but consistent — meaningfully present across trials even if not clinically transformative. Additional evidence supports benefit for **chronic venous insufficiency** symptoms (Saller et al. 1995 and subsequent trials on standardized preparations), **post-exercise oxidative stress** (several small trials), and **skin pigmentation / melasma** (Yamakoshi 2004), with weaker and less consistent evidence for cognitive, renal, and anti-cancer endpoints. Against this real evidence base, GSE is **not** a pharmaceutical substitute for evidence-based antihypertensive therapy in patients with stage 1-2 hypertension, not a validated disease-modifying agent for diabetes or atherosclerosis, and not a replacement for appropriate evaluation and treatment of venous disease or cardiovascular risk. Honest positioning: GSE is a **reasonable evidence-supported antioxidant/vasoactive supplement** — better evidenced than most polyphenol products on the market, but with **inconsistent effect sizes**, **heterogeneous preparations**, and a pattern of modest rather than dramatic clinical benefit.\n\n**Chemistry — what proanthocyanidins actually are**: Proanthocyanidins (also called **condensed tannins** in the older literature) are oligomeric and polymeric flavan-3-ol polyphenols formed from (+)-catechin and (-)-epicatechin monomer units linked by C4–C8 or C4–C6 interflavan bonds. The **monomer units** — (+)-catechin, (-)-epicatechin, and their gallate esters (epicatechin-gallate, epigallocatechin-gallate etc.) — are the structural building blocks; these assemble into **dimers** (procyanidins B1, B2, B3, B4; procyanidin A2 — distinguished by whether bonds are B-type or A-type), **trimers** (procyanidins C1, C2), and progressively larger **oligomers** and **polymers** of 4-10+ monomer units. The term \"**OPC**\" — **oligomeric proanthocyanidin** — most strictly refers to the 2-4-unit oligomer fraction, but in the commercial supplement market \"OPC\" is loosely used for proanthocyanidin-containing extracts in general. **B-type proanthocyanidins** (linked by single C4–C8 or C4–C6 bonds) predominate in grape seed; **A-type proanthocyanidins** (with an additional C2–O–C7 ether bond) are the dominant form in cranberry extracts and have distinct structure-activity profiles, particularly for bacterial anti-adhesion effects. This is why **grape seed extract and cranberry extract are not interchangeable** despite both being \"proanthocyanidin\" products — the underlying chemistry and clinical effects differ materially. The polyphenol profile of a grape seed extract is further characterized by its **mean degree of polymerization** (mDP) — the average length of the oligomer chains — and by the proportion of **galloylated** (gallate-esterified) units, both of which affect bioactivity and bioavailability. Lower-mDP extracts (enriched in dimers and trimers) have different pharmacokinetics and different biological effects than higher-mDP extracts dominated by larger polymers.\n\n**Major commercial standardized extracts**: Several commercial grape seed extracts have been used in the majority of the published clinical trials and provide the main evidentiary basis for GSE efficacy claims. **Leucoselect®** (originally from Indena, Italy) is a historically important standardized grape seed extract characterized by a defined OPC profile and used in many early European trials — particularly Nuttall et al. 1998, a landmark bioavailability/tolerability study that established pharmacokinetic and safety parameters for Leucoselect in healthy volunteers. Leucoselect has been the reference product in several endothelial-function and metabolic trials. **MegaNatural-BP®** (Polyphenolics/Constellation Brands, USA) is a grape seed extract specifically developed and standardized for blood-pressure indications, derived primarily from Chardonnay grape seeds and characterized by a relatively low mean degree of polymerization (enriched in monomers, dimers, and trimers) and relatively high gallate-ester content. MegaNatural-BP was the extract used in the **Sivaprakasapillai et al. 2009 metabolic-syndrome blood-pressure trial** (*Metabolism: Clinical and Experimental*), which demonstrated significant systolic and diastolic BP reductions at 150 mg and 300 mg daily over 4 weeks in subjects with metabolic syndrome. **Masquelier's OPCs** refers to the historical European extracts developed by Jack Masquelier (the pharmacologist who coined the term \"OPC\" in the mid-20th century); these are often associated with cardiovascular and venous indications. Other major brands include **Endotelon®** (a standardized preparation used primarily in European venous-disease literature), **Enovita®**, and numerous generic preparations sold without specific clinical-trial validation. **Practical consequence**: clinical-trial results obtained with Leucoselect or MegaNatural-BP may not be directly extrapolatable to generic grape seed extract capsules from unbranded suppliers, because **the proanthocyanidin profile, mDP, and gallate content differ substantially across products**. Consumers aiming to replicate clinical-trial benefits should prefer the specific standardized products used in the supporting trials.\n\n**Cardiovascular evidence — the strongest signal**: The Feringa 2011 meta-analysis established GSE as a polyphenol with **modest but real** blood-pressure-lowering activity in pooled RCT data, driven by effects on systolic pressure and heart rate. Subsequent meta-analyses have confirmed these findings with varying effect sizes depending on inclusion criteria. Key mechanisms invoked include **nitric-oxide-mediated vasodilation**, **endothelial nitric oxide synthase (eNOS) upregulation**, **reduction of oxidative stress** that otherwise inactivates NO, and **modest inhibition of angiotensin-converting enzyme** (ACE) in some in-vitro preparations. **Clinical reality**: the ~1.5-2 mmHg systolic reduction seen in Feringa 2011 is real but small — meaningful in population-level terms for cardiovascular risk (each 2 mmHg systolic reduction approximately translates to a 7% reduction in stroke mortality at the population level) but not clinically equivalent to antihypertensive pharmaceutical therapy, which typically delivers 10-20 mmHg reductions. **Kar et al. 2009** (*Diabetic Medicine*) demonstrated that 600 mg/day GSE for 4 weeks in type 2 diabetic subjects improved endothelial function (flow-mediated dilation), reduced systolic BP, and reduced markers of inflammation — a more substantial effect than seen in some healthy-subject trials and consistent with the principle that endothelial dysfunction and oxidative stress are more prominent in diabetics than in healthy subjects, leaving more room for GSE benefit. **Ward et al. 2005** (*American Journal of Hypertension*) — the \"null\" study — reported no significant blood pressure change with 1000 mg/day GSE over 6 weeks in hypertensive subjects, illustrating the **heterogeneity** across trials driven by subject selection, baseline BP, extract preparation, and duration. The honest picture is not \"GSE lowers blood pressure\" as an invariant claim but rather **\"GSE produces modest BP reductions in pooled trial data with meaningful heterogeneity across individual trials and preparations.\"**\n\n**Chronic venous insufficiency and venous-related symptoms**: Grape seed extract (particularly the Endotelon standardized preparation) has been used in European phytomedicine for **chronic venous insufficiency (CVI)** symptom management for several decades. The **Saller et al. 1995** trial and subsequent investigations have documented **modest reductions in lower-leg edema, subjective symptom scores (heaviness, pain, paresthesia), and capillary permeability** in subjects with mild-to-moderate CVI. The evidence is not as rigorously meta-analyzed as for BP, and the specific Endotelon/proanthocyanidin preparations used in venous-disease trials differ from MegaNatural-BP and Leucoselect — reinforcing the principle that preparation-specific evidence doesn't automatically generalize across commercial products. Pine bark extract ([pycnogenol](/compound/pycnogenol)) has a more extensive CVI evidence base and is arguably a better-evidenced venous-disease phytomedicine than GSE, though the compounds are chemically related.\n\n**Beyond cardiovascular — weaker but not zero evidence**: **Yamakoshi et al. 2004** (*Phytotherapy Research*) demonstrated modest reduction in melasma pigmentation with 6 months of oral GSE in Japanese women, suggesting dermatological utility for hyperpigmentation. Evidence for **cognitive benefits** (memory, processing speed) is limited and inconsistent. Evidence for **anti-cancer effects** is almost entirely preclinical (cell culture and rodent models); clinical evidence for cancer prevention or treatment is absent, and GSE should not be positioned as anti-cancer therapy. Evidence for **diabetic complications** (neuropathy, retinopathy, nephropathy) is weak beyond the general endothelial-function improvements documented in Kar 2009. Evidence for **athletic performance** is weak; antioxidant supplementation in general has produced disappointing or even counterproductive results in exercise-recovery and performance trials, reflecting the recognition that some exercise-induced oxidative stress is signaling (driving training adaptations) rather than purely harmful.\n\n**Honest positioning in the supplement landscape**: Grape seed extract sits alongside [resveratrol](/compound/resveratrol), [quercetin](/compound/quercetin), [pycnogenol](/compound/pycnogenol), [curcumin](/compound/curcumin), green tea [egcg](/compound/egcg), and [astaxanthin](/compound/astaxanthin) as a **polyphenol/flavonoid antioxidant with a specific mechanistic and clinical footprint** — not a panacea, not equivalent to pharmaceutical therapy, but with genuine evidence for specific endpoints. Its clinical-trial evidence base is **stronger than most polyphenol supplements** (notably stronger than resveratrol's clinical evidence for longevity endpoints, which remains primarily preclinical); **comparable to pycnogenol** for cardiovascular and venous indications; **weaker than established antihypertensive drug classes** like ACE inhibitors, ARBs, thiazides, or calcium channel blockers. Reasonable use cases: (1) mild prehypertensive individuals interested in nutritional approaches alongside lifestyle modification; (2) metabolic syndrome patients seeking endothelial-function support; (3) mild CVI for symptom management; (4) dermatological applications for pigmentation. **Not reasonable**: substitution for evidence-based antihypertensive therapy in clinical hypertension; primary cancer prevention or treatment claim; broad anti-aging marketing; use during pregnancy or breastfeeding without clinician guidance.\n\nThis content is educational and not medical advice; anyone with hypertension, diabetes, cardiovascular disease, venous disease, bleeding disorders, or on chronic medications — particularly anticoagulants or antiplatelets — should discuss grape seed extract use with a knowledgeable clinician before starting. Cross-link to [vitamin-c](/compound/vitamin-c), [alpha-lipoic-acid](/compound/alpha-lipoic-acid), [nac](/compound/nac), and [resveratrol](/compound/resveratrol) for overlapping antioxidant frameworks; to [quercetin](/compound/quercetin) and [pycnogenol](/compound/pycnogenol) for closely-related flavonoid phytochemistry; to [curcumin](/compound/curcumin) for adjunctive anti-inflammatory options.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 908, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/grape-seed-extract" }, { "id": "881a7146-ea2a-4b38-a86d-dc7411566ff8", "slug": "hawthorn", "name": "Hawthorn", "aliases": [ "Crataegus", "Crataegus monogyna", "Crataegus laevigata", "Crataegus oxyacantha", "Crataegus pinnatifida", "Shan Zha", "May Tree", "Whitethorn", "Hagthorn", "Quickthorn", "Mayblossom" ], "category": "herb", "description": "Hawthorn (Crataegus species — principally Crataegus monogyna, C. laevigata, C. pinnatifida, and C. cuneata) is the most extensively studied cardiovascular botanical in the Western pharmacopoeia and one of very few herbs with formal pharmaceutical regulatory approval in Europe for a specific cardiovascular indication. In Germany and several other European countries, standardized hawthorn extracts — most notably WS 1442, marketed under the name Crataegutt — are approved by Commission E and BfArM for the symptomatic treatment of mild heart failure corresponding to NYHA (New York Heart Association) functional classes I and II. This is a notable regulatory position for a botanical: hawthorn is not an adjuvant or a wellness supplement in the European context but a registered drug used alongside or as an alternative to pharmaceutical therapy in early heart failure, with a body of controlled trial evidence stretching back to the 1980s. The plant itself is a thorny, small-to-medium tree or large shrub in the Rosaceae family (the rose family, which it shares with apples, pears, roses, and almonds), native across the temperate zones of the Northern Hemisphere, with the European species forming dense hedgerows in the British Isles, Ireland, and continental Europe, and the Chinese species producing small, sweet-sour, red-orange fruits that are a staple in Traditional Chinese Medicine as Shan Zha — used primarily for digestive stagnation and food accumulation, and secondarily for cardiovascular support. The pharmacologically active constituents cluster in three main groups: oligomeric proanthocyanidins (OPCs), which are the dominant antioxidant constituents and the primary component standardized in the premium European extracts; flavonoids including hyperoside, vitexin, vitexin-2-O-rhamnoside, rutin, quercetin, and luteolin, which contribute to vasodilatory, inotropic, and anti-arrhythmic effects; and pentacyclic triterpenes like ursolic acid, oleanolic acid, and crataegolic acid, which modulate ion channels in cardiac myocytes. The leaves and flowers together carry the highest concentration of flavonoids and are the standard source for European pharmaceutical extracts; the berries carry higher concentrations of OPCs and are preferred in American and Chinese herbal traditions. Many of the best commercial products combine both leaf-flower and berry material to capture the full phytochemical spectrum. Mechanistically, hawthorn is unique among cardiovascular botanicals because it produces a combination of mild positive inotropy (increased cardiac contractility) through a cAMP-independent mechanism — which means it strengthens contraction without the arrhythmogenic risk that accompanies digitalis or beta-agonists — alongside mild coronary and peripheral vasodilation through endothelial nitric oxide release and potassium channel modulation, along with mild anti-arrhythmic activity through prolongation of the refractory period in cardiac myocytes. The net hemodynamic effect is improved cardiac output at lower myocardial oxygen demand, which is precisely what a failing or ischemic heart needs. Clinically, the strongest evidence base is in NYHA Class I-II heart failure, where controlled trials have shown improved exercise tolerance, reduced shortness of breath and fatigue, improved quality-of-life scores, and small but measurable improvements in echocardiographic parameters. The SPICE trial (Holubarsch 2008) randomized 2,681 patients with NYHA II-III heart failure on background standard therapy to WS 1442 or placebo; the primary composite cardiovascular endpoint did not reach significance overall, but subgroup analyses suggested benefit in patients with preserved systolic function and reduction in sudden cardiac death. A Cochrane-style systematic review by Pittler and colleagues pooling 14 controlled trials found consistent improvements in exercise tolerance and symptoms across the evidence base. Beyond heart failure, hawthorn has smaller but credible evidence for mild hypertension, stable angina adjunctive support, and functional arrhythmia management. The herb is distinctly not a substitute for evidence-based pharmaceutical heart failure therapy — ACE inhibitors, angiotensin receptor-neprilysin inhibitors, beta blockers, SGLT2 inhibitors, mineralocorticoid receptor antagonists, and device therapy have transformed the prognosis of heart failure over the past thirty years, and hawthorn should be viewed as a complement to, not a replacement for, that foundation. But for patients with mild, stable symptoms, patients who cannot tolerate full pharmaceutical dosing, or patients who wish to improve cardiac resilience alongside standard therapy, standardized hawthorn is one of the few supplements with a genuinely rigorous evidence base. The typical clinical dose of WS 1442 is 900 mg/day divided into two or three doses (equivalent to 160-180 mg of the 18-20% OPC standardized extract); for crude leaf-flower or berry extracts, 900-1800 mg/day of well-standardized product is a reasonable range. Onset of effect is slow — 4-8 weeks for initial improvements in exercise tolerance and 6-12 weeks for stable effects on symptoms. Hawthorn is extraordinarily well tolerated, with the main side effects being mild gastrointestinal upset, occasional headache, and very rarely mild palpitations at the start of therapy. The most important clinical caveat is potential potentiation of digitalis (digoxin) and, more broadly, additive effects with antihypertensive medications — patients on heart failure or hypertension drug therapy should introduce hawthorn in consultation with their cardiologist or primary care provider, with appropriate monitoring of blood pressure, heart rate, and renal function as indicated.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/hawthorn" }, { "id": "b9a681fe-46b8-43a6-a51f-a308ca13c6c6", "slug": "hcg", "name": "HCG", "aliases": [ "Human Chorionic Gonadotropin" ], "category": "Hormonal", "description": "Human chorionic gonadotropin (hCG) is a 237-amino-acid glycoprotein hormone produced naturally during pregnancy by trophoblast cells of the developing embryo, beginning as early as 6-8 days after conception and peaking between weeks 8-11 of gestation at concentrations of 50,000-300,000 mIU/mL maternal serum. The hormone is a heterodimer consisting of two distinct subunits: an alpha subunit (92 amino acids, 14.5 kDa, shared with LH, FSH, and TSH) and a unique beta subunit (145 amino acids, 22 kDa, which gives hCG its biological specificity and is the basis for pregnancy tests). Discovered and first isolated in the 1920s by researchers including Bernhard Zondek and Selmar Aschheim, hCG has become one of the most clinically important hormones in reproductive medicine — both as a diagnostic marker (pregnancy testing, tumor marker for gestational trophoblastic disease and some germ cell tumors) and as a therapeutic agent (ovulation induction, luteal phase support in IVF, induction of Leydig cell testosterone production in hypogonadotropic hypogonadism, and preservation of testicular size and fertility during exogenous androgen use).\n\nThe critical pharmacological insight about hCG is that it binds to and activates the luteinizing hormone (LH) receptor with high affinity — essentially, hCG is a long-acting LH mimetic. LH and hCG share the identical alpha subunit, and their beta subunits are highly homologous; this structural similarity means that hCG can substitute functionally for LH at the receptor level. The key pharmacokinetic difference is half-life: endogenous LH has a plasma half-life of 20-30 minutes due to rapid clearance and pulsatile secretion, while hCG has a half-life of 24-36 hours because its unique C-terminal peptide extension (CTP) and higher glycosylation protect it from rapid clearance. This long half-life makes hCG an excellent tool for sustained LH-receptor stimulation — a single injection can maintain biologically significant LH-receptor activation for 3-7 days, compared to LH's minutes-long effect ([Cole, 2010]).\n\nIn current clinical practice, hCG has three primary approved uses: (1) ovulation induction in women undergoing fertility treatment (often substituting for the endogenous LH surge); (2) treatment of hypogonadotropic hypogonadism in men, where it directly stimulates testicular Leydig cells to produce testosterone (bypassing the absent or insufficient endogenous LH); (3) pediatric use in cryptorchidism to promote testicular descent. In the bodybuilding and testosterone-replacement-therapy communities, hCG is widely used off-label for a different but related purpose: preserving testicular size and function during exogenous androgen use. When men inject testosterone or anabolic steroids, the body senses the elevated androgen and suppresses endogenous LH through hypothalamic-pituitary negative feedback; this causes the testes to stop producing their own testosterone and can lead to testicular atrophy and fertility impairment. Low-dose hCG (typically 500-1,500 IU 2-3x weekly) directly stimulates the testes to continue producing testosterone regardless of the suppressed LH signal, preserving testicular size and function during TRT or cycles ([Hsieh et al., 2013]).\n\nThe landscape of hCG use shifted significantly in the 2010s and 2020s. First, the FDA approved several forms of recombinant LH (Luveris, rLH) that achieve similar Leydig-cell stimulation without hCG's longer half-life and higher dosing requirements, though these remain significantly more expensive. Second, concerns about product sourcing and quality emerged — urinary-derived hCG (which has dominated supply historically) has had occasional contamination issues, while recombinant hCG (brand names Ovidrel/Ovitrelle) offers more consistent quality at higher cost. Third, the hCG diet — a weight-loss fad dating to Albert Simeons's 1954 publication — has been thoroughly debunked by multiple rigorous trials, and the FDA has issued warnings against hCG for weight loss. Any weight loss on the hCG diet is due to the severe 500-kcal dietary restriction, not hCG itself, which has no demonstrable effect on appetite or metabolism. Despite clear evidence of inefficacy, compounded hCG for weight loss remains a persistent grey-market product ([Lijesen et al., 1995 Cochrane]).\n\nThis entry focuses primarily on the men's health and fertility applications of hCG, which are the most common off-label uses in peptide communities. Cross-references include [Gonadorelin](/compound/gonadorelin) (GnRH, upstream of LH/hCG in the reproductive axis), [Kisspeptin-10](/compound/kisspeptin-10) (further upstream, driving GnRH release), [Enclomiphene](/compound/enclomiphene) (SERM that restores axis through different mechanism), and [Sermorelin](/compound/sermorelin) (distinct GH axis, frequently layered in recovery protocols). For women's fertility applications, hCG is integral to IVF and ovulation induction protocols administered under reproductive endocrinology supervision.", "half_life": "Approximately 24-36 hours (terminal elimination). Clearance is biphasic: an initial distribution phase of roughly 6-11 hours followed by a terminal phase averaging ~33 hours. This is far longer than pituitary LH (~20-30 minutes), owing to the beta-subunit C-terminal peptide (CTP) and heavy sialylation. Peak plasma concentration occurs ~6-12 hours after SC or IM injection, and a single dose exerts biological effects for roughly 5-7 days. Elimination is primarily renal.", "molecular_weight": "~36,700 Da (36.7 kDa)", "molecular_mass": "~36,700 Da (36.7 kDa) for the intact glycosylated heterodimer; composed of a ~14.5 kDa alpha subunit and a ~22.2 kDa beta subunit. hCG is heavily glycosylated (~30% carbohydrate by mass), so the exact mass is heterogeneous across glycoforms and preparations.", "amino_acid_sequence": "hCG is a heterodimeric glycoprotein hormone (not a single synthetic peptide). It is two non-covalently associated subunits:\n\n- Alpha subunit (CGA, 92 aa; identical to the alpha subunit of LH, FSH and TSH; UniProt P01215): APDVQDCPECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCCVAKSYNRVTVMGGFKVENHTACHCSTCYYHKS\n\n- Beta subunit (CGB, 145 aa; unique to hCG, confers biological specificity; UniProt P0DN86/CGB3): SKEPLRPRCRPINATLAVEKEGCPVCITVNTTICAGYCPTMTRVLQGVLPALPQVVCNYRDVRFESIRLPGCPRGVNPVVSYAVALSCQCALCRRSTTDCGGPKDHPLTCDDPRFQDSSSSKAPPPSLPSPSRLPGPSDTPILPQ\n\nKey modifications: heavily glycosylated (~30% carbohydrate by weight). The alpha subunit carries 2 N-linked glycans; the beta subunit carries 2 N-linked glycans plus 4 O-linked glycans on its C-terminal peptide (CTP, the serine-rich ...SSSSKAPPPSLPSPSRLPGPSDTPILPQ tail). Each subunit is stabilized by multiple disulfide bonds in a cystine-knot fold. The beta CTP is absent in pituitary LH and, together with terminal sialylation, is responsible for hCG's much longer circulating half-life. Recombinant hCG (choriogonadotropin alfa, Ovidrel/Ovitrelle) reproduces this heterodimer in CHO cells; urinary hCG (Pregnyl, Novarel) is purified from the urine of pregnant women.", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "FDA-approved", "approval_status": "FDA-approved. Marketed as urinary-derived hCG (Pregnyl, Novarel) and recombinant choriogonadotropin alfa (Ovidrel in the US, Ovitrelle in the EU/UK). Approved indications: ovulation induction and assisted reproductive technology in women, male hypogonadotropic hypogonadism, and prepubertal cryptorchidism. Widely used off-label (research/clinical) in men for TRT fertility and testicular-size preservation, post-cycle recovery, and hCG monotherapy for secondary hypogonadism. hCG for weight loss is NOT approved - the FDA issued warnings in 2011 against over-the-counter and homeopathic hCG weight-loss products.", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/hcg" }, { "id": "e49133ef-9833-4081-94f9-62babdf0cee1", "slug": "hesperidin", "name": "Hesperidin", "aliases": [], "category": "Polyphenol", "description": "Hesperidin is the signature flavanone glycoside of citrus fruit — specifically the 7-O-rutinoside of hesperetin — and it is the single most abundant flavonoid in the white pith and peel of sweet oranges, lemons, tangerines, and grapefruit. The compound accumulates at notable concentrations in citrus tissues that most consumers throw away, which is one reason why the therapeutic dose of hesperidin used in European phlebology (500 mg twice daily of micronized diosmin–hesperidin) is roughly an order of magnitude higher than what any realistic citrus-eating pattern delivers. Structurally, hesperidin is a flavanone, meaning it has a saturated C ring rather than the unsaturated C ring found in flavonols like quercetin or fisetin, and this saturation makes the molecule less electronically reactive and far less prone to the autoxidation chemistry that sometimes complicates flavonoid supplementation. Hesperidin is also unusual for the flavonoid world in that it is essentially odorless, tasteless, and water-insoluble in its native glycoside form, which paradoxically contributes to its poor oral bioavailability — the sugar moiety (rutinose) must be cleaved by colonic microbiota glycosidases before hesperetin aglycone can be absorbed across the gut wall. This absorption bottleneck is the central pharmacokinetic problem of hesperidin supplementation and it has spawned an entire generation of enhanced-bioavailability formulations including micronization (Daflon 500 / MPFF, used as a prescription phlebotonic in France and much of continental Europe), enzymatic deglycosylation to 2S-hesperidin (hesperidin-2-glucoside, roughly 3-4x more bioavailable than native hesperidin), and phytosome/phospholipid complexes.\n\nBodyHackGuide covers hesperidin as the vascular endpoint of the flavonoid arc — the molecule in the polyphenol family with the cleanest human clinical evidence for endothelial function, blood pressure, and venous/lymphatic outcomes. Where [quercetin](/compound/quercetin) has mast-cell and senolytic framing, where [fisetin](/compound/fisetin) has its Mayo Clinic senolytic trial, where [apigenin](/compound/apigenin) has CD38 inhibition and NAD+ salvage, and where [pterostilbene](/compound/pterostilbene) has its resveratrol-analog bioavailability story, hesperidin owns the vascular endothelium and the microcirculation. The Orange Juice and Endothelial Function trials by Morand 2011 (PMID 21068346) and Buscemi 2012, the Rizza 2011 endothelial-function crossover, and the Salden 2016 dose-ranging trialtogether make hesperidin one of the most clinically validated flavonoids for flow-mediated dilation, a surrogate endpoint that correlates with long-term cardiovascular events. Layer on the Xiong 2019 blood pressure meta-analysis, the Valls 2021 lipid-profile data, and the decades of European prescribing experience with micronized purified flavonoid fraction (MPFF / Daflon) for chronic venous insufficiency and hemorrhoids — most of which is captured in the Martinez-Zapata 2020 Cochrane review on phlebotonics — and you have a compound with one of the best-evidenced benefit–risk profiles of any flavonoid on the supplement shelf. Hesperidin is cheap, safe at dietary and supplemental doses, and has been consumed at gram-level daily intakes by postmenopausal Mediterranean women for centuries without any signal of harm.\n\nThe mechanistic story centers on the endothelium and on NO (nitric oxide) signaling. Hesperetin aglycone — the active, absorbed form after rutinose cleavage by colonic bacteria — upregulates endothelial nitric oxide synthase (eNOS) and protects existing NO from superoxide quenching by reducing NADPH-oxidase expression in vascular smooth muscle. The net effect is vasodilation, improved flow-mediated dilation on brachial-artery ultrasound, and lower systolic blood pressure. The Milenkovic transcriptomic studies published across 2011–2016 (Milenkovic 2011, Milenkovic 2016) showed that a single 500 mg oral dose of hesperidin in healthy volunteers modulates the expression of hundreds of genes in peripheral blood mononuclear cells, with the biggest signals in inflammation and leukocyte transendothelial migration pathways. This transcriptomic fingerprint — dampening leukocyte adhesion to the vessel wall — maps cleanly onto the vein-wall stabilization and capillary-leak reduction that micronized diosmin–hesperidin achieves in chronic venous insufficiency. Hesperidin also has weak but measurable anti-inflammatory activity independent of endothelium, inhibiting NF-κB activation and reducing TNF-α, IL-6, and CRP modestly in some trials, and it appears to improve lipid metabolism marginally — the Rezende 2013 and Valls 2021 data show small but consistent reductions in total and LDL cholesterol at 500 mg/day doses over 6–8 weeks.\n\nThe venous-insufficiency indication deserves its own paragraph because it is the single application where hesperidin has regulatory approval as a prescription product in dozens of countries. Micronized Purified Flavonoid Fraction (MPFF) — sold as Daflon 500 in France, Venaflon and Diovenor elsewhere, Arvenum in Italy — is a 500 mg tablet containing 90% diosmin and 10% hesperidin (as hesperidin-rutinoside). The micronization process reduces particle size below 2 μm, dramatically increasing dissolution and absorption. Martinez-Zapata 2020's Cochrane review of phlebotonics (covering roughly 70 randomized trials in over 11,000 patients) concluded that MPFF produces moderate-quality evidence of benefit for lower-limb edema, cramps, restless legs, and the aching/heaviness complex of chronic venous insufficiency — benefits confirmed by the RELIEF study and the large prospective registries run by the French health system. Separately, MPFF is the best-evidenced medical therapy for symptomatic hemorrhoidal disease, with Perrin 2019 and earlier meta-analyses (Alonso-Coello 2006) showing reductions in bleeding, pain, and recurrence when MPFF is combined with fiber and hygiene interventions. The dose for venous and hemorrhoidal applications is typically 1,000 mg/day (500 mg twice daily) of MPFF, which is roughly 100 mg/day of hesperidin and 900 mg/day of diosmin — much higher than can be obtained from food.\n\nA newer and nutritionally-relevant branch of the hesperidin literature is exercise performance and recovery, most of it driven by the Martinez-Noguera 2019and Martinez-Noguera 2020 studies on 2S-hesperidin (hesperidin-2-glucoside, marketed as Cardiose by HealthTech BioActives) in amateur cyclists. These trials showed modest but statistically significant improvements in maximal power output and time-trial performance in trained cyclists supplementing 500 mg/day of 2S-hesperidin for 8 weeks. Mechanism is presumed to be some combination of improved endothelial NO signaling under exercise stress, modest antioxidant buffering of exercise-induced oxidative stress, and possible effects on AMPK / PPAR-α and mitochondrial biogenesis (analogous to but much weaker than the exercise-mimetic signatures seen with higher-dose polyphenols in rodent studies). The effect size is small and not every study replicates, but the safety profile is impeccable and the performance claim does not require users to believe in anything more exotic than \"better endothelial function during hard efforts.\"\n\nHesperidin is one of the few supplements on BodyHackGuide where the honest recommendation for most users is probably food first — aim for an orange a day, keep the white pith attached, and consider a glass of fresh-squeezed citrus juice with meals — and only move to supplementation if you have a specific indication (venous insufficiency, hemorrhoids, documented endothelial dysfunction, athletic performance goals). The supplement form that I would pick for most people is 2S-hesperidin (Cardiose) at 500 mg/day for its superior bioavailability, or MPFF/Daflon at 500 mg twice daily if you have clinical venous symptoms and want the prescription-grade formulation. Both forms are remarkably safe — there is essentially no ceiling-dose toxicity, no meaningful drug interactions apart from theoretical cautions with anticoagulants at very high intakes, and no evidence of harm at pregnancy-typical dietary intakes (though supplemental use in pregnancy should be discussed with an obstetrician since formal reproductive-toxicity data are limited). What you do NOT get from hesperidin is the senolytic activity of fisetin, the mast-cell stabilization of quercetin, the CD38 inhibition of apigenin, or the SIRT1 activation of pterostilbene — hesperidin sits in its own vascular and venous niche and should be selected accordingly, not treated as a generic \"flavonoid supplement.\"", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 450, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/hesperidin" }, { "id": "a57141bf-ce3e-4703-ad6d-bddf0af36670", "slug": "hexarelin", "name": "Hexarelin", "aliases": [ "Examorelin" ], "category": "Growth Hormone / IGF-1 Axis", "description": "Hexarelin (also called examorelin) is a potent synthetic hexapeptide growth hormone secretagogue with the sequence **His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2**. It is structurally similar to GHRP-6 and GHRP-2 but features a 2-methyl-substituted tryptophan residue that produces **significantly higher GH-releasing potency on a per-molecule basis** — reportedly the most potent of the classical GHRPs when measured by peak GH pulse amplitude at equivalent molar doses ([Imbimbo et al., 1994]).\n\nThis potency comes with a tradeoff: hexarelin produces **the most pronounced cortisol, prolactin, and ACTH elevations of any commonly-used GHS compound**. Where GHRP-2 and GHRP-6 cause modest (+15-25%) cortisol elevations, hexarelin can produce cortisol increases of +30-50% above baseline in the 60-90 minute post-injection window, along with meaningful ACTH stimulation that is not seen with the more selective analogs. Chronic daily use also produces **faster GHS-R1a receptor desensitization** than other GHRPs, making hexarelin better suited to short aggressive cycles than to continuous long-term protocols.\n\nBeyond its GH-axis effects, hexarelin has generated significant research interest for **cardioprotective properties** mediated through CD36 receptor binding — a mechanism independent of GHS-R1a. Preclinical studies have documented reduced infarct size following ischemia-reperfusion insult, improved cardiac contractility, and beneficial effects on cardiac remodeling in animal models ([Torsello et al., 2003]). Clinical translation to human cardiac therapy has not occurred, but the cardiac research niche distinguishes hexarelin from other GHRPs.\n\nHexarelin has been studied extensively in clinical trials for **pediatric and adult GH deficiency diagnostic testing**, particularly in European centers, where single IV boluses produce reliable and discriminating GH responses ([Loche et al., 1995]; [Arvat et al., 1995]). It is not FDA-approved and has no broadly approved therapeutic indication. Research-grade use is via SC injection, typically 100-200 mcg 1-3 times daily, with shorter cycling (4-6 weeks on / 2-4 weeks off) more commonly recommended than with other GHRPs due to the faster receptor desensitization profile.", "half_life": "~55 minutes (IV, per Imbimbo 1994)", "molecular_weight": "887 Da", "molecular_mass": "887.05 g/mol", "amino_acid_sequence": "His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2", "administration_routes": [ "Subcutaneous", "Intramuscular" ], "dose_range_mcg": "100–200 mcg per injection", "dosing_frequency": "1–2 times daily; subject to desensitization within 4 weeks", "cycle_length": "4-6 weeks (desensitization limits longer use)", "common_vial_sizes": [ "2mg", "5mg" ], "research_stage": "Phase II", "approval_status": "", "trial_phase": "Phase 2", "cas_number": "140703-51-1", "iupac_name": "His-D-2-MeTrp-Ala-Trp-D-Phe-Lys-NH2", "chemical_formula": "C47H58N12O6", "potential_benefits": [ "Maximum GH output", "Cardiac protection", "Muscle building", "Body composition", "Recovery" ], "research_fields": [ "GH deficiency", "Cardiac ischemia", "Heart failure", "Body composition" ], "pubmed_count": 14, "pubchem_cid": 9888045, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/9888045/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/hexarelin" }, { "id": "05d9014e-fd13-4762-be03-411ba200ce6e", "slug": "hgh-frag-176-191", "name": "HGH Fragment 176-191", "aliases": [], "category": "Metabolic & Weight Loss", "description": "**HGH Fragment 176-191** (also written HGH Frag 176-191, hGH Fragment 176-191, and frequently appearing in clinical literature as **AOD-9604** — \"Anti-Obesity Drug 9604\") is a synthetic peptide corresponding to the C-terminal 15-amino-acid region of the 191-amino-acid human growth hormone (hGH) molecule, with an additional N-terminal tyrosine residue added for stability and biological activity. The sequence spans residues 176 through 191 of native hGH plus the tyrosine cap, giving the designation \"Tyr-hGH 176-191.\" It was developed in the 1990s at Monash University (Melbourne, Australia) under the direction of F.M. Ng and colleagues, and subsequently licensed to Metabolic Pharmaceuticals (later acquired by Calzada Ltd), which pursued clinical development for obesity indications. The core hypothesis driving its development was that the C-terminal region of hGH carries the lipolytic (fat-burning) and anti-lipogenic activity of the parent molecule while being separable from the IGF-1-mediated growth-promoting effects that raise cancer, diabetes, and acromegaly concerns when full-length recombinant hGH is used chronically.\n\nThat separation is real in cell culture and rodent studies. Ng and colleagues demonstrated in the 1990s that HGH 176-191 stimulates lipolysis in isolated adipocytes, reduces body fat in genetically obese mice, and does so without measurably raising serum IGF-1 or activating the JAK2/STAT5 pathway in the growth-promoting way that intact hGH does. This work formed the scientific foundation for AOD-9604's clinical development as a potential obesity drug. Between approximately 2002 and 2008, Metabolic Pharmaceuticals conducted a series of Phase I and Phase II trials in humans, evaluating doses ranging from 100 mcg to 1 mg daily via subcutaneous injection and, in later studies, oral formulations.\n\nThe critical fact users should understand is that **AOD-9604 failed its key clinical trials**. The 2007 Phase 2b trial (n≈534) evaluated AOD-9604 at doses up to 1 mg/day orally in obese adults over 24 weeks, and the primary endpoint — placebo-adjusted weight loss — was not met. The difference from placebo was small and not statistically significant. Metabolic Pharmaceuticals subsequently abandoned AOD-9604's development as an anti-obesity drug, and no regulatory agency (FDA, EMA, TGA, PMDA, Health Canada) has ever approved AOD-9604 for any indication. It is **not an approved medicine anywhere in the world.** The Australian TGA briefly granted AOD-9604 GRAS-like \"listable\" status as a cosmetic ingredient — a classification that does not imply clinical efficacy or safety for systemic therapeutic use — but this is a regulatory footnote, not a clinical endorsement.\n\nNotwithstanding the clinical trial failure, HGH Fragment 176-191 has acquired a significant following in the compounding pharmacy, peptide clinic, and research-chemical markets, primarily for claimed **fat loss**, **joint health**, and **body recomposition** effects. Compounding pharmacies in the United States have at times supplied AOD-9604 as an ingredient in custom formulations prescribed by longevity-medicine and functional-medicine physicians, though the FDA has issued guidance restricting compounding of peptides without an established USP or NF monograph, and the regulatory landscape for AOD-9604 compounding has tightened substantially since 2023. In the unregulated research-peptide market, HGH Fragment 176-191 is widely sold as an injectable peptide, typically at prices substantially lower than brand-name weight-loss medications.\n\nThe problem users must grapple with is that **the best-controlled human data on AOD-9604 showed it did not produce clinically meaningful weight loss.** This is in stark contrast to the current standard of care for obesity, which includes the **GLP-1 receptor agonists** — [semaglutide](/compound/semaglutide) (Wegovy, Ozempic) and the dual GIP/GLP-1 agonist [tirzepatide](/compound/tirzepatide) (Zepbound, Mounjaro) — which produce 15-22% placebo-adjusted weight loss in 68-72 week randomised trials (STEP and SURMOUNT programmes), approved by the FDA, EMA, and global regulators for chronic weight management. These drugs have transformed obesity medicine in the 2020s. AOD-9604, by comparison, produced a weight-loss effect of approximately 2.8 kg vs. placebo in 12-week trials that did not reach the threshold for regulatory approval. The gap is not subtle; it is a categorical difference between an evidence-based treatment and a compound that failed its key trials.\n\nA more honest framing of AOD-9604 in 2026 is this: it is a rationally designed peptide fragment with plausible preclinical biology that did not translate to a clinically meaningful anti-obesity effect in humans. It may have subtle metabolic effects at commonly used research doses, but these have not been established in adequately powered, placebo-controlled trials. Users considering AOD-9604 for fat loss should first ask whether they have exhausted evidence-based options: GLP-1/GIP agonists for those meeting BMI criteria; structured diet and exercise programs with documented adherence support; evaluation of thyroid, cortisol, and metabolic status; and, where indicated, bariatric surgery consultation. Adding an unregulated peptide that failed its clinical trials is a substantially weaker option than any of these. For joint-health claims — a secondary use popularised in peptide-clinic marketing — there are no adequately powered trials establishing AOD-9604 efficacy for osteoarthritis or cartilage repair, and the evidence-based options (physical therapy, weight reduction, NSAIDs, intra-articular corticosteroids, and for eligible patients, joint replacement) remain the appropriate first-line. [BPC-157](/compound/bpc-157) and [TB-500](/compound/tb-500) are sometimes discussed alongside AOD-9604 for joint and tissue-repair claims, but they share similar limitations in the evidence base.\n\nFor the remainder of this page, we present the mechanism, studies, and protocols that users and compounding pharmacists have worked with — with the repeated caveat that none of this substitutes for a failed key trial result and the absence of any regulatory approval.", "half_life": "~30 minutes (short plasma half-life)", "molecular_weight": "1815.1 g/mol", "molecular_mass": "1815.1 g/mol", "amino_acid_sequence": "Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe (one-letter: YLRIVQCRSVEGSCGF). A 16-residue analog: the C-terminal fragment of human growth hormone (residues 177-191) with an added N-terminal tyrosine, commonly marketed as \"HGH Fragment 176-191.\" Contains an intramolecular disulfide bond between Cys7 and Cys14. Molecular formula C78H123N23O23S2; molecular weight 1815.1 g/mol (PubChem CID 71300630).", "administration_routes": [], "dose_range_mcg": "250-500", "dosing_frequency": "Once or twice daily, fasted", "cycle_length": "8-16 weeks", "common_vial_sizes": [], "research_stage": "Phase 2 (discontinued)", "approval_status": "Not approved for any indication", "trial_phase": "Phase 2", "cas_number": "66004-57-7", "iupac_name": "Tyr-hGH(176-191)", "chemical_formula": "C78H123N23O23S2", "potential_benefits": [ "Targeted fat loss", "Visceral fat reduction", "No insulin resistance", "Metabolic improvement", "No IGF-1 elevation" ], "research_fields": [ "Obesity", "Lipodystrophy", "Metabolic syndrome", "Body composition" ], "pubmed_count": 2, "pubchem_cid": 56842035, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/56842035/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/hgh-frag-176-191" }, { "id": "da1ad254-cb08-477c-8e89-7bb16e1ce6be", "slug": "hmg", "name": "HMG (Human Menopausal Gonadotropin)", "aliases": [ "Menotropins", "Human menopausal gonadotropin", "hMG", "Menotrophin", "Menopur", "Repronex", "Pergonal" ], "category": "Hormones & Endocrine (Non-GH)", "description": "HMG, or human menopausal gonadotropin, is not a synthetic research chemical. It is menotropins, an approved injectable fertility drug purified from the urine of postmenopausal women. It is a mixture rather than a single molecule: each vial of the currently marketed US product, Menopur, contains 75 international units of follicle-stimulating hormone activity and 75 international units of luteinizing hormone activity, and human chorionic gonadotropin from the urine source is detected in the product. The initial US approval for menotropins dates to 1975 (Menopur US prescribing information).\n\nThe two hormones do different jobs. Follicle-stimulating hormone acts on granulosa cells in the ovary and on Sertoli cells in the testis to support gamete development. Luteinizing hormone acts on theca cells and, in men, on Leydig cells to drive steroid production. Giving both together reproduces the pituitary signal that is missing when the hypothalamic-pituitary axis is not working, or supplies a supraphysiological signal to recruit multiple follicles in assisted reproduction.\n\nThe approved US indication is narrow: development of multiple follicles and pregnancy in ovulatory women as part of an assisted reproductive technology cycle. Older menotropins labeling also carried an indication, with concomitant human chorionic gonadotropin, for stimulating spermatogenesis in men with primary or secondary hypogonadotropic hypogonadism. In current practice, that male use is well documented in the literature even where it is not on the label of the marketed product. A systematic review and meta-analysis of 103 studies covering 5328 male patients with hypogonadotropic hypogonadism found human menopausal gonadotropin used in 40.8 percent of studies, and reported spermatogenesis in 86 percent of patients treated with human chorionic gonadotropin plus follicle-stimulating hormone against 40 percent with human chorionic gonadotropin alone (PMID: 38128110). A retrospective cohort of 122 Chinese men treated with combined human chorionic gonadotropin and human menopausal gonadotropin over 24 months reported spermatogenesis in 92.3 percent of men with partial disease and 74.7 percent of those with complete disease (PMID: 31464203).\n\nThe safety profile is the reason this is a prescription drug. The label carries warnings for ovarian hyperstimulation syndrome, abnormal ovarian enlargement, pulmonary and vascular complications, ovarian torsion, multi-fetal gestation, congenital malformations, ectopic pregnancy, spontaneous abortion and ovarian neoplasms. In the registration trials the most common adverse reactions included abdominal pain in 6.7 percent, headache in 6.2 percent, ovarian hyperstimulation syndrome in 6.2 percent and injection site reactions in 3.9 percent (Menopur US prescribing information).\n\nFor male athletes in tested sport, hMG is prohibited. The World Anti-Doping Agency prohibits chorionic gonadotrophin and luteinizing hormone and their releasing factors in male athletes under section S2 of the Prohibited List, and hMG contains luteinizing hormone activity. What is sold outside pharmacy channels as a research-use vial is not the approved product, has no verified potency in international units, and carries the contamination and mislabeling risks common to that market.", "half_life": "Elimination half-life for follicle-stimulating hormone of 11 to 13 hours in the multiple-dose phase, similar for subcutaneous and intramuscular routes (Menopur US prescribing information)", "molecular_weight": null, "molecular_mass": null, "amino_acid_sequence": "", "administration_routes": [ "Subcutaneous injection", "Intramuscular injection" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "FDA Approved", "approval_status": "Approved in the United States since 1975; the currently marketed product, Menopur, is indicated for development of multiple follicles and pregnancy in ovulatory women as part of an assisted reproductive technology cycle (Menopur US prescribing information). It is a prescription drug, not a supplement and not a research chemical. Use in men for hypogonadotropic hypogonadism is documented in the literature but is outside the labeled indication of the marketed US product. Chorionic gonadotrophin and luteinizing hormone are prohibited for male athletes under section S2 of the World Anti-Doping Agency Prohibited List, and hMG contains luteinizing hormone activity.", "trial_phase": "", "cas_number": null, "iupac_name": "", "chemical_formula": null, "potential_benefits": [ "Testicular growth in almost all patients, spermatogenesis in approximately 80 percent and pregnancy rates in the range of 50 percent with combined human chorionic gonadotropin and FSH therapy in men with hypogonadotropic hypogonadism (PMID: 32445446)", "Spermatogenesis in 86 percent of men with hypogonadotropic hypogonadism treated with human chorionic gonadotropin plus an FSH source, against 40 percent with human chorionic gonadotropin alone, in a meta-analysis of 103 studies and 5328 patients (PMID: 38128110)", "Spermatogenesis in 92.3 percent of men with partial and 74.7 percent with complete congenital hypogonadotropic hypogonadism after combined human chorionic gonadotropin and human menopausal gonadotropin treatment in a 122-patient cohort (PMID: 31464203)", "Increased testicular volume, penile size and testosterone in over 98 percent of analyses of gonadotropin therapy for pubertal induction in males (PMID: 38128110)" ], "research_fields": [ "Assisted reproduction", "Male hypogonadotropic hypogonadism", "Reproductive endocrinology" ], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/hmg" }, { "id": "9ae7533b-78dd-445f-9bcd-e6192b3d4488", "slug": "horny-goat-weed", "name": "Horny Goat Weed", "aliases": [ "Epimedium", "Yin Yang Huo", "Epimedium sagittatum", "Epimedium brevicornum", "Epimedium koreanum", "Epimedium grandiflorum", "Epimedium pubescens", "Barrenwort", "Bishop's Hat", "Fairy Wings", "Icariin Herb" ], "category": "herb", "description": "Horny Goat Weed — also called Epimedium, Yin Yang Huo (µ╖½τ╛èΦù┐) in Traditional Chinese Medicine, and barrenwort or bishop's hat in Western botanical nomenclature — is a genus of flowering plants in the Berberidaceae family, with roughly 60 species concentrated in China, Korea, and Japan, of which Epimedium sagittatum, E. brevicornum, E. koreanum, E. grandiflorum, E. pubescens, and E. wushanense are the most medicinally important. The English common name derives from a traditional Chinese folk story about a goat herder named Yang who noticed that his goats became unusually sexually active after grazing on the plant — a story that has attached to the herb for at least 2,000 years and that captures, in folk form, one of its two most established pharmacological effects. The Chinese name Yin Yang Huo literally translates as \"licentious goat herb,\" and the plant has been used in Traditional Chinese Medicine since the Shen Nong Ben Cao Jing (the oldest Chinese materia medica, dating to approximately 200 CE) for a constellation of indications that map onto what TCM calls \"kidney yang deficiency\" — a pattern including sexual dysfunction, fatigue, cold extremities, low back and knee pain, weakness of the legs, frequent urination, poor memory, and age-related decline. Modern pharmacological research has validated major components of this traditional use through work centered on the plant's distinctive prenylflavonoid compounds, particularly icariin, icariside II, baohuoside I, and the associated icaritin — compounds found almost exclusively in Epimedium species and rarely elsewhere in the plant kingdom. The pharmacology is genuinely unusual because icariin acts through multiple distinct mechanisms that collectively explain the herb's traditional reputation. First and most famously, icariin is a weak phosphodiesterase-5 (PDE5) inhibitor — the same class of drug that includes sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra). The PDE5 inhibition is far weaker than the pharmaceutical drugs (roughly 10,000-100,000 times less potent per unit mass), but it is real and demonstrable in vitro and in isolated tissue preparations, and it provides a plausible mechanism for the herb's traditional use in erectile dysfunction. Second, icariin has mild aromatase inhibition, endothelial nitric oxide synthase (eNOS) enhancement, and direct effects on penile smooth muscle calcium handling, which collectively support erectile function through pathways distinct from PDE5 inhibition. Third, icariin and its active metabolites have bone-anabolic effects mediated by selective estrogen receptor modulation (SERM-like activity at estrogen receptor alpha, particularly in bone tissue), which has led to substantial Chinese clinical research on Epimedium extracts for post-menopausal osteoporosis and age-related bone loss. Fourth, icariin has neuroprotective effects mediated by reduction of oxidative stress, mitigation of beta-amyloid neurotoxicity in experimental models, and modulation of BDNF signaling — mechanisms that align with the traditional use for memory and cognitive decline in aging. Fifth, and perhaps surprisingly, icariin has cardioprotective effects through improvements in endothelial function, modulation of lipid metabolism, and anti-inflammatory activity in vascular tissue. The clinical evidence base is moderate in size, mostly Chinese, and concentrated in three areas: erectile dysfunction and sexual function (small-to-moderate trials showing mild-to-moderate benefits, particularly for mild ED), post-menopausal osteoporosis and bone loss (larger Chinese trials with favorable bone density and marker outcomes), and neurocognitive effects in aging (smaller trials and extensive preclinical work). Most commercial products are either whole leaf extract (marketed as a general \"Horny Goat Weed\" supplement) or icariin-standardized extracts (10%, 20%, 40%, 60%, or 98% icariin, depending on the product tier). Traditional Chinese preparations use the whole processed leaf in decoctions, typically 3-9 grams per day. Modern extract dosing varies dramatically with standardization — a 10% icariin extract at 500 mg twice daily provides approximately 100 mg/day of icariin, while a 20% extract at the same gram dose provides 200 mg/day, which spans the range used in most clinical trials. Horny Goat Weed is generally well-tolerated but is not a trivial supplement; it has genuine cardiovascular and endocrine effects, should not be combined with pharmaceutical PDE5 inhibitors or nitrate medications, and has theoretical interactions with estrogen-sensitive conditions, aromatase modulation, and blood pressure management.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/horny-goat-weed" }, { "id": "de7d90ea-2ec1-49af-bf73-bb3031b2de8e", "slug": "humanin", "name": "Humanin", "aliases": [ "HNG" ], "category": "Recovery", "description": "Humanin is a 24-amino-acid peptide (MAPRGFSCLLLLTSEIDLPVKRRA) encoded within the mitochondrial 16S ribosomal RNA gene and translated from a short open reading frame that was not recognized as biologically active until 2001, when Hashimoto and colleagues identified it in a screen for factors that protect neurons from Alzheimer's disease-associated toxicity ([Hashimoto et al., 2001]). The discovery was methodologically elegant: using a cDNA library from the occipital lobe of a patient who had died of Alzheimer's disease but whose specific brain region had remained clinically unaffected, they identified a peptide that protected cultured neurons from beta-amyloid toxicity, and traced its origin back to an unexpected locus in the mitochondrial genome. The finding launched an entire field — mitochondrial-derived peptides or MDPs — that now includes humanin, MOTS-c, SHLP1 through SHLP6, and related small peptides encoded within mitochondrial DNA that have systemic endocrine and autocrine signaling functions. Humanin itself has since been shown to protect cells from a range of stressors including beta-amyloid toxicity, Bax-induced apoptosis, oxidative stress, hypoxia-reoxygenation, and serum starvation ([Guo et al., 2003]; [Tajima et al., 2002]; [Zhai et al., 2005]). It also has metabolic effects including improved insulin sensitivity, enhanced glucose disposal, and protection against atherosclerosis in mouse models ([Muzumdar et al., 2009]). Plasma humanin concentrations are relatively high in young humans and decline with age, which has prompted speculation that restoring humanin to youthful levels could be a longevity intervention ([Cobb et al., 2016]). The practical reality of humanin as a research peptide is more complicated than the mechanism summary suggests. The endogenous peptide has a short circulating half-life (minutes), is rapidly cleared, and does not cross the blood-brain barrier efficiently in its native form. Synthetic analogs with substitutions to improve stability and potency have been developed — the most studied is HNG (humanin S14G), which is roughly 1000-fold more potent than wild-type humanin in several assays and has been used in most of the preclinical therapeutic work ([Hashimoto et al., 2001]; [Yen et al., 2013]). Other analogs with different substitution patterns (HNA, [Gly14]-HN, colivelin which fuses humanin with the activity-dependent neurotrophic factor peptide) have been generated for various experimental purposes. What is being sold as \"humanin\" by research-chemical peptide vendors is typically the wild-type 24-amino-acid sequence, not HNG, and the wild-type peptide has substantially less in vivo activity than the published HNG data would suggest. Consumers reading mechanism summaries that cite HNG mouse studies and then buying wild-type humanin are effectively purchasing a different compound than the one described in the research. Humanin has not been developed as an FDA-approved drug and has no human trial data establishing a therapeutic dose or efficacy profile. It remains an investigational peptide with strong mechanistic rationale, extensive preclinical evidence, and no clinical validation. This entry covers what the peptide actually does, how it signals through its receptor complex, what the animal data show in models of aging, neurodegeneration, diabetes, and cardiovascular disease, where the evidence is strongest and where it is thin, and what realistic use looks like for someone interested in mitochondrial-derived peptide biology. If the goal is neuroprotection or metabolic improvement, FDA-approved interventions (lifestyle, approved medications) should be fully explored first. If the goal is participating in the cutting edge of mitochondrial peptide research as a self-experimenter, this page is the most honest summary available of what the evidence does and does not support.", "half_life": "Short - on the order of minutes. Wild-type 24-amino-acid humanin is rapidly cleared from plasma (rodent data); the S14G analog (HNG) is more metabolically stable. No human pharmacokinetic data exist.", "molecular_weight": "2687.26 Da", "molecular_mass": "2687.26 g/mol", "amino_acid_sequence": "MAPRGFSCLLLLTSEIDLPVKRRA", "administration_routes": [], "dose_range_mcg": "Research compound — no established human doses", "dosing_frequency": "Once daily subcutaneous in anecdotal use (some split twice daily for the short half-life); no validated human regimen", "cycle_length": "Anecdotally 4-12 weeks on / 4-8 weeks off; no clinical basis", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Not approved for human use (research use only)", "trial_phase": "", "cas_number": "312781-62-3", "iupac_name": "Met-Ala-Pro-Arg-Gly-Phe-Phe-Ser-Cys-Leu-Leu-Leu-Thr-His-Ser-Glu-Ile-Asp-Leu-Pro-Val-Lys-Arg-Arg-Ala", "chemical_formula": "C127H204N34O35S", "potential_benefits": [ "Cytoprotective effects", "Anti-apoptotic properties", "Neuroprotective potential", "Cardioprotective effects", "Cellular stress resistance" ], "research_fields": [], "pubmed_count": 257, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/humanin" }, { "id": "58ee338d-6319-4dbd-9ff3-8a5636c7b341", "slug": "hydroxytyrosol", "name": "Hydroxytyrosol", "aliases": [ "HT", "3,4-DHPEA", "DOPET", "Hytolive", "Benolea" ], "category": "Polyphenol", "description": "Hydroxytyrosol (3,4-dihydroxyphenylethanol, abbreviated HT or 3,4-DHPEA) is the smallest of the natural phenolic compounds produced by the olive tree and — pharmacologically — the single most important molecule in the olive polyphenol family. Chemically, hydroxytyrosol is a catechol: a benzene ring substituted with two adjacent hydroxyl groups at the 3' and 4' positions, connected through a two-carbon ethyl bridge to a terminal hydroxyl. This catechol motif is what makes hydroxytyrosol so biologically active — the same structural feature that gives catecholamines (dopamine, norepinephrine, epinephrine) their extraordinary chemical reactivity, and the same feature that gives EGCG, quercetin, and other catechol-bearing polyphenols their antioxidant kinetics. Hydroxytyrosol differs from dopamine by a single nitrogen: it is the \"dopamine without the amine,\" a biosynthetic cousin of our endogenous neurotransmitters. This structural simplicity gives hydroxytyrosol exceptional radical-scavenging kinetics, tight affinity for LDL particles, ready crossing of the blood-brain barrier, and a pharmacology that bridges the polyphenol and catecholamine worlds.\n\nHydroxytyrosol is found in olive leaves (up to several hundred mg/kg), olive fruit (200–4,000 mg/kg depending on cultivar and ripeness), olive mill wastewater (a major agricultural waste product that is one of the richest natural hydroxytyrosol sources and a focus of \"circular bioeconomy\" extraction technology), and — critically — in extra-virgin olive oil, where it appears both as free hydroxytyrosol and as the hydrolysis product of oleuropein during oil pressing, storage, and gastric passage. Premium high-polyphenol EVOO delivers 10–30 mg/kg of free hydroxytyrosol plus 100–500 mg/kg of hydroxytyrosol-releasing secoiridoids (oleuropein and oleuropein aglycone), which are hydrolyzed to hydroxytyrosol during digestion. This is why olive polyphenol content is reported as \"hydroxytyrosol and its derivatives\" in both EFSA regulation and the scientific literature — the hydroxytyrosol equivalent is the biologically meaningful unit.\n\nBodyHackGuide covers hydroxytyrosol as the most clinically validated polyphenol molecule in the olive family and — alongside its precursor [oleuropein](/compound/oleuropein) — the centerpiece of the Mediterranean-diet cardiovascular-protection mechanism. Hydroxytyrosol has the singular distinction of being the only natural polyphenol with an EFSA-approved cardiovascular health claim. Since 2012, the European Food Safety Authority has authorized the claim that \"olive oil polyphenols contribute to the protection of blood lipids from oxidative stress\" for any olive oil providing at least 5 mg of hydroxytyrosol and its derivatives per 20 g serving. No other polyphenol — not resveratrol, not EGCG, not curcumin, not any flavonoid — has received an approved EFSA Article 13.5 health claim. The EFSA decision was driven by the mechanistic depth and clinical reproducibility of the hydroxytyrosol oxidation-protection signal, anchored in the Covas 2006 EUROLIVE trial, which demonstrated dose-dependent reductions in circulating oxidized LDL in 200 healthy men given olive oils of increasing polyphenol content over three 3-week intervention periods.\n\nThe clinical case for hydroxytyrosol rests on four main evidence pillars. First, the EUROLIVE trial established that olive polyphenol content — not fatty-acid composition — drives LDL oxidation protection. Second, the PREDIMED cardiovascular primary-prevention trial (Estruch 2013 PMID 23432189 and 2018 reanalysis PMID 29897866) demonstrated that adding high-polyphenol EVOO to a Mediterranean dietary pattern reduced major cardiovascular events by 30% over a median 4.8-year follow-up in 7,447 high-risk adults — an effect size matching high-intensity statin therapy and attributable primarily to the hydroxytyrosol/oleuropein polyphenol load of the intervention oil. Third, a growing body of smaller RCTs with direct hydroxytyrosol isolates (Hytolive, Benolea) at 5–50 mg/day has shown consistent signals for improved endothelial function, reduced oxidized LDL, modest blood pressure reduction, and improved lipid profile. Fourth, the mechanistic literature is unusually deep for a food polyphenol — hydroxytyrosol is one of the best-characterized dietary antioxidants in terms of pharmacokinetics, phase-II metabolism, Nrf2 activation, and direct radical-scavenging kinetics.\n\nCommercially, hydroxytyrosol is available as branded standardized ingredients from the olive supply chain. Hytolive (Genosa, Spain) is derived from olive mill wastewater via a patented aqueous extraction, standardized to 10–25% hydroxytyrosol, and has been the ingredient in most published hydroxytyrosol RCTs. Benolea (Frutarom/IFF) is olive-leaf-derived, standardized to similar hydroxytyrosol and oleuropein content. Olivactiv, Bioactive HT, and other branded HT ingredients occupy the same space. Consumer products range from low-dose cardiovascular blends (5–10 mg HT per capsule) to athletic-performance formulations (25–50 mg HT per serving). Prices run $0.20–$1.50 per mg of standardized HT, making dedicated hydroxytyrosol a premium-tier supplement relative to raw olive leaf extract or culinary EVOO. For most users, high-polyphenol EVOO (2–3 tablespoons daily) remains the most cost-effective and evidence-aligned hydroxytyrosol delivery vehicle; standardized HT supplementation is reserved for specific use cases where precise dose control, rapid absorption, or maximum polyphenol density is required.\n\nThe hydroxytyrosol literature also extends beyond cardiovascular medicine into neuroprotection (Parkinson's disease models, cognitive aging studies), metabolic disease (insulin sensitization, hepatic lipid reduction in NAFLD models and early clinical trials), athletic performance (exercise-induced oxidative stress, muscle recovery), skin biology (UV protection, fibroblast protection from oxidative damage), and emerging anti-cancer mechanistic work (particularly in colorectal and breast cancer preclinical models). The neuroprotective story is notable because hydroxytyrosol crosses the blood-brain barrier more readily than most dietary polyphenols — a consequence of its small size, catechol structure, and modest lipophilicity — and because dopaminergic neurons in the substantia nigra are uniquely vulnerable to oxidative stress from dopamine auto-oxidation, which hydroxytyrosol (as a structural cousin of dopamine) may help buffer. Clinical evidence in neurological disease is still preclinical and early-translational, but the mechanistic rationale is strong.\n\nHydroxytyrosol is best understood as the absorbed, bioavailable, pharmacologically active form of the olive polyphenol family. Oleuropein delivers it via hydrolysis; high-polyphenol EVOO delivers it as a matrix effect with oleocanthal and other secoiridoids; direct hydroxytyrosol isolates deliver it unmodified with maximum dose precision. For users who want a known, standardized polyphenol dose — particularly athletes, users with specific cardiovascular or metabolic indications, or those whose dietary EVOO intake is constrained — direct hydroxytyrosol supplementation is the cleanest approach. For routine cardiovascular protection within a Mediterranean pattern, high-polyphenol EVOO wins on cost, nutritional matrix, and cultural sustainability.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 2277, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/hydroxytyrosol" }, { "id": "6f7f512f-3de1-48fe-a63a-b348800fa51b", "slug": "igf-1-des", "name": "IGF-1 Des(1-3)", "aliases": [ "IGF-1 DES", "DES IGF-1", "IGF-1 Des-1-3" ], "category": "Anabolic Peptide", "description": "IGF-1 Des(1-3) is a truncated variant of insulin-like growth factor-1 missing the first three N-terminal amino acids (Gly-Pro-Glu). The truncation reduces binding affinity to IGF binding proteins (IGFBPs) ~10-fold, leaving more free peptide available to bind IGF-1 receptors at the injection site. Net effect: higher local potency than standard IGF-1 LR3 at the same molar dose.\n\nMost popular among bodybuilders and research peptide users for site-specific intramuscular injections post-workout. Rapid onset, short serum window.", "half_life": "~20-30 minutes serum", "molecular_weight": "~7,371 Da", "molecular_mass": "", "amino_acid_sequence": "TLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA", "administration_routes": [ "Subcutaneous", "Intramuscular" ], "dose_range_mcg": "20-100 mcg", "dosing_frequency": "Once daily on training days", "cycle_length": "4-6 weeks per cycle, 4 weeks off", "common_vial_sizes": [ "1mg" ], "research_stage": "Preclinical / Research peptide", "approval_status": "Not FDA-approved.", "trial_phase": "Preclinical / Research peptide", "cas_number": "", "iupac_name": "", "chemical_formula": "~7649 Da (truncated IGF-1)", "potential_benefits": [ "Higher local potency than IGF-1 LR3 (reduced IGFBP binding)", "Site-specific hypertrophy when injected intramuscularly", "Activates PI3K-Akt for protein synthesis", "Used in research-peptide bodybuilding protocols" ], "research_fields": [ "Skeletal muscle hypertrophy", "IGF receptor signaling", "IGF binding proteins" ], "pubmed_count": 32, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/igf-1-des" }, { "id": "3f67c2d8-cf62-4643-9cbc-54a6e214813d", "slug": "igf-1-lr3", "name": "IGF-1 LR3", "aliases": [ "IGF-1 Long R3" ], "category": "Growth Hormone / IGF-1 Axis", "description": "IGF-1 LR3 (Long R3 IGF-1) is a synthetic analog of human insulin-like growth factor 1 modified at two positions to dramatically extend its serum half-life and amplify its tissue bioactivity compared to native IGF-1. The \"LR3\" designation describes the two key modifications:\n\n- **\"L\" (Long):** A 13-amino-acid N-terminal extension peptide added to the native 70-amino-acid IGF-1 sequence\n- **\"R3\":** An arginine substitution at position 3 (replacing the native glutamic acid)\n\nTogether these modifications produce a critical pharmacologic consequence: **dramatically reduced binding affinity for the insulin-like growth factor binding proteins** (IGFBPs), particularly IGFBP-3 which normally sequesters 95-99% of circulating IGF-1 in an inactive reservoir. Free (unbound) IGF-1 is the bioactive form that binds the IGF-1 receptor and drives muscle protein synthesis. By escaping IGFBP sequestration, IGF-1 LR3 produces:\n\n- **Serum half-life of 20-30 hours** (native IGF-1: ~12 minutes)\n- **3-10 times higher bioactive concentration** in target tissues\n- **Stronger and more sustained IGF-1 receptor signaling** per dose\n\nIGF-1 LR3 was originally developed by [Francis et al. in the early 1990s] at CSIRO Australia for cell culture applications — specifically, driving growth of mammalian cell lines in bioreactors where the IGFBPs from fetal bovine serum would otherwise neutralize added growth factor. This commercial research-chemical origin is the reason IGF-1 LR3 has been widely available in the research-peptide supply chain for decades despite never pursuing a clinical drug approval pathway.\n\n**There is no FDA-approved indication for IGF-1 LR3** in human use. Mecasermin (recombinant native human IGF-1, Increlex) is FDA-approved for severe primary IGF-1 deficiency in children but is mechanistically very different — it is native IGF-1 with normal IGFBP binding and a short half-life.\n\nOff-label and research-chemical use of IGF-1 LR3 is concentrated in the bodybuilding and athletic performance community, typically at doses of 20-60 mcg SC once daily or post-workout. It is one of the **most potent anabolic peptides** available but also one of the **highest-risk** due to hypoglycemia (cross-reactivity at the insulin receptor), unintended peripheral tissue growth (IGF-1R is expressed on virtually every tissue in the body including the intestine, organs, and connective tissue), and theoretical cancer-promotion risk from sustained supraphysiologic mitogenic signaling. Users who choose IGF-1 LR3 should understand the risk profile differs fundamentally from GHRH/GHS peptides that work through the body's native pituitary axis.", "half_life": "20-30 hours (community/vendor estimate; no published human PK study of IGF-1 LR3) vs ~12 minutes for native IGF-1", "molecular_weight": "9117 Da", "molecular_mass": "9117.6 g/mol", "amino_acid_sequence": "MFPAMPLSSLFVNGPRTLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA (83 residues; average MW ~9117 Da). Structure: a 13-amino-acid N-terminal extension (MFPAMPLSSLFVN) fused to the 70-residue mature human IGF-1 sequence carrying an arginine-for-glutamate substitution at position 3 (Glu3Arg).", "administration_routes": [ "Subcutaneous", "Intramuscular" ], "dose_range_mcg": "20-80 mcg per day", "dosing_frequency": "Once daily, typically post-workout or in the morning", "cycle_length": "4–6 weeks maximum (to prevent receptor desensitization and hypoglycemia risk)", "common_vial_sizes": [ "100mcg", "1mg" ], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "Phase 2", "cas_number": "946870-92-4", "iupac_name": "Insulin-like growth factor I, 7-70-peptide (synthetic) 1-[(2S)-2-amino-2-carboxyethyl] compound", "chemical_formula": "C400H625N111O115S9", "potential_benefits": [ "Muscle hypertrophy", "Recovery", "Protein synthesis", "Fat metabolism", "Glucose uptake" ], "research_fields": [ "Muscle wasting", "Myopathy", "Growth disorders", "Body composition" ], "pubmed_count": 40, "pubchem_cid": 91976740, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/91976740/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/igf-1-lr3" }, { "id": "980e7d63-b4fc-4d56-87a5-81222d177b3a", "slug": "indole-3-propionamide", "name": "Indole-3-propionamide (IPAM)", "aliases": [ "Indolepropionamide", "Indole-3-propionamide", "3-(1H-indol-3-yl)propanamide", "NSC523262" ], "category": "Other", "description": "IPAM is the market abbreviation for indole-3-propionamide, the amide of indole-3-propionic acid and a close structural relative of melatonin. It is a defined and identifiable molecule, PubChem CID 351791, CAS 5814-93-7, but the literature behind it is unusually thin: essentially one substantive biological paper, published in 2010 (PMID: 20421998).\n\nThat paper is worth describing carefully, because almost everything claimed for the compound traces back to it. The authors designed the amide from indole-3-propionic acid to obtain a less polar molecule that crosses membranes more easily, then discovered that it also occurs naturally. After an oral tryptophan load of 300 mg/kg in one-month-old male Sprague-Dawley rats, brain levels of indole-3-propionamide, melatonin and indole-3-propionic acid all rose to reproducibly measurable amounts. When 0.5 mg/kg was given intraperitoneally, indole-3-propionamide reached high brain concentrations at 2, 4 and 8 h while melatonin and indole-3-propionic acid at the same dose did not raise their own barely detectable baselines (PMID: 20421998).\n\nThe proposed mechanism is mitochondrial rather than receptor-mediated. The compound appears to act at complex I of the respiratory chain as a recyclable electron and proton carrier, stabilizing electron flow and reducing electron leakage, so that fewer reactive oxygen species are produced in the first place rather than scavenged afterwards. In brain mitochondria from young and 20-month-old rats it antagonized the age-related fall in membrane potential and blocked the collapse of proton potential caused by doxorubicin, antimycin A and the uncoupler FCCP. In mouse brain mitochondria at 10 nM it increased complex I and complex IV activity. In a hydroxyl radical generating system it reduced radical formation without producing pro-oxidant intermediates, and it reduced hydroxyl radical mediated DNA damage in rat forebrain homogenate with an IC50 of 0.18 micromolar against 1.4 micromolar for melatonin (PMID: 20421998).\n\nThe headline result in that paper is a lifespan experiment in the bdelloid rotifer Philodina acuticornis odiosa, where mean lifespan rose from 24.6 days to 90.5 days at the highest concentration tested, with larger body size and more offspring per animal. A rotifer is a very long way from a person, and no vertebrate lifespan or healthspan study has followed.\n\nTwo cautions belong on this page. First, no toxicology study, no pharmacokinetic study beyond those brain concentration measurements in rats, and no human exposure of any kind has been published for this compound. Second, recent medicinal chemistry papers describing 1H-indole-3-propionamide compounds as selective NaV1.7 inhibitors for pain concern a series of substituted derivatives rather than indole-3-propionamide itself, and should not be read as evidence about this molecule (PMID: 39881860, PMID: 42503835). Indole-3-propionamide has no FDA or EMA record, no clinical development program and no registered trial, and material sold as IPAM is a research-use-only compound in the US market.", "half_life": "Not established in humans; after intraperitoneal administration of 0.5 mg/kg to one-month-old male Sprague-Dawley rats, brain concentrations were 691 pg indole per mg protein at 2 h, 562 at 4 h and 361 at 8 h, which the authors described as a long half-life relative to melatonin (PMID: 20421998)", "molecular_weight": "188.23 g/mol", "molecular_mass": "188.23 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Intraperitoneal injection (rodent studies)", "Oral (form sold on the research chemical market)" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Not approved anywhere and not in clinical development; there is no FDA or EMA record for indole-3-propionamide and no registered clinical trial. All published biological work is in cell-free systems, rodent mitochondrial preparations, rats and rotifers (PMID: 20421998). Material sold as IPAM is a research-use-only compound in the US market.", "trial_phase": "", "cas_number": "5814-93-7", "iupac_name": "", "chemical_formula": "C11H12N2O", "potential_benefits": [ "Reversed the age-related fall in mitochondrial membrane potential in brain mitochondria from young and 20-month-old Sprague-Dawley rats at 10 nM (PMID: 20421998)", "Prevented the collapse of mitochondrial proton potential caused by doxorubicin, antimycin A and FCCP in rat brain mitochondria (PMID: 20421998)", "Increased complex I and complex IV activity in brain mitochondria from young and old male Swiss Webster mice (PMID: 20421998)", "Extended mean lifespan of the bdelloid rotifer Philodina acuticornis odiosa from 24.6 to 90.5 days at the highest concentration tested, with increased body size and offspring number (PMID: 20421998)", "Reduced hydroxyl radical mediated DNA damage in rat forebrain homogenate with an IC50 of 0.18 micromolar, against 1.4 for melatonin and 7.46 for indole-3-propionic acid (PMID: 20421998)" ], "research_fields": [ "Mitochondrial bioenergetics", "Antioxidant chemistry", "Aging research", "Tryptophan metabolites" ], "pubmed_count": 0, "pubchem_cid": 351791, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/indole-3-propionamide" }, { "id": "a960b611-3637-4c20-9df2-54cd4170cbe5", "slug": "inositol", "name": "Inositol", "aliases": [ "Myo-inositol", "D-chiro-inositol", "DCI", "Cyclohexanehexol", "Vitamin B8 (historical, now disputed)", "meso-inositol", "Inofolic", "Inofolic Plus" ], "category": "Nootropic", "description": "**Inositol** is a naturally-occurring **cyclic sugar alcohol (cyclohexanehexol)** that functions as a critical structural component of cell membranes and a **second-messenger precursor** in intracellular signaling. Of the nine possible stereoisomers of inositol, only two — **myo-inositol (myo-I)** and **D-chiro-inositol (DCI)** — have significant biological activity in human physiology. These two isomers serve complementary roles: myo-inositol is the dominant form (~99% of tissue inositol), supports phosphatidylinositol signaling and serves as the precursor for inositol polyphosphates (IP3, IP4, etc.) that mediate insulin signaling and calcium release; D-chiro-inositol is a minor form (~1%) but has distinct insulin-related effects including roles in glycogen synthesis and lipid metabolism. The body synthesizes ~4 grams/day of inositol endogenously from glucose (primarily in kidneys) and obtains additional inositol from diet (fruits, beans, grains, nuts), so frank inositol deficiency is rare in healthy adults. However, **supplemental inositol at pharmacologic doses (2-18g/day)** produces substantial clinical effects that are used therapeutically across several domains including **polycystic ovary syndrome (PCOS)**, **insulin resistance and metabolic syndrome**, **anxiety and panic disorders**, **obsessive-compulsive disorder**, **depression**, **gestational diabetes prevention**, and **fertility/IVF tuning**.\n\nThe therapeutic history of inositol supplementation reflects parallel lines of research in psychiatry and reproductive endocrinology. In psychiatry, **Levine et al. 1995-1997** and **Fux et al. 1996, 1999** (PMIDs: 8780423, 10071466) established that high-dose oral myo-inositol (12-18g/day) produces anxiolytic effects equivalent to fluvoxamine (Luvox, an SSRI) for panic disorder and agoraphobia, and clinically meaningful improvement in obsessive-compulsive disorder symptoms. In reproductive endocrinology, **Unfer and colleagues** at the Unfer Institute in Rome established that **myo-inositol supplementation (2-4g/day)** improves ovulation, reduces hyperandrogenism, and improves pregnancy rates in women with PCOS — with meta-analyses consolidating these findings across 20+ trials (**Unfer 2017** *Int J Endocrinol*, **Laganà et al. 2018**). In obstetrics, **D'Anna and colleagues** at the University of Messina demonstrated that **myo-inositol 4g/day** taken from early pregnancy reduces the incidence of **gestational diabetes mellitus (GDM)** in high-risk pregnancies by approximately 50% (**D'Anna 2013, 2015** PMIDs: 23345600, 25829487) — findings with substantial public-health implications that have been incorporated into some international guidelines for GDM prevention.\n\nThe **40:1 myo-inositol to D-chiro-inositol ratio** has emerged as the dominant combination convention for PCOS and fertility applications, based on research by **Nordio, Unfer, and colleagues** showing that this ratio approximates the physiological ratio in follicular fluid and produces superior outcomes compared to either isomer alone or other ratios. This 40:1 ratio (typically 2000mg myo-I + 50mg DCI) is embodied in commercial products like Inofolic Plus and is the default recommendation for most reproductive applications. For non-reproductive applications (anxiety, OCD, depression, insulin resistance), myo-inositol alone at higher doses is more commonly used.\n\n**Mechanistic understanding of inositol's clinical effects** centers on its role in **insulin signaling** and **phosphoinositide second messenger systems**. Insulin binding to its receptor triggers a signaling cascade that includes generation of inositol phosphoglycans (IPGs) from glycosylphosphatidylinositol (GPI) lipids — myo-inositol-containing IPGs (MI-IPG) activate enzymes promoting glucose uptake and utilization, while D-chiro-inositol-containing IPGs (DCI-IPG) activate enzymes promoting glycogen synthesis. Insulin-resistant states — including PCOS (where ovarian insulin resistance is a core feature), obesity-related metabolic syndrome, and type 2 diabetes precursors — involve dysregulation of these IPG systems. Supplemental inositol appears to partially restore signaling efficiency, producing improvements in insulin sensitivity, reduced compensatory hyperinsulinemia, reduced ovarian androgen production, improved ovulation, and (in pregnancy) reduced gestational diabetes risk. In psychiatric applications, the mechanism is less clear but likely involves the phosphatidylinositol-linked neurotransmitter signaling systems (serotonin 5-HT2, muscarinic cholinergic, adrenergic-α1 receptors all signal partly through PI-PLC/IP3), with inositol depletion potentially implicated in lithium's mood-stabilizing mechanism (the \"inositol depletion hypothesis\" of Berridge).\n\n**Regulatory status is complex**: Inositol is classified as a **dietary supplement** in the United States and most countries, available without prescription. It is generally-recognized-as-safe (GRAS) at typical doses. In some European countries, pharmaceutical-grade inositol preparations are marketed for PCOS and gestational diabetes prevention with more formal regulatory oversight. It was historically designated \"Vitamin B8\" but this classification has been largely abandoned since humans synthesize sufficient inositol endogenously. The safety profile across extensive clinical use (including high-dose 12-18g/day psychiatric use and millions of pregnancies exposed to 4g/day for GDM prevention) is excellent.\n\nSee also [Metformin](/compound/metformin), [Berberine](/compound/berberine), [DHEA](/compound/dhea), [Ashwagandha](/compound/ashwagandha), [Magnesium](/compound/magnesium), [N-acetylcysteine](/compound/n-acetyl-cysteine), [Vitamin D](/compound/vitamin-d), and [Omega-3](/compound/omega-3) for adjacent insulin-sensitizing, anti-inflammatory, and hormonal-support compounds commonly used in PCOS and metabolic tuning. This is educational content and not medical advice — while inositol is very safe, clinical applications (particularly in pregnancy, with psychotropic medications, or with diabetes medications) warrant physician-level guidance.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 3870, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/inositol" }, { "id": "c75a0c5b-2546-44b2-bb1f-d10d7c060011", "slug": "iodine", "name": "Iodine", "aliases": [ "I", "I-", "Iodide", "Potassium iodide", "KI", "Sodium iodide", "NaI", "Molecular iodine", "I2", "Lugol's solution", "Lugol's iodine", "Iodoral", "SSKI", "Nascent iodine", "Iosol", "Kelp iodine", "Bladderwrack iodine" ], "category": "Mineral", "description": "Iodine is a halogen trace mineral and an obligate substrate for thyroid hormone synthesis — the single biochemical fact that dominates all clinical thinking about iodine. Without adequate iodine the thyroid gland cannot synthesize thyroxine (T4) or triiodothyronine (T3), and the downstream consequences of thyroid hormone deficiency range from fatigue and weight gain in mild adult deficiency to irreversible neurodevelopmental impairment (endemic cretinism) in offspring of severely deficient mothers. Iodine deficiency is the leading global cause of preventable intellectual disability, which the WHO has pursued aggressively through universal salt iodization programs since the 1990s, driving dramatic reductions in goiter prevalence and cretinism in previously affected regions. The adult RDA is 150 mcg/day, pregnancy 220 mcg/day, lactation 290 mcg/day, and the tolerable upper limit for adults is 1,100 mcg/day — a relatively narrow therapeutic window compared to most minerals, reflecting the fact that both deficiency and excess can destabilize thyroid function. The iodine story is geographically and historically uneven: populations living far from coastlines and consuming iodine-poor soils (the Alpine countries, the Great Lakes region of the United States, central Africa, parts of Southeast Asia, and the Himalayan plateau) developed endemic goiter and cretinism over generations before iodized salt became routine. The United States began salt iodization in 1924 in response to the \"goiter belt\" around the Great Lakes, and iodine deficiency became rare in subsequent decades — but recent NHANES data show that median urinary iodine concentrations have been trending downward since the 1970s, mild-to-moderate iodine insufficiency has re-emerged in some US subpopulations especially pregnant women, and the iodine content of commercial dairy (historically a major American iodine source via iodophor sanitizers and iodine-supplemented feed) has become more variable. At the same time a vocal subculture promotes high-dose iodine supplementation — Lugol's solution, Iodoral, \"SSKI\" (saturated solution of potassium iodide), and nascent iodine products delivering 12.5–50 mg per dose, which is 100–400× the RDA — citing Abraham's \"iodine project\" claims of breast and thyroid benefits. This high-dose iodine philosophy is not supported by mainstream endocrinology: the tolerable upper limit of 1,100 mcg/day exists because doses above that have caused iodine-induced hyperthyroidism in susceptible individuals (Jod-Basedow phenomenon) and paradoxical iodine-induced hypothyroidism (Wolff-Chaikoff effect escape failure) in others, and chronic high-dose iodine has precipitated or worsened autoimmune thyroid disease in people with underlying Hashimoto susceptibility. Iodine is also the substrate for radioiodine therapy (I-131) used to treat hyperthyroidism and thyroid cancer, and stable iodine (potassium iodide, KI) is the FDA-approved prophylaxis against radioactive iodine uptake in nuclear emergencies. Dietary sources concentrate in seafood (seaweed especially kelp and kombu, which can deliver 1–2 mg per gram dry weight, followed by cod, tuna, shrimp), iodized salt (the dominant population-level source), dairy from iodine-supplemented herds, and eggs. See also [Selenium](/compound/selenium) for the obligate thyroid cofactor partnership (selenium-dependent deiodinases activate T4 to T3), [Vitamin D](/compound/vitamin-d) for the broader thyroid-autoimmunity discussion, [Zinc](/compound/zinc) for the pituitary-thyroid axis trace mineral contributions, and [Vitamin B12](/compound/vitamin-b12) for pernicious anemia's association with Hashimoto disease in polyglandular autoimmunity. This overview is educational only and is not medical advice — iodine sits in a narrower therapeutic window than most nutrients, and patients with thyroid disease should not self-dose iodine without endocrinology guidance.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/iodine" }, { "id": "a1000000-0000-0000-0000-000000000007", "slug": "ipamorelin", "name": "Ipamorelin", "aliases": [ "Ipam", "IPA" ], "category": "Growth Hormone / IGF-1 Axis", "description": "Ipamorelin is a **selective pentapeptide ghrelin receptor (GHS-R1a) agonist** — one of the most studied **growth hormone secretagogues (GHS)** in the biohacking community and the modern companion to [CJC-1295 / MOD-GRF 1-29](/compound/cjc-1295). Its five-amino-acid sequence (Aib-His-D-2Nal-D-Phe-Lys-NH₂) was discovered by Novo Nordisk and published in 1998 as \"the first selective growth hormone secretagogue\" ([Raun et al., 1998]).\n\nThe word **\"selective\"** is the critical term. Earlier GHS peptides (hexarelin, GHRP-6, GHRP-2) all release GH but also raise cortisol, prolactin, and ACTH — because the ghrelin receptor is expressed on corticotrophs and lactotrophs as well as somatotrophs. Ipamorelin is the first and only GHS peptide clinically characterized as producing **no significant rise in cortisol, prolactin, ACTH, LH, FSH, or TSH** even at doses 30-fold above the GH-releasing dose ([Johansen et al., 1999]). This makes it functionally clean — you get the anabolic GH/IGF-1 axis activation without the stress-hormone and mammary-tissue side effects that plague GHRP-2 and GHRP-6.\n\nIpamorelin has an in vivo half-life of approximately **2 hours** in humans ([Gobburu et al., 1999]). Each subcutaneous injection produces a single transient GH pulse peaking at 30-60 minutes. Typical dosing is **100-300 mcg SC, 1-3 times daily**, almost always co-administered with a GHRH analog (MOD-GRF 1-29 or sermorelin) to exploit the well-documented **ghrelin × GHRH synergy** — the two pathways converge on pituitary somatotrophs through distinct second messengers and produce a GH pulse 3-5x greater than either agent alone ([Bowers et al., 1991]).\n\nClinical development by Helsinn Therapeutics (licensed from Novo Nordisk) reached Phase 2B for post-operative ileus, where IV ipamorelin demonstrated faster recovery of gastrointestinal transit after abdominal surgery ([Beck et al., 2013]). Development for that indication was subsequently halted, and **ipamorelin is not FDA-approved for any indication**. It remains widely available as a compounding-pharmacy peptide and research-use reagent.\n\nSee our [Ipamorelin Dosage Guide](/guides/dosage/ipamorelin) and [Reconstitution Tool](/tools/reconstitution/ipamorelin) for protocol specifics. The standard stack partner is documented at [/compound/cjc-1295](/compound/cjc-1295).", "half_life": "~2 hours (plasma)", "molecular_weight": "711.9 Da", "molecular_mass": "711.86 g/mol", "amino_acid_sequence": "Aib-His-D-2-Nal-D-Phe-Lys-NH2", "administration_routes": [ "subcutaneous", "intravenous (clinical only)" ], "dose_range_mcg": "100-300 mcg subcutaneous 1-3x daily (most commonly 200-300 mcg pre-bedtime); often combined with CJC-1295 without DAC at 100-300 mcg", "dosing_frequency": "1–3 times daily; most commonly once at bedtime", "cycle_length": "8–16 weeks; can be used long-term with periodic breaks", "common_vial_sizes": [ "2mg", "5mg" ], "research_stage": "Phase 2", "approval_status": "", "trial_phase": "Preclinical", "cas_number": "170851-70-4", "iupac_name": "Aib-His-D-2-Nal-D-Phe-Lys-NH2", "chemical_formula": "C38H49N9O5", "potential_benefits": [ "Increased GH pulse amplitude (selective somatotroph activation)", "Elevated IGF-1 (~30-80% over baseline) with consistent dosing", "Improved slow-wave sleep architecture", "No cortisol / prolactin / ACTH elevation (unique among GHS peptides)", "Accelerated connective tissue and wound repair", "Modest lean body mass gain + fat loss in hypogonadal adults", "Enhanced recovery between training sessions", "Synergistic effect with CJC-1295 / MOD-GRF 1-29" ], "research_fields": [ "Growth hormone deficiency", "Body composition", "Aging", "Bone density" ], "pubmed_count": 11, "pubchem_cid": 9831659, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/9831659/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/ipamorelin" }, { "id": "e2ee9198-d294-4499-b9ac-eee7092d35be", "slug": "iron", "name": "Iron", "aliases": [ "Fe", "Fe2+", "Fe3+", "Ferrous", "Ferric", "Ferrous sulfate", "Ferrous fumarate", "Ferrous gluconate", "Ferrous bisglycinate", "Iron bisglycinate", "Ferrochel", "Ferric maltol", "Accrufer", "Heme iron polypeptide", "HIP", "Proferrin", "Carbonyl iron", "Iron-dextran", "Iron sucrose", "Ferric carboxymaltose", "Injectafer", "Ferumoxytol", "Feraheme", "Sodium ferric gluconate" ], "category": "Mineral", "description": "Iron is a trace mineral with a biochemistry dominated by a single chemical property — the reversible one-electron redox between Fe²⁺ (ferrous) and Fe³⁺ (ferric) — that makes it indispensable for oxygen transport, electron transfer, and hundreds of enzymatic reactions, and simultaneously dangerous when unchaperoned in cells. The adult RDA is 8 mg/day for men and postmenopausal women, 18 mg/day for premenopausal women, 27 mg/day for pregnancy, and 9 mg/day for lactation; the tolerable upper limit is 45 mg/day from all sources combined. Iron deficiency is the most common nutritional deficiency worldwide, affecting over two billion people, and iron-deficiency anemia remains a leading global cause of disability-adjusted life years lost, disproportionately affecting menstruating women, pregnant women, infants, and populations with high parasitic burden or plant-based diets with low bioavailable iron. The clinical presentation ranges from subtle — fatigue, reduced exercise capacity, cognitive fog, restless legs — at early stages of iron-deficient erythropoiesis, to frank microcytic hypochromic anemia with pallor, tachycardia, and exertional dyspnea at advanced stages. Iron deficiency without anemia (low ferritin, normal hemoglobin) is increasingly recognized as clinically meaningful, especially in women with heavy menstrual bleeding and in endurance athletes with elevated losses; trials of iron repletion in non-anemic iron-deficient women have shown improvements in fatigue, physical capacity, and quality of life even in the absence of overt anemia. At the opposite end, iron overload is equally problematic. Hereditary hemochromatosis (most commonly HFE C282Y homozygosity, affecting roughly 1 in 200 people of Northern European ancestry) causes progressive tissue iron loading with eventual cirrhosis, diabetes, cardiomyopathy, hypogonadism, and arthritis if untreated — classically in middle-aged men with a characteristic bronze skin discoloration. Transfusion-dependent iron overload (thalassemia major, sickle cell, myelodysplastic syndromes) produces similar tissue injury through a different route. The body has no regulated excretory mechanism for iron — roughly 1 mg/day is lost through desquamation of intestinal and skin cells, and additional losses through menstruation or bleeding — so iron balance is almost entirely regulated at the absorption level via the hormone hepcidin. When iron stores are high, hepcidin rises and blocks iron absorption by degrading ferroportin on enterocytes; when iron stores are low or erythropoiesis is driven up (via the hormone erythroferrone released from maturing erythroblasts), hepcidin falls and absorption increases. This elegant single-hormone axis, worked out largely by Nemeth and Ganz in the 2000s, revolutionized our understanding of iron disorders — hereditary hemochromatosis is fundamentally a hepcidin-deficiency disease, and anemia of chronic inflammation is a hepcidin-excess disease. Dietary iron exists in two fundamental forms: heme iron from animal sources (hemoglobin and myoglobin of meat, fish, poultry) which is absorbed at 15–35% regardless of dietary context, and non-heme iron from plant sources (grains, legumes, leafy greens, fortified foods) which is absorbed at 2–20% and is highly sensitive to enhancers (vitamin C, meat, acidity) and inhibitors (phytates, tannins, calcium, tea polyphenols). This bioavailability gap is why vegetarians and vegans have higher iron deficiency rates despite similar or higher iron intake compared to omnivores — a point of practical importance for dietary planning. See also [Copper](/compound/copper) for the ceruloplasmin ferroxidase dependency that makes iron utilization copper-sensitive, [Vitamin C](/compound/vitamin-c) for the non-heme iron absorption enhancement, [Vitamin B12](/compound/vitamin-b12) for the shared anemia differential, and [Vitamin D](/compound/vitamin-d) for the hepcidin regulation link. This overview is educational only and is not medical advice — iron supplementation in men and postmenopausal women without confirmed deficiency is not appropriate given the absence of regulated excretion and the real risk of organ iron loading in undiagnosed hemochromatosis carriers.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/iron" }, { "id": "54d7facb-8789-4737-b422-79e7a21ffff4", "slug": "itpp", "name": "ITPP", "aliases": [ "OXY111A" ], "category": "Performance", "description": "ITPP (myo-inositol trispyrophosphate, sometimes written **myo-inositol tripyrophosphate** or **OXY111A** in NormOxys trial documents) is a small-molecule **allosteric effector of hemoglobin** designed to increase the amount of oxygen red blood cells release to tissues. It was developed in the mid-2000s by [Claude Nicolau](https://pubmed.ncbi.nlm.nih.gov/?term=Nicolau+C+inositol+hemoglobin) and collaborators working out of Tufts University and the French biotech **NormOxys**, with the stated goal of creating an oral or injectable drug that could mimic what the body's own 2,3-bisphosphoglycerate (2,3-BPG) does inside red blood cells — only longer-acting and more potent. The molecule was designed by phosphorylating the inositol ring until it carried six phosphate groups arranged as three pyrophosphate units, giving it a negative charge density high enough to penetrate the erythrocyte membrane and bind the central cavity of hemoglobin at the same allosteric site 2,3-BPG uses.\n\nITPP is classified as a **right-shifter** of the oxygen–hemoglobin dissociation curve. In plain language, that means a hemoglobin molecule carrying ITPP lets go of its oxygen more easily than hemoglobin alone. Under ordinary conditions, that is a problem — oxygen dropping off too early would starve the brain and cardiac muscle — but in specific pathological states where tissue is **hypoxic** (cancerous tumors, ischemic heart muscle, sickled erythrocytes, emphysematous lung), the extra unloading pressure can push oxygen into compartments that were previously starved. Preclinical and early clinical work has focused on exactly those states.\n\nIn the research body-hacking community, ITPP entered the conversation because of its theoretical **endurance-improving properties** — the same thing that made it attractive as a heart-failure drug made it attractive to dopers. It became notorious around 2011–2013 after French racehorse trainers were accused of injecting thoroughbreds with ITPP to extend their aerobic capacity; the horse-doping story accelerated the compound's visibility and also shifted how regulators catalogued it. The World Anti-Doping Agency (WADA) added ITPP to its **S2 \"hormones and metabolic modulators\"** class, and most major equine and human sport regulators now explicitly test for it. If you are a tested athlete, assume ITPP will cost you your career.\n\nThis entry takes the position that ITPP is a **research compound with intriguing preclinical data, zero human safety record outside small company-sponsored trials, no approved medical indication, and a banned-substance designation in sport**. It covers mechanism, the small amount of real human data that exists, the doping chapter, practical considerations for readers who insist on engaging with it, and the overwhelming reasons most people should leave it alone. For related oxygen-delivery–adjacent interventions, see [EPO and tissue-protective fragments](/compound/ara-290), [mitochondrial uncouplers](/compound/bam15), and [metabolic exercise mimetics](/compound/slu-pp-915).", "half_life": "", "molecular_weight": "", "molecular_mass": "660.03 g/mol", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "Research compound — IV infusion in studies, no established oral doses", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "3615-82-5", "iupac_name": "myo-Inositol trispyrophosphate", "chemical_formula": "C6H18O24P6", "potential_benefits": [ "Enhanced tissue oxygenation", "Improved aerobic performance", "Anti-tumor effects (reduces tumor hypoxia)", "Potential altitude sickness relief", "Improved exercise capacity" ], "research_fields": [], "pubmed_count": 36, "pubchem_cid": 291079, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/itpp" }, { "id": "a95ed8ad-d3dd-4de7-8a7a-d015a0597a73", "slug": "j-147", "name": "J147", "aliases": [ "J-147", "J 147", "Curcumin-derived phenyl hydrazide", "N-(2,4-dimethylphenyl)-2,2,2-trifluoro-N-((3-methoxyphenyl)methylideneamino)acetamide" ], "category": "Nootropics", "description": "J147 is a synthetic phenyl hydrazide derived from curcumin, made at the Salk Institute for Biological Studies. It came out of a screening strategy that deliberately avoided the amyloid hypothesis: instead of selecting for affinity to one disease-specific target, the group screened compounds against several cell culture models of age-associated pathology. The molecule that emerged was orally active, facilitated memory in normal rodents and prevented the loss of synaptic proteins and cognitive decline in a transgenic Alzheimer disease mouse model (PMID: 22194796). Unlike the racetams on this site, J147 was never a marketed drug anywhere and has always been an investigational compound; consumer-facing material is sold as a research chemical.\n\nThe molecular target was identified in 2018 as the mitochondrial alpha-F1-ATP synthase subunit ATP5A. Modest inhibition of ATP synthase raises intracellular calcium, which produces sustained CAMKK2-dependent activation of the AMPK and mTOR pathway, a longevity mechanism conserved across species. In mice, J147 prevented age-associated drift in the hippocampal transcriptome and plasma metabolome, and it extended lifespan in Drosophila (PMID: 29316249). Related work found that J147 and a second Salk compound increased acetyl-CoA levels by inhibiting acetyl-CoA carboxylase 1 and reduced cognitive decline and markers of aging in rapidly aging SAMP8 mice (PMID: 31742554).\n\nThe strongest preclinical result is the treatment design rather than the prevention design. Twenty-month-old APP/PS1 transgenic mice, at a stage where pathology was already advanced, were fed J147 for three months and showed improved spatial navigational memory in the water maze and rescued contextual fear conditioning, alongside induction of nerve growth factor and brain-derived neurotrophic factor (PMID: 23673233). Efficacy has also been reported in rat models of ischemic stroke, where J147 reduced infarct volume and reduced tissue plasminogen activator associated brain hemorrhage (PMID: 35309561), in mouse traumatic brain injury (PMID: 39245209) and in mouse diabetic neuropathy (PMID: 29122628).\n\nThe animal safety package is unusually detailed for a compound at this stage. Single doses of 2 g/kg in rats and mice produced no acute toxicity, and the Ames test, the hERG assay and CYP3A4 assays were all negative (PMID: 23673233). Because phenyl hydrazides can in principle be metabolized to carcinogenic aromatic amines or hydrazines, the group specifically tested this and found that J147 is not metabolized to those products in human or mouse microsomes or in mouse plasma (PMID: 23582448). A separate panel in a rat hepatoma line put the sustained concentration expected to produce toxicity at about 90 micromolar (PMID: 25364619).\n\nHuman data are the gap. A phase 1 randomized, double-blind, placebo-controlled single ascending dose study in 64 healthy young and elderly volunteers, sponsored by Abrexa Pharmaceuticals, completed in February 2020 with safety and pharmacokinetics as endpoints, and no results have been posted or published (NCT03838185). A phase 2 study of intravenous J147 combined with endovascular therapy in acute ischemic stroke began recruiting in July 2026 (NCT07430917). J147 is not approved anywhere and remains a research-use-only compound in the United States market.", "half_life": "Not established in humans; the phase 1 study measured terminal half-life but has not reported results (NCT03838185). After oral dosing in mice, half-life was about 1.5 hours in plasma and 2.5 hours in brain, with oral bioavailability calculated at 28 percent and a brain to blood ratio of about 0.5 (PMID: 23673233).", "molecular_weight": "350.34 g/mol", "molecular_mass": "350.34 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral", "Intravenous infusion" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Phase 2", "approval_status": "J147 has never been approved by any regulator for any indication. A phase 1 single ascending dose study in 64 healthy young and elderly volunteers, sponsored by Abrexa Pharmaceuticals, completed in February 2020 without posted results (NCT03838185), and a phase 2 trial of intravenous J147 with endovascular therapy in acute ischemic stroke began recruiting in July 2026 (NCT07430917). It is not a controlled substance in the United States, and material sold to consumers is a research-use-only compound with no approved medical use.", "trial_phase": "", "cas_number": "1146963-51-0", "iupac_name": "", "chemical_formula": "C18H17F3N2O2", "potential_benefits": [ "Facilitated memory in normal rodents and prevented loss of synaptic proteins and cognitive decline in transgenic Alzheimer disease mice (PMID: 22194796)", "Rescued spatial navigational memory and contextual fear conditioning in 20-month-old APP/PS1 mice treated after pathology was already advanced, with induction of nerve growth factor and brain-derived neurotrophic factor (PMID: 23673233)", "Prevented age-associated drift in the hippocampal transcriptome and plasma metabolome in mice and extended lifespan in Drosophila through ATP synthase and the AMPK pathway (PMID: 29316249)", "Reduced cognitive decline and metabolic and transcriptional markers of aging in rapidly aging SAMP8 mice (PMID: 31742554)", "Reduced infarct volume and reduced tissue plasminogen activator associated brain hemorrhage in rat models of ischemic stroke (PMID: 35309561)", "Improved neurofunctional recovery and reduced acute neurodegeneration after controlled cortical impact injury in mice (PMID: 39245209)" ], "research_fields": [ "Alzheimer disease", "Mitochondrial ATP synthase", "Brain aging", "Neuroprotection" ], "pubmed_count": 0, "pubchem_cid": 25229652, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/j-147" }, { "id": "6dab1d66-ce4b-4624-88f9-0112f05f9f22", "slug": "kavain", "name": "Kavain", "aliases": [ "Charisma" ], "category": "Nootropics", "description": "Kavain (kawain) is the principal kavalactone in kava (Piper methysticum) and the main compound behind kava's calming, anxiolytic effect. It positively modulates GABA-A receptors outside the benzodiazepine site and dampens voltage-gated Na+ and L-type Ca2+ channels. Sold as a research-use-only / supplement material in some regions; it carries a documented but idiosyncratic liver-injury risk. Research use only.", "half_life": "Not firmly established for isolated kavain in humans. Kavalactones are lipophilic and rapidly absorbed, with subjective effects generally lasting a few hours. Limited pharmacokinetic data preclude a precise elimination half-life.", "molecular_weight": "230.26 g/mol (C14H14O3; PubChem CID 837). Naturally occurring form is the (+)-enantiomer.", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "50000-250000", "dosing_frequency": "1-2 times daily, as needed; not intended for continuous long-term daily use", "cycle_length": "Time-limited - controlled kava-anxiety trials ran ~3-6 weeks [PMID:19430766][PMID:23635869]. Take regular breaks and avoid indefinite daily dosing; longer duration is a documented hepatotoxicity risk factor [PMID:20720265].", "common_vial_sizes": [], "research_stage": "Preclinical for isolated kavain (in-vitro and animal mechanistic data). Human randomized controlled trials exist for the parent standardized kava extract, of which kavain is the principal kavalactone; the single molecule itself has not been trialed alone.", "approval_status": "Not FDA-approved. Sold as a dietary supplement / research-use-only material in some regions. Whole-kava products have been banned or restricted in several countries over hepatotoxicity concerns; isolated D,L-kavain was formerly marketed as a prescription anxiolytic in Germany and later withdrawn. Research use only.", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Reduced anxiety and nervous tension - the parent standardized kava extract (of which kavain is the principal kavalactone) produced a moderate anxiolytic effect versus placebo in generalized anxiety disorder RCTs [PMID:23635869][PMID:19430766]", "Physical and mental relaxation without the heavy sedation or dependence profile of benzodiazepines, since kavain modulates GABA-A outside the benzodiazepine site [PMID:27332705]", "Calming and sleep-onset support, reported anecdotally with evening kava/kavain use (isolated-kavain benefit is extrapolated from extract data plus community use, not directly trialed)", "Mild muscle relaxation and a soothing analgesic feel, consistent with kavain's effects on voltage-gated Na+ and L-type Ca2+ channels [PMID:9690349][PMID:11642654]", "Sociable, clear-headed calm frequently described in traditional and community use of kava beverages" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/kavain" }, { "id": "3fec9838-bbea-4a1e-ad6f-d9659df17b06", "slug": "kisspeptin", "name": "Kisspeptin-10", "aliases": [ "Kisspeptin", "KISS1", "Metastin", "KP-10" ], "category": "Reproductive Hormone", "description": "Kisspeptin-10 is a 10-amino-acid C-terminal fragment of the KISS1 gene product. KISS1 was originally identified as a metastasis suppressor (hence the alternate name Metastin), but its dominant physiological role is upstream regulation of the hypothalamic-pituitary-gonadal (HPG) axis. Kisspeptin neurons in the hypothalamic arcuate nucleus drive pulsatile GnRH secretion - the trigger for LH/FSH release from the pituitary.\n\nClinical research interest is concentrated in male hypogonadism, female anovulation, and as a non-suppressive alternative to HCG for HPG-axis support during testosterone-suppressing protocols.", "half_life": "Very short: approximately 4 minutes in human plasma due to rapid enzymatic degradation. Note: the ~28-minute half-life frequently cited for 'kisspeptin' actually belongs to the longer kisspeptin-54, not kisspeptin-10. Because kisspeptin-10 clears within minutes, a single injection produces only a brief gonadotropin (LH/FSH) pulse, and sustained stimulation of the reproductive axis in research required continuous IV infusion or repeated pulsatile dosing rather than once- or twice-weekly single boluses.", "molecular_weight": "1302.5 g/mol (average; molecular formula C63H83N17O14, amidated free peptide)", "molecular_mass": "1302.5 Da (C63H83N17O14; PubChem CID 25240297)", "amino_acid_sequence": "Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2 (single-letter: YNWNSFGLRF-NH2). C-terminally amidated decapeptide; the bioactive C-terminal fragment of kisspeptin-54, corresponding to metastin 45-54 / kisspeptin 112-121. CAS 374675-21-5.", "administration_routes": [ "Subcutaneous", "Intravenous (research only)" ], "dose_range_mcg": "50-200 mcg single bolus; or 100 mcg every 90 min for pulsatile protocols", "dosing_frequency": "Single subcutaneous bolus or every-90-minute pulses", "cycle_length": "4-12 weeks per protocol depending on goal", "common_vial_sizes": [ "1mg", "5mg" ], "research_stage": "Phase 1-2 (clinical research ongoing for fertility applications)", "approval_status": "Not FDA-approved as of 2026.", "trial_phase": "Phase 1-2 (fertility applications)", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Endogenous LH and FSH stimulation via GnRH pulses", "Alternative to HCG for testicular volume preservation", "Fertility support in male hypogonadism", "Research applications in female anovulation and IVF" ], "research_fields": [ "HPG axis", "Male fertility", "Female fertility", "KISS1 receptor biology", "TRT adjuncts" ], "pubmed_count": 998, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/kisspeptin" }, { "id": "52aaf95b-308f-4140-bd94-ca38507337cc", "slug": "kisspeptin-10", "name": "Kisspeptin-10", "aliases": [ "Kisspeptin" ], "category": "Hormones & Endocrine (Non-GH)", "description": "Kisspeptin-10 (KP-10, metastin 45-54) is the C-terminal decapeptide fragment of kisspeptin, a neuropeptide product of the KISS1 gene that has emerged over the past two decades as the master regulator of reproductive endocrinology in humans and all other vertebrates studied to date. The KISS1 gene was originally cloned in 1996 in Hershey, Pennsylvania (and named after the town's iconic Hershey Kiss), initially as a metastasis-suppressor gene in melanoma cell lines. Its true reproductive function wasn't understood until 2003, when two independent research groups — one led by Nicolas de Roux in Paris and another by Stephanie Seminara at Massachusetts General Hospital — discovered that loss-of-function mutations in the G-protein-coupled receptor GPR54 (now named KISS1R) caused hypogonadotropic hypogonadism with failure of puberty. This finding transformed kisspeptin from an obscure tumor-biology gene into the gatekeeper of the entire hypothalamic-pituitary-gonadal (HPG) axis ([de Roux et al., 2003](https://pubmed.ncbi.nlm.nih.gov/14573733/), [Seminara et al., 2003](https://pubmed.ncbi.nlm.nih.gov/14573733/)).\n\nKisspeptin is synthesized as a 145-amino-acid precursor prohormone that is processed into several bioactive peptides: kisspeptin-54 (KP-54, the longest form), kisspeptin-14, kisspeptin-13, and kisspeptin-10. KP-10 retains essentially all of the biological potency of the parent molecule at the KISS1R receptor, making it the most practical form for research and therapeutic exploration — it is smaller, more stable, easier to synthesize, and equally efficacious. Kisspeptin neurons in the hypothalamus (located in the arcuate nucleus and the preoptic area / AVPV) project to GnRH neurons and release kisspeptin as the essential upstream stimulus that drives GnRH release. Without kisspeptin signaling, GnRH neurons fire infrequently or not at all, and the entire reproductive axis — LH, FSH, testosterone, estrogen, ovulation, spermatogenesis — shuts down. This is why congenital KISS1R mutations cause such a dramatic reproductive phenotype despite the rest of the HPG axis being intact ([Messager et al., 2005]).\n\nIn current clinical and research practice, kisspeptin (usually as KP-10 or KP-54) is being investigated for a range of reproductive applications: as a diagnostic probe for the integrity of the HPG axis (an alternative to or supplement to GnRH stimulation testing), as an ovulation trigger in in-vitro fertilization cycles (where it may reduce ovarian hyperstimulation syndrome risk compared to hCG), as a therapy for hypothalamic amenorrhea and functional hypothalamic hypogonadism, and as an investigational treatment for hypoactive sexual desire disorder (HSDD), with emerging work on mood and anxiety effects as well. Kisspeptin is not currently approved for any indication in the United States, but Phase II data from Imperial College London and other centers have been promising enough that pharmaceutical development is underway ([Dhillo et al., 2005], [Abbara et al., 2015]).\n\nOff-label and peptide-community interest in KP-10 centers on two use cases. First, men using suppressive regimens — testosterone replacement therapy, anabolic steroid cycles, or GnRH-axis-affecting drugs — sometimes use KP-10 during \"post-cycle\" recovery phases on the theory that stimulating endogenous GnRH release may accelerate HPG axis recovery faster than the conventional [Gonadorelin](/compound/gonadorelin) (GnRH) or [HCG (Human Chorionic Gonadotropin)](/compound/hcg) approaches. The evidence base for this use is thin — kisspeptin's efficacy in restoring suppressed axes after exogenous androgens has not been formally studied — but mechanistically plausible. Second, some researchers and a small community of users are interested in kisspeptin's effects on sexual desire and mood, which appear to be separable from its reproductive effects and mediated by kisspeptin receptor expression in limbic structures like the amygdala ([Comninos et al., 2017]).\n\nKP-10 is a legitimate research tool with meaningful clinical promise and an unusually well-characterized physiological mechanism. Unlike many grey-market peptides, the clinical evidence base is growing and the safety profile in short-term human trials at reproductive-axis doses has been clean. This entry covers KP-10's known biology, its current and investigational uses, and the considerable uncertainties that remain — particularly around long-term dosing, optimal regimens for axis recovery, and whether peripheral KP-10 administration reproduces the physiological effects of endogenous kisspeptin neuron firing.", "half_life": "~4 minutes (KP-10, plasma) - reflecting rapid peptidase degradation. The downstream LH/FSH response nonetheless persists ~1-2 hours after a dose. For comparison, kisspeptin-54 has a measured plasma half-life of ~27 minutes.", "molecular_weight": "1302.46 g/mol", "molecular_mass": "1302.46 g/mol", "amino_acid_sequence": "Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2 (single-letter: YNWNSFGLRF-NH2). Human kisspeptin-10 is the C-terminally amidated decapeptide corresponding to metastin/KISS1 residues 45-54 (KISS1 112-121); the C-terminal Arg-Phe-NH2 is the RFamide motif required for KISS1R (GPR54) activation. Formula C63H83N17O14; CAS 374675-21-5.", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Clinical (Phase 1/2)", "approval_status": "Investigational (Not FDA-Approved)", "trial_phase": "Phase 2", "cas_number": "374683-28-0", "iupac_name": "Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2", "chemical_formula": "C63H83N17O13", "potential_benefits": [ "LH/FSH stimulation", "Testosterone support", "Fertility enhancement", "Sexual arousal", "HPG axis activation" ], "research_fields": [ "Hypogonadotropic hypogonadism", "Fertility", "Sexual dysfunction", "Puberty disorders" ], "pubmed_count": 597, "pubchem_cid": 44249291, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/44249291/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/kisspeptin-10" }, { "id": "e006bde2-3392-4fe3-ac1c-18e70d337b65", "slug": "klow-blend", "name": "KLOW Blend", "aliases": [ "KLOW" ], "category": "Recovery", "description": "GHK-Cu + BPC-157 + TB-500 + KPV blend", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "N/A - KLOW is a blend of four distinct peptides, so no single sequence applies. Components: KPV = Lys-Pro-Val; GHK = Gly-His-Lys (delivered as the copper complex GHK-Cu); BPC-157 = Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val (GEPPPGKPADDAGLV); TB-500 = a synthetic fragment of thymosin beta-4.", "administration_routes": [], "dose_range_mcg": "Per manufacturer protocol", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Not approved for human use - research use only.", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "Blend", "potential_benefits": [ "Support for soft-tissue and musculoskeletal recovery (tendon, ligament, muscle)", "Wound healing and skin and connective-tissue repair", "Anti-inflammatory activity", "Angiogenesis and improved local blood supply", "Combines four complementary repair peptides (KPV, GHK-Cu, BPC-157, TB-500) in one blend" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/klow-blend" }, { "id": "9a74c110-3e2d-439a-bc3e-84ded1e9ac56", "slug": "kpv", "name": "KPV", "aliases": [ "Lys-Pro-Val" ], "category": "Recovery", "description": "KPV is a three-amino-acid peptide — Lysine-Proline-Valine — that makes up the C-terminal tail of alpha-MSH (alpha-melanocyte-stimulating hormone). With a molecular weight of only 342.4 Da, it is one of the smallest peptides in the research space, yet it preserves much of the anti-inflammatory activity of the parent 13-amino-acid alpha-MSH hormone without the pigmentation, sexual, or melanocortin-receptor effects that make full-length alpha-MSH (and analogs like [Melanotan II](/compound/melanotan-ii) and [PT-141](/compound/pt-141)) unsuitable for chronic anti-inflammatory use. That \"anti-inflammation without the side-effect profile\" is why KPV has been studied for more than three decades in conditions ranging from ulcerative colitis to atopic dermatitis to allergic airway inflammation.\n\nKPV was first characterized as the minimal anti-inflammatory fragment of alpha-MSH in the 1980s and 1990s. Researchers systematically truncated alpha-MSH (SYSMEHFRWGKPV) from both ends and tested each fragment in inflammatory models. The C-terminal tripeptide KPV turned out to be the \"business end\" for inflammation suppression — while the N-terminal sequences were responsible for pigmentation and melanocortin receptor binding. This finding — that you could keep the anti-inflammatory activity while shedding most of the hormone's other pharmacology — launched a research program that continues today ([Luger et al., 2003]).\n\nThe mechanism is unusual for a tripeptide. KPV does not appear to act primarily through classical melanocortin receptors (MC1R-MC5R). Instead, the current working model is that KPV is taken up into intestinal and immune cells via the peptide transporter PepT1 (SLC15A1), which is upregulated on inflamed epithelium. Once inside, KPV inhibits NF-kB signaling — the master inflammatory transcription factor — and downregulates the production of TNF-alpha, IL-1, IL-6, IL-8, and other pro-inflammatory cytokines. The PepT1 pathway gives KPV a degree of \"self-targeting\" to inflamed tissue, which is part of why oral dosing has shown activity in colitis models despite the peptide being too small to behave like a conventional biologic ([Dalmasso et al., 2008], [Kannengiesser et al., 2008]).\n\nResearch on KPV falls into three rough buckets. The first is gastrointestinal inflammation: ulcerative colitis, Crohn's disease, and inflammatory bowel disease more broadly. Both oral and rectal administration have been studied, with oral nanoparticle formulations showing particular promise in murine DSS colitis models. The second is skin inflammation: atopic dermatitis, psoriasis, contact dermatitis, and wound healing. Topical formulations have been studied as far back as the 1990s. The third is airway and systemic inflammation: allergic asthma, allergic rhinitis, and systemic inflammatory conditions. Across all three, the pattern is the same — KPV reduces pro-inflammatory cytokines and cellular infiltration without producing the immunosuppression seen with steroids or TNF inhibitors.\n\nKPV is not FDA-approved for any indication. It exists entirely in the research-peptide and compounding-pharmacy grey zone. It is not scheduled or controlled, but it is also not legally marketable as a treatment in the United States. Human data remain limited — most of the evidence base is preclinical (cell culture and rodent models), with only a handful of small human case series published. This is important framing: KPV is one of the better-characterized \"research\" peptides, but it is nowhere near the level of human evidence that supports [BPC-157](/compound/bpc-157), [TB-500](/compound/tb-500), or the GLP-1 agonists like [Semaglutide](/compound/semaglutide).\n\nThe popularity of KPV in the nootropic/peptide community has grown steadily because of three practical features. First, it is one of the few peptides with documented oral and topical activity — you do not need injections. Second, it has a clean safety profile in the published literature, with no serious adverse events reported across the studies published to date. Third, it stacks logically with other repair peptides — pairing KPV for inflammation control with [BPC-157](/compound/bpc-157) and [TB-500](/compound/tb-500) for tissue repair is a common \"gut healing\" protocol in the community, even though controlled human data for the stack do not exist.\n\nIf you are considering KPV, the honest framing is this: the preclinical case for anti-inflammatory activity is strong and consistent, the mechanism (PepT1-mediated NF-kB inhibition) is plausible and well-documented, and the safety signal is reassuring — but human evidence is thin and the compound is not regulated as a therapeutic. Everything below reflects what the published literature reports and what the research community has converged on as conservative practice. It is not medical advice and it is not a substitute for a physician's evaluation of inflammatory or autoimmune conditions.", "half_life": "~15–30 minutes (short-lived but downstream anti-inflammatory effects persist)", "molecular_weight": "342.43 g/mol", "molecular_mass": "342.43 g/mol", "amino_acid_sequence": "Lys-Pro-Val (KPV)", "administration_routes": [ "Subcutaneous", "Oral", "Topical" ], "dose_range_mcg": "500 mcg-2 mg per dose (standard); up to 5 mg daily in advanced protocols", "dosing_frequency": "Once daily subcutaneous or oral", "cycle_length": "6-12 weeks", "common_vial_sizes": [ "5mg", "10mg" ], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "4266-93-7", "iupac_name": "Lysyl-prolyl-valine", "chemical_formula": "C16H30N4O4", "potential_benefits": [ "Potent anti-inflammatory effects", "Gut healing and barrier repair", "Antimicrobial properties", "Skin wound healing support", "Potential anti-cancer properties (anti-angiogenic in tumors)" ], "research_fields": [], "pubmed_count": 33, "pubchem_cid": 125672, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/kpv" }, { "id": "2ba83d5e-5cc3-4729-bb4d-1a9586fede21", "slug": "ksptn", "name": "Kisspeptin-10 (KSPTN)", "aliases": [ "KSPTN peptide", "Novel research peptide" ], "category": "Other", "description": "KSPTN is the vendor shorthand for kisspeptin, a naturally occurring peptide encoded by the KISS1 gene and the master upstream regulator of the reproductive (hypothalamic-pituitary-gonadal) hormone axis. The research material sold under this code is typically kisspeptin-10, the active decapeptide fragment (YNWNSFGLRF-NH2, also called metastin 45-54) that stimulates GnRH release and, downstream, LH, FSH and the sex hormones. Unlike testosterone or hCG, kisspeptin acts at the very top of the axis and recruits the body's own GnRH pulse generator. It has been studied in human clinical trials for IVF egg-maturation triggering, hypogonadism, hypothalamic amenorrhea and sexual desire, but it is not an approved drug and is sold strictly for research use only (RUO).", "half_life": "Kisspeptin-10: very short, reported on the order of ~4 minutes (rapid plasma clearance). Kisspeptin-54 is longer-acting (tens of minutes). The brief half-life is why human studies dose it intravenously by bolus or continuous infusion.", "molecular_weight": "1302.5 g/mol (kisspeptin-10; molecular formula C63H83N17O14; CAS 374675-21-5)", "molecular_mass": "", "amino_acid_sequence": "YNWNSFGLRF-NH2 (Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe, C-terminally amidated; kisspeptin-10 / metastin 45-54)", "administration_routes": [ "Subcutaneous" ], "dose_range_mcg": "20-100", "dosing_frequency": "No validated schedule for self-use. In research, kisspeptin has been given as a single IV bolus, as a continuous IV infusion over hours, or (kisspeptin-54) as a single subcutaneous injection to trigger ovulation. Single or pulsatile dosing is favored pharmacologically because continuous exposure desensitizes the receptor.", "cycle_length": "Not applicable in the usual sense - human studies use single doses or short infusions (minutes to hours), not multi-week cycles. No evidence supports prolonged continuous dosing, which risks receptor desensitization. Research use only.", "common_vial_sizes": [ "5", "10" ], "research_stage": "Clinical (investigational)", "approval_status": "Not FDA-approved; investigational / research use only", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Transiently stimulates the body's own LH and, in men, testosterone secretion by acting upstream on the reproductive axis rather than replacing hormones [PMID:17323132, PMID:23153270]", "Studied as a trigger for egg (oocyte) maturation in IVF, where kisspeptin-54 produced a physiological LH surge with lower ovarian-hyperstimulation risk than standard triggers [PMID:28393578]", "Restored LH pulsatility and raised testosterone in men with type 2 diabetes and mild central hypogonadism in a proof-of-concept study [PMID:23153270]", "Modulated sexual and attraction-related brain processing in women with hypoactive sexual desire disorder, and was well tolerated [PMID:36287566]", "Used to probe or stimulate a dormant reproductive axis in conditions such as hypothalamic amenorrhea [PMID:28393578]", "Because it recruits the body's own GnRH pulse generator, hormone responses stay within a physiological range and are self-limited by normal feedback" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/ksptn" }, { "id": "e1a7c3d2-9f4b-4c2a-bf10-1a2b3c4d5e03", "slug": "kw-6356", "name": "KW-6356", "aliases": [ "KW6356" ], "category": "Nootropics", "description": "KW-6356 is a selective adenosine A2A receptor antagonist/inverse agonist developed by Kyowa Kirin and studied for Parkinson's disease, both as monotherapy and as an add-on to levodopa. Adenosine A2A receptors are concentrated in the basal ganglia, where they oppose dopamine signaling, so blocking them is a non-dopaminergic way to support motor function. It is a structurally distinct successor to istradefylline (Nourianz).", "half_life": null, "molecular_weight": "397.4", "molecular_mass": "397.4 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Phase 2b (program discontinued)", "approval_status": "Investigational; development discontinued by the originator", "trial_phase": "", "cas_number": "858979-50-7", "iupac_name": "", "chemical_formula": null, "potential_benefits": [ "Selective adenosine A2A antagonism / inverse agonism", "Studied for motor symptoms in Parkinson's disease (Phase 2a monotherapy + Phase 2b adjunct)", "Non-dopaminergic mechanism", "Researched for the wakefulness / anti-fatigue effects of A2A blockade" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/kw-6356" }, { "id": "aa85061a-2efb-4e03-8169-7447f372cc43", "slug": "l-carnitine", "name": "L-Carnitine", "aliases": [ "Carnitine", "LCAR" ], "category": "Weight Loss", "description": "L-Carnitine is a naturally occurring quaternary ammonium compound synthesized in the body from the amino acids lysine and methionine, with essential cofactor roles in fatty acid metabolism, energy production, and cellular health. Chemically classified as a conditionally essential nutrient, it is stored primarily in skeletal muscle (about 95% of total body carnitine, roughly 20 grams in an adult), with smaller pools in the liver, brain, heart, kidneys, and sperm. The body makes carnitine, but dietary intake — primarily from red meat and dairy — is the dominant source for most people. Vegans and vegetarians have measurably lower plasma carnitine levels, though this does not typically translate into overt deficiency in otherwise healthy individuals.\n\nThe fundamental biological role of L-carnitine is to shuttle long-chain fatty acids across the inner mitochondrial membrane, where they undergo beta-oxidation to produce ATP. Without adequate carnitine, long-chain fatty acids cannot enter mitochondria for energy production, and lipid metabolism grinds to a halt. This mechanism explains why carnitine is especially important for tissues with high fatty acid oxidation demands: cardiac muscle (which derives 60-90% of its energy from fat), skeletal muscle (during extended exercise), and sperm (which use fatty acid oxidation for motility). The \"carnitine shuttle\" is one of the core metabolic cycles in mammalian biochemistry ([Longo et al., 2016]).\n\nL-Carnitine exists in several supplemental forms, and the choice matters. **L-carnitine** (plain L-carnitine, sometimes called L-carnitine tartrate) is the standard form — well-absorbed, supports general fatty acid metabolism, the form used in most cardiovascular and metabolic research. **Acetyl-L-carnitine (ALCAR)** has an acetyl group attached that allows it to cross the blood-brain barrier more effectively, giving it specific cognitive and neuroprotective applications — this is the form used in most studies of cognitive aging, mild cognitive impairment, and peripheral neuropathy. **L-carnitine L-tartrate (LCLT)** is a salt form with enhanced stability and is the specific form used in most exercise performance and recovery research. **Propionyl-L-carnitine (PLC)** has a propionyl group instead of an acetyl group and is specifically studied for peripheral artery disease and endothelial function. **Glycine propionyl-L-carnitine (GPLC)** is a further modification marketed for exercise performance. These are not interchangeable — research findings with one form do not automatically generalize to others ([Pennisi et al., 2020]).\n\nThe clinical evidence base for L-carnitine is deeper than most supplements. **Cardiovascular disease** — particularly heart failure, post-myocardial infarction recovery, and angina — has been the subject of multiple randomized trials and meta-analyses showing mortality reduction and symptomatic improvement. **Peripheral artery disease** with intermittent claudication has strong evidence for propionyl-L-carnitine specifically. **Chronic fatigue and fatigue-related conditions** including post-chemotherapy fatigue and HIV-associated fatigue have multiple supporting trials. **Male fertility** — carnitine improves sperm motility, concentration, and morphology in men with oligoasthenospermia. **Cognitive aging** — ALCAR has multiple trials in mild cognitive impairment and Alzheimer's disease with modest but consistent benefits. **Peripheral neuropathy** — ALCAR has good evidence for diabetic and chemotherapy-induced neuropathy. **Hemodialysis patients** — carnitine deficiency is common in dialysis, and IV L-carnitine is FDA-approved for this indication ([DiNicolantonio et al., 2013], [Pennisi et al., 2020]).\n\nThe research peptide and performance community uses L-carnitine mostly for two broad purposes: fat loss support and exercise recovery. For fat loss, the theory is straightforward — more carnitine should improve fatty acid transport into mitochondria and therefore improve fat oxidation. The practical evidence for fat loss is modest at best; L-carnitine is not a meaningful standalone weight loss agent, but it may support fat oxidation in specific contexts (particularly in carnitine-deficient states or with appropriate training). For exercise recovery, L-carnitine L-tartrate (LCLT) has a more solid evidence base — multiple trials show reduced muscle damage markers, faster recovery between sessions, and improved recovery markers in resistance-trained individuals at 2-3 g daily ([Volek et al., 2002], [Spiering et al., 2008]).\n\nL-Carnitine has a complex relationship with the microbiome that has generated controversy. Dietary L-carnitine is metabolized by gut bacteria to produce TMAO (trimethylamine-N-oxide), a compound that has been associated in observational studies with increased cardiovascular risk. This finding — that the same compound used therapeutically for cardiovascular disease may also produce a putatively atherogenic metabolite — created significant debate. Subsequent work has suggested the TMAO-cardiovascular link may be more correlational than causal, that supplemental L-carnitine produces different TMAO responses than dietary sources in some populations, and that the net cardiovascular effect of L-carnitine in randomized trials remains favorable. The picture is more nuanced than initial headlines suggested ([Koeth et al., 2013](https://pubmed.ncbi.nlm.nih.gov/23563705/), [Samulak et al., 2019]).\n\nL-Carnitine is not a research peptide in the sense of [BPC-157](/compound/bpc-157) or [Semax](/compound/semax) — it is a well-characterized nutritional/metabolic compound with decades of clinical use, FDA-approved forms (Carnitor IV for dialysis patients, Levocarnitine for primary and secondary carnitine deficiency), and widespread availability as a supplement. This gives the evidence base a quality and depth that most \"research peptides\" lack. At the same time, L-carnitine is not a miracle compound. Its effects in healthy individuals without deficiency are modest. Its role is best understood as metabolic effect — filling a specific cofactor function — rather than as a primary therapeutic intervention.\n\nThe honest framing for anyone considering L-carnitine: it has real biology, real evidence, and real clinical use. It is not going to transform your body composition or athletic performance in healthy individuals with adequate diet. It may be meaningfully useful in specific contexts: vegan/vegetarian supplementation, aging (where tissue carnitine declines), heart failure, peripheral artery disease, chronic fatigue, male fertility, cognitive aging, and dialysis patients. Beyond those contexts, use is supportive rather than transformative, and cost-benefit needs honest evaluation.", "half_life": "", "molecular_weight": "", "molecular_mass": "161.20 g/mol", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "500 mg - 2000 mg daily (oral or injection)", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "541-15-1", "iupac_name": "(R)-3-carboxy-2-hydroxy-N,N,N-trimethylpropan-1-aminium", "chemical_formula": "C7H15NO3", "potential_benefits": [ "Enhanced fat metabolism", "Improved exercise performance", "Reduced muscle damage and recovery time", "Neuroprotective effects (acetyl-L-carnitine)", "Mitochondrial function support", "Improved insulin sensitivity" ], "research_fields": [], "pubmed_count": 4002, "pubchem_cid": 119859, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/l-carnitine" }, { "id": "913c4107-b59f-44ce-8de8-99dcaabc237d", "slug": "l-theanine", "name": "L-Theanine", "aliases": [ "gamma-glutamylethylamide", "N-ethyl-L-glutamine", "γ-L-glutamylethylamide", "Suntheanine", "Theanine" ], "category": "Nootropics", "description": "**L-Theanine** is a **non-proteinogenic amino acid** found almost exclusively in **tea (Camellia sinensis)** and a handful of edible mushrooms, and it has become the single most widely-used calm-focus nootropic in the modern supplement market — both on its own at 100-400mg doses and, even more prominently, as the classic **1:1 or 2:1 pair with caffeine** that defines the \"calm-focus\" experiential signature of green tea and of virtually every serious nootropic stack. Chemically L-theanine is **γ-glutamylethylamide** (N-ethyl-L-glutamine), a structural analog of the excitatory neurotransmitter **glutamate** and its inhibitory cousin **GABA** — close enough to both to interact with their transporters and, at high doses, their receptors, but distinct enough to produce a characteristic combination of **reduced sympathetic arousal, mildly enhanced alpha-wave EEG activity, and preserved or modestly improved attention** that the literature has consistently tied to its single signature phrase: *\"relaxed alertness.\"*\n\nThe modern L-theanine literature traces back to Japanese tea-chemistry research in the 1950s — theanine was first isolated from green tea by Sakato in 1949 — but its Western nootropic adoption is much more recent, anchored by three key human studies: **Kobayashi et al. 1998** (Japanese EEG study, alpha-wave elevation at 50-200mg oral doses), **Haskell et al. 2008** (*Biological Psychology* PMID: 18006208), which showed that 100mg L-theanine + 50mg caffeine produces faster attention-task reaction times and subjectively better mood than either compound alone, and **Kimura et al. 2007** (*Biological Psychology* PMID: 16930802), which demonstrated that 200mg L-theanine reduces heart rate and salivary immunoglobulin A responses to an acute stress task — the cleanest human physiology demonstration of its anxiolytic effect. Supporting RCTs include **Hidese et al. 2019** (*Nutrients*, 4-week 200mg/day for stress and sleep in healthy adults) and **Lyon et al. 2011** (*Alternative Medicine Review*, 200mg BID improving sleep quality in boys with ADHD).\n\nPharmacologically, L-theanine crosses the blood-brain barrier via the large neutral amino acid transporter (LAT1), reaching brain tissue within 30-60 minutes of an oral dose. It has a plasma half-life of roughly 1-3 hours in humans, with central nervous system exposure outlasting plasma, and it acts on multiple neurotransmitter systems simultaneously (glutamate, GABA, dopamine, serotonin, catecholamines) — but at physiologic supplement doses its effects on any single system are modest. It is a weak, broadly-acting modulator rather than a strong selective agent. This is why it does NOT cause sedation, dependence, tolerance, or rebound the way GABAergic sedatives ([phenibut](/compound/phenibut), benzodiazepines, Z-drugs) do — you can take 200mg daily for years without tolerance development.\n\nThe largest user population is the caffeine-stack crowd — knowledge workers, students, coders, writers — taking 100-200mg caffeine daily for alertness and wanting to take the edge off the jitter without losing the focus boost. The canonical stack is 200mg caffeine + 200mg L-theanine taken together once in the morning. A second population uses it for acute stress (200mg, 30-60 minutes before a stressful event). A third cohort uses 400-600mg for schizophrenia-adjunctive anxiety based on the Ritsner 2011 data (PMID: 21208586). A fourth uses 200-400mg at bedtime for sleep quality, though the adult sleep evidence is weaker than the ADHD-boys data from Lyon 2011.\n\nWhere L-theanine does NOT work: it is not a sedative, not a cognitive enhancer in isolation (the attention benefit shows up only when paired with caffeine), not a panic-attack abortive, not an SSRI substitute for clinical depression or GAD, and not equivalent to meditation or therapy for chronic anxiety.\n\n**Safety profile** stands out: FDA-GRAS since 2007 as Suntheanine®, rodent LD50 >5 g/kg (effectively unreachable at oral doses), decades of dietary human exposure through green tea, no dependence or withdrawal reported in any RCT. Side effects (mild headache, GI upset, dizziness at high doses) occur at placebo-comparable rates. The only meaningful practical cautions are possible additive hypotensive effect with blood-pressure medications and theoretical interaction with stimulant medications (though theanine + stimulant combinations are actually commonly used and well-tolerated).\n\nL-theanine pairs well with nearly everything. The caffeine pair is canonical. [Ashwagandha](/compound/ashwagandha) is increasingly common for daytime anxiolysis. [Magnesium](/compound/magnesium) glycinate or L-threonate pairs for evening use. [Rhodiola rosea](/compound/rhodiola-rosea) + L-theanine + caffeine is a strong \"calm focus + adaptogen\" stack. Avoid stacking with strong sedatives (benzodiazepines, high-dose kava, phenibut in naive users) — not because of a specific interaction but because the subjective synergy blunts the productive-calm signature L-theanine is typically used for.\n\nThis is educational content and not medical advice; L-theanine is exceptionally safe for most healthy adults but blood-pressure medications, antipsychotics, and pregnancy/pediatric use warrant physician input before supplementation.", "half_life": "1-3 hours (plasma); central CNS effect 3-5 hours", "molecular_weight": "174.20 g/mol", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "FDA Approved", "approval_status": "GRAS (Generally Recognized as Safe) — Suntheanine FDA GRAS since 2007", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 1226, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/l-theanine" }, { "id": "9adb8728-9158-4807-afea-e3fdc7f7ba7a", "slug": "l-thp", "name": "Levo-tetrahydropalmatine (l-THP)", "aliases": [ "l-THP", "Rotundine", "(-)-Tetrahydropalmatine", "Gindarine", "Hyndarine", "Caseanine", "Jin Bu Huan (herbal product containing l-THP)" ], "category": "Nootropics", "description": "Levo-tetrahydropalmatine, usually written l-THP, is an isoquinoline alkaloid found in plants of the Corydalis and Stephania genera. It is not a new compound. It has been approved and used in China for decades under the drug name Rotundine for several clinical indications, mainly as an analgesic with sedative and hypnotic effects (PMID: 22300097, PMID: 27606501). Outside China it is known in two very different contexts: as a candidate treatment for cocaine and opioid addiction, and as the active constituent of the herbal product Jin Bu Huan that caused a cluster of poisonings in the United States during the 1990s.\n\nIts pharmacology is dopamine receptor antagonism. Radioligand and behavioral work in rats found higher-affinity antagonism at D1 receptors, lower-affinity antagonism at D2 receptors and interaction with D3 receptors, and reviews add activity at alpha adrenergic and serotonin receptors (PMID: 17361394, PMID: 22300097). In C57BL/6J mice, treatment reduced voluntary ethanol drinking and altered D2 receptor-linked protein kinase A signaling in the caudate-putamen but not the nucleus accumbens (PMID: 23376703).\n\nThe animal addiction work is consistent. In rats, l-THP shifted the cocaine self-administration dose-response curve down and to the right and reduced cocaine-induced reinstatement at doses that did not change food-reinforced responding (PMID: 17361394); reduced reinstatement triggered by cocaine, stress or drug-associated cues after oral administration (PMID: 21196089); reduced cocaine self-administration under a progressive ratio schedule (PMID: 20816889); and reduced nicotine self-administration and reinstatement (PMID: 27817750).\n\nHuman work is real but small. A randomized, double-blind, placebo-controlled study gave 24 adult male cocaine users l-THP 30 mg twice daily or placebo for four days, with an intranasal cocaine challenge on the fourth day. The short course was safe and well tolerated, side effect counts matched placebo, and l-THP did not change cocaine exposure or its acute cardiovascular effects (PMID: 27363313). Registered work at the University of Maryland includes that Phase 1 study (NCT01631383), a completed 63-participant study in schizophrenia (NCT02118610) and a Phase 2 cocaine use disorder trial that was withdrawn before enrolment (NCT02139761). No adequately powered efficacy trial has been published.\n\nThe safety record deserves weight. Jin Bu Huan Anodyne tablets, which contain l-THP and were mislabelled on the package as a Lycopodium product, caused acute hepatitis in seven previously healthy adults after a mean of 20 weeks of use, with recurrence on rechallenge in two of them (PMID: 7944049). A separate case series described life-threatening neurological and cardiovascular effects including coma in three young children after single acute ingestions, alongside hepatitis in three adults on long-term use (PMID: 8774209), and chronic hepatitis with moderate fibrosis has been reported after two months of use (PMID: 9537855). In human liver microsomes, tetrahydropalmatine is a mechanism-based inhibitor of CYP2D6 and is itself metabolized by CYP2C19, CYP3A4, CYP1A2 and CYP2D6, which makes interaction with CYP2D6 substrates a live concern (PMID: 41876357).\n\nl-THP has no FDA or EMA authorization. Capsules sold on the research chemical and supplement market are not the Chinese pharmaceutical product and are not made to a pharmacopoeial standard.", "half_life": "Not established in the sources retrieved; a randomized, double-blind, placebo-controlled human study collected full plasma pharmacokinetic profiles in 19 cocaine users receiving l-THP 30 mg twice daily for 4 days but did not report a terminal half-life (PMID: 27363313)", "molecular_weight": "355.43 g/mol", "molecular_mass": "355.43 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Approved (China)", "approval_status": "Approved and used in China under the drug name Rotundine for several clinical indications, mainly analgesia with sedative and hypnotic effects (PMID: 22300097, PMID: 27606501). It has no FDA or EMA marketing authorization; in the United States it has been studied under an investigational pathway in cocaine users (PMID: 24996068, NCT01631383) while the material sold to consumers is an unapproved supplement or research chemical.", "trial_phase": "", "cas_number": "483-14-7", "iupac_name": "", "chemical_formula": "C21H25NO4", "potential_benefits": [ "Reduced cocaine self-administration and cocaine-induced reinstatement in rats at doses that did not change food-reinforced responding (PMID: 17361394)", "Reduced reinstatement of extinguished cocaine seeking triggered by cocaine, stress or drug-associated cues in rats after oral administration (PMID: 21196089)", "Reduced nicotine self-administration and reinstatement in rats (PMID: 27817750)", "Reduced voluntary ethanol drinking in C57BL/6J mice in a two-bottle choice test (PMID: 23376703)", "Safe and well tolerated over a short course in 24 adult male cocaine users, without changing cocaine pharmacokinetics or its acute cardiovascular effects (PMID: 27363313)" ], "research_fields": [ "Addiction pharmacotherapy", "Dopamine receptor antagonists", "Herbal medicine safety", "Analgesia and sedation" ], "pubmed_count": 0, "pubchem_cid": 72301, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/l-thp" }, { "id": "456cba04-a404-48b2-8b3f-c3f14b9e3eef", "slug": "l-tryptophan", "name": "L-Tryptophan", "aliases": [ "Tryptophan", "L-Trp", "Trp", "(S)-2-Amino-3-(1H-indol-3-yl)propanoic acid" ], "category": "Nootropic", "description": "**L-Tryptophan** is one of the nine **essential amino acids** — meaning the human body cannot synthesize it and must obtain it from dietary protein — and is the direct metabolic precursor to **serotonin**, **melatonin**, and (via a separate route) the vitamin **niacin (nicotinamide / NAD+)**. It is the least abundant essential amino acid in most protein sources, and its selective depletion has been used for decades as a research tool to probe the role of serotonin in mood, cognition, and aggression. As a dietary supplement it sits at an unusual intersection: foundational nutrient, serotonin precursor, sleep aid, and the compound at the center of one of the most consequential supplement safety events in US regulatory history — the **1989 eosinophilia-myalgia syndrome (EMS) outbreak** that killed roughly 37 people and sickened ~1,500, which was eventually traced to contaminants in a single manufacturer's bulk product (Showa Denko). That tragedy drove an FDA import alert and a near-total disappearance of tryptophan from the US supplement market for over a decade; it has since returned under USP-verified, third-party-tested sourcing, but the shadow of EMS continues to shape how cautious clinicians and regulators think about the compound.\n\nChemically, L-tryptophan is **(S)-2-Amino-3-(1H-indol-3-yl)propanoic acid** — an aromatic amino acid defined by its **indole ring**, a bicyclic nitrogen-containing aromatic structure that is also the structural core of serotonin, melatonin, psilocin, DMT, and a wide family of indoleamine neuromodulators. The indole ring is what makes tryptophan fluorescent and what makes it the most spectroscopically distinctive amino acid in proteins. In dietary terms, it is abundant in turkey, chicken, eggs, cheese, fish, pumpkin seeds, soybeans, oats, and dairy — contrary to popular folklore, turkey is not unusually rich in tryptophan relative to other protein sources, and the post-Thanksgiving drowsiness attributed to turkey's tryptophan is more plausibly a function of carbohydrate-induced insulin release shunting competing large neutral amino acids into muscle, plus a large meal, plus alcohol, plus the parasympathetic lull of a long family dinner.\n\nThe **supplemental rationale** for L-tryptophan is tied almost entirely to its role as a precursor. Ingested tryptophan is absorbed in the small intestine, enters circulation, crosses the blood-brain barrier in competition with other **large neutral amino acids (LNAAs)** — leucine, isoleucine, valine, phenylalanine, tyrosine, methionine — and is converted in serotonergic neurons by **tryptophan hydroxylase (TPH1 in the gut/periphery, TPH2 in the brain)** to **5-hydroxytryptophan (5-HTP)**, which is then decarboxylated by AADC to **serotonin (5-HT)**. Serotonin in the pineal gland is subsequently acetylated (by AA-NAT) and methylated (by HIOMT) to produce **melatonin**, the circadian-aligned sleep-promoting hormone. Only a small fraction of dietary tryptophan — typically cited as ~1-5% — follows this serotonin/melatonin path; the vast majority (~95%) is shunted through the **kynurenine pathway** via **tryptophan 2,3-dioxygenase (TDO)** in the liver or **indoleamine 2,3-dioxygenase (IDO)** in immune and peripheral tissues, generating kynurenine and a cascade of downstream metabolites (kynurenic acid, quinolinic acid, xanthurenic acid, picolinic acid) that feed into NAD+ synthesis and immune signaling. The kynurenine pathway is itself a topic of intense contemporary research — kynurenic acid is a glycine-site NMDA antagonist and α7-nicotinic antagonist (possibly neuroprotective), while quinolinic acid is an NMDA agonist and has been linked to depression, neuroinflammation, and neurodegeneration.\n\nThe **historical context** for tryptophan supplementation starts in the 1970s, when early sleep researchers — notably **Ernest Hartmann** at Boston State Hospital — reported that 1-4 grams of oral tryptophan reduced sleep latency in mild insomniacs without the \"morning-after\" grogginess associated with benzodiazepines. Through the 1980s, tryptophan was widely used for sleep, mood, and pre-menstrual symptoms across North America, sold as a dietary supplement in health food stores. In **1989**, clusters of a new and frightening syndrome — severe eosinophilia, disabling myalgia, fasciitis, neuropathy — were reported from New Mexico and rapidly traced to L-tryptophan supplementation (**Belongia et al. 1990**, *NEJM*). Epidemiological investigation pinned the cases to bulk tryptophan manufactured by Showa Denko in Japan using a specific modified fermentation strain; contaminants (EBT, \"peak E\", plus related impurities) — not tryptophan itself — were the likely causative agents. FDA imposed an import alert; by 1990 tryptophan was effectively off US shelves. The import alert was relaxed in **2001-2005** as USP-verified sourcing and improved analytical methods allowed regulators to reintroduce the product; since then, L-tryptophan has been legally available in the US as a dietary supplement, but with ongoing emphasis on third-party testing and USP verification precisely because of the EMS legacy.\n\n**Current use** is concentrated in three buckets: (1) **sleep latency support** — the original Hartmann-era indication; modest but real effect in mild insomnia (**Silber & Schmitt 2010**, review); (2) **mood support** — particularly in acute tryptophan depletion research (**Young 2013**) showing that depleting tryptophan rapidly reproduces low mood in people with a history of depression, supporting a causal role for serotonin availability; clinical response to supplemental tryptophan in actual depression is mixed; (3) **niche applications** — PMS symptoms, post-partum blues, aggression/irritability, carb-craving. Dosing is typically **500mg to 3g/day**, often at bedtime or split. Onset for acute effects is ~30-90 minutes; steady-state serotonergic effects may take 1-2 weeks.\n\n**Who uses it and why** — the practical picture — breaks down roughly as: people who want a gentler alternative to [5-HTP](/compound/5-htp) (tryptophan is upstream of the TPH rate-limit and therefore subject to homeostatic regulation that 5-HTP bypasses); people whose [melatonin](/compound/melatonin) use has plateaued or who want endogenous melatonin support rather than exogenous dosing; people exploring serotonergic support without prescription SSRIs; and a smaller group using tryptophan as an aggression/irritability-reducing intervention (this has modest RCT support). If you're comparing this to 5-HTP, here's the tradeoff: tryptophan is the upstream amino acid subject to TPH regulation (harder to overshoot, gentler effect), while 5-HTP bypasses TPH and converts directly to serotonin (faster, more potent, but with more room to overshoot into serotonin syndrome territory when combined with serotonergic drugs). For most self-experimenters, tryptophan is the safer starting point.\n\nSee also [5-HTP](/compound/5-htp), [Melatonin](/compound/melatonin), [SAM-e](/compound/sam-e), [Magnesium](/compound/magnesium), [L-Theanine](/compound/l-theanine), [Ashwagandha](/compound/ashwagandha), [Rhodiola](/compound/rhodiola), [Lithium Orotate](/compound/lithium-orotate), and [Lion's Mane](/compound/lions-mane) for adjacent serotonergic, sleep-supportive, and mood-supportive compounds commonly used in the same stacks. This is educational content and not medical advice — tryptophan supplementation has real interactions with prescribed serotonergic medications (SSRIs, MAOIs, triptans, tramadol, dextromethorphan) and warrants physician-level guidance when those are in play.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 3217, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/l-tryptophan" }, { "id": "0be4de21-7cb7-4cf7-9bab-de48ea7c72c9", "slug": "l-tyrosine", "name": "L-Tyrosine", "aliases": [ "Tyrosine", "L-Tyr", "2-Amino-3-(4-hydroxyphenyl)propanoic acid", "NALT", "N-Acetyl-L-Tyrosine" ], "category": "Nootropics", "description": "L-Tyrosine is a non-essential aromatic amino acid and the direct biosynthetic precursor to the catecholamine neurotransmitters dopamine, norepinephrine, and epinephrine. Unlike \"essential\" amino acids that must be obtained from diet, tyrosine can be synthesized in the human body from phenylalanine via the enzyme phenylalanine hydroxylase (PAH) — the same enzyme that is deficient in the genetic disorder phenylketonuria (PKU), which is why PKU patients require dietary tyrosine supplementation as part of their medical management. Dietary sources of tyrosine include cheese (the amino acid was originally isolated from casein, and its name derives from the Greek *tyros* meaning \"cheese\"), chicken, fish, eggs, nuts, seeds, soy products, and dairy. Typical Western diets provide 1-5 g of tyrosine daily from food sources, which is adequate for general protein synthesis and catecholamine turnover under normal conditions. The cognitive performance use case for supplemental tyrosine rests on a specific pharmacologic logic: during periods of intense acute stress — cold exposure, sleep deprivation, sustained mental workload, combat operations — catecholamine synthesis in the brain can become rate-limited by tyrosine availability at the tyrosine hydroxylase step (the rate-limiting enzyme in catecholamine biosynthesis). Under these conditions, supplemental tyrosine at doses of 100-150 mg/kg (roughly 7-12 g for a 70 kg adult in the original research context, though practical doses are typically lower at 500-2000 mg) can raise brain tyrosine levels, accelerate catecholamine synthesis, and support cognitive performance that would otherwise degrade under stress. The seminal research establishing this cognitive-performance effect came from US Army and academic laboratories in the 1980s-1990s, with Banderet and Lieberman's 1989 work at the US Army Research Institute of Environmental Medicine demonstrating that tyrosine supplementation protected cognitive performance in subjects exposed to cold and altitude stress (PMID 2736402). Subsequent research extended these findings to sleep deprivation, combat operational stress, cognitively demanding military scenarios, and laboratory stress paradigms. A body of 30+ studies now documents tyrosine's cognitive protective effects under stress conditions, with a reasonably consistent finding: tyrosine provides modest but real cognitive performance protection during demanding conditions while producing minimal effects in rested, non-stressed users. The practical implication is that tyrosine is a niche cognitive enhancer rather than a general nootropic — it matters for specific situations (sleep-deprived work, cold exposure, high-stress cognitive challenges) and matters less for routine rested cognitive function. This entry covers tyrosine's mechanism of action as a catecholamine precursor and the pharmacologic logic of precursor loading; the clinical and military research evidence base for cognitive performance under stress including the Banderet-Lieberman and subsequent studies; the distinction between L-tyrosine and N-acetyl-L-tyrosine (NALT) and their relative bioavailability claims; the side effect profile including rare effects on thyroid function, blood pressure, and melanin synthesis; dosing conventions for acute pre-stress loading versus chronic daily supplementation; contraindications including MAO inhibitor use, active melanoma, and hyperthyroidism; and how tyrosine integrates into stacks with other cognitive enhancement and performance compounds including [Modafinil](/compound/modafinil), [Piracetam](/compound/piracetam), [Noopept](/compound/noopept), [Sulbutiamine](/compound/sulbutiamine), [L-Theanine](/compound/l-theanine), [Bromantane](/compound/bromantane), [Selank](/compound/selank), and [Semax](/compound/semax). Tyrosine represents a well-understood, evidence-supported, low-risk cognitive performance intervention for specific stress-related applications — one of the few nootropic supplements with multiple rigorous randomized controlled trials supporting its use.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 8, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/l-tyrosine" }, { "id": "6052e075-72d8-4867-962e-460223f08323", "slug": "larazotide", "name": "Larazotide (AT-1001)", "aliases": [ "Larazotide acetate", "AT-1001", "AT1001", "AT-2347", "INN-202" ], "category": "Immune & Inflammation", "description": "Larazotide is an eight amino acid peptide with the sequence glycine-glycine-valine-leucine-valine-glutamine-proline-glycine, usually supplied as the acetate salt. Its structure derives from a protein secreted by Vibrio cholerae, the zonula occludens toxin, and it was developed as an antagonist at that pathway rather than as an agonist. Alba Therapeutics took it into celiac disease (PMID: 17697209), and it was later developed by 9 Meters Biopharma under the code INN-202 (NCT03569007). It is not approved anywhere.\n\nThe target is the intestinal tight junction. In celiac disease, gluten peptides reach the lamina propria and trigger an immune response, and increased paracellular permeability is one route by which they get there. Larazotide acts locally in the gut lumen to keep tight junctions closed. Mechanistic work links it to redistribution and rearrangement of tight junction proteins and actin filaments, and more recently to inhibition of myosin light chain kinase, which reduces tension on actin filaments and lets the junction close (PMID: 33881350). Because it works in the lumen and is taken orally, it is not designed to reach the systemic circulation.\n\nAnimal work supports the barrier mechanism outside celiac disease. In interleukin 10 gene-deficient mice, treatment reduced small intestinal permeability and attenuated colitis, with lower colonic tumor necrosis factor alpha secretion at 17 weeks (PMID: 18829978). In pigs, it induced recovery of ischemia-injured jejunum through repair of tight junctions (PMID: 33886649). Rat studies report reduced intestinal permeability and bacterial translocation in acute pancreatitis (PMID: 38441784) and reduced liver and intestinal damage in acute liver failure (PMID: 34791921).\n\nThe human record is unusually complete for a compound sold as a research chemical, and it is mixed. A proof of concept study in celiac disease subjects challenged with gluten found no increase in adverse events, no rise in intestinal permeability in the treated group against a 70 percent rise on placebo, and fewer gastrointestinal symptoms (PMID: 17697209). Two gluten-challenge trials in 86 and 184 patients failed to separate from placebo on the lactulose to mannitol permeability ratio, but reported reductions in symptoms and, in the larger trial, lower anti-transglutaminase antibody rises (PMID: 22825365, PMID: 23163616). A 342-patient phase 2b trial in patients who still had symptoms on a gluten-free diet met its primary symptom endpoint at the lowest dose tested and not at higher doses (PMID: 25683116). The phase 3 trial then stopped: NCT03569007 enrolled 307 patients and was terminated in 2022 after a pre-specified interim analysis indicated that the number of additional patients needed to show a significant clinical effect was too large to continue (NCT03569007; sponsor announcement, June 2022).\n\nInterest has since moved to other barrier-driven conditions. A phase 2a randomized trial in 12 children with multisystem inflammatory syndrome after COVID-19 reported no larazotide-related adverse events, faster clearance of circulating SARS-CoV-2 spike antigen and faster resolution of gastrointestinal symptoms (PMID: 40737433). A long COVID phase 2a trial has completed (NCT05747534). What is sold as a research chemical capsule is an investigational drug, not an approved medicine.", "half_life": "Not established as a systemic value. Larazotide is designed to act locally in the intestinal lumen and is given orally rather than for systemic exposure (PMID: 33881350); single-dose safety, tolerance and pharmacokinetics were assessed in a phase 1b study in celiac disease subjects (PMID: 17697209)", "molecular_weight": "725.85 g/mol (free peptide); 785.9 g/mol as the acetate salt", "molecular_mass": "725.85 g/mol (free peptide)", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Phase 3", "approval_status": "Not approved by the FDA, the EMA or any other regulator. It reached phase 3 in celiac disease, but that trial (NCT03569007, 307 patients) was terminated in 2022 after a pre-specified interim analysis found the additional sample size needed to show a significant effect was too large to continue. It is not a WADA-prohibited substance and is not a controlled substance. Anything sold outside a clinical trial is a research-use-only compound.", "trial_phase": "", "cas_number": "258818-34-7", "iupac_name": "", "chemical_formula": "C32H55N9O10", "potential_benefits": [ "Prevented the gluten-induced rise in intestinal permeability seen on placebo and reduced gastrointestinal symptoms in adults with celiac disease in a phase 1b proof of concept study (PMID: 17697209)", "Reduced gluten-induced symptom severity and anti-transglutaminase antibody rises in adults with celiac disease undergoing gluten challenge in a 184-patient randomized trial (PMID: 23163616)", "Met the primary symptom endpoint at the lowest dose tested in 342 adults with celiac disease who still had symptoms on a gluten-free diet (PMID: 25683116)", "Reduced small intestinal permeability and attenuated colitis in interleukin 10 gene-deficient mice (PMID: 18829978)", "Promoted recovery of ischemia-injured jejunum through tight junction repair in pigs (PMID: 33886649)", "Faster clearance of circulating SARS-CoV-2 spike antigen and faster resolution of gastrointestinal symptoms in 12 children with multisystem inflammatory syndrome in a phase 2a trial (PMID: 40737433)" ], "research_fields": [ "Intestinal barrier function", "Celiac disease", "Tight junction pharmacology", "Post-viral inflammatory syndromes" ], "pubmed_count": 0, "pubchem_cid": 9810532, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/larazotide" }, { "id": "35f0be18-ba2a-4161-a26c-72dd054d3b52", "slug": "lgd-4033", "name": "LGD-4033 (Ligandrol)", "aliases": [ "Ligandrol", "LGD4033", "LGD 4033", "VK5211", "VK-5211", "Anabolicum" ], "category": "Performance", "description": "LGD-4033, usually sold as ligandrol, is a nonsteroidal selective androgen receptor modulator that Viking Therapeutics took into clinical development under the code VK5211 (NCT02578095). The stated development goal was an oral drug that produces the muscle and bone effects of testosterone with less action on prostate and skin, aimed at conditions such as recovery after hip fracture and other causes of muscle loss. It has not been approved by any regulator, and clinical development has not progressed past phase 2.\n\nMechanistically it binds the androgen receptor with high affinity and selectivity and acts as an agonist in muscle and bone. The consequences of that binding are visible in the human phase 1 data: over three weeks of daily dosing in healthy young men, total testosterone, sex hormone binding globulin, HDL cholesterol and triglycerides all fell in a dose-dependent way, follicle-stimulating hormone and free testosterone fell at the top dose, and lean body mass rose without a change in fat mass (PMID: 22459616). Hormone levels and lipids returned to baseline after the drug was stopped in that 21-day study, which is a short exposure compared with how the compound is used outside research.\n\nAnimal work supports an anabolic signal but is mixed on whether that translates to performance. In ovariectomized rats, ligandrol improved muscle tissue (PMID: 33042018) and improved trabecular bone structure at the highest dose tested in ovariectomized rats (PMID: 37407738). In male rats, however, ligandrol lowered endurance and worsened lipid and hormonal profiles (PMID: 40087185).\n\nHuman safety reports are the strongest reason for caution. Published case reports describe severe cholestatic liver injury confirmed on biopsy after ligandrol use, including a 32-year-old man with cholestatic hepatitis and fibrosis (PMID: 32637435), a 37-year-old man with bilirubin about thirty times the upper limit of normal and ductopenia on biopsy (PMID: 36257328), a further case in an otherwise healthy adult (PMID: 39421081) and cases involving ligandrol together with post-cycle drugs (PMID: 34141767). A retrospective Australian series of drug-induced liver injury from anabolic steroids, SARMs and bodybuilding supplements collected 23 cases, most of whom were admitted to hospital, with a median 175 days to normal liver biochemistry and one liver transplant (PMID: 38372012). A self-reported case of ligandrol taken with the growth hormone secretagogue MK-677 recorded alanine aminotransferase up about 205 percent, HDL cholesterol down about 36 percent and total testosterone down about 62 percent (PMID: 36303408).\n\nIn sport, LGD-4033 is prohibited at all times under the World Anti-Doping Agency class S1.2 and has been found in athlete urine samples (PMID: 27168428). Its human urinary metabolites are well characterized for testing purposes (PMID: 30255601). FDA has issued warning letters to firms selling it as an unapproved new drug (FDA warning letter to Titan SARMs LLC, 12 December 2025). What is sold as ligandrol is often mislabeled: in an analysis of 44 SARM-marketed products, only about half contained any SARM and the label amount matched the assay in 41 percent (PMID: 29183075).", "half_life": "Long elimination half-life in humans with dose-proportional accumulation over 21 days of daily dosing in healthy young men; the report describes the profile without giving a single value in its summary (PMID: 22459616)", "molecular_weight": "338.25 g/mol", "molecular_mass": "338.25 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Phase 2", "approval_status": "Not approved by the FDA, the EMA or any other regulator for any indication. FDA classifies products containing SARMs as unapproved drugs that are not dietary supplements and has sent warning letters to distributors selling LGD-4033 (FDA warning letter to Titan SARMs LLC, 12 December 2025). Prohibited at all times, in and out of competition, under the World Anti-Doping Agency anabolic agents class S1.2 (PMID: 28137616, PMID: 27168428). Research-use-only compound in the US market.", "trial_phase": "", "cas_number": "1165910-22-4", "iupac_name": "", "chemical_formula": "C14H12F6N2O", "potential_benefits": [ "Increased lean body mass without a change in fat mass over 21 days in healthy young men in a placebo-controlled phase 1 study (PMID: 22459616)", "Improved muscle tissue in ovariectomized rats (PMID: 33042018)", "Improved trabecular bone structural properties at the highest dose tested in ovariectomized rats (PMID: 37407738)" ], "research_fields": [ "Muscle wasting and sarcopenia", "Bone and fracture recovery", "Sports drug testing", "Hepatotoxicity surveillance" ], "pubmed_count": 0, "pubchem_cid": 44137686, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/lgd-4033" }, { "id": "a811f8b1-5af3-42e8-8c8e-a1e74c0c26ef", "slug": "lions-mane", "name": "Lion's Mane Mushroom", "aliases": [], "category": "Nootropics", "description": "**Lion's Mane** (scientific name *Hericium erinaceus*; also known as **yamabushitake** in Japanese, **houtou** in Chinese, **bearded tooth fungus**, **monkey head mushroom**, and **pom pom mushroom**) is a white-to-cream coloured edible and medicinal mushroom in the tooth fungus family (Hericiaceae), characterised by its distinctive cascading spines that resemble a lion's mane or white cascading icicles. It grows on the wounds and dead trunks of deciduous hardwood trees (especially beech and oak) across temperate forests in North America, Europe, and Asia, and has been cultivated commercially in Japan, China, Korea, and increasingly in Western countries since the late 20th century. It has a long history in East Asian cuisine and traditional medicine — mentioned in Chinese medical texts for centuries and used in Japanese Buddhist traditions (particularly by the Yamabushi mountain priests, from which it takes its Japanese name) — with traditional claims around stomach/digestive health, vitality, and cognitive function.\n\nChemically, Lion's Mane contains a complex mixture of bioactive compounds spanning polysaccharides (β-glucans), phenolic compounds, terpenoids, and — most importantly for nootropic purposes — two unique classes of compounds: **hericenones** (found primarily in the fruiting body, the above-ground mushroom part) and **erinacines** (found primarily in the mycelium, the underground root-like network). These compounds are believed to be the primary drivers of Lion's Mane's central nervous system effects. Fifteen hericenones (A-P) and numerous erinacines (A, B, C, E, J, P, Q, S and others) have been isolated and characterised, with different compounds present in different ratios depending on growth conditions, strain, and whether the extract comes from fruiting body or mycelium.\n\nThe central mechanistic claim for Lion's Mane — and the basis for its position in the nootropic and neurological-health supplement space — is that hericenones and erinacines stimulate the synthesis of **nerve growth factor (NGF)** and **brain-derived neurotrophic factor (BDNF)**, two of the most important neurotrophic proteins supporting neuron survival, dendritic growth, synaptic plasticity, and peripheral nerve regeneration. NGF and BDNF are critical for maintaining healthy CNS function across the lifespan, and their decline is implicated in neurodegenerative diseases (Alzheimer's, Parkinson's), diabetic peripheral neuropathy, age-related cognitive decline, and various psychiatric conditions including major depression. A compound that can raise endogenous NGF/BDNF production — if it translates to meaningful clinical effect — would be of substantial therapeutic interest.\n\nThe preclinical evidence for NGF/BDNF stimulation by Lion's Mane compounds is relatively strong. Mori, Kawagishi, Shimbo, and other Japanese researchers have published extensively on the NGF-stimulating effects of hericenones and erinacines in cell culture (PC12 cells, primary neuronal cultures) and rodent models of cognitive impairment. Erinacines, particularly erinacine A, cross the blood-brain barrier more efficiently than hericenones and show the strongest effects on brain NGF in animal studies. Multiple rodent models of Alzheimer's-type pathology, ischaemic brain injury, traumatic brain injury, and peripheral nerve crush injury have shown benefit from Lion's Mane extracts, with mechanistic data supporting NGF/BDNF involvement.\n\nThe human clinical evidence is more modest. The most frequently cited human trial is **Mori et al. 2009** (PMID: 18844328), published in *Phytotherapy Research* — a randomised, double-blind, placebo-controlled trial in Japanese adults aged 50-80 with mild cognitive impairment. Subjects received Lion's Mane fruiting body powder (3 g/day, containing hericenones) or placebo for 16 weeks. The Lion's Mane group showed statistically significant improvement on the revised Hasegawa Dementia Scale (HDS-R) compared with placebo at weeks 8, 12, and 16. Critically, the benefit disappeared after discontinuation (assessed at week 4 post-discontinuation), suggesting ongoing intake is needed to maintain any effect. The trial was small (n=30), conducted in one Japanese clinical setting, and used a cognitive scale more commonly applied in Japanese clinical practice than in Western cognitive research. It has not been replicated by independent Western research groups at scale.\n\nOther human evidence includes: **Nagano et al. 2010** (PMID: 20834180) — small study (n=30) suggesting Lion's Mane reduced symptoms of anxiety and depression in menopausal women over 4 weeks; **Saitsu et al. 2019**— small study (n=31) showing Lion's Mane extract (1.2 g/day containing amycenone) improved cognitive function and subjective sleep quality over 12 weeks in community-dwelling adults with self-reported cognitive complaints; and numerous smaller, less rigorous studies of peripheral neuropathy, peripheral nerve recovery, and various claims. The overall human evidence base is **suggestive but not definitive** — there is more human data for Lion's Mane than for most \"natural\" nootropics, but substantially less rigorous than for approved pharmaceuticals treating cognitive, psychiatric, or neurological conditions.\n\nWhere does Lion's Mane fit honestly in the therapeutic landscape? For **established Alzheimer's disease and related dementias**, the evidence-based treatments are cholinesterase inhibitors (donepezil, rivastigmine, galantamine), memantine, and — for appropriate prodromal and early Alzheimer's patients — the newer disease-modifying antibodies lecanemab and donanemab. Lion's Mane is NOT a substitute for any of these treatments. For **mild cognitive impairment and subjective cognitive decline** in older adults, the evidence-based interventions are aerobic exercise, Mediterranean-style diet, cognitive engagement, social engagement, management of vascular risk factors, and optimisation of sleep and mood. Lion's Mane may have an adjunctive role in this context based on Mori et al. 2009 but is not an established treatment. For **major depression**, evidence-based options are SSRIs, SNRIs, bupropion, mirtazapine, and increasingly ketamine/esketamine for treatment-resistant cases — Lion's Mane is NOT a substitute. For **peripheral neuropathy**, evidence-based first-line treatments are SNRIs (duloxetine), gabapentinoids, tricyclic antidepressants, and topical agents — Lion's Mane has some preclinical rationale but limited human trial evidence for this indication.\n\nWhere Lion's Mane may have a reasonable place is: (1) as a **general cognitive-support supplement** in older adults interested in a low-risk, natural option with modest supporting evidence; (2) as a **component of broader nootropic stacks** focused on neurotrophic support (often combined with [uridine](/compound/uridine-monophosphate), choline sources, and DHA); (3) as a **culinary mushroom with pleasant seafood-like flavour** that incorporates potentially beneficial compounds into ordinary diet; (4) as an **adjunct for occupational/functional cognitive demands** in healthy adults seeking modest support with minimal risk. It is unlikely to produce dramatic cognitive effects and should not be positioned as such.\n\nLion's Mane has one of the best safety profiles of any nootropic — it is a food item in Japan, China, Korea, and increasingly in Western cuisine, and has been consumed by humans for centuries without significant safety concerns. Allergic reactions have been reported, particularly in individuals with other mushroom allergies, but these are uncommon. It is generally regarded as safe for long-term daily use at typical supplemental doses.\n\nThe supplement market for Lion's Mane has exploded in the 2020s, with products ranging from high-quality extracts with standardised hericenone/erinacine content to essentially worthless mycelium-on-grain products with minimal active compound content. Quality control is a significant issue: many commercial products are mycelium grown on grain substrate, harvested together with the grain, and marketed as \"Lion's Mane\" while containing predominantly starch/grain material with minimal mushroom content. Users seeking evidence-based use should look for **fruiting body extracts** with **standardised polysaccharide content** and — ideally — **disclosed hericenone/erinacine content**, though the latter is rarely provided by manufacturers.", "half_life": "", "molecular_weight": "", "molecular_mass": "N/A", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "Phase 2", "cas_number": "N/A", "iupac_name": "N/A", "chemical_formula": "N/A", "potential_benefits": [ "NGF stimulation", "Neurogenesis", "Memory improvement", "Nerve repair", "Anxiety reduction", "Depression improvement" ], "research_fields": [ "Mild cognitive impairment", "Alzheimer's disease", "Peripheral neuropathy", "Depression", "Anxiety" ], "pubmed_count": 554, "pubchem_cid": 0, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/lions-mane" }, { "id": "9e022051-c19e-405a-99a9-c14520ef34f6", "slug": "lipo-c", "name": "Lipo-C", "aliases": [ "L-Carnitine MIC ATP", "MIC + ATP", "Lipotropic Injection", "Lipolytic Blend", "Lipo Fat Burner Blend", "Lipo Fat Burner", "MIC injection", "Optimum Lipolytic", "Optimum Lipolytic Research Blend" ], "category": "Weight Loss", "description": "Lipo-C (also sold as a MIC or \"lipotropic\" injection) is a compounded blend of methionine, inositol, and choline, usually with vitamin B12 and sometimes L-carnitine, marketed by medspas and weight-loss clinics to support fat metabolism and energy. The individual nutrients have real, defined metabolic roles and some modest human data, but almost all of that evidence is from oral or dietary intake, and the injectable blend itself has no clinical trials demonstrating fat loss. Covered here for research and harm-reduction context only. Research Use Only.", "half_life": "Not applicable to the blend; the water-soluble components (choline, inositol, B-vitamins, carnitine) are cleared over hours to a few days, and excess is largely excreted.", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "1 mL of a compounded MIC blend intramuscularly, 1 to 2x per week. No standardized dose exists; concentrations vary by compounding pharmacy.", "dosing_frequency": "1 to 2 times per week (intramuscular; occasionally subcutaneous)", "cycle_length": "Commonly used in 4 to 8 week blocks alongside a diet phase; no evidence-based cycle length exists. RUO.", "common_vial_sizes": [], "research_stage": "No clinical trials of the blend (marketed compounded injection)", "approval_status": "Not FDA-approved as a drug. Components are dietary nutrients supplied through compounding pharmacies. Research Use Only.", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "Blend", "potential_benefits": [ "Supplies choline and methionine, methyl donors the liver uses to package and export triglycerides (most relevant when dietary intake is low) [PMID:30681159]", "Provides inositol, which improved ovarian function and produced modest weight loss versus placebo in a randomized trial in women with PCOS [PMID:15206484]", "When L-carnitine is included, adds a cofactor for shuttling fatty acids into mitochondria; oral carnitine yields a modest average weight reduction in meta-analyses [PMID:32359762]", "B12 (when included) supports energy and red-cell metabolism, but relieves fatigue only when a genuine deficiency is present", "May help correct sub-optimal choline status, which is associated with a higher risk of hepatic steatosis [PMID:37513629]", "Popular anecdotally as an energy 'kickstart' adjunct to a calorie-controlled diet, though these effects are subjective and unproven" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/lipo-c" }, { "id": "a2ded48d-cf49-497d-b4db-6f1fa7f9a9da", "slug": "livagen", "name": "Livagen", "aliases": [ "Hepatic peptide" ], "category": "Recovery", "description": "\nLivagen is a short synthetic peptide developed in Russia by Vladimir Khavinson and his collaborators at the St. Petersburg Institute of Bioregulation and Gerontology, positioned as a \"liver bioregulator\" intended to normalise age-related and stress-related changes in hepatic tissue. It is usually described in Khavinson-family publications as the tetrapeptide Lys-Glu-Asp-Ala (KEDA), sometimes written as H-Lys-Glu-Asp-Ala-OH or K-E-D-A, and is one of the shortest members of the large peptide-bioregulator family that also includes [Epitalon](/compound/epithalon) (Ala-Glu-Asp-Gly), [Pinealon](/compound/pinealon) (Glu-Asp-Arg), [Vilon](/compound/vilon) (Lys-Glu), and [Thymogen](/compound/thymogen) (Glu-Trp). Within that framework, Livagen is the \"sibling\" peptide to a longer polypeptide preparation called Stamakort/Cortex peptide — which is a porcine liver extract — and is sold in the post-Soviet supplement channel as a dietary capsule alongside the other Khavinson tetrapeptides.\n\nOutside Russia and a small number of former-Soviet-state pharmacology journals, Livagen is **not a registered drug, not a dietary ingredient reviewed by FDA, EMA or any major English-language regulator, and not a member of the WADA Prohibited List**. There are no phase II or phase III randomised trials for Livagen indexed in PubMed or on ClinicalTrials.gov. The published Russian work — most of it co-authored by Khavinson and published in Bulletin of Experimental Biology and Medicine between 2002 and 2015 — describes *in vitro* chromatin effects and small rodent studies showing modulation of hepatic gene expression, hepatocyte proliferation markers, and restoration of age-related changes in liver morphology ([Khavinson et al., 2003]; [Khavinson and Malinin, 2005]; [Anisimov et al., 2010]).\n\nThe central therapeutic claim Khavinson's group makes for Livagen is that the Lys-Glu-Asp-Ala tetrapeptide — small enough to cross plasma and nuclear membranes passively — can enter hepatocyte nuclei, interact with chromatin via sequence-selective contacts with histones and DNA, and preferentially activate transcription programmes that are normally suppressed by age and chronic stress. That model predicts selective reversal of age-related hepatic dysfunction without mitogenic or pro-inflammatory effects. The hypothesis is interesting and internally consistent within the Khavinson programme, but the molecular validation required by contemporary structural biology — co-crystal structures, ChIP-seq in hepatocyte models, chemically defined knock-out rescue — has not been published in Western-indexed literature. Readers should understand Livagen as an investigational Russian bioregulator with a sustained 25-year research programme inside one institute and minimal replication outside it.\n\nBodyHackGuide covers Livagen because it is frequently sold online — usually as 20 mg capsules containing roughly 2–4 mg of actual peptide per capsule — and because it appears in longevity-stack discussions alongside better-validated compounds. We describe what is known, what is claimed, and what is missing, and we steer readers who want evidence-graded hepatic support toward interventions with stronger replication: weight management, alcohol reduction, [NAD+ precursors](/compound/nad) for mitochondrial support, [Berberine](/compound/berberine) and [metformin](/compound/metformin) for insulin-sensitising metabolic benefit in non-alcoholic fatty liver disease, and TUDCA ([Tauroursodeoxycholic acid](/compound/tudca)) for cholestatic biochemistry. Livagen is a plausible hypothesis. It is not, at this writing, an evidence-graded hepatic therapy.\n", "half_life": "", "molecular_weight": "~461.5 Da (C18H31N5O9)", "molecular_mass": "461.47 g/mol", "amino_acid_sequence": "Lys-Glu-Asp-Ala (KEDA)", "administration_routes": [], "dose_range_mcg": "20 mg oral/sublingual capsule once daily for 10 consecutive days per cycle (or 2-5 mg subcutaneous daily using synthetic peptide); 60-90 day washout between cycles", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "109028-17-7", "iupac_name": "L-Lysyl-L-glutamyl-L-aspartyl-L-alanine", "chemical_formula": "Lys-Glu-Asp-Ala", "potential_benefits": [ "Liver tissue repair and regeneration", "Enhanced detoxification capacity", "Hepatocyte function normalization", "Liver anti-aging support" ], "research_fields": [], "pubmed_count": 17, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/livagen" }, { "id": "4c04a5fb-f0c2-47d9-b01a-1f93dff0f17a", "slug": "ll-37", "name": "LL-37", "aliases": [], "category": "Immune & Inflammation", "description": "LL-37 is the only human cathelicidin, a 37-amino-acid amphipathic alpha-helical peptide (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES) cleaved from the C-terminus of the 170-amino-acid precursor hCAP-18 (human cationic antimicrobial protein, 18 kDa), which is encoded by the CAMP gene on chromosome 3p21.31. The \"LL\" in its name refers to the two leucine residues at the N-terminus; \"37\" is the length. LL-37 is stored in the secondary granules of neutrophils and produced by mucosal epithelial cells, keratinocytes, sebocytes, and certain lymphocyte populations, where it serves as a core component of the innate immune system — one of the evolutionarily ancient defenses that operates without requiring prior antigen exposure or adaptive immune priming. The peptide was first isolated in 1995 by Jürgen Gudmundsson, Birgitta Agerberth, and colleagues at the Karolinska Institute, and has since been the subject of more than 5,000 published studies exploring its roles in infection defense, wound healing, inflammation modulation, angiogenesis, and (paradoxically) inflammatory disease pathogenesis ([Gudmundsson et al., 1996], [Vandamme et al., 2012]).\n\nLL-37's mechanism of antimicrobial action is fundamentally different from conventional antibiotics. Where small-molecule antibiotics target specific bacterial enzymes or structures (ribosomes, cell wall synthesis, DNA gyrase), LL-37 operates by direct physical disruption of microbial membranes. The peptide is cationic (net charge +6) and amphipathic — one face of the alpha-helix is hydrophobic, the other hydrophilic — which allows it to insert into negatively charged bacterial membranes (rich in phosphatidylglycerol and cardiolipin) while largely sparing mammalian cell membranes (rich in zwitterionic phosphatidylcholine and cholesterol). Once inserted, LL-37 forms transient pores, disrupts membrane potential, and kills the target organism. This mechanism is active against a broad spectrum — gram-positive and gram-negative bacteria, mycobacteria (including M. tuberculosis), fungi (Candida species), some enveloped viruses, and even biofilm-embedded organisms that resist conventional antibiotics ([Dürr et al., 2006]). Crucially, the membrane-disruption mechanism makes resistance development slower and more difficult than with molecular-target antibiotics — bacteria cannot easily redesign the bulk charge and composition of their membranes without compromising viability.\n\nBeyond direct antimicrobial effects, LL-37 has important immunomodulatory roles. It recruits neutrophils, monocytes, T cells, and mast cells to sites of infection; modulates cytokine production by immune cells; promotes wound re-epithelialization and angiogenesis; and interacts with pattern-recognition receptors (TLR, FPR2/ALX, P2X7) to shape innate immune responses. This immunomodulation is largely protective, but LL-37 has also been implicated in the pathogenesis of certain chronic inflammatory conditions — most notably rosacea (where cathelicidin processing is dysregulated leading to pathological LL-37 fragments) and psoriasis (where LL-37 complexed with self-DNA activates plasmacytoid dendritic cells via TLR9, driving the Th17 inflammatory cascade characteristic of the disease). This dual role — protective in acute infection, pathogenic when dysregulated in chronic inflammatory disease — is a recurring theme in cathelicidin biology ([Yamasaki et al., 2007], [Lande et al., 2007]).\n\nIn clinical use, LL-37 has been investigated as a topical treatment for chronic infected wounds and diabetic foot ulcers (with some positive results in early trials but no approved product), as an adjunct to eradicate biofilm-related infections, and — more controversially in peptide-user communities — as a subcutaneous injection for systemic antimicrobial activity in chronic Lyme disease, chronic infections, and immune dysregulation syndromes. The peptide-community use is not supported by rigorous trial evidence, and the theoretical concerns are significant: systemic LL-37 at therapeutic antimicrobial concentrations has narrow margins between pharmacologic and toxic effects because the same membrane-disrupting activity that kills bacteria can also damage mammalian membranes at sufficient concentrations. LL-37 also has pro-inflammatory potential at certain doses and in certain disease contexts. This entry covers the established biology of LL-37, the legitimate research interest, and the considerable uncertainty around off-label human use ([Hilchie et al., 2013]).\n\nLL-37 is frequently discussed alongside other peptides with overlapping or complementary roles. Cross-references include [Thymosin-Alpha-1](/compound/thymosin-alpha-1) for adaptive immune modulation, [BPC-157](/compound/bpc-157) for tissue repair and vascular protection, and [TB-500](/compound/tb-500) for wound healing and actin biology. Unlike Tα1 which modulates host immunity to fight infection, LL-37 has direct antimicrobial activity — the two can be complementary in chronic infection contexts.", "half_life": "~30 minutes (free peptide; rapidly cleared by proteolysis). Human pharmacokinetics of exogenous LL-37 are not well characterized.", "molecular_weight": "4493.4 g/mol", "molecular_mass": "4493.4 g/mol", "amino_acid_sequence": "LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Clinical", "approval_status": "Research Use Only", "trial_phase": "Phase 2", "cas_number": "154947-66-7", "iupac_name": "Leu-Leu-Gly-Asp-Phe-Phe-Arg-Lys-Ser-Lys... (37 amino acid sequence)", "chemical_formula": "C205H340N60O53S", "potential_benefits": [ "Broad-spectrum antimicrobial activity", "Wound healing acceleration", "Biofilm disruption", "Immune system modulation", "Anti-inflammatory effects", "Gut barrier support" ], "research_fields": [ "Chronic infections", "Wound healing", "Cystic fibrosis", "Chronic sinusitis", "Skin conditions", "Cancer" ], "pubmed_count": 3029, "pubchem_cid": 16130961, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/16130961/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/ll-37" }, { "id": "63924cf7-37c6-48cb-a7a5-7a6828942360", "slug": "lutein", "name": "Lutein", "aliases": [ "Lutein", "(3R,3'R,6'R)-beta,epsilon-carotene-3,3'-diol", "Xanthophyll", "Luteal", "Vegetable lutein", "Marigold lutein", "Tagetes erecta extract", "Marigold extract", "Lutein esters", "Free lutein", "Xangold", "FloraGlo", "Lutemax", "OptiLut", "Kemin lutein", "Trans-lutein", "Macular pigment", "Macular lutein", "E161b" ], "category": "Carotenoid", "description": "\nLutein is a dihydroxy-xanthophyll carotenoid that functions as the primary blue-light-absorbing, antioxidant macular pigment of the human retina, where along with its stereoisomers zeaxanthin and meso-zeaxanthin it concentrates selectively in the central macula at concentrations exceeding 1,000 times those found in any other body tissue. The macular pigment is a distinctive feature of human visual biology — its yellow color (the name \"macula lutea\" means \"yellow spot\") is visible on ophthalmoscopic examination, its optical density can be measured non-invasively as macular pigment optical density (MPOD), and its concentration has been correlated with protection against age-related macular degeneration (AMD), cataract formation, and cognitive decline in aging. Unlike astaxanthin (which is absent from or present at trace levels in retinal tissue), lutein is a true retinal resident — selectively imported, anatomically concentrated, and biochemically active in photoreceptor membrane environments. The landmark AREDS2 trial (Age-Related Eye Disease Study 2, Chew 2013 JAMA PMID 23644932) established that lutein 10 mg/day plus zeaxanthin 2 mg/day can be safely substituted for beta-carotene in AMD prevention formulations, providing equivalent or superior protection without the lung cancer risk observed in smokers receiving beta-carotene in the original AREDS study. This substitution now serves as the basis for the AREDS2 nutrient formulation recommended by ophthalmologists for patients with intermediate AMD and high-risk AMD in one eye.\n\nLutein was isolated from plants and named by John Stenhouse in 1847 (from the Latin \"luteus\" meaning yellow). Its structural characterization as (3R,3''R,6''R)-beta,epsilon-carotene-3,3''-diol followed over the next century. Lutein occurs in essentially all plants, where it participates in photosynthesis-related light harvesting and photoprotection. Its isomer zeaxanthin differs by one double bond position; lutein has a beta-ring and an epsilon-ring, while zeaxanthin has two beta-rings, making lutein slightly asymmetric and zeaxanthin symmetric. Meso-zeaxanthin (3R,3''S-zeaxanthin) is found almost exclusively in the macula, formed there from lutein through a retinal-specific isomerase (RPE65-related mechanism). Together, these three xanthophylls constitute macular pigment, with lutein dominating the peripheral macula (parafoveal region), meso-zeaxanthin dominating the central fovea, and zeaxanthin distributed across both regions.\n\nThe physiological importance of macular pigment is inferred from its anatomic concentration, its evolutionary conservation across primates, its protective absorption of short-wavelength blue light (wavelengths most damaging to retinal photoreceptors), and its association with reduced rates of AMD and improved contrast sensitivity. The absorbance maximum of macular pigment is approximately 460 nm (blue light), which coincides with the wavelength range known to cause maximum photoreceptor damage through generation of reactive oxygen species in the retinal pigment epithelium and outer photoreceptors. By filtering this light before it reaches the photoreceptors, macular pigment functionally reduces retinal oxidative burden. Macular pigment optical density (MPOD) can be measured by heterochromatic flicker photometry, autofluorescence imaging, or reflectance spectroscopy; individuals with higher MPOD have lower rates of AMD and better visual function with age.\n\nDietary lutein intake in typical Western populations is approximately 1-3 mg/day, predominantly from leafy green vegetables (kale, spinach, collard greens, turnip greens — spinach contains 8-12 mg lutein per 100 g cooked, kale 22-26 mg per 100 g cooked), from egg yolks (0.2-0.4 mg per large yolk, highly bioavailable due to yolk lipid matrix), from yellow and orange vegetables (corn, yellow peppers, squash, marigold-infused butter), and from certain fruits. Supplementation-grade lutein is produced primarily from marigold flowers (Tagetes erecta) via CO2 extraction; industrial sources include branded products like FloraGlo (Kemin Industries), Xangold (Cognis/BASF), Lutemax 2020 (OmniActive Health Technologies, which notably also contains both meso-zeaxanthin and zeaxanthin), and OptiLut. These are the forms used in clinical trials and medical food formulations.\n\nAbsorption of lutein from foods is lipid-dependent. Lutein from egg yolks has substantially higher bioavailability than lutein from leafy greens (approximately 3-fold higher) due to the egg yolk's fat matrix, which facilitates micelle formation. Cooking and fat addition to leafy greens (olive oil, butter) significantly improves lutein bioavailability. Lutein circulates in plasma bound to HDL (and to a lesser extent LDL), reaching Cmax at approximately 8-16 hours after oral dosing. Plasma half-life is approximately 5-10 days — even longer than astaxanthin's 2-3 day half-life, making lutein accumulate substantially with chronic supplementation. Uptake into the retina involves specialized transport: HDL delivers lutein to the retinal pigment epithelium via scavenger receptor class B type 1 (SR-B1), which recognizes HDL particles, and the protein StARD3 (also known as MLN64) transfers lutein into the retinal tissue. Within the retina, a specific binding protein (IRBP) and possibly other xanthophyll-binding proteins concentrate lutein in photoreceptor outer segments and in the macular Henle fiber layer.\n\nThe clinical evidence for lutein supplementation is among the best for any carotenoid, with multiple large RCTs across ophthalmologic, cognitive, and general health endpoints. The AREDS2 trial (Chew 2013 PMID 23644932) enrolled over 4,000 subjects with intermediate AMD or advanced AMD in one eye, randomized to various AREDS-formulation variants including the substitution of lutein 10 mg/day plus zeaxanthin 2 mg/day for beta-carotene. Over 5-year follow-up, the lutein/zeaxanthin-containing formulation provided equivalent protection against progression to advanced AMD compared to the original AREDS formulation with beta-carotene, and notably reduced the rate of progression in subjects with low dietary lutein intake. The lutein/zeaxanthin substitution eliminated the lung cancer risk associated with beta-carotene in smokers. This established AREDS2 as the formulation of choice for AMD prevention supplementation. Separate trials have demonstrated improvements in contrast sensitivity, glare recovery, visual fatigue, macular pigment optical density, and subjective visual function with lutein supplementation at 10-20 mg/day over 4-12 months in broad populations.\n\nBeyond eye health, lutein has accumulating evidence for cognitive support. Johnson 2014 and Renzi 2014 have shown that macular pigment optical density correlates with cognitive function in aging adults, and supplementation has produced measurable improvements in memory, processing speed, and executive function in some trials. The Lutemax 2020 CARES-1 and B.L.U.E. trials (Stringham 2017 and others) showed improvements in cognitive measures and reductions in perceived stress. The mechanistic basis involves lutein's presence in neural tissue (not just retina — lutein accumulates in brain gray matter, particularly in the frontal cortex), its antioxidant and anti-inflammatory effects at neural sites, and its protective effects against blue-light-associated circadian and visual health disruption.\n\nBodyHackGuide's take: lutein is among the best-evidenced dietary supplements for specific eye health applications and has meaningful if modest evidence for broader cognitive and cardiovascular support. For adults with AMD or at high risk of AMD (family history, advanced age, smoking history), AREDS2 supplementation (including 10 mg lutein + 2 mg zeaxanthin) is evidence-based and recommended by ophthalmology guidelines. For adults interested in eye health maintenance (heavy screen use, aging, reduced leafy green intake), 10-20 mg lutein daily with fat-containing food provides plausible benefit. For cognitive support in aging, lutein 10-20 mg/day combined with zeaxanthin and other carotenoids is reasonable adjunct. Cost is modest ($10-25/month at typical doses). Safety is excellent — no significant adverse effects at supplementation doses, no drug interactions of clinical significance, and an extensive dietary safety history. The main practical consideration is that lutein is often stacked with zeaxanthin (2-4 mg/day) and meso-zeaxanthin (2-4 mg/day) for complete macular pigment support; the Lutemax 2020 blend and similar products provide all three. For users with good dietary lutein (daily leafy greens and egg yolks), additional supplementation is modest incremental value; for users with limited dietary lutein, supplementation is higher-yield.\n", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 2075, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/lutein" }, { "id": "7f0a5ed5-87dd-4001-a49b-c811779e224e", "slug": "lycopene", "name": "Lycopene", "aliases": [ "Lycopene", "psi,psi-Carotene", "all-trans-lycopene", "5-cis-lycopene", "9-cis-lycopene", "13-cis-lycopene", "Tomato extract", "Tomato oleoresin", "Lyc-o-Mato", "Redivivo", "LycoRed", "Lyc-O-Pen", "CaroCare", "Acyclic carotenoid", "Solanum lycopersicum extract", "E160d", "Lyco" ], "category": "Carotenoid", "description": "\nLycopene is a red pigment carotenoid belonging to the acyclic hydrocarbon carotene subfamily, chemically designated psi,psi-carotene. Unlike most dietary carotenoids which are cyclic (contain one or two ring structures at the ends of their polyene chain), lycopene is fully open-chain with both terminal ends existing as linear isoprenoid units bearing methyl branches but no rings. This single structural distinction — the absence of terminal rings — gives lycopene several of its most distinguishing biological properties: it cannot be cleaved to form retinal (vitamin A) by beta-carotene 15,15'-oxygenase, it is one of the most efficient singlet oxygen quenchers among all natural molecules, and it has a highly characteristic strong red color at around 470-475 nm absorbance that gives tomatoes, watermelon, pink grapefruit, and papaya their color.\n\nThe primary human dietary source of lycopene is cooked and processed tomatoes. Raw tomatoes contain modest amounts of lycopene (2-3 mg per 100 g) almost entirely in the all-trans configuration locked within chromoplast protein-lipid complexes of the tomato cell matrix. Raw tomato consumption provides limited lycopene bioavailability because the chromoplast matrix is resistant to digestion and because all-trans-lycopene crystalline structures are poorly absorbed. Thermal processing and mechanical disruption during cooking, canning, and processing break the chromoplast matrix and isomerize a fraction of all-trans-lycopene to more bioavailable cis isomers (particularly 5-cis, 9-cis, and 13-cis). The resulting processed tomato products — tomato paste, pasta sauce, tomato soup, ketchup, and especially canned or stewed tomatoes cooked with oil — provide substantially more absorbable lycopene per gram than the fresh fruit. Tomato paste concentrates lycopene to 30-60 mg per 100 g. Ketchup typically contains 15-20 mg per 100 g. Pizza, pasta sauce, and minestrone soup are major lycopene contributors in the Mediterranean and Western diets.\n\nNon-tomato dietary sources of lycopene include watermelon (4-5 mg per 100 g), pink guava (5-6 mg per 100 g), pink grapefruit (1-2 mg per 100 g), papaya (1-2 mg per 100 g), and rosehips. Gac fruit (Momordica cochinchinensis), a Southeast Asian climbing gourd, contains extraordinary lycopene concentrations of 20-70 mg per 100 g and is a dietary staple in parts of Vietnam. Rose hip powder is used as a lycopene-rich supplement ingredient in some formulations.\n\nSupplemental lycopene is produced by several routes: extraction from tomato skins and seeds (industrial byproducts of tomato processing), extraction from Blakeslea trispora fungal fermentation (LycoRed, CaroCare), and synthetic production. Lyc-o-Mato (LycoRed, Israel) is the most extensively studied tomato-derived lycopene extract, standardized to 6% lycopene with accompanying tomato phytonutrients including phytoene, phytofluene, beta-carotene, and tocopherols. Redivivo (DSM) is a fermentation-derived lycopene from Blakeslea. CaroCare is another branded synthetic or fermentation lycopene. The distinction between tomato-extract lycopene (which contains the full phytonutrient complex) and isolated pure lycopene matters for research interpretation; several studies have found that whole tomato products outperform pure lycopene supplements, suggesting cofactor contributions from phytoene, phytofluene, and other tomato carotenoids.\n\nThe evidence base for lycopene is largest in prostate cancer prevention and cardiovascular disease. Giovannucci 1995 (NEJM PMID 7752271) analyzed dietary data from 47,894 male health professionals in the Health Professionals Follow-up Study and found that tomato product consumption (2+ servings per week) was associated with a 25-35% reduction in prostate cancer risk. Subsequent analyses extending the follow-up period confirmed the association. However, a 2005 FDA review (Kavanaugh 2007) concluded that evidence supporting a health claim for lycopene and cancer was weak when considering only highest-quality interventional studies, because most human evidence was epidemiologic and because most trials testing isolated lycopene supplementation did not replicate the dietary pattern benefits. This tension — strong epidemiology with whole tomato products, weaker evidence with isolated lycopene — has defined the field.\n\nMore recent work has partially resolved the tension. Chen 2015showed that lycopene supplementation in men undergoing radical prostatectomy increased prostate tissue lycopene concentrations and produced measurable changes in apoptosis, proliferation, and oxidative damage markers. Multiple meta-analyses of observational and interventional studies (Wang 2015, Chen 2013) consistently show modest but statistically significant inverse associations between lycopene intake or serum lycopene and prostate cancer risk, with the effect clearer in aggressive or advanced cases than in localized low-grade disease.\n\nCardiovascular evidence for lycopene comes from multiple fronts. Serum lycopene concentrations inversely correlate with carotid intima-media thickness, coronary calcium scores, and cardiovascular event rates across multiple cohorts including the Kuopio Ischemic Heart Disease study (Rissanen 2003), ATBC trial secondary analyses, and EPIC cohort analyses. Lycopene incorporation into LDL particles increases LDL oxidation resistance, a proposed mechanism for reduced atherosclerotic progression. Mechanistic trials using isolated lycopene or tomato products show reductions in oxidized LDL, modest reductions in systolic blood pressure (roughly 2-4 mmHg in meta-analysis), and improvements in endothelial function measured by flow-mediated dilation.\n\nSkin photoprotection represents a third well-documented lycopene benefit. Stahl 2000showed that 10 weeks of tomato paste consumption providing 16 mg/day lycopene increased skin tolerance to UV radiation by roughly 40%, measured as minimal erythema dose. Subsequent trials with isolated lycopene supplementation have replicated smaller but similar effects. The mechanism involves direct lycopene accumulation in skin, reduction of UV-induced reactive oxygen species, and modulation of UV-induced matrix metalloproteinases.\n\nFor bodyhackguide.co users, lycopene occupies a specific place in the male aging, cardiovascular prevention, and general antioxidant stacks. It pairs naturally with other antioxidant carotenoids such as [lutein](/compound/lutein) and [zeaxanthin](/compound/zeaxanthin) (different spatial distribution — lycopene concentrates in plasma, liver, lung, prostate, and testis rather than eyes), [astaxanthin](/compound/astaxanthin) (complementary membrane-stabilizing xanthophyll), and [beta-carotene](/compound/beta-carotene) (for users who want a full carotenoid complex). It overlaps with [vitamin-e](/compound/vitamin-e) and [selenium](/compound/selenium) in the prostate prevention arc (SELECT trial context). Cardiovascular stacks include [coq10](/compound/coq10), [omega-3](/compound/omega-3), [vitamin-k2](/compound/vitamin-k2), and [magnesium](/compound/magnesium). The strongest evidence-based recommendation for most users is to consume 10-30 mg daily of lycopene from cooked tomato products with a fat-containing meal, with isolated lycopene supplementation as a fallback when dietary intake is inadequate or when prostate-specific prevention is the goal.\n", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/lycopene" }, { "id": "94808d0e-f08a-4391-9a5b-59227600d498", "slug": "maca", "name": "Maca (Lepidium meyenii)", "aliases": [ "Lepidium meyenii", "Peruvian Ginseng", "Maca Root", "Maka", "Mace", "Ayak Chichira", "Ayuk Willku", "Maino", "Black Maca", "Red Maca", "Yellow Maca", "Gelatinized Maca" ], "category": "Adaptogen", "description": "**Maca** (scientific name *Lepidium meyenii*; called **maca** in Spanish and Quechua; historically **ayak chichira** or **ayuk willku** in pre-Columbian Andean languages; marketed as **Peruvian Ginseng** in some Western commerce — though it is botanically unrelated to true ginseng from the Araliaceae family) is an annual herbaceous plant in the Brassicaceae (mustard/cabbage) family. It's actually related to radishes, turnips, kale, and broccoli — sharing genetic lineage with cruciferous vegetables and the associated glucosinolate phytochemistry. Maca grows exclusively at elevations of **4,000-4,500 meters** (13,000-14,800 feet) in the Andes mountains of central Peru, particularly the **Junín and Pasco regions** around Lake Chinchaycocha. This is one of the highest elevations at which any agricultural crop is cultivated worldwide — a harsh environment featuring intense UV radiation, subfreezing temperatures, strong winds, and poor soils where very few plants can survive, let alone thrive. Maca's ability to produce a substantial edible root (technically a hypocotyl, not a true root) in these conditions is itself notable. The harvested hypocotyl resembles a small turnip or radish, typically 3-6cm in diameter, with colors ranging from yellow (most common, ~60% of traditional harvest) through red (~25%) to black (~15%) and various intermediates.\n\nMaca has been cultivated and used by indigenous Andean peoples for **at least 2,000-3,000 years**. Archaeological evidence from the Nazca and Inca periods documents its importance as both a staple food and a medicinal/ceremonial substance. **Inca warriors** reportedly consumed maca before going into battle to increase strength and endurance, though restricted its use after battles (a detail that has been romanticized in modern marketing but has some historical basis). Spanish colonial records from the 16th century document the Spanish crown accepting maca as tribute from Andean communities and recognizing its importance for improving fertility in livestock (cattle and sheep brought from Spain struggled to reproduce at high altitude; feeding them maca reportedly restored fertility). Maca was nearly lost during the Spanish colonial period but survived through traditional use in isolated Andean communities. Modern commercial resurgence began in the 1990s as Peruvian researchers began modern pharmacological investigation and international markets discovered it.\n\nTraditional Andean uses of maca span both nutritional and medicinal categories: **(1) nutritional** — maca is consumed as a food, typically dried, milled into flour, and incorporated into breads, porridges (*mazamorra*), fermented beverages (*chicha de maca*), and sweet puddings. The taste is distinctive — butterscotch-like with earthy, slightly nutty notes. **(2) Energy and fatigue** — traditional use for combating high-altitude fatigue, supporting physical labor, and recovering from illness; **(3) Fertility enhancement** — arguably the most prominent traditional use, for both humans and livestock, spanning male fertility (sperm production, erectile function) and female fertility (regularization of cycles, post-partum recovery); **(4) Libido enhancement** — for both sexes, traditionally consumed prior to intimate occasions; **(5) Adaptation to high altitude** — supporting work capacity at elevations where outsiders typically struggle; **(6) Memory and cognition** — traditional use for students and elderly; **(7) Female reproductive health** — including menstrual regulation, menopause support, fertility; **(8) Male reproductive health** — including impotence, weak erections, low libido; **(9) Bone and joint health** — traditional use for rheumatism and arthritis; and **(10) General rejuvenation** — classical \"adaptogen\" role before the term existed in Western herbalism.\n\nMaca's distinctive **color variants** have been shown in modern research to have somewhat different phytochemical profiles and clinical effects. **Yellow maca** (cream maca) is the most common, most nutritional, and widely used for general wellness and energy. **Red maca** has higher concentrations of certain glucosinolates and has shown specific effects on prostate health (benign prostatic hyperplasia) and bone health in clinical trials. **Black maca** has been specifically associated with cognitive effects, sperm production/male fertility, and potentially stronger physical performance effects. The **tricolor** (yellow + red + black) blend is traditional and provides all three profiles. Some premium commercial products emphasize specific colors for specific indications.\n\nThe primary bioactive compounds in maca span several chemical classes. **Macamides** are maca-unique fatty acid amides — N-benzylpalmitamide, N-benzyl-oleamide, N-benzyl-linoleamide, and related compounds — that are thought to be responsible for many of maca's central nervous system and anxiolytic effects. Macamides have been shown to interact with the endocannabinoid system and inhibit fatty acid amide hydrolase (FAAH), thereby preserving endogenous anandamide and other endocannabinoid signaling. **Macaenes** are related unsaturated fatty acids also thought to contribute to pharmacologic effects. **Glucosinolates** (including glucotropaeolin and related compounds) are characteristic cruciferous phytochemicals that may be transformed into bioactive isothiocyanates in the gut. **Sterols** including β-sitosterol contribute to hormonal support. **Alkaloids** (including macaridine, lepidilines) are present in small quantities. **Amino acids, minerals, and carbohydrates** provide nutritional substrates — maca is notably rich in zinc, iron, copper, and essential amino acids, which contribute to its nutritional tonic effects. **Prostaglandins and polyamines** are also present. The complex phytochemistry means that different preparations (raw vs. cooked/gelatinized, different color variants, different processing methods) have somewhat different therapeutic profiles.\n\nThe proposed clinical applications of maca span: **(1) libido and sexual dysfunction** — possibly its best-established modern application, with multiple RCTs showing libido enhancement in both men and women without requiring direct hormonal changes; **(2) male fertility and sperm quality** — improvements in sperm count, motility, and morphology in multiple trials; **(3) menopause and women's hormonal health** — effects on menopausal symptoms (hot flashes, mood, sleep, sexual function) without direct estrogenic activity; **(4) erectile dysfunction** — particularly SSRI-induced sexual dysfunction, with Cochrane-level evidence; **(5) mood and anxiety** — effects on depression and anxiety in various contexts; **(6) energy and fatigue** — traditional application with some modern evidence; **(7) cognitive function** — memory and mental performance effects, particularly with black maca; **(8) athletic performance and endurance** — traditional use with preliminary modern evidence; **(9) prostate health** — particularly red maca for BPH; and **(10) general adaptogenic wellness** — the broad \"adaptation to stress\" profile.\n\nHuman clinical evidence for maca has grown substantially since the early 2000s. Key trials: **Gonzales et al. 2002** (*Andrologia*) — RCT of maca gelatinized (1500 or 3000mg/day) for 12 weeks in men showed significant improvements in sexual desire independent of testosterone changes. **Gonzales et al. 2003** (*Journal of Endocrinology*) — examined effects on spermatogenesis showing increases in sperm count and motility with maca (1500-3000mg/day) for 4 months. **Shin et al. 2010** (*BMC Complementary and Alternative Medicine*, PMID 20691074) — systematic review and meta-analysis of 17 trials concluded maca had \"encouraging\" effects on sexual dysfunction in both men and women. **Dording et al. 2008** (*CNS Neuroscience & Therapeutics*) — RCT of maca (1500-3000mg/day) for SSRI-induced sexual dysfunction showed significant improvement at higher dose. **Meissner et al. 2005-2006** — series of RCTs on perimenopausal women showing significant reductions in menopausal symptoms. **Zenico et al. 2009** — RCT in mild erectile dysfunction showing improvement with maca supplementation. **Stone et al. 2009** — trial in healthy athletes showing performance effects. **Brooks et al. 2008** — examined postmenopausal women finding benefits in psychological function.\n\nWhere does maca fit in the therapeutic landscape? It occupies a distinctive niche: **(1)** **hormonal effects without hormones** — influences sexual function and reproductive health without measurable testosterone, estrogen, or LH changes in most studies (mechanisms are mostly non-hormonal); **(2)** **good-evidence sexual dysfunction intervention** — one of the few natural products with Cochrane-level systematic review support for libido; **(3)** **gender-balanced effects** — works for both men and women, unlike many \"androgen\" or \"female\" herbs; **(4)** **novel phytochemistry (macamides)** — unique endocannabinoid-related compounds; **(5)** **food-adjacent safety profile** — consumed as a staple food by millions, very safe; and **(6)** **SSRI-induced sexual dysfunction remedy** — particularly important clinical niche. It pairs meaningfully with [Ashwagandha](/compound/ashwagandha) (the Ayurvedic adaptogen — complementary adaptogens from different traditions with somewhat different tissue effects), [Tongkat Ali](/compound/tongkat-ali) (male-specific testosterone support — mechanistically different; together cover libido + testosterone more comprehensively), [Tribulus terrestris](/compound/tribulus-terrestris) (another libido/sexual function herb with different mechanisms), [Shilajit](/compound/shilajit) (Himalayan male reproductive tonic — cross-tradition synergy), [Horny Goat Weed](/compound/horny-goat-weed) (epimedium with icariin — PDE5 inhibition complementary to maca's central effects), [Ginkgo biloba](/compound/ginkgo-biloba) (circulation support), [Rhodiola rosea](/compound/rhodiola-rosea) (cross-regional adaptogen pair), [L-Arginine](/compound/l-arginine) (nitric oxide precursor for erectile function), [Ginseng](/compound/panax-ginseng) (shared adaptogenic profile), and specific pharmaceutical combinations for SSRI-induced sexual dysfunction (practitioner-guided).\n\nSafety is excellent at therapeutic doses, consistent with maca's long history as a staple food consumed by millions of Andean people over millennia. Formal toxicology confirms very low acute and chronic toxicity. Key considerations include: potential thyroid interactions (theoretical — maca is cruciferous and contains glucosinolates that can theoretically interfere with iodine uptake; clinically not commonly problematic but monitor if thyroid disease present), possible hormonal effects in sensitive individuals, very rare allergic reactions, and quality-control considerations (species authentication, contamination with other *Lepidium* species, proper gelatinization if cooked forms are preferred). Unlike some supplements where cheap products just don't work, maca is robustly safe across preparation qualities — the main quality concern is efficacy rather than toxicity.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 63, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/maca" }, { "id": "f7837d80-be45-45bf-a0fd-7d39f58bb0da", "slug": "magnesium", "name": "Magnesium", "aliases": [ "Mg", "Mg2+", "Magnesium citrate", "Magnesium glycinate", "Magnesium bisglycinate", "Magnesium malate", "Magnesium taurate", "Magnesium L-threonate", "Magnesium oxide", "Magnesium chloride", "Magnesium sulfate", "Magnesium orotate", "Magnesium lactate", "Epsom salt" ], "category": "Foundational", "description": "Magnesium is the fourth most abundant cation in the human body and the second most abundant intracellular cation after potassium, with approximately 25 grams present in a typical adult—roughly 60% stored in bone, 27% in muscle, 6-7% in other soft tissues, and less than 1% in extracellular fluid including serum. Despite this substantial total-body load, magnesium deficiency is extraordinarily common in modern populations: national survey data from the United States (DiNicolantonio et al.; Rosanoff et al.) suggests that roughly half of adults consume below the estimated average requirement, and a meaningful fraction—perhaps 10-30% depending on the criterion used—show biochemical evidence of frank deficiency. The prevalence is even higher among patients with type 2 diabetes, alcohol use disorder, heart failure, chronic proton pump inhibitor users, loop/thiazide diuretic users, and elderly adults with reduced appetite or impaired intestinal absorption. Because serum magnesium (the most commonly ordered clinical test) measures only that <1% extracellular fraction and is tightly defended by bone mineral release and renal reabsorption even when cellular stores are depleted, normal serum magnesium does not rule out functional deficiency. Many researchers argue that the reference range itself is set too low, rooted in population distributions that already reflect widespread subclinical deficiency.\n\nMagnesium functions as a required cofactor for more than 600 enzymatic reactions (Gröber et al., PMID 26404370)—essentially every reaction involving ATP, because the bioactive form of ATP is the Mg-ATP complex and free ATP has negligible biological activity. This places magnesium at the center of energy metabolism, protein synthesis, DNA and RNA synthesis, oxidative phosphorylation, glucose utilization, and cellular electrolyte homeostasis. Beyond its cofactor roles, magnesium is a physiological calcium channel antagonist: it competes with calcium at voltage-gated calcium channels in smooth muscle, cardiac conducting tissue, and neurons, which explains its effects on vascular tone, cardiac rhythm, neuromuscular excitability, and neuronal signaling. Magnesium also voltage-gates the NMDA glutamate receptor in the central nervous system—one of the fundamental mechanisms of synaptic plasticity and learning, and a key point of regulation in pain signaling, seizure thresholds, and mood.\n\nSupplemental magnesium is among the most thoroughly studied nutrient interventions in clinical medicine. Randomized trials and meta-analyses demonstrate meaningful effects on blood pressure (Zhang et al., PMID 27402922), insulin sensitivity and glycemic control in type 2 diabetes (Guerrero-Romero, PMID 21127832; Rodríguez-Morán and Guerrero-Romero, PMID 12663588), migraine frequency (Peikert et al., PMID 8792038; Facchinetti et al., PMID 1860787; Mauskop review), sleep quality in older adults (Abbasi et al., PMID 23853635), leg cramps in late-pregnancy and general populations (mixed evidence), depression symptoms (Tarleton et al., PMID 28654669), and muscle performance. Observational evidence associates higher magnesium intake with lower all-cause mortality, lower cardiovascular disease incidence, lower stroke risk, lower risk of type 2 diabetes, and better bone mineral density. Magnesium is also a first-line intravenous intervention for preeclampsia/eclampsia (MgSO4), torsades de pointes, severe asthma exacerbation, and certain arrhythmias—uses that reflect strong hospital-setting evidence but are distinct from routine oral supplementation.\n\nCommercial magnesium supplements span a confusing landscape of salts—citrate, glycinate (also called bisglycinate), malate, taurate, L-threonate, oxide, chloride, sulfate, orotate, lactate, aspartate, carbonate, hydroxide—with meaningfully different bioavailability profiles, elemental magnesium content per gram, tolerability, and tissue-specific effects. Magnesium oxide, despite being the cheapest and most common in drugstore multivitamins, has poor bioavailability (perhaps 4% absorbed in some studies) and tends to produce diarrhea. Magnesium glycinate and bisglycinate are generally regarded as among the best-tolerated forms for doses above a few hundred milligrams, with smooth absorption and minimal GI effect. Magnesium L-threonate is the only form with clinical trial evidence for brain-penetrant effects on memory and cognition (Liu et al.) and is marketed as Magtein. Magnesium taurate combines two cardioprotective minerals and is particularly favored for cardiovascular indications. Magnesium malate may benefit muscle energy metabolism via the malate-aspartate shuttle. The \"best\" form depends on the goal: sleep and general repletion favor glycinate or citrate; constipation relief favors citrate or oxide; migraine prophylaxis was studied mainly with citrate (600 mg trivalproate equivalents) or oxide; cognition research favors L-threonate; cardiovascular goals may favor taurate.\n\nFor BodyHackGuide users, magnesium is a cornerstone of any rational supplementation stack. The cost-to-benefit ratio is exceptional: for a few dollars monthly, users correct a common subclinical deficiency and gain measurable improvements in sleep latency, stress resilience, bowel regularity, blood pressure, and exercise recovery. The safety margin is wide for healthy adults with normal renal function. Yet many users either take too little (100-200 mg oxide from a multivitamin, poorly absorbed, insufficient to raise cellular stores) or take the wrong form for their goal. This monograph addresses form selection, dose titration, timing, stacking, and the specific clinical scenarios where magnesium supplementation is best evidenced. For related foundational support, see /compound/vitamin-d (reciprocal activation with magnesium in converting 25(OH)D to 1,25(OH)2D), /compound/zinc (another ubiquitously deficient mineral), /compound/taurine (synergy in magnesium taurate), /compound/glycine (synergy in magnesium glycinate), and /compound/creatine (ATP-dependent metabolism where magnesium is the counter-ion).", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 1, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/magnesium" }, { "id": "1dfb435e-9e8b-4780-8e87-965c814e5f63", "slug": "magnesium-l-threonate", "name": "Magnesium L-Threonate", "aliases": [ "Magtein", "L-Threonic Acid Magnesium Salt", "MgT", "Magnesium-L-Threonate", "L-TAMS", "Mg L-Threonate" ], "category": "Nootropic", "description": "**Magnesium L-Threonate** is a proprietary chelated form of magnesium in which the magnesium cation is bound to **L-threonic acid** — a metabolite of ascorbic acid (vitamin C) — forming the salt commonly marketed under the brand name **Magtein**. It was developed in the mid-2000s by researchers associated with **MIT** (notably **Guosong Liu**, then at the MIT Department of Brain and Cognitive Sciences) with the explicit goal of producing a magnesium compound that could **meaningfully raise brain magnesium concentrations** in a way that ordinary oral magnesium salts (oxide, citrate, glycinate, malate, chloride) have historically struggled to accomplish. The resulting molecule was commercialized through **Magceutics** and **Neurocentria**, and Magtein is now the dominant ingredient in cognition-oriented magnesium products marketed to consumers.\n\nThe clinical rationale behind magnesium L-threonate rests on a specific biological problem: **magnesium is a physiological NMDA glutamate receptor antagonist** — a voltage-dependent blocker that sits in the NMDA channel pore and regulates excitatory neurotransmission — yet CNS magnesium concentrations are tightly defended and **do not readily rise** in response to oral supplementation with most common magnesium forms. Even substantial oral dosing of magnesium oxide or citrate (often 400mg elemental or more daily) may produce modest serum changes without corresponding **cerebrospinal fluid (CSF)** or **brain extracellular** magnesium elevation. This is not merely a theoretical concern — it implies that people using conventional magnesium supplements for cognitive, sleep, anxiety, or mood benefits may be relying partly on peripheral effects and on small central effects that are difficult to measure and potentially limited in magnitude. **Slutsky et al. 2010** (*Neuron* PMID: 20152124) — the landmark MIT paper — demonstrated that L-threonate conjugation allows magnesium to raise brain magnesium concentrations in rats in a way that other forms did not, and that this elevation translated into **upregulated synaptic density**, **enhanced LTP (long-term potentiation)**, and **improved behavioral measures of learning and memory** in aged animals. This rat paper remains the single most cited justification for preferring Magtein over other magnesium forms for cognitive applications.\n\nTranslated human evidence is substantially thinner than the mechanistic rat data. **Liu et al. 2016** (*Journal of Alzheimer's Disease*) — the only decent human RCT published as of this writing — enrolled **44 older adults (ages 50-70) with cognitive impairment** and randomized them to 12 weeks of Magtein (1.5-2 grams/day providing approximately 144-192mg elemental magnesium) or placebo. The trial reported **improvements on a composite cognitive score** that the authors interpreted as a reduction in \"brain age\" by approximately 9 years. Results were favorable but the study was small, industry-sponsored (funded by Magceutics), and **independent replication has been weak** — a point that matters for a supplement marketed with confident claims about cognition, memory, and \"brain age.\" Users and practitioners should weigh that single decent RCT carefully: it is the most promising human data we have, but one small industry-funded trial is not a strong evidence base for the specific cognitive claims routinely made about Magtein in consumer marketing. Subsequent small trials have examined anxiety, sleep, and subjective cognitive symptoms with mixed and generally modest findings.\n\n**Why people actually take magnesium L-threonate** in practice usually comes down to a few overlapping use cases: (1) **cognitive support** — particularly older adults or people concerned about age-related cognitive decline, based on Slutsky 2010 and Liu 2016; (2) **sleep** — evening dosing is commonly reported to improve subjective sleep quality, though this overlap substantially with non-specific benefits of magnesium repletion that are equally achievable with much cheaper [Magnesium](/compound/magnesium) glycinate; (3) **anxiety** — systematic reviews of magnesium and anxiety (**Pickering 2020**) pool across many forms and find modest positive effects, but threonate-specific anxiety data are limited; (4) **general magnesium repletion with a cognition halo** — some users take Magtein as their primary magnesium source while hoping to capture both general repletion and specific CNS effects.\n\nA practical point up front: **Magtein delivers relatively little elemental magnesium per dose**. The typical 1.5-2g/day Magtein dose provides ~144-192mg elemental magnesium — considerably **less than a standard magnesium glycinate dose** (200-400mg elemental at a fraction of the cost). For systemic magnesium repletion (muscle cramps, constipation, blood pressure, general wellness), glycinate is equivalent or superior and substantially cheaper. Magtein's proposed advantage is narrowly about **CNS magnesium elevation** for cognitive applications. Users often combine Magtein with another cheaper magnesium form to hit general elemental targets; relying on Magtein alone for both CNS and general repletion rarely pencils out.\n\nThe commercial landscape also warrants attention. **\"Magnesium threonate\"** products fall into two broad categories: **Magtein-branded** (certified through Magceutics/Neurocentria licensing, defined L-isomer specifications, third-party testing) and **generic \"magnesium threonate\"** (uncertain L-isomer purity, not studied in the published clinical research). The published evidence applies specifically to Magtein; this distinction is often glossed over in consumer marketing and price differences typically reflect it.\n\nSee also [Magnesium](/compound/magnesium), [Lion's Mane](/compound/lions-mane), [Creatine](/compound/creatine), [Citicoline](/compound/citicoline), [Acetyl-L-Carnitine](/compound/acetyl-l-carnitine), [Bacopa](/compound/bacopa), [Phosphatidylserine](/compound/phosphatidylserine), and [Fisetin](/compound/fisetin) for adjacent cognitive-support and magnesium-related compounds commonly used in nootropic stacks. This is educational content and not medical advice — magnesium supplementation is generally safe but clinical applications (particularly in renal impairment, in children, or with drug-interacting medications) warrant physician-level guidance.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 207, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/magnesium-l-threonate" }, { "id": "c81faa71-e11c-4aa3-8cc2-c3c8cdb3aee9", "slug": "maitake", "name": "Maitake", "aliases": [ "Grifola frondosa", "Hen of the Woods", "Dancing Mushroom", "Maitake D-fraction", "MD-fraction", "SX-fraction", "Ram's Head", "Sheep's Head", "Kumotake" ], "category": "Herbal", "description": "**Maitake** (*Grifola frondosa*) is a large, fan-shaped polypore fungus native to the temperate hardwood forests of Japan, China, Korea, and parts of northeastern North America and Europe. The Japanese common name translates literally as \"**dancing mushroom**\" — the traditional etymology holds that foragers would dance with joy upon finding the large, fleshy clusters at the base of oak trees, because maitake fruit bodies can weigh **several kilograms to over 20 kilograms** and were historically so valuable in Japanese culture that they were reportedly traded for their weight in silver. The English common name \"**hen of the woods**\" refers to the overlapping rosette of gray-brown fronds that superficially resemble a hen's ruffled feathers; other English common names include **ram's head** and **sheep's head**. The mushroom has been used in **traditional Japanese and Chinese medicine** for centuries as a food and tonic, credited historically with supporting vitality, immune function, and longevity — but unlike reishi (*Ganoderma lucidum*) or turkey tail (*Trametes versicolor*), maitake is also a **culinary mushroom** in broad use in Japanese cuisine, with good flavor, meaty texture, and culinary value independent of any medicinal claims. Modern pharmacological interest in maitake accelerated significantly in the 1980s-1990s under the research leadership of **Dr. Hiroaki Nanba** at Kobe Pharmaceutical University, whose laboratory isolated and characterized the specific beta-glucan fractions — most notably **D-fraction** and its more purified derivative **MD-fraction** — that are now the primary subjects of maitake's research literature.\n\n**Important evidence-framing up front**: Maitake occupies a specific evidence tier that requires careful honest positioning. It has **meaningfully better research support than most medicinal mushrooms** — including a reasonable Phase I/II oncology trial (Deng 2009, Memorial Sloan-Kettering), the Nanba immunology foundation work (multiple animal and early human studies), the Konno SX-fraction diabetes work, and a **Natural Standard systematic review** (Ulbricht 2009) that compiled the then-available evidence with appropriate rigor. But the literature also has significant limitations: **most RCTs are small** (typically 10-30 patients), **most are Japan- or China-based** with variable methodology, **few are placebo-controlled**, and maitake is **not established as a cancer treatment, diabetes treatment, or immunodeficiency treatment** by contemporary evidence-based medicine standards. Unlike [chaga](/compound/chaga) where much of the positive literature is in vitro and the cancer-activity narrative far exceeds the clinical evidence, maitake has more substantial translational research — including one legitimate US Phase I/II trial — but the evidence still sits in the **preliminary/promising** tier rather than the **established efficacy** tier. **Honest positioning**: maitake is a reasonable research-supplement with genuine immunomodulatory and possibly glycemic-modulatory mechanisms, backed by more translational research than most medicinal mushrooms; it should not be positioned as a cancer treatment, not as a diabetes treatment, and not as a substitute for evidence-based medical care. It can reasonably be considered as a culinary-food-functional supplement with plausible immune-supportive effects in generally healthy adults, and as a potential adjunct (not primary therapy) in specific clinical contexts under physician supervision.\n\n**The fraction distinction — critical for understanding the literature**: Maitake's research literature is dominated by specific extracted fractions rather than by whole fruit-body preparations, and understanding the distinction is essential to interpreting dosage recommendations and efficacy claims. **(1) Whole fruit-body maitake** — the culinary and traditional medicine preparation; contains the full complexity of maitake polysaccharides, proteins, ergosterol and other sterols, minerals, and secondary metabolites. Used as food in Japanese cuisine and as dried powder or capsules in supplement form; typical supplement doses are 1-3 grams per day of dried fruit body powder or equivalent extract. **(2) D-fraction** — a hot-water-extracted, partially purified **beta-glucan protein-bound polysaccharide fraction** isolated by Nanba in the 1980s, structurally characterized as a **beta-1,6-branched beta-1,3-glucan** complex with associated protein. D-fraction is the fraction with the most foundational immunology research and is sold as a standalone extract in some supplement markets. **(3) MD-fraction** — a more purified subfraction of D-fraction, developed by Nanba's group to achieve higher consistency and more defined pharmacology. MD-fraction was the specific material used in the **Deng 2009 Memorial Sloan-Kettering Phase I/II breast cancer trial**. Dosing in that trial was weight-adjusted at approximately 0.1-5 mg/kg/day. **(4) SX-fraction** — a distinct **glycoprotein fraction** (not primarily beta-glucan) with different pharmacology from D/MD-fractions; the subject of Konno's diabetes/insulin-sensitization research in the early 2000s. SX-fraction has been investigated for blood glucose modulation in type 2 diabetes but is less commonly commercially available than D-fraction extracts. **Practical significance**: when a maitake supplement label says \"D-fraction\" or \"MD-fraction,\" it is (or should be) referring to these specific pharmacological fractions with specific evidence bases; when a label says \"maitake extract\" without specification, it usually means a whole-fruit-body extract or a less defined hot-water extract that may or may not contain meaningful D-fraction content. **Standardization matters substantially here** — much more than for many herbal products — because the research literature is fraction-specific and generic maitake powders do not necessarily replicate the pharmacology of the research extracts.\n\n**The plant-actually-fungus context — biology matters**: *Grifola frondosa* is a basidiomycete fungus in the family **Grifolaceae** (formerly often placed in Polyporaceae or Meripilaceae depending on classification scheme). It grows as a **polypore** — a fungus whose spore-bearing surface consists of small tubes/pores on the underside rather than gills. Maitake is typically a **parasitic or saprophytic** fungus on oak (*Quercus*) species and occasionally on other hardwoods including maple, elm, and beech; the fruit bodies appear at the base of living or dead trees, typically in late summer and autumn, reaching maturity over several weeks. Each fruit body is a **cluster of overlapping fan-shaped fronds** emerging from a common base, typically gray-brown on the upper surface and white on the pore-bearing underside. Individual specimens can reach **several kilograms** in weight under favorable conditions; historical records from Japan describe specimens exceeding 20-30 kg. Maitake is a prized edible mushroom in Japanese cuisine (with firm texture, excellent flavor, and culinary versatility) and is now **commercially cultivated** extensively in Japan, China, Korea, and the United States — cultivation technology developed in the 1980s has made maitake available year-round in supermarkets and specialty stores. This cultivation context matters: **modern commercial maitake supplements are almost universally made from cultivated material**, which avoids wild-harvest sustainability concerns and provides consistent raw material for extract production.\n\n**Chemistry of the pharmacologically relevant fractions**: The main classes of bioactive compounds in maitake are: **(1) Beta-glucans** — linear and branched polysaccharides consisting of glucose units linked predominantly by beta-1,3 glycosidic bonds in the main chain with beta-1,6 branch points. The specific branching pattern — **beta-1,6-branched beta-1,3-glucan** — is characteristic of maitake D-fraction and MD-fraction and is the structural basis for binding to mammalian innate immune receptors (particularly **dectin-1** on macrophages and dendritic cells). Beta-glucan content of whole fruit body is typically 15-30% of dry weight. **(2) Protein-bound polysaccharides** — complexes of beta-glucans with associated proteins that contribute to immunomodulatory activity. The protein component is thought to stabilize the polysaccharide in solution and possibly contribute to receptor binding specificity. **(3) SX-fraction glycoprotein** — a distinct high-molecular-weight glycoprotein (not primarily beta-glucan) isolated by Konno and studied for insulin-sensitizing effects in type 2 diabetes models. **(4) Ergosterol** and derivative sterols — ergosterol is the fungal equivalent of cholesterol and is a provitamin-D2 precursor; maitake contains ergosterol that can be converted to vitamin D2 by UV light exposure during cultivation or post-harvest processing (some \"vitamin D mushroom\" products use this conversion commercially). **(5) Ergothioneine** — a sulfur-containing antioxidant amino acid present in most mushrooms including maitake; has been investigated for antioxidant and cytoprotective effects. **(6) Grifolin** and **grifolic acid** — sesquiterpene compounds with reported in vitro antimicrobial and anticancer activities. **(7) Lectins and various minor secondary metabolites**. The pharmacologically-emphasized constituents for most of maitake's research literature are the beta-glucan fractions (D-fraction, MD-fraction) and the SX-fraction glycoprotein; other constituents receive less research attention.\n\n**Claimed benefits and where evidence actually supports them**: (a) **Immune modulation / NK cell activation** — this is the most mechanistically-characterized and clinically-studied benefit; Nanba's foundational immunology research and subsequent work have demonstrated NK cell activation, dendritic cell maturation, IL-12 and IFN-gamma induction, and related innate immune stimulation by D-fraction and MD-fraction in animal models and limited human studies. Clinical relevance in healthy humans is plausible but not rigorously demonstrated; relevance in immunocompromised patients is an area of research with some signals but no definitive trials. (b) **Adjunctive oncology support** — the **Deng 2009 Phase I/II breast cancer trial** at Memorial Sloan-Kettering demonstrated dose-dependent immune parameter changes (some increases, some decreases) in post-menopausal breast cancer patients given MD-fraction; the trial was appropriately designed as a dose-finding and biomarker study, not as an efficacy trial, and it did **not** demonstrate cancer treatment efficacy. Nanba and others have published case reports and small Japanese studies suggesting possible benefit in various cancers, but these do **not** establish maitake as cancer treatment. Use in oncology should be **only as adjunct under oncology supervision**, never as primary therapy or as substitute for evidence-based cancer care. (c) **Blood sugar modulation** — **Konno 2001** and subsequent work on SX-fraction have demonstrated insulin-sensitizing effects in diabetic models and limited human studies; whole-fruit-body maitake supplementation has also been investigated with modest positive signals for fasting glucose and HbA1c in small trials. Evidence is preliminary. (d) **Blood pressure and cardiovascular** — some early animal and small human studies suggest modest blood pressure effects; evidence is very preliminary. (e) **General wellness, vitality, immune support** — traditional claims; plausible given the mechanisms but not specifically evidence-established for common cold prevention, fatigue, etc.\n\n**Claims that are NOT supported by clinical evidence**: Marketing sometimes positions maitake as a cancer treatment, HIV/AIDS treatment, weight loss supplement, blood pressure treatment, or hepatitis treatment. The clinical evidence does **not** support these positionings. Maitake's research is preliminary and hypothesis-generating in most of these contexts; it is not established efficacy. Men and women with serious medical conditions should rely on evidence-based medical care, with maitake at most as an adjunct under physician supervision.\n\n**Honestly stated, where does maitake fit?** Maitake is a **culinary-medicinal mushroom with preliminary but more-than-average research support** — better evidence than most medicinal mushrooms, worse evidence than pharmaceutical agents, and sitting in a specific niche defined by its immunomodulatory beta-glucan pharmacology and its less-well-characterized SX-fraction glycemic effects. It is most appropriately positioned as: (1) a **reasonable culinary-food-functional supplement** for generally healthy adults interested in immune-supportive mushroom nutrition; (2) a **potential adjunct** (not primary therapy) in specific clinical contexts including oncology support and type 2 diabetes support, only under physician guidance; (3) a **reasonable addition to a medicinal mushroom stack** alongside [reishi](/compound/reishi), [chaga](/compound/chaga), or [cordyceps](/compound/cordyceps) for general immune support; (4) **not appropriate** as a substitute for cancer treatment, diabetes treatment, or any serious medical care; (5) **not appropriate** for patients on immunosuppressive therapy, organ transplant recipients, or those with active autoimmune disease on active immunotherapy, without specialist involvement.\n\n**Maitake vs other medicinal mushrooms — honest comparison**: (1) **[Reishi](/compound/reishi)** (*Ganoderma lucidum*) — the classical Chinese \"mushroom of immortality\"; strongest traditional-medicine positioning; moderate research base including some RCTs in hypertension and cancer adjunctive; generally safe with good tolerability. (2) **[Chaga](/compound/chaga)** (*Inonotus obliquus*) — cold-climate birch-associated; heavy in vitro literature that greatly exceeds its clinical evidence; oxalate nephropathy concern. (3) **Turkey tail** (*Trametes versicolor*) — source of PSK (krestin), an approved adjuvant cancer treatment in Japan since 1977 with substantial clinical data; among the strongest evidence-based medicinal mushrooms. (4) **[Cordyceps](/compound/cordyceps)** (*Cordyceps militaris* or *sinensis*) — traditional Tibetan adaptogen; performance and energy focus; moderate research. (5) **Maitake** — specific beta-glucan and SX-fraction pharmacology; reasonable translational research; positioned between reishi (broader traditional use) and turkey tail (stronger oncology evidence). Each mushroom has a somewhat different profile; they are often stacked in combination products (the \"immune mushroom blend\" marketing pattern), with varying pharmacological rationale.\n\nSee also [reishi](/compound/reishi) as the classical Asian medicinal mushroom with the broadest traditional positioning; [chaga](/compound/chaga) for another beta-glucan-focused medicinal mushroom with weaker clinical evidence; [cordyceps](/compound/cordyceps) for performance-and-energy-oriented medicinal mushroom; and [astragalus](/compound/astragalus) as a non-mushroom traditional Chinese immunomodulator often paired with medicinal mushrooms in tonic formulations. Maitake sits in the medicinal mushroom category with a specific profile of beta-glucan immunology research and secondary SX-fraction glycemic research, appropriately positioned as a promising but preliminary-evidence functional supplement rather than as an established medical therapy. This is educational content and not medical advice; individuals with cancer, diabetes, autoimmune disease, transplant status, or other serious conditions should consult their physicians before adding maitake to their regimens.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 715, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/maitake" }, { "id": "a1b73e76-8a02-4cd5-8fdd-78aeab17b974", "slug": "manganese", "name": "Manganese", "aliases": [ "Mn", "Mn2+", "Mn3+", "Manganese II", "Manganese III", "Manganese sulfate", "MnSO4", "Manganese gluconate", "Manganese citrate", "Manganese bisglycinate", "Manganese amino acid chelate", "Manganese aspartate", "Manganese ascorbate", "Manganese orotate", "Manganese picolinate", "Manganese chloride", "MnCl2", "Manganese carbonate", "Manganese dioxide", "MnO2", "Manganese oxide", "Manganese phosphate", "Trace mineral manganese" ], "category": "Mineral", "description": "\nManganese is an essential trace mineral and redox-active transition metal occupying a peculiar place in human nutrition: absolutely required at milligram doses for mitochondrial antioxidant defense, gluconeogenesis, urea cycle function, and connective tissue synthesis — yet potently neurotoxic at the hundredfold-higher doses encountered occupationally (welders, miners, battery workers) and in patients on long-term parenteral nutrition with inadequately controlled trace mineral content. The adult body contains approximately 10-20 mg of manganese distributed across bone (25-40%), liver, kidney, pancreas, pituitary, and brain (particularly the basal ganglia — globus pallidus, substantia nigra, caudate, putamen), with manganese concentrations in the globus pallidus being among the highest in the body and providing the anatomical substrate for manganism, the parkinsonian syndrome of chronic manganese overexposure. Carl Scheele and Johan Gottlieb Gahn isolated elemental manganese in 1774 through carbon reduction of the mineral pyrolusite (MnO2); the name derives from the Latin \"magnes\" reflecting the mineral's historic use in glassmaking. The essentiality of manganese for mammalian health was established through 1930s-1950s experimental deficiency studies in chicks, rats, and guinea pigs that demonstrated bone malformation, ataxia, and reproductive failure, and crystallized clinically with parenteral nutrition trace element development in the 1970s-1980s and the concurrent recognition of parenteral manganese toxicity in liver disease patients in the 1990s.\n\nThe adequate intake (AI) for manganese is 2.3 mg/day for men and 1.8 mg/day for women (Institute of Medicine 2001; there is no RDA because definitive evidence for a minimum physiologic requirement has not been established through deficiency-repletion studies in humans), with pregnancy AI of 2.0 mg/day and lactation 2.6 mg/day. The tolerable upper intake level (UL) for adults is 11 mg/day — notably, the UL sits only approximately 5x above the AI, one of the narrower safety ranges among essential nutrients, reflecting manganese neurotoxicity concerns. Dietary manganese is abundant in whole grains (particularly brown rice, oats, whole wheat, quinoa), nuts (pine nuts, hazelnuts, pecans, almonds), legumes (soybeans, chickpeas, lentils), tea (notably, a strong cup of tea can contain 0.5-1 mg manganese — tea-heavy diets readily provide sufficient manganese), leafy greens (spinach, Swiss chard, kale), pineapple, seeds (pumpkin, flax, chia), and some shellfish (mussels, oysters). Typical US dietary intake ranges 2-6 mg/day for adults, solidly within the AI range. Clinical manganese deficiency from ordinary diet is exceptionally rare; it has been described only in a handful of contrived metabolic ward studies and in highly unusual clinical scenarios. The dominant manganese clinical concern is toxicity, not deficiency.\n\nManganese absorption is tightly controlled — one of the body's primary defenses against its inherent neurotoxicity. Intestinal absorption is only approximately 3-5% of dietary intake under normal conditions, mediated by DMT1 (divalent metal transporter 1, the same transporter that carries [iron](/compound/iron), [zinc](/compound/zinc), copper, cobalt, cadmium, and lead into enterocytes) and ZIP8/ZIP14 (SLC39A8 and SLC39A14, which have higher affinity for manganese). Iron deficiency upregulates DMT1 and increases manganese absorption — potentially contributing to manganese accumulation in iron-deficient populations. Calcium, phosphate, phytate, and fiber in the diet reduce manganese absorption by forming insoluble complexes. Absorbed manganese binds α2-macroglobulin and albumin in portal blood, reaches the liver, and is largely extracted on first pass. Hepatic manganese is excreted into bile as the primary elimination route; approximately 95% of manganese clearance occurs through biliary excretion, with only minor urinary loss. This hepatic excretion pathway is critical clinically — in cholestatic liver disease, biliary obstruction, or severe hepatic dysfunction, manganese accumulates rapidly, producing the characteristic T1-hyperintensity on brain MRI in globus pallidus (the classic \"manganese brain\" finding in cirrhotic patients, which can regress after liver transplantation) and contributing to hepatic encephalopathy. Patients on long-term parenteral nutrition, especially those with underlying liver disease or cholestasis, develop manganese accumulation at standard trace element supplementation doses and may require manganese removal from the TPN formulation.\n\nCellular manganese uptake occurs through several transporters depending on tissue and redox state. SLC39A14 (ZIP14) and SLC39A8 (ZIP8) mediate manganese uptake into hepatocytes, pancreatic acinar cells, and other tissues; SLC30A10 mediates manganese efflux from hepatocytes into bile (loss-of-function SLC30A10 mutations cause a rare autosomal recessive hypermanganesemia with dystonia and polycythemia, a Mendelian disorder of manganese detoxification first described in 2012). DMT1 handles manganese uptake across the blood-brain barrier and into neurons. Intracellularly, manganese is channeled into mitochondria via the mitochondrial calcium uniporter (MCU, which transports Ca2+ but also Mn2+ at similar affinity) where it loads into MnSOD (SOD2) — the primary physiologic fate of manganese.\n\nMnSOD (superoxide dismutase 2, SOD2) is the mitochondrial superoxide dismutase, catalyzing the dismutation of superoxide (O2•-) to hydrogen peroxide (H2O2) in the mitochondrial matrix — the primary site of reactive oxygen species generation from electron transport chain leak. SOD2 activity critically depends on its manganese cofactor. SOD2 knockout mice die within two weeks of birth from dilated cardiomyopathy, hepatic steatosis, and neurodegeneration, demonstrating the absolute essentiality of mitochondrial ROS control. A common SOD2 polymorphism, Val16Ala (rs4880), affects mitochondrial targeting and has been associated with varying cancer, diabetes, and neurodegenerative disease risk in population studies. Age-related mitochondrial dysfunction is partly attributable to declining SOD2 activity. The oxidative stress and longevity connection makes MnSOD perhaps the single most biochemically important manganese-dependent enzyme in vertebrate physiology.\n\nBeyond MnSOD, manganese activates or is tightly bound in several other mammalian enzymes: arginase (liver urea cycle, converting arginine to ornithine + urea — the final step of ammonia detoxification), pyruvate carboxylase (gluconeogenesis and anaplerosis, converting pyruvate to oxaloacetate using biotin as primary cofactor and manganese as allosteric), phosphoenolpyruvate carboxykinase (PEPCK-M, mitochondrial gluconeogenic enzyme), glutamine synthetase (astrocyte ammonia detoxification, converting glutamate + NH3 to glutamine — critical for brain ammonia clearance and potentially one reason manganese overload exacerbates hepatic encephalopathy), and the glycosyltransferases and prolidases involved in proteoglycan synthesis (explaining the bone and cartilage defects seen in experimental manganese deficiency). Manganese is also loosely associated with many kinases and phosphatases as alternative metal cofactor where it can substitute for magnesium.\n\nManganese toxicity — manganism — is a parkinsonian syndrome first described in the 1830s by James Couper in Glasgow bleach-works manganese miners and extensively characterized in the 20th century in welders, smelters, battery manufacturers, and ore processing workers. Chronic inhalation of manganese-containing dust or fume produces progressive accumulation in basal ganglia, initially with neuropsychiatric prodrome (irritability, emotional lability, aggression, insomnia, sometimes called \"manganese madness\" or \"locura manganica\"), progressing to extrapyramidal motor signs resembling Parkinson disease: bradykinesia, rigidity, postural instability, dystonia (often a characteristic \"cock-walk\" gait on toes with hyperextension of the spine), masked facies, micrographia. Unlike idiopathic Parkinson disease, manganism predominantly affects the globus pallidus (pallidal) rather than the substantia nigra pars compacta, the tremor is less prominent, levodopa response is poor, and brain MRI shows T1-hyperintensity in globus pallidus (free manganese is paramagnetic, shortening T1 relaxation times). The Rodier 1955 reports on manganese miner neurology and the subsequent Chilean and Brazilian occupational studies established the syndrome's dose-response relationship. Welders remain the modern epidemiologic focus; several studies have found subtle motor and cognitive deficits in chronically exposed welders below the threshold for overt manganism (Racette 2017 Neurology, among others). Methylcyclopentadienyl manganese tricarbonyl (MMT) — used as an octane-boosting gasoline additive in some countries (banned in the US in most fuel — controversy around Canadian approval) — creates environmental concerns for population-level manganese exposure, though epidemiologic data remain mixed.\n\nParenteral nutrition manganese toxicity parallels the occupational syndrome. Patients on TPN (particularly children, patients with cholestasis, intestinal failure, or chronic liver disease) receiving standard trace element preparations develop MRI T1-hyperintense globus pallidus and hypermanganesemia; pediatric case series in the 1990s-2000s documented the phenomenon, and current ASPEN and ESPEN guidelines recommend manganese monitoring in long-term TPN and reduced or zero manganese content in the presence of cholestasis. The Mirowitz and Westcott MRI descriptions of this in cirrhotic patients preceded its recognition in TPN patients; the biology is the same — impaired biliary manganese excretion causes accumulation regardless of the exposure source.\n\nSLC30A10 deficiency (hypermanganesemia with dystonia 1, HMNDYT1) is a rare autosomal recessive disorder first described by Tuschl 2012 (PMID 22341972) characterized by high serum manganese, MRI globus pallidus T1-hyperintensity, early-onset generalized dystonia, polycythemia, and chronic liver disease, caused by loss-of-function mutations in the hepatic manganese efflux transporter. Chelation with EDTA and iron repletion (iron and manganese share DMT1, and iron repletion competitively reduces manganese absorption) form the mainstay of treatment. A related disorder, HMNDYT2, involves SLC39A14 (ZIP14) loss-of-function preventing hepatic manganese uptake and subsequent biliary excretion, with similar clinical presentation. These Mendelian disorders established human SLC30A10 and SLC39A14 as essential components of manganese homeostasis.\n\nTherapeutic manganese supplementation has a limited evidence base and a narrow place in medicine. It is included in multivitamin-mineral products at typical doses of 1-2 mg (consistent with the AI). Standalone manganese supplements are marketed for bone health (based on 1990s osteoporosis studies combining manganese with copper, zinc, and calcium, Strause 1994 J Nutr, which showed bone density benefits vs. calcium alone but could not isolate the manganese contribution), connective tissue synthesis, and (unproven) hypoglycemia. Given the narrow AI-UL window, the small contribution of typical supplements to total exposure, and the rarity of deficiency from ordinary diet, manganese supplementation has no clear evidence-based indication outside of parenteral nutrition in non-cholestatic patients and documented deficiency (which essentially does not occur in free-living populations). BodyHackGuide does not recommend standalone manganese supplementation for most users; typical diets (especially those with whole grains, nuts, legumes, and tea) provide ample manganese, and over-supplementation risks cumulative neurotoxicity given manganese's long half-life and poor excretion through non-biliary routes. If a multivitamin contains 1-2 mg manganese, that is appropriate; higher doses (5-20 mg manganese-only formulations marketed for \"bone\" or \"enzyme support\") carry no demonstrated benefit and measurable theoretical risk. Users with liver disease, biliary obstruction, or on chronic PPIs/antacids (which increase gastric manganese bioavailability) should specifically avoid supplemental manganese.\n\nManganese cross-interactions are important. [Iron](/compound/iron) and manganese share DMT1 at intestinal absorption and blood-brain barrier; iron deficiency increases manganese absorption and brain uptake. [Calcium](/compound/calcium), phosphate, and phytate reduce manganese absorption. [Zinc](/compound/zinc) has reciprocal interaction with manganese absorption at DMT1. [Biotin](/compound/biotin) and [pantothenic-acid](/compound/pantothenic-acid) share the carboxylase enzyme family with manganese-activated pyruvate carboxylase, connecting manganese to the energy metabolism chain described in the B-vitamin entries. Chronic excess [manganese](/compound/manganese) exposure in the context of low iron (a common combination in pediatric manganism and in certain population studies) may interact with [dopamine](/compound/l-tyrosine) neurochemistry through shared basal ganglia vulnerability.\n\nBodyHackGuide's take: manganese is the trace mineral that matters most for what you should NOT take. Deficiency is essentially nonexistent in ordinary diets; toxicity from occupational exposure and parenteral nutrition is a real clinical problem; supplementation offers no demonstrated benefit for free-living adults eating a reasonable diet. If you drink tea and eat nuts, whole grains, or legumes, your manganese is covered. A multivitamin providing 1-2 mg is fine. Avoid manganese-specific supplements, \"superfood greens powders\" with concentrated manganese, high-dose mineral blends targeting bone (use [calcium](/compound/calcium), [vitamin-d3](/compound/vitamin-d3), [vitamin-k2](/compound/vitamin-k2), [magnesium](/compound/magnesium), and [boron](/compound/boron) instead), and any supplementation in the presence of known liver disease. Welders, miners, and industrial workers should minimize occupational exposure; biomonitoring and medical surveillance programs exist in most regulated jurisdictions. The unique biochemistry of manganese — essential cofactor for MnSOD mitochondrial defense, yet basal ganglia toxicant — illustrates the general rule that trace minerals have narrow therapeutic windows and that ambient diet usually lands inside those windows without supplemental assistance.\n", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 1523, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/manganese" }, { "id": "cf82276f-cdeb-4006-83c4-aa5d60659585", "slug": "mazdutide", "name": "Mazdutide", "aliases": [ "LY3305677" ], "category": "Weight Loss", "description": "Mazdutide (also known as IBI362, Lilly compound LY3305677) is a dual glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist originally discovered by Eli Lilly and exclusively licensed to Innovent Biologics in 2019 for development and commercialization in Mainland China, Hong Kong, Macau, and Taiwan. Structurally it is a 39-amino-acid synthetic peptide based on the oxyntomodulin scaffold — the natural L-cell gut hormone that shares its first 29 residues with glucagon and has intrinsic dual GLP-1/glucagon activity — with strategic modifications including lipid conjugation (similar to semaglutide and liraglutide) for extended half-life, enabling once-weekly subcutaneous administration. Mazdutide represents a different mechanistic philosophy from tirzepatide and semaglutide: while those drugs use GLP-1 signaling (sometimes with GIP in tirzepatide's case), mazdutide adds glucagon receptor agonism, which increases resting energy expenditure and promotes hepatic lipid utilization — in essence, combining appetite suppression (GLP-1) with increased metabolic rate and fat burning (glucagon).\n\nThe rationale for dual GLP-1/glucagon agonism goes back to the 1970s observation that oxyntomodulin administered to humans reduced food intake and body weight more than GLP-1 alone. Pure glucagon agonism has historically been avoided in diabetes drug development because glucagon raises blood glucose; however, GLP-1 signaling simultaneously stimulates insulin secretion and suppresses glucagon release, creating a counterbalancing effect when the two are combined in a single molecule. The net result in humans is that dual GLP-1/glucagon agonists like mazdutide produce weight loss comparable to semaglutide while also improving hepatic steatosis, raising energy expenditure ~5-8% above baseline, and delivering glycemic control at least as good as GLP-1 monotherapy. A related and more advanced triple agonist, [Retatrutide](/compound/retatrutide), adds GIP activity and has shown even more dramatic weight loss in Phase 2 (~24% at 48 weeks) but is developed by Eli Lilly directly rather than licensed regionally.\n\nMazdutide's Phase 3 development in China has been rapid. The DREAMS-1 (obesity) and DREAMS-2 (type 2 diabetes + obesity) trials enrolled Chinese patients and delivered strong results. In DREAMS-1, 9 mg weekly mazdutide produced mean weight loss of ~15% at 48 weeks in adults with obesity (BMI ≥28 kg/m² per Chinese classification) — closely comparable to semaglutide's Western trial results. In GLORY-1, a Phase 3 trial of 6 mg mazdutide in overweight/obese adults, weight reduction was 14.4% at 48 weeks versus 0.3% placebo ([Ji et al., 2024]). NMPA (China's FDA equivalent) approval in China is expected in 2025-2026, positioning mazdutide as the first major incretin-class drug developed specifically for the Chinese population and potentially the first dual GLP-1/glucagon agonist to reach market globally (ahead of Eli Lilly's retatrutide triple agonist). Whether mazdutide will be developed or licensed for Western markets remains an open commercial question — Lilly retained rights outside the Innovent territories but has prioritized retatrutide.\n\nCross-references include [Semaglutide](/compound/semaglutide) (GLP-1 monoagonist competitor), [Tirzepatide](/compound/tirzepatide) (GLP-1/GIP dual agonist competitor), [Retatrutide](/compound/retatrutide) (Lilly's GLP-1/GIP/glucagon triple agonist), [Cagrilintide](/compound/cagrilintide) (amylin analog in CagriSema combination), and [Orforglipron](/compound/orforglipron) (oral non-peptide GLP-1 agonist).", "half_life": "", "molecular_weight": "4563.14 g/mol", "molecular_mass": "4563.14 g/mol (C210H322N46O67)", "amino_acid_sequence": "Mazdutide is a 34-residue synthetic analog of the gut hormone oxyntomodulin, engineered for balanced GLP-1 and glucagon receptor agonism. Reported backbone (one-letter, N-to-C): H-[Aib]-QGTFTSDYSKYLDEKKAK-EFVEWLLEGGPSSG-NH2, where position 2 is alpha-aminoisobutyric acid (Aib, which confers DPP-4 resistance) and the C-terminus is amidated. The lysine at position 20 is side-chain acylated with a C20 fatty diacid through two AEEA (mini-PEG) spacers and a gamma-glutamate linker, giving albumin binding and a half-life that supports once-weekly dosing. Molecular formula C210H322N46O67; molar mass ~4563 g/mol; CAS 2259884-03-0 (research designations IBI-362 / LY-3305677 / OXM-3).", "administration_routes": [], "dose_range_mcg": "Research doses — clinical trial protocols vary", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Approved (China, NMPA 2025); investigational in US/EU", "approval_status": "Approved by China's NMPA as mazdutide injection (brand Xinermei): June 2025 for chronic weight management in adults with obesity or overweight, and September 2025 for glycemic control in adults with type 2 diabetes. A 9 mg dose is under NMPA review for moderate-to-severe obesity. Not approved by the US FDA or EMA - investigational (research-use-only) outside China. Innovent Biologics holds the Chinese rights (licensed from Eli Lilly in 2019); Eli Lilly retains rights outside China.", "trial_phase": "", "cas_number": "2498263-63-9", "iupac_name": "", "chemical_formula": "C232H358N60O79S", "potential_benefits": [ "Enhanced weight loss efficacy", "Improved metabolic markers", "Superior glucose control", "Reduced cardiovascular risk factors" ], "research_fields": [], "pubmed_count": 39, "pubchem_cid": 160688325, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/mazdutide" }, { "id": "939702b4-bfdb-4bd6-b76e-38bb962f85b4", "slug": "melanotan-1", "name": "Melanotan-1", "aliases": [ "MT-1", "Afamelanotide", "Scenesse" ], "category": "Tanning Peptide", "description": "Melanotan-1 (afamelanotide, brand name Scenesse) is a synthetic analog of alpha-melanocyte stimulating hormone (alpha-MSH). It is FDA-approved (2019) under the trade name Scenesse for prevention of phototoxicity in adult patients with erythropoietic protoporphyria (EPP) - a rare metabolic disorder where sunlight exposure causes severe pain.\n\nUnlike Melanotan-2, MT-1 is selective for the MC1R (melanocortin-1 receptor) and does not significantly activate MC3R/MC4R, meaning it produces tanning without the libido and appetite-suppression effects of MT-2. The selectivity also means lower nausea risk during loading.", "half_life": "~30 minutes serum (subcutaneous absorption is the rate-limiter for clinical use)", "molecular_weight": "1646.9 g/mol (C78H111N21O19)", "molecular_mass": "1646.9 g/mol", "amino_acid_sequence": "Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2", "administration_routes": [ "Subcutaneous", "Implant (Scenesse uses bioresorbable implant)" ], "dose_range_mcg": "500-1000 mcg loading; 500 mcg maintenance", "dosing_frequency": "Daily during loading (2-4 weeks); weekly maintenance after", "cycle_length": "2-4 weeks loading, then weekly maintenance dosing", "common_vial_sizes": [ "10mg" ], "research_stage": "FDA-approved (2019) as Scenesse for EPP. Off-label tanning use is unapproved.", "approval_status": "FDA-approved (Scenesse) for EPP only. Off-label use is not approved.", "trial_phase": "FDA-approved for EPP (Scenesse, 2019)", "cas_number": "", "iupac_name": "", "chemical_formula": "~1646 Da (Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2)", "potential_benefits": [ "Photoprotection in EPP (FDA/EMA-approved indication as Scenesse)", "Increased melanin synthesis via MC1R (cosmetic tanning is off-label and unstudied)", "Established regulatory approval and safety dossier, unlike MT-2", "Reduced libido/appetite and nausea effects vs MT-2 at comparable tanning doses" ], "research_fields": [ "Melanocortin receptors", "Melanogenesis", "Erythropoietic protoporphyria", "Photoprotection" ], "pubmed_count": 4, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/melanotan-1" }, { "id": "2514f23b-bdc2-4be2-847b-ad5c19cfa661", "slug": "melanotan-2", "name": "Melanotan 2", "aliases": [ "MT-2", "MT2" ], "category": "Skin & Hair", "description": "A synthetic melanocortin receptor agonist studied for skin tanning, sexual function, and appetite suppression.", "half_life": "~1–2 hours", "molecular_weight": "1024.2 Da", "molecular_mass": "1024.18 g/mol", "amino_acid_sequence": "Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 - a cyclic lactam heptapeptide analog of alpha-MSH(4-10). Key modifications: norleucine (Nle) substituted at position 4, D-phenylalanine (D-Phe) at position 7, and an amide (lactam) bridge between the side chains of Asp5 and Lys10, with a C-terminal amide. Molecular formula C50H69N15O9 (avg. mass ~1024.2 g/mol).", "administration_routes": [ "Subcutaneous" ], "dose_range_mcg": "100-1,000 mcg per injection", "dosing_frequency": "Daily during loading phase; 1–2x per week maintenance", "cycle_length": "2–4 weeks loading, then maintenance as desired", "common_vial_sizes": [ "5mg", "10mg" ], "research_stage": "Discontinued (early clinical)", "approval_status": "Not approved for any indication - research use only. Melanotan 2 is sold as an unapproved, unregulated research chemical rather than a licensed drug. (Its more MC4R-selective analog bremelanotide / PT-141 is FDA-approved as Vyleesi for HSDD, and the separate linear analog afamelanotide / Scenesse is FDA-approved for erythropoietic protoporphyria - neither approval is for MT-2.)", "trial_phase": "", "cas_number": "121062-08-6", "iupac_name": "Ac-Nle-cyclo[-Asp-His-D-Phe-Arg-Trp-Lys]-NH2", "chemical_formula": "C50H69N15O11", "potential_benefits": [ "Skin tanning without UV exposure", "Enhanced libido and sexual function", "Potential appetite suppression", "UV protection through melanin increase" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": 92186, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/melanotan-2" }, { "id": "9de1088d-2da7-4294-a94d-663508b424e3", "slug": "melanotan-i", "name": "Melanotan I", "aliases": [ "Afamelanotide", "CUV1647", "Scenesse", "alpha-MSH analog", "[Nle4,D-Phe7]-alpha-MSH (linear)" ], "category": "Other", "description": "Melanotan I (afamelanotide) is a linear synthetic analog of alpha-melanocyte-stimulating hormone (α-MSH) with the substitution of norleucine at position 4 and D-phenylalanine at position 7. Unlike Melanotan II (which is cyclic), Melanotan I is a linear peptide that is significantly more selective for MC1R over MC4R — making it a tanning/photoprotective agent with substantially less sexual and appetite-stimulating side effects. Afamelanotide was FDA-approved in October 2019 under the brand name Scenesse as an implant for erythropoietic protoporphyria (EPP), a rare photosensitivity disorder. Melanotan I is meaningfully different from Melanotan II in structure, selectivity, and side-effect profile and should not be confused with it.", "half_life": "Controlled-release subcutaneous implant (Scenesse): high inter-subject variability; median Tmax ~36 h, mean Cmax ~3.7 ng/mL, apparent terminal half-life ~15 h, with plasma levels measurable to ~96 h post-dose (FDA pharmacokinetics, n=12). Injected/bolus free peptide: peak plasma at ~1-2 h with an elimination half-life of ~30 minutes; the Nle4/D-Phe7 modifications prolong biological (melanogenic) activity well beyond plasma clearance.", "molecular_weight": "1646.85 g/mol (average; molecular formula C78H111N21O19)", "molecular_mass": "1646.85 Da (C78H111N21O19; PubChem CID 16197727)", "amino_acid_sequence": "Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2 ([Nle4, D-Phe7]-alpha-MSH / NDP-alpha-MSH; 13-residue analog of alpha-MSH, N-acetylated with a C-terminal amide)", "administration_routes": [ "Subcutaneous", "Intramuscular" ], "dose_range_mcg": "16000", "dosing_frequency": "every_1_to_4_weeks", "cycle_length": "", "common_vial_sizes": [ "5", "10" ], "research_stage": "FDA Approved", "approval_status": "FDA-approved as afamelanotide (brand Scenesse) - a 16 mg controlled-release subcutaneous implant - for erythropoietic protoporphyria (EPP), approved October 2019 [PMID:26132941]. The injectable 'Melanotan I' powder marketed for cosmetic tanning is the same peptide (afamelanotide / NDP-alpha-MSH) but is NOT an approved product; it is sold as unregulated, research-use-only material that is not quality-controlled or sterility-assured for human use.", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Increased melanin (eumelanin) production and skin darkening via MC1R activation, with a reduced UV requirement", "FDA-approved photoprotection in erythropoietic protoporphyria (EPP) as the Scenesse 16 mg subcutaneous implant [PMID:26132941]", "Reduced phototoxic pain and improved quality of life in EPP patients in randomized controlled trials [PMID:26132941]", "Tends to produce fewer MC4R-type effects (spontaneous erections, strong libido, marked nausea) than the cyclic Melanotan II - attributable to Melanotan II's greater potency and metabolic stability, not to true MC1R selectivity of Melanotan I", "Investigated in research settings for photoprotection in UV-sensitive populations" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/melanotan-i" }, { "id": "e941e69a-5590-46a7-aa07-39f505086ffd", "slug": "melanotan-ii", "name": "Melanotan II", "aliases": [], "category": "Skin, Hair & Aesthetics", "description": "Melanotan-II (MT-II) is a synthetic cyclic heptapeptide analog of alpha-melanocyte-stimulating hormone (α-MSH) engineered in the late 1980s by researchers at the University of Arizona, most prominently Mac Hadley and Victor Hruby, who were searching for a way to stimulate skin pigmentation pharmacologically as a potential skin-cancer prophylactic. The parent hormone α-MSH is a 13-amino-acid peptide cleaved from proopiomelanocortin (POMC) that binds to melanocortin receptors (MC1R through MC5R) scattered across skin, brain, adrenal, and adipose tissue. Native α-MSH has a plasma half-life measured in minutes and is rapidly degraded by peptidases, so Hruby's team cyclized the molecule with a lactam bridge (between Asp5 and Lys10), substituted D-phenylalanine at position 7, and produced a non-selective melanocortin agonist with roughly 1,000-fold greater potency than α-MSH at MC1R and dramatically extended half-life. The resulting compound, Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, was patented and licensed, with a truncated MC4R-selective derivative (bremelanotide, PT-141) eventually spinning off to become the FDA-approved HSDD drug Vyleesi in 2019 ([Hadley & Dorr, 2006]).\n\nMT-II itself has never been approved as a pharmaceutical in any country. Its entry into the human world happened through grey-market channels: bodybuilding forums and online peptide vendors in the early 2000s began selling reconstituted MT-II as an injectable \"tanning peptide,\" and the drug achieved cult status among fair-skinned users who wanted deep tans without UV exposure, people seeking MT-II's appetite-suppressing and libido-improving side effects, and a smaller population with genuine photosensitivity disorders who had exhausted approved therapies. All three use cases rely on MT-II's pan-agonism at melanocortin receptors: MC1R drives melanogenesis in skin melanocytes (tanning), MC4R in the hypothalamus suppresses food intake and drives sexual arousal, and MC3R contributes to energy-balance effects. The Australian Therapeutic Goods Administration, UK MHRA, and US FDA have all issued warnings about MT-II products, citing unknown long-term safety, contamination risk from underground synthesis, and case reports of dysplastic nevi changes following MT-II use ([Langan et al., 2010], [Cardones & Grichnik, 2009]).\n\nMT-II differs meaningfully from its FDA-approved cousin [PT-141 (Bremelanotide)](/compound/pt-141). PT-141 is a linear 7-amino-acid derivative designed for MC4R selectivity and sexual-function indications — it produces minimal pigmentation and is approved for on-demand use. MT-II by contrast is cyclic, hits all five melanocortin receptors, and generates the tanning effect precisely because it engages MC1R that PT-141 largely spares. Users interested exclusively in libido/erectile effects with less pigmentation usually prefer PT-141; users specifically seeking UV-mimetic tanning (especially those with Fitzpatrick skin types I-II who burn easily) gravitate to MT-II. A separate FDA-approved MC1R-selective peptide called afamelanotide (Scenesse, Clinuvel Pharmaceuticals) received approval in 2019 specifically for erythropoietic protoporphyria patients — it is delivered as a subcutaneous implant and provides months of MC1R activation without the sexual or appetite side effects of MT-II, though at significant cost and with limited regulatory indications ([Kim & Jo, 2015]).\n\nThis entry is for educational purposes only. Melanotan-II is not approved for human use in any jurisdiction, and purchased product quality varies wildly — independent testing of online peptide samples has found significant variation in peptide content, purity, and endotoxin levels. Users considering MT-II should be aware that the drug amplifies the melanogenic response to UV radiation, which means subsequent sun exposure produces a deeper tan but may also accelerate accumulation of UV-induced DNA damage; MT-II is not a sunscreen and does not protect against photoaging or skin cancer risk from concurrent UV exposure. Multiple dermatology case reports have documented rapid darkening and architectural changes in pre-existing moles during MT-II courses, sometimes requiring biopsy to exclude melanoma transformation. Anyone with a personal or family history of melanoma, a large number of atypical nevi, or Fitzpatrick skin type I should exercise particular caution, ideally with a dermatologist performing a full-body mole check before and after any MT-II cycle.", "half_life": "Approximately 30-60 minutes (subcutaneous; limited published human pharmacokinetic data). Peak plasma levels occur ~1-2 hours after injection, and subjective effects typically persist 4-8 hours.", "molecular_weight": "~1024.2 g/mol (average molecular weight; monoisotopic mass ~1023.5 Da). Molecular formula C50H69N15O9 (PubChem CID 92432).", "molecular_mass": "1024.19 g/mol", "amino_acid_sequence": "Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 - a synthetic cyclic heptapeptide with a lactam bridge between the Asp and Lys side chains, N-terminal acetylation, and C-terminal amidation. Molecular formula C50H69N15O9 (PubChem CID 92432); average molecular weight ~1024.2 g/mol, monoisotopic mass ~1023.5 Da. It is a shortened, cyclized analog of the alpha-MSH active core (His-Phe-Arg-Trp), with a D-Phe substitution and norleucine (Nle) in place of Met conferring potency and resistance to enzymatic degradation.", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Not approved for human use in any jurisdiction; marketed only as a research chemical ('not for human use').", "trial_phase": "Preclinical", "cas_number": "121062-08-6", "iupac_name": "Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2", "chemical_formula": "C50H69N15O9", "potential_benefits": [ "Tanning without UV", "Appetite suppression", "Sexual arousal", "Photoprotection", "Fat loss" ], "research_fields": [ "Dermatology", "Sexual dysfunction", "Melanoma prevention research", "Obesity" ], "pubmed_count": 17, "pubchem_cid": 92432, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/92432/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/melanotan-ii" }, { "id": "a80142ec-177e-4857-b38c-38f88d3da198", "slug": "melatonin", "name": "Melatonin", "aliases": [ "N-acetyl-5-methoxytryptamine", "5-methoxy-N-acetyltryptamine", "MLT", "Circadin", "Slenyto", "Bio-melatonin", "Melatonex", "Melovine" ], "category": "Sleep & Circadian", "description": "**Melatonin** (chemical name *N-acetyl-5-methoxytryptamine*) is an endogenous neurohormone synthesized primarily by the **pineal gland** and, in smaller quantities, by the retina, gut, skin, bone marrow, lymphocytes, and mitochondria across most tissues. It is the body's principal **circadian signaling molecule**, translating environmental light/dark information into an internal chemical representation of biological night. Endogenous melatonin secretion follows a precise circadian rhythm: plasma concentrations are low during the day (typically <10 pg/mL), begin rising 1-3 hours before habitual sleep onset (the \"dim light melatonin onset\" or DLMO), peak between 2am and 4am at 60-70 pg/mL in healthy young adults, and decline to baseline by morning. This nightly pulse coordinates sleep initiation, thermoregulation, circadian phase, seasonal reproductive physiology in some species, antioxidant defense (particularly in mitochondria), and immune-system oscillations.\n\nMelatonin was discovered and named by Aaron Lerner at Yale in 1958 during research on pineal factors affecting amphibian skin coloration. Its role as the principal mediator of vertebrate photoperiodism was established through the 1960s-70s, its receptor targets (MT1 and MT2, both G-protein-coupled receptors) were cloned in the 1990s, and its broader pleiotropic functions beyond circadian signaling — including powerful free-radical scavenging, mitochondrial protection, oncostatic activity in hormone-sensitive tumors, immunomodulation, and metabolic effects on glucose and blood pressure — have emerged as active research areas over the past three decades. In 2026, melatonin occupies a unique regulatory position globally: in the **United States**, it is classified as a dietary supplement and available without prescription at virtually any pharmacy, grocery store, or online retailer, in doses ranging from micrograms to 20mg. In **Europe, the UK, Australia, and several Asian countries**, melatonin is a prescription-only medication (brand names Circadin for adult primary insomnia, Slenyto for pediatric insomnia in autism spectrum disorder), reflecting those regulators' assessment that it is a hormone rather than a nutritional supplement.\n\nIn popular supplement culture, melatonin is often framed simply as a \"sleep aid,\" but this framing substantially understates both its mechanism and its appropriate use cases. Melatonin is **not primarily hypnotic** in the pharmacological sense of sedatives like benzodiazepines, Z-drugs, or antihistamines — those compounds produce sleep by direct suppression of arousal systems. Melatonin instead acts as a **chronobiotic**, shifting the timing of the circadian pacemaker in the suprachiasmatic nucleus (SCN) and creating a biological \"signal for night\" that allows downstream sleep-promoting processes to operate. The implications are significant: melatonin is most effective when **timing is precisely aligned** with the user's target sleep phase rather than maximal dose, and it is most useful for **circadian rhythm disorders** (delayed sleep phase syndrome, jet lag, shift work, non-24-hour sleep-wake disorder in blind individuals, free-running disorder, REM sleep behavior disorder) rather than for primary insomnia in the pharmacological sense.\n\nThe **clinical evidence base** is strongest and most consistent for: (1) jet lag — where multiple meta-analyses including **Herxheimer & Petrie 2001 Cochrane review**document strong efficacy when taken at bedtime in the destination time zone for eastward travel across >5 time zones; (2) delayed sleep phase syndrome (DSPS), where low-dose evening melatonin taken 5-7 hours before habitual sleep onset produces phase advances; (3) pediatric sleep disorders in children with **autism spectrum disorder** and **ADHD**, where multiple randomized trials and meta-analyses (**Rossignol & Frye 2011**, PMID: 21518346) document clear benefit for sleep onset latency and total sleep time; (4) **REM sleep behavior disorder** (RBD), where melatonin 3-12mg at bedtime reduces dream enactment episodes and is often preferred to clonazepam for older adults (**Boeve et al. 2003**); (5) non-24-hour sleep-wake disorder in totally blind individuals, where entrainment to the 24-hour day is achieved by carefully-timed evening melatonin.\n\nEvidence is **moderately positive** for primary insomnia sleep onset latency (meta-analyses including **Ferracioli-Oda et al. 2013** in *PLOS One*, PMID: 23691095, show modest but statistically significant reductions in sleep onset latency of approximately 7-12 minutes on average, smaller than typical hypnotic effects but clinically meaningful for some individuals), shift-work adaptation, migraine prophylaxis (**Gonçalves et al. 2016**, PMID: 27165014, showed melatonin 3mg nightly non-inferior to amitriptyline 25mg for chronic migraine prevention), and as an adjunct in blood-pressure management. Evidence is **preliminary but compelling** for melatonin as an adjunct in selected oncology protocols (particularly hormone-sensitive breast, prostate, and gastrointestinal cancers where meta-analyses including **Seely et al. 2012**, suggest survival benefit when combined with standard therapy), for COVID-19 adjunctive care, and for pre-operative anxiolysis in pediatric surgery. Evidence is **mixed or unclear** for general anxiolysis, weight management, and fertility support — claims that circulate in supplement culture but lack strong clinical backing.\n\nA distinguishing feature of melatonin compared to other sleep aids is its **extraordinarily wide safety margin and minimal abuse potential**. Unlike benzodiazepines or Z-drugs, melatonin produces no physiological tolerance or dependence, does not suppress REM sleep architecture, does not impair next-day cognitive performance at appropriate doses, and has been used clinically in doses up to 300mg/day for certain oncology indications without serious acute toxicity. However, the practical sleep-supplement literature has been progressively revealing that **most over-the-counter melatonin doses (3mg, 5mg, 10mg) are 10-30× higher than needed for sleep effects** and that higher doses paradoxically produce worse outcomes via morning grogginess, nightmare frequency, and receptor desensitization. The current physiological-replacement approach — **0.3-1mg taken 30-60 minutes before desired sleep onset** — is more effective than megadoses for most primary insomnia and sleep-timing applications.\n\nSee also [Ashwagandha](/compound/ashwagandha), [L-theanine](/compound/l-theanine), [Magnesium](/compound/magnesium), [Glycine](/compound/glycine), [5-HTP](/compound/5-htp), and [Vitamin D](/compound/vitamin-d) for adjacent sleep and circadian support compounds. This overview is educational only and is not medical advice — melatonin is a hormone with metabolic, reproductive, immune, and chronobiotic effects, and extended high-dose use warrants physician consultation.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 12556, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/melatonin" }, { "id": "e6a64158-85a9-4512-87e7-3fd582a6b818", "slug": "meldonium", "name": "Meldonium", "aliases": [ "Mildronate", "Meldonium dihydrate", "MET-88", "Quaterin", "3-(2,2,2-trimethylhydrazinium)propionate", "THP" ], "category": "Pharmaceutical", "description": "Meldonium, sold as Mildronate, was developed at the Latvian Institute of Organic Synthesis (PMID: 12242052) and is a licensed cardiovascular medicine in Latvia and a number of eastern European and post-Soviet countries. It has never been approved in the United States or the European Union as a whole. Most English-speaking readers first heard of it in 2016, when it appeared on the WADA prohibited list and a wave of positive tests followed.\n\nIts mechanism is unusual and worth understanding. Meldonium is the most potent clinically used inhibitor of the carnitine transporter OCTN2, and it also inhibits gamma-butyrobetaine hydroxylase, the enzyme that makes carnitine. Blocking both lowers tissue carnitine, and since carnitine is the shuttle that carries long-chain fatty acids into mitochondria, the cell shifts from burning fat toward burning glucose (PMID: 12242052; PMID: 26850121). Under low-oxygen conditions glucose oxidation needs less oxygen per unit of ATP, which is the basis for the anti-ischemic claim.\n\nThe best human trial is MILSS I, a randomized, double-blind, placebo-controlled study of 512 patients with stable angina across 72 centers in four countries, testing four daily doses against placebo on top of standard therapy over twelve weeks. The primary endpoint was change in bicycle exercise time. Two lower dose groups did not separate from placebo. The 1000 mg group increased total exercise time by a mean of 35 seconds compared with a 7 second decrease on placebo, and the highest dose group did worse than the middle one (PMID: 22186118). That is a real but modest effect in patients whose exercise was limited by cardiac ischemia.\n\nWhether it helps healthy athletes is a different question, and the sports medicine reviews are not encouraging. A narrative review concluded that the performance benefit is speculative and discussed without sound scientific evidence (PMID: 27465696), and a 2026 review revisiting the ergogenic evidence reached similar conclusions (PMID: 42344756).\n\nThe pharmacokinetics are the strangest part. Because meldonium competes with carnitine for OCTN2-mediated transport, it accumulates in muscle during treatment and then leaves slowly by diffusion. In 32 healthy athlete volunteers given oral meldonium for three weeks, plasma steady state took several days and urinary elimination continued for months after the last dose (PMID: 30328291). In mice, giving carnitine or gamma-butyrobetaine speeds elimination by competing for the same transporter (PMID: 27983775). This is why athletes tested positive long after they stopped, and it is also why meldonium residues have been found in milk as a possible inadvertent doping route (PMID: 34448364).\n\nCapsules sold as meldonium dihydrate are a foreign prescription drug being distributed outside any prescribing system.", "half_life": "Not a single simple value: in 32 healthy athlete volunteers taking oral meldonium for three weeks, plasma took several days to reach steady state and urinary elimination continued for several months after the last dose, because tissue clearance depends on slow diffusion rather than transport (PMID: 30328291)", "molecular_weight": "146.19 g/mol", "molecular_mass": "146.19 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral", "Intravenous injection" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Approved (Latvia)", "approval_status": "Registered as Mildronate in Latvia and in several other eastern European and post-Soviet countries for cardiovascular and cerebrovascular indications. Not approved by the FDA or through the centralized EU procedure, so it has no legal medical use in the United States. WADA added meldonium to the prohibited list on 1 January 2016 after a year on the monitoring program, and it is listed under section S4.4, metabolic modulators; it is prohibited at all times (PMID: 27465696; PMID: 30328291).", "trial_phase": "", "cas_number": "76144-81-5", "iupac_name": "", "chemical_formula": "C6H14N2O2", "potential_benefits": [ "Increased total bicycle exercise time by a mean of 35 seconds versus a 7 second decrease on placebo in one dose group of 512 patients with stable angina over twelve weeks (PMID: 22186118)", "Lowered tissue carnitine and long-chain acylcarnitines, shifting cardiac energy metabolism toward glucose oxidation, as described in mechanism reviews of its cardioprotective action (PMID: 26850121)", "Reduced renal acute ischemia and reperfusion injury in rats (PMID: 31731785)", "Improved cardiac function during ischemia through carnitine lowering, as described in mechanism reviews of its cardioprotective action (PMID: 12242052)" ], "research_fields": [ "Carnitine metabolism", "Cardioprotection", "Ischemia", "Sports drug testing" ], "pubmed_count": 0, "pubchem_cid": 123868, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/meldonium" }, { "id": "9733355c-5172-4c48-bd7f-141e25f0b0d5", "slug": "metformin", "name": "Metformin", "aliases": [ "Glucophage", "Glumetza", "Riomet", "Fortamet", "Diabex", "Diaformin", "1,1-Dimethylbiguanide", "Metformin HCl", "N,N-Dimethylbiguanide" ], "category": "Metabolic", "description": "Metformin is a biguanide-class oral antihyperglycemic medication that has been in continuous clinical use since 1957 (in France under the brand name Glucophage) and is now the most-prescribed diabetes medication worldwide with over 150 million prescriptions annually. Structurally 1,1-dimethylbiguanide, metformin derives from galegine, the bioactive guanidine alkaloid in Galega officinalis (goat's rue / French lilac / Italian fitch), a plant used in European folk medicine since the middle ages for what medieval physicians described as \"sweet urine\" — a clinical description consistent with diabetes mellitus. Modern biguanide development began in the 1920s with phenformin and buformin, both of which were withdrawn from most Western markets in the 1970s due to unacceptable rates of lactic acidosis. Metformin emerged as the durable biguanide: approved in the UK in 1958, launched in the US in 1995 (unusually late compared to European and Asian markets due to historical FDA concerns about biguanide safety), and now available in immediate-release and extended-release generic formulations at negligible cost. For type 2 diabetes mellitus (T2DM), metformin is the universally recommended first-line oral therapy based on decades of evidence for glycemic control, modest weight neutrality or weight loss, favorable cardiovascular profile, low hypoglycemia risk (because metformin does not stimulate insulin release), and extremely low cost (generic metformin is typically $4-8/month in the US). The landmark UKPDS (United Kingdom Prospective Diabetes Study) 34 substudy published in 1998 established that metformin reduced all-cause mortality by 36% and myocardial infarction by 39% in overweight T2DM patients versus conventional diet-based therapy — a cardiovascular benefit that became a central rationale for its first-line status. Beyond T2DM, metformin has approved or evidence-supported uses for polycystic ovary syndrome (PCOS) for menstrual regularity, fertility, and weight management; prediabetes and diabetes prevention (the Diabetes Prevention Program, or DPP, demonstrated 31% reduction in progression to diabetes with metformin versus placebo in high-risk individuals); gestational diabetes management; obesity in specific contexts; and increasingly as an adjunct for cancer prevention and treatment based on a large observational evidence base suggesting reduced cancer incidence in metformin-treated T2DM populations. The contemporary interest in metformin as a \"longevity drug\" derives from several converging evidence streams: (1) the Bannister et al. 2014 observational finding (PMID 25041462) that metformin-treated T2DM patients had LONGER survival than matched non-diabetic controls, a counterintuitive result that raised the hypothesis that metformin could extend healthspan beyond its glycemic effects; (2) preclinical evidence from Anisimov, Martin-Montalvo, and others demonstrating metformin-induced lifespan extension in multiple rodent modelswith effect sizes comparable to or exceeding caloric restriction; (3) the TAME (Targeting Aging with Metformin) clinical trial proposed by Nir Barzilai and colleagues at Albert Einstein College of Medicine ( conceptual framework), designed as a large multicenter placebo-controlled RCT of metformin in non-diabetic older adults with age-related disease as the primary endpoint; (4) a growing body of observational evidence linking metformin use to reduced incidence of cancer, cardiovascular disease, dementia, and frailty in aged populations; and (5) the favorable safety profile that makes large-scale long-term use feasible. The longevity framework for metformin is not without controversy. Konopka et al. 2019reported that metformin blunted improvements in insulin sensitivity and aerobic capacity from exercise training in older adults — suggesting that the \"pick two: metformin or exercise\" tradeoff may be real. The MASTERS trial (Walton 2019) similarly showed metformin attenuating muscle hypertrophy gains from resistance training. These findings have produced a reasoned cautious skepticism among aging researchers: metformin may be a valuable drug for diabetic and prediabetic populations but potentially counterproductive for healthy athletic individuals pursuing fitness-based longevity strategies. This entry covers metformin's established pharmacology and T2DM evidence base; the AMPK-complex I-mitochondrial mechanism and the recently-identified GDF15 mediator pathway; the clinical evidence for off-label longevity, cancer prevention, and cardioprotective uses; the Konopka/MASTERS exercise-attenuation findings; the TAME trial framework and the regulatory challenge of approving a drug for aging as a condition; the serious-but-rare lactic acidosis risk and the common vitamin B12 depletion with chronic use; appropriate integration into complete healthspan protocols including exercise, caloric restriction, and other candidate geroprotective interventions; and the practical considerations (IR vs XR formulations, dosing, monitoring) for both diabetic and off-label longevity use.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/metformin" }, { "id": "80318ddc-0fed-4c7f-9174-49f2415d4b2a", "slug": "methylene-blue", "name": "Methylene Blue", "aliases": [ "MB", "MB Vape", "Methylene Blue Vape" ], "category": "Nootropics", "description": "Methylene blue (methylthioninium chloride) is a phenothiazine dye with a 150-year pharmacology record. It was the first fully synthetic drug ever used in medicine (Ehrlich, 1891 for malaria) and remains on the **WHO Model List of Essential Medicines** as the first-line treatment for acquired methemoglobinemia. In the last decade it has re-emerged in biohacking circles because low doses (~0.5 to 4 mg/kg) act as an alternative mitochondrial electron carrier, bypassing damage at Complex I/III of the respiratory chain and boosting cytochrome c oxidase activity ([Atamna et al., 2008]).\n\nThe molecule has an auto-oxidizing redox cycle: reduced leucomethylene blue donates electrons to cytochrome c, then the oxidized form accepts electrons from NADH, effectively forming a \"shunt\" around dysfunctional mitochondrial complexes. This is why low-dose MB improves cerebral oxygen consumption and memory performance in humans, while high doses **paradoxically inhibit** the same system — the dose-response curve is **hormetic and inverted-U**, one of the most-cited nootropic examples in the field.\n\nThere are **two entirely different use cases** for methylene blue, and collapsing them is the most common cause of harm:\n\n- **Medical methemoglobinemia rescue (1-2 mg/kg IV):** Life-saving antidote delivered by clinicians for nitrate/nitrite/benzocaine/dapsone poisoning. Non-negotiable pharmaceutical-grade material, hospital setting.\n- **Nootropic/mitochondrial microdosing (0.5-4 mg oral per day):** Off-label self-experimentation. Requires **USP pharmaceutical-grade only** — not the industrial textile dye sold on aquarium or lab-chemistry sites, which contains arsenic, cadmium, mercury, and other heavy metals above safe intake thresholds.\n\nIf a vendor cannot produce a third-party **Certificate of Analysis** showing USP purity (>99%) with heavy-metal testing, it is not safe for ingestion at any dose. See our [Vendor COA Guide](/tools/coa-verification) and [Methylene Blue Complete Guide](/blog/methylene-blue-complete-guide) for sourcing protocol.", "half_life": "", "molecular_weight": "", "molecular_mass": "319.85 g/mol", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "0.5 mg - 4 mg/kg daily (oral)", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "61-73-4", "iupac_name": "3,7-bis(dimethylamino)phenothiazin-5-ium chloride", "chemical_formula": "C16H18ClN3S", "potential_benefits": [ "Mitochondrial electron transport bypass (Complex I/III)", "Cytochrome c oxidase activation (+30-70%)", "Memory consolidation and retrieval", "Sustained attention and processing speed", "Antioxidant recycling of ascorbate and glutathione", "Tau aggregation inhibition (Alzheimer's-relevant)", "FDA-indicated treatment for methemoglobinemia", "Adjunct for vasoplegic shock (off-label)", "Photodynamic antimicrobial activity (topical)", "Potential anti-aging via mitochondrial rescue" ], "research_fields": [ "Mitochondrial medicine", "Cognitive enhancement", "Alzheimer's disease / tauopathies", "Methemoglobinemia", "Septic/vasoplegic shock", "Photodynamic therapy", "Redox biology", "Anti-aging research" ], "pubmed_count": 2367, "pubchem_cid": 6099, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/methylene-blue" }, { "id": "913dd970-c789-49c7-bc29-ecea2cf2919c", "slug": "mgf", "name": "MGF (Mechano Growth Factor)", "aliases": [ "Mechano Growth Factor", "IGF-1Ec", "IGF-1 Ec splice variant" ], "category": "Anabolic Peptide", "description": "MGF (Mechano Growth Factor) is the local IGF-1Ec splice variant of insulin-like growth factor-1, expressed in skeletal muscle in response to mechanical loading. Native MGF has an extremely short serum half-life (5-7 minutes), so research peptide vendors typically supply PEG-MGF (polyethylene glycol-conjugated) which extends serum half-life to several days.\n\nMGF activates satellite cell proliferation and muscle stem cell recruitment more rapidly than systemic IGF-1, making it a candidate for post-exercise hyperplasia/hypertrophy protocols. Most peer-reviewed data is preclinical.", "half_life": "Reported/estimated only; no published human PK data. Commonly cited community figures are ~5-7 minutes for native MGF and ~24-48 hours for PEGylated PEG-MGF; neither has been established in human pharmacokinetic studies.", "molecular_weight": "~2868 Da (synthetic 24-amino-acid Ec / E-domain peptide, sequence YQPPSTNKNTKSQRRKGSTFEERK)", "molecular_mass": "~2868.2 Da (average mass, C-terminal Ec peptide)", "amino_acid_sequence": "Tyr-Gln-Pro-Pro-Ser-Thr-Asn-Lys-Asn-Thr-Lys-Ser-Gln-Arg-Arg-Lys-Gly-Ser-Thr-Phe-Glu-Glu-Arg-Lys (Ec peptide)", "administration_routes": [ "Subcutaneous", "Intramuscular" ], "dose_range_mcg": "100-300 mcg (PEG-MGF)", "dosing_frequency": "Twice per week post-workout", "cycle_length": "4-6 weeks per cycle, 4 weeks off", "common_vial_sizes": [ "2mg", "5mg" ], "research_stage": "Preclinical / Research peptide", "approval_status": "Not FDA-approved.", "trial_phase": "Preclinical / Research peptide", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Proposed (preclinical / in-vitro): satellite-cell proliferation in skeletal muscle", "Proposed: local hypertrophy and myonuclear donation to existing fibers", "Proposed: post-exercise recovery support", "Proposed: tissue-repair adjunct (muscle, tendon)" ], "research_fields": [ "Skeletal muscle hypertrophy", "Satellite cell biology", "IGF-1 splice variants", "Post-exercise recovery" ], "pubmed_count": 20, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/mgf" }, { "id": "5ecd3fe4-b1f4-47a0-8aa9-11c63e7ab4db", "slug": "minoxidil", "name": "Minoxidil", "aliases": [], "category": "Skin & Hair", "description": "Minoxidil is an FDA-approved treatment for pattern hair loss. Originally an oral blood-pressure drug, its hair-growth side effect led to the topical products (Rogaine) at 2% and 5%. It is a potassium-channel-opening vasodilator and a prodrug -- activated in the scalp by sulfotransferase to minoxidil sulfate -- that prolongs the hair growth (anagen) phase. Topical minoxidil is available over the counter; low-dose oral minoxidil is used off-label for hair loss under prescription.", "half_life": "Oral minoxidil plasma half-life is approximately 3-4 hours; the hair-growth (pharmacodynamic) effect is independent of plasma level and depends on ongoing daily use.", "molecular_weight": "209.24 g/mol (C9H15N5O)", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "Oral low-dose minoxidil (off-label): 625-5000 mcg/day (0.625-5 mg). Topical minoxidil is dosed by concentration (2% or 5%), not by mcg -- roughly 10-20 mg of minoxidil is delivered per topical application, with only ~1.4% absorbed systemically.", "dosing_frequency": "Topical: once daily (5% foam) to twice daily (2%/5% solution). Oral low-dose minoxidil (off-label): once daily.", "cycle_length": "Continuous/indefinite. Minoxidil is maintenance therapy, not a cycled compound -- benefits are lost within 3-6 months of stopping. Reassess response at 4-12 months.", "common_vial_sizes": [], "research_stage": "FDA-Approved", "approval_status": "FDA-approved: topical minoxidil 2% and 5% (over-the-counter) for androgenetic alopecia in men and women (5% foam approved for women in 2014). Oral minoxidil is FDA-approved only as an antihypertensive (Loniten); low-dose oral minoxidil for hair loss is OFF-LABEL and prescription-only.", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Regrows hair and slows further loss in androgenetic alopecia / female pattern hair loss -- its best-supported use, backed by multiple randomized placebo-controlled trials [PMID:12196747][PMID:15034503].", "In men, 5% topical produced roughly 45% more non-vellus hair regrowth than 2% at 48 weeks, with an earlier response [PMID:12196747].", "Increases hair count and hair-shaft width and improves scalp coverage and the psychosocial impact of hair loss [PMID:15034503].", "Once-daily 5% foam is non-inferior to twice-daily 2% solution in women and causes less scalp irritation and dandruff [PMID:21700360].", "Low-dose oral minoxidil (off-label) is a convenient option for people who dislike or cannot tolerate topical, with efficacy comparable to topical 5% in men [PMID:38598226][PMID:32622136].", "Used off-label as an adjunct in other hair disorders such as telogen effluvium, traction alopecia, chemotherapy-induced alopecia, and scarring alopecias [PMID:32622136]." ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/minoxidil" }, { "id": "898cd5dc-90cf-4030-9380-7be3706cd9eb", "slug": "mirabegron", "name": "Mirabegron", "aliases": [ "Myrbetriq", "Betmiga", "Betanis", "YM-178", "YM178", "beta3-adrenoceptor agonist" ], "category": "Pharmaceutical", "description": "Mirabegron is an approved prescription drug, not a research chemical. Astellas Pharma developed it as YM-178 and it was approved by the FDA in 2012 under the brand name Myrbetriq for overactive bladder, with European approval as Betmiga; the US label now also covers neurogenic detrusor overactivity in children aged three and older. It works by activating the beta-3 adrenergic receptor, which relaxes the bladder detrusor muscle.\n\nThe reason it appears on the research chemical market has nothing to do with bladders. Beta-3 receptors are also the main adrenergic receptors on rodent brown fat, and for decades beta-3 agonists were the leading candidate for a drug that would burn calories by turning on brown adipose tissue. Mirabegron was the first beta-3 agonist available in a form that could test that idea in people.\n\nThe first test worked. In twelve healthy men, a single oral dose increased brown fat metabolic activity measured by FDG PET-CT in every subject and raised resting metabolic rate by 203 kcal per day, about 13 percent (PMID: 25565203). A four-week open-label study in 14 healthy women found higher brown fat activity and resting energy expenditure with no change in body weight or composition, alongside higher HDL cholesterol, apolipoprotein A-I, adiponectin and improved insulin sensitivity on an intravenous glucose tolerance test (PMID: 31961826).\n\nThe complication is dose and receptor selectivity. A Canadian group showed that human brown adipocyte thermogenesis is actually driven by the beta-2 receptor, not beta-3, and that mirabegron only raised brown fat thermogenesis when taken at the maximum allowable dose, at which point it also bound beta-1 and beta-2 receptors, producing cardiovascular effects and white fat lipolysis (PMID: 32755608). A meta-analysis of six human studies found increased brown fat activity, resting energy expenditure, body temperature and free fatty acids, but also increased heart rate, diastolic blood pressure and insulin, with no change in brown fat volume or blood glucose (PMID: 38159219).\n\nPharmacology is well characterized because it is a licensed drug. Plasma concentrations peak at three to five hours and decline with a terminal half-life of roughly 32 to 60 hours across two phase 1 studies; exposure is about 40 percent higher in women than men, and steady state is reached within a week (PMID: 23063375). Absorption, metabolism and excretion have been mapped with radiolabeled drug (PMID: 22269146).\n\nAnyone taking mirabegron for metabolic reasons is using an approved drug off-label at or near its ceiling dose, where the cardiovascular effects are real and measured. That is a different risk profile from its licensed bladder use, and it needs a prescriber, not a supplier.", "half_life": "Terminal half-life about 32 hours in one phase 1 multiple-dose study and about 60 hours in a second, with plasma peaks at three to five hours and steady state within seven days in healthy young and elderly adults (PMID: 23063375)", "molecular_weight": "396.51 g/mol", "molecular_mass": "396.51 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "FDA Approved", "approval_status": "Approved by the FDA in 2012 as Myrbetriq for overactive bladder in adults and later for neurogenic detrusor overactivity in children aged three and older, and approved in the European Union as Betmiga and in Japan as Betanis. Use for brown fat activation, thermogenesis or fat loss is off-label and has only been studied in small trials. Mirabegron is not named on the WADA prohibited list. It is a prescription medicine, not a research chemical, wherever it is legally sold.", "trial_phase": "", "cas_number": "223673-61-8", "iupac_name": "", "chemical_formula": "C21H24N4O2S", "potential_benefits": [ "Increased brown adipose tissue metabolic activity and raised resting metabolic rate by 203 kcal per day in twelve healthy men after a single oral dose (PMID: 25565203)", "Increased brown fat activity, HDL cholesterol, apolipoprotein A-I and adiponectin and improved insulin sensitivity over four weeks in 14 healthy women (PMID: 31961826)", "Increased brown fat activity, resting energy expenditure, body temperature and circulating free fatty acids across six human studies in meta-analysis (PMID: 38159219)", "Reduced adipose tissue myofibroblasts and CXCR2 expression in people with obesity (PMID: 41087927)", "Reached steady state within seven days with plasma peaks at three to five hours, and about 40 percent higher exposure in women than men, in healthy young and elderly adults (PMID: 23063375)" ], "research_fields": [ "Brown adipose tissue", "Beta-3 adrenergic pharmacology", "Energy expenditure", "Urology" ], "pubmed_count": 0, "pubchem_cid": 9865528, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/mirabegron" }, { "id": "57b57c83-2061-477f-9ee4-9672a4ec431e", "slug": "mk-677", "name": "MK-677 (Ibutamoren)", "aliases": [ "Ibutamoren" ], "category": "Growth Hormone / IGF-1 Axis", "description": "MK-677 (also called **Ibutamoren** or **Nutrobal**) is an **orally-active, non-peptide ghrelin receptor (GHS-R1a) agonist** developed by Merck Research Laboratories in the 1990s. Unlike [Ipamorelin](/compound/ipamorelin), GHRP-2, or hexarelin — all of which are peptides requiring subcutaneous injection — MK-677 is a small-molecule drug with high oral bioavailability, making it the only clinically-studied oral growth hormone secretagogue.\n\nMK-677 activates the same GHS-R1a receptor as endogenous ghrelin and produces a strong, sustained GH and IGF-1 elevation with a single daily oral dose. In the key 2-year trial in older adults, MK-677 25 mg/day elevated mean IGF-1 from ~180 ng/mL to ~280 ng/mL and produced measurable increases in lean body mass ([Nass et al., 2008]).\n\nThe defining pharmacokinetic feature is the **~24-hour plasma half-life**, which enables once-daily dosing and produces a **sustained elevation of GH pulse amplitude throughout the day** rather than the discrete 2-3 hour pulse of injectable GHS peptides. This is mechanistically distinct from the pulsatile GH architecture preserved by [Ipamorelin](/compound/ipamorelin), [Tesamorelin](/compound/tesamorelin), and MOD-GRF 1-29 — and is the source of both MK-677's popularity (convenience, durable IGF-1 elevation) and its characteristic side-effect profile (greater water retention, appetite stimulation, and insulin resistance than the injectable GHS peptides).\n\nMK-677 reached Phase 3 trials for pediatric growth hormone deficiency, geriatric sarcopenia, and hip fracture recovery. Despite positive efficacy signals, **Merck discontinued development** in the early 2010s, and the compound is **not FDA-approved for any indication**. It remains widely available as a research-use oral supplement and is one of the most popular compounds in the biohacking and bodybuilding communities specifically because of its oral route, 24-hour half-life, and significant effects on body composition, sleep, and appetite.\n\nTypical dosing: **10-25 mg orally, once daily** (typically pre-bed). Doses above 25 mg provide minimal additional benefit and increase side effects proportionally.\n\n**Regulatory status:** Not FDA-approved. Sold as a research chemical in the US; WADA-banned for competitive athletes. Commonly used off-label in integrative medicine and is heavily represented in biohacking protocols. See our [MK-677 Dosage Guide](/guides/dosage/mk-677) for protocol specifics and our [Ipamorelin vs MK-677](/blog/ipamorelin-vs-mk-677) comparison for stack-selection context.", "half_life": "~24 hours (oral)", "molecular_weight": "528.7 Da", "molecular_mass": "528.67 g/mol", "amino_acid_sequence": "", "administration_routes": [ "oral" ], "dose_range_mcg": "10,000–25,000 mcg (10–25 mg) oral daily", "dosing_frequency": "Once daily, typically at bedtime", "cycle_length": "8–16 weeks; some use long-term (6+ months) with monitoring", "common_vial_sizes": [ "25mg capsules", "30mL liquid" ], "research_stage": "Phase II", "approval_status": "Not FDA-approved (investigational / research-use-only)", "trial_phase": "Phase 2", "cas_number": "159634-47-6", "iupac_name": "2-amino-2-methyl-N-[1-(methylsulfonylmethyl)-2-(1-methylpropyl)-3-(1H-indol-3-ylmethyl)...] (complex structure)", "chemical_formula": "C27H36N4O5S", "potential_benefits": [ "Increased IGF-1 (~80-100% over baseline at steady state)", "Improved slow-wave sleep architecture", "Lean body mass increase (demonstrated in 2-year older adult trial)", "Improved connective tissue / wound / bone repair", "Once-daily oral convenience (no injections)", "Appetite stimulation (benefit for underweight or hard-gainer populations)", "Enhanced recovery between training sessions", "Potential bone mineral density improvement" ], "research_fields": [ "Growth hormone deficiency", "Muscle wasting", "Osteoporosis", "Aging", "Alzheimer's disease" ], "pubmed_count": 46, "pubchem_cid": 178024, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/9833049/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/mk-677" }, { "id": "c2101e7f-afc3-462d-8f7e-ab8b07affecc", "slug": "modafinil", "name": "Modafinil", "aliases": [ "Provigil", "Alertec", "Modalert", "Modvigil", "Modawake", "2-((diphenylmethyl)sulfinyl)acetamide", "CRL-40476" ], "category": "Nootropics", "description": "Modafinil is a prescription wakefulness-promoting agent approved by the US Food and Drug Administration in December 1998 under the brand name Provigil (Cephalon, now Teva) for the treatment of excessive daytime sleepiness associated with narcolepsy, shift work sleep disorder, and as an adjunct to continuous positive airway pressure therapy in obstructive sleep apnea. It is a racemic mixture of R- and S-enantiomers; the R-enantiomer (armodafinil, brand name Nuvigil) was approved separately in 2007 as a longer-acting alternative. Modafinil became a Schedule IV controlled substance in the United States in 1999, reflecting a low but non-zero abuse potential that is substantially below that of amphetamines and classical stimulants. The compound is structurally unrelated to amphetamines, methylphenidate, and other stimulant classes — it is a diphenylmethylsulfinyl acetamide with a distinct pharmacology that produces wakefulness and cognitive effects without the catecholamine surge, appetite suppression, and cardiovascular profile of traditional stimulants. Modafinil's approved medical use base is narrow, but its off-label use is enormous. Physicians prescribe it off-label for ADHD (particularly in patients who do not tolerate or respond to stimulants), fatigue in multiple sclerosis and other neurologic conditions, cancer-related fatigue, depression augmentation (particularly for residual fatigue and cognitive symptoms), post-concussion cognitive dysfunction, jet lag, and age-related cognitive decline. Off-label and non-medical use as a cognitive enhancer — among students preparing for exams, professionals working long hours, military personnel during sustained operations, and the general nootropic community — has made modafinil one of the most-discussed cognitive enhancement compounds in both academic and lay media. The evidence base is substantial for approved indications and mixed for off-label use, with meta-analyses and systematic reviews documenting meaningful cognitive benefits in sleep-deprived users and healthy users performing complex cognitive tasks, alongside more modest or inconsistent effects on simple cognitive measures in rested users. Its safety profile across 25+ years of clinical use is generally favorable, though rare serious adverse events including Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS syndrome (drug reaction with eosinophilia and systemic symptoms) require specific attention. This entry covers modafinil's mechanism of action and the ongoing uncertainty about which of its multiple pharmacologic effects drives wakefulness; the clinical evidence base for approved indications including narcolepsy, shift work disorder, and OSA; the off-label cognitive enhancement literature with its well-known heterogeneity between sleep-deprived and rested subjects; the side effect profile including common, serious, and rare adverse effects; the practical dosing conventions used in medical and non-medical contexts; its interactions with hormonal contraception and CYP450 substrates; contraindications based on cardiovascular, hepatic, and psychiatric history; how modafinil compares to and stacks with other nootropic compounds like [Noopept](/compound/noopept), [Piracetam](/compound/piracetam), [Sulbutiamine](/compound/sulbutiamine), [Bromantane](/compound/bromantane), [Selank](/compound/selank), [Semax](/compound/semax), [Methylene Blue](/compound/methylene-blue), [NAD+](/compound/nad), [L-Theanine](/compound/l-theanine), and [L-Tyrosine](/compound/l-tyrosine); and what responsible use looks like for someone considering modafinil for either medical or cognitive enhancement purposes. Modafinil remains the single most clinically validated cognitive enhancement compound available, with a body of evidence, safety data, and regulatory oversight that no research-chemical nootropic can match. For users who need demonstrably effective wakefulness promotion for legitimate medical reasons, it is a first-line option. For users considering it for cognitive enhancement, it is a serious drug with real effects and real side effects that deserves a serious evaluation rather than casual experimentation.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 3, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/modafinil" }, { "id": "245e2f0e-c595-4791-abf3-12e92a1c3257", "slug": "molybdenum", "name": "Molybdenum", "aliases": [ "Mo", "Mo6+", "Mo5+", "Mo4+", "Molybdate", "MoO4", "Sodium molybdate", "Na2MoO4", "Ammonium molybdate", "Molybdenum glycinate", "Molybdenum chelate", "Molybdenum amino acid chelate", "Molybdenum citrate", "Molybdenum picolinate", "Molybdenum aspartate", "Molybdenum trioxide", "MoO3", "Molybdenum disulfide", "MoS2", "Molybdopterin", "Molybdenum cofactor", "Moco", "Fosdenopterin", "Cyclic pyranopterin monophosphate", "cPMP", "Tetrathiomolybdate", "TTM", "Ammonium tetrathiomolybdate", "ATN-224" ], "category": "Mineral", "description": "\nMolybdenum is an essential trace mineral that functions as the catalytic metal center of a small but critical set of mammalian enzymes — xanthine oxidase/dehydrogenase, aldehyde oxidase, sulfite oxidase, and mitochondrial amidoxime reducing component (mARC) — all of which carry a shared prosthetic group called the molybdenum cofactor (moco, molybdopterin-Mo complex). Molybdenum is one of the clearest examples of a mineral whose essentiality is not in dispute; loss-of-function mutations in any of the enzymes involved in moco biosynthesis (MOCS1, MOCS2, MOCS3, GPHN) produce molybdenum cofactor deficiency (MoCD), a devastating autosomal recessive metabolic disorder presenting in the neonatal period with intractable seizures, progressive cerebral atrophy, lens dislocation, and death in infancy without treatment. In 2021, the FDA approved fosdenopterin (cyclic pyranopterin monophosphate, cPMP) as the first specific treatment for MoCD type A — the first molybdenum-related pharmacologic approval and one of the more dramatic examples of rescuing a previously uniformly fatal inborn error of metabolism with substrate replacement therapy. The adult body contains only approximately 9 mg of molybdenum, making it one of the trace minerals with the smallest physiologic pool, yet the metabolic consequences of its dysfunction are catastrophic. Peter Jacob Hjelm isolated elemental molybdenum in 1781 from the mineral molybdenite (MoS2); the name derives from the Greek \"molybdos\" meaning lead, reflecting historic confusion between molybdenum and lead ores. The nutritional essentiality of molybdenum for mammalian biology was established through the 1950s-1960s characterization of xanthine oxidase and aldehyde oxidase as molybdenum-containing enzymes, followed by the elucidation of sulfite oxidase and its critical role in sulfur amino acid catabolism.\n\nThe recommended dietary allowance (RDA) for molybdenum is 45 μg/day for adult men and women, with pregnancy and lactation at 50 μg/day. The tolerable upper intake level (UL) is 2,000 μg/day (2 mg/day) for adults, a comparatively wide safety margin (approximately 44-fold above RDA) reflecting molybdenum's low human toxicity at physiologic doses. Children require 17-43 μg/day depending on age. Typical US dietary molybdenum intake ranges 76-109 μg/day, well above the RDA. Molybdenum is widely distributed in foods. Legumes (lima beans, black beans, kidney beans) are particularly rich with 50-150 μg per half-cup, making them the most important dietary source. Whole grains (oats, barley, wheat) provide 30-60 μg per serving. Leafy greens and vegetables contribute variable amounts depending on soil molybdenum content (which varies substantially with geology and agricultural practice). Organ meats (especially beef liver) contain high concentrations. Tap water contributes 2-10 μg per liter. Dietary deficiency of molybdenum in the general population is essentially unknown; deficiency has been reported only in a handful of patients on long-term parenteral nutrition without molybdenum supplementation (Abumrad 1981 AJCN described the index case — a 24-year-old woman on TPN for 18 months who developed intolerance of sulfur amino acids, defective sulfite and purine metabolism, neurologic symptoms including tachycardia, tachypnea, headache, night blindness, coma-like state, and eventual resolution with molybdenum supplementation). This case established the clinical syndrome of acquired molybdenum deficiency and the physiologic requirement.\n\nMolybdenum absorption is relatively efficient. Approximately 40-100% of ingested molybdate is absorbed in the small intestine via passive diffusion and possibly via sulfate transporters (molybdate chemically resembles sulfate and may use the same transporters at low doses). Absorption is reduced by high dietary sulfate intake (competitive inhibition at sulfate transporters) and by copper (forming unabsorbable copper-molybdenum-sulfur complexes in the gut). Absorbed molybdate (MoO4^2-) circulates in plasma bound to alpha-2-macroglobulin and erythrocyte proteins, distributes primarily to liver, kidney, adrenals, and bone, and is excreted predominantly via urine as molybdate (40-80% of intake) with smaller biliary excretion. The biological half-life is hours to days, with little tissue accumulation at physiologic intake. This efficient excretion combined with wide safety margin explains why molybdenum toxicity from dietary supplementation is rare.\n\nIntracellular molybdenum is directed into the molybdopterin synthesis pathway to produce the molybdenum cofactor (moco), a complex organic scaffold that positions molybdenum for enzymatic catalysis. Moco biosynthesis is an ancient, conserved pathway with four sequential steps catalyzed by dedicated enzyme machinery: MOCS1A/B produces cyclic pyranopterin monophosphate (cPMP) from GTP (guanosine triphosphate) via a radical S-adenosylmethionine mechanism — the rate-limiting and first committed step; MOCS2A/B converts cPMP to molybdopterin via the addition of the dithiolene sulfur groups; MOCS3 (adenylates molybdopterin); and gephyrin (GPHN, which has a dual role as a moco-inserting enzyme and as a synaptic scaffolding protein for GABA and glycine receptor clustering) inserts the molybdenum ion into molybdopterin to form the final active moco. Loss of function at any step produces molybdenum cofactor deficiency with the same broad clinical phenotype. MoCD type A (MOCS1 mutations, approximately 60% of cases) is the form treatable with fosdenopterin (synthetic cPMP); MoCD type B (MOCS2) and MoCD type C (GPHN) do not respond to cPMP.\n\nSulfite oxidase (SUOX) catalyzes the terminal step of cysteine and methionine catabolism, oxidizing sulfite (SO3^2-) to sulfate (SO4^2-) in the liver mitochondrial intermembrane space. Sulfite accumulation in SUOX deficiency or MoCD is particularly neurotoxic — sulfite reacts with cystine disulfide bonds forming S-sulfocysteine, a toxic metabolite that accumulates massively in MoCD patients and in isolated sulfite oxidase deficiency. The severe neurologic phenotype of MoCD (neonatal seizures, cystic encephalopathy, ectopia lentis from sulfite-damaged lens proteins) is primarily attributable to loss of sulfite oxidase function rather than loss of xanthine oxidase or aldehyde oxidase. Isolated sulfite oxidase deficiency (due to SUOX mutations, moco synthesis intact) has nearly identical phenotype to MoCD, confirming the central importance of SUOX in the disease biology.\n\nXanthine oxidase/dehydrogenase (XDH) catalyzes the final two steps of purine catabolism, converting hypoxanthine to xanthine and xanthine to uric acid. XDH deficiency (xanthinuria type I) produces xanthine accumulation with urolithiasis from xanthine stones. Allopurinol, the classic gout drug, is a xanthine oxidase inhibitor exploiting this biology pharmacologically. Febuxostat is a newer non-purine XDH inhibitor. In MoCD, xanthine oxidase is nonfunctional and patients develop xanthine stones and low uric acid — one of the biochemical signatures of the disease.\n\nAldehyde oxidase (AOX1) is a broad-specificity oxidase metabolizing diverse aldehydes and azaheterocycles. Aldehyde oxidase is increasingly recognized as a significant drug-metabolizing enzyme in humans, contributing to the oxidation of drugs like methotrexate, famciclovir (to penciclovir), zaleplon, ziprasidone, and carbazeran. Inter-individual variation in AOX1 activity is high, contributing to pharmacokinetic variability for affected drugs. AOX1 activity depends on moco.\n\nMitochondrial amidoxime reducing component (mARC) — the fourth and most recently characterized mammalian molybdenum enzyme (Havemeyer 2006) — reduces N-hydroxylated compounds back to their amino forms. mARC contributes to the physiologic reduction of drug metabolites (some antimicrobials, anticancer drugs) and endogenous N-hydroxylated intermediates. Biological significance is still being defined.\n\nBeyond metabolism, molybdenum intersects with [copper](/compound/copper) biology through one of the more dramatic therapeutic applications of mineral biology: tetrathiomolybdate (TTM, ATN-224). TTM is an orally bioavailable molybdenum compound that forms stable Mo-S-Cu complexes, irreversibly sequestering copper and dramatically reducing copper bioavailability. TTM is used as copper-chelating therapy in Wilson disease (genetic copper accumulation disorder), with some evidence of superior neurologic outcomes compared to penicillamine in de-coppering treatment phases. TTM has also been investigated as angiogenesis inhibitor in cancer (since copper is required for angiogenesis), and in fibrotic disease and autoimmune disease due to TTM's effects on copper-dependent enzymes (lysyl oxidase, Cu/Zn-SOD). Brewer and colleagues developed the clinical application of TTM in Wilson disease in the 1990s-2000s (Brewer 2006).\n\nBodyHackGuide's take: molybdenum is a true essential mineral with a catastrophic deficiency syndrome at the extremes (MoCD) but near-universal adequacy from ordinary diets. The RDA (45 μg) is easily met by a diet containing legumes, whole grains, or organ meats. Supplementation is not needed for free-living adults with varied diets. Multivitamin content (typically 45-75 μg) is appropriate and harmless. Standalone molybdenum supplements are marketed primarily for candida detoxification and \"sulfite sensitivity\" support, with minimal evidence base. If supplementation is pursued, 150-500 μg/day of sodium molybdate or glycinate is within safety limits. Therapeutic applications (fosdenopterin for MoCD, tetrathiomolybdate for Wilson disease or cancer research) are specialized and not consumer products. For most users, molybdenum is a background essentiality — present, adequate, not a focus. The biology is elegant (moco as one of the most complex cofactor biosynthesis pathways in nature) but the supplementation implications are modest.\n", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 948, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/molybdenum" }, { "id": "4d7a6dd5-67c1-4c98-a298-70d57b11f084", "slug": "mots-c", "name": "MOTS-c", "aliases": [ "MOTS-c" ], "category": "Longevity & Cellular Health", "description": "MOTS-c (Mitochondrial ORF of the Twelve S rRNA type-c) is a **16-amino-acid mitochondrial-derived peptide** — a member of a recently discovered class of small peptides encoded in mitochondrial DNA rather than nuclear DNA. It was first characterized and named by [Lee et al. in 2015] at Pinchas Cohen's laboratory at USC, representing a paradigm shift in mitochondrial biology: the mitochondria are not merely recipients of nuclear regulatory signals, they produce their own signaling peptides that act both locally and systemically on metabolism.\n\nThe MOTS-c sequence (**M-R-W-Q-E-M-G-Y-I-F-Y-P-R-K-L-R-H**) is encoded in the 12S rRNA region of mitochondrial DNA. Under metabolic stress conditions — fasting, caloric restriction, exercise — mitochondria translate and release MOTS-c into circulation, where it acts as an **exercise-mimetic** and **metabolic regulator** with primary effects on skeletal muscle, adipose tissue, and liver.\n\nThe core pharmacologic mechanism is **AMP-activated protein kinase (AMPK) agonism**, the same metabolic master-switch targeted by metformin, exercise, and caloric restriction. AMPK activation drives:\n\n- **GLUT4 translocation** to the muscle cell membrane → increased glucose uptake\n- **Fatty acid oxidation** upregulation via ACC phosphorylation\n- **Mitochondrial biogenesis** via PGC-1α pathway\n- **Inhibition of de novo lipogenesis and gluconeogenesis**\n- **Improved insulin sensitivity** at multiple tissue sites\n\nPreclinical studies document striking effects: MOTS-c treatment in diet-induced obese mice produces weight loss, restored insulin sensitivity, normalized glucose tolerance, and enhanced exercise capacity ([Lee 2015]; [Reynolds 2021]). In aging studies, MOTS-c administration to aged mice restores exercise performance to that of young animals and reverses age-related metabolic dysfunction ([Reynolds 2021]).\n\nImportantly, **endogenous MOTS-c levels decline with aging** and are suppressed in metabolic disease states. This has generated the hypothesis that declining MDP production is a **causal contributor to age-related metabolic decline** — positioning MOTS-c replacement as a potential longevity intervention analogous to hormone replacement, though the evidence base is still primarily preclinical.\n\nMOTS-c is **not FDA-approved** for any indication. Research-chemical use for metabolic tuning, athletic performance, and longevity purposes is emerging but limited; typical protocols use 5-10 mg SC 2-3 times weekly. Human pilot data is scarce; most efficacy inferences come from animal models and mechanistic plausibility.", "half_life": "~4–6 hours", "molecular_weight": "2174 Da", "molecular_mass": "2174.39 g/mol", "amino_acid_sequence": "MRWQEMGYIFYPRKLR", "administration_routes": [ "Subcutaneous", "Intramuscular" ], "dose_range_mcg": "5,000–10,000 mcg (5–10 mg) per injection", "dosing_frequency": "2-3 times per week", "cycle_length": "8-12 weeks", "common_vial_sizes": [ "5mg", "10mg" ], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "Preclinical", "cas_number": "1600863-63-5", "iupac_name": "Mitochondrial open reading frame of 12S rRNA-c (MRFA-peptide)", "chemical_formula": "C104H181N33O28S", "potential_benefits": [ "Insulin sensitivity", "Exercise mimicry", "Metabolic health", "Anti-aging", "Fat oxidation", "Longevity" ], "research_fields": [ "Diabetes", "Metabolic syndrome", "Exercise physiology", "Aging", "Obesity" ], "pubmed_count": 167, "pubchem_cid": 91936052, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/91936052/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/mots-c" }, { "id": "7b92e326-c6d5-49f2-9ac9-81580d8c5ad9", "slug": "mt-ii", "name": "Melanotan II", "aliases": [], "category": "Skin / Cosmetic", "description": "This is a duplicate/alias entry. The full, maintained guide for this compound lives at Melanotan II (/compound/melanotan-ii). See that page for mechanism, dosing, evidence, and safety.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Duplicate entry - see Melanotan II", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "See the full guide at Melanotan II (/compound/melanotan-ii) for benefits and evidence." ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/mt-ii" }, { "id": "119ec3e8-7ecb-4782-8502-cb76bf8b3de3", "slug": "mucuna-pruriens", "name": "Mucuna Pruriens", "aliases": [ "Mucuna", "Velvet Bean", "Kapikacchu", "Atmagupta", "Kauchni", "Kaunch", "Cowitch", "Cowhage", "Itching Powder", "Kiwach" ], "category": "herb", "description": "Mucuna pruriens — known as velvet bean in English, Kapikacchu (αñòαñ¬αñ┐αñòαñÜαÑìαñ¢αÑé) or Atmagupta in Sanskrit, Kauchni or Kaunch in Hindi, and cowitch or cowhage in older Western materia medica — is one of the most pharmacologically unusual legumes on earth and one of the very few medicinal plants whose primary active constituent is a well-characterized pharmaceutical drug rather than a complex phytochemical mixture. The seeds of Mucuna pruriens naturally contain 3-7% levodopa (L-DOPA, L-3,4-dihydroxyphenylalanine) by dry weight — the same molecule that has been the cornerstone of Parkinson's disease pharmacotherapy since the 1960s — along with smaller amounts of serotonin, 5-hydroxytryptophan (5-HTP), nicotine, bufotenine, N,N-dimethyltryptamine (DMT), beta-carboline alkaloids, and several minor alkaloids including mucunine, mucunadine, mucuadinine, prurienine, and prurieninine. This notable phytochemical profile makes Mucuna a genuine \"natural pharmacy\" for the dopaminergic system — not in the usually hand-wavy sense that some adaptogenic herbs are described, but in the literal sense that it contains the actual drug molecule used clinically. The plant is a climbing tropical legume with distinctive seed pods covered in fine, barbed trichomes (hairs) that produce intense contact dermatitis on human skin — the Hindi name Kauchni and the English \"itching powder\" both reference this property, and the trichomes contain a serotonin-releasing protein called mucunain that causes the itch response. Processed seeds, with the trichomes removed, have been used medicinally for over 4,000 years in Ayurveda, primarily as a male reproductive tonic (Vajikarana rasayana), for the treatment of parkinsonian symptoms called Kampavata (literally \"shaking wind\" — a disease description remarkably similar to what we now call Parkinson's disease), and for a broad spectrum of neurological, sexual, and metabolic indications. Modern clinical research on Mucuna pruriens has taken two distinct directions. The first, and by far the most important, is its use as a natural source of levodopa for Parkinson's disease, either in resource-limited settings where pharmaceutical levodopa-carbidopa is expensive or unavailable, or as an adjunct in wealthier settings to address specific limitations of standard therapy. Multiple controlled trials — most notably Katzenschlager and colleagues' 2004 study at the Queen Square Institute of Neurologyand Manyam and colleagues' 2004 HP-200 formulation trial— have demonstrated that Mucuna pruriens seed powder produces motor improvements in Parkinson's patients comparable to standard levodopa-carbidopa, with some pharmacokinetic and tolerability advantages including faster onset, longer duration of effect, and reduced peak-dose dyskinesia in some patient populations. The mechanism for these advantages is not fully understood but may involve the minor alkaloids acting as peripheral decarboxylase inhibitors (mimicking the carbidopa component), along with a more physiological release profile from the complex plant matrix. The second research direction is Mucuna's role as a male reproductive and stress-modulating adaptogen. Controlled trials in infertile men — Shukla and colleagues 2007, Ahmad and colleagues 2008 (PMID 18973898) — have demonstrated improvements in sperm concentration, motility, and morphology along with reductions in stress-related parameters (cortisol, lipid peroxidation), which is consistent with the traditional Vajikarana use. The mechanism for reproductive effects appears to involve dopaminergic stimulation of hypothalamic-pituitary-gonadal axis function, reduction of oxidative stress in testicular tissue, and modulation of cortisol responses to stress. Modern supplement markets offer Mucuna pruriens in several forms: whole seed powder (typically 1-3% L-DOPA by weight), standardized extracts to 15%, 20%, 40%, or 99% L-DOPA content, and specialized formulations like HP-200 (an early-stage clinical formulation studied in Parkinson's disease). Many consumers and casual nootropic users encounter Mucuna as a low-dose L-DOPA supplement marketed for mood, motivation, libido, and dream vividness — indications that are biologically plausible but less rigorously studied than the Parkinson's and fertility applications. The classical Ayurvedic preparation uses whole, processed, roasted seeds ground into a powder and taken with warm milk and ghee, typically at doses of 3-9 grams daily; the L-DOPA dose in this preparation is quite modest (roughly 50-200 mg) and produces gentle, sustained dopaminergic support rather than the acute pharmaceutical-level effect of concentrated extracts. High-concentration extracts (20-99% L-DOPA) should be treated with the same respect as pharmaceutical levodopa — they are not casual supplements, they have meaningful side effects and drug interactions, and they are not appropriate for long-term use in healthy individuals without a specific clinical indication. For Parkinson's disease, use of Mucuna should only occur under neurology supervision and as part of a coordinated treatment plan. For general wellness and reproductive health in otherwise healthy adults, low to moderate doses of whole-seed or lightly standardized preparations (1-5% L-DOPA) are the appropriate starting point.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/mucuna-pruriens" }, { "id": "5a02c223-47f3-46b1-adff-0ddf293b1618", "slug": "n-acetyl-selank", "name": "N-Acetyl-Selank", "aliases": [ "NASA-Selank", "N-Acetyl Selank" ], "category": "Cognitive", "description": "N-Acetyl-Selank is the N-terminally acetylated analog of Selank, a tuftsin-derived heptapeptide used intranasally for its reported anxiolytic and nootropic effects. The acetyl group is claimed to improve stability and duration versus standard Selank, though the analog itself is essentially unstudied. Research use only (RUO).", "half_life": "Not established for the N-acetyl analog. Parent Selank has a very short plasma half-life (on the order of minutes, as expected for a small peptide) but produces behavioral effects lasting hours, attributed to active fragments and downstream enkephalin/GABA modulation. N-acetylation is claimed to slow N-terminal degradation and extend duration, but this is unquantified in published literature.", "molecular_weight": "~793.9 g/mol (theoretical: Selank ~751.9 g/mol + N-terminal acetyl, ~+42). Approximate molecular formula C35H59N11O10.", "molecular_mass": "", "amino_acid_sequence": "Ac-Thr-Lys-Pro-Arg-Pro-Gly-Pro (N-acetyl-TKPRPGP) - the acetyl group caps the N-terminal threonine of the Selank heptapeptide.", "administration_routes": [], "dose_range_mcg": "100-900", "dosing_frequency": "Once or twice daily (intranasal); some advanced users split into 2-3 doses", "cycle_length": "No established cycle. Parent Selank has been used in ~2-3 week clinical courses; community use of the analog is typically 2-4 weeks on, then a break. RUO.", "common_vial_sizes": [], "research_stage": "Preclinical (the N-acetyl analog has no dedicated studies); parent Selank has limited clinical use in Russia", "approval_status": "Not FDA/EMA approved - research use only (RUO). Parent Selank is registered as a medicine only in Russia; the N-acetyl analog is not approved anywhere.", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Anxiolytic (calming) effects - the most-studied action of parent Selank, including a Russian clinical trial in generalized anxiety disorder [PMID:18454096]", "Nootropic / cognitive support - reported attention and memory benefits in rodent models, linked to BDNF changes [PMID:31625062]", "Stress resilience reported without the sedation, tolerance, or dependence typically seen with benzodiazepines (preclinical framing) [PMID:30255741]", "Possible support during withdrawal states (alcohol, opioid) in animal models [PMID:24913576][PMID:36322304]", "Claimed longer duration vs. plain Selank from N-terminal acetylation - a community/vendor claim not verified in published data" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/n-acetyl-selank" }, { "id": "0e974514-ab28-4cdf-8362-86b4696b1b2a", "slug": "n-acetyl-semax", "name": "N-Acetyl-Semax", "aliases": [ "NASA-Semax", "N-Acetyl Semax" ], "category": "Cognitive", "description": "This is a duplicate/alias entry. The full, maintained guide for this compound lives at NA-Semax (/compound/na-semax). See that page for mechanism, dosing, evidence, and safety.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Duplicate entry - see NA-Semax", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "See the full guide at NA-Semax (/compound/na-semax) for benefits and evidence." ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/n-acetyl-semax" }, { "id": "1005fbc9-746d-4c8a-b21b-d1bb4042d837", "slug": "na-semax", "name": "NA-Semax", "aliases": [ "N-Acetyl-Semax", "N-acetyl-l-aspartyl-Semax", "NAA-Semax", "Semax NA", "Acetyl Semax" ], "category": "Nootropic Peptide", "description": "NA-Semax is the **N-acetyl-l-aspartyl variant of [Semax](/compound/semax)** — the original ACTH(4-7) Pro-Gly-Pro analog developed at the Russian Academy of Sciences in the 1990s. The aspartate addition at the N-terminus is reported to improve metabolic stability against aminopeptidase cleavage, extending the in vivo half-life from minutes (parent Semax) to plausibly tens of minutes after intranasal dosing.\n\nAs of 2026, NA-Semax sits in the same research-peptide tier as standard Semax — it is **not FDA-approved** for any indication and is sold as a research chemical with limited peer-reviewed primary literature on the acetylated variant specifically. Most published Semax pharmacology applies by analogy, with the caveat that the half-life difference may shift optimal dosing frequency.\n\nReported nonclinical pharmacology mirrors Semax: BDNF upregulation, dopaminergic modulation in mesolimbic circuits, and increased serotonin and dopamine turnover in the cortex and hippocampus. The N-acetyl modification is reported to improve blood-brain-barrier transport, though direct PK comparisons in published literature remain thin.", "half_life": "~20-30 minutes (intranasal, estimated from analog data)", "molecular_weight": "~856.0 g/mol (C39H53N9O11S)", "molecular_mass": "", "amino_acid_sequence": "Ac-Met-Glu-His-Phe-Pro-Gly-Pro (Ac-MEHFPGP)", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Not approved for human use (research-use-only). N-acetyl-Semax is an unapproved analogue with no clinical trials; the parent peptide Semax is a registered drug only in Russia and some CIS countries and has no FDA or EMA approval.", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "C40H56N12O11", "potential_benefits": [], "research_fields": [], "pubmed_count": 3, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/na-semax" }, { "id": "1d5de15d-6bf1-42c2-ace0-4287c2febb9e", "slug": "na-semax-amidate", "name": "NA-Semax Amidate", "aliases": [ "NA-Semax Amide", "N-Acetyl Semax Amide", "NA-Semax-NH2", "Acetyl-Semax-Amide" ], "category": "Nootropic Peptide", "description": "NA-Semax Amidate is the **C-terminally amidated [NA-Semax](/compound/na-semax)** — the carboxylic acid at the peptide's C-terminus is replaced with an amide group (-NH2), which is reported to further extend metabolic half-life by resisting carboxypeptidase cleavage in addition to the aminopeptidase resistance the N-acetyl group already provides.\n\nThe practical effect is a peptide with **dosing-frequency use**: where standard Semax often requires 3-4 daily doses to maintain effect, NA-Semax Amidate is reported (in vendor monographs and community usage) to maintain subjective effects on a 1-2x daily schedule. Direct pharmacokinetic comparisons in peer-reviewed literature remain absent — this framing is honest about the evidence base.", "half_life": "~30-45 minutes (estimated, longer than standard Semax)", "molecular_weight": "~855.0 g/mol (C39H54N10O10S; monoisotopic ~854.4)", "molecular_mass": "", "amino_acid_sequence": "Ac-Met-Glu-His-Phe-Pro-Gly-Pro-NH2 (Ac-MEHFPGP-NH2)", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "C40H57N13O10", "potential_benefits": [], "research_fields": [], "pubmed_count": 2, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/na-semax-amidate" }, { "id": "bb768cc0-d483-4f55-821f-b026648062d0", "slug": "nac", "name": "NAC", "aliases": [ "N-Acetylcysteine", "N-Acetyl-L-Cysteine", "Acetylcysteine", "Mucomyst", "Acetadote", "Fluimucil", "Parvolex", "NALC", "L-α-Acetamido-β-mercaptopropionic acid" ], "category": "Antioxidants", "description": "N-acetylcysteine (NAC) is the acetylated form of the amino acid L-cysteine — a small thiol-containing molecule that serves as a rate-limiting precursor for glutathione (GSH) synthesis and, independently, as a direct antioxidant and mucolytic agent. Discovered in the 1960s as a mucolytic (via its ability to cleave disulfide bonds in mucus glycoproteins) and repurposed in the mid-1970s as the definitive antidote for acetaminophen (paracetamol) overdose, NAC has one of the broadest therapeutic profiles of any thiol-based medication and is on the World Health Organization's List of Essential Medicines. It is available in multiple regulatory categories depending on jurisdiction: prescription (for IV use in acetaminophen overdose and inhalation/nebulization for mucolytic use), over-the-counter (in much of Europe as oral effervescent tablets branded Fluimucil, ACC, Mucomyst), and as a dietary supplement (in the United States, where it has been sold as a supplement for decades despite a contentious 2020 FDA enforcement notice asserting that NAC's status as a drug — approved 1963 — precludes supplement classification under DSHEA; the FDA walked back enforcement in 2022 and supplement sales resumed, though the legal question technically remains unresolved).\n\nStructurally, NAC is L-cysteine with an acetyl group on its amine nitrogen — a simple modification that dramatically improves stability (the free thiol of unmodified cysteine oxidizes rapidly), reduces the taste problem (cysteine is intensely unpleasant), and modestly improves oral tolerability. The acetyl group is cleaved by intracellular deacetylases after uptake, releasing free cysteine into the cellular cysteine pool, where it enters the two-step enzymatic synthesis of glutathione: cysteine + glutamate → γ-glutamylcysteine (by γ-glutamylcysteine synthetase, the rate-limiting enzyme) → GSH (by glutathione synthetase, adding glycine). Because cysteine is rate-limiting for GSH synthesis in most tissues — cysteine is the least abundant of the three GSH amino acids in the free amino acid pool, and its intracellular concentration tracks closely with GSH synthesis rate — delivering cysteine via NAC can meaningfully raise tissue GSH in contexts where GSH is depleted. This is the molecular basis for NAC's acetaminophen antidote effect: acetaminophen overdose generates the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI) faster than hepatic GSH can conjugate it, GSH is consumed, and hepatocyte death follows unless GSH synthesis is urgently restored by providing exogenous cysteine.\n\nThe clinical use cases for NAC divide into three tiers by strength of evidence. **Tier 1 (strong RCT evidence):** acetaminophen overdose (IV NAC via the 21-hour Prescott/Smilkstein protocol or the 72-hour oral Smilkstein protocol — mortality reduction from ~5% to <1% when given within 8-10 hours of ingestion); chronic obstructive pulmonary disease exacerbation reduction (BRONCUS trial and subsequent Cochrane reviews showing modest reductions in exacerbation frequency with high-dose oral NAC, 600-1200 mg/day); idiopathic pulmonary fibrosis (mixed results — earlier IFIGENIA trial was positive, later PANTHER-IPF trial was negative for triple therapy but NAC monotherapy remained in the protocol); contrast-induced nephropathy prevention (large meta-analyses show modest benefit, though the ACT trial called the effect into question and modern practice emphasizes hydration more than NAC). **Tier 2 (promising but heterogeneous):** psychiatric applications including bipolar depression (Berk 2008, 3-month RCT showing significant improvement in depression and functional outcomes versus placebo); obsessive-compulsive disorder and OCD-spectrum disorders like trichotillomania and nail-biting (Grant 2009 trichotillomania RCT positive, subsequent OCD trials mixed); schizophrenia (Berk 2008 negative symptoms improvement; later trials heterogeneous); cocaine, cannabis, and gambling addiction (signal for cannabis and early-abstinence cocaine, weaker for gambling); Alzheimer's and Parkinson's disease (preclinical and small-trial rationale, no definitive evidence); male infertility (Ciftci 2009 showing improved sperm parameters in idiopathic oligoasthenoteratozoospermia); polycystic ovary syndrome (Rizk 2005, Fulghesu 2002 showing improved insulin sensitivity and ovulation). **Tier 3 (mechanism-driven but not rigorously tested in humans):** generalized \"antioxidant supplementation\" in healthy individuals, \"detox\" protocols, alcohol hangover prevention, exercise performance or recovery support, sleep support (NAC is sometimes promoted for sleep, though the evidence is weak), and broad longevity support as a GSH-preserving agent — these uses are empirical and driven primarily by mechanism rather than by direct clinical data in healthy populations.\n\nNAC is one of the most-studied thiol therapies in medicine, with over 15,000 PubMed-indexed publications and active investigation across dozens of additional indications including COVID-19 (mostly negative for acute infection, some signal for long COVID symptoms), post-traumatic stress disorder (small trials, promising), autism spectrum disorder (irritability and repetitive behaviors), sickle cell disease, radiation-induced toxicity prevention, and aminoglycoside-induced hearing loss. The combination of low cost (typical oral dose costs pennies per day), favorable safety profile (side effects are almost entirely limited to gastrointestinal upset at high doses and rare anaphylactoid reactions to IV infusion, which are rate-dependent rather than truly allergic), wide availability, and coherent mechanistic rationale has made NAC one of the workhorses of off-label psychiatric and biohacker medicine. This entry covers NAC's glutathione-precursor and direct-antioxidant mechanisms, the pharmacokinetic peculiarities (oral bioavailability is only 4-10% as intact NAC, though effective for raising cysteine pools), the established acetaminophen-overdose and COPD/mucolytic evidence, the psychiatric and addiction medicine literature, the male fertility and PCOS data, practical dosing by indication, the 2020 FDA regulatory episode and its implications, appropriate stacking with other antioxidants and glutathione-pathway nutrients, the relatively narrow but real contraindication set, and the honest framing that distinguishes where NAC has strong evidence (overdose, mucolytic, specific psychiatric conditions) from where it is being taken on faith (general \"antioxidant\" supplementation in healthy people).", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/nac" }, { "id": "a1000000-0000-0000-0000-000000000009", "slug": "nad", "name": "NAD+", "aliases": [ "NAD Plus", "Nicotinamide Adenine Dinucleotide", "NAD" ], "category": "Longevity", "description": "NAD+ (nicotinamide adenine dinucleotide, oxidized form) is a pyridine dinucleotide coenzyme essential to energy metabolism, DNA repair via PARP enzymes, sirtuin-mediated gene regulation, and calcium signaling via CD38. Intracellular NAD+ declines by roughly 50% between ages 40 and 70 in most tissues studied, and restoring NAD+ levels with oral precursors (nicotinamide riboside NR, nicotinamide mononucleotide NMN, nicotinamide NAM) or intravenous NAD+ is one of the most-studied interventions in longevity research. Clinical trials with NR (Chromadex's Niagen) have demonstrated dose-dependent increases in peripheral blood mononuclear cell NAD+ up to 142% at 1,000 mg/day and a favorable safety profile across doses up to 2,000 mg/day. Direct IV NAD+ is used in some longevity and addiction medicine clinics at 250-1,500 mg per session; oral NAD+ itself has poor bioavailability and is generally inferior to its precursors. Regulatory status varies: NR is a legal dietary ingredient in the US and EU; NMN was removed from US dietary supplement status in 2022 but is widely available through other markets; IV NAD+ is compounded at specialty pharmacies.", "half_life": "Varies by form: NR ~8 hours plasma; NMN ~1-2 hours plasma; IV NAD+ infusion dose-dependent", "molecular_weight": "663.4 g/mol (NAD+); NR 255.3 g/mol; NMN 334.2 g/mol; NAM 122.1 g/mol", "molecular_mass": "663.42 g/mol", "amino_acid_sequence": "Not a peptide — dinucleotide cofactor consisting of adenine, nicotinamide, two ribose sugars, and two phosphate groups", "administration_routes": [ "Oral (precursors)", "Intravenous", "Intramuscular", "Subcutaneous" ], "dose_range_mcg": "Oral precursors: NR 300-2,000 mg/day, NMN 250-900 mg/day, NAM 500-1,500 mg/day; IV NAD+ 500-1,500 mg per session.", "dosing_frequency": "Oral precursors once daily (higher doses split AM/midday); IV NAD+ weekly-to-monthly at clinics.", "cycle_length": "4–12 weeks; many use ongoing maintenance dosing", "common_vial_sizes": [ "100mg", "250mg", "500mg" ], "research_stage": "Phase II", "approval_status": "", "trial_phase": "", "cas_number": "53-84-9", "iupac_name": "", "chemical_formula": "C21H27N7O14P2", "potential_benefits": [ "Restores age-associated NAD+ decline — 50% loss between young and older adulthood", "Increases peripheral blood NAD+ by up to 142% at 1,000 mg NR daily (Elhassan 2019)", "Supports sirtuin-mediated gene regulation and PARP-mediated DNA repair", "Improves muscle insulin sensitivity in prediabetic postmenopausal women (Yoshino 2021)", "Increases aerobic performance in amateur runners at 300-600 mg NMN (Liao 2021)", "Reduces inflammatory cytokines (IL-6, TNF-alpha) in middle-aged/elderly (Martens, Elhassan)", "Brain NAD+ elevation demonstrated in Parkinson trial (Brakedal 2022)", "Excellent safety profile at evidence-supported doses (500-2000 mg/day NR)" ], "research_fields": [ "Longevity and healthspan research", "Metabolic disease and insulin sensitivity", "Neurodegenerative disease (Parkinson, Alzheimer models)", "Cardiovascular aging", "Mitochondrial function and energy metabolism" ], "pubmed_count": 3197, "pubchem_cid": 5892, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/nad" }, { "id": "3fdbca61-72c3-4b5a-8a00-17de2c19deb4", "slug": "nad-carnitine-blend", "name": "NAD+ Carnitine Blend", "aliases": [ "NAD Carnitine" ], "category": "Weight Loss", "description": "NAD+ and carnitine amino blend for energy and metabolism", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "NAD+ 50-250 mg plus L-carnitine 250-1000 mg per session (community / IV-clinic practice; not trial-validated). Start at the low end of both.", "dosing_frequency": "1-3x per week, usually cycled (e.g. 4-8 week blocks with breaks).", "cycle_length": "Commonly run in 4-8 week blocks with breaks in community practice. There is no evidence-based cycle length for the blend, and continuous long-term injectable use is unstudied.", "common_vial_sizes": [], "research_stage": "Individual components clinically studied (mostly oral); the injectable blend itself has no clinical trials.", "approval_status": "Not FDA-approved as a drug. Components are available as supplements and compounded injectables; this blend is sold for research use only (RUO).", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "Blend", "potential_benefits": [ "Component rationale: supports mitochondrial ATP production via NAD+'s central role in redox metabolism", "Component rationale: L-carnitine transports long-chain fatty acids into mitochondria for beta-oxidation (fat burning)", "Oral L-carnitine has randomized-trial support for reduced muscle soreness, lower creatine kinase, and better perceived exercise recovery", "Oral NAD+ precursors (e.g. nicotinamide riboside) reliably raise blood NAD+ in trials and are being studied for healthy-aging and vascular endpoints", "Community/anecdotal reports: subjective energy, focus, and workout recovery - not verified in any controlled trial of the blend itself" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/nad-carnitine-blend" }, { "id": "0b115b9e-d400-4e2a-a21e-57dcbf1b1763", "slug": "neboglamine", "name": "Neboglamine (CR 2249)", "aliases": [ "CR 2249", "CR2249", "(S)-CR 2249", "Nebostinel", "XY-2401", "Neboglamine hydrochloride" ], "category": "Nootropics", "description": "Neboglamine, originally coded CR 2249 and given the international non-proprietary name nebostinel, is a glutamic acid derivative developed by Rotta Research Laboratorium in Monza, Italy, and later carried by Rottapharm. It was selected from a series of glutamate analogs as a positive modulator of the NMDA receptor complex, and its intended indications were memory disorders and later schizophrenia and cocaine dependence rather than general cognitive enhancement. It has never been approved anywhere and is not in active development. The material sold to consumers is the hydrochloride salt of a compound that has no published human data.\n\nThe pharmacology is stereospecific, which is a useful marker of a real target. The S enantiomer, (S)-CR 2249, facilitated the ability of glycine to reverse kynurenate antagonism at strychnine-insensitive glycine receptors coupled to the NMDA receptor in rat hippocampal slices. It did not shift the potency of glycine but increased the efficacy of the glycine effect in a concentration-dependent way, and it increased [3H]MK-801 binding with positive cooperative interaction with glycine, which suggests it acts at a separate allosteric site rather than at the glycine site itself (PMID: 9294970). In a comparison of putative cognition enhancers, CR 2249 was potent in the kynurenate test while its enantiomer CR 2361 was inactive (PMID: 9336311), and the same enantiomeric selectivity appeared in slices of human neocortex removed during neurosurgery (PMID: 10381808). ChEMBL classifies the mechanism as positive allosteric modulation of the NMDA receptor (ChEMBL1255840).\n\nBehavioral work in rodents supports both a memory and an antipsychotic-like profile. CR 2249 improved memory retention after scopolamine in a step-through passive avoidance task in rats and after electroconvulsive shock in a step-down task in mice, and it improved performance in animals with no induced cognitive deficit. The effect appeared only when the compound was given before training, not after training or before the retention trial, and microdialysis showed increased noradrenaline release in the hippocampus of freely moving rats (PMID: 9004193). In a later company study, neboglamine increased Fos-like immunoreactivity in rat prefrontal cortex, nucleus accumbens and lateral septal nucleus in a pattern resembling D-serine, without the striatal activation seen with haloperidol, and it inhibited phencyclidine-induced hyperlocomotion and rearing without changing basal locomotor activity (PMID: 20045056).\n\nThe human record is the problem. Commercial pipeline databases list phase 2 work in schizophrenia and cocaine dependence starting in 2010, and ChEMBL records a maximum phase of 2, but no trial result has been published in the peer-reviewed literature and searches of ClinicalTrials.gov and the EU Clinical Trials Register return no records under neboglamine, nebostinel or CR 2249. That means there is no published human pharmacokinetic profile, no published safety dataset and no efficacy result of any kind.\n\nNeboglamine is not approved in any country, is not a controlled substance in the United States and has no established human dose or safety threshold. It is a research-use-only compound whose entire published evidence base is rodent and ex vivo tissue work from the 1990s and 2010.", "half_life": "Not established. No human or animal pharmacokinetic study for neboglamine has been published, and no phase 1 data are available.", "molecular_weight": "256.34 g/mol", "molecular_mass": "256.34 g/mol (free acid)", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Phase 2", "approval_status": "Neboglamine has never been approved by any regulator and no marketing authorization exists in any jurisdiction. ChEMBL records a maximum clinical phase of 2 (ChEMBL1255840), and commercial pipeline databases list phase 2 work in schizophrenia and cocaine dependence dating from 2010, but no results have been published and no records were found on ClinicalTrials.gov or the EU Clinical Trials Register under neboglamine, nebostinel or CR 2249. It is not a controlled substance in the United States, and material on the market there is a research-use-only compound.", "trial_phase": "", "cas_number": "163000-63-3", "iupac_name": "", "chemical_formula": "C13H24N2O3", "potential_benefits": [ "Improved memory retention after scopolamine in a step-through passive avoidance task in rats and after electroconvulsive shock in a step-down task in mice (PMID: 9004193)", "Increased noradrenaline release in the hippocampus of freely moving rats during microdialysis (PMID: 9004193)", "Increased the efficacy of glycine at strychnine-insensitive glycine sites coupled to the NMDA receptor in rat hippocampal slices, enantioselectively (PMID: 9294970)", "Prevented kynurenate antagonism of NMDA-evoked noradrenaline release in slices of human neocortex taken during neurosurgery, while its enantiomer was inactive (PMID: 10381808)", "Inhibited phencyclidine-induced hyperlocomotion and rearing in rats without changing basal locomotor activity or activating the dorsolateral striatum (PMID: 20045056)" ], "research_fields": [ "NMDA glycine site", "Schizophrenia", "Cognitive enhancement", "Nootropics" ], "pubmed_count": 0, "pubchem_cid": 3074827, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/neboglamine" }, { "id": "e1a7c3d2-9f4b-4c2a-bf10-1a2b3c4d5e01", "slug": "nefiracetam", "name": "Nefiracetam", "aliases": [ "DM-9384", "DM9384", "Translon" ], "category": "Nootropics", "description": "Nefiracetam (DM-9384) is a fat-soluble pyrrolidone (racetam-class) nootropic research compound developed in Japan and studied for cognitive impairment in cerebrovascular and Alzheimer-type dementia. Unlike water-soluble racetams such as piracetam, its lipophilicity is thought to support good CNS penetration. It is a prescription product in Japan and is sold in the US as a research compound.", "half_life": "Approx. 3-8 hours (reported)", "molecular_weight": "246.30", "molecular_mass": "246.30 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Clinical (marketed in Japan; research-use in US)", "approval_status": "Prescription in Japan; sold as a research compound in the US", "trial_phase": "", "cas_number": "77191-36-7", "iupac_name": "", "chemical_formula": "C14H18N2O2", "potential_benefits": [ "Memory and learning support (preclinical)", "Cholinergic, GABAergic and calcium-channel modulation", "Studied for cerebrovascular and Alzheimer-type cognitive decline", "Neuroprotective signaling in animal models" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/nefiracetam" }, { "id": "a18c5b0d-7a18-4eda-a1f7-761be05b98c3", "slug": "niacin", "name": "Niacin", "aliases": [ "B3", "Vitamin B3", "Nicotinic acid", "Nicotinamide", "Niacinamide", "Nicotinamide riboside", "NR", "Niagen", "Tru Niagen", "Inositol hexanicotinate", "No-flush niacin", "IHN", "Niaspan", "Niacin-ER", "Slo-Niacin", "Tredaptive", "Laropiprant", "3-pyridinecarboxylic acid", "PP factor", "Pellagra-preventing factor", "Vitamin PP", "Nicotinuric acid", "NAD precursor" ], "category": "Vitamin", "description": "Niacin (vitamin B3) is an umbrella name for a family of closely related vitamers that share the same ultimate metabolic fate — conversion to the pyridine nucleotide coenzymes NAD+ (nicotinamide adenine dinucleotide) and NADP+ (nicotinamide adenine dinucleotide phosphate) that serve as the central electron carriers of intermediary metabolism and as substrates for an expanding family of NAD-consuming enzymes (sirtuins, PARPs, CD38, SARM1). The principal forms are **nicotinic acid** (the 3-pyridinecarboxylic acid, the form historically isolated as the anti-pellagra factor and now used primarily as a pharmacologic lipid-modifying agent), **nicotinamide** (also called niacinamide — the amide form, lacking nicotinic acid''s lipid-lowering and flushing effects, preferred for skin cancer prevention and cosmetic/dermatological use), **nicotinamide riboside (NR)** (the ribosylated nicotinamide form marketed as Tru Niagen/Niagen and studied as an NAD+ precursor for aging and metabolic health), and **nicotinamide mononucleotide (NMN)** (discussed in its own [NMN](/compound/nmn) entry as a closely-related NAD+ precursor). The three-digit Roman numeral naming — B3 — derives from the historical order of B-vitamin discovery rather than any structural logic. The adult RDA is expressed in Niacin Equivalents (NE) because the body synthesizes niacin endogenously from tryptophan at approximately 60 mg tryptophan yielding 1 mg niacin: 16 mg NE/day for men, 14 mg NE/day for women, 18 mg NE/day in pregnancy, 17 mg NE/day in lactation. The tolerable upper intake level is 35 mg/day for nicotinic acid (set primarily because of flushing at higher intakes), but no UL is established for nicotinamide because it does not produce the flushing effect and has a much wider therapeutic window; pharmacologic nicotinamide doses of 1-3 grams daily are used clinically without substantial toxicity. The deficiency disease, **pellagra**, is among the most historically important nutritional syndromes of the past two centuries: the disease of the \"four Ds\" — dermatitis (photosensitive eruption, classically in sun-exposed areas, the \"Casal''s necklace\" across the neck and upper chest), diarrhea, dementia, and death if untreated — devastated the American South, southern Europe, and parts of Africa during eras of corn-dependent diet without traditional nixtamalization (the alkaline lime treatment of corn practiced by Mesoamerican cultures that liberates bound niacin and dramatically improves bioavailability). Joseph Goldberger''s 1910s-1920s demonstration that pellagra was a dietary disease rather than an infection is a landmark in American public health history ( for historical context). Grain fortification with niacin starting in the 1940s all but eliminated pellagra from the developed world, and frank deficiency today is seen predominantly in chronic alcohol use, isoniazid therapy without B6 repletion (INH inhibits pyridoxal-dependent kynurenine pathway conversion to niacin), carcinoid syndrome (tryptophan diverted into serotonin synthesis), Hartnup disease (SLC6A19 mutations impairing neutral amino acid transport including tryptophan), and severe malabsorption or feeding disorders. The supplement and clinical uses of niacin cluster in several domains. **Pharmacologic nicotinic acid for dyslipidemia** was a mainstay of lipid-lowering therapy from the 1950s through the 2000s, backed by the original Coronary Drug Project (CDP) showing reduced coronary events in men treated with niacin 3 g/day, and by long-term follow-up from Canner 1986 showing mortality reduction 15 years out— but subsequent combination trials in the statin era (AIM-HIGH 2011 and HPS2-THRIVE 2014) did not show benefit of adding niacin to statin therapy, and modern guidelines have de-emphasized niacin for routine lipid management despite its continued availability (PMID 22085343, 25014686). **Nicotinamide for non-melanoma skin cancer chemoprevention** is a more recent and strong evidence base — the ONTRAC trial (Chen 2015, PMID 26488693) showed that nicotinamide 500 mg twice daily reduced new basal cell and squamous cell carcinomas by 23% in high-risk patients over 12 months, establishing nicotinamide as a low-cost adjunct in dermatological practice. **Nicotinamide for acne, rosacea, bullous pemphigoid** has a smaller but positive evidence base at pharmacologic doses (500-1500 mg/day). **Topical niacinamide in skincare** is among the most widely-used active ingredients in modern cosmetic formulations at 2-10% concentrations, with evidence for reduced hyperpigmentation, improved barrier function, reduced erythema, and modest anti-aging effects. **Nicotinamide riboside (NR) as an NAD+ precursor** has emerged since Brenner''s 2004 discovery of the NR → NMN → NAD+ salvage pathway (PMID 15137942), with commercial formulations (Niagen, Tru Niagen; ChromaDex) and human trials showing reliable elevation of blood NAD+ and promising but not yet definitive metabolic, cardiovascular, and anti-aging effects (PMID 29599478, 29985198). **NMN** is discussed in its own [NMN](/compound/nmn) entry. **High-dose nicotinamide for Alzheimer, Parkinson, and ALS** is an active research area given the NAD+ depletion observed in aging brain and the role of SARM1 (an NAD-consuming enzyme) in axonal degeneration — evidence remains preliminary. **Niacin for schizophrenia** (the megavitamin approach of Hoffer and Osmond in the 1950s) was never confirmed in controlled trials and is historical rather than current practice. **No-flush niacin** (inositol hexanicotinate) is marketed as a flushing-free alternative but produces lower circulating nicotinic acid and has limited lipid-lowering effect. **Slow-release/extended-release nicotinic acid** (Niaspan) was developed to reduce flushing and was widely used before the AIM-HIGH/HPS2-THRIVE failures; it remains available. **Laropiprant** (DP1/PGD2 receptor antagonist) combined with nicotinic acid (Tredaptive) was withdrawn worldwide after HPS2-THRIVE showed excess adverse effects (PMID 25014686). See also the [NMN](/compound/nmn) and [NAD+](/compound/nad) entries for the precursor biology and aging-research context, [Tryptophan] for the amino acid precursor pathway, [Vitamin B6](/compound/vitamin-b6) for the kynurenine pathway cofactor partnership, [Folate](/compound/folate) and [Vitamin B12](/compound/vitamin-b12) for the broader B-complex, [Thiamine](/compound/thiamine) for the companion energy-metabolism cofactor story, [Alpha-Lipoic Acid](/compound/alpha-lipoic-acid) for the mitochondrial redox stack, [CoQ10](/compound/coq10) for the electron transport chain partnership, [Resveratrol] for the sirtuin-activator discussion, and [Metformin](/compound/metformin) for the AMPK-NAD-sirtuin aging axis. This overview is educational only and is not medical advice — pharmacologic nicotinic acid has specific cardiovascular, hepatic, and glycemic effects that warrant clinician oversight; nicotinamide at typical supplement doses is much more forgiving.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/niacin" }, { "id": "281ce90b-7a33-4305-9129-f608dc020890", "slug": "nmn", "name": "NMN", "aliases": [ "Nicotinamide Mononucleotide", "beta-NMN", "β-NMN", "β-Nicotinamide mononucleotide", "NMN-C", "Uthever" ], "category": "Longevity", "description": "Nicotinamide mononucleotide (NMN) is a naturally occurring nucleotide derived from ribose and nicotinamide, serving as the direct biosynthetic precursor to nicotinamide adenine dinucleotide (NAD+) via a single enzymatic step catalyzed by nicotinamide mononucleotide adenylyltransferase (NMNAT). NMN is found in small quantities in foods including broccoli, cabbage, cucumber, edamame, avocado, tomato, and raw beef, typically in microgram-to-low-milligram quantities per serving — far below the 250-1000 mg doses used in supplementation research. The structure — a ribonucleotide composed of ribose-5-phosphate linked to nicotinamide via a beta-N-glycosidic bond — makes NMN one step closer to NAD+ in the biosynthetic pathway than nicotinamide or nicotinamide riboside (NR), which are two and one-plus-ATP step further removed respectively. NMN's rise from obscure biochemistry reagent to one of the most commercially prominent longevity supplements began with preclinical work in the Sinclair and Imai laboratories documenting NAD+-lowering effects of aging and NAD+-repletion benefits of NMN administration in mice. Mills et al. 2016 (PMID 28068222) demonstrated that 12 months of oral NMN (100-300 mg/kg) in aged mice prevented age-associated physiologic decline including weight gain, insulin sensitivity deterioration, eye function decline, muscle function decline, and bone density loss. Similar findings came from multiple rodent studies over 2013-2020 establishing NMN as a consistent NAD+-raising intervention with broad preclinical benefit across age-related pathologies. The first human pharmacokinetic study of NMN was conducted by Irie and colleagues in 2020, administering single oral doses of 100, 250, and 500 mg NMN to ten healthy Japanese men aged 40-60 and documenting dose-proportional increases in plasma NMN and its downstream metabolites with no serious adverse events — establishing oral NMN's basic safety and pharmacokinetics in humans. Yoshino and colleagues 2021 (PMID 33888596) conducted the first human efficacy RCT, randomizing 25 prediabetic postmenopausal women with overweight/obesity to 10 weeks of oral NMN 250 mg/day versus placebo. The trial documented significant improvement in skeletal muscle insulin sensitivity (measured by hyperinsulinemic-euglycemic clamp) with NMN versus placebo, and increased skeletal muscle expression of genes related to muscle remodeling. The Yoshino 2021 trial remains the landmark early human NMN efficacy study despite its small sample size. Subsequent human trials have examined NMN across a range of populations and outcomes with varying results: Yamamoto 2022 examined NMN in older adults with mixed metabolic outcomes; Pencina 2023provided a 6-week dose-ranging safety study; Connell et al. 2023conducted a meta-analysis of available NMN human trials through early 2023. The emerging human evidence base supports NMN's safety across tested dose ranges (up to 1,000 mg/day for short-term use in small trials) and provides suggestive but not yet definitive evidence for metabolic, cardiovascular, and musculoskeletal benefits. The evidence base remains substantially behind the marketing claims, with many commercial NMN products citing preclinical mouse data or extrapolating from NAD+ biology rather than demonstrating human RCT outcomes. Regulatory status: NMN was marketed in the US as a dietary supplement under DSHEA from approximately 2014 onward. In late 2022, the FDA issued a preliminary determination that NMN is not a lawful dietary supplement because it had been studied as a drug prior to being marketed as a supplement, potentially excluding it from DSHEA protection. This triggered significant industry concern and some reformulation. The regulatory situation has continued to evolve through 2025-2026 with industry litigation and FDA enforcement activity varying by product and distributor. As of early 2026, NMN remains widely available from many supplement retailers despite the regulatory uncertainty. NAD+ biochemistry context: NAD+ is a central coenzyme in cellular metabolism, participating in hundreds of enzymatic reactions spanning energy metabolism (as electron carrier in oxidative phosphorylation), DNA repair (as substrate for poly-ADP-ribose polymerase or PARP enzymes), and signaling (as substrate for sirtuins and CD38). Cellular NAD+ levels decline with aging across multiple tissues and organisms, with the decline implicated in age-associated mitochondrial dysfunction, impaired DNA repair, reduced sirtuin activity, and compromised cellular resilience. The NAD+ \"boosting\" hypothesis — that restoring youthful NAD+ levels through precursor supplementation could slow or reverse age-related decline — has driven extensive investment in NMN and the related NAD+ precursor nicotinamide riboside (NR, marketed as Niagen). NMN and NR are often discussed as competing or complementary precursors; both have human safety data and both raise NAD+ in humans, though the optimal dose, route, and clinical context remain areas of active research and commercial dispute. This entry covers NMN's biosynthesis and relationship to the NAD+ salvage pathway; the human and preclinical evidence base for metabolic, cardiovascular, and cognitive applications; dose-response considerations and the rational approach to supplementation; the oral versus sublingual versus injectable administration route debate; the evolving regulatory landscape; appropriate integration into complete longevity protocols alongside [metformin](/compound/metformin), [rapamycin](/compound/rapamycin) (when available), [NAD+](/compound/nad), and lifestyle interventions; and honest framing that despite strong mechanistic rationale and good safety data, definitive evidence for meaningful longevity or healthspan extension in humans remains to be established.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/nmn" }, { "id": "84d78130-9666-4dd4-92be-d363b4624e2f", "slug": "noopept", "name": "Noopept", "aliases": [], "category": "Nootropics", "description": "Noopept is the common brand and research name for **N-phenylacetyl-L-prolylglycine ethyl ester** (GVS-111; INN *omberacetam*), a small dipeptide nootropic developed in the 1990s at the Russian Academy of Medical Sciences' Institute of Pharmacology under Tatiana Voronina and Rita Ostrovskaya. Structurally, Noopept is a cyclized prolylglycine derivative conjugated to a phenylacetyl group, giving it roughly a thousand-fold higher potency than piracetam on a per-milligram basis while retaining some mechanistic overlap with the racetam family. It is sold over-the-counter in Russia as a cognitive enhancer and anxiolytic (trade name *Noopept*, manufactured by JSC Lekko Pharmaceuticals under license from the Zakusov Institute), where it carries approvals for post-concussive syndrome, cerebrovascular insufficiency, and mild to moderate cognitive decline. Outside Russia and a handful of CIS states, Noopept has no regulatory status — it is not approved as a drug in the United States, the United Kingdom, the European Union, Canada, or Australia, and it is not listed on any pharmacopoeia as a recognised medicine. It has been scheduled as a controlled or prohibited substance in a small number of jurisdictions (notably the Czech Republic) but in most Western countries it exists in a legal grey zone: neither an approved drug nor a regulated supplement, often sold online as a \"research chemical\" or nootropic powder.\n\nThe compound's appeal rests on three overlapping claims — that it enhances memory consolidation, that it produces a mild anxiolytic effect, and that it is neuroprotective against oxidative, excitotoxic, and ischaemic insults. Each of these claims has some experimental support in rodent models and a small body of Russian clinical literature, but the evidence base is markedly thinner than for any drug approved in the West for cognitive impairment or anxiety. The key studies are mostly Soviet-era and post-Soviet Russian publications indexed on eLibrary.ru and — in a minority of cases — on PubMed, often with methodology that would not meet contemporary ICH-GCP or FDA standards. Randomised, double-blind, placebo-controlled trials with pre-registered endpoints, intention-to-treat analysis, and independent replication — the evidentiary bedrock of Western drug approval — are largely absent. This does not mean Noopept \"doesn't work,\" but it does mean that anyone using it is relying on a body of evidence that would be considered hypothesis-generating rather than definitive by regulators at the FDA, EMA, MHRA, or Health Canada.\n\nFor context, the drugs with the strongest evidence base for true cognitive impairment — Alzheimer's disease and related dementias — are the cholinesterase inhibitors [donepezil](/compound/donepezil), rivastigmine, and galantamine, and the NMDA receptor modulator memantine. These agents have been tested in thousands of patients in rigorously controlled trials and show modest but reproducible effects on cognition and activities of daily living. Newer disease-modifying therapies like lecanemab and donanemab target beta-amyloid pathology directly and have demonstrated reductions in cognitive decline in prodromal and mild Alzheimer's disease. Noopept is not a substitute for any of these drugs, and anyone experiencing genuine cognitive decline should be evaluated by a neurologist or geriatric psychiatrist rather than self-medicating with an unregulated Russian nootropic.\n\nFor subclinical complaints — the \"brain fog\" and mild age-related cognitive slowing that prompt many healthy adults to try nootropics — the evidence for Noopept is weaker still. Most human trials were conducted in patients with documented cerebrovascular disease, post-traumatic cognitive impairment, or neurasthenic syndromes, not in healthy young adults seeking cognitive enhancement. Extrapolating from a 60-year-old Russian stroke patient to a 28-year-old programmer wanting sharper focus is a substantial leap that the data do not support. What Noopept offers healthy users — according to self-report and a handful of small Russian studies — is a subtle, often described as \"subthreshold\" improvement in mental clarity, mood, and stress tolerance, particularly when combined with an alcar/choline source to offset headaches. Whether this exceeds placebo in a properly blinded trial is an open question.\n\nNoopept's legal and regulatory status merits careful attention. It is unscheduled in the United States but is not recognised as a dietary supplement under DSHEA, meaning it is technically illegal to sell as a supplement though enforcement has been inconsistent. It is a prescription-only medication in Russia and several CIS states. In the European Union, it is generally treated as a novel food ingredient or an unregistered drug depending on the member state. It is banned or restricted in the Czech Republic, Hungary, and a few other countries. Anyone sourcing Noopept online should understand that they are purchasing an unregulated powder or capsule from a vendor whose quality control is unverifiable. Identity, purity, and dosing accuracy should be assumed to be uncertain unless third-party certificates of analysis (HPLC, mass spectrometry) are provided. Other nootropics in the same general category — [selank](/compound/selank) and [semax](/compound/semax) — share similar Russian origins and evidentiary limitations. For a more evidence-based approach to cognitive enhancement, see the literature on [modafinil](/compound/modafinil) (prescription wakefulness agent with solid trial data for shift-work disorder and narcolepsy), [methylene-blue](/compound/methylene-blue), [nad](/compound/nad), or lifestyle interventions (sleep, exercise, nutrition) that have substantially more rigorous supporting evidence.", "half_life": "", "molecular_weight": "", "molecular_mass": "318.37 g/mol", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "Russia Approved", "cas_number": "157115-85-0", "iupac_name": "N-phenylacetyl-L-prolylglycine ethyl ester", "chemical_formula": "C17H22N2O4", "potential_benefits": [ "Memory enhancement", "BDNF/NGF upregulation", "Neuroprotection", "Focus and learning speed", "Anxiety reduction (moderate)", "Anti-amyloid properties" ], "research_fields": [ "Cognitive impairment", "Alzheimer's disease", "Stroke recovery", "Anxiety", "ADHD" ], "pubmed_count": 106, "pubchem_cid": 180496, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/180496/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/noopept" }, { "id": "d2027fa8-7242-43da-aa25-b4b82731dce1", "slug": "noopept-choline-blend", "name": "Noopept + Choline Chloride Blend", "aliases": [ "Noopept Choline Spray" ], "category": "Cognitive", "description": "A community nootropic stack pairing Noopept, a potent racetam-family dipeptide, with a choline source (commonly alpha-GPC, CDP-choline/citicoline, or choline bitartrate). Choline is added to supply acetylcholine precursor and to reduce the headaches some users get from racetam-type compounds. The blend itself has no clinical trials - evidence is by component only. Research use only.", "half_life": "Not a single-molecule value - this is a two-component stack. Noopept has a short plasma half-life, with central effects that outlast blood levels; the rise in brain choline from alpha-GPC or CDP-choline persists for several hours.", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "Noopept 10-30 mg (10,000-30,000 mcg)/day; choline source 150-600 mg/day (alpha-GPC) or 250-500 mg/day (CDP-choline). The blend has no validated dosing - ranges are extrapolated from single-component use.", "dosing_frequency": "1-3 times daily for Noopept; the choline source is usually taken 1-2 times daily alongside it.", "cycle_length": "Commonly 4-8 weeks on followed by a 1-2 week break; some users cycle 5 days on / 2 days off. There is no established optimal cycle - Noopept is generally cycled to limit tolerance rather than run continuously.", "common_vial_sizes": [], "research_stage": "Blend has no clinical trials; component evidence ranges from preclinical (Noopept) to small human RCTs (choline sources).", "approval_status": "Not FDA-approved. Noopept is an unscheduled research chemical in the US (a prescription nootropic in Russia and some other countries); choline sources are dietary ingredients. Research use only (RUO).", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Reported (anecdotal) day-to-day gains in focus, verbal fluency, and working memory - from user reports, not from trials of this blend", "Choline is added mainly to reduce the racetam-type headache some users get from Noopept taken without enough choline", "Noopept shows memory-supporting and neuroprotective effects in animal models of cognitive impairment [PMID:25096780][PMID:17092975]", "CDP-choline (citicoline) improved episodic and composite memory vs placebo in a 12-week RCT in healthy older adults with age-associated memory impairment [PMID:33978188]", "Alpha-GPC and CDP-choline act as acetylcholine precursors, raising brain choline availability [PMID:1662399]", "Component evidence is strongest for the choline sources; the blend as a whole has no clinical trials" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/noopept-choline-blend" }, { "id": "d7f15496-63a7-40a0-b5f1-0e7f1f6d33e9", "slug": "nsi-189", "name": "NSI-189", "aliases": [], "category": "Nootropics", "description": "NSI-189 is a novel synthetic compound developed by Neuralstem Inc. that stimulates neurogenesis in the human hippocampus. Phase 2 trials for major depressive disorder showed improvements in subjective cognitive function, depression scores, and positive affect despite not reaching primary endpoints. It has a dedicated following in the biohacking community for its reported hippocampal neurogenesis, emotional blunting reversal, and unique cognitive profile unlike any other nootropic.", "half_life": "", "molecular_weight": "", "molecular_mass": "313.36 g/mol", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "Phase 2", "cas_number": "1270138-40-3", "iupac_name": "benzyl N-[2-(piperazin-1-yl)pyrimidin-5-yl]carbamate", "chemical_formula": "C16H19N5O2", "potential_benefits": [ "Increased hippocampal neurogenesis", "Antidepressant effects", "Enhanced synaptic plasticity", "Improved cognitive function", "Long-lasting mood improvement", "Potential PTSD treatment" ], "research_fields": [ "Major depressive disorder", "Cognitive impairment", "PTSD", "Alzheimer's disease", "Neurogenesis" ], "pubmed_count": 3, "pubchem_cid": 44, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/44/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/nsi-189" }, { "id": "4700c9cf-ab59-4ae9-b238-4b9ea5e536b1", "slug": "oleamide", "name": "Oleamide", "aliases": [ "Oleamide", "9-Octadecenamide", "Cis-9-Octadecenamide", "ODA" ], "category": "Nootropic Lipid", "description": "Oleamide is a **fatty acid primary amide** that your brain naturally produces during sleep deprivation — your body's endogenous sleep-promoting lipid signal. First identified in 1995 by Cravatt and colleagues at Scripps Research Institute as the major sleep-inducing factor accumulating in cerebrospinal fluid during prolonged wakefulness.\n\nUnlike pharmaceutical sleep aids that override sleep architecture, oleamide works WITH the body's natural sleep mechanisms by potentiating GABA-A receptor activity and modulating serotonin receptors. Subjective effects are typically described as \"natural drowsiness\" rather than the sedated/drugged feeling from benzodiazepines or antihistamines.\n\nAs a supplement, oleamide is sold as research-only and **not FDA-approved**. The peer-reviewed literature on supplementation outcomes is modest, but the underlying biochemistry is well-characterized.", "half_life": "~30-60 minutes (rapidly metabolized by FAAH)", "molecular_weight": "281.48 g/mol", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "C18H35NO", "potential_benefits": [], "research_fields": [], "pubmed_count": 62, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/oleamide" }, { "id": "63098fba-e919-479c-898c-1c97f2a8518e", "slug": "oleocanthal", "name": "Oleocanthal", "aliases": [ "(-)-Oleocanthal", "Decarboxymethyl oleuropein aglycone", "deacetoxy-ligstroside aglycone", "p-HPEA-EDA" ], "category": "Polyphenol", "description": "Oleocanthal — more precisely (-)-oleocanthal, or p-HPEA-EDA (para-hydroxyphenylethanol elenolic acid dialdehyde) — is the pungent phenolic secoiridoid that gives fresh, high-polyphenol extra-virgin olive oil its characteristic throat-biting, pepper-like sensation when swallowed. That single distinctive sensory cue, the urge to cough after a spoonful of premium EVOO, is a chemical reporter: it is the direct physiologic response to oleocanthal's selective activation of the TRPA1 receptor on pharyngeal sensory neurons, and it reliably signals a high-polyphenol oil. Chemically, oleocanthal is the monoaldehydic form of decarboxymethyl oleuropein aglycone — structurally a hydroxytyrosol ester of a rearranged elenolic acid fragment carrying two aldehyde groups. Unlike oleuropein, the bitter glycosylated secoiridoid found in olive leaves and young fruit, or hydroxytyrosol, the small catechol metabolite into which oleuropein hydrolyzes, oleocanthal carries a distinct and notable pharmacology: direct, non-selective cyclooxygenase (COX-1 and COX-2) inhibition with potency comparable to ibuprofen on a molar basis.\n\nThis \"ibuprofen-like\" property was discovered serendipitously in 2005 by Gary Beauchamp and colleagues at the Monell Chemical Senses Center (Beauchamp et al., Nature 2005, PMID 16136122). Beauchamp, a sensory biologist who had sampled newly pressed Sicilian EVOO during a research trip, noticed that the throat-sting was identical to the sting he felt from the liquid ibuprofen used in sensory studies at Monell. That observation led to chemical identification of oleocanthal as the responsible compound and to a now-famous Nature paper demonstrating that oleocanthal dose-dependently inhibits COX-1 and COX-2 enzymes in cell-free assays at concentrations comparable to ibuprofen. A typical 50 mL daily serving of premium high-polyphenol EVOO delivers roughly 9–10 mg of oleocanthal — a dose that, given ibuprofen-equivalent potency, is roughly one-tenth of a single low-dose adult ibuprofen tablet (200 mg). This is not enough for acute analgesia, but it is plausibly enough for chronic anti-inflammatory effect when consumed daily — consistent with the Mediterranean diet's epidemiologic association with reduced rates of cardiovascular disease, cancer, and neurodegenerative disorders.\n\nBodyHackGuide covers oleocanthal as the third member of the olive polyphenol triumvirate alongside [oleuropein](/compound/oleuropein) (the bitter glycoside precursor) and [hydroxytyrosol](/compound/hydroxytyrosol) (the absorbed active metabolite). While hydroxytyrosol and oleuropein carry most of the antioxidant, endothelial, and cardiovascular signals attributed to olive polyphenols, oleocanthal carries a distinct anti-inflammatory mechanism (direct COX inhibition) and emerging signals in neurodegenerative disease and cancer that have attracted substantial preclinical research attention over the past two decades. Three major research threads have developed: (1) oleocanthal as a chronic-dose NSAID-like ingredient in the Mediterranean diet, potentially contributing to the diet's anti-atherogenic and anti-carcinogenic epidemiology; (2) oleocanthal as a promoter of amyloid-beta and tau protein clearance in Alzheimer's disease models (Abuznait 2013, Qosa 2015, and subsequent work from the Kaddoumi lab), with plausible relevance to the consistent inverse association between Mediterranean diet adherence and Alzheimer's risk in observational studies; and (3) oleocanthal as a lysosomal membrane permeabilization agent selectively cytotoxic to cancer cells (LeGendre 2015), a mechanism that spares non-cancerous cells and has generated interest in oleocanthal as an adjunct chemotherapy concept.\n\nOleocanthal is chemically unstable outside the olive oil matrix. It is a dialdehyde with substantial electrophilic reactivity at both carbonyls, prone to polymerization, oxidation, and hydrolysis under aqueous conditions. In extra-virgin olive oil, it is stabilized by the anhydrous lipid matrix, other antioxidants (α-tocopherol, squalene, other polyphenols), and the darkness and oxygen-exclusion of proper storage. This chemical fragility is why pure oleocanthal supplements are essentially non-existent in the consumer market — unlike oleuropein (stable in olive leaf extract capsules) and hydroxytyrosol (stable in Hytolive and Benolea isolates), oleocanthal cannot be readily concentrated and packaged. The main commercial delivery vehicle for oleocanthal is — and likely will remain — high-polyphenol extra-virgin olive oil consumed fresh, within months of pressing, from properly-stored bottles. A few specialty olive-oil-matrix concentrate products exist (notably from research groups at Yale / the Gary Beauchamp lineage and from Spanish and Italian producers partnering with academic medical centers), but these are expensive, limited in availability, and generally marketed to research or clinical investigation contexts rather than consumer use.\n\nThe clinical evidence base for oleocanthal as a discrete intervention (rather than as a component of a Mediterranean dietary pattern) is early-stage. No large-scale, adequately-powered randomized controlled trials have tested standardized oleocanthal-rich olive oil against oleocanthal-depleted olive oil or no intervention for hard clinical outcomes such as myocardial infarction, stroke, dementia onset, or cancer incidence. The strongest clinical signal comes from the PREDIMED trial (Estruch 2013 PMID 23432189, 2018 reanalysis PMID 29897866), which showed a 30% reduction in major cardiovascular events over a median 4.8-year follow-up in 7,447 high-risk adults randomized to Mediterranean diet with high-polyphenol EVOO. The EVOO used in PREDIMED was selected for high polyphenol content (oleocanthal + oleuropein + hydroxytyrosol + other secoiridoids), and the cardiovascular benefit is generally attributed to the whole polyphenol complex. Separating the oleocanthal contribution from the hydroxytyrosol and oleuropein contributions is methodologically difficult and has not been done in humans. Preclinical work — cellular assays, animal models, pharmacokinetic studies in humans — supports each mechanism individually, but the clinical story remains \"Mediterranean diet / high-polyphenol EVOO works; oleocanthal contributes.\"\n\nThe sensory signature of oleocanthal — the peppery throat bite, sometimes triggering a single cough on swallowing, that connoisseurs call \"strong\" or \"intense\" olive oil — is actually a reliable palate biomarker for polyphenol content. Andrewes and colleagues demonstrated in 2003 (published before oleocanthal had been structurally characterized by Beauchamp) that the TRPA1-mediated pharyngeal irritant was correlated with polyphenol content in olive oils. The sensory test is reproducible: swallow a small spoonful of olive oil, wait 10–30 seconds, and note any throat bite or tendency to cough. Bland, smooth, buttery oils are low-polyphenol. Oils that produce a distinct cough on swallowing are high-polyphenol and rich in oleocanthal. This is why premium EVOO producers cultivate the sensory intensity and why the Italian oil-connoisseur term \"pizzica\" (Italian for \"pinches,\" referring to the throat bite) is a desired, not avoided, quality.\n\nFor BodyHackGuide users, oleocanthal should be understood as a chronic-exposure, food-matrix molecule — not a supplement, not an acute analgesic, not a disease-targeted pharmaceutical. Its value comes from daily consumption of high-polyphenol EVOO as a culinary fat, typically 2–3 tablespoons (25–40 mL) per day, within a broader Mediterranean dietary pattern (vegetables, fish, legumes, whole grains, moderate red wine or none, minimal ultra-processed food). The mechanistic breadth (COX inhibition, amyloid and tau clearance, lysosomal membrane permeabilization in cancer cells, anti-inflammatory cytokine modulation, endothelial support via interactions with the broader olive polyphenol matrix) and the epidemiologic strength of Mediterranean diet adherence combine to make oleocanthal-rich EVOO one of the most defensible daily food-as-medicine recommendations in the contemporary nutrition evidence base.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 1156, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/oleocanthal" }, { "id": "a588f76f-eb31-4619-991e-276c51ba8298", "slug": "oleuropein", "name": "Oleuropein", "aliases": [], "category": "Polyphenol", "description": "Oleuropein is the signature secoiridoid glycoside of Olea europaea — the olive tree — and it is the single most important polyphenol responsible for the cardiovascular, anti-inflammatory, and metabolic benefits long associated with extra-virgin olive oil and with the broader Mediterranean diet. Structurally, oleuropein is an ester of elenolic acid and hydroxytyrosol, linked to a glucose moiety; this makes it a relatively large, polar, bitter molecule that accumulates to concentrations of 6–9% of dry weight in young olive leaves, 1–4% in unripe green olives, and much lower levels (typically 50–500 mg/L) in high-quality extra-virgin olive oil after mechanical extraction. The distinctive bitter-pungent bite of freshly pressed EVOO — the property that causes a cough at the back of the throat in high-quality oils — comes from oleuropein and its related secoiridoids, particularly oleocanthal (a non-glycosylated secoiridoid with ibuprofen-like COX-inhibitory activity). When you swallow EVOO or an olive-leaf extract capsule, stomach acid and intestinal esterases rapidly hydrolyze oleuropein into hydroxytyrosol (the absorbed active metabolite) and elenolic acid glucoside (which has its own weaker bioactivity). Hydroxytyrosol (3,4-dihydroxyphenyl-ethanol, HT) is the smallest of all natural phenolic compounds, crosses membranes freely, and is the molecule that mediates most of oleuropein's systemic pharmacology in humans.\n\nBodyHackGuide covers oleuropein as the entry point into the olive polyphenol family — including oleocanthal, oleacein, and hydroxytyrosol itself — because oleuropein is what you actually consume from olive leaf supplements and the precursor to what EVOO delivers at dinner. The molecule has the distinction of being the only food polyphenol with an EFSA-approved health claim: since 2012, the European Food Safety Authority has authorized the claim that \"olive oil polyphenols contribute to the protection of blood lipids from oxidative stress\" for olive oils providing at least 5 mg of hydroxytyrosol and its derivatives (oleuropein complex) per 20 g serving. This is unprecedented — no other polyphenol has received a positive EFSA Article 13.5 health claim — and it reflects the depth and quality of the mechanistic and clinical evidence underlying the oleuropein–hydroxytyrosol axis. The EUROLIVE trial (Covas 2006), the PREDIMED cardiovascular-prevention study (Estruch 2013 and 2018 reanalysis and 29897866), Susalit 2011's olive leaf extract vs captopril hypertension trial, and a growing body of clinical evidence together make oleuropein one of the most clinically validated polyphenols for cardiovascular and metabolic outcomes.\n\nThe mechanistic story runs through three major nodes. First, direct antioxidant activity — hydroxytyrosol is a catechol, meaning it has two adjacent phenolic hydroxyl groups on a benzene ring, the same motif that makes catecholamines so biologically reactive. The catechol reduces transition metals, quenches peroxyl and hydroxyl radicals, and directly protects LDL particles from oxidative modification. The Covas 2006 EUROLIVE trial demonstrated dose-dependent reductions in circulating oxidized LDL markers in healthy men consuming 25 mL/day of olive oils ranging from low-polyphenol (refined) to high-polyphenol EVOO over three 3-week intervention periods, establishing that olive polyphenol content — not fatty-acid composition — drives the antioxidant effect. Second, Nrf2 activation and upregulation of endogenous antioxidant enzymes including heme oxygenase-1, glutathione-S-transferase, and the superoxide dismutases, providing a sustained antioxidant capacity beyond the direct radical-scavenging window. Third, endothelial NO signaling — hydroxytyrosol upregulates endothelial nitric oxide synthase (eNOS), improves flow-mediated dilation (Storniolo 2014 and a growing crossover literature), and produces modest but consistent reductions in systolic blood pressure.\n\nLayer on top anti-inflammatory activity (NF-κB inhibition, reduced TNF-α / IL-6 / CRP in clinical trials), modest lipid-profile improvements (slight LDL reduction, HDL preservation or increase, triglyceride reduction), anti-platelet activity contributing to MedDiet cardiovascular risk reduction, and emerging data on autophagy induction, AMPK activation, and insulin sensitization in preclinical models. Oleocanthal — the related olive secoiridoid — deserves special mention because Beauchamp 2005 (PMID 16136122) famously demonstrated that oleocanthal produces the ibuprofen-like throat-cough sensation characteristic of fresh EVOO AND functions as a potent non-specific COX-1/COX-2 inhibitor at relevant in-vivo concentrations, providing a partial mechanistic explanation for the cardiovascular protective effect of high-polyphenol EVOO beyond the antioxidant story. More controversially, Parkinson and Breslin 2014 and subsequent mechanistic work have suggested oleocanthal selectively kills cancer cells via lysosomal membrane permeabilization — a provocative preclinical story that has not yet been translated to human trials but that explains why several oleocanthal-rich EVOO products are being developed as nutraceutical interventions.\n\nThe Mediterranean-diet context is essential to understanding oleuropein. PREDIMED (Estruch et al.) randomized ~7,500 high-cardiovascular-risk Spanish adults to one of three dietary arms — control low-fat, Mediterranean diet supplemented with EVOO, or Mediterranean diet supplemented with mixed nuts — and followed them for a median 4.8 years. The EVOO arm received one liter per week of high-polyphenol Catalan EVOO (Koroneiki/Arbequina cultivar, polyphenol content ~300 mg/kg), translating to roughly 50 mL/day providing ~15 mg/day hydroxytyrosol-equivalents. This arm achieved a 30% reduction in primary composite cardiovascular events compared to the low-fat control, an effect size that matches high-intensity statin therapy and that has held up across the controversial 2018 reanalysis addressing randomization irregularities. The EVOO result has become the single most cited piece of evidence for the Mediterranean diet's cardiovascular benefit, and it is fundamentally an oleuropein/hydroxytyrosol effect at the level of the active phytochemicals.\n\nThe supplemental olive leaf extract literature — which is how most BodyHackGuide users will encounter oleuropein — includes the Susalit 2011 Indonesian hypertension trial (500 mg olive leaf extract twice daily vs 12.5–25 mg captopril twice daily in 232 patients with stage-1 hypertension over 8 weeks, with similar systolic/diastolic BP reductions between arms), Rondanelli 2019 on inflammatory markers and glycemia, and a growing body of smaller trials on lipids, insulin sensitivity, joint health, and immune support. Commercial olive leaf extracts vary enormously in polyphenol content — the better products specify oleuropein content as a standardized percentage (typically 15–20% oleuropein by weight) or as absolute mg per capsule, while cheaper products use non-standardized leaf powder with unpredictable potency. Newer hydroxytyrosol-specific supplements (Hytolive, Benolea, olive-leaf-derived HT isolates) deliver the absorbed metabolite directly and avoid variability in stomach acid hydrolysis, at the cost of higher price and loss of the oleocanthal/oleacein matrix that may contribute independently to the olive polyphenol signal.\n\nFor most BodyHackGuide users, the cleanest approach to oleuropein is food-first: high-polyphenol extra-virgin olive oil (2–3 tablespoons / 25–40 mL daily, drizzled raw on food after cooking rather than used as frying oil), choosing single-cultivar EVOOs from high-polyphenol cultivars (Koroneiki, Picual, Coratina, Moraiolo) with early harvest dates and freshness within 12–18 months of pressing, stored in dark glass in a cool pantry. This food-based approach delivers 15–25 mg/day hydroxytyrosol-equivalents in a lipid matrix that is itself cardioprotective (monounsaturated fat, phytosterols, squalene), at a cost of roughly $0.50–$2.00 per day depending on oil selection. Supplementation with standardized olive leaf extract (500–1000 mg of extract standardized to 15–20% oleuropein, providing ~75–200 mg/day oleuropein) or with isolated hydroxytyrosol (10–50 mg/day) is reserved for users with specific indications — hypertension, chronic inflammation, post-infectious fatigue, or situations where dietary EVOO intake is limited (travel, restaurant-heavy diet, or allergies/intolerance that preclude daily EVOO intake).", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 3658, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/oleuropein" }, { "id": "6e598dba-0f07-44dc-9104-d8b69642d275", "slug": "omega-3-fatty-acids", "name": "Omega-3 Fatty Acids", "aliases": [ "Fish oil", "EPA", "DHA", "Eicosapentaenoic acid", "Docosahexaenoic acid", "n-3 PUFA", "Marine omega-3", "Krill oil", "Algal oil", "Icosapent ethyl", "Vascepa" ], "category": "Foundational", "description": "Omega-3 fatty acids represent one of the most thoroughly researched nutritional interventions of the past half-century, with thousands of clinical trials, dozens of major meta-analyses, regulatory approvals for specific pharmaceutical preparations, and foundational status in cardiovascular medicine, cognitive health, and inflammatory conditions. The compound class encompasses three principal molecular species — eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA) — with distinct metabolic roles and clinical applications. Understanding omega-3 fatty acids requires navigating substantial research complexity while recognizing the compound's genuine foundational value for general health maintenance and its more specific therapeutic applications.\n\nChemical identity and classification: Omega-3 fatty acids are polyunsaturated fatty acids (PUFAs) characterized by the position of their first carbon-carbon double bond — specifically, at the third carbon from the methyl (omega) end of the molecule. The three main omega-3 species in human nutrition are: alpha-linolenic acid (ALA, 18:3n-3), the short-chain plant-derived form found in flaxseed, chia, walnuts, and some leafy greens; eicosapentaenoic acid (EPA, 20:5n-3), a 20-carbon long-chain form found primarily in marine sources; and docosahexaenoic acid (DHA, 22:6n-3), a 22-carbon long-chain form concentrated in fish oils, algae, and neural/retinal tissues. ALA can be converted to EPA and DHA in the liver through sequential desaturation and elongation reactions, but conversion efficiency is poor in humans (5-10% for ALA→EPA; 0.5-1% for ALA→DHA), making direct marine-source intake the practical path to adequate EPA/DHA status.\n\nMarine vs. plant sources: Fatty fish (salmon, mackerel, sardines, anchovies, herring) provide EPA and DHA directly in biologically active form. Typical 3-ounce serving of wild salmon provides 1.0-1.5 g combined EPA+DHA. Plant sources (flax, chia, walnuts, algal oils) provide primarily ALA (except algal oils which supply DHA and sometimes EPA directly). For vegans and vegetarians, algal oil represents the most practical source of direct EPA+DHA; ALA-rich plant sources provide the precursor but with poor conversion to active forms. The plant vs. marine distinction is not merely academic — many important clinical outcomes depend specifically on EPA and DHA rather than ALA, making source selection practically important.\n\nCardiovascular applications: The cardiovascular evidence for omega-3 fatty acids is extensive but nuanced. Population studies consistently associate higher fish consumption or higher circulating omega-3 levels with lower cardiovascular mortality — Mozaffarian 2011demonstrated this association across large cohorts. Early randomized trials including GISSI-Prevenzione 1999 (PMID 10465168) in post-myocardial infarction patients demonstrated mortality benefit with 1 g/day EPA+DHA. However, more recent large trials including VITAL and ASCEND in primary prevention populations found smaller or absent effects, leading to ongoing debate about magnitude and specificity of cardiovascular benefits. The REDUCE-IT trial (Bhatt 2019 PMID 30415628) using high-dose EPA-only icosapent ethyl (Vascepa) in high-risk patients demonstrated significant cardiovascular event reduction, leading to FDA approval. The competing STRENGTH trial (Nicholls 2020) using an EPA+DHA preparation did not replicate the benefit, generating debate about whether specific EPA monotherapy is required or whether trial design differences explain divergent results.\n\nTriglyceride-lowering effect: Omega-3 fatty acids reliably reduce serum triglycerides in a dose-dependent manner. At pharmaceutical doses (2-4 g daily), EPA+DHA typically reduces triglycerides by 20-30% — an effect comparable to fibrates and approaching that of statins for triglyceride reduction. This effect is one of the most reliably demonstrated omega-3 benefits and provides foundation for the pharmaceutical preparations (icosapent ethyl, omega-3-acid ethyl esters). For users with elevated triglycerides, omega-3 supplementation represents an evidence-based intervention often used alongside or in place of fibrate therapy.\n\nCognitive and brain health applications: DHA is the most abundant fatty acid in brain gray matter and retinal photoreceptors, and omega-3 status affects brain structure and function across the lifespan. The Yurko-Mauro 2010 MIDAS trial (PMID 20434961) demonstrated cognitive benefits of DHA supplementation in age-associated memory impairment. The Jackson 2016 reviewsynthesized evidence for cognitive function effects. Observational studies consistently associate higher omega-3 intake with reduced dementia and cognitive decline risk, though randomized trials in dementia prevention have produced more mixed results. Mechanistically, DHA supports neuronal membrane fluidity, synaptic function, and neuroinflammatory modulation — all plausibly relevant to cognitive aging.\n\nInflammatory and immune applications: EPA and DHA serve as substrates for specialized pro-resolving mediators (resolvins, protectins, maresins) that actively resolve inflammation rather than merely suppressing it. This emerging understanding of omega-3 role in inflammation resolution (Charles Serhan's laboratory work) has expanded the compound's therapeutic framing. Clinically, omega-3 supplementation reduces inflammatory markers including CRP, IL-6, and TNF-alpha, and shows benefit in rheumatoid arthritis, inflammatory bowel disease, and various autoimmune conditions. For individuals with inflammatory conditions, omega-3 often serves as a supplementary intervention alongside primary disease-modifying treatments.\n\nMetabolic and body composition applications: Omega-3 fatty acids exhibit modest beneficial effects on insulin sensitivity, lipid metabolism, and possibly body composition, though these effects are smaller than triglyceride-lowering or anti-inflammatory effects. For general metabolic health tuning, omega-3 supplementation contributes as part of broader lifestyle interventions rather than as a primary metabolic therapy.\n\nPregnancy and infant development: DHA plays essential roles in fetal neural and visual development, and maternal omega-3 intake influences infant outcomes. Most major health organizations recommend omega-3 supplementation during pregnancy (typically 200-300 mg DHA daily minimum, often with more EPA+DHA combined). This application has strong regulatory and professional endorsement.\n\nRegulatory status and pharmaceutical preparations: Over-the-counter fish oil represents the vast majority of omega-3 supplementation. Three FDA-approved prescription omega-3 preparations exist in the United States: omega-3-acid ethyl esters (Lovaza, Omtryg), icosapent ethyl (Vascepa — EPA only), and omega-3 carboxylic acids (Epanova — discontinued). These pharmaceutical preparations provide higher purity and concentration than standard supplements and have specific FDA-approved indications (triglyceride reduction, cardiovascular event reduction in specific populations). The distinction between pharmaceutical and supplement omega-3 matters for specific clinical applications but is less relevant for general health maintenance.\n\nQuality and contamination considerations: Omega-3 supplementation involves genuine quality variability. High-quality products use molecularly distilled oil to remove heavy metals (mercury, lead) and environmental contaminants (PCBs, dioxins). Third-party testing (IFOS — International Fish Oil Standards Program, NSF Certified) provides independent quality assurance. Lower-quality products may contain rancid oil (damaged fatty acids from oxidation), inadequate purification, or mislabeled concentrations. For users investing in omega-3 supplementation, quality selection matters substantially.\n\nPositioning in longevity stacks: Omega-3 fatty acids represent a foundational element of evidence-based longevity supplementation. Alongside /compound/vitamin-d, /compound/creatine, quality protein, and magnesium, omega-3 forms the core of sensible longevity supplementation. The evidence base, while complex, is among the strongest for any nutritional supplement class. Cost-benefit analysis favors omega-3 supplementation for most adults, particularly those with lower fish intake from diet.\n\nHistorical arc: The modern omega-3 era began with Bang and Dyerberg's 1970s observations of low cardiovascular disease rates in Greenlandic Inuit populations consuming high marine diets. Subsequent research identified EPA and DHA as likely mediators of cardiovascular protection. The 1980s-1990s saw expanding understanding of mechanisms and therapeutic applications. The 2000s brought large randomized trials and regulatory approvals. The 2010s-2020s produced more nuanced understanding of specific populations and preparations providing benefit, with ongoing debate about magnitude and specificity of effects. As of 2026, omega-3 fatty acids remain one of the most prescribed and recommended nutritional interventions globally.\n\nThis summary positions omega-3 fatty acids as a foundational longevity compound with strong mechanistic rationale, extensive clinical research, specific therapeutic applications, favorable safety profile, and practical accessibility — making it among the most defensible elements of evidence-based longevity supplementation.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 12, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/omega-3-fatty-acids" }, { "id": "4e069c45-8c6c-4381-a468-c325f7a82684", "slug": "orforglipron", "name": "Orforglipron", "aliases": [], "category": "Weight Loss", "description": "Orforglipron (also known as LY3502970) is Eli Lilly's oral, non-peptide, small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist, approved in the US for weight management and submitted to the FDA for type 2 diabetes. Unlike virtually every other GLP-1 receptor agonist on the market ([Semaglutide](/compound/semaglutide), [Tirzepatide](/compound/tirzepatide), [Liraglutide](/compound/liraglutide), [Dulaglutide](/compound/dulaglutide), exenatide), which are peptide-based and require either subcutaneous injection or strict oral dosing conditions to survive gastric degradation, orforglipron is a small molecule with a molecular weight of approximately 883 Daltons. It binds a distinct pocket in the upper helical bundle of the receptor and acts as a partial agonist biased toward cAMP signaling ([Kawai et al., 2020](https://pubmed.ncbi.nlm.nih.gov/33177239/)), without needing the peptide's complex 3D structure. This pharmacology delivers two big advantages: (1) it can be taken as a once-daily pill without food or beverage restrictions, and (2) it does not require refrigeration, cold-chain distribution, or manufacturing capacity constrained to specialized peptide synthesis. Together, these address two of the biggest barriers to global GLP-1 access.\n\nOrforglipron's Phase 3 ACHIEVE and ATTAIN programs reported their main results in 2025 and 2026, and they show that a daily oral non-peptide GLP-1 receptor agonist can deliver meaningful weight loss, though somewhat less than injectable semaglutide 2.4 mg. In ATTAIN-1 (obesity), 36 mg orforglipron once daily produced mean weight loss of 11.2% at 72 weeks in a trial of 3,127 adults with obesity but without diabetes (12.4% among those who stayed on treatment), below the 14.9% seen with subcutaneous semaglutide 2.4 mg weekly (Wegovy) over 68 weeks in STEP-1. The 14.7% figure sometimes quoted for orforglipron comes from its 36-week Phase 2 trial. In ACHIEVE-1 (early type 2 diabetes, 559 adults), orforglipron at 3 mg, 12 mg, and 36 mg lowered HbA1c by 1.24, 1.47, and 1.48 percentage points over 40 weeks from a baseline of 8.0%, against 0.41 with placebo, alongside 4.5-7.6% weight loss. The FDA approved it as Foundayo for weight management on April 1, 2026.\n\nWhy this matters commercially and clinically: demand for injectable peptide GLP-1s outran manufacturing capacity for years, and the FDA listed semaglutide injections in shortage from 2022 until it declared that shortage resolved in February 2025. Small-molecule orforglipron can be manufactured in traditional API facilities using standard organic chemistry, dramatically expanding global supply, reducing cost-of-goods, and enabling distribution to low- and middle-income countries where refrigerated peptides are logistically difficult. A generic-analog small-molecule GLP-1 class could ultimately bring retail cost from $1,000+/month for brand-name injectables to potentially under $50/month for oral generics, with parallels to how statins democratized cholesterol management. Cross-references include [Semaglutide](/compound/semaglutide) (injectable GLP-1 peptide), [Tirzepatide](/compound/tirzepatide) (injectable GLP-1/GIP peptide), [Mazdutide](/compound/mazdutide) (injectable GLP-1/glucagon peptide for China), [Retatrutide](/compound/retatrutide) (injectable GLP-1/GIP/glucagon triple agonist peptide), and [Cagrilintide](/compound/cagrilintide) (amylin analog used in combination with GLP-1s).", "half_life": "~29-49 hours (supports once-daily oral dosing)", "molecular_weight": "882.97 g/mol", "molecular_mass": "882.97 g/mol (C48H48F2N10O5; PubChem CID 137319706)", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "Once daily", "cycle_length": "", "common_vial_sizes": [], "research_stage": "FDA Approved", "approval_status": "FDA-approved on April 1, 2026 as Foundayo (orforglipron) for chronic weight management in adults with obesity, or overweight with at least one weight-related comorbidity. It is the first oral, small-molecule GLP-1 receptor agonist approved. Lilly reported in August 2026 that it had submitted Foundayo to the FDA for type 2 diabetes (ACHIEVE Phase 3 program); the current label covers weight management only. Additional filings are pending in dozens of other countries.", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/orforglipron" }, { "id": "0a15a3f2-161f-4f81-ae5d-5327cf9e28e0", "slug": "ostarine", "name": "Ostarine (Enobosarm, MK-2866)", "aliases": [ "Enobosarm", "MK-2866", "MK2866", "GTx-024", "S-22", "Ostabolic" ], "category": "Performance", "description": "Ostarine is the market name for enobosarm, a nonsteroidal selective androgen receptor modulator first developed by GTx Inc under the codes GTx-024, MK-2866 and S-22. It was designed to switch on the androgen receptor in muscle and bone while acting only weakly on prostate and other reproductive tissue, and it was taken into clinical development for muscle wasting in cancer, for age-related loss of muscle, for androgen receptor positive breast cancer and for stress urinary incontinence. It has never been approved by the FDA or the EMA for any indication. Development rights now sit with Veru Inc, which is testing it as an add-on to GLP-1 receptor agonists to limit the loss of lean mass that accompanies rapid weight reduction.\n\nThe androgen receptor is a nuclear receptor. Testosterone and dihydrotestosterone bind it, move it into the cell nucleus and change which genes are read. Enobosarm binds the same receptor but recruits a different set of co-regulator proteins, which is why its effects on muscle and bone are stronger than its effects on prostate and skin. Work in mice showed that the muscle response does not come only from satellite cells, since enobosarm still restored muscle weight in animals lacking the androgen receptor in that cell lineage (PMID: 26393303).\n\nIn animals, enobosarm improved bone healing in ovariectomized rats (PMID: 31531719), improved muscle tissue in ovariectomized rats (PMID: 33042018) and improved bone in orchiectomized rats used as an osteoporosis model (PMID: 37378829). Not every animal result is favorable: in rats it blunted the effect of endurance training on submaximal endurance (PMID: 38451281) and did not add to the metabolic effect of exercise in obese rats (PMID: 37865959). In humans, a 12-week phase 2 trial in 120 healthy older men and postmenopausal women reported gains in total lean body mass and physical function against placebo (PMID: 22031847), and a phase 2 trial in patients with cancer-related weight loss reported gains in lean body mass (PMID: 23499390).\n\nThe safety record is the part most often left out of marketing. Cholestatic and hepatocellular liver injury after ostarine use has been published as individual case reports, including a young man who needed albumin dialysis and took six months to return to normal bilirubin (PMID: 37871633), a hepatocellular case that resolved after stopping the supplement (PMID: 35655632) and cases involving ostarine with post-cycle drugs (PMID: 34141767). A systematic review of safety in healthy adults collected fifteen published cases of drug-induced liver injury across the SARM class along with a tendon rupture and a rhabdomyolysis case (PMID: 37218811). The FDA states that these products are unapproved drugs, are not dietary supplements, and lists liver injury and acute liver failure, heart attack, stroke, psychosis, infertility and testicular shrinkage among reported risks (FDA, Certain Bodybuilding Products Put Consumers at Risk, page updated December 2025).\n\nWhat is sold online is often not what the label says. In an analysis of 44 products marketed as SARMs, only 52 percent contained a SARM at all, 39 percent contained a different unapproved drug, and the labeled amount matched the measured amount in only 41 percent (PMID: 29183075).", "half_life": "Not established from a retrieved human report; in rats the mean elimination half-life of radiolabeled GTx-024 was 0.6 h in males and 16.4 h in females (PMID: 24074268). Human plasma pharmacokinetics were characterized in phase 1 drug-interaction studies (PMID: 27105861)", "molecular_weight": "389.33 g/mol", "molecular_mass": "389.33 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Phase 3", "approval_status": "Not approved by the FDA or the EMA for any indication. FDA states that products containing SARMs are unapproved drugs and are not dietary supplements, and has issued warning letters to distributors selling ostarine as an unapproved new drug (FDA warning letter to Panther Sports Nutrition, 23 October 2017). Listed by the World Anti-Doping Agency under class S1.2, other anabolic agents, and prohibited both in and out of competition (PMID: 38499138). Sold in the United States only as a research-use-only compound.", "trial_phase": "", "cas_number": "841205-47-8", "iupac_name": "", "chemical_formula": "C19H14F3N3O3", "potential_benefits": [ "Increased total lean body mass and improved physical function in healthy older men and postmenopausal women in a 12-week phase 2 trial (PMID: 22031847)", "Increased total lean body mass in patients with cancer-associated weight loss in a phase 2 trial (PMID: 23499390)", "Clinical benefit at 24 weeks in about a third of women with androgen receptor positive, estrogen receptor positive, HER2 negative advanced breast cancer in a phase 2 trial (PMID: 38342115)", "Improved bone healing in ovariectomized rats (PMID: 31531719)", "Improved muscle tissue in ovariectomized rats (PMID: 33042018)" ], "research_fields": [ "Muscle wasting and cachexia", "Sarcopenia", "Oncology", "Sports drug testing" ], "pubmed_count": 0, "pubchem_cid": 11326715, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/ostarine" }, { "id": "016db694-8365-4718-a104-587010c11c86", "slug": "ovagen", "name": "Ovagen", "aliases": [ "GI peptide" ], "category": "Liver/Digestive", "description": "\nOvagen is a short synthetic peptide developed in Russia by Vladimir Khavinson and collaborators at the St. Petersburg Institute of Bioregulation and Gerontology, positioned as an \"ovarian bioregulator\" intended to support female reproductive tissue, follicular reserve markers, and age-related ovarian decline, as well as broader hepatobiliary function in some historical formulations. It is usually described in Khavinson-family publications as the tetrapeptide Lys-Glu-Asp-Gly (KEDG), sometimes rendered H-Lys-Glu-Asp-Gly-OH or K-E-D-G. Ovagen sits alongside [Pinealon](/compound/pinealon), [Thymogen](/compound/thymogen), [Vilon](/compound/vilon), [Epitalon](/compound/epithalon), [Livagen](/compound/livagen), [Bronchogen](/compound/bronchogen), [Cardiogen](/compound/cardiogen), [Cartalax](/compound/cartalax), and [Chonluten](/compound/chonluten) within the Khavinson short-peptide bioregulator family, and is positioned as the female-reproductive counterpart to [Testagen](/compound/testagen) (male reproductive bioregulator).\n\nOutside Russia, Ovagen is **not a registered pharmaceutical, not FDA- or EMA-reviewed, not listed in WADA categories**, and does not appear in ASRM, ESHRE, or NICE guidelines for ovarian dysfunction, premature ovarian insufficiency, or menopause management. Published Russian work — authored primarily by Khavinson and collaborators — comprises in vitro ovarian follicle culture studies, rodent aging and ovariectomy experiments, and small uncontrolled observational series in women with age-related ovarian decline and perimenopausal transition ([Khavinson et al., 2011]; [Anisimov et al., 2010]; [Kuznik et al., 2011]).\n\nThe central claim for Ovagen is the standard Khavinson short-peptide bioregulator model applied to ovarian tissue: passive membrane permeation into granulosa and theca cells, nuclear import, and sequence-selective chromatin modulation producing preferential upregulation of follicular-survival, steroidogenic, and anti-apoptotic programmes. The tissue-specific targeting claim — that KEDG selectively supports ovarian rather than testicular, hepatic, or other tissue — is asserted but not supported by structural biology, modern biodistribution, or transcriptomic characterisation of ovarian tissue after KEDG exposure. The hypothesis is internally consistent within the Khavinson programme; it is substantially less validated than evidence-graded management of reproductive aging, perimenopause, and premature ovarian insufficiency.\n\nBodyHackGuide covers Ovagen because it is sold online in post-Soviet supplement channels (typically 20 mg oral capsules) and appears occasionally in longevity and female-health discussions as a reproductive-support bioregulator. We describe what is known, what is claimed, and what is missing — and we steer readers seeking evidence-graded management of reproductive aging toward interventions with substantial replication: complete hormonal assessment (FSH, LH, estradiol, AMH, thyroid, prolactin), lifestyle optimisation (weight management, smoking cessation, stress management), evidence-based hormone therapy when indicated and not contraindicated (estradiol + progestogen for perimenopausal symptoms, with individualised risk-benefit discussion), specific fertility treatment (ovulation induction, IVF) for age-related fertility decline, and proven supplements for reproductive aging (vitamin D, omega-3, CoQ10 with modest evidence for ovarian function, myo-inositol for PCOS). Ovagen is a plausible hypothesis. It is not, in 2026, an evidence-graded reproductive therapy.\n", "half_life": "Not established - no human or animal pharmacokinetic data have been published. As a small, unprotected tripeptide, EDL is expected to be hydrolysed by peptidases within minutes in the circulation.", "molecular_weight": "~375 Da (tripeptide; molecular formula C15H25N3O8)", "molecular_mass": "375.38 g/mol", "amino_acid_sequence": "Glu-Asp-Leu (EDL)", "administration_routes": [], "dose_range_mcg": "No validated human dose. Khavinson cytomax convention for oral short peptides is about 10 mg once daily in 10-day courses; research suppliers of the lyophilised synthetic EDL tripeptide list roughly 1-2 mg subcutaneously daily. These are conventions, not trial-derived figures.", "dosing_frequency": "Once daily during short courses (Khavinson cytomax convention)", "cycle_length": "10 consecutive days per course, repeated a few times per year with washout periods of one to three months. No trial supports any particular schedule.", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Not approved by FDA, EMA, or any other regulator. No regulatory filings and no pharmacopoeial monograph. Sold only as an experimental research compound (research use only).", "trial_phase": "", "cas_number": "", "iupac_name": "L-Lysyl-L-glutamyl-L-aspartyl-L-glutamine", "chemical_formula": "Lys-Glu-Asp-Gln", "potential_benefits": [ "Proposed liver support / hepatoprotection (preclinical only)", "Proposed gastrointestinal and digestive-enzyme support (related-peptide animal data)", "Geroprotective gene-expression signal shown for the EDL peptide in cell culture", "Experimental research compound - no proven human benefit" ], "research_fields": [], "pubmed_count": 19, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/ovagen" }, { "id": "01e6a6f3-05e4-464b-a963-e5b70873eb6f", "slug": "oxiracetam", "name": "Oxiracetam", "aliases": [ "ISF 2522", "CGP 21690E", "Neuromet", "Hydroxypiracetam", "S-oxiracetam", "L-oxiracetam", "4-hydroxy-2-oxo-1-pyrrolidineacetamide" ], "category": "Nootropics", "description": "Oxiracetam is a hydroxylated analog of piracetam, developed in Italy in the early 1980s under the code ISF 2522 and also known as CGP 21690E. It was authorized for marketing in Italy under the trade name Neuromet on 21 April 1984 and was studied through the 1980s and 1990s in older patients with degenerative and multi-infarct dementia and with organic brain syndrome. It remains in clinical use in China, where oxiracetam served as the active comparator arm in a multicenter phase 3 trial run from 2019 to 2024 (PMID: 41381424). It has never been approved in the United States. Consumer-facing oxiracetam is sold as bulk powder or capsules under research-chemical terms.\n\nThe molecule carries a chiral center and is normally supplied as the racemate. The S enantiomer, marketed and studied in China as S-oxiracetam or L-oxiracetam, is the active one: in rats with chronic cerebral hypoperfusion, S-oxiracetam and not R-oxiracetam relieved spatial learning and memory impairment, reduced neuron damage and white matter lesions and increased cerebral blood flow (PMID: 28855592). This matters for anyone reading the literature, because racemic and single-enantiomer studies are not interchangeable.\n\nMechanistically oxiracetam is less well defined than aniracetam. Rodent work links its behavioral effects to cholinergic function: it antagonized both scopolamine-induced behavioral disruption and the scopolamine-induced fall in hippocampal and cortical acetylcholine in rats, with matching bell-shaped dose-effect curves (PMID: 2602443), and it prevented mecamylamine-induced impairment of active avoidance in mice (PMID: 2356212). It also acts on glutamatergic signaling: it prevented kynurenic acid antagonism of NMDA-evoked noradrenaline release in rat hippocampal slices (PMID: 9336311) and in slices of human neocortex taken during neurosurgery (PMID: 10381808). More recent work in APP/PS1 mice reports that oxiracetam slows desensitization of the GluA1 and GluA2 AMPA receptor subunits (PMID: 41739317).\n\nHuman results are inconsistent across four decades. Positive placebo-controlled results were reported in a 289-patient multicenter trial in degenerative, multi-infarct and mixed dementia (PMID: 2693996) and in several smaller Italian studies. Clearly negative results came from a 24-patient double-blind study in Alzheimer disease, where a broad neuropsychological battery showed no improvement in any patient (PMID: 1444879), and a 106-patient trial in solvent-related organic brain syndrome (PMID: 3296624). The largest modern trial, a 500-patient study commissioned by the South Korean Ministry of Food and Drug Safety, found no difference from placebo on either co-primary endpoint after 36 weeks (PMID: 41614470).\n\nRegulators have acted on those results. In February 2023 the South Korean drug regulator revoked the vascular cognitive impairment indication and ordered oxiracetam products withdrawn and destroyed after they failed clinical reassessment, and insurance coverage was suspended for seven products. In the United States, the Food and Drug Administration stated in a February 2019 warning letter that oxiracetam is not a dietary ingredient and that products bearing cognitive claims are unapproved new drugs.", "half_life": "About 8 hours in healthy adults. Mean terminal half-life was 7.7 hours in healthy non-geriatric subjects and 12.3 hours in elderly patients after oral dosing (PMID: 2253653), and 10.6 to 68.1 hours in patients with renal impairment, correlating with creatinine clearance (PMID: 2253654). More than 90 percent of an intravenous dose is recovered unchanged in urine within 48 hours, and absolute oral bioavailability was 75 percent in healthy volunteers (PMID: 6519128).", "molecular_weight": "158.16 g/mol", "molecular_mass": "158.16 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral", "Intravenous infusion" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Approved (Italy)", "approval_status": "Oxiracetam was first authorized for marketing in Italy as Neuromet on 21 April 1984 and remains in clinical use in China, where marketed oxiracetam was the active comparator arm of a 590-patient phase 3 trial run in 51 hospitals between 2019 and 2024 (PMID: 41381424). It has never been approved by the United States Food and Drug Administration, which stated in a February 2019 warning letter that oxiracetam is not a dietary ingredient and that products carrying cognitive claims are unapproved new drugs. In February 2023 the South Korean Ministry of Food and Drug Safety revoked the vascular cognitive impairment indication and ordered oxiracetam products withdrawn after they failed a clinical reassessment; in the United States market it is a research-use-only compound and is not a controlled substance.", "trial_phase": "", "cas_number": "62613-82-5", "iupac_name": "", "chemical_formula": "C6H10N2O3", "potential_benefits": [ "Antagonized scopolamine-induced amnesia and the associated fall in hippocampal and cortical acetylcholine in rats (PMID: 2602443)", "Prevented mecamylamine-induced impairment of active avoidance learning in mice (PMID: 2356212)", "Facilitated two-way shuttle avoidance acquisition in normal mice (PMID: 3244203)", "S-oxiracetam, and not R-oxiracetam, relieved spatial learning and memory impairment and reduced white matter lesions in rats with chronic cerebral hypoperfusion (PMID: 28855592)", "Improved cognitive scores versus placebo over 12 weeks in 289 patients with degenerative, multi-infarct or mixed dementia (PMID: 2693996)", "Higher Loewenstein cognitive assessment scores than placebo at 90 days for the single enantiomer L-oxiracetam, an advantage not demonstrated for the racemate, in a 590-patient phase 3 trial in mild to moderate traumatic brain injury (PMID: 41381424)" ], "research_fields": [ "Cognitive enhancement", "Vascular cognitive impairment", "Traumatic brain injury", "Nootropics" ], "pubmed_count": 0, "pubchem_cid": 4626, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/oxiracetam" }, { "id": "03edd08e-3be4-4c7d-9a58-f74ae4412162", "slug": "oxytocin", "name": "Oxytocin", "aliases": [ "OT" ], "category": "Hormones & Endocrine (Non-GH)", "description": "Oxytocin is a nine-amino-acid cyclic peptide hormone (Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2) synthesized in magnocellular neurons of the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON), then transported along axons to the posterior pituitary for release into systemic circulation. Vincent du Vigneaud synthesized oxytocin in 1953, becoming the first scientist to chemically synthesize a peptide hormone and earning the 1955 Nobel Prize in Chemistry for the achievement. The isolation and characterization of oxytocin marked the beginning of modern peptide pharmacology and established the template for all subsequent peptide drug development. Oxytocin's classical roles — uterine contraction during labor and milk ejection during breastfeeding — have been understood since the early 20th century and form the basis of its FDA approval as Pitocin (synthetic oxytocin) for labor induction and augmentation, postpartum hemorrhage control, and lactation support.\n\nThe story of oxytocin as something far more interesting than a reproductive hormone began in the 1990s, when researchers including Sue Carter, Thomas Insel, and Larry Young discovered that oxytocin released centrally in the brain (rather than peripherally through the posterior pituitary into blood) acts as a profound modulator of social behavior, pair bonding, trust, empathy, maternal behavior, and sexual response. Prairie vole studies showed that central oxytocin (and its sister peptide vasopressin) mediates the difference between monogamous and promiscuous mating strategies; human studies showed that intranasally administered oxytocin modulates trust, generosity, gaze patterns, and emotional recognition ([Kosfeld et al., 2005](https://pubmed.ncbi.nlm.nih.gov/15931222/), [Insel & Young, 2001]). This \"social neuropeptide\" framing generated enormous scientific and popular interest and motivated clinical trials exploring oxytocin for autism spectrum disorders, post-traumatic stress disorder, social anxiety, schizophrenia-related social dysfunction, and relationship therapy applications.\n\nResults from those clinical trials have been more nuanced than the early excitement suggested. Large randomized controlled trials in autism have shown mixed-to-disappointing results ([Sikich et al., 2021 NEJM]). The initial Kosfeld \"trust\" finding and related social cognition effects have been difficult to replicate consistently, leading to a reckoning about methodological issues in the early oxytocin literature ([Nave et al., 2015 meta-analysis]). What has held up is that oxytocin does produce subtle, context-dependent effects on social and emotional processing in some people under some conditions — but it is not the universal love-and-trust drug that early popular science coverage sometimes implied. The pharmacology is more sophisticated than a simple \"love hormone\" narrative allows.\n\nIn current clinical practice, oxytocin has well-established approval for obstetric uses (Pitocin IV for labor, Syntocinon nasal spray for milk letdown in some markets). Off-label and grey-market use of oxytocin — typically via compounded nasal spray or subcutaneous injection — is pursued for three main reasons: (1) improving sexual and emotional connection with partners, which is the most common recreational motivation and the one with the most credible (if limited) evidence base; (2) managing social anxiety, autism-spectrum social challenges, or post-traumatic stress symptoms under self-directed protocols; and (3) adjunctive use during couples therapy, psychotherapy, or other relational contexts where the modest pro-social effects may facilitate the therapeutic process. None of these off-label uses is supported by rigorous efficacy evidence comparable to what exists for approved indications, and the intranasal route that most community use relies on has significant questions about how much centrally active oxytocin actually reaches the brain after nasal administration ([Leng & Ludwig, 2016]).\n\nThis entry covers what oxytocin does biologically, what clinical evidence exists for its various uses, and the practical realities of off-label oxytocin use including route-of-administration uncertainties, duration of effect, and limitations. Unlike many peptides covered here, oxytocin has a genuinely large scientific literature — several thousand published human studies — but separating signal from noise in that literature requires careful reading. Cross-links to related compounds include [PT-141 (Bremelanotide)](/compound/pt-141) for central sexual arousal effects through an independent (melanocortin) mechanism, and [Kisspeptin-10](/compound/kisspeptin-10) for reproductive axis and desire effects through yet another distinct mechanism.", "half_life": "~1-6 minutes (plasma); central/behavioral effects outlast plasma clearance, typically ~30-120 minutes after intranasal dosing", "molecular_weight": "1007.19 g/mol", "molecular_mass": "1007.19 g/mol", "amino_acid_sequence": "Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2 (one-letter: CYIQNCPLG). A 9-residue cyclic nonapeptide with an intramolecular disulfide bond between Cys1 and Cys6 (forming a six-residue ring plus a C-terminal Pro-Leu-Gly tail) and a C-terminal glycinamide (amidated). Molecular formula C43H66N12O12S2. Differs from vasopressin at just two positions: Ile3 (vs Phe) and Leu8 (vs Arg).", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "As needed (on-demand), timed 20-45 minutes before a target social/intimate window; research protocols have used up to 2-3x daily (commonly 24 IU twice daily) intranasally", "cycle_length": "No fixed cycle required (short half-life, no withdrawal on stopping). On-demand use has no strict limit; continuous daily research dosing has been studied up to ~24 weeks. Long-term daily off-label use is uncharacterized, so periodic breaks are reasonable.", "common_vial_sizes": [], "research_stage": "FDA-Approved", "approval_status": "FDA-approved for obstetric use (labor induction, labor augmentation, and control of postpartum hemorrhage) as Pitocin and generic oxytocin injection; in clinical obstetric use since the 1950s. Behavioral, psychiatric, sexual, and intranasal off-label uses are NOT FDA-approved and remain investigational / research-use-only.", "trial_phase": "FDA Approved", "cas_number": "50-56-6", "iupac_name": "Oxytocin", "chemical_formula": "C43H66N12O12S2", "potential_benefits": [ "Social and emotional bonding (subtle, context-dependent)", "Situational social-anxiety relief", "Enhanced intimacy and post-orgasm bonding", "Labor induction and milk let-down (approved obstetric use)", "Trauma-focused therapy adjunct (investigational)" ], "research_fields": [ "Autism spectrum disorder", "Social anxiety", "PTSD", "Addiction", "Postpartum depression" ], "pubmed_count": 602, "pubchem_cid": 439302, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/439302/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/oxytocin" }, { "id": "9f948409-16ba-4736-9f4e-601bb5379f7d", "slug": "p-21", "name": "P-21", "aliases": [ "P21" ], "category": "Nootropics", "description": "P-21 (also written P021, or Peptide 021) is a synthetic peptidergic compound derived from the neurotrophic region of ciliary neurotrophic factor (CNTF), designed to activate neurogenic and BDNF-producing pathways in the adult brain without triggering the activation of the CNTF receptor that causes the undesirable side effects (cachexia, muscle wasting) that limited CNTF itself as a therapeutic. The compound emerged from a translational neuroscience research program at the New York State Institute for Basic Research in Developmental Disabilities, where Khalid Iqbal and colleagues characterized a region of CNTF that was responsible for the pro-neurogenic and cognitive effects without the adverse peripheral effects, then synthesized short peptides containing that functional motif ([Chohan et al., 2011]; [Blanchard et al., 2010]). P-21 is a small peptide (variable reported sequence across preparations) that has been tested in multiple rodent models including normal aged mice, Alzheimer's disease transgenic mice (3xTg-AD, APP/PS1), and models of age-related cognitive decline. The reported effects include increased hippocampal neurogenesis, elevated BDNF and other neurotrophin expression in the hippocampus and cortex, improved performance on hippocampus-dependent learning tasks (Morris water maze, novel object recognition), and reductions in pathological markers in AD models (amyloid plaque burden, tau hyperphosphorylation, synaptic deficits) ([Chohan et al., 2011]; [Kazim et al., 2014]; [Baazaoui & Iqbal, 2017]; [Bolognin et al., 2014]). These findings have attracted interest from both legitimate academic research (the compound has been evaluated as a potential AD therapeutic) and from biohacker communities seeking cognitive enhancement interventions. The practical reality in April 2026 is that P-21 has not progressed to human clinical trials, has no FDA approval, has no published pharmacokinetic data in humans, and is sold as a research peptide by vendors with variable quality control. Self-experimenters typically administer P-21 intranasally as a spray or drops, which bypasses the blood-brain barrier concerns that complicate peptide CNS delivery, though intranasal bioavailability and tissue distribution in humans are not characterized. Subcutaneous and oral administration are less common for P-21 because the intended target is the central nervous system and systemic administration provides poor brain penetration for most peptides. Enthusiasm for P-21 in biohacker circles is driven partly by its mechanistic story (pro-neurogenic, BDNF-activating, with preclinical data in AD models) and partly by marketing that sometimes conflates rodent efficacy data with implied human benefit. The honest framing is that P-21 is a mechanistically interesting research compound with good preclinical data in narrow model systems and no human validation. FDA-approved interventions for cognitive concerns — addressing cardiovascular risk factors, treating depression and anxiety, hearing and vision correction, social engagement, cognitive stimulation, exercise, adequate sleep, and specific interventions for diagnosed conditions (cholinesterase inhibitors, memantine for AD dementia; SSRIs for depression-related cognitive symptoms) — have evidence bases orders of magnitude stronger than any research peptide for cognitive or neurological outcomes. P-21 sits in the experimental category and should be framed accordingly rather than positioned as a legitimate cognitive enhancer or AD prevention strategy. This entry covers what P-21 actually does in the preclinical literature, how the CNTF-derived mechanism works, what the limitations of the evidence are, what the theoretical and practical concerns are for human use, and what a realistic approach looks like for anyone considering experimentation with the compound.", "half_life": "", "molecular_weight": "578.67 g/mol (C27H42N6O8)", "molecular_mass": "578.67 g/mol", "amino_acid_sequence": "Ac-DGGL(A)G-NH2 - an acetylated, C-terminally amidated synthetic peptide with an adamantylated glycine; derived from the active 4-residue region of ciliary neurotrophic factor (CNTF). The adamantane modification confers blood-brain-barrier permeability and resistance to exopeptidase degradation. It is the optimized derivative of the 11-mer parent 'Peptide 6' (residues from the active region of human CNTF).", "administration_routes": [], "dose_range_mcg": "500-2000 mcg (0.5-2 mg) daily, most commonly 500-1000 mcg (community/self-experimentation range; no clinical validation)", "dosing_frequency": "Once daily (some users divide into twice daily), typically dosed in the morning", "cycle_length": "Typically 4-24 weeks on, 4-12 weeks off, with 2-3 cycles per year (community practice; no clinical validation)", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Not approved - research use only (RUO)", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "C104H167N29O30S", "potential_benefits": [ "Enhanced hippocampal neurogenesis (preclinical)", "Improved learning and memory (preclinical, rodent)", "Elevated BDNF and other neurotrophin expression", "Neuroprotective effects in Alzheimer's disease models (preclinical)", "Reduced tau hyperphosphorylation and soluble amyloid-beta in transgenic mice (preclinical)" ], "research_fields": [], "pubmed_count": 98, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/p-21" }, { "id": "8364ed21-8058-47b9-80b6-d4b28d10fe88", "slug": "p21", "name": "P-21", "aliases": [ "P21", "Cyclo(L-prolyl-glycine)", "Cyclo-Pro-Gly", "Russian P-21", "Selank Fragment" ], "category": "Nootropic Peptide", "description": "P-21 is a **synthetic cyclic dipeptide** — Cyclo(L-prolyl-glycine) — derived from the Selank/Semax C-terminal Pro-Gly-Pro motif. It was isolated and characterized by the Institute of Molecular Genetics at the Russian Academy of Sciences as a metabolic fragment of [Selank](/compound/selank), and shown in animal studies to recapitulate much of Selank's anxiolytic and nootropic profile in a smaller, more BBB-penetrant molecule.\n\nUnlike linear peptides that require intranasal administration to bypass enzymatic degradation, P-21's cyclic structure confers **oral bioavailability** — a significant practical advantage. Reported research applications include stress-induced cognitive deficit reversal, anxiolytic effects without sedation, and acute neuroprotection in MCAO (middle cerebral artery occlusion) stroke models.\n\nAs of 2026, P-21 is **not FDA-approved**. The published literature is concentrated in Russian-language journals from the 2010s; English-language peer-reviewed studies are sparse.", "half_life": "Not formally characterized in published work. P021 has only been studied in rodents (oral/dietary and subcutaneous dosing); no human pharmacokinetic data exist.", "molecular_weight": "578.7 g/mol (molecular formula C27H42N6O8; PubChem CID 56599151)", "molecular_mass": "578.7 Da (C27H42N6O8)", "amino_acid_sequence": "Ac-DGGL(A)G-NH2 - N-acetyl-Asp-Gly-Gly-Leu tetrapeptide capped with a C-terminal adamantylated glycinamide (3-carbamoyl-1-adamantyl). The DGGL core is derived from the active region of ciliary neurotrophic factor (CNTF). Linear peptidomimetic, not cyclic.", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Not approved. Preclinical / research use only - no human trials.", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "C7H10N2O2", "potential_benefits": [], "research_fields": [], "pubmed_count": 4, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/p21" }, { "id": "d2957d4d-2aa8-410a-8f12-9522c28f25a7", "slug": "p21-amidate", "name": "P-21 Amidate", "aliases": [ "P21 Amide", "P-21 Amide", "P-21-NH2", "Cyclo-Pro-Gly-Amide" ], "category": "Nootropic Peptide", "description": "P-21 Amidate is the **amide-modified variant of [P-21](/compound/p21)**, the cyclic dipeptide derived from [Selank](/compound/selank). The C-terminal amidation is reported to further improve oral bioavailability and metabolic stability beyond what the cyclic structure alone provides.\n\nThe practical positioning: P-21 is already orally active; the amidate variant pushes that further, with vendor and community reports of higher subjective potency at equivalent doses. Peer-reviewed comparative data for the amidate form remains thin — most published P-21 research uses the unmodified cyclic form.", "half_life": "No established human PK - unknown. P-21 (P021) is a preclinical compound; rodent studies used chronic oral or subcutaneous dosing and demonstrated oral bioavailability and blood-brain-barrier penetration, but no validated human half-life data exist.", "molecular_weight": "~592.7 g/mol (free base; molecular formula C28H44N6O8)", "molecular_mass": "592.69 g/mol", "amino_acid_sequence": "Ac-DGGL(A)G-NH2", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Not approved for human use - preclinical research compound (research use only).", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "C7H11N3O2", "potential_benefits": [], "research_fields": [], "pubmed_count": 1, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/p21-amidate" }, { "id": "854206f1-e32e-42d4-a050-970cde16af7a", "slug": "panax-ginseng", "name": "Panax ginseng", "aliases": [ "Korean Red Ginseng", "Asian Ginseng", "Chinese Ginseng", "Ren Shen", "G115", "Cheong Kwan Jang", "Ginsana", "Ginsenosides", "KRG", "White Ginseng" ], "category": "Adaptogen", "description": "Panax ginseng is the canonical Asian adaptogen, the compound that gave \"ginseng\" its name in the global supplement lexicon, and the most extensively studied herbal medicine in the Asian pharmacopeia. Native to the mountainous forests of northeastern China, the Korean peninsula, and the Russian Far East, Panax ginseng has been cultivated and wild-harvested for at least 2,000 years, with the earliest written references in the Shennong Ben Cao Jing (Divine Farmer's Materia Medica) of Han Dynasty China describing it as a superior herb that \"nourishes the five internal organs, tranquilizes the spirit, and prolongs life.\" The genus name \"Panax\" derives from the Greek \"panacea\" (all-healing), reflecting the classical reputation of the herb across Chinese, Korean, and Russian traditional medicine systems. Panax ginseng is one of three commercially significant Panax species: Panax ginseng (Asian/Korean), [Panax quinquefolius](/compound/american-ginseng) (American, a different pharmacological profile with higher Rb1:Rg1 ratio producing more calming and less stimulating effects), and Panax notoginseng (Chinese \"tian qi,\" traditionally used for hemostasis and cardiovascular indications). These three species share ginsenoside chemistry but differ in ginsenoside ratios, clinical profiles, and traditional indications — knowing which Panax species you're taking is the first rule of ginseng supplementation.\n\nThe bioactive constituents are the ginsenosides, a family of more than 40 triterpenoid saponins unique to the Panax genus. The most pharmacologically significant ginsenosides are Rb1, Rg1, Rb2, Rd, Re, Rc, Rf, and the gut-microbiome-produced metabolite compound K (CK, also called M1). Ginsenoside Rg1 is the major stimulating and cognitive-improving ginsenoside, increasing in concentration after steaming (the classical \"red ginseng\" processing method); Rb1 is the major calming, anti-inflammatory, and vasodilatory ginsenoside; Rd and compound K are the major anti-cancer and insulin-sensitizing ginsenosides. The critical pharmacokinetic fact is that ginsenosides are poorly absorbed intact from the GI tract (bioavailability of parent ginsenosides is <5%) — most of the clinical effect of oral ginseng comes from gut microbiome metabolism of parent ginsenosides into smaller, more bioavailable compound K, PPD (protopanaxadiol), and PPT (protopanaxatriol) metabolites by intestinal bacteria including Prevotella, Bacteroides, and Bifidobacterium. This means that (1) individuals with disrupted gut microbiomes (recent antibiotics, IBD, low-fiber diets) may have reduced ginseng bioavailability, and (2) products marketed as \"compound K\" or \"fermented ginseng\" pre-convert the ginsenosides to their active metabolites, providing more predictable absorption. See [Korean Red Ginseng](/compound/korean-red-ginseng) for the specific-extract profile.\n\nThe distinction between red, white, black, and wild ginseng matters pharmacologically. **White ginseng** is air-dried raw root with the highest preservation of native ginsenoside spectrum, skewed toward the Rg1/Rb1/Re parent ginsenosides. **Red ginseng** is steamed then dried, a processing method that dehydrates and partially hydrolyzes some ginsenosides into new compounds (notably Rg3, Rh2, Rk1, Rg5 \"red-specific ginsenosides\" that have anti-cancer and anti-inflammatory effects not found in unsteamed root). Korean Red Ginseng (KRG, Cheong Kwan Jang being the largest commercial producer) is the most-studied red ginseng preparation. **Black ginseng** is multi-steamed (typically 9 times), producing even higher Rg3/Rh2 content but at significantly higher cost. **Wild ginseng** (rare, expensive, from old-growth forests in Korea, Manchuria, and Russia) is the traditional premium form but is now nearly all cultivated. For most users, Korean Red Ginseng or a standardized extract like G115 (Pharmaton, 4% ginsenosides) is the appropriate clinical form.\n\nThe mechanism of action operates across at least seven molecular pathways that differ from the other major adaptogens. Unlike [rhodiola rosea](/compound/rhodiola-rosea) (MAO inhibition, monoamine modulation), [ashwagandha](/compound/ashwagandha) (GABA, HPA suppression), or [bacopa monnieri](/compound/bacopa-monnieri) (BDNF, dendritic plasticity), Panax ginseng's mechanism centers on: (1) nitric oxide synthase upregulation producing vasodilation (the primary mechanism for erectile-function benefits), (2) insulin sensitization via AMPK activation and GLUT4 translocation (the mechanism for type 2 diabetes benefits), (3) mitochondrial biogenesis and ATP synthesis enhancement (the mechanism for fatigue reduction), (4) modest cholinergic enhancement (cognitive benefits), (5) HPA-axis modulation via corticotropin-releasing hormone suppression (stress resilience), (6) immune modulation including NK cell activation, macrophage activation, and T-cell proliferation (immune support), and (7) anti-cancer effects via compound K-mediated apoptosis in multiple tumor cell lines.\n\nClinical indications with the strongest evidence are: (1) chronic fatigue and cancer-related fatigue (Kim 2010, Kim 2013, Barton 2013 Wisconsin — Wisconsin Ginseng, which is Panax quinquefolius, showed strong cancer-fatigue benefit, and Korean Red Ginseng has similar evidence in Asian populations); (2) erectile dysfunction (multiple meta-analyses showing ~20% effect-size improvement on IIEF scores at 1-3 g/day KRG for 4-12 weeks); (3) cognitive performance under demanding conditions (Reay 2010 series using G115 extract); (4) type 2 diabetes as adjunct to diet/medication (Vuksan 2008 meta-analysis showing modest but significant HbA1c reductions at 3-9 g/day); and (5) immune support during cold/flu season (McElhaney 2004 showing reduced respiratory infections in elderly). Panax ginseng is not well-supported for major depression (unlike rhodiola), anxiety (unlike ashwagandha), or memory consolidation (unlike bacopa) — choose the right adaptogen for the right indication.\n\nWhere Panax ginseng fits in the overall adaptogen landscape: it's the \"physical vitality\" adaptogen — appropriate for fatigue, stamina, exercise capacity, erectile function, immune support, and metabolic health, rather than the cognitive-stress-mood indications where other adaptogens dominate. Koreans often take Korean Red Ginseng as a daily tonic (typically 1-3 g/day of whole red root, or 200-600 mg of concentrated extract); Chinese traditional use includes it in countless formula combinations; Russian adaptogen research in the 1950s-1970s gave it state-sanctioned performance-enhancer status for Soviet athletes and cosmonauts alongside [rhodiola](/compound/rhodiola-rosea) and [eleuthero](/compound/eleuthero). For the user of this site, the decision rule: choose Panax ginseng for physical vitality, exercise tolerance, fatigue, or ED; choose [rhodiola](/compound/rhodiola-rosea) for stress-related fatigue and mild depression; choose [ashwagandha](/compound/ashwagandha) for anxiety, sleep, and testosterone; choose [bacopa](/compound/bacopa-monnieri) for chronic memory support. Many users benefit from rotating or combining multiple adaptogens. See also [american ginseng](/compound/american-ginseng) (calming profile, different ginsenoside ratio), [cordyceps](/compound/cordyceps) (oxygen utilization focus), and [schisandra](/compound/schisandra) (liver tonic with adaptogen properties).", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 6421, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/panax-ginseng" }, { "id": "ee915b1d-c1de-4000-a05c-f0e07f351d4b", "slug": "pantothenic-acid", "name": "Pantothenic Acid", "aliases": [ "B5", "Vitamin B5", "Pantothenate", "Calcium pantothenate", "D-calcium pantothenate", "Calcium D-pantothenate", "Sodium pantothenate", "D-pantothenic acid", "(R)-pantothenic acid", "Dexpanthenol", "D-panthenol", "Panthenol", "Provitamin B5", "Pantethine", "Bis(pantetheine) disulfide", "Pantetheine", "4'-phosphopantetheine", "Coenzyme A precursor", "CoA precursor", "Pantoyl-beta-alanine" ], "category": "Vitamin", "description": "\nPantothenic acid is the water-soluble B-complex vitamin — officially vitamin B5 — that every aerobic cell on the planet converts into Coenzyme A (CoA) and the 4'-phosphopantetheine prosthetic arm of acyl carrier protein (ACP). The name comes from the Greek \"pantothen,\" meaning \"from everywhere,\" a nod to its ubiquity in plant and animal foods and the near-impossibility of developing deficiency on a varied diet. Roger Williams isolated and named it at Oregon State in 1933 while hunting the yeast growth factor responsible for pellagra-adjacent syndromes; Fritz Lipmann's 1953 Nobel laureate work on Coenzyme A finally explained why this pale-yellow acid sat at the center of intermediary metabolism. Essentially every reaction that makes, breaks, or transfers a two-carbon acyl group — from acetyl-CoA feeding the TCA cycle to succinyl-CoA stoking heme synthesis to acetyl-CoA carboxylase (ACC, a [biotin](/compound/biotin) enzyme) committing carbons to fatty acid synthesis — requires a pantothenate-derived thiol handle. Without B5, the central metabolic hub simply does not spin.\n\nStructurally pantothenic acid is a conjugate of D-pantoic acid and β-alanine linked through an amide bond. Humans cannot synthesize it and must obtain it from diet; the RDA is a modest 5 mg/day for adults, and the Institute of Medicine has not set a tolerable upper limit because toxicity is exceedingly rare at intakes up to several grams per day. Whole grains, eggs, organ meats, legumes, avocados, mushrooms, sweet potato, sunflower seeds, broccoli, and fermented dairy all provide generous amounts; food processing and alkaline cooking water destroy a portion, and prolonged frozen storage incrementally degrades it. Intestinal absorption occurs via the sodium-dependent multivitamin transporter SMVT (gene SLC5A6), the same carrier that transports [biotin](/compound/biotin) and [alpha-lipoic acid](/compound/alpha-lipoic-acid) — a shared logistics pipeline that creates the theoretical concern that megadose biotin might competitively inhibit pantothenate uptake, though no clinically meaningful case of this has been documented. Once absorbed, pantothenate is not stored in any meaningful depot; free pantothenate circulates in plasma at low micromolar concentrations, while tissues hold the vitamin almost entirely as CoA and its acyl-thioester derivatives (acetyl-CoA, malonyl-CoA, succinyl-CoA, palmitoyl-CoA, HMG-CoA, acyl-CoA intermediates).\n\nInside cells pantothenate is funneled through a five-step biosynthesis to CoA. Pantothenate kinase (PANK, encoded by PANK1-4) performs the committed, rate-limiting phosphorylation to 4'-phosphopantothenate. PPCS and PPCDC ligate cysteine and decarboxylate to yield 4'-phosphopantetheine. PPAT adds AMP, and DPCK phosphorylates to finish the molecule. Loss-of-function mutations in PANK2 cause pantothenate kinase-associated neurodegeneration (PKAN), historically called Hallervorden-Spatz disease, a devastating autosomal recessive disorder of childhood-onset dystonia, pigmentary retinopathy, and iron deposition in the globus pallidus producing the pathognomonic \"eye-of-the-tiger\" MRI sign. PMID 11479594 (Zhou, Nature Genetics 2001) cloned the PANK2 gene; mutations in CoASY — the bifunctional enzyme that completes CoA biosynthesis — cause a closely related syndrome called CoPAN (PMID 24183309). Both diseases sit within the larger spectrum called neurodegeneration with brain iron accumulation (NBIA), and both illustrate that when CoA biosynthesis falters even locally, neurons suffer catastrophically. Pantethine and 4'-phosphopantetheine rescue experiments in model systems have motivated ongoing trials of fosmetpantotenate and CoA-replacement strategies (fosmetpantotenate's key FORT trial in 2019 unfortunately did not meet its primary endpoint), but the biology robustly establishes why B5 sits at the foundation of cellular metabolism.\n\nThe metabolic reach of CoA is almost impossible to overstate. Acetyl-CoA is the universal two-carbon currency produced from pyruvate (by the [thiamine](/compound/thiamine)-dependent pyruvate dehydrogenase complex), from β-oxidation of fatty acids (by acyl-CoA dehydrogenases using FAD from [riboflavin](/compound/riboflavin)), from ketone body catabolism, and from ketogenic amino acid degradation. Acetyl-CoA then feeds the TCA cycle via citrate synthase, donates acetyl groups to histone acetyltransferases writing the histone acetylation code that regulates gene expression, acetylates hundreds of non-histone proteins regulating everything from metabolism to autophagy, is the starting substrate for de novo cholesterol synthesis (via HMG-CoA reductase, the statin target), is the precursor for ketogenesis during fasting, and is the carbon source for fatty acid biosynthesis (through malonyl-CoA generated by ACC, the [biotin](/compound/biotin) carboxylase). Succinyl-CoA feeds heme synthesis (via δ-ALA synthase) and the GABA shunt. Acyl-CoAs drive protein acylation (palmitoylation, myristoylation) anchoring signaling proteins to membranes. The 4'-phosphopantetheine arm, covalently tethered to serine residues on acyl carrier protein (ACP) in fatty acid synthase and on peptidyl carrier protein domains in non-ribosomal peptide synthetases, is the swinging boom that shuttles growing acyl and peptidyl intermediates between catalytic domains — a physical shuttle that depends on B5 being present in sufficient quantity. Every cell, every day.\n\nPantothenic acid is commercially available in three main forms. Calcium D-pantothenate is the most common, a stable white crystalline salt used in food fortification and most multivitamins. D-pantothenic acid free acid is hygroscopic and less convenient. Dexpanthenol (D-panthenol) is the alcohol analog that is rapidly oxidized to pantothenate in vivo; it is the workhorse of topical dermatology (Bepanthen cream, Panthenol foam, nasal sprays, eye ointments) and provides well-documented moisturizing, barrier-restoring, and wound-healing effects on skin, mucous membranes, and hair shaft. Pantethine is pantetheine-disulfide, the dimeric form of 4'-phosphopantetheine's precursor; it bypasses PANK regulation and can raise intracellular CoA more efficiently than pantothenate at equimolar dose. A body of older Italian and Japanese literature ( Rumberger meta-analysis EFSA scientific opinion context) documented 10–15% reductions in LDL and triglycerides with 900 mg/day pantethine — modest effects by modern standards but real and sustained in small trials. A 2014 randomized controlled trial by Rumberger and colleaguesof 120 low-to-moderate cardiovascular risk subjects on a TLC diet showed pantethine 600 mg/day for 16 weeks produced a 4% LDL and 11% triglyceride reduction vs. placebo, reaching statistical significance. Pantethine is not a statin and should not be framed as one, but it is an interesting adjunct with a tolerability profile dramatically better than niacin.\n\nDeficiency is the exception, not the rule. Controlled depletion studies in conscientious objectors during the 1950s, and in POWs during WWII, produced the classic \"burning feet syndrome\" (dysesthesias in the plantar surfaces), mood changes, fatigue, and eventually peripheral neuropathy — but only after weeks of semi-synthetic diets deliberately free of B5, sometimes combined with the pantothenate antagonist ω-methyl-pantothenate. No endemic B5 deficiency exists in modern populations. Subclinical insufficiency may contribute to symptomatology in severe malabsorption syndromes (Crohn's, short bowel, celiac), alcohol use disorder (impaired absorption and increased turnover), and rare inherited pantothenate kinase and CoASY mutations described above. The supplement industry's \"adrenal fatigue\" narrative — claiming pantothenic acid supports stressed adrenals because steroidogenesis uses CoA — is reductionist and unsupported by controlled trials; adrenal steroid hormone production is CoA-dependent but is not rate-limited by pantothenate at normal dietary intakes. Stress physiology matters, but B5 megadosing is not its solution.\n\nTwo niche clinical literatures are worth honest framing. First, acne: Leung's 1995 open-label trial ( conceptual echo; original J Orthomolecular Med) of 10,000 mg/day calcium pantothenate in 100 acne patients reported dramatic lesion reduction within 4–8 weeks, a finding replicated by a small 2012 placebo-controlled study (Yang et al., J Cosmetic Dermatol) in 48 subjects using a pantothenic-acid-based supplement showing roughly 50% lesion reduction at 12 weeks. The mechanistic story — that CoA limitation impairs sebum fatty acid elongation and drives follicular hyperkeratinization — is chemistry-plausible but not rigorously proven, and the enormous doses required (10 g/day) raise questions about which bioactive is actually responsible. Second, dermatology: dexpanthenol 5% cream is one of the best-studied OTC wound-healing and barrier-restoring agents; Proksch 2017 complete reviewsynthesized 57 studies showing reliable benefit for atopic dermatitis, irritant dermatitis, diaper rash, and post-procedure skin recovery. These are real topical effects and do not imply systemic B5 deficiency.\n\nBodyHackGuide's take: pantothenic acid is the quiet foundation of nearly every metabolic pathway you improve with other nutrients. You cannot out-train, out-supplement, or out-biohack a CoA deficit, but given how abundant B5 is in food, you almost certainly do not have one. A B-complex providing 10–100 mg/day is reasonable insurance and carries essentially zero risk; pantethine 600–900 mg/day is a legitimate lipid-modifying option with a decent evidence base for the patient who does not tolerate or qualify for statins; dexpanthenol topical is a first-line dermatology tool. Mega-dose calcium pantothenate for acne sits in the \"interesting but unproven\" bucket — it is low-risk but should not supplant tretinoin, benzoyl peroxide, or isotretinoin for moderate-to-severe disease. Pantothenic acid belongs alongside [thiamine](/compound/thiamine), [riboflavin](/compound/riboflavin), [niacin](/compound/niacin), [vitamin B6](/compound/vitamin-b6), [biotin](/compound/biotin), [folate](/compound/folate), and [vitamin B12](/compound/vitamin-b12) as the chassis of the B-complex — not because any of them are glamorous, but because cellular energetics collapse without them.\n", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 4023, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/pantothenic-acid" }, { "id": "727113af-74a4-42d3-9dfa-0e7896fb85f9", "slug": "papain", "name": "Papain", "aliases": [ "Papaya proteinase I", "Carica papaya latex", "EC 3.4.22.2", "Papayotin" ], "category": "Enzyme", "description": "**Papain** is a proteolytic enzyme extracted from the milky latex of the unripe fruit of the papaya tree (*Carica papaya*), a tropical plant native to southern Mexico and Central America and now cultivated across the tropics. It is classified biochemically as a **cysteine protease** (EC 3.4.22.2) — meaning that its catalytic machinery depends on a reactive cysteine residue at its active site — and is approximately **23 kilodaltons** in molecular mass, consisting of a single 212-amino-acid polypeptide chain folded into two distinct domains separated by a catalytic cleft. Papain is the archetypal member of the **papain-like cysteine protease superfamily** (clan CA, family C1), which encompasses hundreds of enzymes across plants, animals, and microorganisms, including cathepsins B, L, S, K, and H in mammalian lysosomes, bromelain from pineapple stem and fruit, ficin from fig latex, and the actinidin from kiwifruit. Historically, papain was one of the first enzymes to be isolated in pure crystalline form and one of the first proteases whose three-dimensional structure was solved by X-ray crystallography (Drenth et al., *Nature* 1968), making it a foundational tool in the development of twentieth-century protein biochemistry and enzyme kinetics. The aliases **\"Papaya proteinase I\"**, **\"Papayotin\"** (an older pharmaceutical name), and **\"Carica papaya latex\"** all refer to the same or closely related enzyme preparations.\n\n**The single most important framing for anyone considering papain, stated up front**: In **February 2008**, the **US Food and Drug Administration issued a MedWatch safety alert and required manufacturers to stop marketing all unapproved topical papain-containing drug products**, most notably papain-urea wound-debridement ointments that had been sold in the United States for decades as over-the-counter and prescription enzymatic debriding agents. The FDA cited **serious adverse events including hypotension, tachycardia, and anaphylaxis** attributable to topical papain exposure on open wounds. Prior to the 2008 ban, papain-urea products (brand names including *Accuzyme*, *Gladase*, *Panafil*, *Kovia*, *Ethezyme*, among others) were widely used for debridement of necrotic tissue in pressure ulcers, diabetic foot ulcers, venous stasis ulcers, and burns. Within months of the FDA action, **all topical papain prescription and OTC products were withdrawn from the US market**. Papain-urea wound debriding products are **no longer FDA-approved and are no longer legally sold as drugs in the United States**. This is not a hypothetical or theoretical safety concern — it is a regulatory action taken by the FDA after a specific pattern of reported adverse events, and it fundamentally reshaped how papain is viewed as a therapeutic agent. Any content, blog, or vendor website that continues to promote topical papain-urea as a wound-debriding agent without acknowledging the 2008 FDA action is operating outside current US regulatory reality.\n\nBeyond the 2008 FDA topical ban, there is a second critical safety context: **latex-fruit syndrome cross-reactivity**. Patients who are allergic to natural rubber latex (which comes from the *Hevea brasiliensis* tree, not papaya) show cross-reactivity to several tropical fruits including papaya, avocado, banana, kiwi, and chestnut, through shared IgE-binding epitopes in class I chitinases and other pathogenesis-related proteins. Because papain is derived from papaya latex, individuals with natural rubber latex allergy have elevated risk of IgE-mediated hypersensitivity reactions to both oral and topical papain — including urticaria, angioedema, bronchospasm, and anaphylaxis. This cross-reactivity is well-documented in allergology literature and is a practical screening consideration before any papain use.\n\n**Historical and current uses of papain span several domains with dramatically different evidence bases**: **(1) Industrial meat tenderization** — papain is widely used in commercial meat processing as an enzymatic tenderizer, applied by direct application, marinade, or intramuscular injection (in pre-slaughter livestock, in some jurisdictions) to hydrolyze collagen and muscle proteins. This is the dominant commercial use by volume and is not controversial — papain's ability to hydrolyze mammalian collagen and muscle fibers is well-established industrial enzymology. **(2) Oral digestive-enzyme supplementation** — papain is sold as a digestive aid in capsules, tablets, and combination enzyme products, often alongside bromelain (pineapple protease), trypsin, chymotrypsin, pancreatin, and lipase. Evidence for clinical digestive benefit is weak; the enzyme is largely denatured by gastric hydrochloric acid and pepsin unless enterically coated. **(3) Historical topical wound debridement** — discussed above; **banned by FDA in 2008** for US drug marketing. **(4) Anti-inflammatory / sports-injury / bruising** — older trials (1960s-80s) tested papain or enzyme blends for post-surgical swelling, sports injuries, and bruising; methodological quality was generally poor by modern standards. **(5) Brewing and textile industries** — papain is used to prevent chill-haze in beer (hydrolyzing haze-forming proteins) and in wool/silk processing. **(6) Biochemical research tool** — papain is a standard laboratory reagent for generating Fab and Fc fragments from antibodies, for cell dissociation in tissue culture, and as a model enzyme in kinetics and structural biology teaching.\n\n**Evidence-honesty on digestive benefit**: Despite widespread marketing of papain as a digestive aid, **the clinical evidence for oral papain providing meaningful digestive benefit in healthy adults is weak**. The key issue is **gastric denaturation**: papain's optimal activity is at pH 5-7; at the strongly acidic pH of the stomach (pH 1.5-3), papain is largely inactivated. Enterically coated preparations (designed to release in the alkaline small intestine rather than dissolve in the stomach) partially address this, but even then the clinical evidence for benefit in indications like \"bloating,\" \"gas,\" or \"improved digestion\" is thin. Placebo-controlled trials specifically isolating papain are scarce; most positive trials used multi-enzyme blends making it impossible to attribute effect to papain specifically. For individuals with actual pancreatic exocrine insufficiency (cystic fibrosis, chronic pancreatitis, post-Whipple), the evidence-based treatment is **pharmaceutical pancreatic enzyme replacement therapy** (pancrelipase products like Creon, Zenpep, Pertzye — all FDA-approved) — **not papain supplements**. Papain is not an appropriate substitute for prescription pancreatic enzymes in diagnosed pancreatic disease.\n\n**Evidence-honesty on sports-injury / anti-inflammatory claims**: A small number of older, methodologically weak trials (often from the 1960s-1980s, often open-label or with small sample sizes, often using multi-enzyme blends rather than isolated papain) suggested that systemic proteases — papain, bromelain, or combination enzyme products like *Wobenzym* — might reduce post-surgical swelling, bruising, or recovery time from sports injuries. **Modern, rigorous, placebo-controlled RCTs specifically for oral papain have not consistently replicated these findings**, and the proposed mechanism (systemic anti-inflammatory activity of orally administered intact enzyme) has a fundamental pharmacokinetic problem: the amount of intact papain that reaches systemic circulation after oral administration is very small, particularly without enteric coating. This does not mean papain has no effect, but it does mean that strong clinical efficacy for sports-injury and anti-inflammatory indications is **not established** by the standards of modern evidence-based medicine.\n\n**Chemistry and structure**: Papain's three-dimensional structure, first solved by Drenth and colleagues in 1968, revealed a bilobal enzyme with two domains (the L-domain and R-domain) separated by a cleft containing the active site. The catalytic machinery is a classical **cysteine-histidine-asparagine triad** — **Cys25, His159, and Asn175** in the mature enzyme — in which the cysteine's thiol group acts as the nucleophile attacking the substrate peptide bond, the histidine acts as a general base abstracting a proton, and the asparagine stabilizes the histidine orientation. This catalytic architecture is structurally distinct from the serine proteases (trypsin, chymotrypsin, elastase; Ser-His-Asp triad) despite catalyzing analogous hydrolysis reactions. Papain has broad substrate specificity — it hydrolyzes peptide bonds in a wide range of proteins with a general preference for bulky hydrophobic residues (phenylalanine, tryptophan, valine) at the P2 position. It is **activated** by reducing agents (cysteine, dithiothreitol, glutathione) that keep its catalytic cysteine in the reduced thiol state, and **inhibited** by oxidizing agents, heavy metal ions (mercury, lead, silver — which bind thiols), and specific cysteine-protease inhibitors (E-64, iodoacetic acid, cystatins).\n\n**Production and purification**: Commercial papain is produced by tapping the green (unripe) papaya fruit — making shallow incisions in the skin with a knife or comb-like tool — and collecting the milky latex that exudes. The raw latex is dried and processed to yield crude papain, which may be further purified by ammonium sulfate precipitation, ion-exchange chromatography, and affinity chromatography to produce laboratory-grade enzyme with higher specific activity. Commercial papain product grades vary widely — food-grade, technical-grade, pharmaceutical-grade, and USP-reference-grade — with corresponding variation in contaminant levels (other papaya latex enzymes, plant debris, microbial contamination). Lower-grade papain products may contain additional papaya proteases (chymopapain, caricain, glycyl endopeptidase) as well as non-protease contaminants.\n\n**Context within the protease landscape**: Papain is often sold alongside or confused with bromelain, the pineapple-derived cysteine protease mixture from *Ananas comosus* stem and fruit. The two are distinct enzymes with distinct substrate specificities and regulatory histories; bromelain has more extensive (though still limited) clinical trial data for certain indications, while papain's clinical research base is thinner and its topical medicinal application was FDA-banned. **Serrapeptase**, another proteolytic enzyme, is derived from bacterial sources (*Serratia*) and represents yet another distinct enzyme with its own evidence base and safety profile. Related plant proteases include **ficin** (fig) and **actinidin** (kiwifruit). See also [curcumin](/compound/curcumin), [boswellia](/compound/boswellia), and [quercetin](/compound/quercetin) for plant-derived anti-inflammatory compounds with substantially stronger clinical evidence bases than papain; [ashwagandha](/compound/ashwagandha), [rhodiola-rosea](/compound/rhodiola-rosea), and [tulsi](/compound/tulsi) for better-studied adaptogens; [berberine](/compound/berberine) for metabolic effect; [probiotics](/compound/probiotics) for digestive health (with more coherent clinical framing than papain); and [bpc-157](/compound/bpc-157) for tissue-recovery peptide research.\n\n**Honest positioning**: Papain is a genuinely important enzyme in industrial biotechnology and classical biochemistry, with a rich structural and kinetic history. As a therapeutic agent — whether topical or oral — its role is more constrained than marketing implies. The FDA's 2008 ban on topical papain-urea drug products eliminated its principal medicinal application in the United States. For oral digestive enzyme supplementation, evidence for clinical benefit is weak and prescription pancreatic enzyme replacement products are the evidence-based choice for diagnosed enzyme insufficiency. For anti-inflammatory and sports-injury applications, the clinical evidence does not meet modern RCT standards. Against this backdrop, papain carries real allergy and anaphylaxis risks — particularly in patients with latex allergy, prior papaya exposure reactions, or history of enzyme sensitivity. Any prospective user of papain should understand these evidence limitations and safety realities before proceeding, and should **never use any residual, grey-market, or imported topical papain-urea wound product in the United States** — these are unapproved drugs and carry the specific FDA-cited risks that prompted the 2008 withdrawal. This is educational content and not medical advice; clinical decisions around papain should involve a physician, particularly for patients with any history of drug allergy, food allergy, latex allergy, prior enzyme sensitivity, asthma, or other atopic conditions.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 41, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/papain" }, { "id": "57e97bac-4b53-4d9d-9ff6-55e183998b98", "slug": "pdrn", "name": "PDRN", "aliases": [ "Polydeoxyribonucleotide", "Placentex", "Nucleofill", "Salmon DNA", "Nucleotide polymer" ], "category": "Skin & Hair", "description": "PDRN (Polydeoxyribonucleotide) is a biotechnological compound derived from salmon sperm DNA (Oncorhynchus mykiss) through extraction, purification, and fractionation. It consists of polynucleotide chains with molecular weights ranging from 50 to 1500 kDa. PDRN is widely used in Asian aesthetic medicine (particularly South Korea) for skin rejuvenation, wound healing, and hair loss treatment. It is available as an injectable sterile solution (Placentex Integro) licensed in several countries, as well as topical formulations and cosmetic creams. PDRN's mechanism centers on adenosine A2A receptor activation, stimulating collagen synthesis, cellular proliferation, and anti-inflammatory pathways. It is one of the few compounds in this catalog with a substantial published clinical (Phase 4) evidence base in aesthetic applications.", "half_life": "Short (oligonucleotides degraded rapidly; tissue effects persist longer)", "molecular_weight": "No single value - PDRN is a heterogeneous mixture of deoxyribonucleotide polymers (chain lengths ~50-2000 bp, roughly 50-1500 kDa) rather than one defined molecule [PMID:19860658].", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [ "Subcutaneous", "Intradermal", "Topical" ], "dose_range_mcg": "0", "dosing_frequency": "weekly", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Phase 4", "approval_status": "Not FDA-approved in the US (research use only). Approved and marketed abroad as a drug or medical device for tissue repair and aesthetic indications (e.g., Placentex in Italy; PDRN products in South Korea).", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Wound healing acceleration - enhanced angiogenesis, fibroblast proliferation, and collagen synthesis", "Diabetic foot ulcer healing - supported by a randomized, double-blind, placebo-controlled trial (complete healing 37.3% vs 18.9% for placebo) [PMID:24483158]", "Skin rejuvenation - clinical studies suggest improved texture and elasticity, though a 2024 systematic review found the aesthetic evidence base inconsistent [PMID:39198280]", "Hair loss - preliminary evidence only; a small uncontrolled study in female pattern hair loss reported improved hair count and thickness (not established for androgenetic alopecia) [PMID:25524027]", "Anti-inflammatory tissue remodeling - reduction of pro-inflammatory cytokines via adenosine A2A receptor signaling", "Aesthetic skin treatments - widely used in South Korean and European clinical practice" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/pdrn" }, { "id": "3a095e0b-ad36-486f-bacc-3f566516142d", "slug": "pe-22-28", "name": "PE-22-28", "aliases": [ "PE2228" ], "category": "Nootropics", "description": "PE-22-28 is a synthetic seven-amino-acid peptide (sequence PAGASRLLLLTGEIDLP derivative, commonly truncated to PE-22-28 as shorthand for \"position 22-28\" within the parent humanin-family sequence) that was designed as an analog of [Humanin](/compound/humanin) with specific interest in activity at glutamate transporter regulation and cytoprotective signaling relevant to depression and neuroprotection. The peptide emerged from a research program characterizing short analogs of humanin that retain bioactivity while simplifying the structure for synthetic accessibility and potential therapeutic development. PE-22-28 specifically attracted attention when preclinical work suggested antidepressant-like activity in rodent models of depression, with a proposed mechanism involving glial cell modulation and glutamate transporter 1 (GLT-1/EAAT2) regulation. The compound sits in the broader field of peptide-based neuropsychiatric therapeutics, alongside compounds like [Selank](/compound/selank) and [Semax](/compound/semax) that have been used in Russia for decades but remain investigational in Western markets. PE-22-28 is distinctive within this space because of its mechanistic grounding in humanin biology and glutamate homeostasis, which connects it to contemporary understanding of depression pathophysiology that emphasizes the role of glutamatergic signaling, astrocyte function, and neuroinflammation alongside the classical monoamine framework. The practical reality in April 2026 is that PE-22-28 remains a preclinical research peptide with limited published literature, no approved human use, no registered clinical trials, and a small but active self-experimentation community among biohackers interested in short peptide therapeutics for mood and cognitive applications. The compound is sold by research-chemical peptide vendors with the standard \"for research purposes only\" framing, and individual users have accumulated anecdotal experience with it in protocols typically involving daily or every-other-day subcutaneous dosing. The evidence base for PE-22-28 is substantially thinner than for [BPC-157](/compound/bpc-157), [Selank](/compound/selank), or [Semax](/compound/semax) in terms of published animal studies and translational groundwork; the peptide's profile rests on specific rodent behavioral studies and mechanistic biology inferred from its relationship to humanin and its proposed interactions with glutamate transporter regulation. This entry covers what is published about the peptide, the mechanistic rationale connecting it to humanin biology and glutamate homeostasis, the specific preclinical behavioral data that sparked interest in depression applications, realistic interpretation of that data in the context of the replication crisis in preclinical depression research, the theoretical and practical concerns with self-administration of a minimally characterized peptide, how PE-22-28 fits into the peptide stacking landscape alongside other cytoprotective and neuropsychiatric peptides, and what conservative thinking about this molecule looks like for someone considering it seriously rather than as a novelty.", "half_life": "Not characterized in humans. As a small 7-amino-acid peptide a short plasma half-life is expected; in mice the parent peptide spadin lost antidepressant activity by about 7 hours after a single dose, while modified analogs (e.g., G/A-PE 22-28) extended the behavioral effect to roughly 21-23 hours [PMID:28955242].", "molecular_weight": "773.9 g/mol", "molecular_mass": "773.9 g/mol (average; molecular formula C35H55N11O9)", "amino_acid_sequence": "GVSWGLR (Gly-Val-Ser-Trp-Gly-Leu-Arg) - an unmodified 7-residue peptide corresponding to residues 22-28 of the 44-amino-acid sortilin/neurotensin receptor-3 (NTSR3) propeptide. It is the C-terminal fragment of spadin (spadin = PE 12-28).", "administration_routes": [], "dose_range_mcg": "250-2000 mcg subcutaneous per dose (empirical research-chemical community range; no clinically validated human dose exists; effective preclinical rodent doses were far lower, ~3 mcg/kg).", "dosing_frequency": "Once daily or every other day (research-chemical community protocols; no validated clinical dosing schedule).", "cycle_length": "Community protocols run roughly 4-12 week cycles with 2-4 week breaks between them; this is convention, not clinically validated.", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Not approved for any indication. Preclinical (rodent) research only; sold as a research-use-only (RUO) chemical.", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "C141H237N43O40S", "potential_benefits": [ "Antidepressant-like effects in rodent models of depression (preclinical only)", "Potent, selective inhibition of the TREK-1 (K2P2.1) potassium channel (IC50 ~0.12 nM)", "Rapid-onset (~4-day) antidepressant profile in animals, unlike the multi-week lag of SSRIs", "Increased hippocampal neurogenesis in mice", "Increased cortical synaptogenesis (PSD-95) and BDNF expression in preclinical studies", "No human-validated benefits; not approved for any use (research use only)" ], "research_fields": [], "pubmed_count": 1, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/pe-22-28" }, { "id": "9f88088a-4853-41dd-8dd9-cca3753a7d08", "slug": "peg-mgf", "name": "PEG-MGF", "aliases": [ "Pegylated Mechano Growth Factor", "PEGylated IGF-1 Ec", "MGF", "Mechano Growth Factor", "IGF-1 splice variant" ], "category": "Performance", "description": "PEG-MGF (Pegylated Mechano Growth Factor) is a synthetic, PEGylated form of Mechano Growth Factor (MGF) — an alternatively spliced variant of IGF-1 produced locally in muscle and other tissues in response to mechanical loading or damage. MGF differs from systemic IGF-1 in that it has a unique E-domain peptide (the Ec peptide, or MGF peptide) that activates satellite cells (muscle stem cells) rather than IGF-1 receptor signaling. Pegylation (attachment of polyethylene glycol chains) dramatically extends MGF's plasma half-life from minutes to approximately 24 hours, enabling systemic administration in research protocols. PEG-MGF is researched primarily for its muscle satellite cell activation, tissue repair, and recovery applications.", "half_life": "Native MGF: very short (minutes) due to rapid proteolysis. PEG-MGF: PEGylation is intended to extend this substantially (community estimates up to roughly 1 day), but there are no published human pharmacokinetic data to confirm a specific value.", "molecular_weight": "Free MGF 24-aa peptide: approximately 2,867-2,868 Da (reported molecular formula ~C121H199N41O40). PEG-MGF is heavier: the conjugated polyethylene glycol adds a variable mass (commonly a few kDa) on top of the peptide, so total mass depends on the PEG used.", "molecular_mass": "Free peptide approximately 2,867-2,868 Da (24-aa MGF E-peptide). The total mass of PEG-MGF is greater and is not standardized - it depends on the size of the attached PEG chain.", "amino_acid_sequence": "YQPPSTNKNTKSQRRKGSTFEERK - the human MGF / IGF-1Ec C-terminal 24-amino-acid E-domain peptide (Tyr-Gln-Pro-Pro-Ser-Thr-Asn-Lys-Asn-Thr-Lys-Ser-Gln-Arg-Arg-Lys-Gly-Ser-Thr-Phe-Glu-Glu-Arg-Lys). PEG-MGF is this same peptide covalently conjugated to a polyethylene glycol (PEG) moiety to slow proteolytic degradation.", "administration_routes": [ "Subcutaneous", "Intramuscular", "Intravenous" ], "dose_range_mcg": "200", "dosing_frequency": "twice_weekly", "cycle_length": "", "common_vial_sizes": [ "2" ], "research_stage": "Preclinical", "approval_status": "Not approved for human use - research use only. No FDA or EMA approval and no human clinical trials. Prohibited in sport by WADA (S2: peptide hormones, growth factors and mimetics).", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Increases satellite-cell and myoblast proliferation, expanding the cell pool available for muscle repair (in vitro and animal studies)", "May accelerate muscle repair after exercise-induced damage or injury (preclinical)", "Pro-survival, anti-apoptotic signaling reported in muscle and other cell types (preclinical)", "Preclinical cytoprotection: MGF pretreatment improved cardiac function after experimental myocardial infarction (mechanism distinct from IGF-1R, NOT via fibroblast growth factor receptor)", "Preclinical neuroprotection during cerebral ischemia", "PEGylation is intended to extend native MGF's very short half-life to allow less frequent research dosing" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/peg-mgf" }, { "id": "491ccb18-a01f-437b-87f0-f52985d12456", "slug": "phenibut", "name": "Phenibut", "aliases": [ "β-phenyl-γ-aminobutyric acid", "beta-phenyl-GABA", "Noofen", "Anvifen", "Fenibut", "Фенибут", "phenigamma", "phenybut" ], "category": "Nootropics", "description": "Phenibut is the common Western name for **β-phenyl-γ-aminobutyric acid** (beta-phenyl-GABA; Russian trade names *Phenibut*/*Фенибут*, *Noofen*, *Anvifen*), a Soviet-era anxiolytic and nootropic developed in the 1960s at the Herzen State Pedagogical Institute in Leningrad under Vsevolod Vasilievich Perekalin. Structurally, it is the GABA molecule with a phenyl ring attached to the β-carbon — a modification that dramatically increases lipophilicity and allows the compound to cross the blood-brain barrier (unlike GABA itself, which does not meaningfully penetrate the CNS after oral dosing). In the Soviet Union and, later, the Russian Federation and several CIS states, phenibut is a prescription medication approved for asthenia, generalised anxiety, pre-operative anxiety, insomnia related to anxiety, post-traumatic stress reactions, vestibular disorders, motion sickness, stuttering, and several pediatric indications. It was reportedly included in the Soviet cosmonaut medical kit in the 1970s — a detail endlessly repeated in online marketing that is often used to imply safety and efficacy, though the actual context (managing acute stress in a highly selected, closely monitored population) is quite different from the way most contemporary users take it.\n\nOutside of Russia and the CIS, phenibut has no regulatory approval. It is not a recognised medicine in the United States, the United Kingdom, the European Union, Canada, or Australia, and it is not listed on any Western pharmacopoeia. Its legal status is fragmented: Australia classifies it as a Schedule 9 prohibited substance; Hungary and several European countries treat it as a controlled substance; Lithuania, Latvia, Finland, and Italy have placed it under medicines regulation; the United Kingdom controls it under the Psychoactive Substances Act 2016. In the United States, phenibut is unscheduled at the federal level but the FDA has formally warned that it does not meet the statutory definition of a dietary supplement under DSHEA, issuing warning letters to multiple vendors in 2019 and 2020 for marketing phenibut-containing products. Despite this, it has been sold online as a nootropic powder or capsule under names like \"Phenibut HCl\" or \"Phenibut FAA\" (free amino acid form) for over a decade, often at doses and in contexts that Russian prescribers would consider grossly inappropriate.\n\nThe core pharmacology of phenibut is that it is a **GABA-B receptor agonist** — in the same receptor family as baclofen and the recreational drug gamma-hydroxybutyrate (GHB) — with weaker activity at GABA-A receptors and some binding to voltage-gated α2δ calcium channels similar to [pregabalin](/compound/pregabalin) and gabapentin. This combination produces anxiolysis, mild sedation, euphoria at higher doses, and — critically — the capacity to produce severe physical dependence and withdrawal after repeated use. Phenibut's withdrawal syndrome closely resembles combined benzodiazepine and alcohol withdrawal, with insomnia, severe rebound anxiety, tremor, perceptual disturbances, and in case reports, seizures and delirium. The withdrawal risk is the single most important thing any prospective user needs to understand, and it is the primary reason phenibut appears on harm-reduction lists and clinician warning pages.\n\nThe Western nootropic community's relationship with phenibut has shifted over the past decade. Early online discussion (roughly 2010-2016) treated it as a relatively benign \"smart drug\" or occasional anxiolytic, often with inadequate attention to tolerance and withdrawal. Over time — as case reports of severe withdrawal accumulated on PubMed (among others) and as poison control centres in Australia, Finland, and the United States began reporting regular phenibut-related calls — the community has become substantially more cautious. Responsible nootropic resources now categorise phenibut as a compound with legitimate short-term use cases (occasional social anxiety, jet-lag-related anxiety, pre-exam stress) but a narrow therapeutic window and a steep risk curve that escalates rapidly with frequency of use. Anyone considering phenibut needs to read the contraindications and protocol sections below before the description.\n\nFor a more rigorously evidence-based approach to anxiety, Western first-line treatments include SSRIs (sertraline, escitalopram), SNRIs (venlafaxine, duloxetine), and cognitive-behavioural therapy, all with substantially more strong trial data than phenibut. For acute situational anxiety in settings where a prescription is available, a single dose of propranolol or a short-acting benzodiazepine under medical supervision carries its own risks but is a better-characterised option. For a stimulant-free anxiolytic with a much lower dependence profile, see [l-theanine](/compound/l-theanine) — it lacks phenibut's potency but does not produce meaningful tolerance or withdrawal. For Russian-origin nootropics with similar geographic provenance but a very different safety profile, see [selank](/compound/selank) and [semax](/compound/semax), which are peptides without the dependence liability. Phenibut is not in the same safety category as any of those compounds and should not be substituted for them without understanding the differences.", "half_life": "5-8 hours (plasma); central CNS effect 10-16 hours", "molecular_weight": "179.22 g/mol (free base); 215.68 g/mol (HCl salt)", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Prescription Medicine (Russia/CIS) / Unregulated Elsewhere", "approval_status": "Approved prescription medicine in Russia, Ukraine, Belarus, Kazakhstan and some CIS states (Фенибут, Noofen, Anvifen). Not FDA approved in US; FDA warned vendors in 2019-2020 that it does not meet DSHEA supplement definition. Schedule 9 prohibited in Australia; controlled under UK Psychoactive Substances Act 2016; scheduled or regulated in several EU states.", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/phenibut" }, { "id": "c3e98209-3a04-458e-bacd-433e2977dd23", "slug": "phenylpiracetam", "name": "Phenylpiracetam", "aliases": [], "category": "Nootropics", "description": "Phenylpiracetam is a Russian-developed phenyl derivative of piracetam with a dramatically higher potency and stimulant profile. Approved in Russia as Phenotropil/Carphedon for cognitive impairment and stroke recovery. Banned by WADA as a performance-improving drug due to its stimulant effects, significantly improving physical endurance in addition to cognition. One of the most potent and sought-after racetam family members.", "half_life": "", "molecular_weight": "", "molecular_mass": "218.25 g/mol", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "Russia Approved", "cas_number": "77472-70-9", "iupac_name": "(RS)-2-(2-oxo-4-phenylpyrrolidin-1-yl)acetamide", "chemical_formula": "C12H14N2O2", "potential_benefits": [ "Cognitive stimulation", "Physical performance", "Memory enhancement", "Cold tolerance", "Motivation", "Anti-convulsant" ], "research_fields": [ "Cognitive impairment", "Stroke recovery", "Depression", "Athletic performance", "Epilepsy" ], "pubmed_count": 1, "pubchem_cid": 9795570, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/9795570/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/phenylpiracetam" }, { "id": "27529e4c-920a-42bb-b96e-d33b14ffe4ac", "slug": "pinealon", "name": "Pinealon", "aliases": [ "EDR" ], "category": "Nootropics", "description": "Pinealon is a **synthetic tripeptide — glutamyl-aspartyl-arginine (Glu-Asp-Arg, or EDR)** — developed by the St Petersburg Institute of Bioregulation and Gerontology (IBG) under the leadership of **Professor Vladimir Khavinson**, the dominant figure in what is collectively known as the \"Russian short-peptide bioregulator\" school of research. Pinealon was designed as a **peptide analog of signaling molecules found in natural extracts of the pineal gland**, specifically a class of bioactive compounds that Khavinson's group began isolating and characterizing in the late 1980s as \"cytomedins\" — short peptides extracted from specific animal tissues and claimed to carry tissue-specific regulatory signals back to the corresponding tissue type.\n\nThe Khavinson framework is as follows: the pineal gland, like other endocrine and parenchymal organs, contains short regulatory peptides that are involved in cell differentiation, gene expression regulation, and tissue homeostasis. When these natural peptides are purified, sequenced, and synthetic analogs are produced (the short-peptide analogs being the most studied), the synthetic peptides retain the ability to influence the same tissue from which they were derived. Pinealon, as the pineal-derived tripeptide bioregulator, is claimed to act on neural tissue — particularly the brain — to support **neuroprotection, cognitive function, circadian regulation, and protection against age-related neurodegeneration**.\n\nA substantial body of **Russian-language clinical and preclinical literature** supports these claims, going back to the 1990s and continuing through 2026. The work has been led by Khavinson and his collaborators at the Mechnikov North-Western State Medical University in St Petersburg, published in Russian medical journals (Uspekhi Gerontologii, Bulletin of Experimental Biology and Medicine) and selected Western journals (Neuroendocrinology Letters, Biogerontology). Outside Russia, Pinealon is part of a broader group of short-peptide bioregulators that includes [Epitalon](/compound/epithalon), [Thymogen](/compound/thymogen), [Thymalin](/compound/thymalin), [Vilon](/compound/vilon), [Livagen](/compound/livagen), and others — each claimed to be organ-specific based on the source tissue of the original natural peptide extract.\n\nThe Western biomedical community has given Khavinson's work a mixed reception. On the positive side, the theoretical framework — that short peptides could function as tissue-specific gene-expression modulators — is scientifically coherent, and a subset of the claims (particularly around **Epitalon** and telomere biology) has attracted genuine interest and some independent replication. On the skeptical side, **the clinical datasets are predominantly Russian, the independent replication of the most dramatic outcomes is thin, the peptides have never been through standard Western regulatory approval processes, and the commercial availability in Russia through the \"Cytogen\" brand (Cytomed) and various gerontology clinics has driven a significant body-hacking export market without corresponding Western clinical validation**.\n\nThis entry takes the honest position that Pinealon — and the broader Russian short-peptide bioregulator category — **represents a plausible mechanism of action with real Russian clinical use, limited Western replication, and a research-grade user experience outside Russia**. It is not FDA-approved, not widely available through Western prescription pharmacies, and carries the full research-chemical status in most Western jurisdictions. Users engaging with Pinealon are effectively trusting Khavinson's lab and its affiliated clinical collaborators, without the standard Western regulatory and replication infrastructure.\n\nFor readers exploring the Khavinson peptide space, see also [Epitalon](/compound/epithalon), [Thymogen](/compound/thymogen), [Cartalax](/compound/cartalax), [Vilon](/compound/vilon), and related entries. For comparison with other short-peptide neuroprotective compounds, see [Cerebrolysin](/compound/cerebrolysin) (a larger neuropeptide preparation), [Semax](/compound/semax) (Russian ACTH-derived peptide), and [Selank](/compound/selank).", "half_life": "Not formally characterized in humans. Short regulatory peptides of this class are cleared from plasma within minutes; the Khavinson framework proposes durable downstream gene-expression effects that outlast the brief dosing window, which is the stated rationale for pulsed cycling rather than continuous dosing.", "molecular_weight": "418.40 g/mol (C15H26N6O8)", "molecular_mass": "418.40 g/mol", "amino_acid_sequence": "Glu-Asp-Arg (EDR)", "administration_routes": [], "dose_range_mcg": "Subcutaneous (primary route): 2-10 mg/day, typically 3-5 mg, in pulsed 10-20 day cycles, 2-4 cycles/year. Intranasal: 150-800 mcg per nostril daily. Research use only; oral dosing is not recommended because the peptide is largely degraded by GI proteases.", "dosing_frequency": "Once daily during a cycle (morning preferred); some advanced users split into AM + midday doses. Not dosed continuously year-round - cycles are pulsed.", "cycle_length": "10-20 days per cycle (up to 20-30 days in advanced use); 2-4 cycles per year separated by 60-90+ day washouts.", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "L-Glutamyl-L-aspartyl-L-arginine", "chemical_formula": "Glu-Asp-Arg", "potential_benefits": [ "Neuroprotection against oxidative and hypoxic stress (preclinical models)", "Antioxidant support - reduced oxidative DNA damage in aged neurons (in vitro)", "Cognitive and memory support in aging populations (small Russian clinical reports)", "Reduced neuronal apoptosis and support of dendritic-tree integrity in cell models", "Investigated for neuroprotection in Alzheimer's-model systems (preclinical)" ], "research_fields": [], "pubmed_count": 21, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/pinealon" }, { "id": "4e5c2ad0-c03b-4d6d-8e0f-9100111a0ba4", "slug": "pineleon", "name": "Pineleon", "aliases": [ "Pinealon Blend", "Pineal Bioregulator", "Pin-Leon", "Pineleon Stack" ], "category": "Bioregulator Peptide", "description": "Pineleon is a **multi-peptide bioregulator blend** combining motifs from the Khavinson-school short peptides — typically [Pinealon](/compound/pinealon) (Glu-Asp-Arg, a pineal-gland-derived tripeptide) along with epigenetic-tier short peptides like Epitalon and Cortexin-derived sequences. The blend is positioned as an anti-aging cognitive bioregulator targeting circadian rhythm regulation, telomerase activation, and neurotrophic support in a single shot.\n\nThe theoretical framework comes from the Russian bioregulator-peptide tradition (Khavinson, St. Petersburg Institute of Bioregulation and Gerontology). Western peer-reviewed validation of the specific blend is limited; constituent peptides have more individual research backing than the combination as such.", "half_life": "~variable (constituent peptides range 30 min to several hours)", "molecular_weight": "No single value (multi-peptide blend). Constituent short peptides: Pinealon (Glu-Asp-Arg) ~418.4 Da; Epitalon (Ala-Glu-Asp-Gly) ~390.4 Da; cortical polypeptide fraction is an undefined mixture (<10 kDa).", "molecular_mass": "", "amino_acid_sequence": "Blend - no single sequence. Pinealon: Glu-Asp-Arg (EDR). Epitalon: Ala-Glu-Asp-Gly (AEDG). Cortexin: undefined mixed cortical polypeptide fraction.", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Not approved for human use (research use only)", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": null, "potential_benefits": [], "research_fields": [], "pubmed_count": 2, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/pineleon" }, { "id": "fed01f95-64d3-4cd7-a7e4-707f1eeded5b", "slug": "piperine", "name": "Piperine", "aliases": [ "Bioperine", "Black pepper extract", "1-Piperoylpiperidine", "(E,E)-Piperine" ], "category": "Herbal", "description": "**Piperine** is the pungent alkaloid of **black pepper (Piper nigrum)** — the compound responsible for pepper's characteristic heat and aroma — and it has become one of the single most important adjuvants in the modern supplement industry not because of any direct clinical effect of its own, but because of its notable ability to **increase the oral bioavailability of dozens of co-administered drugs, herbs, and nutrients**. At practical supplement doses (typically 5-20mg as standardized **Bioperine** extract), piperine is the reason your [curcumin](/compound/curcumin) capsule is paired with \"black pepper extract,\" the reason your [quercetin](/compound/quercetin) is labeled \"with Bioperine,\" and the reason so many stack products reach meaningful plasma levels of otherwise poorly-absorbed polyphenols. Understanding piperine is, more than anything else, understanding **why** and **when** bioavailability enhancement matters — and, just as importantly, why that same mechanism creates real drug-interaction risk that most supplement labels understate.\n\nChemically, piperine is **1-piperoylpiperidine** — an amide formed between piperic acid and the cyclic secondary amine piperidine, with an (E,E)-configured conjugated diene bridging a methylenedioxyphenyl (piperonyl) ring. It is a pale yellow crystalline solid, poorly water-soluble, reasonably fat-soluble, and present at roughly **3-9% by weight** in dried whole black pepper berries and slightly higher in white pepper. Long black pepper (*Piper longum*) contains piperine plus a closely related alkaloid **piplartine (piperlongumine)** that has attracted independent attention as a senolytic and anticancer research tool — although that's a different molecule with a different risk profile, and the commercial \"piperine\" used in supplements is essentially always the *Piper nigrum* extract, standardized to **≥95% piperine** in the case of the trademarked **Bioperine** product (Sabinsa Corporation, established 1996).\n\nThe **single paper that made piperine famous in the supplement world** is **Shoba et al. 1998** (*Planta Medica* PMID: 9619120) — a small but landmark pharmacokinetic study showing that **co-administration of 20mg piperine with 2g curcumin raised curcumin bioavailability by approximately 2000%** in humans relative to curcumin alone. That single headline number — \"2000 percent increase\" — has been repeated in curcumin marketing copy for nearly three decades, and it is substantially true for oral curcumin specifically (curcumin is one of the worst-absorbed polyphenols ever commercialized; the ceiling is so low that even modest increases are dramatic in relative terms). What the original Shoba paper did *not* say, and what is often elided in marketing, is that the effect is compound-specific — piperine increases the bioavailability of some drugs/nutrients substantially, others modestly, and others not at all, depending on whether that compound's absorption is limited by **Phase II conjugation**, **P-glycoprotein efflux**, or **CYP3A4 first-pass metabolism**. Piperine inhibits all three; if a compound's absorption is limited by something else (e.g., poor intestinal dissolution, bile-acid-dependent micelle formation), piperine does nothing.\n\n**Mechanistically**, piperine works by three main routes: (1) **inhibition of hepatic and intestinal CYP3A4** (the most clinically important cytochrome P450 enzyme, handling ~50% of all prescribed drugs); (2) **inhibition of P-glycoprotein (P-gp, ABCB1)** — an ATP-dependent efflux pump that normally pushes xenobiotics back out of intestinal enterocytes and hepatocytes into the lumen and bile, dramatically limiting absorption and tissue penetration; (3) **inhibition of UDP-glucuronosyltransferases (UGTs)** — the Phase II conjugation enzymes that rapidly glucuronidate flavonoids and polyphenols (quercetin, curcumin, resveratrol, EGCG) into more water-soluble, rapidly-excreted conjugates. In addition, piperine weakly inhibits **CYP2D6**, **CYP1A2**, and **sulfotransferases (SULTs)**, and it may increase intestinal blood flow and disrupt brush-border membrane lipid dynamics in ways that increase passive paracellular absorption. The combined net effect is that a drug or nutrient that would normally be rapidly conjugated, pumped back into the gut lumen, and cleared by first-pass hepatic metabolism instead reaches the systemic circulation at multiples of its unaided concentration.\n\n**Who uses it and why** — the practical picture — breaks down roughly as follows. **Most users never consciously add piperine**: they get it embedded in formulated products. The majority of [curcumin](/compound/curcumin) supplements on the US market include 5-10mg Bioperine. Most [quercetin](/compound/quercetin) products include piperine. Many [fisetin](/compound/fisetin) \"senolytic\" protocols include it. A growing number of resveratrol products include piperine despite the resveratrol literature actually showing that piperine raises resveratrol AUC by a more modest (but still meaningful) ~2-fold rather than 20-fold. Standalone piperine capsules (5-10mg, typically Bioperine-branded) are marketed as a \"universal bioavailability booster\" — to add to any stack where absorption is limiting. Traditional **Ayurvedic and Unani medicine** have used **trikatu** — a formula of black pepper, long pepper, and ginger — for millennia as a digestive and bioenhancer adjunct to herbal preparations; trikatu is essentially the pre-modern, empirical version of a Bioperine stack, and it works for the same pharmacological reasons.\n\n**Where piperine gets you into trouble** is the mirror image of why it's useful. **CYP3A4 is not a niche enzyme** — it metabolizes roughly half of all prescription drugs. Statins (simvastatin, atorvastatin, lovastatin), calcium-channel blockers (amlodipine, felodipine, diltiazem), many benzodiazepines (midazolam, triazolam, alprazolam), most macrolide antibiotics, cyclosporine and tacrolimus (immunosuppressants used in transplant), many antihistamines, many anti-HIV protease inhibitors, many chemotherapy agents, warfarin partly, carbamazepine, and a long list of psychiatric medications all route through CYP3A4. Inhibiting CYP3A4 means **raising plasma levels of every one of those drugs** in a dose-dependent and often clinically meaningful way. The grapefruit-juice interaction familiar to most pharmacists is a CYP3A4 inhibition; piperine is a weaker but real version of the same effect. **Most self-experimenters don't think of their \"5mg black pepper extract\" as a pharmacokinetic enhancer for their statin, calcium-channel blocker, or SSRI — but that's exactly what it is**, and the dose-response is well-characterized in human studies (see Bhardwaj 2002, Volak 2013, Han 2011). This is the single most important safety consideration for piperine: it is **not** pharmacologically inert, and it should be considered a genuine drug-interaction modifier when any prescription medication metabolized by CYP3A4, P-gp, or UGT is in play.\n\nBeyond bioavailability enhancement, piperine has a **secondary literature** of direct biological effects that range from the modest and plausible (mild thermogenic/metabolic activity, transient antidiarrheal effects, anti-inflammatory signaling in cell culture) to the speculative and preliminary (neuroprotection, anticancer adjuvant, melanogenesis modulation, adipogenesis inhibition). None of these direct effects are strong enough to justify piperine as a standalone therapeutic, and most of the cell-culture and rodent findings involve concentrations that are never achieved in human plasma at normal supplement doses. But the direct effects aren't zero, and in the thermogenesis and adipocyte-signaling contexts they may contribute modestly to metabolic stacks. The honest framing: **piperine is a bioavailability enhancer first and a minor direct-effect compound second**. If you're stacking it for curcumin, quercetin, resveratrol, [EGCG](/compound/egcg), or [fisetin](/compound/fisetin) absorption, you're on solid ground. If you're stacking it for its own metabolic or neuroprotective effects, the evidence is thin.\n\nSee also [curcumin](/compound/curcumin), [quercetin](/compound/quercetin), [fisetin](/compound/fisetin), [ashwagandha](/compound/ashwagandha), [rhodiola-rosea](/compound/rhodiola-rosea), [berberine](/compound/berberine), [tulsi](/compound/tulsi), and [EGCG](/compound/egcg) for the compounds most commonly paired with piperine in bioavailability-enhancement stacks. This is educational content and not medical advice — piperine is a real drug-interaction modifier and warrants physician-level guidance when any prescription medication is concurrent. The convenience of \"a little black pepper extract\" in a supplement stack should not obscure the fact that, mechanistically, it is operating on the same enzyme systems as grapefruit juice, St. John's wort, and many prescription pharmacokinetic modifiers.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 2234, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/piperine" }, { "id": "c3ae8695-be65-4912-8421-2e0399b24ca3", "slug": "piracetam", "name": "Piracetam", "aliases": [ "Nootropil", "Lucetam", "Pirabene", "UCB-6215", "2-oxo-1-pyrrolidineacetamide", "2-oxo-1-pyrrolidinylacetamide" ], "category": "Nootropics", "description": "Piracetam is the prototypical nootropic — the compound that inaugurated an entire class of cognitive enhancement drugs and gave the category its name. It was synthesized in 1964 by Romanian-born Belgian chemist Corneliu Giurgea at UCB Pharmaceuticals (Union Chimique Belge) as a chemical derivative of GABA, though paradoxically it has minimal direct GABAergic activity. Giurgea observed that piracetam produced cognitive enhancement without the sedation, stimulation, addiction potential, or toxicity of existing psychoactive compounds, and in 1972 he coined the term \"nootropic\" (from the Greek *nous* for mind and *tropos* for turning) specifically to describe compounds in piracetam's novel category. The defining Giurgean criteria for a nootropic — cognitive enhancement, resistance to hypoxia and injury, facilitation of learning, lack of typical psychopharmacologic side effects, and very low toxicity — were derived from piracetam's clinical profile and remain the reference standard by which other \"nootropics\" are evaluated. Piracetam has been approved in dozens of countries outside the United States for clinical indications including cortical myoclonus (particularly post-hypoxic myoclonus), age-related cognitive decline, vascular dementia in some jurisdictions, cognitive impairment following stroke, dyslexia in children (in certain European countries), alcoholic dementia, and vertigo. In Europe it is sold under brand names including Nootropil, Lucetam, and Pirabene. The US Food and Drug Administration has never approved piracetam for any medical indication, and in 2010 the FDA issued warning letters to companies marketing piracetam-containing products as dietary supplements, stating that piracetam is not a legal dietary ingredient under the Dietary Supplement Health and Education Act of 1994. Despite this regulatory position, piracetam remains widely available in the US through online retailers, research chemical vendors, and compounding pharmacies, operating in a legal grey area similar to several other nootropic compounds. The evidence base for piracetam spans 50+ years of continuous research with thousands of published studies ranging from rigorous randomized controlled trials in cortical myoclonus (where efficacy is well-established) to more heterogeneous trials in age-related cognitive decline (where a 2002 meta-analysis by Waegemans and colleagues found modest but statistically significant cognitive benefits), to controversial and largely negative trials for acute stroke and mild cognitive impairment. The mechanism of action remains partially obscure — piracetam modulates AMPA receptors, enhances membrane fluidity, increases cerebral blood flow, and has subtle effects on cholinergic and glutamatergic systems, but no single mechanism fully explains its clinical effects. What makes piracetam clinically distinctive is its notable safety profile: in 50+ years of clinical use it has produced essentially no reports of serious toxicity, no addictive potential, and no significant withdrawal syndrome, with a side effect burden limited mainly to occasional headache, mild GI effects, and rare psychological activation. This entry covers piracetam's mechanism of action and the ongoing uncertainty about which of its multiple pharmacologic effects drives cognitive enhancement; the clinical evidence base across cortical myoclonus, cognitive decline, stroke, and other indications; the US regulatory situation and its practical implications; the classic racetam side effect profile including the acetylcholine-depletion headache that motivates co-supplementation with choline sources; dosing conventions including the loading dose protocol favored by many users; how piracetam relates to and stacks with other nootropic compounds including [Noopept](/compound/noopept), [Modafinil](/compound/modafinil), [Sulbutiamine](/compound/sulbutiamine), [Bromantane](/compound/bromantane), [Selank](/compound/selank), [Semax](/compound/semax), [Lion's Mane](/compound/lions-mane), [Uridine Monophosphate](/compound/uridine-monophosphate), [NAD+](/compound/nad), [Methylene Blue](/compound/methylene-blue), [L-Theanine](/compound/l-theanine), and [L-Tyrosine](/compound/l-tyrosine); and what disciplined use of the founding nootropic looks like in the context of the modern cognitive enhancement landscape. Piracetam occupies a specific position in nootropic history and practice: not the most potent cognitive enhancer available, not the best-studied for any particular indication, but the compound with the longest safety track record and the broadest global clinical use as a general cognitive enhancement agent. For users seeking a gentle, well-tolerated, evidence-supported entry into cognitive enhancement pharmacology, piracetam remains a defensible first choice.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 23, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/piracetam" }, { "id": "46475fb4-de78-4cce-91e8-b3ab6aac8191", "slug": "pnc-27", "name": "PNC-27", "aliases": [ "PNC-27 peptide", "p53-HDM2 inhibitor peptide", "anti-cancer peptide" ], "category": "Other", "description": "PNC-27 is a p53-derived peptide that selectively induces membranolysis in cancer cells. It contains the p53 transactivation domain (amino acids 17–26) linked to a membrane-penetrating transmembrane domain (HDM2 binding domain). Uniquely, PNC-27 kills cancer cells by binding to HDM2 protein on the cancer cell membrane surface — where HDM2 (the p53 negative regulator) is aberrantly expressed — creating pores in the cancer cell plasma membrane. Normal cells, which do not express surface HDM2, are spared. This selectivity distinguishes PNC-27 from most cytotoxic compounds. Published research comes primarily from Sarafraz-Yazdi et al. and has demonstrated selective pancreatic cancer, leukemia, and breast cancer cell kill in vitro. PNC-27 remains preclinical with no clinical trials completed.", "half_life": "Unknown (no published PK data)", "molecular_weight": "4031.8 g/mol (average); molecular formula C188H293N53O44S", "molecular_mass": "4031.8 g/mol", "amino_acid_sequence": "Pro-Pro-Leu-Ser-Gln-Glu-Thr-Phe-Ser-Asp-Leu-Trp-Lys-Leu-Leu-Lys-Lys-Trp-Lys-Met-Arg-Arg-Asn-Gln-Phe-Trp-Val-Lys-Val-Gln-Arg-Gly (PPLSQETFSDLWKLLKKWKMRRNQFWVKVQRG); 32-amino-acid chimeric peptide - p53 HDM-2-binding domain residues 12-26 (PPLSQETFSDLWKLL) fused to a C-terminal membrane-residency / penetratin-derived leader sequence (KKWKMRRNQFWVKVQRG).", "administration_routes": [ "Subcutaneous", "Intravenous", "Intraperitoneal" ], "dose_range_mcg": "0", "dosing_frequency": "variable", "cycle_length": "", "common_vial_sizes": [ "10" ], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Selective cancer cell membranolysis via surface-expressed HDM2 targeting", "In vitro activity against pancreatic cancer, leukemia, breast cancer, and melanoma cells", "Spares normal cells — no HDM2 surface expression on non-malignant tissue", "Rapid cytotoxic action — membranolysis within minutes of contact in vitro", "Research model for non-apoptotic cancer cell killing mechanisms" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/pnc-27" }, { "id": "24df09c9-dd53-4896-aad3-bbcd11acf1e0", "slug": "pqq", "name": "PQQ (Pyrroloquinoline Quinone)", "aliases": [ "PQQ", "Pyrroloquinoline quinone", "Methoxatin", "PQQ disodium salt", "Pyrroloquinoline quinone disodium", "BioPQQ", "MGCPQQ", "PureQQ", "4,5-dihydro-4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid", "PQQH2", "PQQ hydroquinone", "Reduced PQQ", "Coenzyme PQQ", "Quinone cofactor", "o-Quinone cofactor" ], "category": "Cofactor", "description": "\nPyrroloquinoline quinone (PQQ, methoxatin) is a small tricyclic o-quinone originally discovered in 1964 as the prosthetic group of bacterial methanol dehydrogenase. In methylotrophic and methanotrophic bacteria (organisms that live on methane or methanol), PQQ serves as a redox cofactor for several quinoprotein dehydrogenases — methanol dehydrogenase, glucose dehydrogenase, ethanol dehydrogenase — catalyzing two-electron oxidations of alcohols, aldehydes, and sugars via stable semiquinone intermediates. PQQ is an ancient cofactor, chemically simpler than NAD+ or FAD, and its discovery sparked decades of interest in whether PQQ plays a comparable role in mammalian biology. The answer has been contested and remains incompletely resolved: PQQ is present in mammalian tissues at low concentrations, is found in a wide range of foods (fermented soy, parsley, green tea, kiwi, papaya, breast milk), produces measurable deficiency syndromes in strict PQQ-restricted animal diets, and has been proposed as a novel B vitamin — yet no mammalian apo-enzyme requiring PQQ as a prosthetic group has been definitively characterized, and PQQ's essentiality in humans is not accepted by the IOM or EFSA. This creates a regulatory and scientific ambiguity similar to boron's — PQQ may have biological activity in mammals, but it does not meet formal essentiality criteria, and the evidence for supplementation benefit in healthy humans is mechanistically suggestive but clinically limited.\n\nThe chemistry of PQQ is distinctive and underlies much of its proposed biological activity. The tricyclic aromatic structure contains an ortho-quinone (adjacent carbonyl groups) that can accept electrons to form a semiquinone radical intermediate and then a fully reduced hydroquinone (PQQH2). Unlike many quinones, PQQ undergoes this redox cycling with exceptional catalytic efficiency — a single PQQ molecule can go through an estimated 20,000-100,000 redox cycles before degradation, compared to approximately 4 cycles for vitamin C or 100-200 for other polyphenols before oxidative destruction. This redox stability is the foundation of PQQ's proposed antioxidant role. Additionally, the ortho-quinone chemistry enables PQQ to react with amino groups on amino acids and proteins, forming quinoprotein adducts — a mechanism relevant to the bacterial quinoprotein enzymes and potentially to mammalian signaling. The three carboxylic acid groups make PQQ water-soluble, ionized at physiologic pH, and well-suited for renal excretion.\n\nPQQ was proposed as a novel B vitamin in a 2003 Nature paper (Kasahara 2003) based on studies of mice fed PQQ-deficient diets and analysis of the aminoadipic semialdehyde dehydrogenase (AASDH) enzyme system. The claim was that PQQ was an essential dietary factor required for AASDH activity. Subsequent critical reevaluation and the authors' own follow-up work determined that AASDH does not use PQQ as a cofactor in mammals, and the claim of PQQ being a new B vitamin was not validated. However, PQQ-deficient diets in mice do reliably produce a reproducible syndrome — growth impairment, reproductive failure, skin fragility, impaired neonatal survival — first described by Killgore, Smidt, Steinberg 1989 and refined by subsequent work (Stites 2000; Rucker 2009). This syndrome is ameliorated by dietary PQQ supplementation. Whether this represents true essentiality (deficiency syndrome as with a vitamin) or a pharmacologic effect of a biologically active dietary compound remains debated. The phenotype is subtle enough that formal nutritional essentiality has not been declared, but PQQ is not a trivial dietary factor either.\n\nPQQ is widely distributed in foods, though typically at low concentrations. The highest documented food concentrations are in fermented soybeans (natto) at approximately 61 ng/g, parsley at 34 ng/g, green tea at 30 ng/g, kiwi at 27 ng/g, papaya at 27 ng/g, spinach at 22 ng/g, tofu at 24 ng/g, dark chocolate at 9 ng/g, and human breast milk at approximately 140-180 ng/mL (substantially more concentrated than cow's milk at 4-17 ng/mL, suggesting physiologic concentration into breast milk). The presence in breast milk at meaningful concentrations is one argument for PQQ being a biologically important dietary factor. Typical Western dietary intake is estimated at 0.1-1 mg/day, though accurate intake data are limited because few food composition databases include PQQ.\n\nThe supplementation dose range (10-40 mg/day) is approximately 10-400 times typical dietary intake, placing supplementation firmly in the pharmacologic rather than nutritional replacement range. This is similar to the situation for many polyphenols and flavonoids — dietary exposure is modest, supplementation achieves levels that may produce measurable biological effects, but the relationship to dietary deficiency is indirect. At supplementation doses, PQQ is absorbed with moderate efficiency (estimated 20-40%), circulates briefly in plasma, distributes to tissues (with notable concentration in kidney, liver, heart, and brain), and is excreted via urine predominantly as intact PQQ or PQQ conjugates.\n\nThe most commercially relevant application of PQQ supplementation is mitochondrial biogenesis. Chowanadisai 2010 J Biol Chem demonstrated in mouse and human cell culture that PQQ at physiologic and supraphysiologic concentrations activates the PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) pathway, the master regulator of mitochondrial biogenesis. PGC-1α activation produces increased mitochondrial DNA content, increased expression of mitochondrial proteins (NRF1, NRF2, TFAM), and functionally increased cellular respiratory capacity. This mechanism underlies the marketing claim that PQQ produces \"new mitochondria\" — an oversimplification of a real mechanism. Whether PGC-1α activation in isolated cell culture translates to measurable mitochondrial expansion in human tissue during supplementation is an open question; human studies of mitochondrial biomarkers with PQQ are limited.\n\nThe second major supplementation claim is cognitive/memory enhancement. Nakano 2012 Functional Foods in Health and Disease trial in 41 middle-aged and elderly Japanese subjects supplemented with 20 mg PQQ/day for 12 weeks showed improvements in a cognitive battery (particularly in subjects with lower baseline cognitive function). Nakano 2009 had shown similar effects in a smaller pilot. Itoh 2016 examined sleep and stress and found modest improvements in sleep quality and stress markers. These are small Japanese trials, not replicated in large Western populations. The mechanism is proposed to involve mitochondrial function, NGF (nerve growth factor) stimulation, and antioxidant effects on neural tissue.\n\nThe third area of supplementation claim is cardiovascular — antioxidant protection, improved LDL oxidation resistance, and in pre-clinical models, protection against ischemia-reperfusion injury (Tao 2007 showed PQQ protection of rat hearts in I/R model). No large human cardiovascular outcome trial has been conducted.\n\nBodyHackGuide's take: PQQ is mechanistically interesting and biologically plausible, with a wide safety margin and low toxicity. The mitochondrial biogenesis mechanism is supported by good cell biology data. The human clinical data, however, are limited — a handful of small Japanese trials mostly in cognitive outcomes, limited Western replication, and no large endpoint trials. At 10-20 mg/day (the typical supplementation dose, as BioPQQ disodium salt or equivalent), PQQ is safe, the theoretical mechanism is sound, and modest benefits on cognition and energy have been reported by some users. Whether this translates to meaningful health improvement for the typical user is uncertain. PQQ is a reasonable addition to a mitochondrial-support stack (with [CoQ10](/compound/coq10), [alpha-lipoic acid](/compound/alpha-lipoic-acid), creatine, exercise) but it is not a foundational intervention. The cost is moderate ($30-60/month at typical doses), making it one of the more expensive trace cofactors to supplement. For users interested in the mitochondrial biogenesis angle, PQQ 10-20 mg/day for 3-6 months as a trial, alongside the foundational mitochondrial stack, is a defensible approach. For users without specific mitochondrial or cognitive concerns, PQQ is probably not a high-priority supplement.\n", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 1520, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/pqq" }, { "id": "b11b76fd-b92d-40fc-bc16-3732b509b144", "slug": "prl-8-53", "name": "PRL-8-53", "aliases": [ "PRL 8-53", "PRL8-53", "Methyl 3-(2-(benzyl(methyl)amino)ethyl)benzoate hydrochloride", "3-(2-benzylmethylaminoethyl)benzoic acid methyl ester hydrochloride" ], "category": "Nootropics", "description": "PRL-8-53 is a benzoic acid ester with a benzylmethylamino side chain, first described by N. R. Hansl in a 1974 note in Experientia that presented it as a spasmolytic and central nervous system active agent studied in animals (PMID: 4824605). It is an outlier among the compounds sold as nootropics: almost everything claimed for it traces back to a single small human study published in 1978, and there has been essentially no follow-up research in nearly fifty years.\n\nThat 1978 study, by Hansl and Mead in Psychopharmacology, tested the effect of low oral doses on learning and retention of verbal information under double-blind conditions using the serial anticipation method. The authors reported slight improvement of acquisition and statistically significant improvement of retention of verbal information, with most p values better than 0.01 and some better than 0.001, and no significant change in visual reaction time or motor control compared with placebo (PMID: 418433). PubMed indexes it as a randomized controlled trial. It was never replicated, and the widely repeated claim that volunteers doubled their memory comes from secondary retellings of subgroup results rather than from an independent trial.\n\nSearching PubMed for the acronym PRL-8-53 returns exactly one record, the 1978 human study. There is no published pharmacokinetic study, no repeat-dose toxicology, no receptor binding profile, no modern animal replication and no registered clinical trial. The mechanism is therefore unknown. The compound is a substituted phenethylamine derivative, and the 1974 report described central activity in animals alongside effects on blood pressure and interactions with apomorphine and methamphetamine, but no target has been identified and no mechanistic paper exists. Any confident mechanistic statement about PRL-8-53, including the frequently repeated claims about dopamine, acetylcholine or GABA, is not supported by published primary literature.\n\nThe material sold to consumers is the hydrochloride salt, which is what the chemistry values on this page describe; the free base has a molecular weight of 283.4 g/mol (PubChem CID 39989). Purity and identity of the powder on the research chemical market have never been the subject of a published analysis, which matters more for a compound with one 47-year-old study behind it than for one with a modern regulatory dossier.\n\nPRL-8-53 has never been approved as a medicine in any jurisdiction, has never entered formal drug development, is not a controlled substance in the United States and has no established safe exposure level in humans. It should be read as a historical curiosity with an unusually strong reputation relative to the evidence supporting it, not as a characterized drug. Anyone weighing the compound should treat the total absence of safety data as the central fact about it.", "half_life": "Not established. No pharmacokinetic study in humans or in any animal species has been published for PRL-8-53.", "molecular_weight": "319.83 g/mol (hydrochloride salt)", "molecular_mass": "319.83 g/mol (hydrochloride salt)", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Discontinued", "approval_status": "PRL-8-53 has never been approved as a medicine in any country and has never entered registered clinical development; searches of ClinicalTrials.gov return no records. Its only human exposure data come from a single double-blind study published in 1978 (PMID: 418433), and nothing has appeared since, so the compound is an abandoned line of work rather than an active program. It is not a controlled substance in the United States and is not an approved drug or a recognized dietary supplement ingredient there; material on the market is sold as a research-use-only compound.", "trial_phase": "", "cas_number": "51352-87-5", "iupac_name": "", "chemical_formula": "C18H22ClNO2", "potential_benefits": [ "Improved retention of verbal information in a double-blind study in human subjects using the serial anticipation method, with most p values better than 0.01 (PMID: 418433)", "Produced slight improvement of acquisition of verbal material in the same human study (PMID: 418433)", "Produced no change in visual reaction time or motor control compared with placebo in human subjects, which argues against a general stimulant effect (PMID: 418433)", "Described as centrally active in animal experiments in the original 1974 report (PMID: 4824605)" ], "research_fields": [ "Memory and retention", "Historical nootropics", "Research chemicals" ], "pubmed_count": 0, "pubchem_cid": 70700868, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/prl-8-53" }, { "id": "26f4c324-3391-451a-b356-f73f55bc6459", "slug": "probiotics", "name": "Probiotics", "aliases": [ "Probiotic bacteria", "Live cultures", "Lactobacillus", "Bifidobacterium", "Gut microbiome supplement", "LAB (lactic acid bacteria)" ], "category": "Supplement", "description": "**Probiotics** — defined by the joint FAO/WHO 2001 consensus as **\"live microorganisms which, when administered in adequate amounts, confer a health benefit on the host\"** — are the most widely sold and most widely misunderstood category of dietary supplement. The category encompasses a wide range of bacterial and fungal species across multiple genera (**Lactobacillus**, **Bifidobacterium**, **Saccharomyces**, **Streptococcus**, **Bacillus**, **Lactococcus**, **Enterococcus**), dozens of distinct strains with genuinely different clinical effects, and a product-format range from refrigerated multi-strain capsules to shelf-stable spore preparations to fermented foods. The central and nearly universally violated principle of evidence-based probiotic use is that **strain specificity trumps CFU count**: 10 billion colony-forming units of the wrong strain for your indication does essentially nothing that you couldn't get from yogurt, while 1 billion CFU of a well-studied strain like **Saccharomyces boulardii CNCM I-745** or **Lactobacillus rhamnosus GG (ATCC 53103)** can produce statistically and clinically meaningful effects in the right clinical context. Choosing a probiotic without identifying the specific strain and mapping it to a specific indication is like choosing a medication by tablet count rather than active ingredient — it's the wrong decision variable.\n\nThe genus-species-strain taxonomy is the single most important concept for navigating this category. **Lactobacillus rhamnosus** is a species; **Lactobacillus rhamnosus GG** (also written LGG, ATCC 53103, the Gorbach-Goldin isolate) is a specific strain with its own genome, its own adhesion and colonization characteristics, and its own clinical evidence base. A different *L. rhamnosus* strain — isolated from a different dairy fermentation or a different clinical context — may have meaningfully different properties. The same principle applies across genera: **Bifidobacterium longum** is a species, but **Bifidobacterium longum 35624** (the Align strain, also called Bifantis) has its own clinical trial record in irritable bowel syndrome (Whorwell 2006, *Am J Gastroenterol* PMID: 16863564) that does not transfer to other B. longum strains. **Saccharomyces boulardii CNCM I-745** (the Florastor / Perenterol yeast strain) has a well-developed clinical trial base in antibiotic-associated diarrhea, C. difficile, and H. pylori eradication that does not transfer to generic \"yeast\" supplementation. Product labels that say \"contains Lactobacillus\" or \"contains Bifidobacterium\" without specifying the strain are not evidence-based products — they are microbial flavor assertions with no predictable clinical effect.\n\n**The strongest clinical evidence base for probiotics concentrates on a handful of well-characterized indications**, and the evidence is genuinely strong for several of them. **Antibiotic-associated diarrhea (AAD)** is the most strong indication — multiple meta-analyses (**Hempel 2012** *JAMA* PMID: 22570464, **Szajewska 2015** *Aliment Pharmacol Ther* PMID: 26216624, **McFarland 2006** *Am J Gastroenterol* PMID: 16635227) have consistently shown that specific probiotic strains (**S. boulardii CNCM I-745** and **L. rhamnosus GG** most reliably) reduce AAD incidence by approximately 40-60% when co-administered with antibiotics. **Clostridium difficile infection prevention** — the **Goldenberg 2017 Cochrane review** (PMID: 29257353) showed probiotics given with antibiotics reduce C. difficile-associated diarrhea by roughly 60% in moderate-to-high-risk populations. **Pediatric acute infectious diarrhea** — **Allen 2010 Cochrane** (PMID: 21069673) showed approximately one-day shortening of diarrhea duration. **Irritable bowel syndrome**, particularly with **B. infantis 35624** (Whorwell 2006 PMID: 16863564) and multi-strain products like **VSL#3**. **Helicobacter pylori eradication** as adjunct to standard triple or quadruple therapy — **S. boulardii** meta-analyses (Szajewska 2015 PMID: 25898944) show raised eradication rates and reduced antibiotic side effects. **Ulcerative colitis** — **VSL#3** (now often marketed as Visbiome after a licensing change) has RCT evidence for both remission induction (**Sood 2009** PMID: 19631292) and pediatric maintenance (**Miele 2009** PMID: 19174792). **Traveler's diarrhea prophylaxis** — **S. boulardii** shows meta-analytic benefit (**McFarland 2007** PMID: 17298915).\n\n**Equally important is what probiotics do NOT do reliably**: they do not \"boost immunity\" in any specific measurable way in healthy adults; they do not reliably treat mental health conditions in the general population (the so-called **psychobiotic** literature — starting with **Messaoudi 2011** *Br J Nutr* — shows modest effects at best and has not matured into a strong clinical indication); they do not reliably improve skin conditions, weight loss, or metabolic disease in rigorously designed trials; and they absolutely do not permanently repopulate or \"reset\" the gut microbiome — ingested probiotic strains transit through and are typically undetectable in stool within 1-3 weeks after stopping supplementation. The concept of \"restoring gut flora\" with a generic probiotic overstates what ingestion actually accomplishes. Ingested probiotics act largely as a transient pharmacological intervention — present while being taken, producing effects via transient interactions with gut mucosa, immune cells, and resident microbiota — not as a durable ecological transplant.\n\n**The most serious cautions in the probiotic literature are not about common side effects (which are minimal in healthy people) but about specific high-risk contexts where probiotics have caused measurable harm**. The **PROPATRIA trial** (**Besselink 2008** *Lancet* PMID: 18279948) randomized 296 patients with predicted severe acute pancreatitis to a multi-strain probiotic mixture vs placebo enteral feeding and found **significantly increased mortality in the probiotic arm (16% vs 6%)** — driven by bowel ischemia in the severely ill population. This remains the single strongest negative signal in the probiotic literature and is why **acute severe pancreatitis is an absolute contraindication**. Second, **central venous catheters in immunocompromised patients**: case reports and surveillance studies (reviewed in **Doron & Snydman 2015** *Clin Infect Dis* PMID: 25922398) document **Lactobacillus bacteremia**, **Saccharomyces fungemia**, and other translocation events in patients with central lines, chemotherapy-induced neutropenia, advanced HIV, organ transplant immunosuppression, or short bowel syndrome — probiotics are NOT a benign intervention in these populations. Third, **small intestinal bacterial overgrowth (SIBO)** — for a minority of SIBO patients, especially those with methane-dominant SIBO, adding probiotic bacteria can worsen symptoms rather than improve them; clinical judgment is required. Fourth, the commercial probiotics market has **documented quality control problems**: products with CFU counts far below label claim by end of shelf life, products with misidentified strains, products with contaminating organisms, and products that lost viability during shipping in un-refrigerated trucks. Regulatory oversight in the US (FDA dietary supplement framework) is minimal compared to pharmaceutical probiotics (EcoR1-like regulated products in Europe, or the FDA IND pathway for specific clinical applications).\n\n**Who uses probiotics and why** varies enormously. In evidence-based use: patients starting a course of antibiotics (co-administration of S. boulardii or LGG for AAD/CDI prevention); patients with active or recently-active C. difficile infection (adjunctive to standard antibiotic therapy); patients with specific IBS subtypes (B. infantis 35624 for abdominal pain/bloating, VSL#3 for IBS-D); patients undergoing H. pylori eradication therapy (S. boulardii adjunct); patients with active mild-moderate ulcerative colitis (VSL#3/Visbiome as adjunctive). In more speculative use: general wellness supplementation where specific clinical benefit is unlikely but risk is low in healthy adults; post-antibiotic \"gut restoration\" (minimal evidence of durable benefit beyond AAD prevention during the antibiotic course itself); mood/anxiety (psychobiotic evidence is modest and not a substitute for psychiatric care); athletic and immune support (minimal evidence); skin and acne (limited evidence). In inappropriate use: severe acute pancreatitis, profound immunosuppression with central lines, confirmed SIBO without physician guidance, critically ill ICU patients not in specific probiotic trials.\n\n**Fermented foods represent a food-first alternative** to capsule probiotics, and one worth taking seriously. **Yogurt with live and active cultures** (typically *L. bulgaricus* + *S. thermophilus*, sometimes with added *L. acidophilus* or *Bifidobacterium* strains), **kefir** (a much more diverse consortium of bacteria and yeasts, typically containing 10-30+ species), **sauerkraut and kimchi** (lactic acid bacteria from spontaneous cabbage fermentation, primarily *Lactobacillus plantarum*, *L. brevis*, *Leuconostoc mesenteroides*), **miso and natto** (traditional Japanese soybean ferments with *Bacillus subtilis* and *Aspergillus* species), **kombucha** (symbiotic tea ferment with acetic acid bacteria and yeasts), and **traditional cheeses** all deliver living microbes via food. Fermented foods provide lower but often more ecologically complex microbial exposures than capsule probiotics, come with fiber and prebiotic substrates that support gut microbiota function, and are embedded in food matrices that may support microbial survival and delivery. They do not replace strain-specific evidence-based probiotic use for specific indications (e.g., AAD prevention or IBS with B. infantis 35624), but they are a reasonable foundation for microbiome support in the general population and a sensible default before turning to expensive capsule products for vague indications. Stanford's Sonnenburg lab and colleagues have shown that high fermented-food diets meaningfully shift microbiome composition and inflammatory markers in healthy adults.\n\n**Storage and CFU viability** is where many commercial probiotics fail silently. Most **Lactobacillus** and **Bifidobacterium** strains are sensitive to moisture, oxygen, heat, and time. Refrigerated products typically have longer viable shelf life but face cold-chain breaks during shipping. Shelf-stable products must use spore-forming **Bacillus** strains (which survive heat and desiccation as dormant spores) or freeze-dried formulations with moisture-absorbing packaging. CFU counts on labels usually reflect the amount at manufacture, not at end-of-shelf-life — a product labeled \"50 billion CFU\" may deliver 10-20 billion CFU by the expiration date even in ideal storage conditions, and much less after exposure to warmth or time. The practical implications: check label CFU-at-expiration versus CFU-at-manufacture (reputable brands disclose both); refrigerate products that specify refrigeration; store in cool dark locations; don't buy probiotics from sources with unknown storage history (e.g., warehouse-temperature online sellers); and understand that the dose you actually ingest is inherently uncertain to within a log-order in many products.\n\nSee also [curcumin](/compound/curcumin), [quercetin](/compound/quercetin), [berberine](/compound/berberine), [fisetin](/compound/fisetin), [ashwagandha](/compound/ashwagandha), [rhodiola-rosea](/compound/rhodiola-rosea), [tulsi](/compound/tulsi), [EGCG](/compound/egcg), and [BPC-157](/compound/bpc-157) for compounds frequently stacked with probiotics in gut-support contexts. Berberine in particular interacts closely with gut microbiota (and has its own antibacterial effect on gut flora that should be considered when co-administering with probiotics); BPC-157 is a GI-healing peptide sometimes combined with probiotics in inflammatory bowel and leaky-gut contexts. Prebiotic fibers — inulin, fructooligosaccharides (FOS), galactooligosaccharides (GOS), resistant starches — are the food-for-microbes companion category to probiotics and are often more impactful for durable microbiome health than any ingested live microbial dose. This is educational content, not medical advice — probiotics have real pharmacological effects, real contraindications in specific populations, and deserve indication-specific strain choice rather than generic \"gut health\" purchasing. Patients with immunosuppression, central venous catheters, severe GI disease, or complex medical contexts should involve physicians in probiotic decisions rather than treating the category as a benign over-the-counter wellness product.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 24468, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/probiotics" }, { "id": "0a870ecf-7685-4078-bbd6-79b8df96b060", "slug": "prostamax", "name": "Prostamax", "aliases": [ "Prostate peptide" ], "category": "Other", "description": "\nProstamax is a short synthetic peptide developed in Russia by Vladimir Khavinson and collaborators at the St. Petersburg Institute of Bioregulation and Gerontology, positioned as a \"prostate bioregulator\" intended to support prostatic epithelium and stromal function in age-related benign prostatic hyperplasia (BPH), chronic prostatitis, and post-surgical prostate recovery. It is usually described in Khavinson-family publications as the tetrapeptide Lys-Glu-Asp-Pro (KEDP), sometimes rendered H-Lys-Glu-Asp-Pro-OH or K-E-D-P. Prostamax is the synthetic defined-sequence counterpart to Prostatilen (sometimes marketed as Vitaprost), a polypeptide extract prepared from bovine prostate tissue that has been used clinically in Russia since the 1980s and remains a registered pharmaceutical in the Russian Federation for BPH and chronic prostatitis. Prostamax sits alongside [Pinealon](/compound/pinealon), [Thymogen](/compound/thymogen), [Vilon](/compound/vilon), [Epitalon](/compound/epithalon), [Livagen](/compound/livagen), [Bronchogen](/compound/bronchogen), [Cardiogen](/compound/cardiogen), [Cartalax](/compound/cartalax), [Chonluten](/compound/chonluten), [Ovagen](/compound/ovagen), and [Testagen](/compound/testagen) within the Khavinson short-peptide bioregulator family.\n\nOutside Russia, Prostamax is **not a registered pharmaceutical, not FDA- or EMA-reviewed, not listed in WADA categories**, and does not appear in AUA, EAU, or NICE guidelines for BPH or chronic prostatitis management. Critically, **no PubMed-indexed clinical trial supports Prostamax's prostate or BPH claims.** The evidence attributed to it in vendor and community write-ups traces to Russian-language reports that are not Western-indexed, not placebo-controlled, and not independently verifiable - earlier drafts of this page cited specific author-year studies as support, but on checking, those citations pointed to unrelated papers and have been removed. The parent polypeptide extract (Prostatilen/Vitaprost) has a modestly larger clinical footprint than the synthetic tetrapeptide, with Russian-language reports describing benefit in chronic pelvic pain syndrome and BPH symptom scores; those reports fall short of modern AUA/EAU evidence standards, and we cite no PubMed-indexed trial as support because none exists. The synthetic Prostamax tetrapeptide evidence base is smaller still: Khavinson-group in vitro work, small rodent experiments, and uncontrolled observational series, reported in Russian-language literature without independent replication.\n\nThe central claim for Prostamax is the standard Khavinson short-peptide model applied to prostate tissue: passive membrane permeation into prostatic epithelial and stromal cells, nuclear import, and sequence-selective chromatin modulation producing preferential upregulation of prostatic homeostatic programmes while downregulating inflammatory and hyperproliferative patterns. The tissue-specific targeting claim - that KEDP selectively supports prostate rather than other reproductive or visceral tissue - is asserted within the Khavinson framework but not validated by modern biodistribution, structural biology, or prostate-specific transcriptomics.\n\nBodyHackGuide covers Prostamax because it is sold online in post-Soviet supplement channels (typically 20 mg oral capsules or rectal suppositories) and appears in longevity and male-health discussions as a prostate-support bioregulator. We describe what is known, what is claimed, and what is missing - and we steer readers seeking evidence-graded prostate care toward interventions with substantial replication: PSA screening appropriate for age and risk, evaluation of lower urinary tract symptoms (LUTS) with IPSS scoring and urological workup, evidence-based pharmacotherapy for BPH (alpha-blockers like tamsulosin, 5-alpha reductase inhibitors like finasteride or dutasteride, phosphodiesterase-5 inhibitors like tadalafil for LUTS/ED overlap), evidence-based chronic prostatitis management, proven supplements (saw palmetto with mixed but some evidence, [Pygeum](/compound/pygeum), beta-sitosterol), surgical or minimally invasive procedures where indicated (TURP, Rezum, UroLift, HoLEP), and definitive management of prostate cancer where diagnosed. Prostamax is a plausible hypothesis. It is not, in 2026, an evidence-graded prostate therapy.\n", "half_life": "Not characterized in published pharmacokinetic literature", "molecular_weight": "487.51 g/mol (C20H33N5O9; monoisotopic 487.23 Da)", "molecular_mass": "487.51 g/mol", "amino_acid_sequence": "Lys-Glu-Asp-Pro (KEDP)", "administration_routes": [], "dose_range_mcg": "10 mg oral capsule, 1-2 daily for 10-30 days", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Not approved (not FDA/EMA reviewed; research use only)", "trial_phase": "", "cas_number": "", "iupac_name": "L-Lysyl-L-glutamyl-L-aspartyl-L-proline", "chemical_formula": "Lys-Glu-Asp-Pro", "potential_benefits": [ "Prostate health maintenance", "Prostate tissue repair", "Support for benign prostatic hyperplasia", "Anti-aging effects on prostate tissue" ], "research_fields": [], "pubmed_count": 6, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/prostamax" }, { "id": "610fe5ee-b5d2-453e-875d-8f797c067ec2", "slug": "pt-141", "name": "PT-141 (Bremelanotide)", "aliases": [ "Bremelanotide", "BH-141" ], "category": "Skin, Hair & Aesthetics", "description": "PT-141 (bremelanotide) is a cyclic 7-amino-acid synthetic melanocortin receptor agonist that acts centrally in the brain — not peripherally on genital tissue — to improve sexual desire, arousal, and responsiveness. It is the only FDA-approved peptide for a sexual function indication in women: Vyleesi received FDA approval in **June 2019** for acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women, administered as a 1.75 mg subcutaneous autoinjector on-demand approximately 45 minutes before anticipated sexual activity.\n\nThe pharmacology is fundamentally different from the PDE5 inhibitor class (sildenafil, tadalafil, vardenafil). PDE5 inhibitors work **peripherally** in the corpus cavernosum to maintain erectile blood flow once arousal has already begun. PT-141 works **centrally** in the hypothalamus, specifically on MC4R-expressing neurons, to create the upstream arousal signal itself. This means PT-141 can address sexual dysfunction that PDE5 inhibitors cannot — most notably desire and arousal disorders where the physiologic machinery is intact but the central arousal trigger is not firing.\n\nPT-141 evolved from earlier research on **Melanotan-II**, a broader-spectrum melanocortin agonist originally developed for photoprotective tanning indications. During Melanotan-II trials in the 1990s, an unexpected and consistent side effect emerged: **spontaneous erections** in male volunteers. Palatin Technologies (the developer) isolated the pharmacophore responsible, removed the pigmentation-driving MC1R activity to the extent possible, and produced bremelanotide — a more selective MC4R agonist with a cleaner side effect profile.\n\nClinical trial data from the key **RECONNECT Phase 3 program** ([Kingsberg et al., 2019]) demonstrated statistically significant improvements in the Female Sexual Function Index (FSFI) desire domain and the Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) across two 24-week trials enrolling 1,247 premenopausal women with HSDD. Off-label use in men for erectile dysfunction and both sexes for general libido enhancement is widespread in the peptide research community, with typical subcutaneous doses ranging from **0.5 to 2 mg** taken 30-60 minutes before anticipated activity.\n\nThe most significant safety considerations are transient blood pressure elevation (typically +6-8 mmHg systolic, resolving within 8-12 hours), nausea (the single most commonly reported adverse event, affecting roughly 40% of users in clinical trials), and — with repeated use — dose-related hyperpigmentation caused by residual MC1R cross-reactivity.", "half_life": "~2.7 hours", "molecular_weight": "1025.2 Da", "molecular_mass": "1025.18 g/mol", "amino_acid_sequence": "Ac-Nle-cyclo(-Asp-His-D-Phe-Arg-Trp-Lys)-OH - a cyclic lactam heptapeptide: an N-terminal acetyl group, a side-chain Asp-to-Lys amide (lactam) ring, and a C-terminal carboxylic acid. Residues: N-acetyl-norleucine (Nle), Asp, His, D-Phe, Arg, Trp, Lys. Molecular formula C50H68N14O10 (average mass ~1025.2 g/mol). Standard one-letter codes do not fully apply because Nle (norleucine) is non-proteinogenic and Phe is present as the D-enantiomer. Bremelanotide (PT-141) is the ring-closed metabolite of Melanotan-II, differing only at the C-terminus: MT-II is a C-terminal amide (-NH2), PT-141 is the carboxylic acid (-OH).", "administration_routes": [ "Subcutaneous" ], "dose_range_mcg": "500–2,000 mcg (0.5–2 mg) per dose", "dosing_frequency": "As needed, 45 minutes before sexual activity; max once per 24 hours, max 8 doses/month", "cycle_length": "As needed (not a cycle-based peptide)", "common_vial_sizes": [ "2mg", "10mg" ], "research_stage": "FDA Approved", "approval_status": "FDA-approved as Vyleesi® for HSDD in premenopausal women (2019)", "trial_phase": "FDA Approved", "cas_number": "189691-06-3", "iupac_name": "Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH", "chemical_formula": "C50H68N14O10", "potential_benefits": [ "Sexual desire enhancement", "HSDD treatment", "Erectile dysfunction (central mechanism)", "Non-hormonal approach" ], "research_fields": [ "Female sexual dysfunction", "Male erectile dysfunction", "HSDD", "Melanocortin signaling" ], "pubmed_count": 40, "pubchem_cid": 9941444, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/9941444/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/pt-141" }, { "id": "08cfaa28-d07d-4304-a6ec-b3e46364a584", "slug": "pterostilbene", "name": "Pterostilbene", "aliases": [ "Pterostilbene", "trans-3,5-Dimethoxy-4'-hydroxystilbene", "(E)-1-(3,5-Dimethoxyphenyl)-2-(4-hydroxyphenyl)ethylene", "3',5'-Dimethoxyresveratrol", "trans-Pterostilbene", "pTeroPure", "Pterostilbene phytosome", "Dimethylresveratrol", "Blueberry stilbene", "Pterocarpus marsupium stilbene" ], "category": "Stilbene Polyphenol", "description": "\nPterostilbene is a naturally-occurring stilbene polyphenol (trans-3,5-dimethoxy-4'-hydroxystilbene) that is structurally and functionally related to resveratrol but has substantially superior pharmacokinetic properties. Chemically, pterostilbene differs from resveratrol by the replacement of two hydroxyl groups at the 3 and 5 positions on one of the phenyl rings with methoxy groups. This seemingly small structural difference produces dramatic pharmacokinetic consequences: pterostilbene has much higher oral bioavailability (approximately 80% in rodent studies versus under 5% for resveratrol), a substantially longer plasma half-life (105 minutes versus 14 minutes for resveratrol), much greater metabolic stability, enhanced tissue penetration, and different target affinities. Pterostilbene is often described as a \"bioavailable resveratrol\" in consumer materials, which captures the essential clinical reality that pterostilbene at 50-150 mg reaches tissue concentrations comparable to resveratrol at 500-1500 mg or higher.\n\nPterostilbene was first isolated in 1956 from Pterocarpus marsupium (Indian kino tree), a medicinal plant used in traditional Indian medicine for diabetes and metabolic disorders. The compound is also produced naturally by several plants as a phytoalexin — a defensive compound produced in response to fungal infection or stress. Dietary sources of pterostilbene are dominated by blueberries, which contain 99-520 ng per gram of fresh fruit (approximately 15-100 mcg per cup of blueberries) depending on cultivar. Other notable sources include grape leaves (trace amounts), almonds (trace amounts), and some berries. The blueberry content is sufficient that regular dietary blueberry consumption delivers measurable pterostilbene exposure, though doses corresponding to therapeutic supplementation levels (50-250 mg daily) exceed realistic dietary attainability.\n\nModern scientific interest in pterostilbene derives from three converging lines of research. First, beginning in the late 1990s and early 2000s, researchers studying resveratrol's pharmacokinetic limitations identified pterostilbene as a structural analog with dramatically better bioavailability — offering the possibility of achieving meaningful in vivo drug levels at clinically practical oral doses. Second, mechanistic research established that pterostilbene activates many of the same longevity-associated pathways as resveratrol, including SIRT1, AMPK, and Nrf2, while also having distinct activities including PPAR-alpha modulation and lipid metabolism effects. Third, a series of human clinical trials conducted beginning in 2012 established pterostilbene's human safety and documented effects on blood pressure, lipid profiles, oxidative stress markers, and cognitive function.\n\nKey clinical work includes Riche 2013conducted at the University of Mississippi: a randomized controlled trial of 80 adults with hypertension and dyslipidemia receiving pterostilbene 125 mg twice daily or placebo for 6-8 weeks showed pterostilbene produced small but measurable reductions in systolic blood pressure (approximately 7 mmHg), with modest changes in lipid profile. Riche 2014reported longer-term safety data and noted pterostilbene at high doses (250 mg twice daily) produced a modest increase in LDL cholesterol in a subset of participants, prompting dose refinements in subsequent trials. McCormack 2012provided human pharmacokinetic data confirming pterostilbene is well-absorbed orally with bioavailability in the 70-80% range in human volunteers. Rimando 2002quantified pterostilbene content across blueberry cultivars, establishing blueberries as the dominant dietary source. Tani 2014 and related studies have extended the pharmacokinetic and mechanistic understanding.\n\nPterostilbene has been commercialized primarily through the pTeroPure ingredient developed by ChromaDex, which provides >99% pure synthetic pterostilbene under a standardized manufacturing and testing regime. Commercial finished products containing pTeroPure include Elysium Health's Basis (pterostilbene 50 mg + nicotinamide riboside 250 mg — a combination supplement positioned as a foundational longevity formula), multiple ChromaDex-partner brands, and independently branded pterostilbene products from manufacturers who license the pTeroPure ingredient. Pterostilbene phytosome formulations (lecithin-complexed) provide further bioavailability enhancement for sensitive applications. Typical supplementation doses range from 50 mg daily (low maintenance, often paired with 250-500 mg NR or NMN) to 150-250 mg daily (therapeutic doses used in the Riche hypertension trials). Doses above 250 mg daily are generally not recommended without specific clinical rationale due to the LDL elevation signal observed at higher doses.\n\nThe thematic positioning of pterostilbene in longevity supplementation is as the bioavailable stilbene complement to NAD+ precursors: the Basis formulation pairing pterostilbene with nicotinamide riboside reflects a theoretical model where NR provides substrate for sirtuin enzymes and pterostilbene activates those enzymes, producing a combined effect exceeding either alone. The underlying mechanistic logic has strong preclinical support but limited randomized clinical trial evidence for combined product effects. Nevertheless, pterostilbene has become established as a well-tolerated, bioavailable, orally-effective SIRT1/AMPK activator suitable for long-term daily supplementation in adults pursuing longevity-oriented health goals.\n", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/pterostilbene" }, { "id": "66c8fa2b-5b54-413f-91a5-bdc31a7ab9ef", "slug": "pygeum", "name": "Pygeum", "aliases": [ "Prunus africana", "African cherry", "African plum", "Pygeum africanum", "Tadenan", "Red stinkwood", "Iron wood" ], "category": "Herbal", "description": "**Pygeum** (*Prunus africana*, formerly classified as *Pygeum africanum*) is a lipophilic bark extract derived from the **African cherry tree** — a large, slow-growing evergreen hardwood species native to the mountainous forests of sub-Saharan Africa, from Cameroon and Kenya through Uganda, Tanzania, Ethiopia, Madagascar, and south to South Africa. The tree itself, sometimes called \"red stinkwood\" in English and \"iron wood\" for its dense timber, grows to 30-40 meters in favorable conditions, with dark reddish-brown bark that cracks into characteristic rectangular scales as the tree matures. The bark — not the leaves, fruit, or wood — is the medicinal part, prepared by solvent extraction (typically chloroform, methylene chloride, or ethanol) into a standardized lipid-soluble concentrate. The resulting extract is a dark, viscous, slightly oily material standardized most commonly to **total sterols** (13-14% by weight in the leading French product **Tadenan**, manufactured originally by Laboratoires Debat and its successors) or to **n-docosanol** content. Pygeum has been a cornerstone of European phytotherapy for **benign prostatic hyperplasia (BPH)** and associated **lower urinary tract symptoms (LUTS)** since the 1960s, with particularly strong clinical adoption in France, Italy, Germany, Austria, and other European countries — where it is sold as a regulated phytomedicine rather than as a dietary supplement.\n\n**Important evidence-framing up front**: Unlike the in-vitro-heavy literature of [chaga](/compound/chaga) or the preclinical-centric data of many herbal compounds, **pygeum has a genuine base of placebo-controlled and comparative clinical trial evidence** — modest in absolute size but real, spanning roughly 40-50 years of European BPH research. The **Cochrane systematic review** (Wilt, MacDonald, and Ishani, first published 2002 and updated in 2011) pooled 18 randomized controlled trials including 1,562 men and concluded that *Prunus africana* extract produced **modest but statistically significant symptom improvement** compared to placebo — specifically, men taking pygeum had improved urological symptoms (nocturia, peak flow, residual volume) relative to placebo, with a favorable safety profile. This is meaningfully stronger evidence than most herbal compounds enjoy — but it comes with important caveats: (1) most included trials were small (30-200 patients) and relatively short (30 days to 16 weeks); (2) methodological quality was variable; (3) effect sizes were **modest**, not dramatic — pygeum is symptom-palliative, not disease-modifying; (4) pygeum does **not** shrink the prostate, reduce PSA meaningfully, or halt progression of BPH to the same degree that pharmaceutical 5-alpha-reductase inhibitors like finasteride or dutasteride do; (5) head-to-head comparisons against modern gold-standard BPH drugs (alpha-blockers like tamsulosin, 5-ARIs like finasteride) are limited and do not suggest pygeum is equivalent to pharmaceuticals for severe or progressive disease. **Honest positioning**: pygeum is a reasonable option for men with **mild-to-moderate BPH symptoms** who prefer a phytotherapy approach, who have limited tolerance for pharmaceutical side effects (alpha-blockers cause orthostatic hypotension; 5-ARIs cause sexual side effects and potential depression signals), or who are already on maximal medical therapy and want an additional symptomatic layer. It is **not** an appropriate substitute for pharmaceutical intervention in men with severe LUTS, significant urinary retention, renal impairment from obstruction, recurrent UTIs, gross hematuria, or other complicated BPH — these contexts warrant urological evaluation and evidence-based medical or surgical treatment, not self-directed herbal intervention.\n\n**The plant and its conservation context**: *Prunus africana* belongs to the family **Rosaceae** (the rose family) — the same family as almonds, peaches, plums, cherries, and apples — which is why its English common names reference cherries and plums despite the tree's African origin and the bark (rather than the fruit) being the medicinal material. The tree thrives in cool, high-altitude equatorial montane forests, typically at 1,500-3,000 meters elevation, and grows slowly — it can take 15-20 years before a tree is large enough to be bark-harvested and several more years to regrow sufficient bark for re-harvest without killing the tree. Traditional African medicine has used *Prunus africana* bark preparations for centuries for a variety of complaints including fever, malaria, stomach pain, and urological symptoms. Modern pharmaceutical interest traces to the 1960s when French researchers began systematic investigation of the bark's lipid-soluble constituents, leading to the 1969 patent of **Tadenan** by Laboratoires Debat and subsequent European marketing authorization. **Sustainability concern — this deserves prominent mention**: by the 1990s, massive international demand for pygeum bark — driven by European pharmaceutical production and increasingly by North American dietary supplement markets — had produced significant overharvesting, tree mortality, and forest degradation across Cameroon, Madagascar, and parts of Central Africa. Unsustainable harvest techniques (complete bark girdling, killing the tree) were common. In **1995**, *Prunus africana* was formally listed under **CITES Appendix II** (Convention on International Trade in Endangered Species) — designating it as a species that is not currently threatened with extinction but may become so unless trade is strictly regulated. This means legal international trade in pygeum bark now requires permits documenting sustainable harvest and non-detriment to wild populations. Despite this, illegal and unsustainable harvest persists in parts of the species' range. Consumers should prefer pygeum products sourced from **certified sustainable harvest programs** or from **cultivated plantations** (now expanding in Kenya, Madagascar, and Cameroon) rather than unmarked wild-harvest material. This is not merely an environmental nicety; it is the material ethical context for responsible pygeum use.\n\n**Chemistry of the standardized extract**: The pharmacologically relevant pygeum extract — distinct from traditional crude bark decoction — is a solvent-extracted **lipid-soluble concentrate** containing several classes of putative bioactive compounds. The three principal classes are: **(1) Phytosterols** — primarily **beta-sitosterol**, **beta-sitosterol-3-O-glucoside**, **campesterol**, **stigmasterol**, and notably **n-docosanol** (also spelled n-docosanol; a long-chain fatty alcohol). Beta-sitosterol and related phytosterols are structurally similar to cholesterol and have well-characterized effects on cholesterol absorption; they are also the primary putative actives in the related herbal extracts [saw-palmetto](/compound/saw-palmetto) and [beta-sitosterol](/compound/beta-sitosterol) standardized products. **(2) Pentacyclic triterpenes** — including **ursolic acid**, **oleanolic acid**, **2-hydroxyursolic acid**, **maslinic acid**, **crataegolic acid**, and various glucuronide derivatives. These triterpene acids have been shown in vitro to have anti-inflammatory and anti-edema effects, particularly through inhibition of 5-lipoxygenase and the leukotriene pathway. **(3) Ferulic acid esters** — including docosyl ferulate, tetracosyl ferulate, and other long-chain fatty-alcohol ferulates, which contribute further anti-inflammatory and antioxidant chemistry. Additional minor constituents include tannins, phenolic compounds, and small amounts of other triterpenoid and sterol species. The **Tadenan** product historically set the clinical standard and is still the most-studied pygeum extract globally; its standardization is to **total sterols** at approximately 13-14% by weight, delivering doses of 50 mg twice daily (100 mg/day total) in most clinical trials. More recently, once-daily 100 mg formulations have been studied and demonstrated broadly equivalent efficacy to divided 50 mg twice daily dosing.\n\n**Claimed benefits and where evidence actually supports them**: The clinically supported benefit is specifically **symptomatic improvement of BPH and associated LUTS** — not cure, not shrinkage, not prevention. Within this indication, pygeum has demonstrated in multiple placebo-controlled trials: (a) reduction in **nocturia frequency** (nighttime voiding episodes) — the most consistent finding; (b) modest improvement in **peak urinary flow rate**; (c) reduction in **post-void residual volume**; (d) general improvement in patient-reported LUTS symptom scores. The magnitude of these effects is **modest** — typically 10-20% improvement on outcome measures — clinically meaningful for men with mild-to-moderate symptoms but not transformative. Outside the BPH/LUTS indication, pygeum has been investigated for: **male infertility** (limited evidence suggesting possible improvement in semen parameters through anti-inflammatory effects on accessory sex glands — not robustly established); **chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)** (small trials suggesting possible benefit, often combined with other therapies — not robustly established); **stress incontinence** (very limited evidence, not established); **hair loss** via DHT-related mechanisms (mechanistic speculation extrapolated from saw palmetto literature; not demonstrated for pygeum specifically). Claims that pygeum \"treats\" erectile dysfunction, increases testosterone, enhances libido, or has broader androgenic effects are **not supported by clinical evidence** and reflect marketing extrapolation rather than trial data.\n\n**Honestly stated, where does pygeum fit?** Pygeum is a **phytomedicine with genuine if modest clinical evidence** for symptomatic BPH/LUTS management — more evidence than most herbal compounds, less evidence than pharmaceutical gold standards like tamsulosin or finasteride. It is most appropriately positioned as: (1) a reasonable first-line phytotherapy option for men with **mild-to-moderate BPH symptoms** who prefer a natural approach; (2) an **adjunct to pharmaceutical therapy** in men on alpha-blockers or 5-ARIs who want additional symptomatic support (used alongside, not instead of, mainstream therapy under physician guidance); (3) a reasonable **trial-of-therapy** candidate before escalating to pharmaceutical treatment, with a clear decision point at 8-12 weeks — if no meaningful symptom improvement, escalate to conventional medical therapy; (4) **not appropriate** as a substitute for pharmaceutical or surgical intervention in severe BPH, complicated BPH (retention, renal impairment, recurrent UTI, gross hematuria), or BPH in men with elevated PSA warranting evaluation for prostate cancer. **Pygeum is not FDA-approved for any indication in the United States** — it is sold as a dietary supplement subject to DSHEA regulation rather than pharmaceutical review. In Europe, it is a regulated phytomedicine with marketing authorizations for BPH symptom management in multiple countries. Any man considering pygeum for urological symptoms should first have a **proper urological evaluation** — digital rectal exam, PSA testing in age-appropriate contexts, urinalysis, symptom scoring (International Prostate Symptom Score, IPSS) — to rule out prostate cancer, infection, and other conditions that can mimic BPH symptoms and that warrant specific treatment rather than generic phytotherapy.\n\n**Pygeum vs. conventional BPH pharmacotherapy — an honest comparison**: (1) **Alpha-blockers** (tamsulosin, alfuzosin, silodosin, doxazosin, terazosin) — rapidly reduce LUTS by relaxing prostatic and bladder neck smooth muscle; onset within days to weeks; well-studied; side effects include orthostatic hypotension, dizziness, retrograde ejaculation (especially with tamsulosin and silodosin), intraoperative floppy iris syndrome. Alpha-blockers are substantially **more effective than pygeum** for rapid symptom relief in moderate-to-severe LUTS. (2) **5-alpha-reductase inhibitors** (finasteride, dutasteride) — reduce prostate size over 6-12 months by inhibiting conversion of testosterone to DHT; disease-modifying in that they slow BPH progression; shrink prostate by 20-25%; reduce PSA by approximately 50%; particularly effective in larger prostates (>40 mL); side effects include sexual dysfunction (ED, reduced libido, reduced ejaculate volume), potential depression signal, possible increased risk of high-grade prostate cancer in some analyses, persistent post-finasteride syndrome in a subset of users. **5-ARIs shrink the prostate; pygeum does not**. (3) **Combination therapy** (alpha-blocker + 5-ARI) — standard for moderate-severe BPH; most effective medical option; validated in large trials (MTOPS, CombAT). (4) **Surgical options** — TURP (transurethral resection of prostate), laser therapies (HoLEP, GreenLight), UroLift, Rezum, prostatectomy — reserved for severe, refractory, or complicated BPH; most definitive option when warranted. (5) **Pygeum, saw palmetto, other phytotherapies** — modest symptomatic benefit in mild-to-moderate disease; safer side effect profile than pharmaceuticals (particularly regarding sexual effects); appropriate for men with mild symptoms or who prioritize avoidance of pharmaceutical side effects over maximum symptom reduction. Pygeum should not be positioned as equivalent or alternative to pharmaceuticals for men with significant BPH — it is a **complementary or early-stage option**, not a replacement.\n\nPygeum is frequently stacked with [saw-palmetto](/compound/saw-palmetto) in commercial BPH combination products; the two work through somewhat overlapping mechanisms (both contain phytosterols; both have anti-inflammatory and mild anti-androgenic effects), but the evidence for pygeum + saw palmetto combinations is not substantially stronger than either alone. Other common herbal stacking partners include stinging nettle root (Urtica dioica radix, another European BPH phytotherapy with evidence), [beta-sitosterol](/compound/beta-sitosterol) (often as a standalone purified phytosterol), pumpkin seed oil, and zinc. These combinations have a traditional and commercial basis but the additive benefit is largely inferred from individual-component trials rather than directly validated in rigorous head-to-head comparative trials.\n\nSee also [saw-palmetto](/compound/saw-palmetto) as the most commonly-paired herbal BPH compound; [beta-sitosterol](/compound/beta-sitosterol) as a purified phytosterol with its own BPH evidence; stinging nettle root for another European BPH phytotherapy; and [boswellia](/compound/boswellia) or [curcumin](/compound/curcumin) for more generalized anti-inflammatory phytotherapies. Pygeum sits alongside these compounds as a legitimate European phytomedicine with genuine (if modest) clinical evidence, real sustainability considerations, and a specific, narrow symptomatic indication — not a broad wellness compound, not a disease-modifying agent, and not an appropriate substitute for pharmaceutical or surgical intervention when those are clinically indicated. This is educational content and not medical advice; men with any urinary symptoms warranting investigation — hesitancy, weak stream, nocturia, urgency, incomplete emptying, retention, hematuria, pelvic pain — should see a urologist for proper evaluation before and alongside any self-directed phytotherapy.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 54, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/pygeum" }, { "id": "abc49a35-f56a-4960-905f-27e531f2bf4e", "slug": "quercetin", "name": "Quercetin", "aliases": [ "Quercetin", "3,3',4',5,7-Pentahydroxyflavone", "Quercetin aglycone", "Quercetin dihydrate", "Quercetin glycoside", "Rutin", "Quercetin-3-O-rutinoside", "Quercetin-3-O-glucoside", "Isoquercitrin", "EMIQ", "Enzymatically modified isoquercitrin", "Alpha-glycosyl isoquercitrin", "Quercetin phytosome", "Quercefit", "QuerceMax", "QU995", "Meriva-quercetin" ], "category": "Flavonoid", "description": "\nQuercetin is a polyhydroxylated flavonoid compound (chemically 3,3',4',5,7-pentahydroxyflavone) that occurs widely in edible plants as both the free aglycone and a family of glycosides including rutin (quercetin-3-O-rutinoside), isoquercitrin (quercetin-3-O-glucoside), quercitrin (quercetin-3-O-rhamnoside), and multiple related sugar-conjugated forms. The basic flavonoid skeleton consists of two benzene rings (the A ring and B ring) connected by a three-carbon chain forming a third oxygen-containing ring (the C ring). Quercetin's distinguishing feature is five hydroxyl groups positioned at the 3, 5, 7, 3', and 4' carbons, which together give the molecule its strong antioxidant chemistry, its characteristic yellow color, and its broad spectrum of biological activities. Quercetin is one of the most abundant dietary flavonoids, providing roughly 15-40% of total flavonoid intake in typical Western diets.\n\nThe richest dietary sources of quercetin include capers (180-230 mg per 100 g, the densest known source), red onions (20-50 mg per 100 g concentrated in the outer rings), yellow onions (10-20 mg per 100 g), shallots, kale (2-10 mg per 100 g), apples with skin (4-10 mg per 100 g with 90% in the peel), berries (cranberries 15-25 mg per 100 g, blueberries 2-8 mg per 100 g, blackcurrants 12-16 mg per 100 g), leafy greens, capers, buckwheat, fennel, cherry tomatoes, broccoli florets, green tea, black tea, and red wine. Fresh dill, cilantro, and hot green chili peppers are also rich sources. A typical Mediterranean-style diet with generous allium, berry, and tea consumption provides 15-40 mg of quercetin daily; supplement doses range from 250 mg (low) to 1500 mg (high) daily, an order of magnitude above typical dietary intake.\n\nPharmacokinetic properties of quercetin are the single most important practical consideration when evaluating supplementation. Free quercetin aglycone has poor oral bioavailability (2-10%) due to low aqueous solubility, susceptibility to intestinal and hepatic Phase II conjugation (sulfation, glucuronidation, methylation), and rapid biliary and urinary elimination of the conjugates. Most dietary quercetin reaches systemic circulation as quercetin-3-glucuronide, quercetin sulfates, and methylated (isorhamnetin) derivatives rather than as free aglycone. These conjugates have their own biological activities — often different from, and sometimes opposing, those of the parent molecule — making the interpretation of in vitro data difficult. Enzymatically modified isoquercitrin (EMIQ, alpha-glycosyl isoquercitrin), quercetin phytosome (Quercefit, sunflower-lecithin quercetin), and quercetin bound to sunflower lecithin nanoparticles all substantially improve bioavailability by providing a glycoside form that is efficiently hydrolyzed at the intestinal brush border or by increasing apparent solubility. Bioavailability-enhanced forms can achieve 5-10-fold higher plasma concentrations than standard quercetin aglycone, which matters clinically because many reported benefits of quercetin require plasma concentrations above 1-2 micromol/L that unenhanced aglycone supplements struggle to achieve.\n\nThe evidence base for quercetin supplementation spans multiple therapeutic areas. Cardiovascular applications include blood pressure reduction — Serban 2016 meta-analysis (PMID 27405810) pooled 7 trials and found that quercetin supplementation at doses of 500 mg daily or higher reduced systolic blood pressure by approximately 3.0 mmHg and diastolic by 2.6 mmHg in hypertensive subjects. Edwards 2007 tested quercetin 730 mg daily in stage 1 hypertensive men and found reductions of 7 mmHg systolic and 5 mmHg diastolic. Anti-inflammatory applications include mast cell stabilization via reducing histamine release and modulating cytokine production — quercetin has been used in allergic rhinitis, asthma, atopic dermatitis, and interstitial cystitis contexts with small-trial support. Respiratory applications include modest reductions in upper respiratory infection days with quercetin 1000 mg daily (Nieman 2009 supplement studies in endurance athletes). Metabolic applications include modest improvements in lipid profiles and markers of oxidative stress.\n\nA particularly consequential application is senolytic therapy. Quercetin combined with dasatinib (a tyrosine kinase inhibitor) has been developed as a senolytic cocktail — a combination that selectively eliminates senescent cells in aged or damaged tissues. Kirkland and colleagues at Mayo Clinic published foundational work (Zhu 2015 PMID 25754370) showing that the D+Q combination selectively killed senescent cells in vitro and improved physical function in aged mice. Hickson 2019 published the first human pilot trial (PMID 31542391) using D+Q in 14 patients with diabetic kidney disease, finding reductions in adipose tissue senescent cell markers. Subsequent trials are ongoing in idiopathic pulmonary fibrosis (LaPP trial), Alzheimer's disease, osteoarthritis, and frailty. The senolytic dosing protocol differs from continuous anti-inflammatory dosing: D+Q is typically administered as intermittent high-dose pulses (dasatinib 100 mg + quercetin 1000 mg daily for 3 consecutive days per month or quarter) rather than continuous daily use.\n\nQuercetin has also received attention as a zinc ionophore — a compound that facilitates zinc uptake across cell membranes. Dabbagh-Bazarbachi 2014characterized quercetin as a zinc ionophore in vitro. This mechanism became relevant during the COVID-19 pandemic when quercetin was proposed (alongside hydroxychloroquine and other ionophores) as a potential enhancer of intracellular zinc-mediated antiviral activity. Several small trials have tested quercetin in COVID-19 and upper respiratory infection contexts. Di Pierro 2021tested Quercefit phytosome 1000 mg daily in 152 mildly symptomatic COVID-19 patients and found reduced hospitalization rate and symptom duration. The evidence is preliminary and the clinical significance contested, but the mechanistic rationale has sustained research interest.\n\nFor bodyhackguide.co users, quercetin occupies several intersecting places in the supplement landscape: allergy/histamine management (mast cell stabilization), cardiovascular prevention (blood pressure, endothelial function), senolytic aging protocols (D+Q combination), exercise and athletic performance (endurance and recovery support), and general antioxidant/anti-inflammatory stacking. It pairs naturally with [bromelain](/compound/bromelain) (synergistic anti-inflammatory, often co-formulated), [vitamin-c](/compound/vitamin-c) (regenerates oxidized quercetin and amplifies antihistamine effect), [nettle leaf](/compound/stinging-nettle) (traditional allergy support), [fisetin](/compound/fisetin) (another senolytic flavonoid), [curcumin](/compound/curcumin) (polyphenol synergy), [resveratrol](/compound/resveratrol) (stilbene-flavonoid polyphenol combination), [zinc](/compound/zinc) (ionophore substrate), [EGCG](/compound/egcg) (green tea polyphenol synergy), and [NAC](/compound/n-acetyl-cysteine) (glutathione support). The canonical recommendation for general use is 500-1000 mg daily of a bioavailability-enhanced form (EMIQ, phytosome) with food, tailored for specific indications (allergy, blood pressure, senolytic) as clinical context warrants.\n", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/quercetin" }, { "id": "fc8c7aba-b6f4-4302-b108-c3e43028259e", "slug": "rad-140", "name": "RAD-140 (Testolone)", "aliases": [ "Testolone", "RAD140", "RAD 140", "Vosilasarm", "Testalone" ], "category": "Performance", "description": "RAD-140, sold as testolone and given the international nonproprietary name vosilasarm, is a nonsteroidal selective androgen receptor modulator developed at Radius Health, whose scientists reported the first-in-human trial (PMID: 34565686), and first described in the medicinal chemistry literature as a compound with an oxadiazole core designed for oral androgen receptor activity with tissue selectivity (PMID: 24900290). Radius took it into oncology rather than into muscle wasting, and the only registered human trial is a phase 1 study in postmenopausal women with hormone receptor positive metastatic breast cancer. It is not approved by any regulator.\n\nThe molecule binds the androgen receptor and acts as an agonist, changing which androgen-responsive genes are transcribed. The human phase 1 study used sex hormone binding globulin and prostate-specific antigen as markers of that engagement and saw sex hormone binding globulin fall in all 18 evaluable patients and prostate-specific antigen rise in 16 of 20, with paired tumor biopsies confirming receptor engagement (PMID: 34565686).\n\nPreclinical work covers three separate claims. For neuroprotection, RAD-140 reduced apoptotic cell death in cultured rat hippocampal neurons and protected hippocampal neurons in kainate-lesioned male rats, with the effect depending on MAPK signaling (PMID: 24428527). For oncology, it inhibited growth of androgen receptor positive and estrogen receptor positive breast cancer models (PMID: 28974548). For muscle, a study in young male Sprague-Dawley rats found increased muscle fiber cross-sectional area in unloaded animals but no additional benefit when combined with functional overload, and no change in cortical or trabecular bone over 14 days (PMID: 40680216). Two mouse studies point the other way on health span: in female mice, ten weeks of RAD140 increased frailty and mortality risk and failed to improve strength (PMID: 37758180), and a later study in older male and female mice again reported an effect on frailty (PMID: 40158703).\n\nThe human safety signal is the clearest reason this compound is not a casual purchase. In the phase 1 cancer study, the most frequent treatment-emergent adverse events were raised aspartate aminotransferase in 59.1 percent, raised alanine aminotransferase in 45.5 percent and raised total bilirubin in 27.3 percent, and grade 3 or 4 events occurred in 72.7 percent of the 22 patients (PMID: 34565686). Outside trials, biopsy-confirmed cholestatic drug-induced liver injury after RAD-140 has been reported repeatedly, with peak total bilirubin far above normal and recovery taking months (PMID: 36561105, PMID: 36945289, PMID: 39328701, PMID: 36978171, PMID: 38444893). There are also cardiac case reports: acute myocarditis (PMID: 35233331), myopericarditis in a 16-year-old boy after a first dose (PMID: 39157568) and heart failure (PMID: 38864168).\n\nRAD140 is named in FDA warning letters to firms selling SARM products as unapproved new drugs (FDA warning letter to Titan SARMs LLC, 12 December 2025), and it is prohibited in sport at all times under the World Anti-Doping Agency anabolic agents class (PMID: 28137616).", "half_life": "Terminal half-life 44.7 hours in humans, measured in a first-in-human phase 1 study in postmenopausal women with metastatic breast cancer (PMID: 34565686)", "molecular_weight": "393.83 g/mol", "molecular_mass": "393.83 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Phase 1", "approval_status": "Not approved by the FDA, the EMA or any other regulator; the only registered human trial is a phase 1 oncology study (NCT03088527). FDA treats SARM products as unapproved new drugs that are not dietary supplements and has named RAD-140 in warning letters to distributors (FDA warning letter to Titan SARMs LLC, 12 December 2025). Prohibited in and out of competition under the World Anti-Doping Agency anabolic agents class S1.2 (PMID: 28137616). Research-use-only compound in the US market.", "trial_phase": "", "cas_number": "1182367-47-0", "iupac_name": "", "chemical_formula": "C20H16ClN5O2", "potential_benefits": [ "Reduced apoptotic neuron death in cultured rat hippocampal neurons and protected hippocampal neurons in kainate-lesioned male rats (PMID: 24428527)", "Inhibited growth of androgen receptor positive and estrogen receptor positive breast cancer models, including in animal studies (PMID: 28974548)", "Increased muscle fiber cross-sectional area in young male Sprague-Dawley rats, without additional benefit on top of functional overload and without change in bone microarchitecture over 14 days (PMID: 40680216)", "Documented androgen receptor engagement in humans, with sex hormone binding globulin falling in all 18 evaluable patients in a phase 1 study (PMID: 34565686)", "One partial response and an 18.2 percent clinical benefit rate at 24 weeks in heavily pretreated metastatic breast cancer in that phase 1 study (PMID: 34565686)" ], "research_fields": [ "Oncology", "Neuroprotection", "Muscle and bone anabolism", "Hepatotoxicity surveillance" ], "pubmed_count": 0, "pubchem_cid": 44200882, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/rad-140" }, { "id": "c8300efd-cdea-477f-9e14-7501db10f119", "slug": "rapamycin", "name": "Rapamycin", "aliases": [ "Sirolimus", "Rapamune", "RAPA", "AY-22989", "WY-090217", "NSC-226080", "23,27-Epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine" ], "category": "Longevity", "description": "Rapamycin is a macrocyclic lactone antibiotic discovered in 1972 in soil samples from Rapa Nui (Easter Island) by a bacteriology survey team investigating indigenous Streptomyces species. Named after its place of discovery, rapamycin was initially developed as an antifungal agent before its immunosuppressive properties were recognized and the molecule was repositioned in the 1980s as a transplant rejection prophylaxis. It received FDA approval in 1999 as sirolimus (trade name Rapamune) for prevention of renal transplant rejection, and has since been approved for additional indications including tuberous sclerosis complex (TSC), lymphangioleiomyomatosis (LAM), drug-eluting coronary stent coating, and (as analogs everolimus and temsirolimus) multiple oncology indications. What makes rapamycin the most-discussed molecule in modern longevity medicine is not its approved indications but its position as the first pharmacological agent demonstrated to consistently extend maximum lifespan in mice across multiple genetic backgrounds, sexes, dosing schedules, and starting ages — a finding from the NIA Interventions Testing Program (ITP) that has been replicated and extended in hundreds of subsequent studies and has positioned rapamycin as the leading candidate for translation into human healthspan and lifespan medicine.\n\nStructurally, rapamycin is a complex 31-membered macrolide ring containing an unusual tricarbonyl region that is central to its biological activity. The molecule is poorly water-soluble (logP ~6), highly protein-bound in plasma, and shows complex pharmacokinetics with multiple active metabolites. Its molecular mechanism was elucidated through the 1980s-1990s: rapamycin binds the intracellular protein FK506-binding protein 12 (FKBP12), and the resulting complex binds and inhibits the mechanistic target of rapamycin (mTOR), a serine-threonine kinase that sits at the center of cellular growth, protein synthesis, and autophagy regulation. mTOR exists in two distinct complexes — mTORC1 (with Raptor as a defining component) and mTORC2 (with Rictor) — and acute rapamycin treatment selectively inhibits mTORC1 while leaving mTORC2 largely intact. Chronic rapamycin treatment, however, progressively inhibits mTORC2 as well, which is thought to explain much of the metabolic side-effect profile seen in transplant patients on continuous daily dosing (hyperlipidemia, glucose intolerance, new-onset diabetes). This mTORC1-vs-mTORC2 dosing-schedule distinction is the rationale for the weekly pulsed dosing protocols used in the longevity community, which aim to inhibit mTORC1 intermittently while minimizing mTORC2 impact.\n\nThe longevity case for rapamycin rests on several converging evidence streams. First, the NIA Interventions Testing Program study by Harrison et al. 2009 (PMID 19587680) demonstrated that rapamycin added to mouse chow extended median and maximum lifespan in genetically heterogeneous mice started on treatment at 600 days of age (approximately equivalent to 60 human years) — the first pharmacological agent to extend lifespan in mice when started in mid-to-late life. Subsequent ITP publications have confirmed and extended this finding across multiple dosing regimens (daily, intermittent, varying doses), across both sexes (with larger effect in females initially but demonstrated in males at higher doses), and across multiple genetic backgrounds. Second, studies in other model organisms (yeast, C. elegans, Drosophila) demonstrated that mTOR inhibition extends lifespan across the tree of life, placing mTOR at the center of an evolutionarily conserved aging pathway. Third, studies in non-human primates (marmosets, published by Tardif and colleagues) have shown safety of long-term rapamycin administration with metabolic biomarker signals consistent with caloric restriction mimicry. Fourth, human trials by Mannick and colleagues — originally with the rapamycin analog everolimus and later with rapamycin itself and the analog RTB101 — demonstrated that mTOR inhibition in elderly humans improves immune response to influenza vaccination and reduces incidence of respiratory infections (PMID 25540326), providing human functional evidence that mTOR-inhibition benefits extend beyond mouse longevity signals. Fifth, the PEARL trial (Participatory Evaluation of Aging with Rapamycin for Longevity) conducted by AgelessRx is the first purpose-designed human longevity RCT of rapamycin, with initial results published in 2024 showing improvements in body composition and safety findings consistent with low-dose rapamycin use.\n\nNotwithstanding this substantial evidence base, the honest framing is that rapamycin's case in human longevity remains unproven in the rigorous sense. Mouse lifespan extension does not automatically translate to humans — dozens of interventions have worked in mice without translating (growth hormone receptor knockouts, specific antioxidant regimens, metformin in healthy mice). The human trials to date (Mannick immune response, Kraig pilot, PEARL) provide safety and biomarker signals rather than lifespan or healthspan endpoints that would require decades to establish. The longevity-community enthusiasm for rapamycin — driven by Peter Attia's medicine practice, Mikhail Blagosklonny's hyperfunction theory of aging, Matt Kaeberlein's Dog Aging Project, and a growing network of longevity-focused physicians prescribing rapamycin off-label — is based on a reasonable extrapolation from the most-consistent pharmacological lifespan-extension data in gerontology, but it is extrapolation nonetheless. The drug is real, the mouse data are real, the mechanism is real, and the human safety is reasonable at low doses — but the claim that weekly 5-8 mg rapamycin meaningfully extends human healthspan is still hypothesis, not proven fact.\n\nRegulatory and access status in the United States: rapamycin (sirolimus, Rapamune) is a prescription drug approved for specific indications; off-label prescription for longevity purposes is legal but not supported by any regulatory approval or standard-of-care guideline. Longevity-focused medical practices (notably AgelessRx, Private Medical, and individual concierge longevity physicians) prescribe rapamycin off-label on the basis of informed-consent shared decision-making. The cost of low-dose pulsed rapamycin is modest ($50-200/month depending on pharmacy and insurance status). Generic sirolimus is available at compounding pharmacies and retail pharmacies. Self-sourcing from research-chemical markets or international pharmacies is inadvisable given the need for pharmaceutical-grade product and appropriate medical monitoring.\n\nThis entry covers rapamycin's discovery and development history, the mTORC1/mTORC2 mechanism and the dose-schedule rationale, the detailed ITP mouse lifespan data and its translational limits, the approved clinical indications (transplant, TSC, LAM, cancer), the human longevity evidence (Mannick, Kraig, PEARL), the Blagosklonny hyperfunction theory context, practical dosing protocols (Attia-style weekly 5-8 mg, biweekly variants, pre/post-procedure considerations), the characteristic side-effect profile (stomatitis, hyperlipidemia, glucose dysregulation, thrombocytopenia), drug-drug interactions (particularly grapefruit and strong CYP3A4 modulators), monitoring requirements (CBC, lipids, glucose, liver function, trough levels in some contexts), and the honest epistemic framing that balances real mechanistic evidence against the unresolved human translation question. It is offered as information about a prescription medication; clinical use of rapamycin requires a prescribing physician and appropriate monitoring.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/rapamycin" }, { "id": "14fe79c0-2e02-4f5d-b9b5-87e77b80e090", "slug": "reishi", "name": "Reishi", "aliases": [ "Ganoderma lucidum", "Ganoderma lingzhi", "Lingzhi", "Ling Zhi", "Mannentake", "Mushroom of Immortality", "Mushroom of Spiritual Potency", "Youngzhi", "Reishi Mushroom" ], "category": "Adaptogen", "description": "**Reishi** (scientific name *Ganoderma lucidum*, though the species most commonly cultivated and studied in East Asia is now properly recognized as *Ganoderma lingzhi* following a 2012 taxonomic revision) is a polypore mushroom known in Chinese as **lingzhi** (Θ¥êΦè¥, \"spirit plant\" or \"mushroom of immortality\"), in Japanese as **reishi** (Θ£èΦè¥) or **mannentake** (\"10,000-year mushroom\"), in Korean as **yeongji** (∞ÿü∞ºÇ), and in Vietnamese as **linh chi**. It holds perhaps the most exalted position in East Asian herbal medicine — the *Shen Nong Ben Cao Jing* (the Divine Farmer's Classic of Materia Medica, compiled around 200 BCE and considered the oldest Chinese materia medica) classified lingzhi in the highest category of \"superior herbs\" associated with prolonging life, improving vital energy (*qi*), strengthening cardiac function, improving memory, and nourishing the spirit (*shen*). For over 2,000 years, reishi has been symbolic of spiritual potency, longevity, divine power, and success in traditional Chinese, Japanese, and Korean culture — appearing in imperial robes, religious paintings, literary works, and traditional medicine preparations reserved for emperors and aristocracy. The distinctive kidney-shaped, red-brown, glossy-varnished cap of wild reishi (which grows on dead and dying hardwood trees, especially hemlock, oak, and plum) was so prized in wild form that it commanded extraordinary prices before commercial cultivation techniques were perfected in the 1970s.\n\nUnlike many traditional medicinal mushrooms whose modern preparation relies on ordinary cultivation, reishi has benefited from decades of scientific horticultural refinement. Modern commercial reishi is grown in controlled conditions on hardwood logs, sawdust, or grain substrate, with different growing conditions producing different bioactive profiles. Six color varieties of *Ganoderma* are recognized in traditional Chinese medicine, each with slightly different proposed uses — red reishi (*chizhi*), black reishi (*heizhi*), blue reishi (*qingzhi*), white reishi (*baizhi*), yellow reishi (*huangzhi*), and purple reishi (*zizhi*) — though **red reishi** (*Ganoderma lucidum/lingzhi*) is by far the most commonly cultivated, studied, and commercialized form. Some specialty producers also cultivate **Ganoderma sinense** (purple-black variety) and **Ganoderma applanatum** (artist's conk, the \"cloud mushroom\"), though these are less common in commercial supplements.\n\nChemically, reishi is extraordinarily complex, containing over 400 identified bioactive compounds. The two classes of greatest pharmacological interest are: **(1) triterpenoids**, particularly the **ganoderic acids** (at least 150 different ganoderic acids have been identified, with ganoderic acids A, B, C, D, F, H, K, S, and T being most studied) — these are the compounds responsible for reishi's characteristic bitter taste and contribute to anti-cancer, anti-inflammatory, hepatoprotective, and cardiovascular effects; and **(2) polysaccharides**, particularly **β-(1,3)/(1,6)-glucans** and heteropolysaccharides — these drive reishi's immune-modulating effects and are the basis for several pharmaceutical-grade reishi preparations used as cancer chemotherapy adjuncts in Japan, Korea, and China. Additional bioactives include sterols (ergosterol and its derivatives), proteins (including **LZ-8**, a fungal immunomodulatory protein), alkaloids, nucleotides, and phenolic compounds. The ratio of triterpenoids to polysaccharides varies dramatically based on: (a) which part of the mushroom is used (fruiting body, spores, or mycelium), (b) extraction method (hot water vs alcohol vs dual extraction), and (c) cultivation conditions — making product quality assessment challenging for consumers.\n\nThe proposed clinical applications of reishi span several domains: **(1) Cancer adjunctive therapy** — the single most substantial clinical use in Asia, where pharmaceutical-grade reishi preparations (like the Japanese product **Krestin**/PSK and the more pure reishi-derived polysaccharide products) are prescribed alongside chemotherapy and radiation to reduce side effects and potentially improve outcomes. **(2) Immune function** — both immune enhancement (in infection-prone, immunocompromised, or aging populations) and immune modulation (in allergies, autoimmune tendencies, and chronic inflammation). **(3) Sleep and stress** — reishi has a notable sedating, calming effect and is traditionally used before bed; modern research supports mild anxiolytic and sleep-promoting effects. **(4) Cardiovascular health** — traditional use for \"calming the heart,\" with modern evidence for modest blood pressure, cholesterol, and platelet-aggregation effects. **(5) Liver support** — hepatoprotective effects in various liver injury models; traditional use in chronic hepatitis. **(6) General longevity and anti-aging** — the most speculative but traditionally central claim. **(7) Diabetes** — modest evidence for glucose-lowering effects. **(8) Respiratory conditions** — traditional use in chronic cough, asthma, and bronchitis.\n\nThe human clinical evidence for reishi is moderate in volume but variable in quality, with Asian-language studies predominating. The most strong evidence exists for **cancer adjunctive use**. A 2016 Cochrane systematic review (Jin et al., PMID 27045603) analyzed 5 randomized controlled trials (373 participants) of *Ganoderma lucidum* as adjunct to chemotherapy/radiotherapy. The review concluded that reishi adjunctive therapy may increase tumor response rates (RR 1.50), improve functional status and quality of life, and improve immune parameters (CD3, CD4, CD8, NK cell activity) compared with standard cancer treatment alone. The authors noted that most trials were small, conducted in China, and had methodological limitations, but that the consistent direction of benefit warranted further rigorous investigation. In Japan and China, reishi-derived products like **Krestin (PSK/PSP)** from *Coriolus versicolor* (Turkey Tail — related to but not the same as reishi) are actually prescribed as pharmaceutical products alongside chemotherapy for colorectal, gastric, and lung cancers, with evidence of improved survival in some cases.\n\nThe **sleep/stress** evidence is preliminary but supportive. A small randomized trial (Zhao et al. 2012) in fatigued patients showed improvements in fatigue, depression, and quality of life. Multiple smaller studies in breast cancer survivors, chronic fatigue patients, and anxiety/stress populations have reported improvements in sleep quality and reductions in subjective fatigue. A 2019 systematic review of reishi for neurasthenia and fatigue concluded that evidence is suggestive but limited by trial size and methodology.\n\nFor **cardiovascular effects**, Gao et al. 2004showed reishi extract modestly reduced blood pressure, total cholesterol, and LDL-C in a 12-week trial. However, a 2015 Cochrane review (Klupp et al.) of *Ganoderma* for cardiovascular risk factors was less enthusiastic, concluding that current evidence for routine use is limited despite biological plausibility.\n\nWhere does reishi fit honestly in the therapeutic landscape? For cancer patients, reishi may be considered as an adjunctive option alongside (never in place of) standard oncology care, with oncologist awareness and monitoring — particularly for its potential effects on platelet function and immune markers. For healthy adults seeking general immune support, longevity tuning, sleep/stress management, or as a traditional adaptogen, reishi is a reasonable, well-tolerated option with moderate supporting evidence. It is NOT a substitute for evidence-based cancer therapy, antihypertensive medication, sleep medications (for clinically diagnosed insomnia), or mental health treatment. It sits comfortably alongside [Cordyceps](/compound/cordyceps) as a performance/respiratory mushroom, [Lion's Mane](/compound/lions-mane) as a cognitive mushroom, [Chaga](/compound/chaga) as an antioxidant mushroom, and [Turkey Tail](/compound/turkey-tail) as an immune mushroom — forming a traditional \"functional mushroom\" framework in modern Western nutraceutical practice.\n\nSafety with reishi is generally excellent at standard supplemental doses, though several considerations warrant attention. The most common adverse effect is mild GI upset. Rare but documented risks include hepatotoxicity (particularly with powdered, unextracted reishi fruiting body taken in large doses over extended periods — two case reports of fatal fulminant hepatitis have been associated with high-dose powder), allergic reactions, and antiplatelet effects. The pharmacologically active principles (especially triterpenoids) are significantly better extracted by dual extraction (hot water + alcohol) than by either method alone, and consumers should prefer **dual-extracted fruiting body tinctures** or **standardized extracts** (standardized to triterpenoid and/or polysaccharide content) over unextracted reishi powder.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 951, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/reishi" }, { "id": "a1000000-0000-0000-0000-000000000005", "slug": "retatrutide", "name": "Retatrutide", "aliases": [ "Triple Agonist", "GLP-3", "4x Blend", "RC-3R", "PEP-3R", "GLP-3 RT", "GLP-R", "Ion Peptide Retatrutide", "GIP/GLP/Glucagon", "ION-3R", "GLP-3R", "Retatrutide", "Reta", "BHG-3R", "BHG-3" ], "category": "Metabolic & Weight Loss", "description": "Retatrutide (also coded **LY3437943**) is an **investigational once-weekly triple-agonist** at the **GLP-1, GIP, and glucagon receptors**. It is the third-generation incretin-based therapy developed by Eli Lilly. Where [Semaglutide](/compound/semaglutide) activates GLP-1 alone and [Tirzepatide](/compound/tirzepatide) activates both GLP-1 and GIP, retatrutide adds glucagon receptor agonism for synergistic effects on energy expenditure, hepatic lipid metabolism, and weight reduction.\n\nAs of September 2026, retatrutide is **not FDA-approved**. Its Phase 3 program covers obesity (the TRIUMPH trials), type 2 diabetes (the TRANSCEND-T2D trials), fatty liver disease, and cardiovascular and kidney outcomes. In the lead obesity trial, TRIUMPH-1, the 12 mg dose produced 28.3% average weight loss at 80 weeks (Eli Lilly topline, May 2026).\n\nThe clinical excitement around retatrutide is driven by the Phase 2 obesity trial data published in NEJM in 2023: participants on retatrutide 12 mg weekly achieved **24.2% body weight reduction at 48 weeks**, more than the main trials of semaglutide (~15% at 68 weeks in STEP-1) and tirzepatide (~21% at 72 weeks in SURMOUNT-1) had shown ([Jastreboff et al., 2023]).\n\nDespite the strong efficacy signal, retatrutide's triple-receptor profile carries **distinct safety considerations** beyond the GLP-1 class:\n\n- **Heart rate elevation**: mean ~6-8 bpm increase (larger than semaglutide or tirzepatide), likely driven by the glucagon-receptor component\n- **Transient elevation of fasting glucose** during uptitration (glucagon receptor effect on hepatic glucose output), usually self-limited\n- **Higher rate of GI adverse events** at the 12 mg maximal dose compared to lower doses and compared to GLP-1-only agents\n- **Unknown long-term cardiovascular outcomes**: the large Phase 3 cardiovascular and kidney outcomes trial, TRIUMPH-Outcomes, is still running\n\n**Regulatory status:** Not FDA-approved. Available only through clinical trials, Eli Lilly's pre-approval expanded access program (requested by a physician, for adults with a BMI of 35 or more and serious obesity-related complications who have run out of approved options and cannot join a trial), research-chemical channels, and (controversially) compounding pharmacies in some jurisdictions using non-commercial retatrutide sourcing. Eli Lilly plans to submit it to the FDA in the first quarter of 2027.\n\nTypical dosing (extrapolated from Phase 2 uptitration schedule): **starting 2 mg weekly SC, titrating to 8-12 mg weekly over 12-20 weeks**. The maximal dose of 12 mg weekly is associated with the largest weight loss and the largest side-effect burden. See our [Retatrutide Dosage Guide](/guides/dosage/retatrutide) for uptitration specifics and our [Semaglutide vs Tirzepatide vs Retatrutide](/blog/glp1-comparison-2026) comparison for class-selection context.", "half_life": "~6 days (plasma, albumin-bound)", "molecular_weight": "4731 g/mol", "molecular_mass": "4731 g/mol", "amino_acid_sequence": "39-amino-acid synthetic peptide; GIP/GLP-1/glucagon triple receptor agonist (Eli Lilly LY3437943; CAS 2381089-83-2). Backbone (N->C, one-letter): YAQGTFTSDYSILLDKKAQAAFIEYLLEGGPSSGAPPPS. Key modifications (per the published structure): 2-aminoisobutyric acid (Aib) at positions 2 and 20; a C20 fatty diacid conjugated to a lysine side chain via a gamma-Glu/AEEA linker (albumin-binding moiety that extends the plasma half-life to ~6 days); C-terminal amidation. Molecular formula C221H342N46O68; molecular weight ~4731 g/mol.", "administration_routes": [ "subcutaneous" ], "dose_range_mcg": "1,000–12,000 mcg (1–12 mg) per week", "dosing_frequency": "Once weekly subcutaneous injection", "cycle_length": "Ongoing; dose escalation over 24+ weeks", "common_vial_sizes": [ "5mg", "10mg" ], "research_stage": "Phase III", "approval_status": "Investigational, not FDA-approved. Phase 3 obesity trials (TRIUMPH-1 to TRIUMPH-4) reported positive topline results between December 2025 and July 2026, and Eli Lilly plans to submit to the FDA in Q1 2027. No regulatory approval in any major market.", "trial_phase": "Phase 3", "cas_number": "2381294-46-4", "iupac_name": "Not fully disclosed (Eli Lilly proprietary)", "chemical_formula": "C221H342N46O68", "potential_benefits": [ "Body weight reduction up to 24% at 48 weeks (Phase 2 data)", "Glycemic control in T2DM: HbA1c reduction similar to tirzepatide", "Hepatic fat reduction: potential MASH/NAFLD therapeutic effect", "Modest increase in resting energy expenditure (3-5%)", "Preferential visceral fat reduction", "Blood pressure and lipid profile improvement (secondary to weight loss)", "Once-weekly dosing convenience", "Average weight loss of 28.3% at 80 weeks on 12 mg in the Phase 3 TRIUMPH-1 trial (Eli Lilly topline)" ], "research_fields": [ "Obesity", "Type 2 diabetes", "Metabolic syndrome", "NASH" ], "pubmed_count": 135, "pubchem_cid": 171390338, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/171390338/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/retatrutide" }, { "id": "a6bf2670-5031-4ab3-b38a-f2f6b4bb3174", "slug": "rhodiola-rosea", "name": "Rhodiola rosea", "aliases": [ "Golden Root", "Arctic Root", "Roseroot", "SHR-5", "Rhodiolin", "RhodioLife", "Rosavins", "Salidroside" ], "category": "Adaptogen", "description": "Rhodiola rosea is a succulent perennial plant that grows in cold, high-altitude regions of the Arctic, Siberia, Scandinavia, Iceland, the Alps, the Pyrenees, and the Carpathian Mountains. Its golden-yellow rhizome has been used for over a thousand years as a tonic against fatigue, cold, and high-altitude exposure in Russian, Siberian, Scandinavian, and Tibetan traditional medicine. The Vikings reputedly consumed it to improve physical strength and endurance before long voyages, the Sherpa used it to tolerate thin mountain air, and Soviet cosmonauts, special forces, and Olympic athletes used it routinely from the 1960s forward as a state-sanctioned performance enhancer under the \"adaptogen\" research program led by Nikolai Lazarev and Israel Brekhman (PMID: 20378318). Where ashwagandha ([withania somnifera](/compound/ashwagandha)) sits at the calming, parasympathetic-biased end of the adaptogen spectrum — lowering cortisol primarily at the adrenal level and producing mild sedation in many users — Rhodiola occupies the opposite pole: it is the stimulating, sympathetic-sparing, monoamine-modulating adaptogen, producing wakefulness, mental clarity, reduced fatigue, and mood elevation without the caffeinergic jitter of stimulants or the serotonergic side-effect burden of SSRIs. For chronically stressed, burned-out, or sub-depressed users — the classic \"tired but wired,\" cortisol-dysregulated presentation — Rhodiola is often the more useful adaptogen than ashwagandha, and for many users the two are complementary: Rhodiola in the morning for energy and focus, ashwagandha in the evening for sleep onset and HPA-axis downshifting.\n\nThe pharmacologically active constituents are the phenylpropanoid glycosides rosavin, rosin, and rosarin (collectively \"rosavins,\" which are diagnostic for the species R. rosea and absent from most other Rhodiola species), the phenylethanoid glycoside salidroside (also called rhodioloside, present across multiple Rhodiola species and in low concentrations in Chinese willow bark Salix matsudana), p-tyrosol (the aglycone of salidroside and, as a side note, the same molecule absorbed from olive oil as a metabolite of [oleuropein](/compound/oleuropein) and [hydroxytyrosol](/compound/hydroxytyrosol) — an overlap worth noting if stacking polyphenols), and a set of monoterpene glycosides and flavonoids including rhodiolin and rhodalin. The clinical standard is \"SHR-5,\" a Swedish Herbal Institute extract standardized to 3% rosavins and 1% salidroside in a roughly 3:1 rosavin-to-salidroside ratio that matches the naturally occurring ratio in wild R. rosea roots. Nearly every positive randomized trial in humans has used SHR-5 or extracts standardized to the same 3%/1% specification; extracts standardized to salidroside only, or to much higher salidroside concentrations (which often signals adulteration with other Rhodiola species such as R. crenulata or synthetic salidroside), do not necessarily reproduce SHR-5's effects. Commercial brands to prefer: NOW Rhodiola (SHR-5), Thorne Rhodiola Rosea (3%/1%), Gaia Herbs Rhodiola (3%/1%), Jarrow Formulas Arctic Root (SHR-5), Pure Encapsulations Rhodiola Rosea (3%/1%), and Life Extension Optimized Rhodiola (3%/1%, with added salidroside).\n\nThe mechanism of action is fundamentally different from ashwagandha and sets Rhodiola apart from every other widely used adaptogen. Rosavins and salidroside modulate monoamine neurotransmission at multiple points: they inhibit monoamine oxidase A (MAO-A) and MAO-B activity, sparing serotonin, dopamine, and norepinephrine from enzymatic degradation (PMID: 19168123); they appear to inhibit catechol-O-methyltransferase (COMT) to a lesser degree; they modulate 5-HT1A and 5-HT2A receptor signaling centrally; and they cross the blood-brain barrier to act on hypothalamic and locus coeruleus monoamine systems directly. This MAO-inhibiting profile partially explains why Rhodiola produces antidepressant-like effects in a time-course (days, not weeks) faster than SSRIs and with much lower side-effect burden, while also explaining the small but real risk of serotonin syndrome when combined with prescription MAO-inhibitors or high-dose SSRIs. Beyond monoamines, salidroside activates AMP-activated protein kinase (AMPK), shifts cellular metabolism toward fat oxidation, and induces heat-shock protein 72 (HSP72) via a nuclear factor-kappa B (NF-κB) and stress-activated JNK pathway that Alexander Panossian's laboratory group at the Swedish Herbal Institute demonstrated across cell, rodent, and human studies (PMID: 20378318, 22265417). The HSP72 induction mechanism is the molecular correlate of the \"adaptogen\" concept proposed by Lazarev: a compound that raises cellular stress resistance non-specifically by priming the heat-shock response, so that subsequent stressors (thermal, oxidative, inflammatory, cognitive) are better tolerated.\n\nClinically, the evidence base is strongest for three indications: (1) stress-related fatigue and burnout, where multiple randomized placebo-controlled trials (Olsson 2009, Edwards 2012, Cropley 2015, Kasper 2019 meta-analysis) consistently show reductions in fatigue scores, subjective stress, and burnout symptoms after 4-12 weeks at 200-400 mg/day of SHR-5 (PMID: 18307390, 22228617, 25172313, 31244915); (2) mild-to-moderate depression, where Darbinyan 2007 and Mao 2015 (Penn Integrative Medicine) demonstrated efficacy comparable to low-dose sertraline with far fewer side effects (PMID: 22228617, 26640839); and (3) short-term cognitive performance under fatigue, demonstrated in the classic Spasov 2000 student exam trial (101 medical students, single dose improved mental capacity by 8-30% across cognitive subtests, PMID: 10839209) and the Darbinyan 2000 night-shift physician trial (56 physicians, 170 mg/day for 2 weeks reduced mental fatigue 20% on complex perceptual tasks, PMID: 11081987). Effects on physical endurance are more mixed: De Bock 2004 showed improved time-to-exhaustion on cycle ergometer after a single 200 mg dose (PMID: 15256690), but multi-dose chronic-exercise trials have been less consistent, and Rhodiola appears to help most when fatigue or sleep deprivation is limiting performance rather than in rested, well-trained athletes.\n\nThis entry is the most complete public synthesis of Rhodiola rosea pharmacology, clinical evidence, dosing strategy, and stacking logic currently available. For context on adaptogen comparison, see [ashwagandha](/compound/ashwagandha), [bacopa monnieri](/compound/bacopa-monnieri), [holy basil](/compound/tulsi), and [schisandra](/compound/schisandra). For complementary stress-resilience nutrients, see [magnesium](/compound/magnesium), [l-theanine](/compound/l-theanine), and [taurine](/compound/taurine). For mood-adjacent compounds, see [saffron](/compound/saffron), [sam-e](/compound/sam-e), and [saffron](/compound/saffron). For athletic performance stacks, see [creatine](/compound/creatine), [beta-alanine](/compound/beta-alanine), and [citrulline](/compound/l-citrulline).", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 695, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/rhodiola-rosea" }, { "id": "f32b4a69-37b7-4157-923a-953419d594c3", "slug": "riboflavin", "name": "Riboflavin", "aliases": [ "B2", "Vitamin B2", "Riboflavin 5-phosphate", "R5P", "FMN", "Flavin mononucleotide", "FAD", "Flavin adenine dinucleotide", "Lactoflavin", "Ovoflavin", "7,8-dimethyl-10-ribityl-isoalloxazine", "Vitamin G", "Hepatoflavin", "Verdoflavin", "Uroflavin", "Riboflavin sodium phosphate", "Riboflavin-5-phosphate sodium" ], "category": "Vitamin", "description": "Riboflavin (vitamin B2) is a water-soluble vitamin that serves as the precursor to two universal flavoprotein cofactors — **flavin mononucleotide (FMN)** and **flavin adenine dinucleotide (FAD)** — which together serve as electron-carrying prosthetic groups in more than 90 human enzymes including Complex I and Complex II of the mitochondrial electron transport chain, the acyl-CoA dehydrogenases of fatty acid β-oxidation, glutathione reductase (the enzyme that regenerates reduced glutathione for antioxidant defense), methylenetetrahydrofolate reductase (MTHFR, the critical folate cycle enzyme), pyridoxine-5-phosphate oxidase (PNPO, which converts dietary B6 vitamers to active PLP), and kynurenine monooxygenase in the tryptophan-to-NAD+ pathway. The breadth of FMN/FAD dependency makes riboflavin a biochemically central vitamin despite its clinical understatement — most vitamin discussions focus on B1 (beriberi/Wernicke''s), B3 (pellagra), B6 (neuropathy), B9 (NTDs), and B12 (pernicious anemia), while B2 operates quietly in the background. The adult RDA is 1.3 mg/day for men, 1.1 mg/day for women, 1.4 mg/day in pregnancy, 1.6 mg/day in lactation. There is no formally established tolerable upper intake level because riboflavin has an exceptionally wide therapeutic window — pharmacologic doses up to 400 mg/day are used clinically for migraine prophylaxis without known organ toxicity, and doses up to several grams per day have been used for Brown-Vialetto-Van Laere syndrome without dose-limiting adverse effects other than the well-known bright yellow-orange urinary fluorescence that indicates excess is being excreted intact. Primary riboflavin deficiency (**ariboflavinosis**) is uncommon in isolated form in Western populations but recurs in chronic alcoholism, severe malabsorption, chronic phenothiazine or tricyclic antidepressant therapy (these drugs compete with riboflavin for intestinal transport and cellular phosphorylation), prolonged phototherapy (UV destroys riboflavin — a historical concern with phototherapy for neonatal jaundice), and specific genetic disorders of riboflavin metabolism. Symptomatic deficiency produces a characteristic picture of **angular cheilitis** (painful fissured corners of the mouth), **glossitis** (red, inflamed tongue), **seborrheic dermatitis** of the nasolabial folds and scrotum, photophobia, corneal vascularization, and normocytic normochromic anemia with reticulocytopenia. Two monogenic disorders of riboflavin transport produce severe clinical syndromes responsive to pharmacologic riboflavin: **Brown-Vialetto-Van Laere syndrome (BVVL)** and **Fazio-Londe syndrome**, caused by SLC52A2 (RFVT2) and SLC52A3 (RFVT3) mutations, present with childhood-onset cranial neuropathies, sensorineural deafness, bulbar palsy, and respiratory failure; aggressive high-dose riboflavin (10-80 mg/kg/day, sometimes up to 1500 mg/day) can halt disease progression and partially reverse neurological deficits, especially when initiated early. **Multiple acyl-CoA dehydrogenase deficiency (MADD, also called glutaric aciduria type II)** can present as a riboflavin-responsive form (RR-MADD) in which pharmacologic riboflavin 100-400 mg/day produces biochemical and clinical response. The supplement and clinical uses of riboflavin cluster in several distinct domains. **Migraine prophylaxis** is the best-established non-deficiency indication: Schoenen''s 1998 randomized trial of 400 mg/day riboflavin for 3 months reduced migraine attack frequency by 50%+ and established riboflavin as an evidence-based migraine preventive (PMID 9484373), adopted by the American Headache Society and American Academy of Neurology as a Level B preventive option for episodic migraine. The mechanism involves mitochondrial support through Complex I and Complex II of the electron transport chain, addressing the mitochondrial dysfunction hypothesis of migraine pathophysiology. **Blood pressure in MTHFR 677TT homozygotes** is a distinctive evidence-based use: McNulty, Wilson, and Horigan''s Irish trials have shown that riboflavin 1.6 mg/day reduces systolic blood pressure by 6-13 mmHg in the 10-15% of European-ancestry individuals homozygous for the MTHFR C677T polymorphism, whose MTHFR enzyme has reduced FAD binding and responds to riboflavin cofactor stabilization. **Corneal crosslinking with riboflavin** is a standard ophthalmological procedure for progressive keratoconus and corneal ectasia: topical riboflavin 0.1% solution plus UVA 370 nm exposure (Dresden protocol from Spoerl and Wollensak 2003) generates reactive oxygen species that form covalent crosslinks between collagen fibrils, stabilizing the cornea and halting ectasia progression. **Glutaric aciduria type I (GA1)** treatment includes riboflavin 50-300 mg/day alongside L-carnitine and protein restriction under pediatric metabolic supervision. **Anemia with deficiency** responds to repletion. **Cataracts and photoprotection**: riboflavin''s antioxidant role in the lens has generated interest for cataract prevention, with observational but not randomized evidence. Food sources concentrate in milk and dairy products (the original name \"lactoflavin\" referred to the vitamin''s isolation from milk), eggs, organ meats (liver, kidney), lean beef and pork, almonds, leafy greens, mushrooms, and fortified grains and cereals. Riboflavin is destroyed by UV light — the historical concern with milk stored in clear glass bottles exposed to sunlight — and by alkaline cooking conditions. See also [Thiamine](/compound/thiamine), [Niacin](/compound/niacin), [Vitamin B6](/compound/vitamin-b6), [Folate](/compound/folate), and [Vitamin B12](/compound/vitamin-b12) for the broader B-complex, [Alpha-Lipoic Acid](/compound/alpha-lipoic-acid) for the shared mitochondrial cofactor role, [CoQ10](/compound/coq10) for the electron transport chain partnership (Complex I/II feed CoQ), [Iron](/compound/iron) for the overlapping role in kynurenine pathway and cytochrome biology, and [Magnesium](/compound/magnesium) for the MTHFR cofactor context. This overview is educational only and is not medical advice — high-dose riboflavin for migraine or specific metabolic conditions should be physician-directed despite the excellent safety profile.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/riboflavin" }, { "id": "6d3c9fd4-5091-4f64-80d5-a442fa122714", "slug": "ru-58841", "name": "RU-58841", "aliases": [ "RU58841", "5-RU", "ManemMaxing" ], "category": "Other", "description": "RU-58841 (also known as **PSK-3841** or **HMR-3841**, and commonly written simply as **RU** in hair-loss forums) is a **non-steroidal androgen receptor antagonist** originally developed by Roussel Uclaf (later absorbed into Sanofi) in the late 1980s and early 1990s. The compound was designed as a potential topical treatment for androgen-dependent skin conditions — including **androgenic alopecia (male pattern hair loss)**, **acne**, and **hirsutism** — by blocking dihydrotestosterone (DHT) at the androgen receptor **at the site of application**, without requiring systemic enzyme inhibition like 5-alpha reductase inhibitors (finasteride, dutasteride).\n\nThe intended use case is elegant in principle. **5-alpha reductase inhibitors** such as finasteride and dutasteride work systemically by reducing DHT conversion from testosterone everywhere in the body — including in tissues where you want DHT to stay intact. That's why oral finasteride carries the side-effect profile that made it famous: sexual dysfunction, post-finasteride syndrome, mood changes in a subset of users. **RU-58841**, by contrast, was designed to be applied only where DHT is unwanted — on the scalp, for hair loss — and to then be metabolized before reaching systemic circulation. On the scalp, it would compete with DHT at the androgen receptor in dermal papilla cells, protecting follicles from miniaturization. Off the scalp, it would theoretically not exist at meaningful concentration.\n\nIn practice, Roussel Uclaf's own preclinical and phase I work suggested that RU-58841 absorbed through the skin in amounts sufficient to cause **measurable systemic antiandrogen effects** — suppression of testosterone-driven organ weights in animal studies, and in human volunteers, hormonal signals suggestive of partial systemic androgen blockade. This was not what the developers wanted, and the compound was quietly shelved in the mid-1990s. It never made it to a registered clinical trial for hair loss, never received regulatory approval anywhere, and essentially disappeared from the pharmaceutical pipeline.\n\nDespite that abandonment, RU-58841 has had an extraordinary **underground second life** in the hair-loss community. From the early 2000s onward, research-chemical suppliers began selling RU-58841 powder to individual buyers who self-compounded topical solutions in ethanol, propylene glycol, and related vehicles. An active Reddit, TressLess, and independent blog ecosystem emerged around RU-58841 use as a \"topical-only finasteride alternative\" — frequently marketed with a claim of equivalent hair regrowth potency and dramatically reduced systemic side-effect risk. That claim is partially supported by animal data and partially refuted by the absorption problems that caused its original abandonment, and the honest user experience on forums reflects both outcomes.\n\nThis entry takes the position that RU-58841 is a **research-grade compound with plausible topical efficacy for androgenic alopecia and genuine systemic-absorption risks that have not been adequately characterized in humans**. It is not a supplement. It is not approved for any human use in any jurisdiction. Users engaging with it are accepting the full research-chemical risk profile. For comparisons, see [finasteride](/compound/finasteride) (if available), topical minoxidil, and the FDA-approved topical antiandrogen [clascoterone](/compound/clascoterone) for acne. For related research-chemical landscape discussion, see [aminotadalafil](/compound/aminotadalafil).", "half_life": "", "molecular_weight": "", "molecular_mass": "489.41 g/mol", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "25 mg - 50 mg topical daily (dissolved in vehicle)", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "154992-24-2", "iupac_name": "", "chemical_formula": "C17H18F3N3O3S", "potential_benefits": [ "Prevention of hair follicle miniaturization", "Hair loss reduction (androgenic alopecia)", "Topical application minimizes systemic effects", "Alternative to finasteride without systemic 5-AR inhibition" ], "research_fields": [], "pubmed_count": 11, "pubchem_cid": 6434444, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/ru-58841" }, { "id": "7577e0a5-1fda-42f3-9113-7c0b7d04d26e", "slug": "sabroxy", "name": "Sabroxy (Oroxylin A)", "aliases": [ "BLITZED" ], "category": "Nootropics", "description": "Sabroxy is a standardized Oroxylum indicum (Indian trumpet tree) bark extract - typically 10% oroxylin A - sold as a nootropic supplement ingredient. Preclinical work points to dopaminergic (dopamine-reuptake-inhibiting) and BDNF-boosting activity, and one small human trial reported memory benefits in older adults. Research use only (RUO).", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "500000-1000000", "dosing_frequency": "Once to twice daily (500 mg per dose)", "cycle_length": "Studied continuously for 12 weeks; users often cycle (e.g., 5 on / 2 off, or 8-12 week blocks with breaks) to limit tolerance - cycling is anecdotal, not trial-derived.", "common_vial_sizes": [], "research_stage": "Preclinical, with one supporting human RCT", "approval_status": "Not FDA-approved as a drug; sold as a dietary supplement ingredient (RUO)", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Episodic memory: in the one human trial, a standardized Oroxylum indicum extract improved episodic memory and immediate word recall versus placebo [PMID:34531736].", "Working memory and learning speed: the same trial reported gains in numeric working memory and a faster rate of learning on a location-learning task [PMID:34531736].", "Focus and attention (preclinical): dopaminergic, stimulant-like activity reduced inattention and impulsivity in an ADHD rat model [PMID:23371806].", "Neuroprotection and BDNF (preclinical): rodent studies show increased BDNF/CREB signaling, less neuroinflammation, and enhanced hippocampal neurogenesis [PMID:17174385][PMID:41330961].", "Antioxidant and mitochondrial support (preclinical): the extract lowered oxidative stress and restored mitochondrial function in mice [PMID:34081735]." ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/sabroxy" }, { "id": "4bc1cf0d-6a75-4ebc-a77d-94cf0d2622af", "slug": "saw-palmetto", "name": "Saw Palmetto", "aliases": [ "Serenoa repens", "Sabal serrulata", "American dwarf palm", "Dwarf palmetto berry", "SPE (saw palmetto extract)", "Permixon (EU pharmaceutical extract)", "Prostamol" ], "category": "Herbal", "description": "**Saw palmetto (Serenoa repens)** is a small palm native to the southeastern United States whose berries have been used medicinally for over a century for urogenital conditions. Historical use in traditional American Indian medicine and 19th-century eclectic medicine was for prostate enlargement, urinary tract conditions, and as a general male tonic. Modern extracts — typically **hexane or ethanol extracts of dried berries standardized to 85-95% free fatty acids and sterols** — became widely available in Europe as phytopharmaceuticals from the 1980s onward, and in the United States as dietary supplements. Saw palmetto is among the most widely-used herbal supplements for **benign prostatic hyperplasia (BPH)** — the age-related non-malignant enlargement of the prostate producing lower urinary tract symptoms (LUTS) in aging men — and has secondary uses for **androgenetic alopecia (male pattern hair loss)**, **chronic prostatitis/pelvic pain syndrome**, and **polycystic ovary syndrome (PCOS)** in women. Global sales exceed several hundred million dollars annually, with strongest markets in Europe (where Permixon and similar extracts are prescription-reimbursed in some countries) and North America.\n\nThe **evidence base for saw palmetto is genuinely mixed and warrants honest framing**. Early smaller trials and meta-analyses (**Wilt et al. 1998** *JAMA* — meta-analysis of 18 trials with 2,939 subjects) suggested saw palmetto produced modest but meaningful improvements in BPH urinary symptoms with effect size comparable to low-dose finasteride or alpha-blockers. However, the **two largest well-designed RCTs** — the **STEP trial (Saw Palmetto Treatment of Enlarged Prostate, Bent et al. 2006** *NEJM*) with 225 men over 1 year and the **CAMUS trial (Complementary and Alternative Medicine for Urological Symptoms, Barry et al. 2011** *JAMA*) with 369 men over 18 months using doses up to 960mg/day — **found no significant benefit of saw palmetto over placebo** for BPH symptoms, urinary flow rates, prostate volume, or quality-of-life measures. The updated **Cochrane review by Tacklind et al. 2012**that incorporated these larger trials concluded saw palmetto was **no more effective than placebo** for BPH treatment. This represents a genuine reversal from earlier positive meta-analyses and is a rare example in nutritional medicine of larger, better-designed trials overturning smaller positive trials. Subsequent analyses have suggested **extract heterogeneity** may explain some differences — the specific **Permixon extract** (Pierre Fabre Médicament, hexane-extracted) has maintained somewhat more positive evidence in specific subgroups — but the **weight of contemporary evidence indicates saw palmetto has limited or no efficacy for BPH symptom management** compared to evidence-based alpha-blockers (tamsulosin, doxazosin) and 5α-reductase inhibitors (finasteride, dutasteride).\n\nDespite this humbling evidence base for BPH, saw palmetto retains clinical utility in several contexts: (1) men with **very mild BPH symptoms** who prefer a natural approach and understand the modest evidence base; (2) **androgenetic alopecia adjunctive use** where smaller trials (**Rossi et al. 2012**) suggest modest hair retention effects, primarily in topical formulations or combined with other hair-loss therapies; (3) **chronic prostatitis/pelvic pain syndrome** where evidence is weaker than for BPH but some users report symptomatic benefit; (4) **hirsutism and mild PCOS androgenic symptoms in women** (particularly post-menopausal) where saw palmetto's weak 5α-reductase activity may contribute to androgenic symptom management; (5) **\"wellness\" and general prostate-health maintenance** where evidence of disease-modification is limited but safety is excellent.\n\nThe **mechanistic rationale** for saw palmetto's putative effects centers on multiple pharmacologically plausible actions: **weak inhibition of both 5α-reductase type I and II isoforms** (approximately 100-1000× less potent than finasteride but theoretically additive), **anti-inflammatory effects** through 5-lipoxygenase and cyclooxygenase modulation, **androgen receptor binding inhibition** in vitro, **spasmolytic effects** on urinary tract smooth muscle, and possibly **alpha-1 adrenergic receptor antagonism** (similar to prescribed BPH drugs like tamsulosin). However, **in vitro pharmacologic effects do not consistently translate to meaningful clinical effects at feasible oral doses**, and bioavailability of active constituents varies substantially between extract preparations.\n\n**Regulatory status varies globally**: In the **United States**, saw palmetto is classified as a **dietary supplement** without prescription, available in standardized extracts, raw berry preparations, and combination products. In **France, Germany, Italy**, and some other European countries, **Permixon** (hexane extract) is a **prescription phytopharmaceutical** with more formal regulatory oversight for BPH. Italian and French urology guidelines still reference saw palmetto as a potential treatment option for mild LUTS. **American Urological Association (AUA) guidelines** do not recommend saw palmetto for BPH treatment, reflecting the negative evidence from STEP and CAMUS trials. **European Association of Urology (EAU)** guidelines mention saw palmetto with neutral-to-negative recommendation quality.\n\nSee also [Finasteride](/compound/finasteride), [Dutasteride](/compound/dutasteride), [Beta-Sitosterol](/compound/beta-sitosterol), [Stinging Nettle](/compound/stinging-nettle), [Pygeum](/compound/pygeum), [Lycopene](/compound/lycopene), and [Zinc](/compound/zinc) for adjacent prostate-health, urinary-symptom, and anti-androgen compounds. This is educational content and not medical advice — BPH, hair loss, and prostatitis all warrant physician-level evaluation rather than self-treatment with herbal supplements, particularly given the evidence that more effective options exist for symptomatic BPH.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 740, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/saw-palmetto" }, { "id": "9e5ea29c-77bb-4615-8a22-80d0002102ac", "slug": "schisandra", "name": "Schisandra", "aliases": [ "Schisandra chinensis", "Schizandra", "Wu Wei Zi", "Five-Flavor Fruit", "Five-Flavor Berry", "Omija", "Magnolia Vine", "Chinese Magnolia Vine", "Schisandrin", "Gomisin", "Northern Schisandra" ], "category": "Adaptogen", "description": "**Schisandra** (scientific name *Schisandra chinensis*; called **wu wei zi** in Chinese, literally \"five-flavor fruit\" — referring to the berry's unique property of exhibiting all five basic tastes simultaneously: sweet, sour, salty, bitter, and pungent/spicy — **omija** in Korean, and **gomishi** in Japanese) is a deciduous woody vine native to the cold temperate forests of Northeast China, Korea, eastern Russia (particularly the Russian Far East, Primorsky region, and parts of Siberia), and Japan, producing distinctive bright-red berries in dense clusters during late summer and autumn. It belongs to the family Schisandraceae (sometimes placed in Magnoliaceae in older classification), and a related species *Schisandra sphenanthera* (southern schisandra) is also medicinally used in southern China, though *S. chinensis* (northern schisandra) is more studied and commercially important. Schisandra has been documented in Chinese materia medica for over 2,000 years, classified in the *Shen Nong Ben Cao Jing* (the Divine Farmer's Classic of Materia Medica, ~200 BCE) as a **superior herb** category member — the same elite classification given to ginseng and reishi — with applications for calming the spirit, nourishing the kidneys, astringent tonification, liver protection, and promoting longevity.\n\nSchisandra occupies a particularly interesting position in adaptogen research because it served as one of the central herbs in the **Soviet/Russian adaptogen research program** from the 1940s-1990s, alongside Siberian ginseng ([Eleuthero](/compound/eleuthero)) and [Rhodiola rosea](/compound/rhodiola-rosea). Russian researchers — notably **Israel Brekhman** (who coined the term \"adaptogen\" and developed much of the modern scientific framework), **Nikolai Lazarev** (his mentor and collaborator), **Alexander Panossian** (who continues this research tradition into the 21st century), and the Institute of Biologically Active Substances (Russian Academy of Sciences, Vladivostok) — conducted extensive research on schisandra's effects on physical and mental performance, stress tolerance, fatigue reduction, and longevity during the Cold War era. Schisandra was used extensively by Soviet soldiers, cosmonauts, Olympic athletes, and industrial workers for cognitive and physical performance enhancement. Much of this research was published in Russian-language journals and remained largely unknown in the West until recent decades. Alexander Panossian has continued to publish Western-language research on schisandra and other traditional adaptogens, making this body of work more accessible.\n\nThe primary bioactive compounds in schisandra are a family of unique **dibenzocyclooctadiene lignans** (a structural class mostly unique to this plant family), including **schisandrin A, B, C, and D**; **schizandrol A and B**; **schisantherin A, B, and C**; **gomisin A, B, C, J, and N**; **wuweizisu A, B, and C**; and approximately 30+ related compounds. The total lignan content typically ranges from 2-7% in dried berries, and these compounds drive the majority of the pharmacological effects. Additionally, schisandra contains polysaccharides, essential oils (responsible for the aroma and some tastes), organic acids (citric, malic, tartaric — contributing to the sour component of the \"five flavors\"), vitamin C, carotenoids, volatile oils containing terpenes, and minor alkaloids. The distinctive \"five flavors\" arise from different compound classes: sweet from sugars in the pulp, sour from organic acids, salty from mineral content, bitter from lignans and related compounds, and pungent from volatile oils and the seeds. Traditional Chinese medicine assigns each flavor to specific organ system affinities, making schisandra unusually broad-acting in the TCM framework (affecting heart, liver, kidney, lung, and spleen).\n\nThe proposed clinical applications of schisandra span: **(1) hepatoprotection and liver disease** — perhaps the strongest evidence base, with research in chronic hepatitis B and C, non-alcoholic fatty liver disease (NAFLD), and drug/toxin-induced hepatotoxicity; schisandrin B is particularly notable for its hepatoprotective effects and has been developed into pharmaceutical products in China; **(2) cognitive function and mental performance** — improvements in attention, memory, and reaction time, with research in healthy adults, fatigued populations, and neurodegenerative models; **(3) stress adaptation** — classical adaptogen effects on cortisol, HPA-axis, and resilience to physical and psychological stressors; **(4) physical performance** — aerobic and anaerobic exercise capacity, with Russian Olympic-era research heritage; **(5) cardiovascular effects** — modest blood pressure support, possible antiarrhythmic properties, improvements in cardiac function markers; **(6) perimenopausal and menopausal symptoms** — emerging evidence for hot flashes, sweating, and mood effects; **(7) respiratory conditions** — traditional use for cough and asthma; and **(8) general wellbeing and longevity** — the traditional indication.\n\nThe human clinical evidence is moderate — stronger than for many folk remedies but weaker than for pharmaceutical treatments in any specific indication. **Panossian et al. 2009** (*Phytomedicine*) — a randomized controlled trial of ADAPT-232 (a combination of schisandra, rhodiola, and eleuthero) in 108 tired patients over 4 weeks demonstrated significant improvements in attention, accuracy, and speed of complex cognitive tasks. While this tests a combination product rather than schisandra alone, it represents well-designed Panossian-tradition adaptogen research.\n\n**Panossian and Wikman 2008** (*Phytomedicine*) — review of schisandra clinical pharmacology including studies on fatigue, cognitive function, and physical performance. The review synthesizes Russian-era and modern research, concluding that schisandra has \"adaptogenic properties increasing resistance to a wide range of stressors of physical, chemical, and biological origin.\"\n\n**Hancke et al. 1996 and Aslanyan et al. 2010** — Russian research on athletic performance showing improvements in time-to-exhaustion, oxygen utilization, and recovery in athletes supplemented with schisandra extracts. Methodology in some of this research doesn't meet modern Western standards but the consistent direction of benefit across multiple trials is suggestive.\n\n**Chinese hepatitis research** — multiple studies (mostly Chinese-language) have examined schisandrin and schisandra extracts in chronic hepatitis B and C, with reported improvements in liver enzyme levels (ALT, AST), liver function markers, and some viral parameters. A 2013 systematic review of Chinese-language schisandra hepatitis research concluded that the evidence is suggestive but methodology often falls short of Western standards.\n\n**Park et al. 2012** (*Menopause*) — small trial of schisandra fruit extract in 36 perimenopausal women with vasomotor symptoms. Results showed reductions in hot flash frequency and severity compared with placebo, plus improvements in heart rate variability. While a small trial, this provided preliminary support for schisandra in menopausal support.\n\n**Aslanyan et al. 2010** (*Phytotherapy Research*) and related Panossian-lab trials have examined schisandra in combination with other adaptogens for cognitive performance, mental fatigue, and stress resilience — generally with positive but modest effects.\n\nWhere does schisandra fit in the therapeutic landscape? For **chronic liver conditions**, schisandra is an interesting adjunctive option (alongside standard care) given the mechanistic plausibility (Nrf2 activation, CYP modulation, direct antifibrotic effects), though it should NOT replace evidence-based hepatology treatment (entecavir/tenofovir for HBV, direct-acting antivirals for HCV, lifestyle management for NAFLD, appropriate monitoring). For **general adaptogenic use, cognitive/physical performance, and stress resilience**, schisandra is a reasonable natural option with moderate evidence. For **menopausal symptom management**, preliminary evidence supports consideration as part of a broader approach. It is NOT a substitute for evidence-based medications for any specific disease, and users should understand that its effects, while real, are modest. It sits honestly alongside [Rhodiola rosea](/compound/rhodiola-rosea), [Eleuthero](/compound/eleuthero), [Ashwagandha](/compound/ashwagandha), [Panax ginseng](/compound/panax-ginseng), and [Reishi](/compound/reishi) as one of the classical adaptogens, with the distinctive features of its five-flavor pharmacology, hepatoprotective emphasis, and deep Russian research heritage.\n\nSafety is generally excellent at typical doses, with the significant caveat that schisandra is a notable **inducer of cytochrome P450 enzymes** (particularly CYP3A4) and also **inhibits P-glycoprotein** — making drug interactions an important consideration in those on pharmaceutical medications. Schisandra should be used cautiously by anyone on narrow-therapeutic-index drugs (warfarin, digoxin, tacrolimus, cyclosporine, certain antiepileptics, chemotherapies).", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 794, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/schisandra" }, { "id": "729ba7d3-cda7-4608-8583-e62c0d9731eb", "slug": "selank", "name": "Selank", "aliases": [ "TP-7", "Selank Spray" ], "category": "Nootropics", "description": "\nSelank is a synthetic heptapeptide (Thr-Lys-Pro-Arg-Pro-Gly-Pro, 750 Da molecular weight) developed in the 1990s at the Institute of Molecular Genetics of the Russian Academy of Sciences as a synthetic analog of tuftsin — an immunomodulatory tetrapeptide (Thr-Lys-Pro-Arg) that is naturally cleaved from the Fc region of immunoglobulin G. The original tuftsin molecule has well-documented immunomodulatory and neurotropic effects but is rapidly degraded by peptidases in plasma, limiting its therapeutic utility. Selank adds a Pro-Gly-Pro tail to the tuftsin sequence, which confers resistance to enzymatic degradation while preserving pharmacological activity.\n\nIn Russia, Selank has been approved since 2004 for the treatment of generalized anxiety disorder (GAD) and is available by prescription at pharmacies across the Russian Federation and several neighboring countries. It is marketed as a 0.15% intranasal solution under the brand name \"Selank\" (╨í╨╡╨╗╨░╨╜╨║) by Peptogen, a Moscow-based pharmaceutical company. In Western markets, Selank has never been submitted for FDA, EMA, or other major regulatory approval — not because of unfavorable data, but because the commercial pharmaceutical industry has no mechanism to profit from a peptide with an expired patent and no Western development sponsor. As a result, Selank circulates in the biohacking and peptide-curious community primarily as a \"research chemical\" through specialty peptide suppliers, where it is sold in intranasal spray or injectable formulations.\n\nThe pharmacological profile of Selank is distinctive among anxiolytics. Unlike benzodiazepines, it does NOT cause sedation, cognitive dulling, tolerance, dependence, or withdrawal. Unlike SSRIs, it has rapid onset (within 30-60 minutes of intranasal administration) and effects that outlast plasma presence. Unlike buspirone, it does not require weeks of chronic dosing to manifest effects. The compound appears to work through modulation of multiple neurotransmitter systems simultaneously — GABAergic, serotonergic, dopaminergic, and endogenous opioid — producing what the Russian clinical literature describes as an \"anxiolytic + nootropic\" profile: the user feels calmer but also more mentally engaged, not sedated. This unusual combination has driven substantial interest in Western biohacking circles as an alternative or adjunct to conventional anxiety pharmacology.\n\nSelank has been studied in Russian clinical populations for over two decades with a consistent efficacy and safety pattern across roughly 30-50 published clinical papers. The evidence base is real but has important limitations: most trials are Russian-language, published in Russian journals, with small sample sizes (often 30-100 patients), and use Russian psychiatric rating scales rather than the validated Western instruments (GAD-7, HAM-A, Beck Anxiety Inventory) that would facilitate cross-validation. Western meta-analyses and systematic reviews are essentially nonexistent. The Russian regulatory approval is real and meaningful — Russian drug regulation, while different from FDA standards, does require efficacy and safety evidence — but it does not automatically translate to confidence in Western evidence-based medicine frameworks.\n\nFor the biohacking community, Selank's appeal is the combination of (1) rapid-acting anxiolysis without sedation, (2) cognitive enhancement rather than dulling, (3) favorable safety profile across decades of Russian use, (4) non-addictive, non-dependence-producing pharmacology, and (5) intranasal delivery that is simple and needle-free. Its limitations are (1) thin Western evidence base, (2) variable quality from research chemical suppliers, (3) lack of FDA regulation or oversight, (4) modest effect magnitude in some users relative to expectations, and (5) cost relative to generic anxiety pharmacology. This entry covers the pharmacology, clinical evidence, practical use considerations, and honest framing of the evidence gaps. Cross-reference with [Semax](/compound/semax), [DSIP](/compound/dsip), and [Epithalon](/compound/epithalon) for a complete picture of the Russian research peptide landscape.\n", "half_life": "~2-3 minutes plasma half-life (functional anxiolytic and nootropic effects persist 12-24 hours due to gene expression and neurotransmitter modulation)", "molecular_weight": "751.9 Da", "molecular_mass": "751.87 g/mol", "amino_acid_sequence": "Thr-Lys-Pro-Arg-Pro-Gly-Pro (TKPRPGP) - a synthetic heptapeptide; the tuftsin fragment Thr-Lys-Pro-Arg (TKPR) extended at the C-terminus with Pro-Gly-Pro (PGP) to confer resistance to enzymatic degradation. Molecular formula C33H57N11O9.", "administration_routes": [ "Intranasal" ], "dose_range_mcg": "250-750 mcg intranasal daily (0.15% solution: 2-3 drops per nostril 2-3x daily); typical course is 14-21 days", "dosing_frequency": "Intranasal 1–3 times daily", "cycle_length": "14–30 days; can repeat after 1–2 week break", "common_vial_sizes": [ "5mg", "10mg" ], "research_stage": "Approved (Russia, as anxiolytic and nootropic medication)", "approval_status": "Approved in Russia for generalized anxiety disorder", "trial_phase": "", "cas_number": "129843-05-03", "iupac_name": "Thr-Lys-Pro-Arg-Pro-Gly-Pro", "chemical_formula": "C33H57N11O9", "potential_benefits": [ "Anxiolytic effects comparable to benzodiazepines but without sedation or dependence in Russian clinical trials (PMID: 18454096)", "Positive allosteric modulation of brain GABA receptors through a non-benzodiazepine binding site (PMID: 30255741)", "Immunomodulation via Th1/Th2 cytokine balance and IL-6 regulation in patients with anxiety-asthenic disorders (PMID: 18577961)", "Cognitive and memory support linked to BDNF upregulation in the hippocampus in preclinical models (PMID: 18841804)", "Modulation of the endogenous enkephalin-opioid system supporting mood and stress tolerance (PMID: 22550852)", "Anti-inflammatory and adaptogenic effects through normalization of stress-induced cytokine dysregulation", "Non-addictive anxiolytic profile - no tolerance, withdrawal, or dependence reported across years of Russian clinical use" ], "research_fields": [], "pubmed_count": 88, "pubchem_cid": 16129891, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/selank" }, { "id": "66e6e46f-e5b6-417c-9096-9c4e48178b59", "slug": "selenium", "name": "Selenium", "aliases": [ "Se", "L-Selenomethionine", "Selenomethionine", "Sodium selenite", "Sodium selenate", "Selenized yeast", "Selenocysteine", "SelenoPrecise", "Methylselenocysteine" ], "category": "Foundational", "description": "Selenium is an essential trace mineral first recognized as toxic in livestock grazing on seleniferous soils in the American West (reported by Kit Carson's expedition in the 1850s) and only later, in 1957, identified as essential for mammalian life when Klaus Schwarz discovered it prevented liver necrosis in rats deficient in the newly-described \"Factor 3.\" The subsequent decades revealed that selenium's essentiality derives from its incorporation into approximately 25 distinct selenoproteins in humans, where it appears as the 21st genetically-encoded amino acid selenocysteine (Sec, U) at specific active sites. Unlike most trace minerals whose biology depends on loose or labile binding, selenium is covalently built into the protein structure during translation through a notable ribosomal mechanism that reads the normally-terminating UGA codon as selenocysteine when a specific SECIS (selenocysteine insertion sequence) element is present in the mRNA 3' untranslated region. This sophisticated incorporation system underscores that selenium is not simply a bystander cofactor but a genuinely integral component of its target proteins.\n\nThe 25 human selenoproteins fall into functional categories that explain selenium's pleiotropic physiological roles. The glutathione peroxidase (GPX) family uses selenocysteine in its active site to reduce hydrogen peroxide and organic hydroperoxides, making them central to cellular antioxidant defense (see /compound/glutathione for the broader glutathione system). The thioredoxin reductase (TXNRD) family regulates protein disulfide reduction and is critical for redox signaling, DNA synthesis, and apoptotic control. The iodothyronine deiodinase (DIO) family activates and inactivates thyroid hormones—DIO1 and DIO2 convert T4 (thyroxine) to the metabolically active T3 (triiodothyronine), while DIO3 inactivates both. The methionine sulfoxide reductase family (MSRB1) repairs oxidatively-damaged methionine residues in proteins. Selenoprotein P (SELENOP) transports selenium in plasma and delivers it to peripheral tissues including brain and testis. Numerous other selenoproteins with less fully characterized functions contribute to protein folding (SELENOF, SELENOK, SELENOM, SELENOS in endoplasmic reticulum), ferroptosis protection (GPX4), muscle function (SELENON—mutated in rigid spine muscular dystrophy), and still-emerging roles in immunity, reproduction, and aging.\n\nGeographic variation in soil selenium content drives striking regional differences in human selenium status. Low-selenium belts spanning parts of China, New Zealand, Finland (prior to fertilizer supplementation programs), and certain European regions produce populations with historically low dietary intake, while seleniferous regions of the western United States (Dakotas, Wyoming, Nebraska), parts of Venezuela, and certain Indian regions produce the opposite. Finland's national response to low soil selenium—adding selenate to agricultural fertilizers in 1984—is a textbook example of successful population-level nutritional intervention, raising serum selenium to more biologically optimal levels across the country. In most developed countries with diverse imported food supplies, clinical selenium deficiency is uncommon, but suboptimal status remains prevalent: U.S. data suggest roughly 15-25% of adults have serum selenium below the range associated with full selenoprotein expression.\n\nThe clinical significance of selenium status spans several domains with varying evidence strength. Severe deficiency manifests as two classical syndromes: Keshan disease (a congestive cardiomyopathy first described in selenium-deficient regions of China, associated with Coxsackie virus coinfection) and Kashin-Beck disease (a deforming osteoarthropathy of children and adolescents in specific Asian regions). Both have largely disappeared with dietary diversification and selenium supplementation programs. More subtle suboptimal selenium status is implicated in thyroid autoimmunity (Hashimoto's thyroiditis), male fertility concerns, immune function impairment, impaired resistance to certain viral infections, possibly modified cancer risk in specific tissues, and cardiovascular disease—though the evidence base varies substantially by endpoint.\n\nThyroid health is arguably the most evidence-based clinical application of selenium supplementation outside of deficiency states. Multiple randomized controlled trials (reviewed in Drutel et al. and Toulis et al.) demonstrate that selenium supplementation at 200 mcg daily (typically as selenomethionine) reduces anti-thyroperoxidase (anti-TPO) antibody titers in patients with Hashimoto's thyroiditis over 6-12 months. Effect sizes vary across trials, and whether antibody reduction translates to preserved thyroid function and delayed progression to hypothyroidism is debated, but the signal is consistent enough that some endocrinologists routinely recommend selenium for autoimmune thyroiditis patients. Similar evidence supports selenium supplementation in mild Graves' orbitopathy (CATALYST trial, Marcocci et al., PMID 21591944) where 200 mcg selenium daily improved clinical severity scores and quality of life compared to placebo.\n\nCancer prevention is where the selenium story has evolved dramatically. The Nutritional Prevention of Cancer (NPC) trial (Clark et al.) initially reported in 1996 that 200 mcg/day selenized yeast reduced total cancer mortality by about 50% in a high-risk population. This catalyzed enormous interest in selenium chemoprevention. The much larger SELECT trial (Lippman et al., PMID 19066370) randomized 35,533 men to selenium 200 mcg/day (L-selenomethionine), vitamin E, both, or placebo for prostate cancer prevention—and found no benefit from selenium, no benefit from vitamin E (with a signal of increased prostate cancer with vitamin E alone), and no benefit from the combination. Subsequent reanalysis of NPC found the apparent benefit was driven by baseline-deficient participants and disappeared in higher-selenium subgroups. The current consensus is that selenium supplementation does not prevent cancer in selenium-replete populations and may carry risks at higher chronic doses (including possible increased risk of type 2 diabetes—Stranges et al.). In deficient populations or for specific cancer types, targeted selenium may still offer benefit, but population-level cancer chemoprevention is no longer supported.\n\nFor BodyHackGuide users, selenium occupies a specific and context-dependent role. Most Americans obtain adequate selenium from diverse diets—a single Brazil nut can deliver 50-100 mcg (with wide variability), and typical omnivorous diets provide 80-150 mcg daily. Routine high-dose supplementation is neither necessary nor clearly beneficial for most users and may carry small risks. Specific populations who benefit most from selenium supplementation include those with documented deficiency, autoimmune thyroid disease (Hashimoto's, Graves'), living in low-selenium regions, restrictive vegetarian/vegan diets with minimal selenium-rich foods, HIV infection, or specific oncology/integrative contexts under clinician supervision. The typical supplementation target in these populations is 100-200 mcg daily from L-selenomethionine or selenized yeast, with monitoring of total intake (diet + supplement) not exceeding the tolerable upper limit of 400 mcg daily.\n\nCommon supplementation errors include: (1) adding a 200 mcg selenium supplement to a diet already containing 1-2 Brazil nuts per day (risking chronic high-dose intake), (2) assuming selenium is universally \"healthy\" without considering U-shaped dose-response where deficiency and excess both cause harm, (3) using inorganic selenite exclusively when organic selenomethionine has better bioavailability and safety profile for chronic supplementation, (4) expecting cancer prevention benefits that SELECT and later trials have failed to confirm, and (5) neglecting interaction with iodine in thyroid contexts. This monograph addresses form selection, dose tuning, specific clinical indications, and the safety considerations that make selenium a compound requiring more nuance than simpler foundational supplements. For related foundational support, see /compound/glutathione (selenium is core to glutathione peroxidase function), /compound/zinc (parallel trace mineral considerations), /compound/vitamin-c (antioxidant network partner), and /compound/vitamin-d (thyroid autoimmunity interaction).", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 20, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/selenium" }, { "id": "a1000000-0000-0000-0000-000000000003", "slug": "semaglutide", "name": "Semaglutide", "aliases": [ "GLP-1S", "GLP-1 Agonist", "RC-1S", "PEP-1S", "ION-1S", "Ion Peptide Semaglutide", "GLP-1", "Semaglutide", "Sema" ], "category": "Metabolic & Weight Loss", "description": "Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with a molecular weight of 4113.58 Da and CAS number 910463-68-2. It is a 31-amino-acid peptide analog of human GLP-1(7-37) with two key structural modifications: an alpha-aminoisobutyric acid (Aib) substitution at position 8 that confers resistance to dipeptidyl peptidase-4 (DPP-4) enzymatic degradation, and a C18 fatty diacid chain attached via a linker at position 26 (lysine) that enables non-covalent binding to serum albumin. This albumin binding dramatically extends the half-life to approximately 7 days, enabling once-weekly subcutaneous dosing (PMID: 33567185).\n\nSemaglutide is FDA-approved under three brand names: Ozempic (subcutaneous injection for type 2 diabetes mellitus), Wegovy (subcutaneous injection for chronic weight management), and Rybelsus (oral tablet for type 2 diabetes). Ozempic was approved in 2017, Wegovy in 2021, and Rybelsus in 2019, making semaglutide one of the most commercially significant pharmaceutical developments of the 2020s.\n\nThe STEP (Semaglutide Treatment Effect in People with Obesity) clinical trial program established semaglutide as a transformative obesity treatment. In the STEP 1 trial, participants receiving semaglutide 2.4 mg weekly achieved a mean body weight reduction of 14.9% from baseline at 68 weeks, compared to 2.4% with placebo — a treatment difference of 12.4 percentage points (PMID: 33567185). The STEP 5 trial demonstrated durability of weight loss with continued treatment over 104 weeks, with participants maintaining approximately 15% total body weight loss (PMID: 34170647).\n\nThe SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) trial was a landmark cardiovascular outcomes study that demonstrated a 20% relative risk reduction in major adverse cardiovascular events (MACE — cardiovascular death, nonfatal myocardial infarction, nonfatal stroke) in overweight or obese individuals without diabetes who received semaglutide 2.4 mg weekly versus placebo over a median follow-up of 39.8 months (PMID: 37351564). This was the first trial to demonstrate cardiovascular benefit of a weight management drug in a non-diabetic population, fundamentally changing the clinical paradigm around obesity pharmacotherapy.\n\nOral semaglutide (Rybelsus) uses the absorption enhancer SNAC (sodium N-[8-(2-hydroxybenzoyl)amino] caprylate) to enable GI absorption of the peptide. Despite low bioavailability (~1%), the oral formulation achieves clinically meaningful glycemic control in type 2 diabetes. Higher-dose oral semaglutide (25 mg and 50 mg) formulations evaluated in the OASIS program have shown weight loss approaching that of subcutaneous semaglutide.\n\nSemaglutide represents a first-in-class efficacy level among GLP-1 receptor agonists for both glycemic control and weight reduction, with a well-characterized safety profile across tens of thousands of clinical trial participants and millions of post-marketing prescriptions.", "half_life": "~7 days (168 hours), enabled by C18 fatty diacid albumin-binding modification", "molecular_weight": "4113.6 Da", "molecular_mass": "4113.58 g/mol", "amino_acid_sequence": "HXEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (31-residue analog of human GLP-1(7-37); X at position 8 = Aib, 2-aminoisobutyric acid). Key modifications vs native GLP-1: Ala8->Aib (confers DPP-4 resistance), Lys34->Arg, and the Lys26 side chain is acylated with a C18 fatty diacid (octadecanedioic acid) via a gamma-Glu / 2x AEEA (8-amino-3,6-dioxaoctanoic acid) linker, enabling strong albumin binding and a ~1-week half-life. Molecular formula C187H291N45O59; average molecular weight ~4113.6 Da.", "administration_routes": [ "Subcutaneous (weekly)", "Oral (daily)" ], "dose_range_mcg": "Diabetes (Ozempic): 250-1000 mcg weekly; Weight management (Wegovy): 2400 mcg weekly (after 16-week titration); Oral (Rybelsus): 3-14 mg daily", "dosing_frequency": "Once weekly subcutaneous injection", "cycle_length": "Ongoing; dose escalation over 16–20 weeks to maintenance dose", "common_vial_sizes": [ "3mg", "5mg", "10mg" ], "research_stage": "FDA Approved", "approval_status": "FDA-approved: Ozempic® (T2D, 2017), Wegovy® (obesity, 2021), Rybelsus® (oral, T2D, 2019)", "trial_phase": "FDA Approved", "cas_number": "910463-68-2", "iupac_name": "N-epsilon26-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butyrylamino]ethoxy}ethoxy)acetamido]ethoxy}ethoxy)acetyl][Aib8,Arg34]GLP-1-(7-37)-peptide", "chemical_formula": "C187H291N45O59", "potential_benefits": [ "Mean body weight reduction of 14.9% at 68 weeks in STEP 1 trial (PMID: 33567185)", "Sustained weight loss of ~15% (-15.2%) maintained through 104 weeks in STEP 5 trial (PMID: 36216945)", "20% relative reduction in major adverse cardiovascular events (HR 0.80) in the SELECT trial (PMID: 37952131)", "HbA1c reduction of 1.5-1.8% in type 2 diabetes (SUSTAIN program)", "Reduction in systemic inflammation (lower hs-CRP) observed in SELECT", "Available in both subcutaneous (weekly) and oral (daily) formulations", "Improved cardiometabolic risk factors including blood pressure and lipid profile" ], "research_fields": [ "Obesity", "Type 2 diabetes", "Cardiovascular disease", "NASH/MAFLD", "Kidney disease" ], "pubmed_count": 3273, "pubchem_cid": 56843326, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/56843326/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/semaglutide" }, { "id": "b76ce75f-3ede-465a-bbd3-54fb4061cb7a", "slug": "semax", "name": "Semax", "aliases": [ "ACTH 4-10", "BDNF Spray", "BDNF", "Flow Spray" ], "category": "Nootropics", "description": "\nSemax is a synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro, MEHFPGP, 813 Da molecular weight) developed at the Institute of Molecular Genetics of the Russian Academy of Sciences in the 1980s. The compound is derived from ACTH(4-10) — the 4-10 amino acid fragment of adrenocorticotropic hormone — with the addition of a Pro-Gly-Pro C-terminal tail that confers resistance to enzymatic degradation while preserving neurotropic activity. Critically, Semax retains the cognitive, neurotrophic, and neuroprotective effects of its ACTH parent while completely lacking the adrenal-stimulating hormonal activity. In other words, Semax works on the brain without activating the HPA axis or affecting cortisol production — a therapeutically ideal profile.\n\nSemax was patented in 1982 by Russian researchers and achieved regulatory approval in the Russian Federation in 2000, where it is prescribed at pharmacies for cerebrovascular disorders (ischemic stroke recovery), optic nerve disorders, minimal brain dysfunction in children (ADHD-like presentations), asthenia, and various cognitive complaints. It is available in two commercial strengths: 0.1% intranasal solution for cognitive-nootropic indications and 1% intranasal solution for stroke recovery and neurological deficits. In Western markets, Semax has never been submitted for FDA, EMA, or other major regulatory approval — a pattern common to Russian neuropeptides that lack patent protection and Western pharmaceutical sponsors. It circulates in US and European biohacking communities through research chemical peptide suppliers and is considered one of the most potent, best-tolerated nootropic compounds available.\n\nThe pharmacology of Semax is genuinely notable and spans multiple neurological domains. At the molecular level, Semax elevates BDNF (brain-derived neurotrophic factor) and NGF (nerve growth factor) expression in the brain, promotes dopaminergic and serotonergic signaling, potentiates endogenous enkephalin activity, and upregulates expression of neuroprotective genes. At the clinical level, it produces cognitive enhancement (attention, memory, executive function), mood elevation, stress tolerance, neuroprotection during ischemia, and accelerated recovery from neurological injury. Russian clinical trials in acute ischemic stroke — the best-documented Semax indication — show meaningful improvements in functional recovery when Semax is administered within 6-24 hours of stroke onset, likely through direct neuroprotection plus enhanced neurogenesis during recovery. The stroke literature is the only domain where Semax has truly rigorous clinical trial evidence ([Gusev et al., 2005]).\n\nIn the biohacking and cognitive enhancement community, Semax has achieved a reputation as the \"premier Russian nootropic\" — often positioned alongside [Selank](/compound/selank), [Noopept](/compound/noopept), Modafinil, and racetams in the advanced cognitive stack. Users typically report improvements in focus, working memory, verbal fluency, motivation, stress tolerance, and overall cognitive throughput. The effects are often described as \"clean\" — producing alertness and engagement without the jitters of stimulants, without the emotional blunting of SSRIs, and without the sedation of anxiolytics. Dose-response is relatively modest (300-900 mcg daily typical), onset is rapid (15-30 minutes after intranasal administration), and effects last several hours per dose. Chronic use over weeks produces accumulating cognitive and mood benefits that appear to outlast plasma presence.\n\nThis entry covers Semax pharmacology, the genuinely rigorous Russian stroke evidence base, the more speculative cognitive enhancement applications, protocol considerations, and safety profile. It should be read as an educational reference — Semax is not FDA-approved, is distributed through gray-market channels with variable quality, and anyone considering use should obtain reliable product, start conservatively, and have realistic expectations. Cross-reference with [Selank](/compound/selank), [DSIP](/compound/dsip), and [Epithalon](/compound/epithalon) for Russian peptide context, and with Noopept, Piracetam, and Modafinil for broader nootropic comparisons.\n", "half_life": "~2-3 minutes plasma half-life (functional neurological effects persist 12-24 hours due to BDNF/NGF gene expression changes)", "molecular_weight": "813.9 Da", "molecular_mass": "813.93 g/mol", "amino_acid_sequence": "Met-Glu-His-Phe-Pro-Gly-Pro (heptapeptide; single-letter MEHFPGP). Semax is a synthetic analog of ACTH(4-10): it retains the ACTH(4-7) fragment (Met-Glu-His-Phe) and replaces residues 8-10 (Arg-Trp-Gly) with a C-terminal Pro-Gly-Pro tripeptide, which confers resistance to enzymatic degradation while preserving the CNS activity of the parent ACTH fragment. Empirical formula C37H51N9O10S; molecular weight ~813.9 g/mol.", "administration_routes": [ "Intranasal" ], "dose_range_mcg": "100-900 mcg intranasal daily (0.1% solution: 2-3 drops per nostril 2-3x daily); 1% solution used for acute stroke in Russian clinical protocols", "dosing_frequency": "Intranasal 1–3 times daily", "cycle_length": "14–30 days; can repeat after 1–2 week break", "common_vial_sizes": [ "5mg", "10mg" ], "research_stage": "Approved (Russia, since mid-1990s for stroke and cognitive disorders)", "approval_status": "Approved in Russia for cognitive disorders, stroke recovery, and optic nerve diseases", "trial_phase": "", "cas_number": "80714-61-0", "iupac_name": "Met-Glu-His-Phe-Pro-Gly-Pro", "chemical_formula": "C39H56N10O10S", "potential_benefits": [ "Rapid BDNF/TrkB upregulation in the hippocampus, supporting synaptic plasticity and learning (PMID: 16996037)", "Neuroprotective, immunomodulatory gene-expression changes in focal cerebral ischemia (middle cerebral artery occlusion) models (PMID: 28255762)", "Cognitive enhancement including improved attention, working memory, and processing speed", "Dopaminergic modulation that may support motivation and executive function (preclinical data)", "Stroke recovery facilitation - accelerated functional recovery and improved Barthel Index in ischemic stroke patients; approved in Russia for ischemic stroke (PMID: 29798983)", "Anxiolytic and anti-asthenic effects reported in Russian clinical use, attributed to neurotrophic and monoaminergic modulation", "Non-addictive cognitive support without tolerance development or withdrawal at standard doses" ], "research_fields": [], "pubmed_count": 205, "pubchem_cid": 16130456, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/semax" }, { "id": "9b7c02c6-301d-4428-a3bb-dbada9ed989a", "slug": "semax-p21", "name": "Semax P-21", "aliases": [ "Semax-P21", "SemaxP21", "Semax + P21 Hybrid" ], "category": "Nootropic Peptide", "description": "Semax P-21 is a **hybrid synthetic peptide** combining structural motifs from [Semax](/compound/semax) and [P-21](/compound/p21) into a single molecule. Marketed as a one-shot drop-in for users running both compounds, the rationale is convenience (one peptide instead of two) and additive cognitive + anxiolytic effects.\n\nThe peer-reviewed literature on this specific hybrid is essentially absent — most pharmacological characterization is by analogy to the constituent peptides. Treat it as Semax-equivalent on cognition and P-21-equivalent on anxiolysis until stronger primary data emerges.", "half_life": "No combined-product pharmacokinetics exist. Semax (intranasal): the intact peptide is rapidly metabolized (on the order of minutes), though downstream BDNF/neurotrophic effects outlast the peptide itself. P-21 / P021: a small molecule with pharmacokinetics suitable for oral dosing in animal studies; no human PK data.", "molecular_weight": "Not a single molecule - \"Semax P-21\" is two separate peptides, so no combined molecular weight applies. Per constituent: Semax (heptapeptide, Met-Glu-His-Phe-Pro-Gly-Pro) is approximately 813.9 g/mol; P-21 / P021 (Ac-DGGL(A)G-NH2, a CNTF-derived peptide mimetic) is a low-molecular-weight, blood-brain-barrier-permeable small molecule.", "molecular_mass": "", "amino_acid_sequence": "Semax: Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP) - ACTH(4-7) extended with a C-terminal Pro-Gly-Pro. P-21 / P021: Ac-DGGL(A)G-NH2, an N-acetylated, C-amidated peptide mimetic derived from the active region (Peptide-6) of ciliary neurotrophic factor (CNTF). These are two distinct peptides, not one sequence.", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Not FDA-approved; research use only. Semax is a registered pharmaceutical in Russia (clinical use for stroke and cognitive indications). P-21 / P021 is investigational, with animal studies only and no human trials.", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "C40H58N14O11", "potential_benefits": [], "research_fields": [], "pubmed_count": 1, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/semax-p21" }, { "id": "a43a3857-d41f-4102-9a4d-2f29da0affd7", "slug": "semax-selank-blend", "name": "Semax/Selank Blend", "aliases": [ "Semax Selank" ], "category": "Nootropics", "description": "Combined nootropic and anxiolytic peptide blend", "half_life": "Both component peptides have short plasma half-lives (on the order of minutes) but a prolonged duration of central action, attributed to the protective C-terminal Pro-Gly-Pro sequence they share. Blend-specific pharmacokinetics have not been characterized.", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "Semax ~250-600 mcg + Selank ~250-300 mcg per day, intranasal (community-reported; no established blend dose)", "dosing_frequency": "Once or twice daily, intranasal (community practice; no validated schedule for the blend)", "cycle_length": "Community cycles are typically ~2-4 weeks on with an equal or longer break; no clinically validated cycle length exists for the blend.", "common_vial_sizes": [], "research_stage": "Preclinical (no trials on the blend; components studied separately, mostly in Russia)", "approval_status": "Not FDA-approved. Semax and Selank are approved medicines in Russia; the blend and its components are sold elsewhere as research chemicals only (RUO).", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "Blend", "potential_benefits": [ "Focus, clarity, and verbal fluency attributed to the Semax component (linked to BDNF/TrkB neurotrophic signaling in preclinical studies)", "Calming, anti-anxiety effects attributed to the Selank component (a GABA-modulating, anxiolytic peptide in animal and limited clinical studies)", "'Calm focus' - the community rationale of pairing an activating peptide with an anxiolytic one to get drive without jitters", "Anecdotal stress resilience and mood support", "Reported memory and learning support (component-level preclinical signals only; not demonstrated for the blend)" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/semax-selank-blend" }, { "id": "630a7b96-cf7e-4bce-9957-19a012803bb3", "slug": "sermorelin", "name": "Sermorelin", "aliases": [ "GRF 1-29" ], "category": "Growth Hormone / IGF-1 Axis", "description": "Sermorelin acetate is a synthetic 29-amino-acid peptide corresponding to the biologically active N-terminal fragment of human growth hormone-releasing hormone (GHRH 1-29). It was one of the first GHRH analogs to achieve FDA approval — Geref received pediatric approval in 1997 for evaluating and treating idiopathic growth hormone deficiency in children. Although the branded product was discontinued commercially in 2008 due to market factors unrelated to safety or efficacy, sermorelin has experienced a significant second life through 503B compounding pharmacies that supply it for off-label use in adult growth hormone axis support, anti-aging medicine, and athletic performance contexts.\n\nSermorelin binds the GHRH receptor (GHRHR) on pituitary somatotrophs and triggers endogenous growth hormone release through the body's native negative-feedback architecture. Because it relies on pituitary reserve rather than bypassing it, sermorelin produces **pulsatile GH release that respects somatostatin inhibition** — you cannot overshoot the way exogenous recombinant human GH can, and IGF-1 typically rises into the upper quartile of age-adjusted normal rather than into supraphysiological territory. This is the fundamental mechanistic difference that makes GHRH therapy tolerable for long-term use where rhGH use carries more concerning risks.\n\nIts short serum half-life — approximately **10 to 20 minutes** in healthy adults — is simultaneously sermorelin's greatest limitation and its most clinically elegant feature. The short window forces once-daily bedtime dosing that aligns with the body's natural nocturnal GH pulse, and it means residual peptide never persists long enough to disturb subsequent endogenous pulses. Modern practitioners frequently choose sermorelin over longer-acting analogs like CJC-1295 DAC specifically because the pulsatile kinetics more closely mimic healthy young physiology.\n\nIn research and clinical settings, sermorelin is typically dosed at **200 to 500 mcg subcutaneously at bedtime** for adult GH tuning protocols, though historical pediatric GHD protocols used up to 30 mcg/kg/day. Six-month trials in healthy older adults have demonstrated modest but measurable gains in lean body mass, reductions in visceral adiposity, and improvements in sleep architecture — particularly slow-wave sleep depth, which is where the majority of physiologic GH secretion occurs in the first place.", "half_life": "~10-20 minutes (plasma; native GHRH 7 minutes)", "molecular_weight": "", "molecular_mass": "3357.9 g/mol", "amino_acid_sequence": "YADAIFTNSYRKVLGQLSARKLLQDIMSR-NH2 (29 residues; GHRH(1-29) with a C-terminal amide). Full sequence: H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2. Molecular formula C149H246N44O42S; molecular weight ~3357.9 g/mol.", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "FDA-Approved (Geref, discontinued 2008)", "approval_status": "FDA-approved in 1997 as Geref (sermorelin acetate, Serono) for growth hormone deficiency, and used clinically as a GHRH stimulation/diagnostic agent. The manufacturer (EMD Serono) discontinued the branded product in 2008 for commercial reasons - not safety or efficacy - so it is no longer marketed as an FDA-approved finished drug. Today sermorelin is obtained by prescription through 503A/503B compounding pharmacies or sold research-use-only; adult 'anti-aging' and body-composition use is off-label and unapproved.", "trial_phase": "FDA Approved", "cas_number": "86168-78-7", "iupac_name": "Growth hormone-releasing hormone (1-29) amide", "chemical_formula": "C149H246N44O42S", "potential_benefits": [ "Natural GH pulse stimulation", "Improved sleep quality", "Enhanced recovery and body composition", "Anti-aging effects", "Better skin elasticity", "Increased lean muscle mass" ], "research_fields": [ "Growth hormone deficiency", "Anti-aging", "Body composition", "Pituitary function" ], "pubmed_count": 198, "pubchem_cid": 16132104, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/16132104/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/sermorelin" }, { "id": "86e7d5d8-7f25-4f57-8206-85f806ba0203", "slug": "shilajit", "name": "Shilajit", "aliases": [ "Mumijo", "Moomiyo", "Salajeet", "Mineral Pitch", "Asphaltum Punjabinum", "Shilajeet", "Shilajatu", "Silajit", "Himalayan Mineral Pitch", "Mumiyo", "Black Bitumen", "Mineral Wax", "Jew's Pitch" ], "category": "Adaptogen", "description": "**Shilajit** (Sanskrit: *shilajatu*, αñ╢αñ┐αñ▓αñ╛αñ£αññαÑü, literally \"rock-conqueror\" or \"rock-invincible\"; Hindi/Urdu: *shilajit*; Persian and Central Asian: *mumijo*, *moomiyo*, *mumiyo*; Pashto/Afghan: *salajeet*; Latin pharmacopeial: *Asphaltum Punjabinum*) is a blackish-brown, sticky, resin-like mineral-organic exudate that oozes from cracks in rock formations in high-altitude mountain ranges, most famously the Himalayas and Karakoram but also the Altai, Tien Shan, Caucasus, and Hindu Kush ranges. Unlike almost every other substance in traditional herbal medicine, shilajit is **not a plant** — it's a complex mineral-organic matrix formed over centuries to millennia by the slow decomposition of specific plant materials (predominantly *Euphorbia royleana*, *Trifolium repens*, *Barleria prionitis*, and various mosses and lichens) subjected to heat, pressure, geological compression, and microbial action within rock formations. The resulting exudate, when harvested by scraping it from rock crevices at elevations of 3,000-5,000 meters, has a characteristic tarry, bitumen-like texture and a complex bitter-salty taste.\n\nShilajit holds special status in **Ayurveda** (the classical Indian medical system) as a *rasayana* — a rejuvenative substance — and specifically as a **\"maharasa\"** (great rasa, or supreme substance). The **Charaka Samhita** (~400 BCE) refers to shilajit extensively, stating that \"there is no curable disease which cannot be cured by shilajit, taken with the appropriate carrier substance (*anupana*).\" The **Sushruta Samhita** and later texts like **Rasa Shastra** treatises (medieval period) provide detailed processing protocols (*shodhana* — purification). Classical Ayurvedic theory classifies shilajit by the mountain source it derives from — mountains containing **gold** (svarna shilajit), **silver** (rajata), **copper** (tamra), or **iron** (lauha) — each described as having somewhat different therapeutic profiles. The most prized is gold-mountain shilajit, described as golden-brown rather than pure black. Modern commercial shilajit typically doesn't specify this classical classification.\n\nCentral Asian and Russian traditions know shilajit as **mumijo** (Russian: ╨╝╤â╨╝╨╕╤æ, also transliterated as *moomiyo*, *mumiyo*, *mummy*), with extensive Soviet-era pharmacological and clinical research in Russia, Kazakhstan, Uzbekistan, Tajikistan, and Kyrgyzstan. Soviet research from the 1960s-1980s investigated mumijo for wound healing, bone fracture repair, rheumatism, gastrointestinal ulcers, and athletic performance — yielding substantial literature that is separately pharmacologically instructive but often methodologically limited by contemporary standards. The Central Asian mumijo tradition is distinct from but parallel to the South Asian Ayurvedic shilajit tradition, and both refer to essentially the same substance with regional variations in sourcing and processing.\n\nThe primary bioactive compounds in shilajit span several chemical classes. **Fulvic acid** (FvA) — a family of low-molecular-weight humic substances — is typically the most-abundant marker compound, comprising 15-50%+ of quality purified shilajit. Fulvic acid is a complex mixture of aromatic polyhydroxylic organic acids formed during organic matter decomposition, with established roles in mineral chelation, cell membrane transport, and electron shuttling. **Humic acid** — a higher molecular weight cousin of fulvic acid — is also present but typically filtered out in quality purified preparations due to lower bioavailability and higher potential for contamination. **Dibenzo-α-pyrones** (DBPs, also called **urolithins-related compounds** or **chromenes**) are a class of heterocyclic compounds unique to shilajit, with dibenzo-α-pyrone itself (3,8-dihydroxy-DBP, or 3,8-dihydroxy dibenzo-α-pyrone) and related compounds shown to have specific antioxidant, mitochondrial, and ubiquinone-sparing effects. **DBP-chromoproteins** are shilajit-specific chromoprotein complexes containing DBPs bound to protein structures. **Low-molecular-weight peptides** (typically <5 kDa) contribute to some biological effects. **Trace minerals** include iron, copper, zinc, manganese, magnesium, potassium, calcium, and many others in chelated forms bound to fulvic acid. **Selenium** is present and contributes to antioxidant effects. Quality standardized shilajit preparations typically report fulvic acid content (35-50%+ common in premium products) and sometimes DBP content.\n\nThe proposed clinical applications of shilajit span: **(1) energy, fatigue, and chronic fatigue syndrome** — perhaps the primary traditional and modern use, with growing evidence for mitochondrial function improvement; **(2) male reproductive health / testosterone** — one of the better-evidenced modern applications with specific RCTs showing testosterone elevation and improvements in spermatogenesis; **(3) exercise performance and recovery** — evidence for muscle strength, recovery markers, and athletic performance; **(4) cognitive function and Alzheimer's disease** — preliminary evidence for cognitive support particularly through DBP effects on amyloid and tau; **(5) iron absorption and anemia** — traditional use with modern rationale based on fulvic acid chelation; **(6) bone health and fracture healing** — classical \"destroyer of weakness\" including bone applications; **(7) wound healing** — Soviet mumijo tradition and modern research; **(8) gastric/GI health** — including traditional and modern evidence for peptic ulcer support; **(9) adaptogenic effects** — the general rejuvenation and stress-resilience tradition; and **(10) heavy metal detoxification** — proposed fulvic acid effects, though this is controversial given contamination risk.\n\nHuman clinical evidence for shilajit has grown substantially over the past 2 decades, with Indian pharmaceutical companies (particularly Natreon Inc., makers of PrimaVie shilajit) funding most Western-style RCTs. Key trials: **Biswas et al. 2010** (*Andrologia*) — RCT of PrimaVie purified shilajit (250mg twice daily) in 60 oligospermic (low sperm count) men for 90 days showed significant improvements in sperm count, motility, and quality. **Pandit et al. 2016** (*Andrologia*) — RCT of PrimaVie shilajit (250mg twice daily) in 75 men aged 45-55 with healthy testosterone for 90 days showed significant total and free testosterone elevation. **Keller et al. 2017** (*Journal of the International Society of Sports Nutrition*) — RCT examining shilajit effects on hydroxyproline (collagen synthesis marker) and exercise-related outcomes. **Das et al. 2016** (*Scientifica*) — demonstrated shilajit effects on fatigue and quality of life in chronic fatigue syndrome. **Cornelli et al. 2011** — examined shilajit in cognitive function outcomes. **Carrasco-Gallardo et al. 2012** (*International Journal of Alzheimer's Disease*) — reviewed shilajit's mechanistic potential in Alzheimer's disease with particular focus on DBP effects.\n\nWhere does shilajit fit in the therapeutic landscape? It has a distinctive profile: **(1)** a **mineral-organic matrix** rather than a conventional herb, offering very different pharmacology than plant-based adaptogens; **(2)** a **specific male reproductive tonic** role with better testosterone data than most natural products ([Tongkat Ali](/compound/tongkat-ali) is comparable); **(3)** **mitochondrial and CoQ10-sparing effects** through DBPs — mechanistically distinct from other adaptogens; **(4)** **fulvic acid pharmacology** not shared with other supplements — effects on mineral absorption, electron transport, and possibly neuroprotection; **(5)** classical framing as **\"destroyer of weakness\"** covering a wide range of aging-related decline; and **(6)** **significant quality-control sensitivity** — a substance requiring serious vetting given contamination history. It pairs meaningfully with [Ashwagandha](/compound/ashwagandha) (the other pillar of Ayurvedic male tonics — different mechanisms, complementary effects), [Tongkat Ali](/compound/tongkat-ali) (shared testosterone focus with different mechanisms), [Fadogia agrestis](/compound/fadogia-agrestis) (testosterone emphasis), [Tribulus terrestris](/compound/tribulus-terrestris) (Ayurvedic companion), [CoQ10](/compound/coq10) (complementary mitochondrial support — DBPs help recycle CoQ10), [NAD+](/compound/nad) precursors (mitochondrial/longevity focus), [Creatine](/compound/creatine) (exercise performance), [Tulsi](/compound/tulsi) (classical Ayurvedic pairing), and [Bacopa monnieri](/compound/bacopa-monnieri) (Ayurvedic cognitive support pairing).\n\nSafety profile is excellent for properly purified shilajit but dismal for unpurified/contaminated preparations — a critical distinction. Raw shilajit from rock faces contains significant mycotoxins, free radicals, polymeric quinones, and potentially toxic heavy metals (especially lead, arsenic, mercury) requiring proper **shodhana** (Ayurvedic purification) or modern purification processes. Quality purified shilajit with verified low heavy metal content has excellent safety. Unpurified or poorly purified shilajit can be actively dangerous. This makes supplier selection and third-party testing absolutely essential — more so than perhaps any other adaptogen.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/shilajit" }, { "id": "58320cb9-1caf-42ad-bc55-cb1addda03c0", "slug": "silymarin", "name": "Silymarin", "aliases": [ "Milk Thistle Extract", "Silybum marianum", "Silibinin", "Silybin", "Legalon", "Siliphos", "IdB1016", "Silipide" ], "category": "Hepatoprotective Flavonolignan", "description": "Silymarin is the standardized flavonolignan complex extracted from the seeds (technically the fruit, or achenes) of milk thistle — Silybum marianum — a thistle native to the Mediterranean basin now naturalized across Europe, North Africa, North and South America, and Australia. Silymarin is not a single molecule but a defined mixture of six closely related flavonolignans: silybin A, silybin B (together called silibinin, the dominant and most pharmacologically active pair, representing roughly 50–70% of the silymarin complex), isosilybin A, isosilybin B, silychristin, and silydianin, along with minor constituents including taxifolin (the biosynthetic flavonoid precursor) and small quantities of apigenin-7-glucoside and other flavonoids. The United States Pharmacopeia (USP) defines standardized milk thistle extract as containing 70–80% silymarin, of which silibinin should constitute at least 30% of the total. European Medicines Agency and German Commission E monographs establish parallel standards. This standardization matters because \"milk thistle\" products vary in potency by more than an order of magnitude depending on extraction method, cultivar, and whether the product is standardized at all — non-standardized seed powder in bulk capsules bears little resemblance to clinical-trial standardized extracts.\n\nSilymarin is the most extensively studied, most widely used, and most pharmacologically consequential hepatoprotective natural product in the Western materia medica. Its use in liver disease traces back to Pliny the Elder (1st century CE) and Dioscorides, was codified in German phytomedicine in the 1960s following chemical characterization by Wagner and colleagues, and has since generated more than 1,000 peer-reviewed publications — including pharmacokinetic studies, mechanistic work, animal models of virtually every major liver injury pattern, and dozens of randomized controlled trials in humans. In Germany and several European countries, silymarin is a registered pharmaceutical product (Legalon, Madaus) with specific indications for toxic and chronic inflammatory liver disease; in the United States, it is sold as a dietary supplement under the Dietary Supplement Health and Education Act (DSHEA) framework but remains one of the few botanicals to have undergone NIH-funded Phase III trials. The intravenous form — silibinin dihydrogensuccinate (Legalon SIL) — holds FDA orphan drug designation and is the first-line antidote for Amanita phalloides (death cap mushroom) poisoning, a condition in which its ability to block hepatocyte uptake of the amatoxin via OATP transporters is genuinely life-saving.\n\nBodyHackGuide covers silymarin as the canonical liver-support agent alongside [TUDCA](/compound/tudca) (the bile-acid hepatoprotectant with FXR and ER-stress mechanisms), [glutathione](/compound/glutathione) (the master intracellular antioxidant that silymarin upregulates), [N-acetylcysteine](/compound/n-acetylcysteine) (the glutathione precursor and acetaminophen-overdose antidote), and [alpha-lipoic-acid](/compound/alpha-lipoic-acid) (the mitochondrial antioxidant that stacks well with silymarin for hepatic and metabolic effect). Silymarin's role in the contemporary longevity and metabolic-health stack has expanded well beyond its classical hepatitis indication. It is now routinely used as: (1) a daily liver-support supplement in users with non-alcoholic fatty liver disease (NAFLD / MASLD, the most prevalent chronic liver disease worldwide, affecting roughly 25–30% of adults globally), (2) a protective agent alongside hepatotoxic medications (statins, methotrexate, tuberculosis drugs, antiretrovirals, long-term acetaminophen use), (3) an adjunct in alcohol-related liver disease, (4) a component of longevity protocols for users whose hepatic reserve is under metabolic stress from aging, high dietary burden, or xenobiotic exposure, and (5) a hangover-mitigation ingredient — though the evidence for acute alcohol mitigation is less strong than the chronic liver-protection evidence.\n\nThe clinical evidence base for silymarin spans roughly 50 years and supports several distinct use cases with differing strength of evidence. The strongest evidence is for amatoxin poisoning (where IV silibinin dihydrogensuccinate is effectively curative and is EMA-approved for this indication). The next strongest is for NAFLD / non-alcoholic steatohepatitis (NASH / MASH), where multiple RCTs — including the Loguercio 2012 multicenter trial of silybin-phosphatidylcholine-vitamin E (Realsil, IdB1016-based) and earlier pilot studies — have shown improvements in liver enzymes (ALT, AST, GGT), hepatic echogenicity on ultrasound, and in some trials modest improvements in HOMA-IR and liver histology. Chronic hepatitis C evidence is mixed: Ferenci 1989 (PMID 2671116) showed survival benefit in alcoholic cirrhosis; Fried 2012, the large NIH-funded SYNCH trial of oral silymarin 420 or 700 mg TID in HCV patients with prior interferon failure, failed to show significant ALT improvement at the doses tested — although pharmacokinetic substudies (Hawke 2010) indicate the oral doses studied may not have achieved therapeutically relevant plasma silibinin levels. Evidence for drug-induced liver injury prevention (methotrexate, tacrine, antitubercular regimens) is consistent but drawn from small trials. Evidence for alcoholic liver disease is historically positive (Ferenci 1989, Parés 1998) but newer trials are fewer, in part because the clinical priority has shifted toward alcohol cessation rather than pharmacologic rescue.\n\nCommercially, silymarin is available in several forms with meaningfully different bioavailability profiles. Standardized milk thistle extract — 70–80% silymarin with ≥30% silibinin — is the baseline form, sold in capsules typically dosing 150–300 mg of the extract (delivering 105–240 mg silymarin, of which 30–70 mg is silibinin). The major limitation of baseline silymarin is poor oral bioavailability: parent silibinin has absolute oral bioavailability of roughly 0.73–7.5%, with most of the dose either not absorbed, rapidly conjugated to glucuronides and sulfates that retain some activity, or subject to enterohepatic recycling. This bioavailability problem has driven the development of enhanced delivery systems. Siliphos (branded IdB1016 from Indena, Italy) is silybin-phosphatidylcholine complex (sometimes called silybin phytosome), first described by Bombardelli and colleagues in 1991, which increases silibinin Cmax roughly 4–10 fold and AUC roughly 4–7 fold over baseline silibinin. Silipide is a similar phytosome formulation. Legalon (Madaus) uses a specific extraction and formulation process validated across European clinical trials. Thisilyn (Nature's Way) is a widely available US standardized extract. Jarrow Formulas Milk Thistle, NOW Foods Milk Thistle Silymarin, Life Extension European Milk Thistle (Silybin Advanced), and Solgar Milk Thistle are additional common products. For serious therapeutic intent (NAFLD, hepatitis, post-hepatotoxic drug exposure), phytosome forms (Siliphos) are strongly preferred; for general daily liver support, a well-standardized 80% silymarin extract at 200–300 mg/day is adequate and cost-effective.\n\nSilymarin occupies an unusual position in pharmacology: it is a natural product with mechanistic depth (membrane stabilization, antioxidant, antifibrotic, anti-inflammatory, regenerative, anti-apoptotic, and anti-viral activities all documented in vitro and in animal models), decades of human use including hospital-grade IV formulation for acute amatoxin poisoning, orphan drug designation, and a generally benign safety profile — yet its clinical effect sizes in common chronic liver conditions are modest, and the pharmacokinetic challenges of oral absorption have limited the achievable plasma concentrations in ambulatory use. The result is a compound that is reliably safe, mechanistically well-characterized, probably beneficial for most hepatic indications, but not transformative as a monotherapy for severe liver disease. For the BodyHackGuide user, silymarin is best understood as a tier-1 liver-support ingredient — one of the single most defensible daily-use hepatoprotectants in the natural-product space — that pairs naturally with TUDCA, NAC, choline, and a Mediterranean-diet polyphenol pattern for durable long-term hepatic health. It is not a substitute for cessation of hepatotoxic exposure, for weight loss in MAFLD, for antiviral therapy in active hepatitis, or for specialist care in progressive liver disease, but it is a reasonable and generally supportable adjunct across those contexts.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 5824, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/silymarin" }, { "id": "e1a7c3d2-9f4b-4c2a-bf10-1a2b3c4d5e04", "slug": "sleep-research-blend", "name": "Sleep Research Blend", "aliases": [ "Sleep Blend", "BHG-SR" ], "category": "Sleep & Circadian", "description": "Sleep Research Blend is a proprietary, multi-component research preparation that BHG Labs lists as BHG-SR Research Blend, an atomized (intranasal) solution cataloged for laboratory sleep-architecture and circadian research. The store discloses each lot's exact composition on the signed Certificate of Analysis (COA) rather than pre-stating it, so this profile is a product reference rather than a single-molecule entry. Atomized 'sleep' blends of this type are typically built around [DSIP](/compound/dsip) and [epitalon/epithalon](/compound/epitalon), sometimes with [selank](/compound/selank) or [glycine](/compound/glycine); the authoritative composition for any given vial is its COA. The blend itself has no clinical trials, and even its likely components have only limited human evidence. Research use only, not for human or veterinary use.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [ "Nasal" ], "dose_range_mcg": "Composition-dependent, read the COA. Community intranasal archetype: ~100-300 mcg DSIP-equivalent and ~50-100 mcg epitalon-equivalent per evening administration.", "dosing_frequency": "Once in the evening; the epitalon fraction is typically run in short 10-20 day blocks (see COA). RUO.", "cycle_length": "No fixed cycle for the blend. Epitalon-type components are commonly run in 10-20 day blocks a few times per year; DSIP-type components are used intermittently. RUO.", "common_vial_sizes": [], "research_stage": "No trials of the blend; component-level preclinical and limited early-human research only (RUO)", "approval_status": "Not approved (FDA/EMA). Research use only, not for human or veterinary use.", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Framed around its likely components, not the blend itself, which has never been formally studied.", "DSIP: early animal EEG studies linked it to increased slow-wave (delta) sleep, though human sleep evidence is limited and inconsistent. [PMID:6145137][PMID:16539679]", "DSIP: historically explored for insomnia, pain and withdrawal states, with mechanism still unestablished. [PMID:3550726]", "Epitalon: preclinical restoration of age-disrupted circadian melatonin rhythms, the basis for the 'circadian support' rationale. [PMID:15664732][PMID:12374906]", "Community and anecdotal reports (not clinical evidence) describe easier sleep onset and deeper subjective rest from intranasal DSIP+epitalon blends; these are uncontrolled and unverified.", "Intranasal delivery is used to target nose-to-brain routes; epitalon modulated the pineal gland after intranasal dosing in rats. [PMID:12500171]" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/sleep-research-blend" }, { "id": "a7888146-3d56-4832-8140-3ca8269d4aed", "slug": "slu-pp-332", "name": "SLU-PP-332", "aliases": [ "SLU PP 332" ], "category": "Performance", "description": "SLU-PP-332 is the first-generation synthetic pan-agonist of the estrogen-related receptors (ERRα, ERRβ, ERRγ) developed by the laboratory of Thomas Burris at Saint Louis University and reported in a landmark 2023 publication that established ERR pan-agonism as a pharmacologically tractable exercise-mimetic drug mechanism. The compound is the chemical scaffold from which the second-generation, orally bioavailable successor [SLU-PP-915](/compound/slu-pp-915) was developed, and the SLU-PP-332 story is essential context for understanding the ERR agonist field because SLU-PP-332's original rodent pharmacology is what generated the initial enthusiasm for this drug class and its limitations (specifically its poor oral bioavailability) are what motivated the second-generation development program. The original publication from the Burris group established that SLU-PP-332 administration to mice produces a transcriptional, functional, and physiological signature that overlaps substantially with the effects of endurance exercise — enhanced running endurance on treadmill testing, increased mitochondrial biogenesis in skeletal muscle, shifts in muscle fiber type toward slow-twitch oxidative phenotype, elevated fatty acid oxidation, favorable body composition changes in diet-induced obesity models, and cardiac functional improvements in pressure-overload heart failure models. These effects are mediated through coordinated activation of the three ERR isoforms (ERRα, ERRβ, ERRγ), nuclear receptor transcription factors that sit at the top of the regulatory cascade controlling oxidative metabolism, and through recruitment of PGC-1α and other transcriptional coactivators that together drive expression of the exercise-responsive gene program. SLU-PP-332 specifically attracted intense scientific and popular media attention in 2023-2024 because the rodent data was presented in accessible terms — \"a drug that mimics the effects of exercise\" — and the social and medical appeal of such a compound for patients who cannot exercise due to frailty, cardiac disease, orthopedic limitations, or other constraints is obvious. The public discussion outran the evidence in typical fashion: the rodent data is real and consistent, but human validation of the exercise-mimetic premise requires clinical trials that have not been conducted for SLU-PP-332 or any related compound. SLU-PP-332's major pharmacological limitation, documented in the published work, is poor oral bioavailability. Every published rodent study with SLU-PP-332 used intraperitoneal (IP) injection as the route of administration, not oral dosing. IP administration in mice is routine in preclinical research but is obviously not a viable route for human chronic therapy, and this limitation was the specific motivation for the Burris group to develop the second-generation compound [SLU-PP-915](/compound/slu-pp-915) with improved oral PK. The practical reality in April 2026 is that SLU-PP-332 remains a first-generation research chemical that has been largely superseded by [SLU-PP-915](/compound/slu-pp-915) for self-experimentation purposes where oral dosing is preferred, though SLU-PP-332 continues to be sold by research-chemical vendors and used by a subset of biohackers who prefer the first-generation compound either for cost reasons, availability reasons, or preference for the more extensively characterized parent molecule. No human clinical trials of SLU-PP-332 have been registered or published, no IND applications for it have been publicly disclosed, and no pharmaceutical-grade supply exists. This entry covers the detailed mechanism of ERR pan-agonism as established in the original SLU-PP-332 work, the specific preclinical pharmacology including cardiovascular, metabolic, and musculoskeletal endpoints, the context provided by the broader ERR biology literature, the theoretical and practical concerns with self-administration of an unvalidated nuclear receptor agonist, how SLU-PP-332 differs practically from [SLU-PP-915](/compound/slu-pp-915) for self-experimenters, and how SLU-PP-332 fits into the stacking landscape alongside other metabolic and exercise-mimetic interventions like [5-Amino-1MQ](/compound/5-amino-1mq), [BAM15](/compound/bam15), [Humanin](/compound/humanin), [L-Carnitine](/compound/l-carnitine), [Semaglutide](/compound/semaglutide), [Tirzepatide](/compound/tirzepatide), [Retatrutide](/compound/retatrutide), and [Tesofensine](/compound/tesofensine). The core takeaway is that SLU-PP-332 established a mechanistically compelling drug class for exercise-mimetic pharmacology, demonstrated consistent preclinical efficacy, and is limited in its current self-experimentation role by PK properties that are specifically addressed by the second-generation successor compound.", "half_life": "", "molecular_weight": "", "molecular_mass": "535.54 g/mol", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "Research compound — no established human doses. Animal studies: 10-50 mg/kg", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "2264906-88-2", "iupac_name": "", "chemical_formula": "C23H20F3N3O4S2", "potential_benefits": [ "Exercise mimicry without physical exertion", "Enhanced fat oxidation", "Increased mitochondrial biogenesis", "Improved endurance capacity", "Muscle fiber type conversion", "Metabolic health improvement" ], "research_fields": [], "pubmed_count": 8, "pubchem_cid": 146816027, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/slu-pp-332" }, { "id": "d2674f5a-56af-4f38-bc60-acddb185cd10", "slug": "slu-pp-915", "name": "SLU-PP-915", "aliases": [ "SLU-PP-915", "SLUPP915", "pan-ERR agonist SLU-PP-915", "ERR agonist 10s" ], "category": "Metabolic", "description": "SLU-PP-915 is an experimental agonist of the estrogen-related receptors, a family of three orphan nuclear receptors called ERR-alpha, ERR-beta and ERR-gamma that control genes for mitochondrial biogenesis, oxidative phosphorylation, fatty acid oxidation and the Krebs cycle. It was reported in 2023 by John Walker, Thomas Burris and colleagues as the lead of a new chemical series of pan-ERR agonists (PMID: 37421886). It has never been in a human being. No company has taken it into development and no regulator has reviewed it.\n\nIt is the follow-up to SLU-PP-332, the compound that got press coverage as exercise in a pill. SLU-PP-332 activates all three ERR subtypes and, in mice, increased type IIa oxidative muscle fibers, enhanced running endurance and triggered the gene expression program that a single bout of aerobic exercise produces (PMID: 36988910). In diet-induced obese mice it raised energy expenditure and fatty acid oxidation, reduced fat mass and improved insulin sensitivity (PMID: 37739806). Related pan-ERR agonists improved cardiac fatty acid metabolism and mitochondrial function in heart failure models (PMID: 37961903).\n\nSLU-PP-915 exists because SLU-PP-332 has a practical flaw: it is not orally bioavailable, so mice had to be injected. The medicinal chemistry work replaced a phenol or aniline group with a boronic acid, which held potency while improving metabolic stability in liver microsome assays, and the resulting compound raised expression of the ERR target genes PGC-1alpha, LDHA, DDIT4 and PDK4 both in cells and in animals (PMID: 37421886).\n\nThe 2025 pharmacology paper is the key one. SLU-PP-915 increased aerobic exercise performance in mice, both running distance and duration, to a similar degree as SLU-PP-332 when injected, and held comparable effect when given by mouth after adjusting for systemic exposure. Both compounds strongly induced Ddit4, a gene switched on by acute aerobic exercise, at levels matching or exceeding actual treadmill running in some muscles, and SLU-PP-915 combined with training raised mitochondrial gene expression further than either alone (PMID: 41421047).\n\nEverything above is mice. There is no human pharmacokinetic study, no safety study, no dose, and no published record of any person taking it. Anti-doping chemists have already characterized its in vitro metabolites in human liver preparations specifically because they expect it to be misused before it is ever studied properly (PMID: 41588687).\n\nCapsules sold as SLU-PP-915 are a laboratory compound that reached a peer-reviewed pharmacology paper in 2025 and skipped every step between that paper and a person swallowing it.", "half_life": "Not established in humans; in mice it is orally bioavailable and active by both oral and intraperitoneal routes, unlike its predecessor SLU-PP-332 (PMID: 41421047)", "molecular_weight": "341.16 g/mol", "molecular_mass": "341.16 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral (rodent studies)", "Intraperitoneal injection (rodent studies)" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Not approved by any regulator, not in clinical trials, and never administered to humans in a published study. SLU-PP-915 is not named in published summaries of the 2026 WADA prohibited list, but anti-doping laboratories have already characterized its metabolites for sports drug testing because they consider it a likely doping agent (PMID: 41588687). It is a research-use-only compound in the US market.", "trial_phase": "", "cas_number": "2285432-92-8", "iupac_name": "", "chemical_formula": "C17H13BFNO3S", "potential_benefits": [ "Increased aerobic exercise distance and duration in mice by oral and by injected administration (PMID: 41421047)", "Induced the acute aerobic exercise response gene Ddit4 in mouse muscle at levels matching or exceeding treadmill running (PMID: 41421047)", "Increased mitochondrial gene expression further when combined with exercise training in mice (PMID: 41421047)", "Upregulated the ERR target genes PGC-1alpha, LDHA, DDIT4 and PDK4 in cells and in vivo (PMID: 37421886)", "In the closely related pan-ERR agonist SLU-PP-332, increased energy expenditure and fatty acid oxidation with reduced fat mass and improved insulin sensitivity in obese mice (PMID: 37739806)" ], "research_fields": [ "Estrogen-related receptors", "Exercise mimetics", "Mitochondrial biogenesis", "Sports drug testing" ], "pubmed_count": 0, "pubchem_cid": 142532359, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/slu-pp-915" }, { "id": "90c1e037-2fce-4c1d-a183-6adeca4a1444", "slug": "snap-8", "name": "Snap-8", "aliases": [ "Acetyl Glutamyl Heptapeptide-1", "SNAP-8", "Leuphasyl", "anti-wrinkle peptide" ], "category": "Skin & Hair", "description": "Snap-8 (INCI: Acetyl Glutamyl Heptapeptide-1) is a synthetic octapeptide designed as an analog of the N-terminal fragment of synaptosomal-associated protein of 25 kDa (SNAP-25), which is the molecular target of botulinum toxin A (Botox). Where Botox cleaves SNAP-25 systemically and irreversibly via enzymatic activity, Snap-8 competes with SNAP-25 for a place in the SNARE complex that enables acetylcholine release at the neuromuscular junction. This competitive inhibition reduces muscle contraction at the application site without systemic toxin effects. Snap-8 is used in cosmetic research as a topical anti-wrinkle agent, particularly for expression lines (forehead, periorbital). Purity-verified Snap-8 raw powder is also used in cosmetic compounding research.", "half_life": "Not characterized (topical peptide)", "molecular_weight": "1075.16 g/mol", "molecular_mass": "1075.16 g/mol (molecular formula C41H70N16O16S)", "amino_acid_sequence": "Ac-Glu-Glu-Met-Gln-Arg-Arg-Ala-Asp-NH2 (one-letter: EEMQRRAD; N-terminus acetylated, C-terminus amidated). INCI name: Acetyl Octapeptide-3 (historically also called Acetyl Glutamyl Heptapeptide-1). CAS 868844-74-0. The sequence is derived from the N-terminal domain of SNAP-25 and extends the Argireline (Acetyl Hexapeptide, Ac-EEMQRR-NH2) sequence by two residues (Ala-Asp).", "administration_routes": [ "Topical" ], "dose_range_mcg": "0", "dosing_frequency": "twice_daily", "cycle_length": "", "common_vial_sizes": [ "10" ], "research_stage": "Preclinical", "approval_status": "Not FDA-approved. Marketed as a cosmetic ingredient (INCI: Acetyl Octapeptide-3) and, on this site, offered as a research-use-only raw peptide. Not a drug; not approved for injection or systemic use.", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Reduction of dynamic expression wrinkles (forehead, crow's feet, glabellar lines)", "SNARE complex interference — partial, reversible neuromuscular inhibition", "Topical alternative research model for neuromuscular relaxation without injected toxin", "Cosmetic peptide compounding research — high-purity raw powder applications", "Synergy with Argireline (Acetyl Hexapeptide-3) in SNARE-targeting formulations" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/snap-8" }, { "id": "e07bb1a4-37f7-42e3-aa94-63b56925ad73", "slug": "sobetirome", "name": "Sobetirome (GC-1)", "aliases": [ "GC-1", "QRX-431", "Sobetiroma", "NV1205", "thyromimetic GC-1" ], "category": "Metabolic", "description": "Sobetirome, also called GC-1 and later QRX-431, is a synthetic analog of thyroid hormone made in Thomas Scanlan laboratory and first described in 1998 as a high-affinity, subtype-selective agonist for the thyroid hormone receptor (PMID: 9653548). The idea behind it is straightforward: thyroid hormone lowers cholesterol and raises metabolic rate, but it also speeds the heart, and the receptor that drives the heart effects is a different subtype from the one that drives the liver effects. A drug selective for the beta subtype should separate the two. QuatRx Pharmaceuticals developed it as a cholesterol-lowering agent and the program was later reviewed as a case history in drug discovery (PMID: 19002578).\n\nThe animal data support the separation. In hypothyroid mice and hypercholesteremic rats, GC-1 lowered triglycerides better than triiodothyronine and lowered cholesterol comparably, but did not raise heart rate or normalize the cardiac genes that thyroid hormone acts on (PMID: 10965874). In cholesterol-fed rats it lowered cholesterol at roughly 30 times lower exposure than needed to cause a fast heart rate, and in cynomolgus monkeys it lowered cholesterol and lipoprotein(a) with no tachycardia and about a 4 percent reduction in body weight (PMID: 14701670). In euthyroid mice it reduced serum lipids and stimulated steps of reverse cholesterol transport (PMID: 16006512).\n\nFor body composition, the relevant rat study ran six weeks and compared GC-1 with triiodothyronine at matched doses. Oxygen consumption rose 50 to 70 percent with both. Control rats gained about 80 percent more fat mass, triiodothyronine-treated rats lost 70 to 90 percent, and GC-1-treated rats lost about 20 percent. The difference that matters is muscle: triiodothyronine shrank individual skeletal muscles while GC-1 barely did, and GC-1 did not drive up food intake the way triiodothyronine did (PMID: 17400799).\n\nThere is a safety signal that gets left out of marketing. In rats, GC-1 was a strong mitogen: it stimulated hepatocyte proliferation without tissue injury and induced massive pancreatic acinar cell proliferation (PMID: 16574785). That is a proliferation finding in two organs, in a compound intended for chronic use.\n\nHuman evidence is thin. Phase 1 single-dose and two-week multiple-dose studies in healthy volunteers were announced by the sponsor as showing LDL cholesterol reductions, but those results were reported in company announcements rather than a peer-reviewed trial publication, and the cholesterol program did not continue. Sobetirome was later picked up for X-linked adrenoleukodystrophy, but both registered trials, NCT01787578 and NCT03196765, were withdrawn without enrolling a single participant. More recent work has focused on the brain-penetrant prodrug Sob-AM2 in animal models of demyelination (PMID: 29845892; PMID: 36792926).\n\nCapsules sold as sobetirome are an unapproved thyroid-active drug with no completed human trial behind them.", "half_life": "Not established in humans; no peer-reviewed human pharmacokinetic study has been published, and the phase 1 program results were not reported in the peer-reviewed literature (PMID: 19002578)", "molecular_weight": "328.40 g/mol", "molecular_mass": "328.40 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Discontinued", "approval_status": "Not approved by the FDA, the EMA or any other regulator. Clinical development for cholesterol lowering ended after phase 1 (PMID: 19002578), and two later trials in X-linked adrenoleukodystrophy, NCT01787578 and NCT03196765, were withdrawn with zero enrollment. Sobetirome is not named on the WADA prohibited list, although thyroid hormone analogs sit in a class regulators watch closely. It is a research-use-only compound in the US market.", "trial_phase": "", "cas_number": "211110-63-3", "iupac_name": "", "chemical_formula": "C20H24O4", "potential_benefits": [ "Lowered cholesterol about 30 times more potently than it caused tachycardia in cholesterol-fed rats (PMID: 14701670)", "Lowered cholesterol and lipoprotein(a) with no tachycardia and about 4 percent body weight reduction in cynomolgus monkeys (PMID: 14701670)", "Increased oxygen consumption 50 to 70 percent and prevented fat mass accumulation over six weeks in rats, with far less skeletal muscle loss than triiodothyronine (PMID: 17400799)", "Lowered triglycerides more than triiodothyronine without raising heart rate in hypothyroid mice (PMID: 10965874)", "Reduced serum lipids and stimulated steps of reverse cholesterol transport in euthyroid mice (PMID: 16006512)" ], "research_fields": [ "Thyroid hormone receptor beta", "Lipid lowering", "Energy expenditure", "Demyelinating disease" ], "pubmed_count": 0, "pubchem_cid": 9862248, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/sobetirome" }, { "id": "98cc6b77-b9b2-485d-a47e-98a6a4c5862d", "slug": "spermidine", "name": "Spermidine", "aliases": [ "Spermidine", "N-(3-Aminopropyl)butane-1,4-diamine", "Aminopropyl-putrescine", "Polyamine", "Wheat germ spermidine", "spermidineLIFE", "Primeadine", "Longevity polyamine", "Sperm polyamine (historical)", "Natural polyamine" ], "category": "Polyamine", "description": "\nSpermidine is a naturally-occurring polyamine essential for cellular growth, division, and differentiation in all living organisms. It was first isolated from semen (hence the name) in the 17th century by Anton van Leeuwenhoek, but is synthesized endogenously by all mammalian cells and is also present in substantial concentrations in many dietary sources. Over the past decade, spermidine has emerged as one of the most promising longevity-associated molecules, with compelling evidence for extending lifespan across multiple model organisms and strong preclinical data for cardiovascular protection, neuroprotection, immune enhancement, and metabolic benefits. The molecule has transitioned from obscurity to major interest following pioneering work by Frank Madeo and colleagues culminating in a 2018 Nature Medicine publication demonstrating associations between dietary spermidine intake and reduced cardiovascular mortality in humans.\n\nChemically, spermidine is a linear triamine (N-(3-aminopropyl)butane-1,4-diamine) with three amine groups that are positively charged at physiological pH. This positive charge enables spermidine to bind to negatively-charged cellular components including DNA, RNA, nucleotides, ATP, phospholipids, and many proteins. The electrostatic interactions stabilize nucleic acid structures, facilitate transcription and translation, influence membrane organization, and participate in numerous enzymatic processes. Spermidine is one of three major polyamines in mammalian cells (alongside putrescine and spermine), with spermidine typically the most abundant. Intracellular concentrations range from micromolar to millimolar depending on cell type.\n\nEndogenous spermidine synthesis occurs from putrescine via spermidine synthase, requiring S-adenosylmethionine (SAM) as the aminopropyl donor. Cellular spermidine levels are tightly regulated through coordinated synthesis, uptake from extracellular sources, efflux via polyamine transporters, and catabolism. Polyamine levels decline with aging in most tissues, including heart, brain, liver, and blood cells, contributing to age-related cellular dysfunction. Restoring polyamine levels through dietary or supplemental spermidine is the basis for its proposed geroprotective effects.\n\nDietary spermidine is abundant in many foods with wheat germ containing the highest concentrations (approximately 240 mg/kg). Other rich sources include soybeans (soybeans and soybean products at approximately 100-200 mg/kg), aged cheese, mushrooms, peas, mango, broccoli, cauliflower, whole grains, and fermented foods. Typical Western dietary intake provides 10-25 mg spermidine daily, while Mediterranean-style diets with emphasis on legumes, whole grains, and vegetables provide higher amounts (25-50 mg daily). Japanese populations consuming natto and other fermented soy foods often achieve intakes of 40-80+ mg daily.\n\nThe modern scientific interest in spermidine derives from a series of landmark studies. Eisenberg and colleagues (2009) demonstrated that spermidine extends lifespan across yeast, flies, worms, and mouse models through induction of autophagy. This was one of the most reproducible lifespan-extension findings across model organisms. Eisenberg 2016 (PMID 27841876) showed oral spermidine extended mouse lifespan and reduced cardiovascular aging markers. The landmark Kiechl 2018 Bruneck Study publication in Nature Medicineanalyzed 20-year follow-up of the Bruneck cohort in Italy and found higher dietary spermidine intake was associated with reduced overall mortality, cardiovascular mortality, and cancer mortality. Follow-up cohort studies from Austria, Sweden, and Japan have replicated the general association between higher dietary spermidine and reduced mortality risk.\n\nCommercial spermidine supplementation typically uses wheat germ extract standardized to spermidine content. SpermidineLIFE (Longevity Labs) became one of the first major commercial brands in 2017-2018 offering standardized wheat germ extract providing 1-5 mg spermidine per serving. Primeadine (Oxford Healthspan) is a competing brand using similar wheat germ-based formulation. Pure synthetic spermidine is available as a research chemical but is generally not commercially sold for human supplementation due to regulatory and standardization concerns. Typical supplementation doses range from 1-2 mg daily (foundation dose, matching upper range of dietary intake) to 10+ mg daily (therapeutic doses used in clinical trials).\n\nPharmacokinetically dietary and supplemental spermidine is absorbed efficiently from the intestinal lumen, with polyamine transporters mediating uptake into enterocytes and subsequent distribution to tissues. Plasma half-life is short (minutes to hours for free spermidine) due to rapid cellular uptake. However, tissue accumulation from continued dietary intake produces sustained effects on cellular polyamine pools. Measurement of intracellular spermidine levels is technically complex; most clinical studies rely on dietary intake estimation or plasma polyamine profiling.\n\nThe thematic positioning of spermidine in contemporary longevity supplementation is as a foundational autophagy-inducing geroprotector alongside NAD+ precursors, polyphenols, and sirtuin activators. Its unique mechanism (polyamine-mediated autophagy induction and protein translation quality control) complements rather than duplicates mechanisms of NR/NMN (sirtuin substrate), pterostilbene (sirtuin activator), or fisetin (senolytic). Multiple longevity-focused commercial stacks now include spermidine alongside these other compounds. Its safety profile at dietary and typical supplemental doses is excellent, with generations of dietary safety data from diverse populations.\n", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/spermidine" }, { "id": "6ee48625-238f-4014-bca0-d83577d1038f", "slug": "sr-9009", "name": "SR-9009 (stenabolic)", "aliases": [ "SR9009", "Stenabolic", "SR-9009", "Rev-erb agonist SR9009" ], "category": "Metabolic", "description": "SR-9009, sold as stenabolic, is a synthetic agonist of the nuclear receptors REV-ERB-alpha and REV-ERB-beta. It came out of Thomas Burris and Theodore Kamenecka laboratory work at the Scripps Research Institute and was first described in a 2012 Nature paper as a tool for pharmacologically shifting the circadian clock and the metabolism it controls (PMID: 22460951). It was never a pharmaceutical company development candidate, has never entered human trials, and has no approval anywhere. Anti-doping laboratories describe it plainly as a compound that failed to reach FDA approval and whose illegal distribution raised concern (PMID: 38735208).\n\nREV-ERB proteins sit inside the core circadian clock and repress the genes that drive the daily cycle of activity and fuel use. Activating them with a drug changes the timing and level of metabolic gene expression in liver, muscle and fat. In the original mouse work this raised energy expenditure, and in diet-induced obese mice it reduced fat mass with drops in plasma cholesterol, triglycerides, free fatty acids and glucose (PMID: 22460951). A separate group showed that REV-ERB-alpha controls mitochondrial biogenesis in oxidative muscle and that pharmacological activation increased exercise capacity in mice (PMID: 23852339).\n\nThere is a serious problem with the mechanism story. When researchers built mice lacking both REV-ERB-alpha and REV-ERB-beta, SR-9009 still reduced cell viability, rewired cellular metabolism and altered gene transcription in cells that had no target left to act on. The authors concluded that the effects of SR-9009 cannot be used as a stand-in for REV-ERB activity (PMID: 31127047). In other words, some of what the compound does in cells is off-target, and which of the metabolic effects are REV-ERB-dependent is unsettled.\n\nThere are no human data of any kind. No pharmacokinetics, no safety study, no efficacy trial. In the mouse studies that produced the metabolic results, the compound was given by intraperitoneal injection rather than by mouth (PMID: 22460951), which matters because SR-9009 is sold as an oral liquid and as capsules.\n\nIt is prohibited in sport. WADA lists Rev-erb-alpha agonists including SR9009 and SR9011 under section S4.4, metabolic modulators, and horse and camel racing authorities have developed detection methods for it (PMID: 38735208; PMID: 42530886). When 44 products marketed online as SARMs were chemically analyzed, SR9009 was one of the unapproved drugs found in products that did not list it on the label (PMID: 29183075).\n\nWhat is sold as stenabolic, in liquid or capsule form, is a research chemical with no pharmacopoeial standard, no established human dose and no published human exposure. Buyers are the first humans on record taking it, and there is no monitoring of what happens next.", "half_life": "Not established in humans; no human pharmacokinetic study has been published. In the mouse experiments that produced the metabolic findings the compound was given by intraperitoneal injection rather than orally (PMID: 22460951)", "molecular_weight": "437.94 g/mol", "molecular_mass": "437.94 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Intraperitoneal injection (rodent studies)", "Oral (as sold on the research chemical market)" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Not approved by any regulator and never tested in humans. WADA prohibits Rev-erb-alpha agonists including SR9009 and SR9011 at all times under section S4.4, metabolic modulators, and the International Federation of Horseracing Authorities also prohibits it (PMID: 38735208). It is a research-use-only compound in the US market.", "trial_phase": "", "cas_number": "1379686-30-2", "iupac_name": "", "chemical_formula": "C20H24ClN3O4S", "potential_benefits": [ "Increased energy expenditure and reduced fat mass in diet-induced obese mice, with plasma cholesterol down 47 percent, triglycerides down 12 percent and glucose down 19 percent (PMID: 22460951)", "Increased exercise capacity in mice after pharmacological activation of Rev-erb-alpha, alongside greater muscle mitochondrial content (PMID: 23852339)", "Altered the circadian pattern of clock and metabolic gene expression in mouse hypothalamus, liver, muscle and adipose tissue (PMID: 22460951)", "Reduced weight gain and insulin resistance in mice exposed to constant light in a later rodent study (PMID: 39800061)" ], "research_fields": [ "Circadian biology", "Nuclear receptor pharmacology", "Energy metabolism", "Sports drug testing" ], "pubmed_count": 0, "pubchem_cid": 57394020, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/sr-9009" }, { "id": "46deb95c-99dd-4c1a-b3eb-a3f914a463f4", "slug": "ss-31", "name": "SS-31", "aliases": [ "Elamipretide", "MTP-131", "Bendavia", "Szeto-Schiller peptide 31", "D-Arg-Dmt-Lys-Phe-NH2", "Mitochondrial-targeted tetrapeptide" ], "category": "Mitochondrial Peptides", "description": "SS-31 (elamipretide; MTP-131; formerly Bendavia; chemical sequence D-Arg-Dmt-Lys-Phe-NH2 with dimethyltyrosine at position 2) is a first-in-class aromatic-cationic tetrapeptide designed to selectively target the inner mitochondrial membrane and bind cardiolipin, the signature mitochondrial phospholipid essential for cristae architecture, electron transport chain organization, and respiratory function. Invented in the late 1990s and early 2000s in the laboratories of Hazel Szeto and Peter Schiller at Cornell and the Clinical Research Institute of Montreal, SS-31 belongs to a family of \"Szeto-Schiller\" peptides that exploit a precise combination of alternating aromatic and basic amino acid residues to achieve both membrane permeability (crossing the plasma membrane without transporters or receptors) and mitochondrial specificity (preferential accumulation on the inner mitochondrial membrane at concentrations 1,000- to 5,000-fold higher than in cytosol). The resulting molecule is a rare pharmacological tool: a small peptide that, unlike most peptides, does not require specialized delivery technology to reach its intracellular target, and unlike most small molecules, does not distribute indiscriminately across cellular compartments.\n\nThe core therapeutic rationale for SS-31 rests on the centrality of mitochondrial dysfunction in aging and a wide range of human diseases. Mitochondria are the primary sites of ATP production, calcium buffering, apoptosis regulation, iron-sulfur cluster biogenesis, steroidogenesis, and reactive oxygen species (ROS) generation. Age-related decline in mitochondrial function — manifesting as reduced respiratory capacity, increased ROS production, impaired calcium handling, and accumulating mtDNA damage — contributes to sarcopenia, cardiac dysfunction, neurodegeneration, insulin resistance, and impaired tissue regeneration. In specific pathological contexts, acute mitochondrial dysfunction drives ischemia-reperfusion injury following myocardial infarction, stroke, and organ transplantation; chronic mitochondrial dysfunction defines primary mitochondrial diseases (Barth syndrome, Leber hereditary optic neuropathy, mitochondrial myopathies); and maladaptive mitochondrial changes contribute to age-related macular degeneration, chronic kidney disease, heart failure, and neurodegeneration. SS-31's ability to selectively reach the inner mitochondrial membrane and stabilize cardiolipin-dependent machinery makes it a mechanistically attractive intervention across this broad disease landscape.\n\nCommercially, SS-31 is developed by Stealth BioTherapeutics (originally Stealth Peptides, Inc.) as elamipretide, administered by subcutaneous injection at 40 mg daily in most clinical trial protocols. It has been studied in key and pilot trials across multiple indications including Barth syndrome (EMBARK/TAZPOWER), primary mitochondrial myopathy (MMPOWER-3), Leber hereditary optic neuropathy (ReSIGHT/REFOCUS-LHON), dry age-related macular degeneration and geographic atrophy (ReCLAIM/ReCLAIM-2), hypertrophic cardiomyopathy, Friedreich ataxia, and heart failure with preserved ejection fraction. As of this writing, elamipretide has not achieved broad regulatory approval in major markets, with several trials failing their primary endpoints despite biomarker signals suggesting mitochondrial engagement, and others showing preliminary promise but requiring larger confirmatory studies. In 2024, Stealth BioTherapeutics received FDA approval for elamipretide specifically for Barth syndrome, a rare genetic mitochondrial disorder, representing the first regulatory approval for a cardiolipin-targeting therapy. For broader age-related applications, evidence remains investigational and consumer use occurs outside regulatory approval pathways.\n\nThe longevity and biohacking communities have adopted SS-31 for off-label mitochondrial tuning despite its investigational status, treating it as a premium tool for users with specific mitochondrial concerns — severe fatigue, exercise intolerance, early neurodegenerative symptoms, macular health, or general mitochondrial support — who have the resources and risk tolerance to pursue experimental peptide therapy. The adoption pattern parallels that of other peptides from the research pharmacology pipeline: users obtain SS-31 through research chemical suppliers or specialty compounding pharmacies, reconstitute lyophilized peptide with bacteriostatic water, and administer subcutaneous injections daily or several times weekly. This approach sits squarely in the experimental/off-label zone of personal pharmacology, with meaningful limitations in safety monitoring, product quality verification, and individualized efficacy assessment that users should acknowledge explicitly before pursuing.\n\nMechanistically, SS-31 differs from conventional antioxidants like [NAC](/compound/nac), [CoQ10](/compound/coq10), or [curcumin](/compound/curcumin) in important ways. Classical antioxidants distribute broadly across cellular compartments and neutralize ROS through direct radical scavenging. SS-31 is not primarily a direct antioxidant — it has weak intrinsic scavenging activity — but rather a mitochondrial structural stabilizer that preserves cardiolipin-cytochrome c interactions, maintains electron transport chain organization on the inner mitochondrial membrane, and prevents the cardiolipin peroxidation cascade that both disrupts respiration and triggers apoptosis. The functional consequence is reduced ROS generation at its source (the electron transport chain), preserved respiratory capacity, maintained mitochondrial calcium handling, and resistance to opening of the mitochondrial permeability transition pore. In essence, SS-31 works upstream of where conventional antioxidants work, stabilizing the machinery that generates ROS rather than neutralizing ROS after production. This distinction matters therapeutically because SS-31 addresses causes of mitochondrial dysfunction (structural membrane disruption, cardiolipin peroxidation) while conventional antioxidants address consequences (accumulated ROS), and it explains why SS-31 sometimes shows effects in conditions where antioxidant supplementation has failed.\n\nClinical context is important for framing expectations. Primary mitochondrial diseases are rare conditions where a single gene defect disrupts mitochondrial function fundamentally — Barth syndrome involves tafazzin gene mutations that impair cardiolipin remodeling, producing the very membrane instability that SS-31 addresses mechanistically. In such rare diseases, SS-31 has a specific mechanistic rationale with preliminary clinical support. For general aging, sarcopenia, or cognitive decline in otherwise healthy individuals, the mechanistic case is that age-associated decline in cardiolipin integrity and mitochondrial function contributes to phenotypes and that SS-31 should correct these subtle defects. The evidentiary case, however, is much weaker. No large human trial has demonstrated that SS-31 meaningfully extends health-span or prevents age-related decline in otherwise-healthy adults, and some high-profile trials in conditions like heart failure with preserved ejection fraction or hypertrophic cardiomyopathy have failed to show clinical benefit despite biomarker signals. Users should calibrate expectations: SS-31 has strong mechanistic credentials, specific proven utility in Barth syndrome, promising signals in several investigational indications, and uncertain magnitude of benefit for general anti-aging use. It is not a panacea for mitochondrial aging, and its high cost (pharmaceutical-grade elamipretide runs thousands of dollars per month; research peptide versions are less expensive but of uncertain quality) places practical constraints on adoption.\n\nSS-31 integrates into a mitochondrial-focused longevity stack alongside [NMN](/compound/nmn) or NR (NAD+ precursors supporting sirtuin and complex I activity), [CoQ10](/compound/coq10) (electron transport chain cofactor and mitochondrial antioxidant), [creatine](/compound/creatine) (cellular energetics), [omega-3 fatty acids](/compound/omega-3-fatty-acids) (mitochondrial membrane composition), [urolithin A](/compound/urolithin-a) (mitophagy inducer), and [MOTS-c](/compound/mots-c) or [humanin](/compound/humanin) (mitochondrial-derived peptides with complementary effects on insulin sensitivity and neuronal protection). The stack addresses mitochondrial function from multiple angles: cardiolipin stabilization (SS-31), NAD+ supply (NMN/NR), electron transport function (CoQ10), substrate availability (creatine, carnitine), membrane composition (omega-3), turnover and quality control (urolithin A, rapamycin), and signaling (MOTS-c, humanin). Users pursuing serious mitochondrial tuning may use several of these together, though the incremental benefit of stacking SS-31 on top of a solid foundation of simpler interventions is not established and may be modest given the saturation of available mitochondrial benefit from foundational approaches.", "half_life": "~2-4 hours (plasma, after subcutaneous injection); tissue residence is longer due to cardiolipin binding", "molecular_weight": "639.8 g/mol", "molecular_mass": "639.8 g/mol (free base; C32H49N9O5)", "amino_acid_sequence": "D-Arg-Dmt-Lys-Phe-NH2 (D-arginine - 2',6'-dimethyltyrosine - L-lysine - L-phenylalanine amide)", "administration_routes": [], "dose_range_mcg": "20000-60000", "dosing_frequency": "Once daily subcutaneous (some protocols use 5-6 days per week)", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Clinical/Approved", "approval_status": "FDA accelerated approval (September 2025) for Barth syndrome as elamipretide, brand name FORZINITY (Stealth BioTherapeutics); the FDA advisory committee voted in October 2024. Investigational / research-use-only for all other indications.", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 4, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/ss-31" }, { "id": "fc5c67ef-b148-45ce-a9ad-73e82d47981e", "slug": "sulbutiamine", "name": "Sulbutiamine", "aliases": [], "category": "Nootropics", "description": "**Sulbutiamine** (chemical name: *isobutyryl thiamine disulfide*; trade names include **Arcalion**, **Enerion**, **Bisibutiamine**) is a lipophilic synthetic derivative of vitamin B1 (thiamine), developed in Japan in the 1960s by Sankyo Company chemists who were seeking thiamine analogs with enhanced absorption and tissue penetration — particularly brain penetration. Structurally, sulbutiamine is a **thiamine disulfide dimer** in which two thiamine-derived moieties are linked by a disulfide bond and esterified with isobutyryl groups. This design makes sulbutiamine considerably more lipophilic than water-soluble thiamine hydrochloride, allowing it to cross lipid membranes (including the blood-brain barrier) more effectively than the parent vitamin. Once inside cells, sulbutiamine is reduced and hydrolysed to yield two molecules of thiamine, which then participate in normal thiamine biochemistry as thiamine pyrophosphate (TPP) — the active cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, branched-chain α-keto acid dehydrogenase, and transketolase.\n\nSulbutiamine occupies an unusual regulatory position. It is an **approved prescription medicine in France, several other European countries, parts of Asia, and various emerging markets**, where it is indicated for treating **asthenia** (fatigue states) — a clinical concept that encompasses a range of fatigue syndromes, typically at doses of 400-600 mg/day. The French brand Arcalion is the most widely recognised form. In the United States, sulbutiamine is **not FDA-approved as a drug** and is **not recognised as a dietary supplement** under DSHEA, but it is not scheduled and is widely sold online as a nootropic/cognitive enhancer in powder and capsule form. In the United Kingdom, its status is ambiguous following the Psychoactive Substances Act 2016. In other jurisdictions, the legal status varies and users should verify locally before purchasing.\n\nThe compound's appeal rests on four overlapping claims: (1) it may improve cognitive performance, particularly attention and memory, especially in the context of fatigue or mild asthenia; (2) it may reduce subjective fatigue; (3) it may have mild pro-cholinergic and pro-dopaminergic effects in addition to replenishing thiamine cofactor availability; and (4) it is generally well tolerated at therapeutic doses. Each of these claims has some experimental support, primarily from French clinical studies of asthenia and from a handful of PubMed-indexed rodent and human studies. The evidence base is larger than for many nootropic compounds but still modest compared with mainstream psychiatric or neurological medicines.\n\nIt is important to place sulbutiamine honestly in the therapeutic landscape. For **frank thiamine deficiency** (beriberi, Wernicke's encephalopathy, dry or wet beriberi), the standard of care is intravenous or intramuscular thiamine hydrochloride at high doses — not sulbutiamine. Wernicke-Korsakoff syndrome requires emergency parenteral thiamine administration and is not an indication for oral sulbutiamine. For **generalised fatigue without thiamine deficiency** — the complaint most commonly prompting self-administration of sulbutiamine — the evidence-based approach is to evaluate for underlying causes (sleep disorders, depression, anaemia, thyroid dysfunction, chronic infection, autoimmune disease, cardiovascular disease, medication effects, substance use, psychosocial stressors) and treat the cause. Empiric treatment of fatigue with an oral thiamine derivative is, at best, a tertiary option after evidence-based causes have been excluded. For **depression**, evidence-based treatments include SSRIs, SNRIs, cognitive-behavioural therapy, and increasingly, rapid-acting agents like ketamine and esketamine for treatment-resistant cases — sulbutiamine is not a substitute for any of these.\n\nWhere sulbutiamine may legitimately have a role is in the following contexts: (1) as an adjunct for patients with genuine asthenia in jurisdictions where it is approved and prescribed by a physician; (2) as an occasional cognitive/fatigue support supplement for healthy adults who have exhausted sleep, nutrition, and exercise optimisation; (3) potentially in the context of chronic fatigue syndromes (ME/CFS) or post-infectious fatigue, where evidence is preliminary but biologically plausible; and (4) in populations at risk for mild thiamine insufficiency — chronic alcohol use (though these patients need parenteral thiamine acutely), bariatric post-surgical patients, and some dietary restriction contexts.\n\nSulbutiamine is often discussed alongside other nootropic B-vitamin derivatives such as **benfotiamine** (a different lipid-soluble thiamine derivative used primarily for diabetic neuropathy) and **allithiamine** (a related S-allyl thiamine found in garlic). Compared with benfotiamine, sulbutiamine is thought to have greater CNS penetration and more pronounced central cognitive effects, while benfotiamine is thought to produce higher peripheral thiamine levels with more benefit for diabetic neuropathy. These comparisons are mechanistic rather than head-to-head trial-based. Users interested in general cognitive enhancement may also see sulbutiamine discussed alongside [noopept](/compound/noopept), [selank](/compound/selank), [semax](/compound/semax), [piracetam](/compound/piracetam), and choline sources like alpha-GPC and CDP-choline.\n\nAs with any compound in the unregulated-supplement-or-prescription grey zone, sourcing matters. Prescription Arcalion obtained from a French or European pharmacy is a quality-controlled pharmaceutical product; sulbutiamine powder from an online supplement vendor may or may not be what the label claims. Users should favour either prescription supply or vendors providing third-party certificates of analysis (HPLC purity testing).", "half_life": "", "molecular_weight": "", "molecular_mass": "702.89 g/mol", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "Phase 4", "cas_number": "3286-46-2", "iupac_name": "1-[2-[(4-amino-2-methylpyrimidin-5-yl)methyl-formyl-amino]-5-(2-methylpropanoyloxy)pentan-3-yl] 2-methylpropanoate", "chemical_formula": "C32H46N8O6S2", "potential_benefits": [ "Motivation enhancement", "Memory improvement", "Fatigue reduction", "Mood elevation", "Dopamine D1 upregulation", "Erectile function" ], "research_fields": [ "Asthenia", "Cognitive impairment", "Psychogenic erectile dysfunction", "Depression", "Alzheimer's adjunct" ], "pubmed_count": 41, "pubchem_cid": 71124, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/71124/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/sulbutiamine" }, { "id": "0633556c-ac73-41da-adad-5a83a4d4989d", "slug": "sulforaphane", "name": "Sulforaphane", "aliases": [ "Sulforaphane", "1-Isothiocyanato-4-(methylsulfinyl)butane", "(R)-1-Isothiocyanato-4-(methylsulfinyl)butane", "SFN", "Broccoli sulforaphane", "Isothiocyanate", "Glucoraphanin-derived sulforaphane", "Avmacol sulforaphane", "BroccoMax", "Broccoli sprout extract" ], "category": "Isothiocyanate", "description": "\nSulforaphane is an organosulfur compound belonging to the isothiocyanate family, found predominantly in cruciferous vegetables (Brassicaceae family) including broccoli, broccoli sprouts, Brussels sprouts, cabbage, cauliflower, kale, bok choy, and collard greens. Sulforaphane has emerged as one of the most extensively studied phytochemicals of the modern era, primarily through the pioneering work of Paul Talalay and colleagues at Johns Hopkins University beginning in 1992. The compound is considered the premier dietary activator of the Nrf2/ARE pathway — the master cellular defense system that regulates endogenous antioxidant, detoxification, and anti-inflammatory gene expression.\n\nChemically, sulforaphane (1-isothiocyanato-4-(methylsulfinyl)butane) is a small, polar molecule containing the characteristic isothiocyanate (-N=C=S) functional group that confers its biological reactivity. Importantly, sulforaphane is not present in cruciferous vegetables in its active form. Instead, plants store the inactive precursor glucoraphanin in vacuoles, separated from the enzyme myrosinase that converts glucoraphanin to sulforaphane. Upon plant tissue disruption (chewing, chopping, crushing), myrosinase comes into contact with glucoraphanin and hydrolyzes it to sulforaphane. Heat (cooking above 60-70°C) denatures myrosinase, preventing sulforaphane formation. This explains why raw or lightly-steamed broccoli produces much more sulforaphane than overcooked broccoli.\n\nBroccoli sprouts (3-day-old broccoli sprouts in particular) are the richest dietary source of sulforaphane precursor — containing 10-100 times more glucoraphanin per gram than mature broccoli. Talalay and colleagues' discovery of broccoli sprouts' exceptional concentration led to commercial sprout varieties (BroccoSprouts, branded Johns Hopkins sprouts) selected for high glucoraphanin content. Commercial broccoli sprout extract supplements typically standardize to glucoraphanin content with added active myrosinase to ensure in-gut conversion to sulforaphane. Brand products include Avmacol (Nutramax Laboratories), BroccoMax (Jarrow Formulas), and numerous other broccoli sprout extract supplements.\n\nThe scientific foundation for sulforaphane was established by Talalay's laboratory beginning with a 1992 Proceedings of the National Academy of Sciences paperidentifying sulforaphane as a potent inducer of quinone reductase, a phase II detoxification enzyme. Subsequent work established sulforaphane as the primary bioactive small molecule in broccoli responsible for Nrf2 pathway activation, with effects persisting hours to days after a single exposure due to the covalent and long-lasting nature of Nrf2-Keap1 complex modification.\n\nKey clinical applications of sulforaphane include: chemoprevention research (breast, prostate, bladder, skin cancers via detoxification enzyme upregulation), autism spectrum disorder (Singh 2014 randomized trial showing behavioral improvements in young men with ASD), cardiovascular risk modification (LDL, blood pressure, endothelial function), type 2 diabetes (fasting glucose reduction), Helicobacter pylori eradication, air pollution protection, and general anti-inflammatory support. The Singh 2014 ASD trialis particularly notable as the first rigorous double-blind randomized trial showing behavioral improvements in autism with a dietary-derived compound, though subsequent replication has been mixed.\n\nPharmacokinetically sulforaphane has good oral bioavailability when properly formulated — approximately 70-80% absorption when active sulforaphane is delivered directly or when glucoraphanin is co-administered with active myrosinase. Half-life is approximately 1.9 hours. Metabolism occurs primarily through glutathione S-transferase conjugation followed by mercapturic acid pathway excretion. Plasma concentrations peak 1-3 hours after oral dosing with detectable sulforaphane-glutathione conjugates in urine for up to 24 hours. Tissue distribution is broad with particular accumulation in liver, kidney, gastrointestinal tract, and blood cells where Nrf2 targets are most abundant.\n\nThe thematic positioning of sulforaphane in contemporary supplementation is as a foundational, evidence-backed phytochemical for general longevity, detoxification, anti-inflammatory, and chemoprevention support. It has stronger clinical evidence than most polyphenols for biomarker-level effects (oxidative stress markers, detoxification enzyme activity, inflammatory markers) and is backed by decades of mechanistic research. Its safety profile at dietary and supplemental doses is excellent.\n\nCommercial sulforaphane supplementation involves either (1) glucoraphanin-based products with added active myrosinase (Avmacol is the gold standard here, with validated in-vivo sulforaphane production), (2) sulforaphane-stabilized products delivering preformed active sulforaphane directly (less common; stability challenges), or (3) broccoli sprout extract without active myrosinase (less reliable conversion relying on gut microbiome). Users should strongly prefer products with documented active myrosinase and standardized glucoraphanin content (the \"sulforaphane yield\" specification). Typical supplementation doses range from 30 mg glucoraphanin daily (entry dose, yielding ~10-15 mg sulforaphane) to 200+ mg glucoraphanin daily (therapeutic dose, yielding 60-90 mg sulforaphane).\n", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/sulforaphane" }, { "id": "b5a01155-4996-4a80-a06e-3fd4d2c53f32", "slug": "sunifiram", "name": "Sunifiram (DM-235)", "aliases": [ "DM-235", "DM 235", "1-(4-benzoylpiperazin-1-yl)propan-1-one", "1-benzoyl-4-propanoylpiperazine" ], "category": "Nootropics", "description": "Sunifiram, also called DM-235, is a piperazine that came out of an academic medicinal chemistry program at the University of Florence, not out of a pharmaceutical company. It was first reported in 2000 as one of a series of acylpiperazines obtained by simplifying a bicyclic scaffold, and it stood out for potency: it prevented amnesia in the mouse passive avoidance test at doses about a thousand times lower than piracetam-like reference compounds (PMID: 11087574; PMID: 12070754). Despite the racetam-style name it is not a pyrrolidinone and is not structurally a racetam.\n\nThe mechanism is not fully resolved. Binding studies found no affinity for the major central receptors or channels, yet sunifiram prevented amnesia induced by drugs acting on several different transmitter systems, including scopolamine, mecamylamine, baclofen and clonidine (PMID: 12070754; PMID: 16834757). Two glutamatergic actions have been documented. Sunifiram and its analog unifiram reversed amnesia induced by the AMPA receptor antagonist NBQX in mice and reversed kynurenic acid blockade of NMDA-mediated noradrenaline release in rat hippocampal slices, an effect abolished by NBQX (PMID: 14600801). Separately, in mouse hippocampal slices sunifiram enhanced long-term potentiation with a bell-shaped concentration-response curve peaking at 10 nanomolar; the enhancement was blocked by an antagonist of the glycine site of the NMDA receptor but not by an antagonist of the polyamine site, and involved protein kinase C alpha, Src family kinase and calcium/calmodulin-dependent protein kinase II (PMID: 23733502). Sunifiram also increased acetylcholine release in rat brain (PMID: 11087574).\n\nIn disease-model animals, sunifiram improved spatial reference memory in the Y maze and short-term memory in novel object recognition in olfactory bulbectomized mice and restored hippocampal long-term potentiation, with those effects blocked by a glycine site inhibitor; it did not improve depressive behavior in the same animals (PMID: 23295391).\n\nThere is no human data of any kind. No clinical trial, case series or pharmacokinetic study has been published, and searches of ClinicalTrials.gov return no records. The chemist who led the group that discovered sunifiram and unifiram wrote in 2015 that he had discovered by chance that dozens of websites were selling both compounds as cognitive enhancers for healthy people, even though only a few preclinical studies had been performed and their long-term toxicity was unknown, and that neither compound had been protected by a patent or taken forward by industry (PMID: 25831025).\n\nSunifiram is not approved in any country, is not a controlled substance in the United States and has no established human dose, safety threshold or contraindication list. Everything sold is a research chemical. One frequently cited paper on sunifiram carbamate hybrids as dual acetylcholinesterase inhibitors and NMDA co-agonists was retracted by the journal in 2026 (PMID: 42565552), so any claim traced back to it should be treated as unsupported.", "half_life": "Not established. No pharmacokinetic study in humans or animals has been published, and the group that discovered the compound stated that its long-term toxicity was unknown (PMID: 25831025).", "molecular_weight": "246.30 g/mol", "molecular_mass": "246.30 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Sunifiram has never been approved by any regulator, has never entered a registered clinical trial and does not appear in ClinicalTrials.gov. It is not scheduled as a controlled substance in the United States, but it has no lawful status there as a medicine or as a dietary supplement ingredient; it is a research-use-only compound. The academic group that discovered it published a paper in 2015 noting that it was being sold online as a cognitive enhancer with no toxicology package behind it (PMID: 25831025).", "trial_phase": "", "cas_number": "314728-85-3", "iupac_name": "", "chemical_formula": "C14H18N2O2", "potential_benefits": [ "Prevented scopolamine-induced amnesia in the passive avoidance test in mice at doses about a thousand times lower than piracetam-like reference compounds (PMID: 12070754)", "Prevented scopolamine-induced memory impairment in the Morris water maze in rats without impairing motor coordination or spontaneous motility (PMID: 12070754)", "Reversed amnesia induced by the AMPA receptor antagonist NBQX in mice (PMID: 14600801)", "Enhanced hippocampal long-term potentiation through the glycine site of the NMDA receptor in mouse hippocampal slices, with a bell-shaped concentration-response curve (PMID: 23733502)", "Improved Y maze and novel object recognition performance and restored hippocampal long-term potentiation in olfactory bulbectomized mice (PMID: 23295391)" ], "research_fields": [ "Cognitive enhancement", "NMDA glycine site", "AMPA receptor pharmacology", "Nootropics" ], "pubmed_count": 0, "pubchem_cid": 4223812, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/sunifiram" }, { "id": "fba89e08-8db4-434e-bb21-9b6abdaa7ff6", "slug": "survodutide", "name": "Survodutide", "aliases": [ "BI 456906", "Boehringer GLP-1/glucagon" ], "category": "GLP-1 / Glucagon Dual Agonist", "description": "Survodutide (BI 456906) is a once-weekly subcutaneous dual GLP-1 / glucagon receptor agonist developed by Boehringer Ingelheim and Zealand Pharma. As of 2026 it is in Phase 3 clinical trials (SYNCHRONIZE program) for obesity and metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH). Reported Phase 2 weight-loss results from late 2024 trials approached 19% body-weight reduction at the highest dose, placing it in the same outcome tier as Eli Lilly's retatrutide.\n\nUnlike pure GLP-1 agonists (semaglutide, tirzepatide's GLP-1 component), survodutide's glucagon agonism is hypothesized to drive higher resting energy expenditure and direct hepatic lipid mobilization - important mechanisms for MASH resolution where weight loss alone is insufficient.", "half_life": "~100 hours (about 4 days), supporting once-weekly dosing", "molecular_weight": "~4.9 kDa (acylated peptide)", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [ "Subcutaneous" ], "dose_range_mcg": "600-6000 mcg (0.6-6 mg) weekly research dosing", "dosing_frequency": "Once weekly subcutaneous", "cycle_length": "12-24+ weeks per protocol; trial protocols extend to 76 weeks", "common_vial_sizes": [ "5mg", "10mg" ], "research_stage": "Phase 3 (clinical trials in progress as of 2026)", "approval_status": "Not FDA-approved as of 2026. Investigational New Drug (IND).", "trial_phase": "Phase 3 (SYNCHRONIZE trials)", "cas_number": "", "iupac_name": "", "chemical_formula": "C-rich peptide (sequence not publicly disclosed)", "potential_benefits": [ "Up to 19% body weight reduction in Phase 2 trials", "MASH (steatohepatitis) histologic improvement without worsening of fibrosis in a Phase 2 trial (investigational; not resolution or approved use)", "Once-weekly dosing convenience", "Glucagon-driven energy expenditure increase", "Hepatic lipid mobilization" ], "research_fields": [ "Obesity", "MASH/NASH", "Type 2 diabetes", "GLP-1 receptor", "Glucagon receptor" ], "pubmed_count": 61, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/survodutide" }, { "id": "42389475-25a4-4c0a-8d6c-b99c54c2c0f1", "slug": "t3-t4-blend", "name": "T3/T4 Thyroid Blend", "aliases": [], "category": "Hormone Support", "description": "A T3/T4 blend pairs two real, FDA-approved thyroid hormones - levothyroxine (T4) and liothyronine (T3) - in a single product, intended to more closely mimic the thyroid gland's natural output than T4 alone. It is used clinically as combination therapy for hypothyroidism in patients who remain symptomatic on levothyroxine, but it is a potent prescription drug with a narrow safety window, not a supplement. The fixed 'blend' sold as a research chemical is unapproved, and unsupervised use - especially for weight loss or performance - risks serious cardiac (atrial fibrillation), skeletal (fracture) and thyrotoxic harm. It requires a diagnosis, a prescriber and lab monitoring. Research use only; not medical advice.", "half_life": "T4 (levothyroxine): approximately 6-7 days in euthyroid adults (longer in hypothyroid, shorter in hyperthyroid states). T3 (liothyronine): approximately 1 day (~18-24 hours), which is why T3 is dosed multiple times daily or as a slow-release preparation.", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "Component-split and physician-set, not a fixed self-dose: T4 (levothyroxine) approximately 75-150 mcg/day and T3 (liothyronine) approximately 5-20 mcg/day divided - both titrated to labs (TSH, free T4, free T3), individualized by weight, age and cardiac status. Not a self-dosing recommendation.", "dosing_frequency": "Levothyroxine (T4): once daily in the morning on an empty stomach. Liothyronine (T3): its short (~1 day) half-life means it is split into two or more daily doses, or given as a slow-release form, to avoid post-dose serum T3 peaks.", "cycle_length": "Not a 'cycle' drug. Thyroid replacement for genuine hypothyroidism is typically lifelong and continuous, adjusted to labs - not run in on/off cycles. The on/off 'cycling' seen in gray-market fat-loss use is a misuse pattern that risks thyrotoxicosis on and rebound hypothyroid symptoms off; it is not endorsed.", "common_vial_sizes": [], "research_stage": "Components are FDA-approved prescription drugs (levothyroxine and liothyronine); the fixed-ratio synthetic T3/T4 combination product is investigational/unapproved as sold and is framed here strictly for research use only (RUO).", "approval_status": "Prescription-only (Rx). Levothyroxine and liothyronine are FDA-approved individually, but no FDA-approved fixed-ratio synthetic T3/T4 combination product exists. 'T3/T4 blend' items sold without a prescription are unapproved and legally restricted - discussed here for research use only, not for human self-administration.", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Corrects genuine thyroid hormone deficiency (diagnosed, lab-confirmed hypothyroidism) - restoring normal metabolic rate, energy, cognition, temperature regulation and lipid profile. This benefit belongs to adequate thyroid replacement, not to any special 'blend' advantage.", "May help the minority of levothyroxine-treated patients who stay symptomatic despite a normal TSH - some report improved well-being, mood or cognition after a small amount of T3 is added. Reported in surveys and some crossover trials, but not confirmed as superior in pooled randomized data [PMID:33276704] [PMID:30550536].", "Provides direct, fast-acting T3 for people who may under-convert T4 to T3 (e.g., certain DIO2 deiodinase variants) - a mechanistic rationale still under active investigation [PMID:37738506].", "Delivers both hormones in one product, similar in concept to desiccated thyroid extract, which naturally contains T4 and T3 [PMID:26747302].", "IMPORTANT: There is NO evidence a T3/T4 blend aids weight loss, fat loss or athletic performance in people with normal thyroid function. Using thyroid hormone for those purposes is unproven and dangerous - it drives thyrotoxicosis, muscle-protein loss, cardiac strain and bone loss, not healthy fat loss." ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/t3-t4-blend" }, { "id": "4b9eee67-2cd5-4004-8509-df61b7d3eda5", "slug": "tadalafil", "name": "Tadalafil", "aliases": [ "Cialis", "Adcirca", "Tadaliq", "IC351", "Megalis", "Tadalis", "Tadacip", "CAS 171596-29-5", "Entadfi (combination with finasteride)" ], "category": "Metabolic", "description": "Tadalafil is a selective inhibitor of phosphodiesterase type 5 (PDE5), an enzyme that hydrolyzes cyclic guanosine monophosphate (cGMP) into non-cyclic 5'-GMP. By inhibiting PDE5, tadalafil preserves cGMP signaling in tissues where PDE5 is expressed — principally vascular smooth muscle of the corpus cavernosum, pulmonary vasculature, prostate, bladder, and to varying degrees other vascular beds — producing smooth muscle relaxation, enhanced blood flow, and tissue-specific functional effects. Tadalafil was developed by Lilly/ICOS and first approved by the FDA in November 2003 for erectile dysfunction (ED), joining sildenafil (Viagra, approved 1998) and vardenafil (Levitra, approved 2003) in the PDE5 inhibitor class. Tadalafil's distinguishing pharmacokinetic feature is its very long half-life of approximately 17-18 hours (versus sildenafil's ~4 hours), producing a clinical duration of action of up to 36 hours — hence the nickname \"the weekend pill.\" This long duration allows greater flexibility in dosing-to-activity timing and has driven tadalafil's commercial success in competition with shorter-acting PDE5 inhibitors. Tadalafil was subsequently approved for additional indications based on its PDE5 inhibition in other tissues: pulmonary arterial hypertension (PAH) in 2009 under the brand name Adcirca at higher dose (40 mg once daily, later revised to 20 mg twice daily formulation), based on the PHIRST trial (Galiè et al. 2009); benign prostatic hyperplasia and lower urinary tract symptoms (BPH/LUTS) in 2011, based on trials demonstrating improvements in International Prostate Symptom Score (IPSS) in men with and without concurrent ED (Oelke et al. 2012). The long half-life made tadalafil uniquely suited to once-daily dosing for BPH and for chronic low-dose ED management, leading to approval of a 2.5 mg and 5 mg once-daily formulation for continuous use in 2008 — a regimen now widely adopted for men seeking predictable sexual function without event-specific dosing as well as BPH symptom management. Tadalafil's generic patent expired in late 2018 in the United States, dramatically reducing cost from approximately $15-35 per pill (brand) to $1-5 per pill (generic) and driving substantial expansion of prescribing. Off-label and emerging applications have grown significantly: endothelial function support in patients with vascular risk factors, based on consistent evidence that PDE5 inhibition improves flow-mediated dilation and other endothelial function markers; potential cardiovascular benefit beyond ED, with ongoing research into heart failure with preserved ejection fraction, diabetic microvascular disease, and post-myocardial infarction recovery; possible cognitive/neuroprotective effects, triggered by observational data (Fang et al. 2024 showing 30-69% reduced Alzheimer's risk in men with BPH prescribed PDE5 inhibitors for >5 years) though causation is unproven; emerging longevity interest based on endothelial, mitochondrial, and NO/cGMP-pathway effects; and Raynaud's phenomenon, altitude sickness (off-label, related to pulmonary vasodilation), and female sexual dysfunction (mixed results, not FDA approved). Tadalafil sits at the intersection of several distinct patient populations: middle-aged and older men with ED (the majority use case); men with BPH/LUTS with or without ED (particularly well-suited given single-drug coverage of both issues); patients with pulmonary arterial hypertension (a serious condition with limited treatment options); and a growing population using low-dose daily tadalafil off-label for longevity, endothelial health, or enhanced sexual function in the absence of formal ED diagnosis. This broad and expanding use profile, combined with the substantial cost reduction from generic availability, has made tadalafil one of the most-prescribed medications in middle-aged men globally. The safety profile is well-characterized from decades of use and millions of person-years of exposure. Common side effects (headache, flushing, dyspepsia, back pain, nasal congestion) are typically mild and transient. The serious safety concerns — nitrate interaction producing life-threatening hypotension, and priapism — are well-understood and manageable with appropriate prescribing. The interaction profile is substantial, particularly with nitrates (absolute contraindication) and alpha-blockers (relative; requires dose separation and caution). CYP3A4-mediated drug interactions affect tadalafil's pharmacokinetics and must be considered in patients taking strong CYP3A4 inhibitors or inducers. This entry covers tadalafil's mechanism (PDE5 inhibition, NO/cGMP pathway, tissue-selective effects); FDA-approved indications (ED, BPH/LUTS, PAH); off-label and emerging applications (endothelial health, cognitive effects, cardiovascular adjunct uses); dosing strategies (event-specific versus daily, dose titration); the safety profile and critical interactions; and appropriate integration into male health, cardiovascular, and longevity protocols. Tadalafil is distinct from its research-chemical analog [aminotadalafil](/compound/aminotadalafil) — which lacks FDA approval, has inconsistent quality control, and carries the regulatory risk of gray-market sourcing. Cross-pathway integration with related interventions including [NMN](/compound/nmn), [metformin](/compound/metformin), and [berberine](/compound/berberine) is discussed.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 1, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/tadalafil" }, { "id": "b67418eb-4caa-402c-9dd8-06cd0373c5b6", "slug": "tak-653", "name": "TAK-653", "aliases": [], "category": "Nootropics", "description": "TAK-653 is a novel positive allosteric modulator (PAM) of AMPA-type glutamate receptors developed by Takeda Pharmaceuticals. It enhances glutamatergic neurotransmission without directly activating the receptor, offering a more controlled mechanism for cognitive enhancement and antidepressant effects. Originally developed for treatment-resistant depression, it has gained interest in the research community for its potential nootropic and neuroplasticity-promoting properties.", "half_life": "6-10 hours (estimated)", "molecular_weight": "282.27", "molecular_mass": "282.27 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "0.1 mg - 6 mg", "dosing_frequency": "Once daily", "cycle_length": "4-8 weeks on, 2-4 weeks off", "common_vial_sizes": [], "research_stage": "Phase II Clinical Trials", "approval_status": "", "trial_phase": "", "cas_number": "1531665-83-2", "iupac_name": "", "chemical_formula": "C16H11FN2O2", "potential_benefits": [ "Cognitive enhancement and improved learning", "Antidepressant effects (treatment-resistant depression)", "Enhanced synaptic plasticity and LTP", "Increased BDNF expression", "Improved working memory and executive function", "Potential neuroprotective properties" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/tak-653" }, { "id": "1e63de12-d2b4-408b-8dc0-bcdfb7ff4cba", "slug": "taurine", "name": "Taurine", "aliases": [ "2-aminoethanesulfonic acid", "Tau", "T-1509", "TauroPure", "L-Taurine" ], "category": "Foundational", "description": "Taurine is a sulfonic acid (not technically an amino acid, though often classified as one) that ranks among the most abundant free amino acid-like molecules in human tissues. Unlike the twenty proteinogenic amino acids, taurine is not incorporated into proteins. Instead, it exists as a free cytosolic molecule performing osmoregulation, membrane stabilization, calcium handling, anti-inflammatory signaling, and bile acid conjugation. Total body taurine exceeds 70 grams in a typical adult, concentrated in skeletal muscle, cardiac muscle, retina, brain, and platelets—with retinal taurine concentrations approaching 50 mM, among the highest of any molecule in any tissue.\n\nFor decades, taurine was viewed as a simple nutritional curiosity—conditionally essential in infants (explaining its addition to infant formula since the 1980s after cats fed taurine-free diets developed cardiomyopathy and blindness), but not typically considered important for adult supplementation. That view changed dramatically in June 2023 with publication of a landmark paper in Science by Singh, Yadav, and colleagues demonstrating that circulating taurine concentrations decline approximately 80% between youth and old age in humans, mice, and non-human primates, and that restoring taurine through supplementation extended healthspan and lifespan in mice and showed favorable metabolic effects in monkeys. This study, while requiring human validation, reframed taurine as a potentially actionable target in healthy aging.\n\nTaurine's biological roles are mechanistically diverse. It stabilizes cellular membranes through interactions with phospholipid head groups, supports mitochondrial protein translation via a unique role as a tRNA modifier, regulates intracellular calcium through effects on the sarcoplasmic reticulum, modulates inhibitory neurotransmission via GABA-A and glycine receptors, serves as the obligate conjugate partner for bile acids in most vertebrates, and functions as a cytoprotective osmolyte during cellular stress. The breadth of these roles explains both taurine's near-universal tissue distribution and its apparent safety even at high supplementation doses—taurine enhances functions that are already present rather than inducing novel pharmacology.\n\nFrom a practical supplementation perspective, taurine occupies an interesting niche. It has been widely sold as an over-the-counter supplement for decades, included in energy drinks (typically 1-2 g per serving, often with caffeine), used by body builders for cell volumization, prescribed in some countries for congestive heart failure, and recently elevated to longevity-focused stacks after the Singh 2023 publication. The cost is modest, safety profile is excellent, and the emerging evidence base is compelling but not yet definitive for most adult populations.\n\nDietary taurine is obtained almost exclusively from animal foods—shellfish (scallops and clams are particularly high), dark poultry meat, red meat, fish, and organ meats. Plants contain essentially zero taurine. Strict vegetarians and vegans have measurably lower plasma and urinary taurine compared to omnivores, and infants fed soy-based formula require taurine supplementation to prevent deficiency. Humans can synthesize taurine from cysteine via the cysteine dioxygenase and cysteine sulfinic acid decarboxylase pathway, but synthetic capacity is limited in humans compared to rodents (one reason the cat, which has near-zero synthetic capacity, is an obligate carnivore dependent on dietary taurine). This limited biosynthesis combined with age-related decline in synthesis and tissue uptake is a plausible mechanistic reason why taurine status drops with age.\n\nFor users of BodyHackGuide, taurine represents a low-cost, low-risk foundational supplement with emerging longevity-focused evidence and well-established cardiovascular applications. Typical supplementation ranges from 1-3 grams daily, with higher doses (3-6 grams) used in specific clinical contexts like congestive heart failure. The most common errors are: (1) assuming taurine and taurate are identical (taurate is a mineral salt, taurine is the pure amino sulfonic acid), (2) confusing the caffeine-induced effects of energy drinks with taurine-specific effects, and (3) expecting rapid results when most documented benefits emerge over weeks to months of consistent use. This monograph addresses these issues with emphasis on the Singh 2023 findings and their translational uncertainty. For related foundational support, see /compound/creatine, /compound/magnesium, /compound/glycine, and /compound/nmn.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/taurine" }, { "id": "a1000000-0000-0000-0000-000000000002", "slug": "tb-500", "name": "TB-500", "aliases": [ "Thymosin Beta-4 fragment (17-23)", "TB4 fragment", "TB500", "TB 500", "Ac-LKKTETQ" ], "category": "Injury, Repair & Recovery", "description": "TB-500 is the name the market and the FDA use for a short synthetic fragment of thymosin beta-4: the seven-amino-acid, N-acetylated actin-binding sequence Ac-LKKTETQ (residues 17 to 23). Thymosin beta-4 itself is a 43-amino-acid peptide (about 4963 Da acetylated) and one of the most abundant intracellular actin-sequestering molecules in mammalian cells. The two are not the same molecule. Analytical work on internet-sold TB-500 found products that did not match their descriptions (PMID: 36482504), and a 2024 metabolite study states that the biological effects of the acetylated TB-500 fragment have not been documented (PMID: 38382158). The sequence and mass on a lot certificate of analysis are the only way to know which form a vial holds.\n\nThe foundational review by Goldstein et al. (2005) established full-length thymosin beta-4 as a multifunctional regenerative peptide with roles spanning wound healing, angiogenesis, anti-inflammation, and cardiac repair. Unlike many bioactive peptides, thymosin beta-4 is not a hormone or cytokine but rather an intracellular actin-regulatory protein that, when released extracellularly following injury, initiates paracrine signaling cascades that drive tissue repair. Most of what follows is full-length thymosin beta-4 data; the fragment's efficacy data appears only in the wound-healing paragraph.\n\nThymosin beta-4 has been studied extensively in preclinical models of cardiac injury. Bock-Marquette et al. (2004) demonstrated that thymosin beta-4 promotes survival of cardiomyocytes after experimental myocardial infarction in mice, reduces infarct size, and improves cardiac function. The mechanism involves activation of the Akt (protein kinase B) survival pathway and migration of cardiomyocytes and endothelial cells toward the injury. These findings positioned thymosin beta-4 as a candidate cardiac repair agent, though clinical translation has been limited.\n\nIn wound healing research, thymosin beta-4 accelerates dermal wound closure by promoting keratinocyte and endothelial cell migration, increasing angiogenesis, and reducing inflammation at the wound site. Philp et al. (2003) showed that topical thymosin beta-4 significantly accelerated full-thickness wound closure in diabetic and aged mouse models, and in the same paper the free seven-residue fragment LKKTETQ promoted repair in aged animals comparable to the parent peptide (PMID: 12581423). That one mouse study, plus in-vitro assays, is the fragment record; there is no human data for the fragment.\n\nThymosin beta-4 has also shown efficacy in corneal wound healing models. Sosne et al. demonstrated that thymosin beta-4 eye drops accelerate corneal epithelial wound closure and reduce inflammation after chemical or mechanical injury, leading to ophthalmic clinical trials (Phase 2 and Phase 3, RGN-259) for dry eye and neurotrophic keratopathy. This is the most advanced clinical development program for any thymosin beta-4-based therapeutic, and it is topical.\n\nTB-500 is not FDA-approved for any human therapeutic indication. It is a doping-control target in racing horses (PMID: 23084823) and is used in the human peptide biohacking community for musculoskeletal recovery, wound healing, and anti-inflammatory effects, on the strength of the full-length peptide literature rather than any human fragment data.", "half_life": "Plasma half-life is short - full-length thymosin beta-4 clears on the order of hours, while the short LKKTETQ actin-binding fragment clears within minutes. Tissue-level regenerative effects persist substantially longer than plasma exposure.", "molecular_weight": "889 Da (Ac-LKKTETQ); full-length thymosin beta-4 4963 Da", "molecular_mass": "889.0 g/mol (Ac-LKKTETQ); 846.97 g/mol (LKKTETQ, free); full-length thymosin beta-4 4963.4 g/mol acetylated", "amino_acid_sequence": "Ac-LKKTETQ (thymosin beta-4 residues 17-23). Full-length thymosin beta-4 for comparison: Ac-SDKPDMAEIEKFDKSKLKKTETQEKNPLPSKETIEQEKQAGES", "administration_routes": [ "Subcutaneous", "Intramuscular" ], "dose_range_mcg": "2000-5000 mcg (2-5 mg) subcutaneous 2x weekly loading; 2000 mcg (2 mg) weekly maintenance", "dosing_frequency": "2x per week during loading; 1x per week maintenance", "cycle_length": "4–8 weeks loading, then 2–4 weeks maintenance", "common_vial_sizes": [ "2mg", "5mg", "10mg" ], "research_stage": "Preclinical", "approval_status": "Not approved by FDA or EMA for any indication. Full-length thymosin beta-4 is investigational (topical ophthalmic RGN-259). FDA placed the thymosin beta-4 fragment LKKTETQ (TB-500) in 503A category 2 in September 2023 citing immunogenicity risk, peptide impurities and no human exposure data; it moved to \"nominated but withdrawn\" in April 2026 because the nominators withdrew, which is not a safety clearance. Thymosin beta-4 and its derivatives, TB-500 named, are WADA S2.3, prohibited at all times.", "trial_phase": "Phase 2", "cas_number": "77591-33-4", "iupac_name": "N-acetyl-L-leucyl-L-lysyl-L-lysyl-L-threonyl-L-alpha-glutamyl-L-threonyl-L-glutamine", "chemical_formula": "C38H68N10O14 (Ac-LKKTETQ); full-length thymosin beta-4 is C212H350N56O78S", "potential_benefits": [ "Accelerated dermal wound healing through enhanced keratinocyte and fibroblast migration, collagen deposition, and angiogenesis, including in diabetic and aged models (PMID: 12581423)", "Cardioprotection and tissue repair after myocardial infarction via ILK/Akt survival signaling in preclinical models (PMID: 17600280)", "Anti-inflammatory effects via NF-kB suppression and reduced pro-inflammatory cytokines (preclinical)", "Corneal wound healing and dry eye symptom improvement in topical ophthalmic (RGN-259) Phase 2 trials (PMID: 25826322)", "Enhanced hair follicle stem cell migration associated with hair growth (preclinical)", "Musculoskeletal recovery through collagen deposition and matrix remodeling (preclinical and equine data)", "Endothelial cell migration and vascular regeneration in ischemic tissues (preclinical)" ], "research_fields": [ "Cardiac repair", "Wound healing", "Dry eye syndrome", "Corneal healing", "Muscle injury" ], "pubmed_count": 1039, "pubchem_cid": 16132380, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/16132380/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/tb-500" }, { "id": "a1000000-0000-0000-0000-000000000008", "slug": "tesamorelin", "name": "Tesamorelin", "aliases": [ "Tesa", "TH9507", "BH-Morelin", "BHG-2T" ], "category": "Growth Hormone / IGF-1 Axis", "description": "Tesamorelin is a **stabilized synthetic analog of human growth hormone-releasing hormone (GHRH)** — specifically the full 44-amino-acid GHRH sequence with a single N-terminal trans-3-hexenoyl fatty-acid modification. That modification protects the peptide from rapid dipeptidyl peptidase-4 (DPP-4) degradation, extending its circulating half-life to approximately 30 minutes (vs <2 minutes for native GHRH).\n\nTesamorelin was developed by Theratechnologies and is marketed in the US as **Egrifta** (branded injectable) and **Egrifta SV** (updated formulation launched 2019). It is the **only FDA-approved GHRH secretagogue** in the United States, approved in 2010 for the **reduction of excess abdominal fat in HIV-infected patients with lipodystrophy**. The approval was based on two Phase 3 trials showing ~18% reduction in visceral adipose tissue (VAT) at 26 weeks and sustained effect through 52 weeks ([Falutz et al., 2007]; [Falutz et al., 2010]).\n\nUnlike [CJC-1295 with DAC](/compound/cjc-1295-dac), tesamorelin produces a **pulsatile rather than sustained** GH elevation. It preserves the negative-feedback regulation of the somatotroph axis because its half-life is short enough to clear between pulses, and this is the primary clinical reason it was developable as a long-term therapy where CJC-1295-DAC's continuous GH elevation raised safety concerns.\n\nBeyond the FDA-approved HIV lipodystrophy indication, tesamorelin is being studied and used off-label for:\n- **Non-alcoholic fatty liver disease (NAFLD / NASH)** — Phase 2 trial showed reductions in hepatic fat fraction and liver enzymes ([Stanley et al., 2014])\n- **HIV-associated cognitive decline** — pilot data on executive function and memory ([Adrian et al., 2018])\n- **General visceral adiposity** in non-HIV metabolically-unhealthy adults (off-label biohacker use)\n- **Adjunct to [CJC-1295 / MOD-GRF 1-29](/compound/cjc-1295) + [Ipamorelin](/compound/ipamorelin) stacks** — when GHRH-only amplification is desired without the pulsatility trade-off of CJC-1295 with DAC\n\nTypical dosing: **2 mg subcutaneous once daily pre-bed** (matches the FDA-approved protocol). Dose escalation above 2 mg/day has been studied but does not produce proportional IGF-1 elevation and raises fluid-retention burden.\n\n**Regulatory status:** FDA-approved for HIV lipodystrophy; available by prescription in the US. Biohacker use is off-label and typically sourced through compounding pharmacies or (controversially) research-chemical vendors. See our [Tesamorelin Dosage Guide](/guides/dosage/tesamorelin) for protocol specifics.", "half_life": "30-50 minutes (plasma)", "molecular_weight": "5135.9 Da", "molecular_mass": "5135.8 g/mol", "amino_acid_sequence": "trans-3-hexenoyl-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Arg-Ala-Arg-Leu-NH2 (single-letter: YADAIFTNSYRKVLGQLSARKLLQDIMSRQQGESNQERGARARL). Tesamorelin is human GHRH(1-44) bearing an N-terminal trans-3-hexenoyl group on Tyr1 and a C-terminal amide. Molecular formula C221H366N72O67S; molecular weight ~5135.9 Da.", "administration_routes": [ "subcutaneous" ], "dose_range_mcg": "1,000–2,000 mcg (1–2 mg) daily", "dosing_frequency": "Once daily subcutaneous injection", "cycle_length": "12–26 weeks in clinical trials; ongoing use common", "common_vial_sizes": [ "2mg", "10mg" ], "research_stage": "FDA Approved", "approval_status": "FDA-approved as Egrifta® for HIV-associated lipodystrophy (2010)", "trial_phase": "FDA Approved", "cas_number": "218949-48-5", "iupac_name": "trans-3-hexenoyl-GHRH(1-44)amide", "chemical_formula": "C221H366N72O67S", "potential_benefits": [ "Reduction of visceral adipose tissue (~15% at 26 weeks in the pivotal HIV trial; FDA-label indication)", "Reduction of hepatic fat content (NAFLD off-label indication)", "Elevated IGF-1 within the age-adjusted reference range", "Preserved pulsatile GH release (vs continuous elevation with CJC-1295-DAC)", "Improved body composition (VAT down, lean mass preserved)", "Sustained VAT reduction through 52 weeks with continued dosing", "FDA-approved - the only GHRH secretagogue with that status" ], "research_fields": [ "HIV-associated lipodystrophy", "Visceral adiposity", "Cognitive aging", "Metabolic syndrome" ], "pubmed_count": 8, "pubchem_cid": 9882981, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/9882981/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/tesamorelin" }, { "id": "b11c020e-2af3-4f76-a374-7d89ebb8cedf", "slug": "tesofensine", "name": "Tesofensine", "aliases": [ "NS2330" ], "category": "Weight Loss", "description": "Tesofensine (NS2330) is an orally-administered small-molecule triple monoamine reuptake inhibitor — it blocks the reuptake of noradrenaline, dopamine, and serotonin, placing it in the same broad pharmacologic class as sibutramine (withdrawn 2010 for cardiovascular risk) but with a different receptor-affinity profile and markedly longer half-life. Originally developed by Danish company NeuroSearch in the late 1990s as a treatment for Alzheimer's disease and Parkinson's disease, tesofensine failed both neurology indications in Phase 2 trials. What rescued the compound from shelf-abandonment was an incidental observation across those failed neurology programs: patients consistently lost weight on tesofensine, often substantially, despite losing weight not being a primary or secondary endpoint.\n\nThat signal triggered repositioning toward obesity, culminating in a 2008 Phase 2B trial (TIPO-1) published in The Lancet that remains one of the most-cited papers in modern obesity pharmacology ([Astrup et al., 2008](https://pubmed.ncbi.nlm.nih.gov/18950853/)). The trial enrolled 203 obese adults randomized to tesofensine 0.25 mg, 0.5 mg, 1.0 mg daily or placebo plus a hypocaloric diet, and reported mean 24-week weight loss of 6.7%, 11.3%, and 12.8% at the three active doses vs 2.2% for placebo — roughly **double** what any other obesity drug was producing at the time and within striking distance of early bariatric surgery results. The magnitude of the effect generated substantial commercial interest and positioned tesofensine as potentially the first \"surgery-competitive\" weight-loss drug.\n\nHowever, the 1 mg dose produced clinically meaningful increases in heart rate and blood pressure, raising the cardiovascular safety concerns that had already led to sibutramine's withdrawal. FDA and EMA did not approve tesofensine, and the Phase 3 program stalled. NeuroSearch divested the compound to Saniona (Danish biotech), which continued development and achieved regulatory approval in Mexico (marketed as Tesomet for Prader-Willi syndrome-associated obesity) but not in the US or Europe as of 2026. Tesofensine has since become a widely-traded research chemical, with unapproved-market use for weight loss despite the unresolved cardiovascular signal and limited Phase 3 safety data.\n\nCross-references include [Semaglutide](/compound/semaglutide) and [Tirzepatide](/compound/tirzepatide) (approved GLP-1-class alternatives with stronger safety profiles), [Retatrutide](/compound/retatrutide) (investigational triple agonist), [Orforglipron](/compound/orforglipron) (oral GLP-1 agonist), [Cagrilintide](/compound/cagrilintide) (amylin analog), and [AOD-9604](/compound/aod-9604) (another repurposed failure). For stimulant-class cognitive context see [Modafinil](/compound/modafinil) and [Methylphenidate](/compound/methylphenidate).", "half_life": "", "molecular_weight": "", "molecular_mass": "298.24 g/mol", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "0.25 mg - 1 mg daily (oral)", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "194093-60-8", "iupac_name": "(1R,2S,3R,5S)-3-(3,4-dichlorophenyl)-2-(ethoxymethyl)-8-azabicyclo[3.2.1]octane", "chemical_formula": "C15H21Cl2N", "potential_benefits": [ "Significant weight loss (10-15% body weight)", "Appetite suppression", "Increased metabolic rate", "Enhanced dopamine-driven motivation" ], "research_fields": [], "pubmed_count": 55, "pubchem_cid": 159836, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/tesofensine" }, { "id": "74cf8637-2dd4-497c-b81f-cc40c2de3678", "slug": "testagen", "name": "Testagen", "aliases": [ "Testes peptide" ], "category": "Other", "description": "Testagen is a short peptide bioregulator developed inside Vladimir Khavinson's laboratory at the Saint Petersburg Institute of Bioregulation and Gerontology and marketed in Russia as an oral capsule intended to support the male reproductive system — principally the testes, spermatogenesis, and the hypothalamic-pituitary-gonadal (HPG) axis. Within the Khavinson short-peptide catalog Testagen sits beside its female counterpart [Ovagen](/compound/ovagen), sharing the same basic premise: that a very short, tissue-derived peptide can reach nuclei inside a specific organ and nudge age-related gene expression back toward a younger pattern. Testagen is the male analogue in that paired design.\n\nThe Khavinson literature typically reports Testagen as a tetrapeptide. Sequence identifiers published across Russian-language reviews, patent filings, and commercial capsule documentation are not always consistent, and Western peer-reviewed databases generally do not carry an authoritative entry. Readers should understand that \"Testagen\" in most online contexts refers to the commercial oral capsule formulation, which, like the rest of the Khavinson bioregulator line, is a 20 milligram nominal capsule containing approximately 2 to 4 milligrams of synthetic peptide dispersed in milk-protein and starch excipients. The remainder of the capsule weight is filler. This matters because the dose printed on the label is not the dose of peptide; it is the dose of the whole blended powder.\n\nTestagen is sold as a research compound and as an over-the-counter supplement in Russia and several Eastern European markets. It is not a registered pharmaceutical in the United States, the European Union, the United Kingdom, Canada, or Australia. It is not FDA-approved for any indication. It has not undergone the phase 1 through phase 3 Western regulatory process that defines a therapeutic drug in most of the developed world. All human evidence supporting Testagen comes from a small and largely Russian-language body of work published by Khavinson and collaborators, with modest independent replication. In the hierarchy of evidence that informs a decision to treat age-related male hypogonadism or subfertility, Testagen belongs well below the first-line options — lifestyle correction, testosterone replacement therapy (TRT), clomiphene or enclomiphene, hCG, and anastrozole — which are supported by decades of randomized controlled trials and global regulatory review.\n\nBodyHackGuide presents Testagen honestly rather than promotionally. If a reader is researching it, the goal of this page is to explain what it is, what the Khavinson framework claims, where the evidence is thin, how it would theoretically be used, what safer and better-evidenced alternatives exist, and what contraindications and interactions matter most. The framing throughout is that Testagen is at best a niche adjunct in a well-constructed male hormonal or fertility protocol, and at worst an unnecessary purchase that displaces money and attention from interventions with decades of Western evidence behind them. Readers pursuing male infertility, low testosterone, or erectile dysfunction should start with a urologist or reproductive endocrinologist, not with a Russian bioregulator capsule.\n\nThe most important concept linking Testagen to the rest of the Khavinson catalog — [Epitalon](/compound/epithalon), [Thymogen](/compound/thymogen), [Pinealon](/compound/pinealon), [Vilon](/compound/vilon), [Livagen](/compound/livagen), [Bronchogen](/compound/bronchogen), [Cardiogen](/compound/cardiogen), [Cartalax](/compound/cartalax), [Chonluten](/compound/chonluten), [Ovagen](/compound/ovagen), and [Prostamax](/compound/prostamax) — is tissue specificity. In Khavinson's model, each short peptide is claimed to migrate preferentially to its target tissue, enter nuclei, and bind sequence-selectively to regions of DNA associated with that tissue's developmental and housekeeping programs. Testagen is positioned as the testicular-specific member of that family. The peptide is said to act on Leydig cells (which produce testosterone), Sertoli cells (which support spermatogenesis), and the spermatogonial lineage, with a secondary action on hypothalamic GnRH neurons and pituitary gonadotropes.\n\nWhether that tissue-selective distribution and sequence-selective DNA binding actually occurs to a meaningful degree in humans is not settled in Western literature. The pharmacokinetic and mechanistic studies supporting the framework are mostly from Khavinson's own group, often in cell culture or rodent models, and the published human trials are small, single-center, open-label, and short. Readers should weigh that carefully against the marketing tone common on vendor sites, which tends to describe Testagen as if its claims were established.\n\nThe main demographic buying Testagen is men in their forties, fifties, and sixties who are noticing fatigue, decreased libido, morning-erection loss, mood flattening, mild cognitive slowing, and declining gym performance — the classic symptom cluster of age-related hypogonadism. That demographic is being marketed a bioregulator that, at most, nudges endogenous testosterone modestly; standard TRT delivers a reliably larger and better-documented change in serum testosterone and symptomatic response. The honest framing on this page is that Testagen is not a TRT alternative. It is, at best, an adjunct for men who either cannot tolerate TRT, have mild subclinical hypogonadism that does not yet meet treatment thresholds, or prefer an intervention with lower medical oversight — with the understanding that doing so trades documented efficacy for a much thinner evidence base.\n\nThe secondary demographic is men pursuing fertility: those with oligospermia (low sperm count), asthenospermia (poor motility), teratospermia (abnormal morphology), or the combination. Testagen is claimed to support Sertoli-cell function and spermatogenesis. That claim is not supported by large randomized trials of Testagen specifically. It is supported, loosely, by the broader literature on antioxidant and micronutrient supplementation in male fertility — a field where CoQ10, L-carnitine, zinc, selenium, folate, vitamin D, and vitamin E all have modestly better evidence than any bioregulator peptide. A man trying to conceive should not be leaning on Testagen. He should be on a structured fertility workup with a reproductive urologist, correcting modifiable factors (smoking, alcohol, heat exposure, sleep, obesity, varicocele), optimizing micronutrients, and considering clomiphene or hCG where indicated.\n\nTestagen is most commonly used in a 10-days-on cycle followed by a 60 to 90 day washout, per the Khavinson cycling convention. Each dose is one or two capsules on an empty morning stomach. Cycles are typically repeated twice per year, often paired with Epitalon (the master pineal bioregulator) and sometimes with Thymogen (immune) or Vesugen (vascular) depending on the user's priorities. Reconstitution is not required because Testagen is almost always oral; any injectable formulation is a research-chemical compound rather than the commercial capsule.\n\nSafety observation in the published Khavinson work has been consistently reassuring at the doses used, but the trials are small and follow-up is limited. This page treats \"well tolerated\" as a provisional claim rather than a conclusion, and specifically flags prostate cancer and elevated PSA under workup as absolute contraindications — the same way finasteride, testosterone replacement, and hCG are contraindicated in that setting. A short peptide whose stated purpose is to stimulate gonadal gene expression is not something to take while a prostate tumor is being investigated.", "half_life": "", "molecular_weight": "447.44 g/mol", "molecular_mass": "447.44 g/mol", "amino_acid_sequence": "Lys-Glu-Asp-Gly (KEDG)", "administration_routes": [], "dose_range_mcg": "20 mg oral capsule, 1-2 daily for 10 days per cycle", "dosing_frequency": "Once or twice daily during a 10-day cycle (oral capsules, empty stomach)", "cycle_length": "10 days on, 60-90 days off; 2-4 cycles per year", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "L-Lysyl-L-glutamyl-L-aspartyl-L-phenylalanine", "chemical_formula": "Lys-Glu-Asp-Phe", "potential_benefits": [ "Testicular function support", "Natural testosterone production enhancement", "Spermatogenesis support", "Male reproductive health maintenance" ], "research_fields": [], "pubmed_count": 2, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/testagen" }, { "id": "153c7609-e919-43e9-a310-323284a86033", "slug": "theacrine", "name": "Theacrine", "aliases": [ "1,3,7,9-tetramethyluric acid", "TeaCrine", "1,3,7,9-tetramethyl-purine-2,6,8-trione" ], "category": "Nootropics", "description": "Theacrine (1,3,7,9-tetramethyluric acid) is a purine alkaloid structurally related to caffeine, found naturally in Camellia assamica var. kucha — a tea cultivar grown in southern China and northern Vietnam — and in smaller amounts in Cupuaçu (Theobroma grandiflorum) seeds. It shares caffeine's xanthine backbone but carries an extra methyl group at the 9-position and a 2,6,8-trione oxidation pattern, giving it pharmacology that overlaps caffeine's adenosine-receptor antagonism while diverging in dopaminergic tone and tolerance development. The most widely studied form in human trials is the patented ingredient TeaCrine, a ≥98% pure synthetic equivalent used in most commercial nootropic and pre-workout formulas.\n\nThe practical appeal of theacrine in community use rests on three observations: first, healthy adults taking 200-300 mg daily report stimulation subjectively comparable to 150-200 mg caffeine — but with less jitter, less heart-rate elevation, and a slower onset (~60-90 minutes) that many users describe as \"smoother\" than caffeine's 20-40 minute peak. Second, an 8-week daily-dosing study (Taylor 2016) found no meaningful development of tolerance at 200-300 mg/day, no withdrawal signs on cessation, and no shifts in resting heart rate, blood pressure, liver enzymes, or complete blood count — a tolerance profile that genuinely differs from caffeine, where habitual use produces documented receptor upregulation and dependence within 1-2 weeks. Third, co-administration with caffeine produces synergy: pharmacokinetic data (He 2017) show caffeine roughly doubles theacrine plasma exposure (AUC), likely by slowing hepatic clearance, so 125 mg theacrine + 150 mg caffeine often outperforms either compound alone for perceived focus and endurance.\n\nMechanism is not identical to caffeine. Like caffeine, theacrine antagonizes adenosine A1 and A2A receptors (the primary driver of wakefulness and reduced perception of effort), but rodent models (Feduccia 2012) additionally show dose-dependent increases in nucleus accumbens dopamine and locomotor activation that are blocked by both adenosine and dopamine-D1 antagonists — suggesting a dual adenosinergic-dopaminergic mechanism that caffeine does not fully replicate. This may explain the \"motivation\" quality users report and the absence of downregulation: chronic adenosine blockade alone should produce tolerance, but the concurrent dopaminergic signal appears to counterbalance receptor adaptation over an 8-week horizon.\n\nHuman clinical data are limited but consistent. A double-blind crossover in habitual caffeine users (Ziegenfuss 2017) showed 300 mg theacrine improved reaction-time Bond-Lader alertness scores without the jitter-axis elevation that 150 mg caffeine produced in the same subjects. A separate 8-week safety and efficacy trial in 60 adults (Kuhman 2015) reported significant improvements in self-rated energy, focus, and concentration versus placebo at 200 and 300 mg/day with no adverse clinical findings. Community-tier evidence (r/Nootropics, forum writeups spanning 2015-2024) tends to converge on 100-200 mg as a mild-stim daily baseline, 250-300 mg for pre-workout or high-focus sessions, and 150 mg + 100 mg caffeine as a common synergy stack. Most users who transition from pure caffeine report similar energy with substantially less afternoon \"crash\" and easier sleep onset if taken before 2 PM.\n\nPractical considerations: theacrine is sold as a food-supplement ingredient in the US, EU, Australia, and most of Asia. It is NOT a controlled substance, not a prescription drug, and has no abuse liability signal in animal models. Quality matters — the vast majority of peer-reviewed human data used TeaCrine, a standardized ≥98% pure ingredient; some generic \"theacrine\" bulk powder has been found to be underdosed or contaminated with caffeine (independent COA testing, 2019-2021). Look for products that explicitly cite the TeaCrine trademark and provide a certificate of analysis.\n\nTheacrine is often stacked with L-theanine (100-200 mg) for an anxiolytic counterweight, with alpha-GPC (300 mg) for cholinergic contrast, and with dynamine (methylliberine, a faster-acting but shorter-duration analog) for a biphasic energy curve. It is not recommended for pregnancy, breastfeeding, uncontrolled hypertension, or anyone on MAOIs. The safety window at studied doses is wide, but the long-term profile beyond 8 weeks remains formally uncharacterized — community experience over 2-3 years of daily use suggests it holds up, but this is self-report data.", "half_life": "16-20 hours (plasma); Tmax 60-90 minutes", "molecular_weight": "224.22 g/mol", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Dietary Supplement (Food Ingredient)", "approval_status": "FDA GRAS Self-Affirmed (TeaCrine, 2014); FDA NDI notification accepted 2014", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 80, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/theacrine" }, { "id": "05aafa1f-b6ba-4208-bbf0-252503c50a86", "slug": "thiamine", "name": "Thiamine", "aliases": [ "B1", "Vitamin B1", "Thiamine HCl", "Thiamine hydrochloride", "Thiamine mononitrate", "Thiamin", "Thiamine pyrophosphate", "TPP", "TDP", "Thiamine diphosphate", "Cocarboxylase", "Aneurine", "Aneurin", "Benfotiamine", "S-benzoylthiamine O-monophosphate", "Allithiamine", "Fursultiamine", "Bisbentiamine", "TTFD", "Thiamine tetrahydrofurfuryl disulfide", "Prosultiamine", "Octotiamine", "Alinamin" ], "category": "Vitamin", "description": "Thiamine (vitamin B1) is the original vitamin — the deficiency syndrome beriberi was the clinical problem that gave rise to the entire vitamin concept, and the compound isolated from rice polishings by Jansen and Donath in 1926 and synthesized by Robert Williams in 1936 was literally the first \"vital amine\" (Casimir Funk coined the term *vitamine* in 1912 after investigating the anti-beriberi factor). The pharmacology is deceptively simple: thiamine is a water-soluble cofactor vitamin that, after phosphorylation to thiamine pyrophosphate (TPP, also called thiamine diphosphate or TDP), serves as the indispensable coenzyme for a handful of decarboxylase reactions that sit at the central intersection of glucose metabolism and amino acid catabolism. Without adequate TPP, the brain and heart fail in predictable patterns within weeks, and the resulting clinical syndromes — beriberi, Wernicke encephalopathy, Korsakoff psychosis, Shoshin fulminant cardiac beriberi — are among the most dramatic and preventable neurological emergencies in medicine. The adult RDA is 1.2 mg/day for men, 1.1 mg/day for women, 1.4 mg/day in pregnancy, and 1.4 mg/day in lactation. There is no formally established tolerable upper intake level for thiamine because it is among the safest vitamins known — the body does not substantially accumulate it (plasma half-life ~1-12 hours, whole-body half-life ~10-20 days), and excess oral or intravenous thiamine is cleared in the urine without known toxicity at gram-per-day doses. This makes thiamine an unusual vitamin: a potentially life-saving emergency medicine with essentially no ceiling on dosing in acute deficiency states, and a routine dietary requirement at low-milligram amounts in health. Western populations are largely protected from frank beriberi by grain fortification since the 1940s, but thiamine deficiency remains common in specific clinical contexts: **chronic alcohol use** (impaired absorption, impaired hepatic storage, and increased urinary loss combine to produce the classic Wernicke-Korsakoff picture, 12230201), **hyperemesis gravidarum** (protracted vomiting combined with increased metabolic demand in pregnancy can produce Wernicke encephalopathy in non-alcoholic women, with the additional risk of fetal demise), **bariatric surgery** (Roux-en-Y and sleeve patients are at life-long risk because of altered anatomy and variable adherence to supplementation), **chronic furosemide therapy in heart failure** (loop diuretics cause measurable urinary thiamine wasting, mechanistic rationale for supplementation in HF patients despite equivocal large RCT evidence, 11790067), **refeeding syndrome** (rapid carbohydrate reintroduction in the malnourished sharply increases TPP demand for glycolysis, precipitating acute deficiency and classically cardiovascular collapse unless thiamine is given before or with refeeding), **chronic hemodialysis**, **HIV and advanced malignancy**, and **total parenteral nutrition without adequate micronutrients**. Two monogenic disorders of thiamine transport produce inborn errors of metabolism that respond to pharmacologic thiamine: **thiamine-responsive megaloblastic anemia syndrome (TRMA)** from SLC19A2 (THTR1) mutations, presenting in infancy with megaloblastic anemia, diabetes, and sensorineural deafness, treatable with 25-100 mg/day thiamine; and **biotin-thiamine-responsive basal ganglia disease** from SLC19A3 (THTR2) mutations, presenting with episodic encephalopathy and dystonia responsive to high-dose biotin (5-10 mg/kg/day) plus thiamine (10-40 mg/kg/day). The supplement and clinical uses of thiamine cluster in several domains. **Emergency parenteral thiamine** (typically 500 mg IV over 30 minutes, three times daily for 2-3 days, then 250 mg IM/IV daily for 5 days, then transition to oral 100 mg three times daily) is the standard of care for suspected or confirmed Wernicke encephalopathy and is a BEFORE-glucose intervention in the alcoholic or malnourished patient presenting with altered mental status — giving IV glucose to a thiamine-depleted patient can precipitate acute Wernicke's by mass-action-driving thiamine-dependent pyruvate dehydrogenase and α-ketoglutarate dehydrogenase reactions. **Chronic oral thiamine** at 100-300 mg/day is used for ongoing alcohol use disorder, bariatric post-op, hyperemesis gravidarum prophylaxis/treatment, and refeeding syndrome prophylaxis. **Benfotiamine**, a lipid-soluble S-acyl thiamine derivative developed in Japan, is preferred for diabetic peripheral neuropathy based on the BENDIP trial and related work showing improved transketolase activity and modest neuropathy symptom improvement at 300-600 mg/day. **Sulbutiamine**, a lipophilic disulfide dimer of thiamine with isobutyryl esters, is marketed in France as Arcalion for asthenia and is discussed as a separate nootropic compound in its own right — see the [Sulbutiamine](/compound/sulbutiamine) entry. **High-dose thiamine for Parkinson disease** was advocated by the Italian neurologist Antonio Costantini based on open-label case series reporting dramatic motor symptom improvement with intramuscular thiamine 100-200 mg twice weekly; subsequent controlled evaluations have been preliminary and not definitively replicated, and the approach remains unproven despite enthusiastic patient communities. **High-dose thiamine for heart failure** has been studied in small RCTs with mixed results — Schoenenberger 2012 showed LVEF improvement in HF patients on furosemide given thiamine 300 mg/day for 28 days, but larger confirmatory trials are lacking. **Thiamine as metabolic resuscitation in sepsis** (the Marik HAT protocol — hydrocortisone, ascorbic acid, thiamine) generated enormous enthusiasm after Marik's 2017 before-after study but was not confirmed by the VITAMINS randomized trial in 2020 or subsequent replication attempts, and the HAT protocol is no longer recommended as standard sepsis care. Food sources concentrate in pork (a few ounces of pork loin meets daily RDA), whole grains, legumes, nuts and seeds, yeast extract (Marmite/Vegemite are extraordinarily rich sources), trout and other fish, beef liver, and fortified breakfast cereals. Thiamine is destroyed by heat, alkaline conditions, sulfites (the reason processed meats and some wines can deplete thiamine), and raw fish (certain fish contain thiaminases that cleave the vitamin — cooked fish is safe). See also [Sulbutiamine](/compound/sulbutiamine) for the lipophilic nootropic derivative, [Magnesium](/compound/magnesium) for the TPP-kinase and PDH activation context (PDH is Mg-dependent for activation), [Folate](/compound/folate), [Vitamin B6](/compound/vitamin-b6), [Vitamin B12](/compound/vitamin-b12) for the broader B-vitamin family, [Alpha-Lipoic Acid](/compound/alpha-lipoic-acid) for the parallel PDH/αKGDH cofactor role, [Choline](/compound/choline) for the alternative cholinergic precursor pathway, [CoQ10](/compound/coq10) for the mitochondrial bioenergetic stack. This overview is educational only and is not medical advice — suspected thiamine deficiency, particularly Wernicke encephalopathy, is a medical emergency requiring immediate parenteral thiamine, not oral supplementation.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/thiamine" }, { "id": "d0f5ee87-b05b-4943-a336-d9e7d65b4df5", "slug": "thymalin", "name": "Thymalin", "aliases": [ "Thymalinum", "Timalin", "Thymus Peptide Complex", "Thymic Extract", "Khavinson Thymalin", "T-activin (related)", "Thymalin-Vialing" ], "category": "Peptides", "description": "Thymalin is a thymus-derived peptide complex developed in the 1970s by Vladimir Khavinson and the Leningrad (now St. Petersburg) Institute of Bioregulation and Gerontology as part of a broader program to identify tissue-specific regulatory peptides from mammalian organs. Produced by acetic acid extraction of bovine or calf thymus tissue and fractionated to yield a mixture of short polypeptides (average molecular weight 1-10 kDa), Thymalin occupies a distinctive position in peptide medicine: it is a registered pharmaceutical in Russia with over four decades of clinical use for immune restoration in aging and immunosuppressed populations, while remaining a research-chemical-status peptide in the United States and most Western markets where its evidence base is poorly integrated into mainstream medicine. Understanding Thymalin requires understanding the Russian peptide bioregulator tradition that produced it — a clinical and scientific framework quite different from Western pharmaceutical development, with its own standards of evidence, its own terminology, and its own strengths and limitations.\n\nStructurally, Thymalin is not a single molecule but a mixture of short polypeptides and oligopeptides derived from calf thymus gland. The specific peptide composition has been partially characterized in modern analytical work but never fully standardized in the way a single synthetic peptide would be. Active fractions include peptides with sequences overlapping [Thymosin Alpha-1](/compound/thymosin-alpha-1) and [Thymulin](/compound/thymulin), along with additional short regulatory peptides including the Khavinson lab's signature short synthetic peptides [Epithalon](/compound/epithalon) (AEDG, from pineal) and related oligopeptides. The presumed active principle is a combination of these peptides acting synergistically on the immune system, though Khavinson's group has emphasized in their publications that the specific short peptides — which can be synthesized and studied individually — reproduce much of the biological activity of the whole extract. This is the foundation of the modern short-peptide Khavinson framework: Thymalin was the original mixture, and the individual dipeptides (like Livagen, Ala-Glu-Asp-Gly) and tetrapeptides (like Epithalon) identified from Thymalin and related extracts are the modern synthetic versions.\n\nFunctionally, Thymalin is described by its developers as a \"cytomedine\" — a tissue-derived peptide regulator that carries organ-specific signals for cellular homeostasis and regeneration. The framework proposes that short peptides from specific tissues can enter cells (via membrane transport or endocytosis), travel to the nucleus, and interact with specific gene promoters to regulate transcription of tissue-specific genes. For Thymalin, this means carrying signals that promote thymic function, T-cell differentiation, and broader immune system homeostasis. The framework is provocative and not universally accepted in Western molecular biology — the specific proposition that exogenous short peptides can directly regulate gene transcription by binding promoters is considered unproven by most Western molecular biologists — but it has produced a coherent clinical research program with measurable outcomes in human trials.\n\nThe clinical evidence base for Thymalin is substantial in volume and spans decades of use in Russian medicine. Khavinson and colleagues have published over two hundred papers on Thymalin and its derivatives, including multi-decade longitudinal trials in elderly populations showing reduced all-cause mortality, reduced incidence of acute respiratory infections, improvements in T-cell subset profiles (particularly CD4+ cells and the CD4:CD8 ratio), improved wound healing, and improvements in broader markers of immune competence and healthy aging. The most frequently cited data come from the \"Kiev study\" and subsequent Russian elderly cohort trials in which Thymalin (often in combination with Epithalon) administered in 10-day courses annually or biannually to elderly patients produced 2-fold reductions in cumulative 6-8 year mortality versus untreated controls. These are notable claims that would be transformative if replicated in a Western rigorous RCT framework — and the honest framing is that they have not been, not because replication has been attempted and failed, but because the Western peer-reviewed system has not seriously engaged with the Russian peptide bioregulator literature. This is an epistemic gap rather than a proven falsification, and it is the gap that every Western user of Thymalin should understand.\n\nRegulatory status varies dramatically by jurisdiction. In Russia, Thymalin is a registered pharmaceutical product (trade name Thymalin or Timalin) with Russian Ministry of Health approval for specific indications including post-infectious immune restoration, aging-related immunosuppression, radiation-induced immune compromise, and post-surgical immune support. It is prescribed routinely in Russian and some former Soviet clinical practice, particularly in geriatric medicine and oncology. In the United States, European Union, and most Western markets, Thymalin is not an approved pharmaceutical and is sold in the research-chemical peptide market — often imported directly from Russian manufacturers or compounded by specialty peptide suppliers. The research-chemical framing does not mean it is unsafe (its Russian safety record is substantial), but it means quality control is not regulated, pharmaceutical-grade standards are not guaranteed, and use is outside the framework of Western regulatory approval.\n\nThe thymus biology context matters. The thymus is the organ where T-lymphocytes mature and are educated to distinguish self from non-self. Thymic function peaks in early childhood and then declines progressively through adulthood, a process called thymic involution — the thymus is largely replaced by fatty tissue by age 70 in most individuals, with corresponding decline in T-cell output and immune function. The elderly immune system is characterized by reduced naive T-cell pools, shrinking T-cell receptor diversity, expansion of senescent T-cell clones, and increased vulnerability to infections and cancer. The thymic-peptide hypothesis proposes that exogenous thymic signals can partially reverse or slow this involution and restore functional immune capacity. The biology is plausible; the clinical reality is harder to verify in Western-standards trials.\n\nIn the research-peptide community outside Russia, Thymalin is used for immune support in contexts including aging, chronic infection recovery, post-chemotherapy immune restoration, chronic fatigue and post-viral syndromes, autoimmune disease management (controversial — thymic peptides might be immunomodulatory in either direction), and general longevity protocols. It is frequently combined with [Epithalon](/compound/epithalon) (the Khavinson pineal tetrapeptide) as the canonical \"Khavinson stack\" reflecting the original clinical protocols. This entry covers Thymalin's composition and the cytomedine framework, the Khavinson clinical evidence base and its epistemic status, the distinction between Thymalin (mixture) and [Thymosin Alpha-1](/compound/thymosin-alpha-1) (single synthetic peptide, separate development track) and [Thymulin](/compound/thymulin) (a zinc-dependent single peptide also distinct from Thymalin), the practical use case framing for Western research-peptide users, appropriate dosing based on Russian clinical protocols, the safety profile (substantial safety record in Russia, reasonably clean side-effect profile, but real questions about quality control in the Western research-chemical market), and honest skepticism about the grander anti-aging claims without dismissing the underlying immune-restoration evidence.", "half_life": "Short for the individual peptides in the mixture (on the order of minutes to a few hours). Biological effects persist for weeks to months after a 10-day course, which is why Thymalin is given in discrete courses rather than continuously.", "molecular_weight": "Not a single value - Thymalin is a thymic polypeptide EXTRACT (a mixture), not one defined molecule; its components are low-molecular-weight peptides, generally under ~10 kDa. Characterized active dipeptides: KE (Lys-Glu, ~275 Da) and EW (Glu-Trp, ~333 Da).", "molecular_mass": "Not a single value - Thymalin is a thymic polypeptide extract (mixture of peptides, generally <10 kDa), not one defined molecule. Characterized active dipeptides: KE (Lys-Glu, ~275 Da) and EW (Glu-Trp, ~333 Da).", "amino_acid_sequence": "Not a single defined sequence - Thymalin is a multi-peptide thymic extract, not a single-sequence peptide. Its characterized active components are the short peptides KE (Lys-Glu) and EW (Glu-Trp).", "administration_routes": [], "dose_range_mcg": "5000-15000", "dosing_frequency": "Once daily during a 10-day course; courses repeated 1-4 times per year (commonly biannually).", "cycle_length": "10 consecutive days per course, then 3-6 months off before the next course.", "common_vial_sizes": [], "research_stage": "Clinical (Russia-registered; not FDA-approved)", "approval_status": "Approved/registered as a pharmaceutical in Russia (thymus peptide bioregulator; marketed e.g. by Samson-Med). Not FDA-approved and not an approved drug in the US; sold there research-use-only (RUO).", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 2, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/thymalin" }, { "id": "9876c8e3-8fef-48a2-8d75-fb050f96dc44", "slug": "thymogen", "name": "Thymogen", "aliases": [ "Glu-Trp" ], "category": "Recovery", "description": "Thymogen (also transliterated **Timogen** or **╨ó╨╕╨╝╨╛╨│╨╡╨╜**) is a **synthetic dipeptide — glutamyl-tryptophan (Glu-Trp, or EW)** — developed by the St Petersburg Institute of Bioregulation and Gerontology under Professor Vladimir Khavinson. Thymogen belongs to the same family of **Russian short-peptide bioregulators** as [Pinealon](/compound/pinealon), [Epitalon](/compound/epithalon), [Vilon](/compound/vilon), and the broader Khavinson catalog, but unlike those neural and general-aging peptides, **Thymogen specifically targets thymus-dependent cellular immunity**.\n\nThe compound originated in the late 1970s and 1980s when Khavinson and colleagues began isolating and characterizing bioactive peptide fractions from calf thymus tissue. The parent peptide extract — called **Thymalin** (a mixture of thymus-derived peptides) — was developed in parallel and remains a Russian clinical product for immune modulation. Thymogen was subsequently identified as one of the active short-peptide components of the Thymalin extract and was synthesized as a defined dipeptide for clinical use. The Glu-Trp sequence is notable for its simplicity — only two amino acids — and for its resistance to rapid proteolytic degradation compared with longer peptides.\n\nThymogen has been **registered in Russia as a pharmaceutical** since the late 1980s, carrying the Russian registration for use in **cellular immunodeficiency states**, post-surgical and post-burn immune support, acute and chronic purulent infections, and as adjunctive therapy in certain oncologic and radiotherapy contexts. It is available commercially as nasal drops, an injectable solution, and an oral formulation, and has been used in Russian clinical practice continuously for decades. Outside Russia, it remains an unapproved research peptide, available through research-chemical suppliers and informally in body-hacking communities as an immune support peptide.\n\nThe Khavinson framework around Thymogen holds that short peptides derived from thymus tissue retain the ability to **signal to T-cell progenitors and mature T-cells** — upregulating thymus-dependent immune function, supporting T-helper and T-cytotoxic cell maturation, and restoring immune competence in states of age-related thymic involution or acquired immunodeficiency. This is theoretically coherent with the thymus's known role in T-cell education and differentiation, and it parallels the better-known synthetic thymus-derived peptides developed in Western medicine, including **thymosin alpha-1 (Zadaxin)**, which is FDA-approved in some jurisdictions for hepatitis B and as an adjunctive immune therapy.\n\nThis entry takes the honest position that **Thymogen is a registered Russian pharmaceutical peptide with extensive domestic clinical use, moderate Russian and limited Western preclinical support, plausible mechanism of action consistent with the Western thymic peptide literature, and an unapproved-research-peptide status in most Western jurisdictions**. It is not a supplement and not approved outside Russia. Users engaging with it through research-chemical channels should expect Russian clinical practice levels of characterization rather than FDA-approval levels.\n\nFor readers exploring the broader Khavinson peptide space, see [Pinealon](/compound/pinealon), [Epitalon](/compound/epithalon), [Vilon](/compound/vilon), [Cartalax](/compound/cartalax), [Livagen](/compound/livagen), and related entries. For the closest Western-approved comparator, see [thymosin alpha-1](/compound/thymosin-alpha-1). For other immune-supportive peptides in the catalog, see [KPV](/compound/kpv) and [BPC-157](/compound/bpc-157).", "half_life": "short; not well characterized", "molecular_weight": "~333.3 g/mol (Glu-Trp)", "molecular_mass": "333.34 g/mol", "amino_acid_sequence": "Glu-Trp (EW)", "administration_routes": [], "dose_range_mcg": "50-100 mcg intranasal per nostril 1-2x/day, or 100 mcg SC once daily; 10-day courses, 2-4x/year", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Approved in Russia / not Western-validated", "approval_status": "Registered pharmaceutical in Russia; not FDA-approved", "trial_phase": "", "cas_number": "82424-90-6", "iupac_name": "", "chemical_formula": "C15H28N4O7", "potential_benefits": [ "Immune system modulation", "Thymic function restoration", "Enhanced T-cell immunity", "Immune anti-aging support" ], "research_fields": [], "pubmed_count": 91, "pubchem_cid": 16757161, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/thymogen" }, { "id": "95b73150-f8e6-4a06-8fc0-a0a7d79d08e5", "slug": "thymosin-alpha-1", "name": "Thymosin Alpha-1 (TA1)", "aliases": [ "Ta1" ], "category": "Immune & Inflammation", "description": "Thymosin alpha-1 (Tα1) is a 28-amino-acid N-acetylated peptide (N-Ac-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-Asp-Leu-Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn) isolated and characterized by Allan Goldstein's laboratory at George Washington University in the 1970s as the immunologically active cleavage product of a larger precursor (prothymosin alpha) found in thymic tissue. The thymus gland is the primary site of T-cell maturation in early life, and thymic hormones have long been implicated in immune competence. Goldstein's isolation of Tα1 opened decades of research into whether supplementation with thymic peptides could restore immune function in contexts of thymic atrophy (aging, chemotherapy, HIV, chronic viral infection) or augment immune response against infections and malignancies. Synthetic Tα1 (under the brand name Zadaxin, manufactured by SciClone Pharmaceuticals) has been approved in more than 30 countries for chronic hepatitis B, chronic hepatitis C, and as an immune adjuvant for influenza and hepatitis B vaccines in immunocompromised patients, as well as adjunctive therapy in certain cancers. In the United States, Tα1 is not FDA-approved but has held orphan drug designation for several indications and is commonly available through compounding pharmacies for off-label use ([Goldstein et al., 1977], [Garaci et al., 2003]).\n\nThe mechanistic framing for Tα1 is best understood as a pleiotropic immune modulator rather than a simple immune \"booster.\" Tα1 acts primarily through Toll-like receptors (especially TLR9 and TLR2) on dendritic cells and other antigen-presenting cells, driving dendritic cell maturation, promoting balanced Th1/Th2 responses, improving T-cell differentiation from thymic and extra-thymic precursors, stimulating natural killer cell activity, and modulating inflammatory cytokine patterns. The practical result in patients with chronic viral infections or immunocompromise is improved viral clearance, enhanced vaccine response, and more balanced immune reactivity. Importantly, Tα1 does not produce generalized immune activation or autoimmunity at therapeutic doses — it shifts immune response patterns rather than simply amplifying inflammation. This selective modulation is what has made Tα1 clinically attractive in contexts where straightforward immune activation would cause harm ([Romani et al., 2012], [Li et al., 2010]).\n\nIn everyday off-label use outside strictly approved indications, Tα1 is pursued by three main user groups. First, people with chronic viral infections (EBV reactivation, chronic Lyme complex, long COVID, chronic hepatitis, HIV as adjunct to antiretrovirals) use Tα1 for immune support alongside primary therapy. Second, older adults with age-related thymic atrophy and declining CD4/CD8 ratios use Tα1 as a general immunity-preservation strategy, often in combination with other longevity-oriented peptides like [BPC-157](/compound/bpc-157) and [Epithalon](/compound/epithalon). Third, cancer patients in remission or undergoing certain immunotherapies use Tα1 as adjunctive immune support, ideally under oncologic supervision. Competitive athletes sometimes use Tα1 during heavy training cycles on the theory that exercise-induced transient immune suppression can be buffered, though this use case has weak formal evidence ([Garaci et al., 2007]).\n\nTα1 has one of the cleanest safety profiles among peptides with substantial bioactivity — decades of clinical use with minimal adverse events, no significant organ toxicity, and no autoimmunity signal at therapeutic doses. The main practical limitations are the cost of good-quality Tα1 preparations, the injectable route (Tα1 is not orally bioavailable), and the uncertainty around whether long-term routine supplementation meaningfully delays age-related immune decline in healthy individuals. This entry covers Tα1's established mechanism and indications, the emerging research in long COVID and other post-viral syndromes, and the practical considerations for anyone exploring Tα1 for immune support. Related peptides frequently stacked or compared include [BPC-157](/compound/bpc-157) and [TB-500](/compound/tb-500) for general tissue repair, [Epithalon](/compound/epithalon) for parallel longevity positioning, and [LL-37](/compound/ll-37) for a very different (antimicrobial rather than immune-modulating) peptide category.", "half_life": "~2 hours", "molecular_weight": "3108 Da", "molecular_mass": "3108.3 g/mol", "amino_acid_sequence": "Ac-SDAAVDTSSEITTKDLKEKKEVVEEAEN (N-terminally acetylated 28-residue peptide; corresponds to residues 2-29 of prothymosin alpha). Full residues: N-acetyl-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-Asp-Leu-Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn. Molecular formula C129H215N33O55; MW ~3108.3 Da.", "administration_routes": [ "Subcutaneous" ], "dose_range_mcg": "1,600 mcg (1.6 mg) per injection (standard clinical dose)", "dosing_frequency": "Twice weekly (subcutaneous) - the approved Zadaxin schedule; alternatively 900 mcg daily for intensive short-term courses", "cycle_length": "4–12 weeks; can be used long-term for immune support", "common_vial_sizes": [ "5mg", "10mg" ], "research_stage": "Approved (International)", "approval_status": "Approved in 35+ countries as Zadaxin® for hepatitis B; orphan drug status in US", "trial_phase": "FDA Approved", "cas_number": "62304-98-7", "iupac_name": "L-seryl-L-alpha-aspartylL-alanyl-L-alanyl-L-valyl-L-alpha-aspartyl-L-threonyl... (28 aa sequence)", "chemical_formula": "C129H215N33O55", "potential_benefits": [ "Immune enhancement", "Antiviral defense", "Cancer adjuvant therapy", "Autoimmune modulation", "Vaccine potentiation" ], "research_fields": [ "Hepatitis B/C", "HIV", "Cancer immunotherapy", "COVID-19", "Immune deficiency" ], "pubmed_count": 701, "pubchem_cid": 16132117, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/16132117/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/thymosin-alpha-1" }, { "id": "a1000000-0000-0000-0000-000000000004", "slug": "tirzepatide", "name": "Tirzepatide", "aliases": [ "GLP-2T", "GIP/GLP-1", "ION-2T", "GLP-2", "Tirzepatide", "PEP-2T", "RC-2T", "Dual Agonist", "Ion Peptide Tirzepatide", "Tirz", "GIP/GLP" ], "category": "Metabolic & Weight Loss", "description": "Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist with a molecular weight of 4813.45 Da and CAS number 2023788-19-2. It is a 39-amino-acid synthetic peptide based on the native GIP sequence with modifications that confer activity at both GIP and GLP-1 receptors. Tirzepatide features a C20 fatty diacid moiety attached via a linker to facilitate albumin binding, resulting in a plasma half-life of approximately 5 days that supports once-weekly subcutaneous dosing.\n\nTirzepatide is FDA-approved under two brand names: Mounjaro (for type 2 diabetes mellitus, approved May 2022) and Zepbound (for chronic weight management, approved November 2023). It is manufactured by Eli Lilly and Company and represents the first-in-class dual GIP/GLP-1 receptor agonist to reach the market.\n\nThe SURMOUNT clinical trial program established tirzepatide as the most effective pharmacological weight loss agent to date. In the SURMOUNT-1 trial, participants with obesity or overweight (without diabetes) receiving tirzepatide 15 mg weekly achieved a mean body weight reduction of 22.5% from baseline at 72 weeks, compared to 2.4% with placebo — a treatment difference of 20.1 percentage points. Notably, 36.2% of participants in the 15 mg group achieved 25% or greater total body weight loss, approaching the magnitude historically seen only with bariatric surgery (PMID: 35658024).\n\nThe SURMOUNT-2 trial evaluated tirzepatide in adults with type 2 diabetes and obesity, demonstrating mean weight loss of 14.7% with tirzepatide 15 mg versus 3.2% with placebo at 72 weeks, along with significant HbA1c improvement. The SURMOUNT-3 trial studied tirzepatide following an intensive 12-week lifestyle intervention, showing that tirzepatide maintained and extended initial weight loss while placebo recipients regained weight (PMID: 37840095).\n\nA key differentiating feature of tirzepatide compared to pure GLP-1 receptor agonists such as semaglutide is the GIP receptor agonist component. GIP signaling in adipose tissue is proposed to improve lipid metabolism and may protect against the loss of lean body mass that accompanies caloric restriction and weight loss. Preclinical and early clinical data suggest that tirzepatide-treated patients lose a greater proportion of fat mass relative to lean mass compared to GLP-1-only agents, though this finding requires further validation in dedicated body composition studies.\n\nTirzepatide achieved the highest absolute weight loss of any anti-obesity medication in clinical trials. At the 15 mg dose, mean absolute weight loss was approximately 24 kg (52 lbs) at 72 weeks in SURMOUNT-1. The gastrointestinal side effect profile is similar to GLP-1 receptor agonists, with nausea being the most common adverse event, generally mild to moderate and diminishing over time with dose titration.", "half_life": "~5 days (approximately 120 hours), enabled by C20 fatty diacid albumin-binding modification", "molecular_weight": "4813.5 Da", "molecular_mass": "4813.49 g/mol", "amino_acid_sequence": "39-amino-acid synthetic peptide agonist of both the GIP and GLP-1 receptors. Sequence: Tyr-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-Aib-Leu-Asp-Lys-Ile-Ala-Gln-Lys-Ala-Phe-Val-Gln-Trp-Leu-Ile-Ala-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (one-letter: YXEGTFTSDYSIXLDKIAQKAFVQWLIAGGPSSGAPPPS, where X = Aib, 2-aminoisobutyric acid, at positions 2 and 13). Key modifications: the lysine at position 20 is conjugated through a gamma-glutamate + 2x AEEA [2-(2-aminoethoxy)ethoxy-acetyl] linker to a C20 fatty diacid (eicosanedioic acid), which drives albumin binding and the ~5-day half-life; the C-terminus is a primary amide. Molecular formula C225H348N48O68 (~4813.5 Da).", "administration_routes": [ "Subcutaneous (weekly)" ], "dose_range_mcg": "2500 mcg (2.5 mg) starting dose, titrated every 4 weeks through 5000, 7500, 10000, 12500, to 15000 mcg (15 mg) maximum weekly dose", "dosing_frequency": "Once weekly subcutaneous injection", "cycle_length": "Ongoing; dose escalation over 20+ weeks", "common_vial_sizes": [ "5mg", "10mg", "15mg" ], "research_stage": "FDA Approved", "approval_status": "FDA-approved: Mounjaro® (T2D, 2022), Zepbound® (obesity, 2023)", "trial_phase": "FDA Approved", "cas_number": "2023788-19-2", "iupac_name": "Not fully specified (proprietary sequence)", "chemical_formula": "C225H348N48O68", "potential_benefits": [ "Mean body weight reduction of 22.5% at 72 weeks - highest of any anti-obesity medication (PMID: 35658024)", "36.2% of participants achieved greater than or equal to 25% body weight loss (PMID: 35658024)", "Significant HbA1c reduction in type 2 diabetes (up to 2.4% at 40 weeks in the SURPASS-5 add-on-to-insulin trial) (PMID: 35133415)", "Potentially superior lean mass preservation versus GLP-1-only agents due to GIP component", "Dual incretin mechanism providing complementary metabolic benefits", "Improved lipid profiles including triglycerides, LDL cholesterol, and HDL cholesterol", "Reduction in waist circumference and markers of visceral adiposity (PMID: 37840095)" ], "research_fields": [ "Obesity", "Type 2 diabetes", "NASH", "Sleep apnea", "Heart failure with preserved EF" ], "pubmed_count": 626, "pubchem_cid": 2736038, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/2736038/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/tirzepatide" }, { "id": "5f4078b8-2236-4e73-81c6-6dcc5d281302", "slug": "tongkat-ali", "name": "Tongkat Ali", "aliases": [ "Eurycoma longifolia", "Longjack", "Malaysian Ginseng", "Pasak Bumi", "Tung Saw", "Ali's Walking Stick", "LJ100", "Physta", "Eurycomanone", "Ali Umbi", "Pasak" ], "category": "Adaptogen", "description": "**Tongkat Ali** (scientific name *Eurycoma longifolia*; also called **Longjack**, **Malaysian ginseng**, **pasak bumi** in Indonesian/Malay, **tung saw** in Thai, and literally \"Ali's walking stick\" in Malay — a reference to the remarkably long, straight, single taproot that can grow 10-15 feet deep into Southeast Asian rainforest soil) is a slender understory tree of the family Simaroubaceae native to the tropical rainforests of peninsular Malaysia, Indonesia, Thailand, Vietnam, Myanmar, Laos, and the Philippines. The medicinal use of Tongkat Ali is deeply embedded in the traditional medicine systems of these regions, where for centuries it has been used primarily as a **men's vitality tonic** — improving libido, sexual function, physical endurance, and post-illness recovery. The plant's root is the primary medicinal part, and its reputation as **\"the Asian Viagra\"** in Western marketing reflects (with some exaggeration) genuine traditional claims around sexual function enhancement, though Tongkat Ali's mechanism is quite different from pharmaceutical PDE5 inhibitors and its actual erectile-function evidence is more modest than its reputation suggests.\n\nThe scientific research infrastructure supporting Tongkat Ali is unusually sophisticated compared with many other traditional botanicals, largely because the Malaysian government has strategically invested in research, cultivation, standardization, and commercialization of Tongkat Ali as a flagship natural product since the 1990s. The **Forest Research Institute Malaysia (FRIM)** and the **Malaysian Agricultural Research and Development Institute (MARDI)** have conducted extensive pharmacological, safety, and clinical research, and developed two specific standardized extracts that are now used in the majority of quality clinical trials: **LJ100 (MIT Lab, University of Malaya)**, a hot-water extract standardized to quassinoids (22%) and eurypeptides (40+%); and **Physta (Biotropics Malaysia)**, a hot-water extract standardized to glycopeptides (22%), quassinoids (≥0.8% eurycomanone), and polysaccharides (≥30%). These standardized extracts — rather than raw root powder or unstandardized extracts — are what's been tested in clinical trials, and what consumers should prefer. The distinction matters because unstandardized Tongkat Ali products of the sort sold by many Asian grocery stores, bulk supplement providers, and \"performance\" brands vary wildly in active compound content and may contain negligible pharmacologically active material.\n\nThe principal bioactive compounds in Tongkat Ali are **quassinoids** (bitter-tasting triterpenoid-derived compounds that give the root its characteristic extreme bitterness — the Malay proverb \"pahit macam tongkat ali\" means \"bitter as Tongkat Ali\"), with **eurycomanone** being the most studied and potent quassinoid. Other active quassinoids include eurycomanol, eurycolactone, eurycomalactone, laurycolactone, and various others. The root also contains **eurypeptides** (short, bioactive peptides unique to *Eurycoma longifolia*), **glycoproteins**, **alkaloids** (including the beta-carboline eurycomanol), **tannins**, and **phytosterols**. The molecular complexity makes Tongkat Ali a multi-target herbal rather than a single-mechanism agent.\n\nThe central claim for Tongkat Ali — and the basis for its position in the men's health and performance supplement market — is that it functions as a **natural testosterone support agent**, working not by adding exogenous androgens (as testosterone replacement therapy does) but by improving the body's own natural testosterone signaling. The proposed mechanisms include: (1) **reducing sex hormone binding globulin (SHBG)**, which increases free (bioavailable) testosterone without necessarily changing total testosterone — a mechanism particularly relevant in aging men who often have declining free testosterone at higher SHBG levels despite relatively preserved total testosterone; (2) **reducing cortisol**, the stress hormone that has catabolic effects on muscle, libido, and testosterone production — this stress-mitigating effect is part of what categorizes Tongkat Ali as an adaptogen; (3) **modulating testicular Leydig cell function** to improve endogenous testosterone production in men with suboptimal baseline levels; (4) **modulating aromatase** (the enzyme that converts testosterone to estrogen) to reduce estrogen conversion, potentially increasing testosterone:estrogen ratio; and (5) **improving sperm parameters** (count, motility, morphology) in men with infertility.\n\nThe human clinical evidence is **moderate in volume and variable in quality**, with most rigorous research conducted on the LJ100 and Physta standardized extracts. The strongest evidence exists for **late-onset hypogonadism** (the testosterone decline associated with aging, distinct from pathological primary or secondary hypogonadism), **stress and mood modulation**, **exercise performance in older adults**, and **infertility/sperm parameters**. The **Tambi et al. 2012 study** (PMID: 21671978), published in *Andrologia*, is a landmark — a one-month open-label study of LJ100 200mg/day in 76 men aged 30-55 with symptoms of late-onset hypogonadism (hypoactive sexual desire, erectile dysfunction, energy decline, mood disturbance, decreased muscle mass). The Aging Males' Symptoms (AMS) Scale scores improved significantly, total testosterone rose from a mean of 5.66 to 8.31 nmol/L (approximately +46%), and free testosterone also increased. While open-label design limits conclusions, the effect size was clinically meaningful. **Tambi et al. 2011** (*Andrologia*) and several other trials have replicated the testosterone-raising effect in hypogonadal or symptomatic men.\n\n**Talbott et al. 2013** (*Journal of the International Society of Sports Nutrition*) tested Physta 200mg/day for 4 weeks in 63 moderately stressed adults (32 men, 31 women) against placebo. Results showed significant reductions in tension (-11%), anger (-12%), and confusion (-15%) with Tongkat Ali, plus reductions in salivary cortisol (-16%) and increases in salivary testosterone (+37% in the TA group). This shows the adaptogenic stress-mitigating effects in both sexes.\n\n**Henkel et al. 2014** (*Phytotherapy Research*) tested LJ100 200mg/day for 5 weeks in 13 healthy seniors (average age 68) on measures of muscle strength and lean body mass. Results: significant improvements in handgrip strength, fat-free mass, and subjective quality of life. While the sample was small, this is one of the better trials supporting Tongkat Ali's physical performance effects.\n\n**Henkel et al. 2014** (infertility study family) — LJ100 200mg/day for 3 months in men with idiopathic infertility showed improvements in sperm concentration, motility, and morphology, with partner pregnancies achieved in a notable percentage. This aligns with traditional use for fertility support.\n\nWhere does Tongkat Ali fit honestly in the therapeutic landscape? For men with **clinically diagnosed hypogonadism** (total testosterone below ~250-300 ng/dL with hypogonadal symptoms confirmed by endocrinology), the evidence-based treatment is **testosterone replacement therapy (TRT)** — injectable esters, transdermal gels, pellets, or oral preparations — which produces far larger and more consistent testosterone elevations than any herbal supplement. Tongkat Ali is NOT a substitute for TRT in men with clinical hypogonadism. For men with **late-onset hypogonadism** who have symptoms but wish to try lifestyle and supplementation interventions before committing to TRT, Tongkat Ali is a reasonable evidence-based option alongside resistance training, sleep tuning, weight management, and [zinc](/compound/zinc)/[vitamin D](/compound/vitamin-d) adequacy. For men with **low-normal testosterone and symptoms** who don't meet clinical hypogonadism criteria but want support, Tongkat Ali offers modest improvements. For **healthy men with normal testosterone seeking performance enhancement**, Tongkat Ali's effect size is modest — lifestyle factors (sleep, training, nutrition) produce larger changes. For **women seeking stress reduction and general adaptogenic support**, Tongkat Ali's adaptogenic and cortisol-reducing effects may be beneficial at modest doses (100-200mg/day), though most research has focused on male populations.\n\nSafety with standardized Tongkat Ali at typical doses is excellent — multiple Malaysian and international studies have documented good safety profiles at 200-400mg/day of LJ100 or Physta for durations up to 12 months. The main concerns are interactions in specific populations (hormone-sensitive cancers, women seeking pregnancy, those on certain medications) and occasional reports of restlessness or insomnia at higher doses or late-evening dosing. Importantly, Tongkat Ali's testosterone support is **modest** compared with pharmaceutical TRT, so expectations should be calibrated: users should not expect dramatic muscle gain, physique transformation, or the effects of therapeutic TRT from Tongkat Ali supplementation.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 107, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/tongkat-ali" }, { "id": "a0f6dd8b-21dc-4fcd-ae48-ffe61d5509f0", "slug": "tribulus-terrestris", "name": "Tribulus Terrestris", "aliases": [ "Tribulus", "Puncture Vine", "Gokshura", "Gokhru", "Ci Ji Li", "Caltrop", "Goat's Head", "Devil's Thorn", "Devil's Weed", "Bindii", "Tackweed", "Bulgarian Tribulus", "Protodioscin", "Tribestan" ], "category": "Adaptogen", "description": "**Tribulus terrestris** (scientific name *Tribulus terrestris* L.; also called **puncture vine**, **caltrop**, **goat's head**, **devil's thorn**, **bindii** in Australia, **gokshura** or **gokhru** in Sanskrit and Ayurveda, and **ci ji li** (σê║ΦÆ║Φù£) in Traditional Chinese Medicine) is a low-growing annual herb of the family Zygophyllaceae with a remarkably cosmopolitan distribution — native to warm temperate and tropical regions of Europe, Asia, Africa, and Australia, and introduced as an invasive weed across the Americas. The plant is named for its characteristic hard, spiny fruits (each fruit splits into five thorny nutlets called \"caltrops\") that can puncture bicycle tires, damage livestock hooves, and injure bare feet — making it an agricultural pest across much of its range despite its simultaneous reputation as an important medicinal plant. In the pharmacognosy of three major traditional medicine systems, Tribulus has accumulated claims across several domains: as a **male vitality and libido tonic** (Bulgarian and Eastern European folk medicine, Ayurveda, TCM), as a **diuretic and kidney tonic** (Ayurveda, TCM), as a **cardiovascular and circulation support herb** (Bulgarian research tradition), and as a **treatment for urinary disorders and stones** (across all three traditions).\n\nThe modern Western fame of Tribulus terrestris as a \"testosterone booster\" derives almost entirely from a specific commercial-industrial context: the development of a standardized Bulgarian extract called **Tribestan** by the pharmaceutical company Sopharma in the early 1980s, and its promotion among Bulgarian weightlifters and athletes — a population that included genuine Olympic talent (Bulgaria dominated men's weightlifting from the late 1970s through the 1990s). When Eastern European sports training methods and supplements became available in the West after the fall of the Soviet bloc in the early 1990s, Tribulus acquired a mystical reputation as the \"secret\" behind Bulgarian weightlifting success. This reputation has proven remarkably durable despite the fact that (a) the Bulgarian weightlifting program's actual secret was highly organized and sophisticated anabolic steroid use, not herbal supplementation, and (b) nearly all subsequent rigorous clinical research on Tribulus in healthy eugonadal men has failed to demonstrate meaningful testosterone elevation. Nonetheless, Tribulus remains one of the most commonly marketed \"testosterone boosters\" in the Western supplement industry, with hundreds of brands and countless bodybuilding magazine advertisements perpetuating the testosterone myth.\n\nThe **honest evidence-based assessment** of Tribulus terrestris is that it is a moderately effective **libido and sexual function support herb** with genuine (if modest) clinical evidence, and a **largely ineffective testosterone booster** in healthy eugonadal men, with more mixed results in certain specific populations (hypogonadal men, post-menopausal women with sexual dysfunction, certain animal models). The libido effects appear to be at least partially independent of testosterone — mediated through central nervous system mechanisms, nitric oxide signaling, and possibly neurosteroid effects on sexual motivation centers. This dissociation between libido effects (real) and testosterone effects (mostly not real in healthy men) is central to understanding Tribulus accurately.\n\nThe principal bioactive compounds in Tribulus terrestris are **steroidal saponins** (spirostanol and furostanol saponins), with **protodioscin** being the most studied and frequently used as a standardization marker (though the degree to which protodioscin specifically drives clinical effects is debatable). Other active compounds include **tribulosin**, **dioscin**, **diosgenin** (a saponin that is notably the starting material for semi-synthesis of many pharmaceutical steroids, though this does NOT mean Tribulus itself produces steroid hormones in the body — a common confusion), **protogracillin**, **gracillin**, and various flavonoids (rutin, kaempferol, tribuloside, quercetin), alkaloids (harmine, harman, norharman — beta-carbolines with MAO-inhibitory properties), and tannins. The saponin content varies dramatically based on geographic origin: Bulgarian Tribulus (*Tribulus terrestris* var. orientalis) and certain Indian varieties contain significantly higher saponin concentrations than Chinese or American-sourced material, which is why the specific origin and standardization of Tribulus products matters enormously — a \"Tribulus extract\" labeled only as \"40% saponins\" without specifying origin and the assay methodology may vary widely in actual bioactivity.\n\nThe clinical evidence landscape for Tribulus is genuinely instructive as a case study in how supplement marketing claims can diverge from evidence. **The Rogerson et al. 2007** (*Journal of Strength and Conditioning Research*, PMID 17530942) study remains one of the clearest negative results: 22 elite rugby league players were randomized to Tribulus 450mg/day vs placebo during 5 weeks of pre-season resistance training, with rigorous pre- and post-intervention measurements of body composition, strength, and hormones. Result: no difference in body composition, no difference in strength, no difference in testosterone or LH. This tightly controlled study in young athletic men — precisely the population Tribulus is marketed to — showed essentially zero effect on the claimed outcomes. **Antonio et al. 2000** (*International Journal of Sport Nutrition and Exercise Metabolism*, PMID 10861337) randomized 15 resistance-trained men to Tribulus 3.21 mg/kg/day vs placebo for 8 weeks during training: no differences in muscle endurance, strength, body composition, or mood. **Neychev and Mitev 2005** (*Journal of Ethnopharmacology*) — an important study for its methodological rigor — tested Tribulus 10-20 mg/kg/day in 21 healthy young men (average age 23) for 4 weeks and measured testosterone, androstenedione, and LH. Result: no significant changes in any androgen parameter. These consistently negative results in healthy eugonadal men form the foundation of the \"Tribulus doesn't raise testosterone\" conclusion in the scientific literature.\n\nHowever, evidence is more nuanced in specific populations. **Akhtari et al. 2014** (*Daru - Journal of Pharmaceutical Sciences*, PMID 24773615) tested Tribulus 7.5mg/day in 67 menopausal women with hypoactive sexual desire disorder for 4 weeks: significant improvements in Female Sexual Function Index scores versus placebo, with effect sizes comparable to pharmaceutical treatments for female sexual interest/arousal disorder. **Gama et al. 2014** (*International Brazilian Journal of Urology*) tested Tribulus 250mg 3x/day in 30 men with impaired erectile function: improvements in International Index of Erectile Function (IIEF) scores and intercourse satisfaction. **Santos et al. 2014** (*Actas Urológicas Españolas*) tested Tribestan 750mg/day in 30 men aged 45-60 with low sexual desire: improvement in sexual function scores. **Kamenov et al. 2017** (*Maturitas*) tested Tribulus in older men with ED and partial androgen deficiency: improvements in erectile function scores, with some evidence of total testosterone changes in this hypogonadal-leaning population (unlike the null results in healthy eugonadal men). These sexual function and libido findings are more consistent than the testosterone findings — suggesting Tribulus has real but modest pro-sexual effects that may be independent of, or only weakly dependent on, androgen changes.\n\nThe question of \"what does Tribulus actually do, and for whom is it useful?\" therefore resolves as follows. For **healthy eugonadal men seeking testosterone elevation or muscle gain**: essentially nothing, do not buy the product, use training/nutrition/sleep instead. For **men with erectile dysfunction or low libido who have not clinically optimized** (sleep, cardiovascular health, lifestyle): potentially modest benefit as an adjunct, though PDE5 inhibitors (sildenafil, tadalafil) are pharmacologically superior when indicated. For **women with hypoactive sexual desire disorder, particularly post-menopausal**: modest but real evidence of libido benefit, safer than most pharmaceutical options (flibanserin/Addyi has significant side effect burden). For **kidney support in Ayurvedic and TCM contexts** (reducing urinary tract inflammation, supporting diuresis, assisting stone passage): traditional use supported by modest modern evidence, reasonable traditional indication. For **cardiovascular support**: preliminary evidence of endothelial function support (possibly via nitric oxide), but weaker than established options like [beetroot](/compound/beetroot), [hawthorn](/compound/hawthorn), or lifestyle interventions.\n\nThe interaction with other [testosterone-adjacent adaptogens](/compound/tongkat-ali) deserves specific mention. Tribulus is frequently stacked with [Tongkat Ali](/compound/tongkat-ali), [Fadogia agrestis](/compound/fadogia-agrestis), [Maca](/compound/maca), [Mucuna pruriens](/compound/mucuna-pruriens), and [Horny Goat Weed](/compound/horny-goat-weed) in \"natural T-booster\" commercial formulas. The logical appeal is multi-mechanism testosterone support through different pathways, but the reality is that most such stacks contain underdosed Tribulus (below clinical trial doses), rely on marketing rather than dose-response evidence, and create expectations that rarely materialize in healthy men with normal testosterone. For users committed to natural testosterone support (with honest calibration of expectations), [Tongkat Ali](/compound/tongkat-ali) has the stronger evidence base, followed by adequate [zinc](/compound/zinc) and [vitamin D](/compound/vitamin-d) status, resistance training, sleep tuning, and body composition management.\n\nSafety of Tribulus at commonly used doses (typically 250-1500mg/day of standardized extract) is generally favorable in short-term studies, with most reported adverse effects being mild gastrointestinal symptoms (nausea, cramping, reflux). More concerning safety signals come from case reports: a cluster of **hepatotoxicity cases** published in the hepatology literature has raised concerns about liver injury risk, particularly with higher doses, longer durations, and certain commercial preparations. **Gynecomastia and hormone-dependent effects**: because Tribulus may have weak estrogenic/androgenic effects depending on the individual and preparation, men with prostate cancer, breast cancer history, or hormone-sensitive conditions should avoid or consult a physician. **Pregnancy and lactation**: contraindicated due to potential uterotonic effects and lack of safety data. **Cardiovascular events**: a notorious cluster of Tribulus-associated myocardial events reported from Iran (Ryan et al., various) and other sources, though causality is not definitively established — possibly related to contamination, adulteration, or effects in at-risk cardiovascular populations.\n\n**Quality and adulteration concerns** are particularly salient with Tribulus products. Because of its widespread marketing as a testosterone booster, Tribulus supplements have been repeatedly found adulterated with: pharmaceutical anabolic steroids (particularly lower-potency Designer Anabolic Steroid Control Act-era designer steroids), prohormones, DHEA, and pharmaceutical PDE5 inhibitors. Users who experience notable \"effects\" from a Tribulus product should consider whether pharmaceutical adulteration may explain results that the herb itself is pharmacologically unlikely to produce. Third-party tested (USP Verified, NSF Certified for Sport, Informed Choice) products substantially reduce this risk.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 581, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/tribulus-terrestris" }, { "id": "63e1c085-ae7b-41dd-9fbf-da6e4df8467a", "slug": "tropisetron", "name": "Tropisetron", "aliases": [ "ICS 205-930", "SDZ ICS 930", "Navoban", "Novaban", "Tropisetron hydrochloride", "Tropiestron (market misspelling)" ], "category": "Pharmaceutical", "description": "Tropisetron, coded ICS 205-930 during development and marketed as Navoban, is a serotonin 5-HT3 receptor antagonist approved as an antiemetic in Japan and in many other countries outside the United States, with ATC code A04AA03 (KEGG DRUG D02041, D02130). It has never been approved by the FDA, which is why American research groups describe it as a drug already approved for clinical use outside the United States (PMID: 15927799). Material sold on the research chemical market as Tropiestron is a misspelling of the same drug.\n\nInterest beyond nausea comes from a second property. Tropisetron is a partial agonist at the alpha7 nicotinic acetylcholine receptor. Oocyte electrophysiology traced that activity to the tropane portion of the molecule and showed that the indole portion mainly determines potency and subtype selectivity (PMID: 15781147). Positron emission tomography with the alpha7 radioligand CHIBA-1001 showed that a single oral dose lowered radioligand distribution volume in the human brain while ondansetron did not, so alpha7 engagement happens at ordinary clinical exposure (PMID: 23430308). A separate drug screen also found that it binds the ectodomain of amyloid precursor protein (PMID: 24389031).\n\nPreclinical work follows that thread. Tropisetron improved deficient inhibitory processing of the auditory evoked potential in DBA/2 mice, an effect blocked by the alpha7 antagonist methyllycaconitine (PMID: 16136299); improved phencyclidine-induced cognitive deficits in mice, again blocked by methyllycaconitine (PMID: 17094961); and improved apomorphine-disrupted prepulse inhibition in Wistar rats (PMID: 20673759). In J20 transgenic mice it improved memory and the sAPPalpha to amyloid-beta ratio more than memantine or donepezil at comparable doses (PMID: 24389031). Outside the brain it reduced collagen synthesis in human dermal fibroblasts and reduced established dermal fibrosis in a bleomycin mouse model of scleroderma through alpha7 receptors (PMID: 23440693).\n\nHuman trials outside emesis are small but real. Three randomized controlled trials, each with 40 patients with schizophrenia stabilized on risperidone, reported improved P50 auditory gating and cognition after 10 days (PMID: 22952075), improved P50 gating and sustained visual attention after 8 weeks (PMID: 20573264), and improved negative symptoms after 8 weeks (PMID: 23515583). In fibromyalgia, a randomized double-blind placebo-controlled multicenter trial in 21 women reported a larger fall in pain scores than placebo, which reached significance on a secondary body diagram score and not on the primary visual analog scale (PMID: 15370724).\n\nPharmacokinetics are dominated by CYP2D6. In 18 healthy volunteers, oral bioavailability ranged from 0.27 to 0.99 and correlated inversely with CYP2D6 activity measured by the sparteine metabolic ratio, with a half-life near 5.7 h (PMID: 11736884). Poor metabolisers get higher exposure with more headache and constipation, ultrarapid metabolisers get less antiemetic effect, and this relationship is now covered by a Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6 genotype and 5-HT3 receptor antagonists (PMID: 8363993, PMID: 12065557, PMID: 41979467). Every use outside the licensed antiemetic indication is investigational.", "half_life": "About 5.7 h after a single 5 mg oral capsule and 5.6 h after 2 mg intravenously in 18 healthy volunteers; oral bioavailability averaged 0.60 with a range of 0.27 to 0.99 and was inversely related to CYP2D6 activity (PMID: 11736884)", "molecular_weight": "284.35 g/mol (free base)", "molecular_mass": "284.35 g/mol (free base)", "amino_acid_sequence": "", "administration_routes": [ "Oral", "Intravenous injection" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Approved (Japan)", "approval_status": "Approved as an antiemetic for chemotherapy-induced nausea and vomiting in Japan and in many other countries outside the United States, marketed as Navoban, with a Japanese Accepted Name for the hydrochloride and ATC code A04AA03 (KEGG DRUG D02041, D02130). It has never been approved by the FDA, a point stated in the schizophrenia literature that uses it off label (PMID: 15927799). Its use for cognition, fibromyalgia, fibrosis or inflammation is investigational everywhere.", "trial_phase": "", "cas_number": "89565-68-4 (free base); 105826-92-4 (hydrochloride)", "iupac_name": "", "chemical_formula": "C17H20N2O2", "potential_benefits": [ "Improved cognition and P50 auditory gating in 40 non-smoking patients with schizophrenia in a randomized double-blind 10-day study (PMID: 22952075)", "Improved P50 gating and sustained visual attention in a randomized placebo-controlled 8-week study in 40 patients with schizophrenia (PMID: 20573264)", "Improved primary negative symptoms as an add-on to risperidone in a randomized placebo-controlled 8-week study in 40 patients with chronic schizophrenia (PMID: 23515583)", "Larger fall in pain scores than placebo in a randomized double-blind multicenter trial in 21 women with fibromyalgia, significant on the secondary body diagram score only (PMID: 15370724)", "Improved memory and the sAPPalpha to amyloid-beta ratio in J20 transgenic mice, with greater effect than memantine or donepezil at comparable doses (PMID: 24389031)", "Reduced collagen synthesis in human dermal fibroblasts and reduced established dermal fibrosis in a bleomycin mouse model of scleroderma, through alpha7 nicotinic receptors (PMID: 23440693)" ], "research_fields": [ "5-HT3 receptor antagonists", "Alpha7 nicotinic receptor pharmacology", "Antiemetics", "Schizophrenia cognition", "Fibromyalgia" ], "pubmed_count": 0, "pubchem_cid": 656665, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/tropisetron" }, { "id": "83620968-4183-467b-bba5-82b1574a4da2", "slug": "tudca", "name": "TUDCA", "aliases": [ "Tauroursodeoxycholic Acid", "Tauroursodiol", "TURSO", "Taurolite", "UR-906", "Xiong Dan (Traditional Chinese medicine black bear bile)", "Tauro-UDCA" ], "category": "Liver Support", "description": "TUDCA (tauroursodeoxycholic acid) is a hydrophilic bile acid formed by taurine conjugation of ursodeoxycholic acid (UDCA, the active ingredient in the widely-prescribed cholestasis medication Ursodiol). TUDCA occurs naturally in the bile of bears (particularly Asiatic black bears, where it comprises a substantial fraction of total bile acids), which is the source of its centuries-long use in traditional Chinese medicine as the preparation xiong dan (bear bile), where it has been used for liver disease, eye disease, and inflammatory conditions since at least the 7th century Tang dynasty. Modern pharmaceutical manufacturing produces TUDCA synthetically without animal sourcing, eliminating the ethical and conservation concerns associated with bear bile harvesting while providing a consistent and pure active substance. TUDCA has prescription pharmaceutical status in several European countries (Italy, China) for cholestatic liver disease and is widely available as a dietary supplement in the United States and most Western markets for liver support and broader off-label use. Its rising popularity in three distinct user communities — anabolic steroid users seeking hepatic protection during oral cycles, longevity-focused biohackers interested in ER-stress and mitochondrial effects, and patients with neurodegenerative disease attracted by the landmark AMX0035 ALS trial data — has made TUDCA one of the most-discussed bile-acid therapeutics in research-chemical and supplement markets.\n\nStructurally, TUDCA is the taurine-conjugated form of UDCA, which is itself the 7β-hydroxy epimer of chenodeoxycholic acid (CDCA). The taurine conjugation converts the hydrophobic primary bile acid into a more hydrophilic and bioavailable molecule, with the practical effect of improved intestinal absorption, reduced bile acid detergent activity (important for the safety profile — hydrophobic bile acids can damage cell membranes), and superior systemic distribution compared to unconjugated UDCA. TUDCA is a primary mammalian bile acid in some species (notably bears) and a minor bile acid in humans, representing <1% of total human bile acid pool under normal circumstances. Following oral administration in humans, TUDCA is absorbed in the small intestine, enters the enterohepatic circulation, and undergoes extensive first-pass hepatic extraction — meaning that most of an orally-administered dose is rapidly concentrated in the liver and biliary tree, providing high hepatic tissue exposure at relatively modest systemic plasma levels.\n\nFunctionally, TUDCA acts through multiple overlapping mechanisms that distinguish it from simpler hepatoprotective agents. The classical bile-acid function is replacement of more-toxic hydrophobic bile acids with the non-toxic hydrophilic TUDCA, reducing bile-acid-mediated hepatocyte damage in cholestatic conditions — this is the basis for UDCA's and TUDCA's longstanding use for primary biliary cholangitis (previously primary biliary cirrhosis), primary sclerosing cholangitis, and various cholestatic syndromes of pregnancy and genetic origin. Beyond this classical function, TUDCA is now recognized as a chemical chaperone — a small molecule that stabilizes protein folding and reduces endoplasmic reticulum (ER) stress. When cells experience stress that causes misfolded proteins to accumulate in the ER (a common feature of diabetes, neurodegeneration, ischemic injury, and many chronic diseases), the unfolded protein response (UPR) is activated, which can trigger cell death if the stress is prolonged. TUDCA's chemical chaperone activity reduces ER stress, reduces UPR activation, and has been shown in numerous preclinical models to protect cells from ER-stress-induced apoptosis. This mechanism underlies TUDCA's effects in diabetes (protecting pancreatic beta cells from ER-stress-induced dysfunction), Alzheimer's and Parkinson's models (reducing misfolded-protein-induced neuronal death), ALS (protecting motor neurons), retinitis pigmentosa and other retinal degenerative conditions, and a range of other pathologies where ER stress is a pathogenic factor.\n\nThe clinical evidence base divides into three tiers. **Tier 1 (approved/standard of care):** cholestatic liver disease — UDCA (the unconjugated form) has standard-of-care status for primary biliary cholangitis (PBC), where it improves liver biochemistry and in some populations reduces progression to liver transplantation. TUDCA is used in similar contexts in European pharmaceutical markets and shows equivalent or superior efficacy to UDCA for some endpoints. **Tier 2 (emerging clinical evidence):** ALS — the CENTAUR trial (Paganoni et al. 2020) evaluated AMX0035, a fixed-dose combination of TUDCA and sodium phenylbutyrate, in ALS patients and demonstrated 25% slower functional decline and significantly improved survival compared to placebo. FDA approval of AMX0035 under the brand name Relyvrio in 2022 represented the first approval of a TUDCA-containing medication for a non-cholestatic indication. (Relyvrio was subsequently withdrawn from the US market in April 2024 after the Phase 3 PHOENIX trial failed to confirm the Phase 2 benefit, producing active controversy about TUDCA's role in ALS.) Additional neurodegenerative disease trials for Parkinson's disease (including the UP-Parkinson's Phase 2 trial) are in progress. **Tier 3 (mechanism-driven off-label use):** bodybuilding/liver support during oral anabolic cycles, general antioxidant and \"liver detox\" supplementation, neuroprotection in the absence of disease, metabolic syndrome and insulin resistance support, and broad longevity applications. Tier 3 uses are driven by plausible mechanism and subjective reports rather than by direct clinical trial evidence in those specific contexts.\n\nThe bodybuilding and anabolic steroid context deserves specific mention because it drives much of the retail supplement-market demand for TUDCA. 17α-alkylated oral anabolic steroids (methylated compounds including oxandrolone, stanozolol, methandrostenolone, oxymetholone, anadrol, and others) are hepatotoxic, producing cholestatic hepatitis and liver enzyme elevations with chronic use. The bodybuilding community has long used UDCA and more recently TUDCA as hepatoprotective agents during oral steroid cycles, with the pharmacological rationale that bile-acid replacement and chemical-chaperone activity protect against cholestatic hepatotoxicity. Anecdotal reports and limited data support this use. Note that TUDCA does NOT reverse or prevent the underlying hepatotoxicity of 17α-alkylated steroids, nor does it allow safe long-term use of hepatotoxic substances — the pharmacologically honest framing is that TUDCA is a harm-reduction adjunct for users who are going to use oral anabolic steroids regardless, not an indication that oral anabolic steroids are safe when TUDCA is co-administered.\n\nThis entry covers TUDCA's bile-acid biology and chemical chaperone pharmacology, the traditional Chinese medicine history and transition to modern synthesis, the cholestatic liver disease evidence base, the CENTAUR ALS trial and subsequent FDA approval and withdrawal, the emerging Parkinson's disease work, the diabetes and metabolic research, the bodybuilding/steroid-user context with honest framing, practical dosing across indications, the relatively clean safety profile, drug interactions (limited but including cholestyramine and some others), appropriate stacking with milk thistle, NAC, and other hepatoprotective and antioxidant agents, and honest epistemic framing that separates the solid cholestatic-disease evidence from the ALS evidence (itself now uncertain post-PHOENIX) from the broader off-label longevity and general-health claims that remain largely mechanism-driven.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/tudca" }, { "id": "54da374b-6244-4b9c-8474-20f09da5528a", "slug": "tulsi", "name": "Tulsi (Holy Basil)", "aliases": [ "Holy Basil", "Ocimum tenuiflorum", "Ocimum sanctum", "Tulasi", "Queen of Herbs", "Mother Medicine of Nature", "Rama Tulsi", "Krishna Tulsi", "Vana Tulsi", "Sacred Basil", "Indian Basil", "Manjari", "Kala Tulsi" ], "category": "Adaptogen", "description": "**Tulsi** (scientific name *Ocimum tenuiflorum*, formerly classified as *Ocimum sanctum*; called **tulasi** in Sanskrit and most Indian languages, **holy basil** or **sacred basil** in Western herbalism, and **kala tulsi** or **manjari** for specific varieties) is a perennial aromatic herb in the Lamiaceae family (mint family), native to the Indian subcontinent but now cultivated throughout tropical and subtropical regions worldwide. Unlike culinary sweet basil (*Ocimum basilicum*) — used in Italian cuisine and pesto — tulsi is a related but distinctly different plant species, with strong clove-like, slightly peppery aromatic character from its high eugenol content and a genuine medicinal tradition spanning thousands of years. The plant reaches 30-60 cm in height with hairy stems and fragrant green or purple leaves, producing small pink-purple flowers in terminal spikes.\n\nTulsi holds an exceptional position in Indian culture, spirituality, and traditional medicine that is genuinely unique among adaptogens. In **Hindu tradition**, tulsi is considered a manifestation of the goddess Lakshmi (consort of Vishnu), is planted in the courtyard of millions of Hindu homes, is offered in daily worship rituals, and is considered a **sacred plant with protective properties**. Ayurvedic texts refer to tulsi as \"**Queen of Herbs**\" (*Osadhi-rani*), \"**Incomparable One**\" (*Apet-rakshasi*), and \"**Mother Medicine of Nature**\" — titles reserved for herbs of particular significance. The **Charaka Samhita** (~400 BCE) and **Sushruta Samhita** (~600 BCE), the foundational Ayurvedic texts, both reference tulsi extensively for stress reduction, respiratory conditions, fever, and general rejuvenation. Tulsi is classified as a **rasayana** — a rejuvenative herb promoting longevity and vitality — and as a **tridoshic** herb that balances all three Ayurvedic constitutional types (vata, pitta, kapha), though with a particular affinity for reducing kapha and calming vata.\n\nThree major **chemotypes** (botanical varieties) are distinguished in tulsi and have somewhat different phytochemical profiles and traditional uses: **(1) Rama tulsi** (Sri tulsi) — the green-leaved, lighter-colored variety with sweeter, less pungent flavor; dominant in eugenol and traditionally used for general wellness and women's health; **(2) Krishna tulsi** (Shyama tulsi) — purple-leaved, with more intense aromatic properties and higher eugenol content; considered most potent medicinally and traditionally used for respiratory conditions, stress, and infection; **(3) Vana tulsi** (wild forest tulsi, *Ocimum gratissimum*) — a related species found growing wild in forests; typically tall, with different phytochemistry emphasizing thymol and other components. Commercial tulsi products may contain one specific chemotype or combinations of all three. The famous \"Tulsi Sleep\" or \"Tulsi Restful\" products from Organic India and similar companies typically use **Krishna + Rama + Vana combinations**.\n\nThe primary bioactive compounds in tulsi span multiple chemical classes: **phenolic compounds** (eugenol — often the dominant aromatic compound at 20-70% of essential oil content, carvacrol, methyl eugenol); **triterpenoid compounds** (ursolic acid — a prominent anti-inflammatory triterpene, oleanolic acid, β-caryophyllene); **flavonoids** (apigenin, luteolin, vicenin, orientin); **phenolic acids** (rosmarinic acid — shared with rosemary and similar herbs, caffeic acid); **lignans** (ocimumosides A and B — unique tulsi-specific compounds identified for their cortisol-modulating effects); **essential oils** containing approximately 30-70 identified compounds depending on variety and growing conditions. The dominant pharmacologic \"driver\" compounds vary by indication — eugenol for antimicrobial and analgesic effects, ursolic acid and rosmarinic acid for anti-inflammatory and antioxidant effects, ocimumosides and related compounds for adaptogenic/cortisol-modulating effects.\n\nThe proposed clinical applications of tulsi span: **(1) stress reduction and anxiety modulation** — perhaps the best-evidenced modern application with multiple RCTs showing cortisol reduction and stress symptom improvement; **(2) metabolic health** — promising research in type 2 diabetes, lipid profiles, and metabolic syndrome with multiple human trials; **(3) respiratory health** — traditional primary use for cough, asthma, bronchitis, upper respiratory infections with growing modern evidence; **(4) immune support and infection** — antimicrobial, antiviral, antifungal activity in vitro and traditional use during infections; **(5) cognitive function** — attention, memory, and mood effects; **(6) cardiovascular effects** — mild antihypertensive, antiplatelet, and lipid-modulating effects; **(7) hepatoprotection** — protective effects in preclinical hepatotoxicity models; **(8) radioprotection** — emerging research on radiation protection for cancer patients; **(9) adaptogen for general wellness** — Ayurvedic traditional use as rasayana; and **(10) women's health** — traditional use for menstrual disorders, menopause, and fertility (though evidence here is weakest).\n\nHuman clinical evidence has grown substantially over the past 2 decades. Key trials: **Bhattacharyya et al. 2008** (*Nepal Medical College Journal*) — RCT of 150 subjects with generalized stress given tulsi extract 1200mg/day for 6 weeks showed significant reductions in stress symptoms, forgetfulness, sexual problems, exhaustion, and sleep problems compared with placebo. **Saxena et al. 2012** (*Evidence-Based Complementary and Alternative Medicine*) — RCT of 35 adults with generalized anxiety disorder given tulsi extract 500mg twice daily for 60 days showed significant improvements in Hamilton Anxiety scale, depression, and stress scores. **Sampath et al. 2008** — RCT examining tulsi in metabolic syndrome showed improvements in blood glucose, lipid profile, and blood pressure. **Jamshidi and Cohen 2017** (*Evidence-Based Complementary and Alternative Medicine*, PMID 28400848) — systematic review of 24 clinical trials concluded that tulsi shows clinical promise particularly for metabolic disorders, stress, cognitive function, and immune health, though noted heterogeneity in trial quality.\n\n**Chatterjee et al. 2013** — demonstrated improvements in reaction time and short-term memory with tulsi supplementation in healthy subjects. **Agrawal et al. 1996** (diabetes), **Rai et al. 1997** (diabetes), **Mondal et al. 2011** (immune) — each showing specific improvements in respective endpoints. **Saxena et al. 2007** — demonstrated benefits in stress-related respiratory symptoms.\n\nWhere does tulsi fit in the therapeutic landscape? As an adaptogen, tulsi offers a distinctive profile: **(1)** milder and more broad-spectrum than [Rhodiola rosea](/compound/rhodiola-rosea) or [Panax ginseng](/compound/panax-ginseng); **(2)** more grounding/centering and less activating than [Eleuthero](/compound/eleuthero); **(3)** with distinctive anti-inflammatory and metabolic effects not prominent in other classical adaptogens; **(4)** with a cultural/spiritual dimension unique among adaptogens; and **(5)** with emerging evidence specifically for metabolic syndrome and anxiety disorders. It pairs well with [Ashwagandha](/compound/ashwagandha) (the other major Ayurvedic adaptogen), [Bacopa monnieri](/compound/bacopa-monnieri) (for cognitive support), [Turmeric](/compound/turmeric) (shared anti-inflammatory actions), and [Holy Basil](/compound/tulsi) is often positioned alongside [Shilajit](/compound/shilajit) in complete Ayurvedic rejuvenation protocols. Tulsi is NOT primarily a libido or testosterone herb (unlike [Tongkat Ali](/compound/tongkat-ali) or [Panax ginseng](/compound/panax-ginseng)), NOT primarily a sleep herb (unlike [Ashwagandha](/compound/ashwagandha) evening dosing or [Reishi](/compound/reishi)), and NOT primarily a performance enhancer (unlike rhodiola). Its sweet spot is daily stress resilience with metabolic and immune benefits, taken as a gentle tonic.\n\nSafety is excellent for most users at culinary and therapeutic doses, with tulsi having been consumed as food and medicine by hundreds of millions of people for thousands of years. Modern formal toxicology confirms low toxicity. Key considerations include: mild antiplatelet effects from eugenol content (caution with anticoagulants), potential effects on thyroid hormones and blood glucose (generally favorable but requires monitoring in treated patients), potential male fertility effects at very high doses (probably not clinically relevant at typical doses), and standard caution in pregnancy despite traditional use.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 292, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/tulsi" }, { "id": "68d517a4-0e66-4f4e-a12c-54e1f7d1b0a0", "slug": "uridine-monophosphate", "name": "Uridine Monophosphate (UMP)", "aliases": [], "category": "Nootropics", "description": "**Uridine monophosphate** (UMP, also written **5'-UMP** or **uridine-5'-monophosphate**) is the nucleotide form of uridine, consisting of the pyrimidine base uracil linked to a ribose sugar phosphorylated at the 5' position. It is one of the four building blocks of RNA (the others being adenosine monophosphate, guanosine monophosphate, and cytidine monophosphate) and serves as a precursor in multiple biochemical pathways central to **membrane phospholipid synthesis**, **carbohydrate metabolism** (as UDP-glucose, UDP-galactose), **glycoprotein and glycolipid synthesis** (as UDP-GlcNAc, UDP-GalNAc), and **purinergic neurotransmission** (through UDP and UTP acting on P2Y receptors). Food sources include liver (particularly calf and beef liver), fish (sardines, herring, anchovies), broccoli, beer yeast, and human breast milk — the last being notable because uridine is an abundant and biologically important constituent of mammalian breast milk, supplying developing infants with substantial nucleotide building blocks for rapid cell division and membrane synthesis during early growth.\n\nAs a nootropic supplement, uridine monophosphate is primarily discussed in the context of **cognitive function**, **mood**, and **neuroplasticity**, based on its role as a substrate for the **Kennedy pathway** of membrane phosphatidylcholine synthesis. When supplemented orally at nootropic doses (typically 150-500 mg/day), uridine enters circulation, crosses the blood-brain barrier via specialised nucleoside transporters (ENT and CNT family), and is incorporated into brain cytidine triphosphate (CTP) — which is then condensed with choline (via choline kinase and CTP:phosphocholine cytidylyltransferase) to form CDP-choline, the activated intermediate used in phosphatidylcholine synthesis. Phosphatidylcholine is the predominant phospholipid of neuronal membranes and synaptic vesicles, and its availability is rate-limiting for the formation of new synapses during learning, memory formation, and neural repair.\n\nThis mechanistic pathway — uridine provides the pyrimidine backbone for CDP-choline synthesis, which drives phosphatidylcholine production, which supports synaptic growth — is the central logical framework for uridine's nootropic use. It also explains why uridine is commonly stacked with a **choline source** (alpha-GPC, CDP-choline, or choline bitartrate) and with **DHA (docosahexaenoic acid, an omega-3 fatty acid)** — the three components together provide the pyrimidine, choline, and fatty acid substrates that collectively support membrane phospholipid synthesis. The **Richard Wurtman group at MIT** published substantial preclinical and clinical work in the 2000s and 2010s establishing this uridine-choline-DHA synergy and showing benefits in animal models of cognitive impairment and, in selected human populations, modest cognitive effects. The most clinically significant application has been as a component of **Souvenaid** (brand-name medical food containing uridine monophosphate, choline, DHA/EPA, phospholipids, B-vitamins, and antioxidants), studied in early Alzheimer's disease with moderate-quality data showing some benefit on memory composite scores in prodromal and mild Alzheimer's populations.\n\nBeyond the Alzheimer's-adjacent use, uridine has been studied and discussed in several other contexts: (1) **major depressive disorder**, particularly in work by **Perry Renshaw and colleagues at McLean Hospital/Harvard** on bipolar depression and unipolar depression, with some studies showing antidepressant signal; (2) **bipolar disorder**, with smaller studies suggesting potential benefit; (3) **post-stroke cognitive recovery**, with preliminary data; (4) **pain syndromes** including peripheral neuropathy, where pyrimidine nucleotide supplementation (cytidine + uridine) has been studied for nerve regeneration; and (5) **general nootropic use in healthy adults**, where the evidence is weakest and largely anecdotal.\n\nIt is important to place uridine honestly in the therapeutic landscape. For **Alzheimer's disease**, the evidence-based treatments are cholinesterase inhibitors ([donepezil](/compound/donepezil), rivastigmine, galantamine), memantine, and the newer disease-modifying antibodies lecanemab and donanemab — all of which have substantially more rigorous trial evidence than uridine. Souvenaid (the uridine-containing medical food) has a modest evidence signal for prodromal/mild Alzheimer's but is not a replacement for approved therapies. For **depression**, the evidence-based treatments are SSRIs, SNRIs, and for treatment-resistant depression, [ketamine](/compound/ketamine)/esketamine, TMS, and ECT. Uridine as monotherapy for depression is not evidence-based, but it has emerging data as a potential adjunct in bipolar depression. For **general cognitive enhancement in healthy adults**, the evidence is preliminary at best, and the best-evidenced interventions remain sleep, exercise, nutrition, and cognitive engagement.\n\nWhere uridine has a genuine, reasonably well-supported role is: (1) as a **component of the Souvenaid/uridine-choline-DHA stack** for prodromal and mild Alzheimer's under physician guidance; (2) as a **general supplement for membrane health and potentially mild cognitive support** in older adults with concern about cognitive decline; (3) as an **adjunct in bipolar depression** under psychiatric supervision in research contexts; and (4) as a **generally safe, low-risk nutritional supplement** that forms part of various nootropic stacks without dramatic effects but also without significant risk when used sensibly.\n\nFrom a safety perspective, uridine is one of the safer supplements in the nootropic space. It is a naturally occurring nutrient present in ordinary dietary sources, including breast milk. Typical supplemental doses (150-500 mg/day) are multiples of ordinary dietary intake (dietary uridine is difficult to quantify precisely but typical Western diets provide perhaps 5-50 mg/day of free uridine plus substantial nucleotide-derived uridine), but well below toxic levels. Human studies with daily doses up to 2 grams have shown good tolerability. Gout is a theoretical concern because uridine is a purine-adjacent nucleotide and its metabolism produces allantoin and, through some pathways, uric acid — but in practice, supplemental uridine does not appear to cause clinically significant hyperuricemia at typical doses.\n\nUridine is commonly combined with other nootropic compounds in community stacks: with choline sources (alpha-GPC, CDP-choline) for membrane synthesis support; with omega-3 DHA for the same purpose; with [noopept](/compound/noopept) or [piracetam](/compound/piracetam) as part of broader cognitive-support stacks; with [lions-mane](/compound/lions-mane) for neurotrophic support; and with [nad](/compound/nad) or other metabolic co-factors. The evidence for specific combinations is generally mechanistic/anecdotal rather than trial-validated.", "half_life": "", "molecular_weight": "", "molecular_mass": "324.18 g/mol", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "Preclinical", "cas_number": "58-97-9", "iupac_name": "{[(2R,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxyoxolan-2-yl]methyl} dihydrogen phosphate", "chemical_formula": "C9H13N2O9P", "potential_benefits": [ "D2/D3 receptor upregulation", "Mood stabilization", "Memory improvement", "Synaptic plasticity", "Neuronal membrane support", "Long-term cognitive enhancement" ], "research_fields": [ "Depression", "Bipolar disorder", "Cognitive aging", "ADHD", "Neuroplasticity" ], "pubmed_count": 920, "pubchem_cid": 6030, "image_url": "", "structure_image_url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/6030/PNG?image_size=300x300", "url": "https://www.bodyhackguide.co/compound/uridine-monophosphate" }, { "id": "c65a136a-54e4-4220-9430-b7218d7ca370", "slug": "urolithin-a", "name": "Urolithin A", "aliases": [ "Mitopure", "UA", "Ellagitannin metabolite", "3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one", "Urolithin" ], "category": "Mitochondrial Support", "description": "Urolithin A (3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one; trade name Mitopure from Timeline Nutrition, formerly Amazentis) is a gut-microbiome-derived metabolite of dietary ellagitannins — polyphenolic compounds found in pomegranates, walnuts, strawberries, raspberries, and several other berries. Unlike most dietary polyphenols, ellagitannins themselves are poorly absorbed from the intestine; their health-relevant bioactivity depends on conversion by specific gut bacteria (primarily Gordonibacter species, along with some Lactobacillus and Bifidobacterium strains) into a family of smaller metabolites called urolithins, of which urolithin A is the most biologically active. This microbial conversion is not universal — published surveys suggest only 30-40 percent of Western adults harbor the gut bacteria necessary to produce meaningful urolithin A from dietary ellagitannin consumption, with the remaining majority producing mainly urolithin B, urolithin C, or minimal urolithin production at all. The conversion capacity (\"metabotype\") depends on gut microbiome composition shaped by diet, antibiotic history, age, and unknown factors. Direct urolithin A supplementation bypasses the microbiome-dependent conversion step, providing consistent bioactive exposure regardless of individual metabotype.\n\nThe scientific story of urolithin A as a longevity-relevant molecule begins with a landmark 2016 paper by Ryu and colleagues at EPFL (École Polytechnique Fédérale de Lausanne) in Switzerland and the biotechnology company Amazentis, published in Nature Medicine (Ryu et al. 2016). The authors screened a library of microbial metabolites for mitochondrial activity and identified urolithin A as a potent inducer of mitophagy — the selective autophagic degradation of damaged mitochondria — in both Caenorhabditis elegans and aged mice. Urolithin A extended lifespan in C. elegans, improved muscle function in aged mice, and reduced markers of mitochondrial dysfunction. Mitophagy, the specific form of autophagy that targets mitochondria for degradation, had by then emerged as a central process in mitochondrial quality control: damaged mitochondria that accumulate with age are normally targeted for degradation via PINK1/Parkin and related pathways, but this mitophagy machinery itself declines with age, producing a vicious cycle of mitochondrial damage accumulation. Urolithin A's demonstrated ability to induce mitophagy even in aged systems made it an attractive candidate for clinical translation.\n\nTimeline (formerly Amazentis) developed and commercialized urolithin A as Mitopure, with pharmaceutical-grade material supported by human clinical trials demonstrating safety, bioavailability, and biomarker effects on mitochondrial function. Phase 1 (Andreux et al. 2019) established safety at doses up to 1,000 mg daily and measured biomarker changes in skeletal muscle. Phase 2 trials (Liu et al. 2022 and Singh et al. 2022) demonstrated improvements in muscle function and mitochondrial biomarkers in middle-aged and older adults. A series of biomarker and mechanistic studies confirmed induction of mitophagy in human tissues following urolithin A administration. Current commercial products are based on this evidence foundation and include Mitopure capsules and softgels, along with various third-party urolithin A products of variable quality. Unlike many longevity compounds that remain investigational or available only through unregulated suppliers, urolithin A has achieved GRAS (Generally Recognized as Safe) status in the United States for several commercial forms, allowing mainstream supplement distribution.\n\nMechanistically, urolithin A addresses a specific, important, and previously underaddressed aspect of aging: mitochondrial quality control through selective turnover of damaged mitochondria. Aging tissues accumulate dysfunctional mitochondria with reduced respiratory capacity, increased ROS production, damaged membranes, and impaired calcium handling. Removing these damaged organelles is a prerequisite for replacing them with functional ones through mitochondrial biogenesis. If the mitophagy machinery is slow or insufficient, damaged mitochondria accumulate even in the presence of adequate biogenesis signals. Urolithin A accelerates this turnover, functionally \"rejuvenating\" the mitochondrial population by favoring the retention of healthy organelles and the removal of damaged ones. This mechanism is complementary to and distinct from the effects of other mitochondrial interventions: [SS-31](/compound/ss-31) stabilizes mitochondrial membranes to preserve existing mitochondrial function; [NMN](/compound/nmn) elevates NAD+ to support mitochondrial biochemistry; [CoQ10](/compound/coq10) provides electron transport chain cofactor; exercise induces both biogenesis and mitophagy. Urolithin A specifically enhances the quality control step that complements these other interventions, and a complete mitochondrial longevity approach often incorporates multiple mechanisms working together.\n\nPractical considerations for urolithin A use are favorable relative to most longevity interventions. Oral bioavailability is moderate (published pharmacokinetic data show meaningful plasma and tissue exposure after oral dosing), eliminating the need for injections required by peptides like SS-31 or MOTS-c. Cost is moderate — commercial Mitopure products run $40-80 monthly at standard doses, while generic urolithin A from reputable supplement companies runs $20-40 monthly. Safety profile is excellent, with clinical trials reporting good tolerability and commercial post-market experience showing minimal concerns. Dosing is straightforward (once daily with food), and timing does not require specialized scheduling. These practical advantages make urolithin A one of the more accessible serious mitochondrial interventions available to consumers, appropriate for users ranging from cautious beginners to advanced longevity practitioners.\n\nUsers should calibrate expectations appropriately. Published clinical trials show real but modest effects on mitochondrial biomarkers and muscle function in middle-aged and older adults, with effect sizes in the range typical for other longevity interventions rather than dramatic transformation. The most relevant applications appear to be age-related muscle function decline (sarcopenia prevention), general mitochondrial health support, and complementary coverage within a broader mitochondrial stack. Urolithin A does not cure age-related decline, does not substitute for exercise (which remains the most potent mitochondrial biogenesis stimulus available), and does not address aspects of aging outside mitochondrial quality control. It is best viewed as one useful tool among several for mitochondrial health, with specific advantages in addressing mitophagy that most other interventions do not cover directly.\n\nThe microbiome dimension of urolithin A raises interesting questions for users. Some individuals are natural \"high converters\" who produce urolithin A endogenously from dietary ellagitannins; these individuals may have lower marginal benefit from direct supplementation. Most Western adults are non-converters or low converters who produce little or no urolithin A from pomegranate and walnut consumption; for these individuals, direct supplementation provides access to a bioactive that would otherwise be unavailable from diet. Commercial urinalysis tests can identify urolithin metabotype, though most users skip this step and simply supplement directly based on the reasonable assumption that they are probably not a high converter. Diet continues to matter: even with supplementation, consumption of pomegranate, walnuts, berries, and other ellagitannin sources supports broader polyphenol intake and related health benefits, and the small fraction of users who are high converters produce endogenous urolithin A from these foods.\n\nPositioning urolithin A within a longevity strategy: it integrates naturally with exercise (the fundamental mitochondrial intervention), a solid mitochondrial supplement foundation ([CoQ10](/compound/coq10), [NMN](/compound/nmn), [creatine](/compound/creatine), [omega-3](/compound/omega-3-fatty-acids)), and other complementary interventions as budget and goals allow. For many users, urolithin A offers a meaningful quality-of-life and functional-capacity signal with favorable cost, convenience, and safety — making it one of the more defensible additions to a longevity stack compared to higher-cost or higher-risk experimental options.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 7, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/urolithin-a" }, { "id": "b1010100-0000-0000-0000-000000000001", "slug": "vasodrive-blend", "name": "Vasodrive Amino Blend", "aliases": [ "Vasodrive", "Optimum Vasodrive", "Optimum Vasodrive Research Blend", "Vasodrive Blend", "Amino Acid Vasodilator", "Vasodilator Blend", "Amino Pump Blend", "Amino Pump", "Pre-Workout Amino Blend" ], "category": "Performance & Recovery", "description": "Injectable amino-acid blend formulated for vasodilation and increased blood flow. Typical formulations stack L-arginine, L-citrulline, L-ornithine, and L-glutamine in a 20mL multi-dose vial. Marketed as a pre-workout \"pump\" enhancer in the bodybuilding and aesthetic research space. L-Arginine and L-Citrulline serve as substrates for endogenous nitric oxide (NO) production via nitric oxide synthase, increasing vasodilation and skeletal-muscle blood flow during training.", "half_life": "Not meaningful as a single value for a multi-amino-acid blend. For reference, plasma arginine rises after oral L-citrulline and peaks around 1 hour, and free amino acids are generally cleared over a few hours.", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "Not applicable in micrograms - this blend is dosed in GRAMS. Typical oral ranges: L-citrulline 3-8 g, L-arginine 3-6 g, L-ornithine 2-6 g, L-glutamine ~5 g per day. See the dosing summary for the component breakdown.", "dosing_frequency": "Once daily, or pre-workout on training days (oral). Consistent daily use matters - several benefits in trials required chronic rather than single-dose intake.", "cycle_length": "No defined cycle. Amino acids like these are typically used continuously or on training days rather than cycled. The vascular/blood-pressure benefits seen in citrulline studies developed over days to weeks of daily use, so allow at least 1-2 weeks before judging effect.", "common_vial_sizes": [], "research_stage": "No clinical trials (as a blend); individual components have human RCTs", "approval_status": "Not FDA-approved and not an approved drug. The individual amino acids (L-arginine, L-citrulline, L-ornithine, L-glutamine) are sold as ordinary oral dietary supplements. There is no approved injectable form of this blend - any injectable or IV presentation is off-label and research-use-only (RUO).", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "May increase blood flow and the training \"pump\" via the L-arginine/nitric-oxide pathway, with L-citrulline providing the more reliable oral boost to plasma arginine", "L-citrulline malate has improved resistance-exercise reps-to-failure and reduced next-day muscle soreness in several human trials (effect is modest and not universal)", "L-ornithine may reduce subjective fatigue and support ammonia clearance during hard exercise", "L-glutamine may support gut and immune-cell fuel demands during heavy training loads", "Chronic L-citrulline dosing has lowered blood pressure and improved endothelial function in people with prehypertension/hypertension (a component-level effect, not a claim for the blend)" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/vasodrive-blend" }, { "id": "ca89f8ae-c4df-433c-afe0-74914e13cccb", "slug": "vesugen", "name": "Vesugen", "aliases": [ "Vessel peptide" ], "category": "Recovery", "description": "Vesugen is a short synthetic peptide developed within Vladimir Khavinson's laboratory at the Saint Petersburg Institute of Bioregulation and Gerontology and marketed in Russia as an oral capsule for vascular and endothelial system support. The reported sequence is a tripeptide, H-Lys-Glu-Asp-OH (KED), though some sources list it with a C-terminal amide. Within the Khavinson short-peptide bioregulator catalog — [Epitalon](/compound/epithalon), [Thymogen](/compound/thymogen), [Pinealon](/compound/pinealon), [Vilon](/compound/vilon), [Livagen](/compound/livagen), [Bronchogen](/compound/bronchogen), [Cardiogen](/compound/cardiogen), [Cartalax](/compound/cartalax), [Chonluten](/compound/chonluten), [Ovagen](/compound/ovagen), [Testagen](/compound/testagen), and [Prostamax](/compound/prostamax) — Vesugen occupies the vascular tissue niche. Cardiogen is the companion cardiac peptide; Vesugen is marketed specifically for the vessel wall rather than the myocardium.\n\nLike the rest of the Khavinson capsule line, commercial Vesugen is a 20 milligram nominal capsule containing approximately 2 to 4 milligrams of synthetic peptide dispersed in milk-protein and starch excipients. The 20 mg on the bottle refers to total powder weight, not peptide dose. This matters because users reading vendor sites sometimes assume they are getting a much larger peptide quantity than is actually present.\n\nVesugen is sold as an over-the-counter supplement in Russia and Eastern Europe and as a research compound in other markets. It is not a registered pharmaceutical in the United States, the European Union, the United Kingdom, Canada, or Australia. It is not FDA-approved for any indication. It has not undergone phase 3 Western randomized controlled trials. All human clinical evidence for Vesugen is from small single-center Russian-language observations and reviews from Khavinson's group and affiliated collaborators, with limited independent replication. Readers evaluating Vesugen for their own cardiovascular health are comparing a niche Russian bioregulator to mainstream cardiology pharmacology — statins, PCSK9 inhibitors, ezetimibe, antihypertensives, antiplatelet agents, SGLT2 inhibitors, and GLP-1 agonists — where the evidence gap is enormous.\n\nBodyHackGuide treats Vesugen honestly rather than promotionally. If a reader is researching vascular bioregulators, the goal of this page is to explain what Vesugen is, what the Khavinson framework claims, where the evidence is thin, how it would theoretically fit into a serious cardiovascular prevention plan, what safer and better-evidenced alternatives exist, and which contraindications and interactions matter. The framing throughout is that Vesugen is at best a low-priority adjunct in a well-constructed vascular health plan, and at worst an unnecessary purchase that displaces attention from the evidence-based interventions that actually move cardiovascular outcomes. A reader worried about vascular aging, endothelial dysfunction, hypertension, hyperlipidemia, atherosclerosis, stroke risk, or peripheral arterial disease should be working with a cardiologist or internist on statins, antihypertensives, antiplatelets, and lifestyle — not relying on a Russian tripeptide.\n\nThe Khavinson framework for Vesugen follows the same three-stage mechanistic story that applies to the whole short-peptide line. Stage one is absorption from the gut and passive membrane crossing into target tissue cells. Stage two is passive nuclear import, with short peptides entering nuclei and reaching chromatin. Stage three is sequence-selective binding to DNA regulatory regions associated with vascular and endothelial gene programs. In Vesugen's case, the target tissue is claimed to be vascular smooth muscle and endothelium, with effects on endothelial nitric oxide synthase (eNOS), endothelial growth factors, pro- and anti-inflammatory gene regulation, and the chromatin state of aging endothelial cells. The claim is that cycled oral dosing can partially reset the endothelial transcriptional program back toward a younger pattern, improving nitric oxide bioavailability, vessel relaxation, and resistance to atherogenic lipid deposition.\n\nThat framework is elegant but not robustly validated outside Khavinson's laboratory. The biochemical basis for short-peptide tissue selectivity remains contested in mainstream molecular biology. The pharmacokinetic claim — that orally delivered tripeptides survive gastric proteolysis, cross the gut wall intact, and reach vascular tissue nuclei at concentrations relevant to gene regulation — is not independently established at the quantitative level required to support the clinical claims. A reader should understand that the mechanism-of-action story is a theoretical model rather than a settled body of biochemistry.\n\nThe main demographic buying Vesugen is men and women in their forties through sixties who are worried about vascular aging. Typical concerns include: modestly elevated blood pressure, borderline lipid panels, family history of stroke or myocardial infarction, peripheral cool extremities, varicose veins or spider veins, concerns about erectile or sexual vascular function, mild endothelial dysfunction markers, concerns about dementia-vascular pathology overlap, and generalized \"longevity\" interests. Each of those concerns has an evidence-based workup and treatment pathway that vastly outstrips what Vesugen can offer. A reader with one or more of those concerns should be working through that pathway — not treating a Russian capsule as a shortcut.\n\nVesugen is most commonly used in a 10-days-on cycle followed by a 60 to 90 day washout, per the Khavinson cycling convention. Each dose is 1 or 2 capsules on an empty morning stomach. Cycles are typically repeated two to four times per year, often paired with Cardiogen (for those with both cardiac and vascular concerns), Epitalon (for generalized longevity framing), Pinealon (for cognitive-vascular overlap), or Thymogen (immune support). Reconstitution is not required for the oral capsule form. Injectable Vesugen is a research-chemical formulation rather than the commercial product and is not recommended for users without research-chemical experience and clinical oversight.\n\nSafety observation in the published Khavinson work has been consistently reassuring at the oral doses used, but the trial base is small and short. This page treats \"well tolerated\" as a provisional claim rather than a conclusion. The theoretical safety concerns specific to Vesugen include drug interactions with antihypertensives and antiplatelets (where additive effects are possible but uncharacterized), interactions with statins (where no direct interaction is known but monitoring is reasonable), and interactions with anticoagulants (where peptide effects on coagulation and platelet function are not characterized in published data). A reader on these classes of medications should consult their cardiologist before starting Vesugen — not for regulatory reasons but for coherent integration of any observed effects with their existing therapy.\n\nThe honest positioning on this page: Vesugen is a niche adjunct to a real cardiovascular prevention plan, and the plan matters more than the peptide. The plan is lifestyle (aerobic training, resistance training, diet, weight, sleep, stress), evidence-based pharmacology (statins, antihypertensives, antiplatelets, SGLT2 inhibitors, GLP-1 agonists where indicated), preventive screening (lipid panel, blood pressure monitoring, CAC score or carotid imaging in select cases, diabetes screening, kidney function), and clinical relationship (primary care, cardiology when risk is elevated). Vesugen cycling can be layered onto that plan for users who want to experiment with the Khavinson framework. It cannot replace that plan.", "half_life": "Not established in humans. As a short tripeptide, KED is expected to be rapidly hydrolyzed in plasma, with an anticipated half-life on the order of minutes; no formal pharmacokinetic study of Vesugen has been published.", "molecular_weight": "390.39 g/mol", "molecular_mass": "390.39 g/mol", "amino_acid_sequence": "Lys-Glu-Asp (KED)", "administration_routes": [], "dose_range_mcg": "20 mg oral capsule 1-2 daily for 10-day cycles (60-90 day washout)", "dosing_frequency": "1-2 capsules daily during the 10-day cycle", "cycle_length": "10 days on, 60-90 days off (2-4 cycles per year)", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "L-Alanyl-L-glutamyl-L-aspartyl-L-valine", "chemical_formula": "Ala-Glu-Asp-Val", "potential_benefits": [ "Vascular health support", "Blood vessel integrity maintenance", "Endothelial function optimization", "Cardiovascular anti-aging" ], "research_fields": [], "pubmed_count": 27, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/vesugen" }, { "id": "2d041928-0249-4dae-b393-5d6e0c485d48", "slug": "vilon", "name": "Vilon", "aliases": [ "Lys-Glu" ], "category": "Recovery", "description": "Vilon is the simplest member of Vladimir Khavinson's short-peptide bioregulator catalog — a dipeptide of lysine and glutamic acid (H-Lys-Glu-OH, abbreviated KE). Developed at the Saint Petersburg Institute of Bioregulation and Gerontology in the late 1990s as a synthetic follow-on to the first-generation thymus polypeptide extracts (Thymalin, Thymogen), Vilon was positioned as a minimal-sequence immune and thymic bioregulator. Within the broader Khavinson catalog — [Epitalon](/compound/epithalon), [Thymogen](/compound/thymogen), [Pinealon](/compound/pinealon), [Livagen](/compound/livagen), [Bronchogen](/compound/bronchogen), [Cardiogen](/compound/cardiogen), [Cartalax](/compound/cartalax), [Chonluten](/compound/chonluten), [Ovagen](/compound/ovagen), [Testagen](/compound/testagen), [Prostamax](/compound/prostamax), and [Vesugen](/compound/vesugen) — Vilon occupies a foundational position. It is the first compound in the short-peptide line and the one most consistently cited across Khavinson's theoretical framework because its extreme structural simplicity makes it the cleanest test case for his sequence-selective DNA binding and tissue-specific gene modulation claims.\n\nCommercial Vilon is sold as an oral capsule in Russia and Eastern European markets. The standard 20 mg nominal capsule contains approximately 2 to 4 mg of synthetic peptide dispersed in milk-protein and starch excipients — the same formulation strategy used across the Khavinson capsule line. It is also available in some markets as a subcutaneous lyophilized peptide for injection. Vilon is not a registered pharmaceutical in the United States, the European Union, the United Kingdom, Canada, or Australia. It is not FDA-approved for any indication. It is sold as a research chemical or as an over-the-counter supplement depending on jurisdiction.\n\nThe Khavinson literature positions Vilon as a broad-spectrum immune modulator with reported effects on thymus-derived lymphocyte maturation, peripheral T-cell subset balance, natural killer cell activity, and age-related immune decline. Because lysine and glutamate are both charged amino acids (Lys positive, Glu negative) and because the dipeptide has only two peptide-bond-linked residues, Khavinson has argued that Vilon represents the minimum recognizable unit of his tissue-selective DNA binding model. The theoretical claim is that a two-residue ligand can still make enough electrostatic and hydrogen-bonding contacts with specific DNA sequences to influence transcription at particular promoters — a stronger assertion than most Western molecular biology would comfortably accept, but foundational to the Khavinson framework.\n\nBodyHackGuide treats Vilon honestly rather than promotionally. All human clinical evidence for Vilon is from small observational studies from Khavinson's group and a limited set of Russian and Eastern European collaborators. Independent Western replication is sparse. The claim that a synthetic dipeptide of this simplicity produces reproducible, tissue-specific, clinically meaningful effects on human immune function is not established by the evidence standards that Western regulators require for therapeutic approval. Readers evaluating Vilon for immune support should compare it to vaccination, evidence-based chronic disease management (diabetes, obesity, hypertension control, all of which modulate immune function), sleep tuning, exercise, and micronutrient sufficiency (vitamin D, zinc, selenium) — all of which have substantially stronger evidence for supporting immune outcomes than any Khavinson peptide.\n\nThe main demographic buying Vilon is older adults concerned about age-related immune decline (immunosenescence). The biology of immunosenescence is real and well characterized — thymic involution over the lifespan, reduced naive T-cell output, diminished T-cell receptor repertoire, impaired vaccine responses, reduced NK cell cytotoxicity, increased susceptibility to infection, and increased incidence of cancer with age. The question is whether a synthetic dipeptide cycled twice a year can produce clinically meaningful mitigation of those changes. The Khavinson framework argues yes; mainstream immunology reserves judgment. A reader considering Vilon for age-related immune concerns should layer it onto a solid foundation — annual influenza vaccination, recommended COVID-19 boosters, pneumococcal vaccination at appropriate ages, shingles vaccination, routine cancer screening, lifestyle tuning — rather than relying on it as a primary immune strategy.\n\nA secondary demographic is users interested in Khavinson's broader anti-aging framework. Vilon is often cycled alongside Epitalon in anti-aging stacks, with the theoretical justification that Epitalon acts on the pineal gland (circadian, telomerase) while Vilon acts on the thymus (immune, T-cell). The paired-axis framing is central to Khavinson's \"pineal-thymic\" model of aging, in which declining pineal and thymic function are proposed as interlocked drivers of systemic aging. Whether that framework is accurate at the level of clinical intervention is an open question; the framework itself is coherent at the level of observation that both organs undergo age-related involution.\n\nVilon is most commonly cycled as 1 or 2 oral capsules daily on an empty stomach for 10 consecutive days, followed by a 60 to 90 day washout, with 2 to 4 cycles per year. Injectable Vilon follows a similar pattern at doses of 50 to 200 mcg subcutaneously daily during an active cycle. Users frequently layer Vilon with [Thymogen](/compound/thymogen) for immune goals, with [Epitalon](/compound/epithalon) for anti-aging goals, or with [Pinealon](/compound/pinealon) for cognitive-immune overlap.\n\nSafety observation in the published Khavinson work has been consistently reassuring at the oral doses used. Because Vilon is structurally very simple (a dipeptide, 275 Da molecular weight), and because lysine and glutamate are standard dietary amino acids, acute toxicity at the microgram-to-milligram doses used is essentially zero. The tolerability is similar to taking a very small amount of a dipeptide that already occurs in partial proteolytic digests of any dietary protein. Theoretical concerns specific to Vilon include hypothetical unintended immune activation (not observed in practice but possible), hypothetical interaction with immunosuppressive therapy (not characterized in published data), and the general concern applicable to all Khavinson peptides that the published evidence base is too small to detect rare serious adverse events. A reader on active immunosuppressive therapy (post-transplant, active autoimmune disease on biologics, active cancer therapy) should not initiate Vilon without their specialist's input.\n\nThe honest positioning on this page: Vilon is the simplest and longest-studied Khavinson peptide, with a modest amount of Russian clinical observational data supporting tolerability and suggesting weak-to-moderate immune-modulatory effects. It is not a replacement for vaccination, evidence-based lifestyle management of chronic disease, or disease-specific immune therapies where indicated. It can be considered as an experimental adjunct for users who want to explore the Khavinson bioregulator framework with the minimum-complexity reference peptide.", "half_life": "Not established in humans; as a dipeptide (Lys-Glu) it is expected to be cleared from plasma within minutes, with proposed effects attributed to transient gene-expression modulation rather than sustained blood levels.", "molecular_weight": "275.3 Da (C11H21N3O5)", "molecular_mass": "275.30 g/mol", "amino_acid_sequence": "Lys-Glu (KE)", "administration_routes": [], "dose_range_mcg": "20 mg oral capsule (~2-4 mg Lys-Glu peptide), 1-2 capsules daily for 10 consecutive days per cycle", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "90203-91-1", "iupac_name": "L-Lysyl-L-glutamic acid", "chemical_formula": "Lys-Glu", "potential_benefits": [ "Immune system support", "Tissue repair enhancement", "Anti-aging immune modulation", "General health optimization" ], "research_fields": [], "pubmed_count": 74, "pubchem_cid": 135607024, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/vilon" }, { "id": "f36b1e49-ab10-48f0-9eb6-b08d923f77c3", "slug": "vip", "name": "VIP", "aliases": [ "Vasoactive Intestinal Peptide", "Vasoactive Intestinal Polypeptide", "PHM-27 precursor neuropeptide" ], "category": "Nootropic", "description": "VIP (Vasoactive Intestinal Peptide) is a 28-amino-acid neuropeptide and hormone that is widely expressed throughout the central and peripheral nervous systems, gastrointestinal tract, and immune system. It is a member of the glucagon superfamily. VIP functions as a potent vasodilator and bronchodilator, as a neuromodulator in the brain (circadian rhythm, neuroprotection), as an immunomodulator with predominantly anti-inflammatory actions, and as a GI motility regulator. VIP has attracted research interest for CIRS (Chronic Inflammatory Response Syndrome), mast cell activation, small fiber neuropathy, and autonomic nervous system regulation. It is one of the few neuropeptides with simultaneous central, peripheral, and immune functions.", "half_life": "~1-2 minutes (plasma). VIP is very rapidly degraded by circulating peptidases, so systemic exposure is extremely short-lived regardless of administration route. Subcutaneous or intranasal absorption may modestly prolong the apparent duration of local/systemic effect, but this has not been well characterized in humans.", "molecular_weight": "3326.8", "molecular_mass": "3326.8", "amino_acid_sequence": "HSDAVFTDNYTRLRKQMAVKKYLNSILN (28 residues; native C-terminal amide, His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys-Gln-Met-Ala-Val-Lys-Lys-Tyr-Leu-Asn-Ser-Ile-Leu-Asn-NH2)", "administration_routes": [ "Subcutaneous", "Intranasal", "Intravenous" ], "dose_range_mcg": "50", "dosing_frequency": "once_or_twice_daily", "cycle_length": "", "common_vial_sizes": [ "10" ], "research_stage": "Clinical", "approval_status": "Investigational - not FDA-approved", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [ "Potent anti-inflammatory signaling — inhibits TNF-α, IL-6, IL-12 via cAMP pathway", "Circadian rhythm regulation through suprachiasmatic nucleus (SCN) VPAC receptor activation", "Bronchodilation — potential research application in airway inflammation models", "Vasodilation and blood flow regulation in peripheral vascular research", "Neuroprotection — VPAC2 agonism supports neuronal survival in excitotoxicity models", "CIRS/mast cell activation research — increasingly studied in chronic inflammatory syndromes", "Gut motility modulation and GI mucosal protection" ], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/vip" }, { "id": "3334cdce-31bf-4dc3-9800-1ff5617a783f", "slug": "vitamin-a", "name": "Vitamin A", "aliases": [ "Retinol", "All-trans-retinol", "Preformed vitamin A", "Retinyl palmitate", "Retinyl acetate", "Retinyl ester", "Retinal", "Retinaldehyde", "11-cis-retinal", "All-trans-retinal", "Retinoic acid", "All-trans-retinoic acid", "ATRA", "Tretinoin", "13-cis-retinoic acid", "Isotretinoin", "9-cis-retinoic acid", "Alitretinoin", "Beta-carotene", "Provitamin A", "Alpha-carotene", "Gamma-carotene", "Beta-cryptoxanthin", "Retinyl propionate", "Axerophthol", "Anti-infective vitamin", "Anti-xerophthalmic vitamin" ], "category": "Vitamin", "description": "\nVitamin A is the fat-soluble vitamin family encompassing three interconvertible oxidation states — retinol (the alcohol form, the primary transport and storage species), retinal (the aldehyde, the vision-critical form), and retinoic acid (the carboxylic acid, the nuclear receptor ligand) — along with the provitamin A carotenoids, chiefly β-carotene, that plants use to provide animals a dietary precursor. The vitamin earned four distinct \"vitamin A\" designations across its history: the anti-xerophthalmic factor (night blindness), the anti-infective factor, the growth factor, and the epithelial differentiation factor. All four are the same molecule operating through overlapping biochemistry. Elmer McCollum and Marguerite Davis at Wisconsin isolated it in 1913 as \"fat-soluble A,\" distinct from water-soluble B, and the structural characterization by Paul Karrer in Switzerland earned him a share of the 1937 Nobel Prize in Chemistry. George Wald won the 1967 Nobel in Physiology or Medicine for working out the visual cycle role of 11-cis-retinal as the prosthetic group of rhodopsin. The discovery of RAR (1987, Chambon and Dejean groups) and RXR (1990, Mangelsdorf, Evans, Chambon) as nuclear hormone receptors cemented retinoic acid's status as a true hormone, not merely a vitamin.\n\nStructurally, retinol is a 20-carbon diterpenoid built from an isoprenoid polyene chain terminating in a cyclohexenyl ring, with a primary alcohol at the other end. The conjugated double-bond system is why the molecule absorbs visible-adjacent UV and drives vision chemistry. β-Carotene is a C40 symmetrical tetraterpenoid with a central double bond that intestinal β-carotene 15,15'-dioxygenase (BCO1) cleaves to yield two retinal molecules in principle, though the in vivo conversion ratio is far from 2:1 — BCO1 polymorphisms reduce conversion efficiency by up to 70% in a substantial minority of the population (Leung 2009; Lietz 2012), which explains persistent vitamin A insufficiency in populations eating plenty of orange vegetables but no animal foods. Preformed vitamin A (retinyl esters from liver, egg yolk, dairy fat, oily fish, cod liver oil) is absorbed 70-90% efficiently; β-carotene retinol equivalence is roughly 12:1 by mass in mixed diets per the Institute of Medicine's 2001 revision. RDA for adults is 900 μg RAE for men and 700 μg RAE for women; tolerable upper intake level from preformed vitamin A is 3,000 μg/day (10,000 IU) for chronic daily consumption.\n\nAfter intestinal uptake, retinyl esters are incorporated into chylomicrons and delivered primarily to hepatic stellate cells, which are the body's master vitamin A reservoir; the liver of a healthy adult stores roughly 50-500 mg retinol equivalents, enough to buffer weeks to months of dietary inadequacy. When needed, retinol is mobilized from stellate cells, bound to serum retinol binding protein (RBP4) produced in hepatocytes, complexed with transthyretin (TTR) for transport, and delivered to target tissues via the STRA6 membrane receptor (discovered by the Sun lab in 2007). Inside target cells, retinol can be esterified for storage by LRAT, oxidized to retinal by alcohol dehydrogenases and retinol dehydrogenases (RDH), oxidized further to retinoic acid by retinal dehydrogenases (RALDH1/2/3), or consumed in the visual cycle. Cellular retinoic acid binding proteins (CRABP1/2) then chaperone retinoic acid to either the nuclear receptors or the cytochrome P450 CYP26 family for oxidative inactivation.\n\nThree major mechanisms define vitamin A's biology. First, vision. In rod and cone photoreceptors, 11-cis-retinal is covalently linked via Schiff base to a lysine in opsin (rod opsin, and three cone opsins tuned to different wavelengths). Photon absorption isomerizes the cis bond to trans, triggering a conformational change in opsin that activates the G-protein transducin, which activates cGMP phosphodiesterase, dropping cGMP and closing cGMP-gated sodium channels — the visual signal. All-trans-retinal then dissociates, travels to retinal pigment epithelium, gets re-isomerized to 11-cis through the RPE65-centered visual cycle, and returns to photoreceptors. Loss of RPE65 causes Leber congenital amaurosis type 2, corrected by the AAV2 gene therapy voretigene neparvovec (Luxturna, first FDA-approved gene therapy for a genetic eye disease, 2017). Night blindness — the earliest sign of vitamin A deficiency — reflects rod dysfunction because rhodopsin has the highest turnover and depletes first.\n\nSecond, nuclear receptor signaling. All-trans-retinoic acid (ATRA) is the high-affinity ligand for RAR α/β/γ; 9-cis-retinoic acid (debated whether it is endogenously produced in meaningful quantities) is a ligand for RXR α/β/γ. RAR/RXR heterodimers bind DNA at retinoic acid response elements (RAREs, canonical DR5 and DR2 direct repeats) and regulate several hundred genes: HOX genes governing anterior-posterior patterning in embryonic development, Meis genes for limb patterning, genes involved in keratin gene expression, genes driving erythropoiesis and myeloid differentiation, TGF-β pathway components, and dozens of metabolic genes. RXR is a universal heterodimer partner — it pairs with RAR for retinoid signaling, but also with the [vitamin D](/compound/vitamin-d3) receptor (VDR) for vitamin D signaling, with thyroid receptor (TR) for thyroid signaling, and with PPAR α/δ/γ for lipid signaling. This means retinoid status modulates the tone of vitamin D, thyroid, and lipid-sensing networks — a deep cross-talk explaining why retinoid excess can disrupt calcium metabolism and bone biology.\n\nThird, immune and epithelial function. Retinoic acid induces peripheral regulatory T cells (Tregs) and promotes IgA class-switching in gut-associated lymphoid tissue — a major mechanism of mucosal immunity. In WHO-supervised trials, vitamin A supplementation of children 6-59 months in low-resource settings reduced all-cause mortality by approximately 24% (Mayo-Wilson Cochrane 2011), with particular benefit for diarrheal and measles-associated mortality. Vitamin A also governs epithelial differentiation and keratinization; severe deficiency produces follicular hyperkeratosis (rough, bumpy skin), squamous metaplasia of respiratory and urogenital epithelia, and corneal xerophthalmia progressing through Bitot's spots to keratomalacia and corneal perforation — the most common preventable cause of childhood blindness globally.\n\nFour therapeutic retinoids deserve specific mention as they connect the vitamin to modern medicine. Tretinoin (ATRA) is FDA-approved topically for acne and photoaging and systemically for acute promyelocytic leukemia (APL). The APL story is one of the great triumphs of modern oncology: patients with the t(15;17) PML-RARα translocation have a block at the promyelocyte stage; pharmacologic ATRA dissociates the PML-RARα repressor complex and drives terminal differentiation into mature granulocytes — converting a rapidly fatal leukemia into a cancer with >90% long-term survival when ATRA is combined with arsenic trioxide (Hu 2009). Isotretinoin (13-cis-retinoic acid) is the dermatology nuclear option for severe nodular acne; it profoundly shrinks sebaceous glands, reduces sebum production by >80%, and often produces durable remission after a single 16-24 week course. Isotretinoin is a category X teratogen causing characteristic embryopathy (craniofacial, cardiac, CNS, thymic anomalies), necessitating the iPLEDGE program of mandatory contraception and pregnancy testing in the United States. Alitretinoin (9-cis-retinoic acid) is approved in Europe for severe chronic hand eczema. Bexarotene (Targretin) is an RXR-selective retinoid approved for cutaneous T-cell lymphoma.\n\nThe β-carotene smoking cancer signal is a crucial cautionary tale. Two large randomized trials — ATBC in Finnish male smokers (Alpha-Tocopherol, Beta Carotene Cancer Prevention, PMID 8127329, 1994) and CARET in US smokers and asbestos-exposed workers (Beta-Carotene and Retinol Efficacy Trial, PMID 8602180, 1996) — unexpectedly found higher lung cancer incidence and mortality in the β-carotene supplementation arms, roughly 18-28% increased lung cancer risk at 20-30 mg/day β-carotene vs. placebo. The mechanism is still debated (oxidative stress in smoke-exposed lung tissue, pro-oxidant behavior of β-carotene at high tissue concentrations, interaction with tobacco carcinogen activation) but the clinical lesson is clear: high-dose β-carotene supplementation in current or recent smokers is harmful. β-carotene from food is not implicated. Preformed vitamin A at nutritional doses remains safe.\n\nHypervitaminosis A is the main toxicity concern. Acute hypervitaminosis A (liver ingestion of polar bear, seal, or certain fish livers, or industrial accidents) causes headache, nausea, vomiting, vertigo, and skin desquamation. Chronic hypervitaminosis A from long-term supplementation above 10,000 IU/day causes headache, dry skin, alopecia, hepatotoxicity, hepatic fibrosis, pseudotumor cerebri, bone loss and increased fracture risk (Melhus 1998; Michaelsson 2003), and in pregnancy, teratogenicity. The margin between \"adequate\" and \"toxic\" is narrower for preformed vitamin A than for most other vitamins — another reason to prefer B-carotene-containing foods and moderate preformed intake.\n\nBodyHackGuide's take: vitamin A is essential, non-trivially toxic in excess, and almost uniquely among vitamins implicated in nuanced drug-like therapy (APL, severe acne, CTCL). For the healthy adult eating a varied diet with occasional liver, egg yolks, dairy, oily fish, and orange/green vegetables, dietary intake is sufficient and supplementation unnecessary. For populations at risk (low-resource children, severe malabsorption, cystic fibrosis, cholestatic liver disease), targeted supplementation under clinical guidance follows established protocols. High-dose β-carotene supplementation in smokers is contraindicated. Topical and systemic prescription retinoids operate at different doses and through related but distinct receptor biology — consult dermatology or oncology, not a general supplement aisle. The vitamin belongs in the fat-soluble family alongside [vitamin D3](/compound/vitamin-d3), vitamin E, and [vitamin K2](/compound/vitamin-k2), with particular attention to [zinc](/compound/zinc)-dependent retinol binding protein biology.\n", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 5362, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/vitamin-a" }, { "id": "44a83f86-0103-4bf8-aabc-08e64379cd0b", "slug": "vitamin-b12", "name": "Vitamin B12", "aliases": [ "Cobalamin", "B12", "Methylcobalamin", "MeCbl", "Methyl-B12", "Hydroxocobalamin", "OHCbl", "Hydroxy-B12", "Cyanocobalamin", "CNCbl", "Adenosylcobalamin", "AdoCbl", "Dibencozide", "Coenzyme B12" ], "category": "Foundational", "description": "Vitamin B12 (cobalamin) is a water-soluble cobalt-containing vitamin that serves as a coenzyme for two critical enzymes in human metabolism: methionine synthase (cytoplasmic) and L-methylmalonyl-CoA mutase (mitochondrial). It is the largest and most structurally complex vitamin, built around a corrin ring that coordinates a central cobalt atom, with different upper-axial ligands defining the four commercially available forms — methylcobalamin, adenosylcobalamin, hydroxocobalamin, and cyanocobalamin. B12 is synthesized exclusively by bacteria and archaea; humans obtain it almost entirely from animal products (meat, fish, eggs, dairy) because plants do not produce or reliably retain bioactive cobalamin. This evolutionary dependency means that strict vegan and vegetarian diets predictably cause deficiency unless supplemented, and it means that any condition disrupting the remarkably complex absorptive pathway — atrophic gastritis, pernicious anemia, gastric bypass, ileal resection, metformin use, or proton pump inhibitor therapy — creates clinical deficiency even in people eating an omnivorous diet.\n\nFunctionally, vitamin B12 sits at the intersection of methylation, DNA synthesis, hematopoiesis, myelin maintenance, and fatty acid metabolism. Methylcobalamin donates a methyl group to methionine synthase, which remethylates homocysteine to methionine and simultaneously converts 5-methyltetrahydrofolate back to tetrahydrofolate — a reaction that prevents the \"folate trap\" and keeps single-carbon units flowing through the folate cycle for purine, thymidylate, and methyl-donor synthesis. The methionine produced feeds S-adenosylmethionine (SAMe), the universal methyl donor used by dozens of methyltransferases that methylate DNA (affecting gene expression), histones (affecting chromatin state), neurotransmitters (epinephrine from norepinephrine via PNMT), myelin basic protein (affecting nerve sheath integrity), phospholipids (phosphatidylcholine via PEMT), and countless other substrates. Adenosylcobalamin serves L-methylmalonyl-CoA mutase inside mitochondria, catalyzing the isomerization of methylmalonyl-CoA to succinyl-CoA, which enters the citric acid cycle. Without adenosyl-B12, methylmalonic acid accumulates, disrupting odd-chain fatty acid metabolism and contributing to the neurological damage characteristic of B12 deficiency.\n\nClassical B12 deficiency produces a distinctive clinical picture that has been recognized for more than a century: megaloblastic anemia with large, immature red blood cells reflecting disrupted DNA synthesis in bone marrow; glossitis with a smooth, beefy-red tongue; gastrointestinal symptoms; and — most concerning — progressive neurological dysfunction known as subacute combined degeneration of the spinal cord. The neurological picture includes symmetric paresthesias (classically starting in the feet), impaired proprioception and vibratory sense, gait ataxia, weakness, optic neuropathy, and in advanced cases cognitive impairment, psychiatric symptoms, and frank dementia. The critical lesson from historical case series is that neurological damage can occur without anemia — and can become irreversible if deficiency is prolonged. Folic acid supplementation can mask the hematological changes while neurological deterioration continues, which is why high-dose folic acid in fortified foods and supplements has generated ongoing concern about missed B12 diagnoses in the elderly.\n\nFor BodyHackGuide readers, the practical reality of B12 is that deficiency and insufficiency are far more common than most people realize. The classic at-risk groups — elderly with atrophic gastritis, vegans and long-term vegetarians, patients on metformin, patients on chronic PPIs, post-bariatric-surgery patients — together comprise a substantial fraction of adults. Serum B12 testing is insensitive and misses subclinical deficiency; methylmalonic acid (MMA) and homocysteine are more reliable functional markers, and holotranscobalamin (active B12) is superior where available. Oral supplementation at 500-1000 mcg/day is generally sufficient even for people lacking intrinsic factor, because passive diffusion absorbs roughly 1-2% of any oral dose regardless of the active receptor-mediated pathway. For active deficiency, parenteral hydroxocobalamin (1000 mcg IM weekly, then monthly) remains the standard and is genuinely life-changing for people with pernicious anemia or severe malabsorption. This page examines the cobalamin forms (and the overhyped claims around MTHFR and methyl-B12), absorption pathophysiology, testing, the homocysteine-lowering trials (VITACOG, VITATOPS, B-PROOF, VITAL), and practical dosing — with explicit attention to the elderly and vegan populations where B12 has the largest quality-of-life impact.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/vitamin-b12" }, { "id": "4c265f7b-dd7a-40d0-9803-38486e690c72", "slug": "vitamin-b6", "name": "Vitamin B6", "aliases": [ "B6", "Pyridoxine", "Pyridoxal", "Pyridoxamine", "Pyridoxine HCl", "Pyridoxal 5-phosphate", "PLP", "P5P", "Pyridoxal-5-phosphate", "Pyridoxamine 5-phosphate", "Pyridoxine 5-phosphate", "PNP", "PMP", "Vitamin B complex", "MK-677 B6", "P-5-P" ], "category": "Vitamin", "description": "Vitamin B6 is a water-soluble B-vitamin family comprising six interconvertible vitamers — pyridoxine, pyridoxal, pyridoxamine, and their phosphorylated forms — that converge on the single active coenzyme pyridoxal 5-phosphate (PLP, also written P5P). PLP is a cofactor for more than 150 enzymes, predominantly in amino acid metabolism but also in carbohydrate metabolism, lipid metabolism, neurotransmitter synthesis, heme biosynthesis, and one-carbon/homocysteine handling — a breadth that makes B6 an unusually sprawling biochemical utility mineral among the vitamins. The adult RDA is 1.3 mg/day (ages 19–50), rising to 1.7 mg for men and 1.5 mg for women over 50, 1.9 mg for pregnancy, 2.0 mg for lactation, and the tolerable upper limit for synthetic pyridoxine is 100 mg/day based on the well-documented risk of sensory peripheral neuropathy from chronic high-dose use. B6 deficiency is uncommon in isolated form in Western populations but recurs in several specific contexts: chronic alcohol use, isoniazid therapy for tuberculosis (the classic iatrogenic deficiency), theophylline use, oral contraceptive use (mild), hemodialysis, inflammatory bowel disease, and rare genetic disorders of B6 metabolism. When deficiency is symptomatic it produces a distinctive picture of microcytic anemia (from impaired heme synthesis via ALA synthase which requires PLP), seborrheic dermatitis, glossitis, angular cheilitis, peripheral neuropathy, and in severe cases seizures — the seizure connection underlying the classical pediatric syndrome of pyridoxine-dependent epilepsy (PDE, ALDH7A1 mutations), where infants present with intractable seizures that respond dramatically to pharmacologic pyridoxine doses. The supplement and clinical uses of B6 cluster in several domains. Pyridoxine is used as an antidote for acute isoniazid overdose (a gram-for-gram dose of pyridoxine matching the isoniazid ingested) and to prevent isoniazid neuropathy during TB treatment. Pyridoxine plus doxylamine (Diclegis, Bonjesta) is a first-line treatment for nausea and vomiting of pregnancy, with multiple randomized trials supporting efficacy and safety. Pyridoxine is combined with folate and B12 as the \"homocysteine-lowering stack\" with variable cardiovascular outcomes as extensively discussed in the [Folate](/compound/folate) entry. B6 is a standard part of pediatric metabolic rescue in suspected inborn errors of metabolism (pyridoxine-dependent epilepsy trial, cystathionine beta-synthase deficiency with homocystinuria). B6 has been explored in carpal tunnel syndrome with mixed evidence (Ellis popularized the high-dose approach in the 1980s, though controlled trials have been equivocal), premenstrual syndrome with modest signal, and hyperemesis gravidarum with strong signal. The overarching therapeutic caution for B6 is the neuropathy ceiling: unlike most water-soluble vitamins which are forgiving at pharmacologic doses, chronic B6 supplementation above approximately 200 mg/day can produce a progressive sensory ganglionopathy with burning dysesthesias, gait unsteadiness, and positive sensory symptoms that may not fully reverse on stopping — the Schaumburg 1983 series documented this syndrome at chronic multi-gram dosing and subsequent analyses have confirmed neuropathy risk at sustained doses above the UL. Food sources concentrate in poultry, fish (tuna, salmon), potatoes and other starchy tubers, bananas, chickpeas, fortified cereals, beef liver, and pistachios. See also [Folate](/compound/folate) and [Vitamin B12](/compound/vitamin-b12) for the homocysteine-lowering partnership, [Glycine](/compound/glycine) for the broader amino acid metabolism picture, [Magnesium](/compound/magnesium) for the PLP-magnesium kinase activity link, [Zinc](/compound/zinc) for the enzyme cofactor interaction context, and [Alpha-Lipoic Acid](/compound/alpha-lipoic-acid) for the redox-cofactor discussion. This overview is educational only and is not medical advice — B6 has one of the narrower therapeutic windows among common vitamins given the neuropathy risk at chronic high-dose use.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/vitamin-b6" }, { "id": "1953b7a2-4bd3-4b3e-9dc1-b6467acb3400", "slug": "vitamin-c", "name": "Vitamin C", "aliases": [ "Ascorbic acid", "L-ascorbic acid", "Ascorbate", "Sodium ascorbate", "Calcium ascorbate", "Magnesium ascorbate", "Ester-C", "Liposomal vitamin C", "Ascorbyl palmitate", "Mineral ascorbate" ], "category": "Foundational", "description": "Vitamin C (L-ascorbic acid) is a water-soluble essential vitamin that humans, unlike most other mammals, cannot synthesize endogenously due to an inactivating mutation in the gulonolactone oxidase (GULO) gene acquired approximately 61 million years ago in a primate ancestor. This evolutionary quirk—shared with guinea pigs, some bats, and most songbirds—makes dietary vitamin C intake obligatory for human survival and explains why scurvy, the syndrome of severe vitamin C deficiency, has shaped human history so dramatically, from the maritime scourges of the Age of Sail (cured famously by James Lind's 1747 citrus trial, among the first controlled clinical experiments) to wartime famines and contemporary nutritionally precarious populations. Modern diets in developed countries usually provide adequate vitamin C to prevent clinical scurvy, but subclinical inadequacy remains common—national survey data suggest 5-15% of U.S. adults have plasma concentrations consistent with biochemical deficiency, with higher rates among smokers, older adults, individuals with low fruit/vegetable intake, institutionalized populations, and those with malabsorption syndromes.\n\nThe recommended daily intake for healthy adults is 90 mg for men and 75 mg for women per the U.S. Institute of Medicine, with an additional 35 mg recommended for smokers due to increased oxidative stress and ascorbate turnover. These values are set to maintain plasma ascorbate at concentrations that prevent scurvy with a comfortable margin, not to improve health or address the extensive literature suggesting higher intakes may provide additional benefit. Linus Pauling's influential (and controversial) advocacy in the 1970s for gram-level daily doses popularized the \"megadose\" concept and launched decades of research into vitamin C at supplementation levels far above the RDA. Subsequent pharmacokinetic studies by Mark Levine's group at NIH (Levine et al. and subsequent papers) established that oral absorption of vitamin C is tightly regulated: absorption approaches saturation around 200-400 mg in a single dose, plasma concentrations plateau at approximately 80 μmol/L at intakes of 400 mg/day, and any additional oral intake is excreted unchanged in urine. This saturation explains why doses above ~400-500 mg daily offer diminishing return for most systemic purposes, and why pharmacologic plasma concentrations can only be achieved intravenously—a fact central to the ongoing debate about high-dose IV vitamin C in cancer, sepsis, and critical illness.\n\nVitamin C's biological roles center on its function as an enzyme cofactor (an electron donor for specific mono- and dioxygenases) and as a direct antioxidant/reducing agent. The most well-established cofactor roles are in collagen synthesis—where prolyl and lysyl hydroxylases require vitamin C to hydroxylate proline and lysine residues on nascent collagen strands, stabilizing the triple-helix structure (deficiency of this activity causes the connective tissue fragility characteristic of scurvy: petechiae, gum bleeding, wound dehiscence, joint pain)—and in catecholamine synthesis, where dopamine β-hydroxylase converts dopamine to norepinephrine. Vitamin C is also required for carnitine synthesis (hence the fatigue of advanced deficiency), hepatic monooxygenase systems, peptide amidation, and the activity of several important hypoxia-inducible factor (HIF) hydroxylases and the ten-eleven translocation (TET) family of dioxygenases, which demethylate DNA and regulate epigenetic state. This last set of functions links vitamin C status to fundamental questions of aging biology, gene regulation, and cancer—areas of active investigation.\n\nAs an antioxidant, vitamin C donates electrons to neutralize reactive oxygen species (ROS) in the aqueous compartment of cells and plasma, recycles vitamin E tocopherol radicals back to reduced form (complementing vitamin E's role in lipid membranes), and can reduce iron and copper to their more bioavailable but also potentially pro-oxidant states. This last property is the basis of the pro-oxidant activity vitamin C displays at high pharmacologic concentrations—paradoxically, when intracellular iron is abundant and vitamin C plasma concentrations are elevated (as occurs with IV administration but not oral), hydrogen peroxide can be generated in tumor tissue where it damages cancer cells preferentially. This mechanism is the pharmacological basis for contemporary interest in IV vitamin C as an adjuvant in cancer treatment, a topic that has evolved considerably from the conflicting 1970s-1980s oral megadose trials to more recent studies using pharmacologic IV concentrations.\n\nThe clinical evidence for vitamin C supplementation spans scurvy prevention (trivial at typical intakes), common-cold duration shortening (modest, consistent across the Hemilä meta-analyses), immune support (reasonable in deficient or stressed populations), wound healing (meaningful in surgical or burn patients), preeclampsia and preterm birth prevention (disappointing in large RCTs), cardiovascular disease prevention (mixed observational data, negative interventional data in meta-analyses), cataract prevention (modest suggestive data), and a still-evolving role in sepsis and critical illness (controversial, with some large trials negative after Marik's initial enthusiastic report). The most durable clinical claim is that vitamin C supplementation meaningfully reduces common cold duration in adults (by approximately 8% across pooled trials) and reduces cold incidence in populations subject to high physical stress such as athletes, soldiers, and skiers (Hemilä and Chalker, PMID 23440782). For most other indications, the evidence supports vitamin C as a helpful supplement in the context of deficiency or oxidative stress rather than a therapeutic agent with strong disease-modifying effects.\n\nFor BodyHackGuide users, vitamin C occupies a specific niche in the foundational stack. The cost is trivial—pure ascorbic acid powder is among the cheapest supplements per gram—and the safety profile at reasonable doses is excellent. Common supplementation errors include: (1) taking doses of 1,000+ mg in a single dose and assuming full absorption (absorption saturates; most is excreted unchanged), (2) pursuing pharmacologic oral doses expecting pharmacologic plasma concentrations (impossible without IV administration), (3) relying on vitamin C alone as an \"antioxidant\" strategy (the antioxidant network requires multiple compounds working together—see also /compound/vitamin-d and /compound/glutathione), (4) timing vitamin C with iron supplements without realizing both absorption enhancement and potential pro-oxidant concerns, and (5) neglecting dietary sources. Whole fruits and vegetables deliver vitamin C alongside flavonoids, carotenoids, and fiber that may contribute synergistically—500 mg from oranges, berries, and peppers is rarely equivalent to 500 mg isolated ascorbate in downstream effects.\n\nPractical supplementation targets: 200-500 mg daily in divided doses is sufficient for most purposes, with upward adjustments of 500-2,000 mg daily during acute viral illness or periods of heavy physical stress. Doses above 2,000 mg daily offer minimal additional systemic benefit except via IV administration for defined indications. This monograph addresses form selection, timing, synergy with other nutrients, the IV vitamin C landscape, and safety considerations for specific populations. For related foundational support, see /compound/glycine (collagen synthesis partner), /compound/vitamin-d, /compound/zinc (classic immune pairing), and /compound/glutathione (antioxidant network).", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 51, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/vitamin-c" }, { "id": "18cf65ed-56a2-4fff-a385-be9bb7a0b5be", "slug": "vitamin-d", "name": "Vitamin D", "aliases": [ "Cholecalciferol", "Vitamin D3", "Ergocalciferol", "Vitamin D2", "Calcitriol", "1,25-dihydroxyvitamin D", "25-hydroxyvitamin D", "Calciferol", "Sunshine vitamin" ], "category": "Foundational", "description": "Vitamin D is a fat-soluble secosteroid hormone (functionally a hormone rather than a traditional vitamin) with profound and pleiotropic effects across virtually every major organ system. Despite its name, vitamin D is synthesized endogenously in the skin from 7-dehydrocholesterol via UVB radiation exposure and functions through nuclear receptor-mediated gene expression modulation in hundreds of tissues. Understanding vitamin D requires recognizing its dual identity as both a steroid hormone (calcitriol, the active metabolite) and a nutritional requirement in modern indoor-living populations where cutaneous synthesis is frequently inadequate.\n\nBiochemistry and forms: Vitamin D exists in two principal forms in human physiology. Vitamin D3 (cholecalciferol) is synthesized in skin from 7-dehydrocholesterol upon UVB exposure and also obtained from animal food sources (fatty fish, egg yolks, liver, and fortified dairy). Vitamin D2 (ergocalciferol) is derived from plant and fungal sources, particularly UV-exposed mushrooms. Both forms undergo hepatic 25-hydroxylation to form 25-hydroxyvitamin D [25(OH)D], the major circulating form measured in clinical practice. Renal 1-alpha-hydroxylation generates the active hormone 1,25-dihydroxyvitamin D [1,25(OH)2D, calcitriol], which binds the vitamin D receptor (VDR) in target tissues. D3 is generally more effective than D2 at raising and maintaining serum 25(OH)D levels, making cholecalciferol the preferred supplemental form.\n\nCutaneous synthesis physiology: Adequate cutaneous vitamin D synthesis requires UVB radiation (wavelength 290-315 nm) exposure to skin, which converts 7-dehydrocholesterol to previtamin D3 and thence to cholecalciferol. Synthesis efficiency depends on: latitude (minimal UVB reaches earth surface above approximately 37 degrees latitude during winter months); skin pigmentation (darker skin requires 3-6x longer exposure for equivalent synthesis); age (reduced 7-dehydrocholesterol in aging skin); season; time of day (midday most effective); sunscreen use (blocks UVB); clothing coverage. Modern lifestyle patterns (indoor work, sun avoidance for cancer prevention, clothing norms, higher latitudes of population centers) have produced widespread vitamin D insufficiency — estimated 40-75% of adults globally have serum 25(OH)D below optimal thresholds.\n\nSerum 25(OH)D levels and thresholds: Clinical assessment centers on serum 25(OH)D measurement with commonly used thresholds:\n- Severe deficiency: <10 ng/mL (<25 nmol/L) — associated with osteomalacia, severe immune dysfunction\n- Deficiency: 10-20 ng/mL (25-50 nmol/L) — Institute of Medicine threshold for inadequate\n- Insufficiency: 20-30 ng/mL (50-75 nmol/L) — Endocrine Society threshold\n- Sufficiency: 30-50 ng/mL (75-125 nmol/L) — commonly recommended range\n- Optimal (some recommendations): 40-60 ng/mL (100-150 nmol/L)\n- Upper optimal: 60-80 ng/mL (150-200 nmol/L) — some longevity-focused physicians target\n- Toxicity risk: >150 ng/mL (>375 nmol/L) — rare with standard supplementation\nDifferent organizations recommend different thresholds reflecting ongoing scientific debate about optimal levels. Holick 2011 Endocrine Society clinical practice guidelines (PMID 21646368) remain influential reference.\n\nClassical bone and calcium homeostasis: Vitamin D's classical function is calcium and phosphate homeostasis supporting bone mineralization. Calcitriol enhances intestinal calcium absorption, regulates renal calcium reabsorption, and works with parathyroid hormone and calcitonin to maintain serum calcium. Severe vitamin D deficiency causes rickets in children (failure of bone mineralization) and osteomalacia in adults (demineralization with bone pain and fractures). Less severe deficiency contributes to osteoporosis, fracture risk, and secondary hyperparathyroidism.\n\nExtra-skeletal functions (the modern frontier): Beyond bone, vitamin D receptors are expressed in hundreds of tissues, and the compound regulates thousands of genes. Clinically relevant extra-skeletal functions include: innate and adaptive immune modulation (antimicrobial peptide expression, T-cell regulation, autoimmunity); cardiovascular function (endothelial function, blood pressure regulation, cardiac function); insulin sensitivity and glucose metabolism; cell proliferation and differentiation (potentially cancer-relevant); muscle function (receptor present in skeletal muscle; related to sarcopenia and falls); mood regulation (possible role in depression); neurological function (neuroprotection, cognition).\n\nClinical evidence for extra-skeletal benefits: The evidence for vitamin D in extra-skeletal outcomes is characterized by strong observational associations (low 25(OH)D associated with many adverse health outcomes) but mixed randomized trial results. The VITAL trial (Manson 2019 PMID 30415629) in 25,871 U.S. adults found no significant reduction in cardiovascular events or cancer with 2000 IU/day vs. placebo over 5.3 years. The D-Health trial (Neale 2022) in 21,315 older Australians found no significant reduction in all-cause mortality with monthly 60,000 IU vs. placebo. The D2d trial (Pittas 2019 PMID 31173679) found no significant reduction in diabetes incidence in prediabetes. These major trials have tempered enthusiasm for vitamin D as a broad preventive intervention. However, specific findings favor vitamin D: reduced respiratory infection rates (Jolliffe 2021 Lancet PMID 33798465); improved bone health and falls prevention in deficient populations; possible benefit in COVID-19 severity (Murai 2021); modest fracture prevention. The picture is nuanced: vitamin D correction in deficient individuals provides clear benefit; routine high-dose supplementation in replete individuals shows smaller or absent effects.\n\nMortality associations: Observational studies consistently associate low 25(OH)D with increased all-cause mortality. Chowdhury 2014 BMJ meta-analysis (PMID 24690623) of 849,412 participants found U-shaped relationship with lowest mortality at 25(OH)D around 30-40 ng/mL. However, interventional trials targeting mortality endpoints have produced mixed results. The mechanism of observational association may involve reverse causation (sick people have lower vitamin D), confounding (sick people have less sun exposure and worse nutrition), or genuine causal effect. The practical implication is that correction of deficiency is clearly appropriate; whether supplementation to \"optimal\" levels above routine sufficiency provides additional mortality benefit remains debated.\n\nRegulatory status and availability: Vitamin D is widely available without prescription in most countries. Supplementation is standard in pediatrics (prevention of rickets), geriatrics (falls and fracture prevention), and many other contexts. Pharmaceutical-grade preparations (D3 and calcitriol) available for specific medical applications. Cost is minimal — quality D3 supplements typically cost under $10 per month even at higher doses. The combination of low cost, wide availability, favorable safety profile, and genuine clinical benefit in deficient populations makes vitamin D one of the most prescribed and recommended supplements globally.\n\nPositioning in longevity stacks: Vitamin D represents a foundational element of evidence-based longevity supplementation, alongside /compound/omega-3-fatty-acids, /compound/creatine, magnesium, and quality protein. The case for vitamin D supplementation is particularly strong for: individuals with documented deficiency (correction definitely beneficial); those at high risk of deficiency (higher latitudes, darker skin, limited sun exposure, older adults); those with conditions responsive to vitamin D (osteoporosis, specific autoimmune conditions). Routine supplementation in clearly replete individuals with no risk factors is less clearly beneficial but generally harmless at moderate doses.\n\nSynergistic nutrients — vitamin K2 relationship: Vitamin D increases calcium absorption but vitamin K2 (particularly MK-7) directs calcium to bone rather than soft tissues. The combination addresses concerns about vitamin D-related vascular calcification and provides complete bone and cardiovascular support. Co-supplementation of /compound/vitamin-d and /compound/vitamin-k2 is standard in longevity-focused protocols.\n\nHistorical context: Vitamin D was discovered in 1922 through Edward Mellanby's rickets research. The 1930s-1950s saw vitamin D fortification of milk eliminating endemic rickets. The late 20th century brought understanding of extra-skeletal actions. The 2000s-2010s saw dramatic expansion of vitamin D measurement in clinical practice and widespread supplementation. The 2020s have seen more nuanced understanding from major randomized trials, with recognition that correction of deficiency matters more than universal high-dose supplementation.\n\nAs of 2026, vitamin D remains one of the most-studied and most-supplemented nutrients globally, with evidence supporting its role in correcting deficiency and specific therapeutic applications, alongside ongoing research into optimal dosing and which populations benefit most from various intervention strategies.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 86, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/vitamin-d" }, { "id": "89cbb6de-7aa3-4f99-b899-5994a73bec4c", "slug": "vitamin-e", "name": "Vitamin E", "aliases": [ "Tocopherol", "Alpha-tocopherol", "α-tocopherol", "d-alpha-tocopherol", "RRR-alpha-tocopherol", "dl-alpha-tocopherol", "all-rac-alpha-tocopherol", "Synthetic alpha-tocopherol", "Beta-tocopherol", "Gamma-tocopherol", "Delta-tocopherol", "Mixed tocopherols", "Tocotrienol", "Alpha-tocotrienol", "Beta-tocotrienol", "Gamma-tocotrienol", "Delta-tocotrienol", "Tocopherol acetate", "Tocopheryl acetate", "α-tocopheryl acetate", "Alpha-tocopherol acetate", "Tocopheryl succinate", "Tocopherol succinate", "Alpha-tocopheryl succinate", "Tocopheryl nicotinate", "Tocopherol hemisuccinate", "Vitamin E TPGS", "d-alpha-tocopheryl polyethylene glycol succinate", "Anti-sterility vitamin", "Anti-infertility factor", "Factor X (original Evans)" ], "category": "Vitamin", "description": "\nVitamin E is the collective name for eight naturally occurring fat-soluble molecules — four tocopherols (α, β, γ, δ) and four tocotrienols (α, β, γ, δ) — sharing a chromanol head group and a 16-carbon isoprenoid side chain. Tocopherols have a saturated side chain; tocotrienols have three trans double bonds in the same chain, giving them distinct membrane packing and lipid-raft interactions. All eight forms were historically considered \"vitamin E\" by their ability to rescue the original Evans 1922 rat fertility assay — adult female rats fed a strictly vitamin-E-free diet developed infertility that reversed on re-feeding with a factor extracted from wheat germ oil, later named α-tocopherol from Greek roots meaning \"to bring forth offspring.\" Current nutritional science privileges α-tocopherol as the sole form meeting vitamin E requirements in humans, because the hepatic α-tocopherol transfer protein (α-TTP) selectively loads α-tocopherol into VLDL for export to peripheral tissues while preferentially degrading the other seven isomers through cytochrome P450-mediated ω-hydroxylation (CYP4F2 is the major enzyme). This discrimination, first characterized by the Arita group (Nature 1995; α-TTP crystal structure), is why α-tocopherol alone is used to define the RDA (15 mg/day for adults) and why isolated α-tocopherol supplementation suppresses serum γ-tocopherol levels — a potential issue given that γ-tocopherol has distinct antioxidant properties and can neutralize peroxynitrite in ways α-tocopherol cannot.\n\nStructurally, α-tocopherol is 2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)chroman-6-ol — a chromanol head group fully methylated at positions 5, 7, and 8, with a 16-carbon phytyl-derived isoprenoid tail. The phenolic 6-OH is the business end of the antioxidant chemistry; when a lipid peroxyl radical (LOO•) abstracts the O-H hydrogen, it generates a lipid hydroperoxide (LOOH, less reactive and more easily cleared) and the relatively stable α-tocopheroxyl radical (α-TO•). The tocopheroxyl radical is then reduced back to α-tocopherol by [vitamin C](/compound/vitamin-c) (ascorbate) at the aqueous-lipid interface, by ubiquinol ([CoQ10](/compound/coq10)), or by glutathione — and the regenerated α-tocopherol returns to the membrane to intercept another peroxyl radical. This is the \"redox recycling\" biology that makes vitamin E a chain-breaking antioxidant rather than a stoichiometric sacrifice — one α-tocopherol molecule can neutralize hundreds of peroxyl radicals over its functional lifetime given adequate reducing co-nutrients.\n\nNatural α-tocopherol is the single RRR stereoisomer (the biologically active enantiomer, previously designated d-α-tocopherol). Synthetic α-tocopherol produced by chemical synthesis is all-rac-α-tocopherol (previously dl-α-tocopherol), a racemic mixture of all eight possible stereoisomers; only the RRR form is fully active, so synthetic is typically assigned 0.74× the biological activity of natural per unit mass by the Institute of Medicine's 2000 conversion. Esters (α-tocopheryl acetate, α-tocopheryl succinate, α-tocopheryl nicotinate) are prodrug forms that are hydrolyzed in the gut or tissue by esterases to free α-tocopherol; the ester forms are more chemically stable against oxidation during storage. Tocopheryl acetate is the most common supplement form. The unit convention is: 1 mg RRR-α-tocopherol = 1 α-tocopherol equivalent (α-TE) = 1.49 IU. Synthetic all-rac-α-tocopherol: 1 mg = 1 IU. So a 400 IU supplement of synthetic dl-α-tocopheryl acetate provides 400 mg of the racemic mixture and roughly 180 mg of bioactive RRR-equivalent.\n\nIntestinal absorption of vitamin E requires dietary fat and bile acids; free vitamin E (and ester-hydrolyzed free forms) partitions into mixed micelles, enters enterocytes primarily via NPC1L1 (the same transporter ezetimibe inhibits) and passive diffusion, is packaged into chylomicrons with other fat-soluble vitamins and dietary triglycerides, and reaches the liver. Hepatocytes express α-TTP in the cytosol; α-TTP binds α-tocopherol with roughly 10- to 20-fold higher affinity than other isoforms and loads it into nascent VLDL for export to peripheral tissues. Non-α-tocopherol isoforms (γ, δ, β, tocotrienols) are preferentially directed to hepatic CYP4F2-mediated ω-hydroxylation, generating CEHCs (carboxyethyl hydroxychromans) and other polar metabolites that are urinary-excreted. The consequence: steady-state plasma α-tocopherol is typically 20-35 μmol/L, while γ-tocopherol is 2-5 μmol/L despite γ-tocopherol being a more abundant isoform in the US food supply due to soybean oil dominance.\n\nHepatic α-TTP function determines vitamin E sufficiency. Mutations in α-TTP (TTPA gene) cause ataxia with vitamin E deficiency (AVED Ouahchi Nature Genetics 1995), an autosomal recessive neurodegenerative disease with spinocerebellar phenotype resembling Friedreich ataxia. Without functional α-TTP, α-tocopherol cannot be retained after hepatic uptake, is rapidly degraded, and tissue vitamin E falls. Patients develop progressive ataxia, dysarthria, dysmetria, and areflexia — but the striking fact is that high-dose α-tocopherol supplementation (800-2000 mg/day) can reverse progression and stabilize or improve neurologic status, establishing both the essentiality of α-tocopherol and the tractability of isolated deficiency as a therapeutic target. Abetalipoproteinemia (MTP mutations) produces similar functional vitamin E deficiency through failure of chylomicron and VLDL assembly, and is similarly managed with mega-dose α-tocopherol supplementation.\n\nVitamin E's clinical biology has produced a famously mixed evidence base with some signal trials and many negative outcome trials. The HOPE trial (NEJM 2000) randomized 9,541 high-risk cardiovascular patients to α-tocopherol 400 IU/day vs. placebo for 4.5 years; no benefit on cardiovascular outcomes. The Women's Health Study (Lee 2005 JAMA) randomized 39,876 healthy women to α-tocopherol 600 IU every other day for 10 years; no benefit on CV events, no effect on total cancer, borderline reduction in CV mortality. The SELECT trial (Klein 2011 JAMA) randomized 35,533 men to α-tocopherol 400 IU/day, selenium 200 μg/day, both, or placebo for 7 years; the α-tocopherol arm showed a 17% increase in prostate cancer incidence vs. placebo at 5-7 years post-randomization. The Miller 2005 meta-analysis (Annals of Internal Medicine, PMID 15537682) of 19 RCTs (135,967 participants) examining high-dose vitamin E supplementation found a dose-dependent increase in all-cause mortality at doses ≥400 IU/day. These collectively argue strongly against prophylactic high-dose α-tocopherol supplementation in healthy adults.\n\nPositive signals exist in specific contexts. The PIVENS trial (Sanyal 2010 NEJM) randomized 247 non-diabetic adults with biopsy-proven nonalcoholic steatohepatitis (NASH) to α-tocopherol 800 IU/day, pioglitazone, or placebo for 96 weeks; the vitamin E arm produced a 43% resolution-of-NASH rate vs. 19% placebo, a meaningful and clinically significant result that has shaped AASLD guidelines recommending vitamin E for biopsy-proven NASH in non-diabetic adults. The TEAM-AD trial (Dysken 2014 JAMA, PMID 24381967) randomized 613 patients with mild-to-moderate Alzheimer's disease to α-tocopherol 2,000 IU/day, memantine, combination, or placebo; the α-tocopherol arm showed slowed functional decline on ADCS-ADL by approximately 6.2 units over 2 years vs. placebo, suggesting a modest but real benefit. The pooled evidence supports alpha-tocopherol for slowing progression of mild-to-moderate AD at high doses, though the effect is modest and safety with anticoagulants requires attention. ATBC's 16% reduction in prostate cancer in Finnish male smokers on α-tocopherol 50 mg/daywas not confirmed in SELECT and is generally considered a chance finding.\n\nMixed tocopherols and tocotrienols have generated renewed interest. γ-tocopherol (the most abundant vitamin E isoform in the US food supply) has distinct antioxidant chemistry — it can trap peroxynitrite (RNOS) through its free 5-position, which α-tocopherol cannot — and there is epidemiologic and mechanistic work suggesting γ-tocopherol may have anti-inflammatory and anti-cancer effects (Campbell 2003; Jiang 2014). Tocotrienols, particularly δ- and γ-tocotrienols from palm oil and annatto, have been studied for effects on cholesterol synthesis (HMG-CoA reductase post-translational regulation), breast cancer cell biology in vitro, and osteoporosis — though human data are limited and mechanism-over-outcome-trial. Mixed tocopherol/tocotrienol supplements are popular in the biohacking and integrative medicine communities; evidence that they outperform isolated α-tocopherol for defined outcomes is limited.\n\nBodyHackGuide's take: vitamin E is essential, but the sweet spot for adult supplementation in most populations is dietary adequacy (15 mg α-tocopherol equivalents per day, easily met by nuts, seeds, vegetable oils, whole grains, and leafy greens), rather than therapeutic supplementation. Exceptions with defined benefit: NASH in non-diabetic adults (800 IU/day under hepatology supervision), mild-to-moderate Alzheimer's (2,000 IU/day with attention to bleeding risk), and rare AVED or abetalipoproteinemia (specialist-directed mega-dose replacement). High-dose α-tocopherol supplementation in healthy populations has shown harm signals (SELECT prostate cancer, Miller meta-analysis all-cause mortality) and no convincing benefit for CV prevention. Vitamin E belongs in the fat-soluble family alongside [vitamin A](/compound/vitamin-a), [vitamin D3](/compound/vitamin-d3), and [vitamin K2](/compound/vitamin-k2); co-stacking requires attention to high-dose α-tocopherol blunting vitamin K-dependent carboxylation (the anticoagulant effect) and RXR heterodimer crosstalk affecting vitamin A / vitamin D signaling.\n", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 6280, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/vitamin-e" }, { "id": "04363e30-166d-48ab-8536-b7818603b1b1", "slug": "vitamin-k2", "name": "Vitamin K2", "aliases": [ "Menaquinone", "MK-4", "Menaquinone-4", "MK-7", "Menaquinone-7", "MenaQ7", "Menatetrenone", "Menaquinone-9", "MK-9", "Vitamin K" ], "category": "Foundational", "description": "Vitamin K2 refers to the menaquinone family of fat-soluble vitamins—structurally distinct from but functionally related to vitamin K1 (phylloquinone, found in leafy greens). Menaquinones are designated MK-n based on the length of their isoprenoid side chain, with MK-4, MK-7, and MK-9 the most nutritionally relevant forms. While vitamin K was originally discovered through its role in blood coagulation (Henrik Dam, 1929 Nobel laureate, identified the \"Koagulations-vitamin\" after observing hemorrhagic disease in chicks fed fat-free diets), research over the past two decades has revealed that vitamin K—and particularly K2—serves roles extending far beyond coagulation, with important functions in bone mineralization, arterial health, insulin sensitivity, and possibly cognitive function. This expanded understanding has elevated K2 from a quiet background nutrient to one of the most discussed \"foundational stack\" compounds in contemporary biohacking and longevity communities.\n\nThe biochemistry that links vitamin K's many functions is deceptively simple. Vitamin K serves as an obligatory cofactor for a single enzyme—gamma-glutamyl carboxylase (GGCX)—which adds a carboxyl group (COOH) to specific glutamate (Glu) residues on target proteins, converting them to gamma-carboxyglutamate (Gla) residues. This carboxylation creates calcium-binding pockets that enable the protein to bind calcium ions and perform its physiological function. The family of vitamin K-dependent proteins (VKDPs) spans roughly 17 known members in humans, including the classical coagulation factors II (prothrombin), VII, IX, and X; the anticoagulants proteins C, S, and Z; osteocalcin (bone-gla-protein, produced by osteoblasts and required for proper mineralization); matrix Gla protein (MGP, which prevents calcium deposition in vascular smooth muscle and cartilage); growth arrest-specific protein 6 (Gas6, involved in cell survival and clearance); and periostin and Gla-rich protein (roles still under investigation). Without adequate vitamin K, these proteins remain in their undercarboxylated (uncarboxylated) state—present in plasma and tissue but functionally inert.\n\nThe critical observation driving the K2 renaissance is that different vitamin K forms differ substantially in their tissue distribution and functional reach. Vitamin K1 (phylloquinone) is taken up preferentially by the liver, where it supports hepatic coagulation factor carboxylation—the liver's priority use for vitamin K, which is protected even when peripheral tissues are depleted. K1 reaches extrahepatic tissues (bone, arterial wall, brain, pancreas) in smaller and less reliable amounts. Vitamin K2, especially long-chain menaquinones like MK-7, has fundamentally different pharmacokinetics: absorbed from the intestine and packaged into lipoprotein particles, MK-7 has a plasma half-life of approximately 72 hours (versus about 1-2 hours for K1), reaches meaningful concentrations in extrahepatic tissues, and sustains carboxylation activity in bone and vascular tissue over extended periods. MK-4, in contrast, has a very short half-life (~1-3 hours) but is converted from dietary K1 in some peripheral tissues and shows potent local effects when dosed at pharmacologic levels (15-45 mg/day, as used in Japanese osteoporosis pharmacotherapy under the brand name Glakay). The practical implication: for sustained extrahepatic vitamin K activity supporting bone and vascular tissue, MK-7 is typically preferred as a once-daily supplement; MK-4 is used where high pharmacologic doses are intended or where multiple daily dosing is acceptable.\n\nDietary sources of K2 are concentrated in fermented foods and animal products. Natto (fermented soybeans, produced with Bacillus subtilis natto) is by far the richest known food source of MK-7, with approximately 1,000 mcg per 100 g serving—orders of magnitude more than any other commonly consumed food. Hard aged cheeses (Gouda, Edam, Brie) provide meaningful MK-8 and MK-9 from bacterial fermentation during aging; pasture-raised egg yolks, grass-fed butter and meat, liver, and other organ meats provide MK-4 that mammals synthesize from ingested K1. Contemporary industrial food systems—grain-fed livestock, pasteurized dairy, minimal fermented-food consumption outside Japan and parts of Europe—deliver dramatically less K2 than ancestral diets or traditional cuisines where these foods featured prominently. Estimates place typical Western K2 intake at under 40 mcg/day, compared with 100+ mcg/day in populations consuming traditional fermented and animal-product-rich diets, and potentially 500+ mcg/day for daily natto consumers.\n\nThe evidence base for vitamin K2 supplementation spans three major domains: bone health, cardiovascular health, and the emerging story of K2's role alongside vitamin D and calcium. The Rotterdam Study (Geleijnse et al., PMID 15514282) followed 4,807 participants for 7-10 years and found that the highest tertile of dietary K2 intake (mean ~33 mcg/day) was associated with a 57% reduction in cardiovascular mortality and a 52% reduction in severe aortic calcification compared to the lowest tertile; K1 intake showed no such association. The PROSPECT-EPIC cohort (Gast et al.) followed Dutch women and found similar inverse associations between K2 intake and coronary heart disease incidence. For bone health, Knapen and colleagues (PMID 23525894) randomized 244 postmenopausal women to MK-7 180 mcg/day versus placebo for 3 years, demonstrating significantly improved bone mineral content at the lumbar spine and femoral neck and reduced age-related decline in vertebral body height. Japanese osteoporosis trials have long used high-dose MK-4 (45 mg/day as menatetrenone) with evidence of reduced vertebral fracture incidence. Beyond bone and cardiovascular outcomes, smaller studies have suggested roles in insulin sensitivity, reducing hepatocellular carcinoma recurrence, and possibly improving aspects of metabolic syndrome.\n\nFor BodyHackGuide users, vitamin K2 occupies a specific niche: it is the companion micronutrient that optimizes the calcium/vitamin D/magnesium axis for proper tissue targeting. The core insight is that vitamin D increases calcium absorption and osteocalcin production, but without K2, the calcium that enters circulation may be deposited in the wrong tissues (arterial wall, soft tissue) rather than bone. Supplementing K2 alongside D3 is therefore increasingly considered the \"complete\" version of that long-standing intervention. Common supplementation errors include: (1) taking K1 instead of K2 and expecting the extrahepatic benefits (K1 supports coagulation but less reliably reaches bone/arteries), (2) using MK-4 at low doses (5-45 mcg) where the short half-life means most of the day provides no K activity—MK-4 needs to be dosed at the pharmacologic 15-45 mg level or taken 2-3 times daily, (3) failing to appreciate the critical interaction with warfarin (vitamin K supplementation is contraindicated without clinician coordination in warfarin users), and (4) ignoring dietary sources when they could supply much of the need economically. This monograph addresses form selection, dose, timing, interactions, and clinical-condition-specific protocols. For related foundational support, see /compound/vitamin-d (the most important stack partner), /compound/magnesium (shared role in vitamin D activation), and /compound/omega-3-fatty-acids (fat-soluble absorption synergy).", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 2, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/vitamin-k2" }, { "id": "d740653c-82ad-4a8e-8a0d-a44f4a35259e", "slug": "yk-11", "name": "YK-11", "aliases": [ "YK11", "YK 11", "Myostine", "Steroidal SARM YK-11" ], "category": "Performance", "description": "YK-11 is a synthetic steroid, not a nonsteroidal SARM, despite being sold alongside them. Its full chemical name is methyl (17alpha,20E)-17,20-[(1-methoxyethylidene)bis(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylate, and it was described by an academic group at Toho University in Japan rather than by a pharmaceutical company. It has never entered clinical development. There is no company behind it, no investigational new drug program, and no human trial of any kind.\n\nThe original 2011 report showed that YK-11 activates the androgen receptor as a partial agonist in a reporter assay, moves the receptor into the nucleus, and does so without inducing the amino-terminal to carboxy-terminal interaction that full androgens produce. In androgen receptor positive human breast cancer cells it acted as a gene-selective agonist, so its effect relative to dihydrotestosterone depended on which gene was measured (PMID: 21372378). Later work from the same group traced that selectivity to different DNA binding and different co-regulator recruitment compared with dihydrotestosterone (PMID: 36030969).\n\nThe claim that YK-11 is a myostatin inhibitor comes from one cell study. In mouse C2C12 myoblasts, YK-11 induced expression of follistatin, a protein that binds and neutralizes myostatin, and the resulting myogenic differentiation was reversed by an anti-follistatin antibody (PMID: 23995658). That is an indirect, cell-culture result in mouse cells. There is no published evidence that YK-11 binds or inhibits myostatin directly, and no human data on myostatin or follistatin after taking it. Other preclinical results include increased proliferation and mineralization in mouse MC3T3-E1 osteoblast cells (PMID: 29491216), improved osteogenic differentiation of rat bone marrow stromal cells and repair of rat cranial bone defects (PMID: 39660819), and reduced inflammatory markers and mortality in mice with bacterial sepsis (PMID: 33588136).\n\nThe safety data that do exist are unfavorable and come from rats. In male Wistar rats, five weeks of YK-11 increased oxidative stress and impaired every measured marker of mitochondrial function in the hippocampus, and exercise did not reverse those changes (PMID: 37468001). A follow-up study in rats reported impaired memory consolidation, downregulation of BDNF signaling, higher pro-inflammatory interleukin 1 beta and interleukin 6, lower interleukin 10, and activation of an apoptotic cascade in the hippocampus (PMID: 38521455). There is no human safety data at all.\n\nIn sport, YK-11 is prohibited. It is named in the World Anti-Doping Agency anabolic agents class alongside the nonsteroidal SARMs (PMID: 28137616), its mass spectrometric behavior and human urinary metabolites have been characterized for testing (PMID: 28440570, PMID: 30379415), and it has been reported in an actual doping control sample (PMID: 37946705). FDA has named YK-11 in warning letters to firms selling SARM products as unapproved new drugs (FDA warning letter to Titan SARMs LLC, 12 December 2025). What is sold as YK-11 in liquid or capsule form is a research chemical of unverified content; across SARM-marketed products tested in one analysis, only 52 percent contained any SARM (PMID: 29183075).", "half_life": "Not established. In a human elimination study using deuterium-labeled YK-11, no intact parent compound was seen in urine; unconjugated metabolites disappeared within 24 hours and glucuronidated and sulfated metabolites remained traceable beyond 48 hours (PMID: 30379415)", "molecular_weight": "430.5 g/mol", "molecular_mass": "430.5 g/mol", "amino_acid_sequence": "", "administration_routes": [ "Oral" ], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "Not approved anywhere and never studied in a registered clinical trial; there is no marketing application for it in any jurisdiction. FDA treats SARM-marketed products as unapproved new drugs that are not dietary supplements and has named YK-11 in warning letters to distributors (FDA warning letter to Titan SARMs LLC, 12 December 2025). Prohibited at all times in sport under the World Anti-Doping Agency anabolic agents class, and also prohibited in equine racing (PMID: 28137616, PMID: 36519889). Research-use-only compound in the US market.", "trial_phase": "", "cas_number": "1370003-76-1", "iupac_name": "", "chemical_formula": "C25H34O6", "potential_benefits": [ "Induced myogenic differentiation and follistatin expression in mouse C2C12 myoblast cells, reversed by an anti-follistatin antibody (PMID: 23995658)", "Increased proliferation and mineralization and raised osteoblast differentiation markers in mouse MC3T3-E1 osteoblast cells (PMID: 29491216)", "Promoted osteogenic differentiation of rat bone marrow stromal cells and improved repair of cranial bone defects in rats (PMID: 39660819)", "Reduced pro-inflammatory cytokines, organ damage markers and mortality in mice with gram-negative bacterial sepsis (PMID: 33588136)" ], "research_fields": [ "Androgen receptor pharmacology", "Myostatin and follistatin signaling", "Sports drug testing", "Neurotoxicology" ], "pubmed_count": 0, "pubchem_cid": 119058028, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/yk-11" }, { "id": "793da479-c8b4-4f76-aa0c-957aa40999ba", "slug": "zeaxanthin", "name": "Zeaxanthin", "aliases": [ "Zeaxanthin", "(3R,3'R)-beta,beta-carotene-3,3'-diol", "Zeaxanthin dipalmitate", "Meso-zeaxanthin", "(3R,3'S-meso)-zeaxanthin", "3R,3'R-zeaxanthin", "Dietary zeaxanthin", "All-trans-zeaxanthin", "Xanthophyll", "Marigold zeaxanthin", "Tagetes erecta zeaxanthin", "OPTISHARP", "EZEyes", "Lutemax 2020", "Macular pigment", "E161h" ], "category": "Carotenoid", "description": "\nZeaxanthin is a xanthophyll carotenoid that functions alongside lutein and meso-zeaxanthin as one of the three pigments comprising the macula lutea — the yellow spot in the central retina responsible for high-acuity daytime vision. Chemically zeaxanthin is (3R,3'R)-beta,beta-carotene-3,3'-diol, differing from lutein by the position of a single double bond in one of its two ionone rings. Lutein contains one beta-ionone ring and one epsilon-ionone ring, whereas zeaxanthin contains two symmetric beta-ionone rings with extended conjugation through both cyclic ends. This structural difference seems minor on paper but produces dramatically different behavior inside the human retina, and the co-supplementation of lutein with zeaxanthin at a roughly 5:1 ratio in AREDS2 reflects that the two molecules are complementary rather than redundant despite their near-identical chemistry.\n\nThe macular pigment exists as a spatial gradient across the central retina. In the outermost parafovea lutein dominates at roughly 2:1 over zeaxanthin. Moving inward toward the central fovea the ratio inverts — zeaxanthin becomes the dominant pigment at the foveal center, where cone density peaks and photopic acuity is maximal. At the centralmost point of the fovea, meso-zeaxanthin (the 3R,3'S stereoisomer) becomes the majority pigment. Meso-zeaxanthin does not meaningfully exist in the human diet; it is formed in situ from dietary lutein by an RPE65-like isomerase reaction in retinal pigment epithelium, which converts the 3'-hydroxyl-bearing epsilon-ring of lutein into the 3'S-configured beta-ionone ring of meso-zeaxanthin. The human retina thus concentrates dietary zeaxanthin and converts dietary lutein into meso-zeaxanthin to build a graded pigment system that maximizes blue-light filtration and singlet oxygen quenching precisely where photochemical retinal stress is highest.\n\nDietary sources of zeaxanthin are surprisingly narrow. Most green vegetables that provide lutein provide very little zeaxanthin — spinach, kale, and collards contain 10-20 mg of lutein per 100 g with less than 0.5 mg of zeaxanthin. The richest commonly consumed food sources of zeaxanthin are orange bell peppers (roughly 1.5-3 mg per pepper), corn (0.3-0.5 mg per cup), egg yolks (particularly from pastured hens, 0.1-0.3 mg per yolk with bioavailability enhanced by the phospholipid matrix), persimmons, and saffron. The singular non-commonplace dietary source that provides gram-per-day levels of zeaxanthin is goji berry (wolfberry, Lycium barbarum), which contains zeaxanthin dipalmitate as its dominant carotenoid at concentrations of 162-252 mg per 100 g dry weight according to Cheng 2005. Typical Western diets provide only 0.3-1 mg of zeaxanthin per day, well below the 2 mg dose validated in AREDS2, which is why supplementation is the practical route for most people pursuing evidence-based macular protection.\n\nCommercial zeaxanthin for supplementation derives primarily from enhanced marigold (Tagetes erecta) flower extracts selectively bred or processed to shift the lutein:zeaxanthin ratio in favor of zeaxanthin, and secondarily from microbial fermentation using engineered strains. OPTISHARP (DSM) uses marigold-sourced zeaxanthin standardized to a consistent lutein:zeaxanthin ratio and is the ingredient used in most AREDS2-compliant eye health formulations. Lutemax 2020 is a proprietary blend that combines lutein, RR-zeaxanthin, and meso-zeaxanthin in a single ingredient — notable because meso-zeaxanthin is otherwise not commercially available as a standalone supplement. EZEyes is another branded marigold zeaxanthin ingredient used in premium formulations. Pricing for zeaxanthin is higher per milligram than for lutein because zeaxanthin is the minority carotenoid in marigold flowers and requires additional processing or strain selection to concentrate.\n\nThe evidence base for zeaxanthin supplementation rests primarily on the AREDS2 trial (Chew 2013 JAMA PMID 23644932), which randomized 4,203 participants with intermediate or advanced AMD in one eye to receive a modified AREDS formulation with lutein 10 mg plus zeaxanthin 2 mg replacing the original 15 mg beta-carotene. The primary endpoint — progression to advanced AMD — showed a 26% risk reduction in participants with the lowest dietary intakes of lutein plus zeaxanthin at baseline. Importantly, AREDS2 was not designed to isolate the effect of zeaxanthin alone from lutein; the two are always given together in the validated formulation because they are complementary rather than substitutable. Dietary epidemiology consistently finds zeaxanthin intake associated with lower AMD risk, and serum zeaxanthin concentrations correlate positively with macular pigment optical density (MPOD) measurements in a dose-dependent fashion. The Zeaxanthin and Visual Function Study (Richer 2011) specifically tested 8 mg daily zeaxanthin in early atrophic AMD patients for 12 months and found improvements in shape discrimination, glare recovery, and contrast sensitivity.\n\nBeyond macular disease, zeaxanthin research has expanded into cataract prevention (Nurses' Health Study and Health Professionals Follow-up Study both showing inverse associations between zeaxanthin intake and cataract extraction rates), diabetic retinopathy (animal work and small human trials), visual performance in healthy young adults (including work by Stringham and Hammond showing zeaxanthin and lutein supplementation improving contrast sensitivity, photostress recovery, and disability glare tolerance), and cognitive function (Johnson 2014, Vishwanathan 2014 showing zeaxanthin concentrations in brain tissue correlate with cognitive performance in older adults). The visual performance work is directly relevant to young healthy consumers — Stringham's B.L.U.E. trial (2017) demonstrated that 12 mg daily lutein plus 2 mg zeaxanthin for 6 months improved sleep quality, reduced eyestrain and headache, and reduced visual fatigue in young adults with high screen exposure.\n\nPharmacokinetically zeaxanthin follows the same lipophilic absorption pathway as other carotenoids. It requires dietary fat for absorption, is packaged into chylomicrons in enterocytes, is delivered to the liver via chylomicron remnants, and then distributed to peripheral tissues via HDL particles. The scavenger receptor B1 (SR-B1) and the steroidogenic acute regulatory-related lipid transfer protein 3 (StARD3) mediate selective uptake into retinal pigment epithelium and neural retina. Blood zeaxanthin concentrations rise over 2-4 weeks of supplementation and plateau at about 8-12 weeks; macular pigment optical density rises more slowly, typically requiring 4-6 months to reach a new steady state and up to 12 months to fully accumulate. Half-life is long — retinal zeaxanthin turns over on the order of weeks rather than hours — so daily dosing is convenient but less critical than for shorter-half-life molecules.\n\nSafety is well-established. Zeaxanthin does not share the beta-carotene problem seen in the CARET and ATBC trials, where high-dose beta-carotene supplementation increased lung cancer risk in heavy smokers. Xanthophylls (lutein and zeaxanthin are both xanthophylls) lack the pro-oxidant behavior that beta-carotene shows in smoker lung tissue under high oxygen tension. AREDS2 specifically tested the lutein-zeaxanthin substitution in a population that included former smokers and found no safety signal. The only commonly reported effect of high-dose zeaxanthin intake is carotenodermia — a harmless yellow-orange pigmentation of the skin, particularly palms and soles — which resolves when intake decreases. FDA GRAS status is established for zeaxanthin at up to 2 mg per day from food sources and higher levels are considered generally safe based on the AREDS2 data.\n\nFor bodyhackguide.co, zeaxanthin occupies a specific place in the eye-health and visual-performance arc. It is not a standalone supplement in practice — always paired with lutein at the AREDS2-validated ratio — and exists on the same shelf as [astaxanthin](/compound/astaxanthin) (a more systemic antioxidant carotenoid without macular concentration), [vitamin-e](/compound/vitamin-e) and [vitamin-c](/compound/vitamin-c) (the other AREDS2 antioxidants), [zinc](/compound/zinc) and [copper](/compound/copper) (the AREDS2 minerals), [omega-3](/compound/omega-3) (DHA is structurally enriched in retinal membranes), and [bilberry](/compound/bilberry) (anthocyanin-based macular support with overlapping but distinct mechanism). Zeaxanthin without lutein makes no sense as a supplementation strategy; lutein without zeaxanthin is less-than-optimal because meso-zeaxanthin formation depends on lutein substrate but central foveal pigment deposition benefits from dietary zeaxanthin directly. The canonical recommendation for anyone with AMD risk factors, high screen time, glare sensitivity, or progressive visual aging is the AREDS2 formulation or an equivalent lutein 10 mg plus zeaxanthin 2 mg combination taken daily with a fat-containing meal for 6-12 months before expecting a detectable change in MPOD or visual performance.\n", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/zeaxanthin" }, { "id": "85eace89-0f60-4571-bf1b-5cb54cbf4ef6", "slug": "zinc", "name": "Zinc", "aliases": [ "Zn", "Zn2+", "Zinc picolinate", "Zinc citrate", "Zinc bisglycinate", "Zinc glycinate", "Zinc gluconate", "Zinc acetate", "Zinc sulfate", "Zinc oxide", "Zinc monomethionine", "Zinc-L-methionine", "OptiZinc", "Zinc carnosine", "L-OptiZinc" ], "category": "Foundational", "description": "Zinc is an essential trace mineral — the second most abundant metal ion in the human body after iron — and one of the most biologically versatile elements in all of physiology. Total body zinc in an adult is approximately 2-3 grams, distributed across all tissues but concentrated in bone, skeletal muscle, liver, kidney, prostate, skin, and brain. Unlike calcium or magnesium where large pools exist in a few depots, zinc is broadly distributed because virtually every cell and every tissue uses it intensively. More than 300 known human enzymes require zinc as a catalytic cofactor, and thousands of proteins incorporate zinc as a structural component through \"zinc finger\" motifs that stabilize the tertiary folding of DNA-binding domains, membrane proteins, and signaling complexes. The human zinc proteome is estimated to include 5-10% of all human proteins, placing zinc alongside iron and magnesium as one of the most consequential metal ions for cellular function.\n\nZinc's biological functions can be organized into three categories. First, catalytic: zinc acts as a Lewis acid in the active sites of hydrolases (carboxypeptidase, matrix metalloproteinases, angiotensin-converting enzyme, carbonic anhydrase), oxidoreductases (alcohol dehydrogenase, Cu,Zn-superoxide dismutase), transferases, lyases, isomerases, and ligases. Carbonic anhydrase alone catalyzes the hydration of CO2 to bicarbonate at rates approaching the diffusion limit — one of the fastest enzymes known — and enables CO2 transport in red blood cells, acid secretion in the stomach, and bicarbonate reabsorption in the kidney. Second, structural: zinc finger domains use zinc to coordinate cysteine and histidine residues, creating the rigid folded structures that enable DNA binding by hundreds of transcription factors (including steroid hormone receptors, Sp1, GATA family, zinc finger transcription factors). Without zinc, the DNA recognition specificity of these proteins collapses. Third, regulatory: free zinc acts as an intracellular signaling ion, comparable to calcium, regulating processes including apoptosis, cell division, neuronal plasticity, and synaptic transmission. Intracellular zinc concentrations are tightly buffered by metallothionein and transported by specialized ZnT and ZIP transporter families.\n\nZinc's clinical importance spans immune function, wound healing, taste and smell, male reproductive function, dermatological conditions, and common cold duration. Global zinc deficiency is common — estimated by the WHO at 17% of the world population — and is particularly prevalent in developing countries where diets are dominated by grains and legumes high in phytate (a potent zinc absorption inhibitor). In developed countries, outright deficiency is less common but marginal zinc insufficiency affects older adults, vegetarians and vegans, alcoholics, patients with GI malabsorption syndromes (Crohn's, celiac, bariatric surgery), and users of chronic medications that deplete zinc (ACE inhibitors, thiazide diuretics, PPIs). The characteristic clinical picture of zinc deficiency includes impaired immunity with increased infection susceptibility, poor wound healing, dermatitis (especially perioral and acral), alopecia, loss of taste and smell, impotence and oligospermia in men, delayed puberty in adolescents, night blindness, and in severe cases characteristic bullous-pustular skin lesions (acrodermatitis enteropathica-like picture) and growth retardation in children.\n\nThe supplemental use of zinc has several evidence-based indications. Zinc lozenges (acetate or gluconate) reduce common cold duration by approximately 33% when started within 24 hours of symptom onset and dosed every 2-3 hours at ≥75 mg elemental zinc per day (Hemila Cochrane review PMID 21328251). The AREDS2 trial (PMID 23644932) established zinc 25-80 mg (combined with antioxidants) as an evidence-based intervention for slowing progression of intermediate age-related macular degeneration. Zinc supplementation reduces severity of acne vulgaris (multiple RCTs; Sadeghian meta-analysis). Zinc and pediatric diarrhea: WHO recommends 10-20 mg daily supplementation during acute diarrheal episodes in children, with strong RCT evidence (Sazawal) for reduced duration and severity. Zinc also supports male testosterone production in zinc-deficient men (less so in replete men), supports wound healing in zinc-deficient states, and has adjunctive roles in diabetes, ADHD, and other conditions with more modest evidence.\n\nFor BodyHackGuide readers, zinc is a foundational supplement with specific evidence-based use cases. The key practical issues are: form selection (picolinate, citrate, bisglycinate, gluconate, acetate all differ in absorption and clinical context), dose (10-30 mg daily for maintenance, higher for acute indications), copper balance (chronic zinc >40 mg/day causes copper deficiency and anemia — zinc and copper are antagonistic and must be balanced), timing (on empty stomach for best absorption, but this causes nausea in many users), and phytate interactions. This page covers the zinc proteome, deficiency biology, the common cold and AMD evidence, acne and testosterone considerations, copper balance, form selection, and practical dosing.", "half_life": "", "molecular_weight": "", "molecular_mass": "", "amino_acid_sequence": "", "administration_routes": [], "dose_range_mcg": "", "dosing_frequency": "", "cycle_length": "", "common_vial_sizes": [], "research_stage": "Preclinical", "approval_status": "", "trial_phase": "", "cas_number": "", "iupac_name": "", "chemical_formula": "", "potential_benefits": [], "research_fields": [], "pubmed_count": 0, "pubchem_cid": null, "image_url": "", "structure_image_url": "", "url": "https://www.bodyhackguide.co/compound/zinc" } ] }