--- title: "Resveratrol: Research & Side Effects | BodyHackGuide" url: https://www.bodyhackguide.co/compound/resveratrol description: "Resveratrol: mechanism, clinical studies & side effects." lang: en --- Skip to content Compare notes on r/BodyHackGuide (https://reddit.com/r/bodyhackguide) Compare notes with other researchers. Join r/BodyHackGuide (https://reddit.com/r/bodyhackguide) # Resveratrol Longevity: https://www.bodyhackguide.co/wiki#cat-longevity Status Phase 3,, not approved for human use Evidence Not graded on a research bench yet Resveratrol (trans-3,4',5-trihydroxystilbene) is a stilbene polyphenol made by plants and found in grapes, red wine, chocolate and certain berries and roots, and it is widely consumed as a nutritional supplement. Reviewed 4 November 2026 01 Overview ## What Resveratrol is Interest in resveratrol as an anti-aging compound grew from a 2003 report by David Sinclair's group that it activated sirtuin enzymes and extended yeast lifespan by 70 percent, but other laboratories then found that the test-tube activation depended on a fluorescent tag attached to the test peptide (PMID: 12939617, PMID: 15684413, PMID: 15749705). In mice, resveratrol improved survival on a high-calorie diet but did not extend lifespan on a standard diet, as two tests by the US National Institute on Aging's Interventions Testing Program also found (PMID: 17086191, PMID: 18599363, PMID: 20974732, PMID: 22451473). Human trials of resveratrol have given mixed results on metabolic and cognitive measures (PMID: 34320173, PMID: 29548848, PMID: 32244933), and a 142-person phase 3 trial in knee osteoarthritis found no effect on pain at 3 months (PMID: 39137167). ### How it works ### Where resveratrol comes from Resveratrol belongs to a class of polyphenols that plants produce in response to stress (PMID: 15306006). A 1997 study at the University of Illinois at Chicago purified resveratrol and found that it acted as an antioxidant and antimutagen, inhibited cyclooxygenase, and reduced tumor formation in a mouse skin cancer model (PMID: 8985016). These were laboratory and animal results, not human ones. Read the full mechanism Show less ### The sirtuin claim Sirtuins are NAD+-dependent protein deacetylases, and in budding yeast calorie restriction extends lifespan by increasing the activity of the sirtuin Sir2 (PMID: 12939617). In 2003, a team led by David Sinclair reported that resveratrol lowered the Michaelis constant (Km) of human SIRT1 for both its acetylated substrate and NAD+, increased cell survival through SIRT1-dependent deacetylation of p53, and extended yeast lifespan by 70 percent (PMID: 12939617). In 2004, the Sinclair group at Harvard Medical School reported that resveratrol extended lifespan in the worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster in a Sir2-dependent way (PMID: 15254550). BodyHackGuide's NAD+ (https://www.bodyhackguide.co/compound/nad) guide covers the cofactor that sirtuins consume. ### The fluorescent-tag dispute In 2005, groups at the University of Washington and the University of Wisconsin found that resveratrol activated SIRT1 only when the test peptide carried a covalently attached fluorescent group, such as the Fluor de Lys tag, and not when the same peptide lacked it (PMID: 15684413, PMID: 15749705). The Fluor de Lys kit was sold by BIOMOL Research Laboratories, where the first author of the 2003 report of SIRT1 activation by resveratrol worked (PMID: 15749705, PMID: 12939617). The University of Washington group also found no effect of resveratrol on Sir2 activity or lifespan in three yeast strain backgrounds (PMID: 15684413). Scientists at Amgen in 2009 and at Pfizer in 2010 found no SIRT1 activation by resveratrol with native peptide or full-length protein substrates, and the Pfizer team reported evidence that resveratrol and synthetic sirtuin activators bind directly to the fluorophore-tagged peptides (PMID: 19843076, PMID: 20061378). In 2013, the Sinclair laboratory reported that sirtuin-activating compounds do activate SIRT1 with substrates that carry certain hydrophobic motifs, as in PGC-1alpha and FOXO3a, and that a single SIRT1 residue (Glu230) is needed for this; in cells given an activation-defective SIRT1, the metabolic effects of these compounds were blocked (PMID: 23471411). Fourteen authors of the 2013 Sinclair laboratory paper were employees of Sirtris, then a GSK company, and Sinclair disclosed that he was a Sirtris consultant and an inventor on patents licensed to it (PMID: 23471411). These papers disagree on whether resveratrol activates SIRT1 directly, and all of the work was done in test tubes, cells, yeast or animals. ### Indirect routes in mice: phosphodiesterases, AMPK and NAD+ A 2012 study at the US National Heart, Lung, and Blood Institute found that resveratrol competitively inhibits cAMP-degrading phosphodiesterases (PDEs); the rise in cAMP set off a chain through Epac1, calcium, CaMKKbeta and AMP-activated protein kinase (AMPK) that increased NAD+ and SIRT1 activity, and the PDE4 inhibitor rolipram reproduced resveratrol's metabolic effects in mice (PMID: 22304913). The same year, the Sinclair laboratory reported that in adult mice with SIRT1 deleted, a moderate dose of resveratrol no longer increased AMPK activation, muscle NAD+ or mitochondrial function, while a high dose activated AMPK without SIRT1 (PMID: 22560220). ### Estrogen receptor activity (cell studies) Resveratrol is structurally similar to the synthetic estrogen diethylstilbestrol, and at about 3 to 10 micromolar it blocked estradiol binding to the estrogen receptor, switched on estrogen-responsive genes in human breast cancer cells and stimulated growth of estrogen-dependent T47D breast cancer cells (PMID: 9391166). ### How the body handles oral resveratrol In six volunteers given carbon-14-labeled resveratrol, at least 70 percent of a 25 mg oral dose was absorbed, but only trace amounts of unchanged resveratrol (under 5 ng/mL) reached plasma, because the intestine and liver rapidly attach sulfate and glucuronic acid groups (PMID: 15333514). In a phase 1 study of single doses up to 5 g in 40 healthy volunteers, the 5 g dose produced a mean peak plasma level of 539 ng/mL (2.4 micromolar) of resveratrol, while sulfate and glucuronide metabolites reached exposures up to 23 times higher (PMID: 17548692). The authors of that study noted that cancer-preventive effects in cell studies need at least 5 micromolar (PMID: 17548692). In rats given equal molar doses, resveratrol was about 20 percent bioavailable and its dimethyl ether analog pterostilbene (https://www.bodyhackguide.co/compound/pterostilbene) about 80 percent (PMID: 21116625). ### Studied for - Aging biology - Sirtuin biology - Metabolic disease - Cognitive aging - Cancer chemoprevention - Pharmacokinetics ### Benefits listed - Overall cognitive performance over 12 months in 129 postmenopausal women (PMID: 32244933) - Word recall after 30 minutes in a 26-week trial of 46 older adults, not repeated in a 60-person trial (PMID: 24899709, PMID: 29548848) - Muscle AMPK activation and lower systolic blood pressure in an 11-man crossover trial (PMID: 22055504) - A smaller fall in amyloid-beta 40 in spinal fluid and plasma than with placebo in a 119-person Alzheimer disease trial, a change the authors said needs further study (PMID: 26362286) Show 3 more Show less - Short-term HbA1c in type 2 diabetes in a 2021 umbrella review of meta-analyses (PMID: 34320173) - Survival of middle-aged mice on a high-calorie diet (PMID: 17086191) - Lifespan of the short-lived killifish Nothobranchius furzeri (PMID: 16461283) 02 Research Free with email ## What the research shows No research bench grades Resveratrol yet. Benches compare compounds people pair, with the evidence for each. ### Unlock the research summary Enter your email to keep reading. It is free, and it opens these sections on every compound page in this browser. - A summary of the key research - Safety and side effects - A link to the PubMed results You also get the free peptide cheat sheet by email. Unsubscribe anytime. Have an account? Sign in (https://www.bodyhackguide.co/auth) 03 Safety ## Resveratrol side effects and interactions ### Side effects #### Common - Mild to moderate gastrointestinal symptoms at 2.5 and 5 g a day for 29 days in healthy volunteers (PMID: 20935227) - Nausea, diarrhea and weight loss as the most common adverse events in a 52-week Alzheimer disease trial (PMID: 26362286) - Mild adverse events, similar to placebo, in a 40-person study that gave 25 to 150 mg six times a day (PMID: 19194969) #### Serious events - Serious adverse events in 12 of 24 myeloma patients given SRT501, a resveratrol product, at 5 g a day, among them acute renal failure in 3 (ClinicalTrials.gov NCT00920556) - Greater brain volume loss than placebo in a 119-person Alzheimer disease trial (PMID: 26362286) - Inhibition of CYP3A4, CYP2D6 and CYP2C9 activity at 1 g a day in 42 healthy volunteers (PMID: 20716633) - Altered fetal pancreatic islet blood vessels when given in pregnancy to macaques (PMID: 24844258) ### Who should not use it Contraindications Medicines cleared by CYP3A4, CYP2D6 or CYP2C9 are a concern: one gram of resveratrol a day for 4 weeks inhibited these enzymes in healthy volunteers, and the study authors warned of possible adverse drug reactions or altered drug effects (PMID: 20716633). Read all the contraindications and cautions Show less Kidney disease and multiple myeloma are reasons for caution, because kidney failure was recorded in several of the 24 myeloma patients given SRT501, a resveratrol product, at 5 g a day (ClinicalTrials.gov NCT00920556). No human pregnancy data were found; in pregnant macaques, resveratrol changed fetal pancreatic islet blood vessel density, and the authors advised against use in pregnancy (PMID: 24844258). Resveratrol acted as an estrogen receptor agonist and stimulated growth of estrogen-dependent breast cancer cells in laboratory studies (PMID: 9391166), so estrogen-sensitive conditions are a mechanism-based reason for caution. Exercise training in older adults is a concern: in older men, resveratrol blunted several cardiovascular gains from 8 weeks of training (PMID: 23878368). ### Interactions 2 pairings in our record: 1 with a caution and 1 to monitor. - Drugs metabolized by CYP3A4, CYP2D6 or CYP2C9 Caution One gram of resveratrol a day for 4 weeks inhibited the phenotypic activity of CYP3A4, CYP2D6 and CYP2C9 and induced CYP1A2 in 42 healthy volunteers, and the authors warned of possible adverse drug reactions or altered drug effects (PMID: 20716633). - Piperine Monitor In mice, piperine added to resveratrol raised resveratrol exposure (AUC) to 229 percent and peak level to 1,544 percent of resveratrol alone (PMID: 21714124), but in a human crossover study adding 20 mg of piperine to 250 mg of resveratrol did not significantly change plasma resveratrol or its metabolites, measured in a separate group of 6 people (PMID: 24804871). This interaction data is compiled from published research and community reports. It may not be exhaustive. Always consult a healthcare professional before combining compounds. Need bloodwork before starting? Full hormone + metabolic panels from Anabolic Insights. Code CHONCH for first-order discount. Order Bloodwork (https://anabolicinsights.ai/?ref=nwm2zjb) 04 Dosing Free with email ## Dosing No dose on record Our record lists no dose for Resveratrol. This section holds what it does list. ### Unlock the Dosing section - Route 05 Prices ## Resveratrol prices No listings We do not track a vendor for Resveratrol yet, so this page states no price. 06 Chemistry ## Chemistry and structure Molecular formula C14H12O3 Molecular mass 228.24 g/mol CAS number 501-36-0 Half-life About 1 to 3 hours for unchanged trans-resveratrol after single oral doses and 2 to 5 hours after repeated doses, in a 2009 placebo-controlled study of 40 healthy adults, 32 of whom took resveratrol (PMID: 19194969). In a 2004 study of 6 volunteers, total resveratrol-derived radioactivity, most of it from metabolites, had a plasma half-life of about 9.2 hours (PMID: 15333514). View on PubChem (https://pubchem.ncbi.nlm.nih.gov/compound/445154) 07 Related ## Related to Resveratrol ### In the same category - 17-alpha-EstradiolPhase 4 for topical use in hair loss 17-alpha-estradiol (alfatradiol) is a naturally occurring steroid estrogen, the C17 epimer of the main estrogen 17beta-estradiol, that extends lifespan in male mice, where it causes only mild feminizing effects.: https://www.bodyhackguide.co/compound/alpha-estradiol - AcarbosePhase 4 Acarbose is a prescription alpha-glucosidase inhibitor for type 2 diabetes, a complex oligosaccharide produced by fermentation of the bacterium Actinoplanes utahensis, that slows the digestion of starch and table sugar in the small intestine (US prescribing information for Precose).: https://www.bodyhackguide.co/compound/acarbose - Alpha-Ketoglutarate (AKG)Phase 2 Alpha-ketoglutarate (AKG, also called 2-oxoglutarate) is an intermediate of the tricarboxylic acid (Krebs) cycle that cells make from isocitrate and from glutamate, and its calcium salt (Ca-AKG) is the form used in the main aging studies in mice and people.: https://www.bodyhackguide.co/compound/alpha-ketoglutarate-akg - CanagliflozinPhase 4 Canagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor, a C-glucoside discovered by chemists at Mitsubishi Tanabe Pharma, that lowers blood glucose in type 2 diabetes by making the kidneys excrete glucose in the urine; the FDA approved canagliflozin in 2013 as Invokana.: https://www.bodyhackguide.co/compound/canagliflozin - CMS121Phase 1 CMS121 is a synthetic derivative of the flavonol fisetin, made at the Salk Institute for Biological Studies in La Jolla in the Cellular Neurobiology Laboratory of Pamela Maher and David Schubert, as part of a series of more than 160 fisetin derivatives.: https://www.bodyhackguide.co/compound/cms-121 - CortagenPreclinical Cortagen is a synthetic tetrapeptide, Ala-Glu-Asp-Pro (AEDP), made at Vladimir Khavinson's St. Petersburg Institute of Bioregulation and Gerontology from the amino acid analysis of Cortexin, a peptide preparation from the brain cortex.: https://www.bodyhackguide.co/compound/cortagen All compounds (https://www.bodyhackguide.co/wiki) ### Compare Resveratrol - Alternatives to Resveratrol: https://www.bodyhackguide.co/alternatives-to/resveratrol ### Research tools - Peptide Calculator Reconstitution and syringe units: https://www.bodyhackguide.co/tools/reconstitution - Reconstitution Guide How to mix, step by step: https://www.bodyhackguide.co/guides/how-to-reconstitute-peptides - Nasal Spray Calc mL per actuation: https://www.bodyhackguide.co/tools/intranasal - Half-Life Visualizer Decay curves: https://www.bodyhackguide.co/tools/halflife All articles (https://www.bodyhackguide.co/blog) 08 Questions ## Frequently asked questions What is resveratrol? Resveratrol is a stilbene polyphenol found in grapes, red wine, chocolate and certain berries and roots (PMID: 24819981). Resveratrol belongs to a class of polyphenols that plants produce in response to stress (PMID: 15306006). It is widely consumed as a nutritional supplement (PMID: 22304913). Does resveratrol activate sirtuins? Resveratrol was reported in 2003 to activate the human sirtuin SIRT1 and to extend yeast lifespan by 70 percent (PMID: 12939617). Later studies found that resveratrol activated SIRT1 in the test tube only when the test peptide carried a fluorescent tag, and found no effect of resveratrol on Sir2 activity or lifespan in three yeast strains (PMID: 15684413, PMID: 15749705). A 2013 study from David Sinclair's laboratory, the group behind the 2003 report of SIRT1 activation by resveratrol, reported that resveratrol and related compounds can activate SIRT1 directly with certain natural substrates through a SIRT1 site called Glu230; 14 of the study's authors worked for Sirtris, then a GSK company (PMID: 23471411). A 2012 mouse study found that resveratrol raises SIRT1 activity indirectly, by inhibiting phosphodiesterases and activating AMPK (PMID: 22304913). Does resveratrol extend lifespan? Resveratrol extended lifespan in yeast, worms and flies in the original reports, but a later study found no effect of resveratrol on fly lifespan in seven trials and variable effects in worms (PMID: 12939617, PMID: 15254550, PMID: 17875315). Resveratrol increased the survival of mice on a high-calorie diet but did not extend the lifespan of mice on a standard diet when started at 12 months of age (PMID: 17086191, PMID: 18599363). In two tests by the US National Institute on Aging's Interventions Testing Program, resveratrol had no significant effect on the lifespan of male or female mice (PMID: 20974732, PMID: 22451473). A 2012 meta-analysis of resveratrol lifespan studies in six species concluded that few species conclusively show life extension (PMID: 22718956). What have human trials of resveratrol found? In a 12-month trial in postmenopausal women, resveratrol at 75 mg twice a day improved an overall cognitive score compared with placebo (PMID: 32244933). A 26-week resveratrol trial in 60 older adults did not improve its main verbal memory outcome, so an earlier positive result in 46 older adults was not repeated (PMID: 29548848, PMID: 24899709). Resveratrol trials of 4 to 12 weeks in obese men and nonobese women gave mixed metabolic results, and two of these resveratrol trials measured insulin sensitivity by clamp and found no improvement (PMID: 22055504, PMID: 23193181, PMID: 23102619). In a 142-person phase 3 trial in knee osteoarthritis, resveratrol did not reduce pain at 3 months compared with placebo (PMID: 39137167). Why are blood levels of resveratrol so low after an oral dose? In six volunteers, at least 70 percent of a 25 mg oral dose of resveratrol was absorbed, but only trace amounts of unchanged resveratrol appeared in plasma because the gut and liver rapidly convert resveratrol to sulfate and glucuronide forms (PMID: 15333514). A single 5 g dose of resveratrol in a phase 1 study produced a mean peak of 2.4 micromolar unchanged resveratrol, less than the 5 micromolar the authors said cell studies need for cancer-preventive effects (PMID: 17548692). The sulfate and glucuronide metabolites of resveratrol reached plasma exposures up to 23 times higher than resveratrol itself (PMID: 17548692). Is resveratrol safe? In healthy volunteers, resveratrol at 2.5 and 5 g a day for 29 days caused mild to moderate gastrointestinal symptoms (PMID: 20935227). In a 52-week Alzheimer disease trial, the most common adverse events with resveratrol were nausea, diarrhea and weight loss, and brain volume loss was greater than with placebo (PMID: 26362286). A phase 2 myeloma trial of SRT501, a resveratrol product given at 5 g a day, recorded serious adverse events in 12 of 24 participants, among them acute renal failure in 3 (ClinicalTrials.gov NCT00920556). Resveratrol at 1 g a day for 4 weeks inhibited several drug-metabolizing liver enzymes in 42 healthy volunteers (PMID: 20716633). What is resveratrol's regulatory status in the US? Resveratrol is not an FDA-approved drug, and a search of Drugs@FDA through the openFDA API on 26 October 2026 found no product containing resveratrol. In the US, resveratrol is sold as an ingredient in products labeled as dietary supplements (NIH Dietary Supplement Label Database), and the FDA does not approve dietary supplements before they are marketed (FDA, Questions and Answers on Dietary Supplements). The only GRAS notice for resveratrol in the FDA's GRAS Notice Inventory, GRN 224 for use in bottled water, was closed in 2007 when the FDA stopped its evaluation at the notifier's request. Free 2026 Peptide Cheat Sheet (PDF) 38 compounds and blends: vial sizes, BAC water volumes, dosing ranges and bloodwork markers. Download Free (https://www.bodyhackguide.co/guides/peptide-cheat-sheet-download) BodyHackGuide (https://www.bodyhackguide.co/) Your biohacking research hub: compound pricing, brain health protocols, dosing tools, and vendor reviews. support@bodyhackguide.co Join our Discord: https://discord.gg/Mhq5UdRYBA r/BodyHackGuide on Reddit: https://reddit.com/r/BodyHackGuide **Affiliate Disclosure:** We rank every vendor on the same public, reproducible methodology (https://www.bodyhackguide.co/vendors/methodology). 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All rights reserved. - Terms: https://www.bodyhackguide.co/terms - Privacy: https://www.bodyhackguide.co/privacy ## Structured data ```json [ { "@context": "https://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": 1, "name": "Home", "item": "https://www.bodyhackguide.co/" }, { "@type": "ListItem", "position": 2, "name": "Compounds", "item": "https://www.bodyhackguide.co/compare" }, { "@type": "ListItem", "position": 3, "name": "Resveratrol" } ] }, { "@context": "https://schema.org", "@type": "MedicalWebPage", "name": "Resveratrol", "description": "Resveratrol (trans-3,4',5-trihydroxystilbene) is a stilbene polyphenol made by plants and found in grapes, red wine, chocolate and certain berries and roots, and it is widely consumed as a nutritional supplement (PMID: 24819981, PMID: 22304913). Interest in resveratrol as an anti-aging compound grew from a 2003 report by David Sinclair's group that it activated sirtuin enzymes and extended yeast lifespan by 70 percent, but other laboratories then found that the test-tube activation depended on a fluorescent tag attached to the test peptide (PMID: 12939617, PMID: 15684413, PMID: 15749705). In mice, resveratrol improved survival on a high-calorie diet but did not extend lifespan on a standard diet, as two tests by the US National Institute on Aging's Interventions Testing Program also found (PMID: 17086191, PMID: 18599363, PMID: 20974732, PMID: 22451473). Human trials of resveratrol have given mixed results on metabolic and cognitive measures (PMID: 34320173, PMID: 29548848, PMID: 32244933), and a 142-person phase 3 trial in knee osteoarthritis found no effect on pain at 3 months (PMID: 39137167).", "lastReviewed": "2026-11-04T12:08:39.455Z", "url": "https://www.bodyhackguide.co/compound/resveratrol", "author": { "@type": "Person", "name": "BioChonch", "url": "https://www.bodyhackguide.co/about", "jobTitle": "Founder & Lead Researcher", "sameAs": [ "https://reddit.com/r/BodyHackGuide", "https://reddit.com/r/BrainHackGuide", "https://reddit.com/r/Biohackingher" ], "worksFor": { "@type": "Organization", "name": "BodyHackGuide", "url": "https://www.bodyhackguide.co" } }, "reviewedBy": { "@type": "Person", "name": "BioChonch", "url": "https://www.bodyhackguide.co/about", "jobTitle": "Founder & Lead Researcher", "sameAs": [ "https://reddit.com/r/BodyHackGuide", "https://reddit.com/r/BrainHackGuide", "https://reddit.com/r/Biohackingher" ], "worksFor": { "@type": "Organization", "name": "BodyHackGuide", "url": "https://www.bodyhackguide.co" } }, "publisher": { "@type": "Organization", "name": "BodyHackGuide", "url": "https://www.bodyhackguide.co" }, "mainContentOfPage": { "@type": "WebPageElement", "cssSelector": "main" }, "about": { "@type": "Drug", "name": "Resveratrol", "alternateName": [ "trans-Resveratrol", "(E)-Resveratrol", "3,4',5-Trihydroxystilbene", "3,4',5-Trihydroxy-trans-stilbene", "3,4',5-Stilbenetriol", "5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol", "SRT501" ], "description": "Resveratrol (trans-3,4',5-trihydroxystilbene) is a stilbene polyphenol made by plants and found in grapes, red wine, chocolate and certain berries and roots, and it is widely consumed as a nutritional supplement (PMID: 24819981, PMID: 22304913). Interest in resveratrol as an anti-aging compound grew from a 2003 report by David Sinclair's group that it activated sirtuin enzymes and extended yeast lifespan by 70 percent, but other laboratories then found that the test-tube activation depended on a fluorescent tag attached to the test peptide (PMID: 12939617, PMID: 15684413, PMID: 15749705). In mice, resveratrol improved survival on a high-calorie diet but did not extend lifespan on a standard diet, as two tests by the US National Institute on Aging's Interventions Testing Program also found (PMID: 17086191, PMID: 18599363, PMID: 20974732, PMID: 22451473). Human trials of resveratrol have given mixed results on metabolic and cognitive measures (PMID: 34320173, PMID: 29548848, PMID: 32244933), and a 142-person phase 3 trial in knee osteoarthritis found no effect on pain at 3 months (PMID: 39137167).", "activeIngredient": "Resveratrol", "administrationRoute": "Oral, Intravenous", "mechanismOfAction": "Where resveratrol comes from Resveratrol belongs to a class of polyphenols that plants produce in response to stress (PMID: 15306006). A 1997 study at the University of Illinois at Chicago purified resveratrol and found that it acted as an antioxidant and antimutagen, inhibited cyclooxygenase, and reduced tumor formation in a mouse skin cancer model (PMID: 8985016). These were laboratory and animal results, not human ones. The sirtuin claim Sirtuins are NAD+-dependent protein deacetylases, and in budding yeast calorie restriction extends lifespan by increasing the activity of the sirtuin Sir2 (PMID: 12939617). In 2003, a team led by David Sinclair reported that resveratrol lowered the Michaelis constant (Km) of human SIRT1 for both its acetylated substrate and NAD+, increased cell survival through SIRT1-dependent deacetylation of p53, and extended yeast lifespan by 70 percent (PMID: 12939617). In 2004, the Sinclair group at Harvard Medical School reported that resveratrol extended lifespan in the worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster in a Sir2-dependent way (PMID: 15254550). BodyHackGuide's NAD+ guide covers the cofactor that sirtuins consume. The fluorescent-tag dispute In 2005, groups at the University of Washington and the University of Wisconsin found that resveratrol activated SIRT1 only when the test peptide carried a covalently attached fluorescent group, such as the Fluor de Lys tag, and not when the same peptide lacked it (PMID: 15684413, PMID: 15749705). The Fluor de Lys kit was sold by BIOMOL Research Laboratories, where the first author of the 2003 report of SIRT1 activation by resveratrol worked (PMID: 15749705, PMID: 12939617). The University of Washington group also found no effect of resveratrol on Sir2 activity or lifespan in three yeast strain backgrounds (PMID: 15684413). Scientists at Amgen in 2009 and at Pfizer in 2010 found no SIRT1 activation by resveratrol with native peptide or full-length protein substrates, and the Pfizer team reported evidence that resveratrol and synthetic sirtuin activators bind directly to the fluorophore-tagged peptides (PMID: 19843076, PMID: 20061378). In 2013, the Sinclair laboratory reported that sirtuin-activating compounds do activate SIRT1 with substrates that carry certain hydrophobic motifs, as in PGC-1alpha and FOXO3a, and that a single SIRT1 residue (Glu230) is needed for this; in cells given an activation-defective SIRT1, the metabolic effects of these compounds were blocked (PMID: 23471411). Fourteen authors of the 2013 Sinclair laboratory paper were employees of Sirtris, then a GSK company, and Sinclair disclosed that he was a Sirtris consultant and an inventor on patents licensed to it (PMID: 23471411). These papers disagree on whether resveratrol activates SIRT1 directly, and all of the work was done in test tubes, cells, yeast or animals. Indirect routes in mice: phosphodiesterases, AMPK and NAD+ A 2012 study at the US National Heart, Lung, and Blood Institute found that resveratrol competitively inhibits cAMP-degrading phosphodiesterases (PDEs); the rise in cAMP set off a chain through Epac1, calcium, CaMKKbeta and AMP-activated protein kinase (AMPK) that increased NAD+ and SIRT1 activity, and the PDE4 inhibitor rolipram reproduced resveratrol's metabolic effects in mice (PMID: 22304913). The same year, the Sinclair laboratory reported that in adult mice with SIRT1 deleted, a moderate dose of resveratrol no longer increased AMPK activation, muscle NAD+ or mitochondrial function, while a high dose activated AMPK without SIRT1 (PMID: 22560220). Estrogen receptor activity (cell studies) Resveratrol is structurally similar to the synthetic estrogen diethylstilbestrol, and at about 3 to 10 micromolar it blocked estradiol binding to the estrogen receptor, switched on estrogen-responsive genes in human breast cancer cells and stimulated growth of estrogen-dependent T47D breast cancer cells (PMID: 9391166). How the body handles oral resveratrol In six volunteers given carbon-14-labeled resveratrol, at least 70 percent of a 25 mg oral dose was absorbed, but only trace amounts of unchanged resveratrol (under 5 ng/mL) reached plasma, because the intestine and liver rapidly attach sulfate and glucuronic acid groups (PMID: 15333514). In a phase 1 study of single doses up to 5 g in 40 healthy volunteers, the 5 g dose produced a mean peak plasma level of 539 ng/mL (2.4 micromolar) of resveratrol, while sulfate and glucuronide metabolites reached exposures up to 23 times higher (PMID: 17548692). The authors of that study noted that cancer-preventive effects in cell studies need at least 5 micromolar (PMID: 17548692). In rats given equal molar doses, resveratrol was about 20 percent bioavailable and its dimethyl ether analog pterostilbene about 80 percent (PMID: 21116625).", "legalStatus": "Not approved for human use (research chemical)", "warning": "For research purposes only. Not for human consumption." } }, { "@context": "https://schema.org", "@type": "FAQPage", "mainEntity": [ { "@type": "Question", "name": "What is resveratrol?", "acceptedAnswer": { "@type": "Answer", "text": "Resveratrol is a stilbene polyphenol found in grapes, red wine, chocolate and certain berries and roots (PMID: 24819981). Resveratrol belongs to a class of polyphenols that plants produce in response to stress (PMID: 15306006). It is widely consumed as a nutritional supplement (PMID: 22304913)." } }, { "@type": "Question", "name": "Does resveratrol activate sirtuins?", "acceptedAnswer": { "@type": "Answer", "text": "Resveratrol was reported in 2003 to activate the human sirtuin SIRT1 and to extend yeast lifespan by 70 percent (PMID: 12939617). Later studies found that resveratrol activated SIRT1 in the test tube only when the test peptide carried a fluorescent tag, and found no effect of resveratrol on Sir2 activity or lifespan in three yeast strains (PMID: 15684413, PMID: 15749705). A 2013 study from David Sinclair's laboratory, the group behind the 2003 report of SIRT1 activation by resveratrol, reported that resveratrol and related compounds can activate SIRT1 directly with certain natural substrates through a SIRT1 site called Glu230; 14 of the study's authors worked for Sirtris, then a GSK company (PMID: 23471411). A 2012 mouse study found that resveratrol raises SIRT1 activity indirectly, by inhibiting phosphodiesterases and activating AMPK (PMID: 22304913)." } }, { "@type": "Question", "name": "Does resveratrol extend lifespan?", "acceptedAnswer": { "@type": "Answer", "text": "Resveratrol extended lifespan in yeast, worms and flies in the original reports, but a later study found no effect of resveratrol on fly lifespan in seven trials and variable effects in worms (PMID: 12939617, PMID: 15254550, PMID: 17875315). Resveratrol increased the survival of mice on a high-calorie diet but did not extend the lifespan of mice on a standard diet when started at 12 months of age (PMID: 17086191, PMID: 18599363). In two tests by the US National Institute on Aging's Interventions Testing Program, resveratrol had no significant effect on the lifespan of male or female mice (PMID: 20974732, PMID: 22451473). A 2012 meta-analysis of resveratrol lifespan studies in six species concluded that few species conclusively show life extension (PMID: 22718956)." } }, { "@type": "Question", "name": "What have human trials of resveratrol found?", "acceptedAnswer": { "@type": "Answer", "text": "In a 12-month trial in postmenopausal women, resveratrol at 75 mg twice a day improved an overall cognitive score compared with placebo (PMID: 32244933). A 26-week resveratrol trial in 60 older adults did not improve its main verbal memory outcome, so an earlier positive result in 46 older adults was not repeated (PMID: 29548848, PMID: 24899709). Resveratrol trials of 4 to 12 weeks in obese men and nonobese women gave mixed metabolic results, and two of these resveratrol trials measured insulin sensitivity by clamp and found no improvement (PMID: 22055504, PMID: 23193181, PMID: 23102619). In a 142-person phase 3 trial in knee osteoarthritis, resveratrol did not reduce pain at 3 months compared with placebo (PMID: 39137167)." } }, { "@type": "Question", "name": "Why are blood levels of resveratrol so low after an oral dose?", "acceptedAnswer": { "@type": "Answer", "text": "In six volunteers, at least 70 percent of a 25 mg oral dose of resveratrol was absorbed, but only trace amounts of unchanged resveratrol appeared in plasma because the gut and liver rapidly convert resveratrol to sulfate and glucuronide forms (PMID: 15333514). A single 5 g dose of resveratrol in a phase 1 study produced a mean peak of 2.4 micromolar unchanged resveratrol, less than the 5 micromolar the authors said cell studies need for cancer-preventive effects (PMID: 17548692). The sulfate and glucuronide metabolites of resveratrol reached plasma exposures up to 23 times higher than resveratrol itself (PMID: 17548692)." } }, { "@type": "Question", "name": "Is resveratrol safe?", "acceptedAnswer": { "@type": "Answer", "text": "In healthy volunteers, resveratrol at 2.5 and 5 g a day for 29 days caused mild to moderate gastrointestinal symptoms (PMID: 20935227). In a 52-week Alzheimer disease trial, the most common adverse events with resveratrol were nausea, diarrhea and weight loss, and brain volume loss was greater than with placebo (PMID: 26362286). A phase 2 myeloma trial of SRT501, a resveratrol product given at 5 g a day, recorded serious adverse events in 12 of 24 participants, among them acute renal failure in 3 (ClinicalTrials.gov NCT00920556). Resveratrol at 1 g a day for 4 weeks inhibited several drug-metabolizing liver enzymes in 42 healthy volunteers (PMID: 20716633)." } }, { "@type": "Question", "name": "What is resveratrol's regulatory status in the US?", "acceptedAnswer": { "@type": "Answer", "text": "Resveratrol is not an FDA-approved drug, and a search of Drugs@FDA through the openFDA API on 26 October 2026 found no product containing resveratrol. In the US, resveratrol is sold as an ingredient in products labeled as dietary supplements (NIH Dietary Supplement Label Database), and the FDA does not approve dietary supplements before they are marketed (FDA, Questions and Answers on Dietary Supplements). The only GRAS notice for resveratrol in the FDA's GRAS Notice Inventory, GRN 224 for use in bottled water, was closed in 2007 when the FDA stopped its evaluation at the notifier's request." } } ] }, { "@context": "https://schema.org", "@type": "Organization", "@id": "https://www.bodyhackguide.co#organization", "name": "BodyHackGuide", "alternateName": "BHG", "url": "https://www.bodyhackguide.co", "logo": { "@type": "ImageObject", "url": "https://www.bodyhackguide.co/logo.png", "width": 512, "height": 512 }, "description": "Evidence-based research reference for peptides and nootropics. 273 compound profiles, interactive dosing calculators, vendor price comparisons, and trust-scored vendor reviews scored on a public, reproducible methodology applied to every vendor. 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