---
title: "Alpha-Ketoglutarate: Research & Side Effects"
url: https://www.bodyhackguide.co/compound/alpha-ketoglutarate-akg
description: "Alpha-Ketoglutarate (AKG): mechanism, clinical studies & side effects."
lang: en
---

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# Alpha-Ketoglutarate (AKG)

Longevity: https://www.bodyhackguide.co/wiki#cat-longevity

Status

Phase 2 (ABLE, ClinicalTrials.gov NCT05706389),, not approved for human use

Evidence

Not graded on a research bench yet

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.

Reviewed 4 November 2026

01 Overview

## What Alpha-Ketoglutarate (AKG) is

In worms, AKG extended lifespan by about 50 percent, and a 2020 Buck Institute study reported longer life in female mice and less frailty in both sexes when Ca-AKG was added to food from 18 months of age (PMID: 24828042, PMID: 32877690). The US National Institute on Aging's Interventions Testing Program found no lifespan gain in either sex when it gave AKG to genetically heterogeneous mice from 18 months at the same dose, or from 7 months at a lower achieved dose (PMID: 38753230, PMID: 41843349). Human evidence consists of small trials from the 1990s and 2000s in surgery, dialysis and bone loss, uncontrolled or cross-sectional company-linked reports of lower DNA methylation age, and a 120-person placebo-controlled trial in Singapore with no results posted or published by 26 October 2026 (PMID: 1898624, PMID: 10383011, PMID: 17896582, PMID: 34847066, PMID: 42166733, PMID: 37217632).

### How it works

### What AKG is

Alpha-ketoglutarate is an intermediate of the tricarboxylic acid (TCA) cycle (PMID: 24828042). Cells make it from isocitrate through the enzyme isocitrate dehydrogenase, and from glutamate through glutamate dehydrogenase or transamination reactions (PMID: 24828042). AKG is the carbon skeleton that corresponds to glutamine, and surgical researchers in Stockholm tested it as a precursor for muscle glutamine synthesis after operations (PMID: 1898624, PMID: 1969067); see BodyHackGuide's L-glutamine (https://www.bodyhackguide.co/compound/l-glutamine) guide.

Read the full mechanism Show less

### A co-substrate for 2-oxoglutarate-dependent oxygenases

A large family of enzymes, the 2-oxoglutarate-dependent oxygenases, uses AKG to carry out hydroxylations and demethylations; in animals these enzymes act in collagen formation, regulation of gene transcription, modification and repair of DNA and RNA, and fatty acid metabolism (PMID: 29494239). In human cells their activity responds to the supply of oxygen, iron and 2-oxoglutarate itself (PMID: 32985654). BodyHackGuide's vitamin C (https://www.bodyhackguide.co/compound/vitamin-c) and collagen (https://www.bodyhackguide.co/compound/collagen) guides cover the collagen-hydroxylating members of this family.

### Worms: ATP synthase and TOR

At the University of California, Los Angeles, AKG extended the lifespan of the worm Caenorhabditis elegans by about 50 percent, with the largest effect at 8 mM (PMID: 24828042). AKG bound and inhibited the beta subunit of ATP synthase (complex V of the mitochondrial electron transport chain), which lowered ATP content and oxygen use and increased autophagy in worms and in mammalian cells; the lifespan gain required ATP synthase subunit beta and depended on TOR signaling (PMID: 24828042). Worm AKG levels rose during starvation, and AKG did not further extend the lifespan of worms on dietary restriction (PMID: 24828042).

### Flies

In fruit flies, AKG added to the diet extended lifespan but reduced reproduction, improved climbing, and increased resistance to heat stress but not to oxidative stress or starvation; treated flies had a lower ATP/ADP ratio, more autophagy, AMPK activation and lower mTOR activity (PMID: 31242135).

### Mice: inflammation rather than TOR

In the 2020 Buck Institute mouse study, three months of Ca-AKG did not lower mTORC1 signaling in the tissues tested; instead, treated female mice largely did not show the age-related rise in most systemic inflammatory cytokines, and T cells from treated female mice made more of the anti-inflammatory cytokine IL-10 (PMID: 32877690). A study in aged mice found that AKG increased bone mass, reduced age-related bone loss and sped bone regeneration, and lowered the histone marks H3K9me3 and H3K27me3 in bone marrow stem cells (PMID: 33154378).

### How the body handles oral AKG

No human pharmacokinetic study of oral AKG supplements was found. In pigs, AKG was absorbed better from the upper small intestine than from lower sections, and AKG infused into the portal vein left the blood with a half-life of less than 5 minutes (PMID: 16401194). In three growing pigs, only about 4 percent of AKG given in feed could be accounted for in the portal vein, and the authors concluded that oral AKG has low availability to the rest of the body (PMID: 15379910). A radiolabeling study in healthy volunteers, done to develop AKG as an oral cyanide antidote, found that splitting 20 g of oral AKG into two 10 g doses taken with 300 mL of water raised measured bioavailability to 40 percent, compared with a single 20 g dose (PMID: 20572756).

### Studied for

- Aging biology
- Mitochondrial metabolism
- Epigenetics
- Bone metabolism
- Clinical nutrition
- Nephrology

### Benefits listed

- Lifespan of the worm Caenorhabditis elegans, extended by about 50 percent (PMID: 24828042)
- Lifespan of female C57BL/6 mice fed Ca-AKG from 18 months, not repeated in two Interventions Testing Program tests, and frailty scores in both sexes (PMID: 32877690, PMID: 38753230, PMID: 41843349)
- Serum CTX, a marker of bone breakdown, in a 6-month trial in 76 postmenopausal women with osteopenia (PMID: 17896582)
- Muscle free glutamine and nitrogen balance after gallbladder surgery in 21 patients (PMID: 1898624)

Show 2 more Show less

- Serum phosphate in dialysis patients, lowered as much as with calcium acetate and with less hypercalcemia (PMID: 10383011)
- Bone mass in aged mice (PMID: 33154378)

02 Research

Free with email

## What the research shows

No research bench grades Alpha-Ketoglutarate (AKG) yet. Benches compare compounds people pair, with the evidence for each.

### Unlock the research summary

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- A summary of the key research
- Safety and side effects
- A link to the PubMed results

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03 Safety

## Alpha-Ketoglutarate side effects and interactions

### Side effects

#### Common

- Vomiting, anorexia, diarrhea or general uneasiness leading 5 of 17 dialysis patients to stop calcium ketoglutarate within 2 weeks (PMID: 9469496)

#### Serious events

- Lower serum albumin than standard feeding with AKG-enriched tube feeding after major abdominal surgery in 20 patients (PMID: 12297206)
- No human study found lasting longer than 36 months, a 14-patient dialysis study (PMID: 8676818)
- No human breastfeeding, pregnancy, pharmacokinetic or drug interaction data found

### Who should not use it

Contraindications

In a dialysis trial, the patients who could not tolerate calcium ketoglutarate all had gastrointestinal symptoms before starting (PMID: 9469496).

In dialysis patients, calcium ketoglutarate lowered serum phosphate as other calcium phosphate binders do and changed blood calcium and amino acid levels (PMID: 10383011, PMID: 9469496, PMID: 8676801), so the salt is not metabolically neutral when the kidneys fail.

No human data were found for pregnancy or breastfeeding.

### Interactions

Not in our record

Our record lists no interactions for Alpha-Ketoglutarate (AKG). That means none are recorded here, not that none exist.

This interaction data is compiled from published research and community reports. It may not be exhaustive. Always consult a healthcare professional before combining compounds.

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04 Dosing

Free with email

## Dosing

No dose on record

Our record lists no dose for Alpha-Ketoglutarate (AKG). This section holds what it does list.

### Unlock the Dosing section

- Route

05 Prices

## Alpha-Ketoglutarate (AKG) prices

No listings

We do not track a vendor for Alpha-Ketoglutarate (AKG) yet, so this page states no price.

06 Chemistry

## Chemistry and structure

Molecular formula

C5H6O5

Molecular mass

146.10 g/mol

CAS number

328-50-7

Half-life

No published human value was found. In pigs, AKG infused into the portal vein was cleared from the blood with a half-life of less than 5 minutes (PMID: 16401194).

View on PubChem (https://pubchem.ncbi.nlm.nih.gov/compound/51)

07 Related

## Related to Alpha-Ketoglutarate (AKG)

### 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
- 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
- NAD+Phase 2 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.: https://www.bodyhackguide.co/compound/nad

All compounds (https://www.bodyhackguide.co/wiki)

### Compare Alpha-Ketoglutarate (AKG)

- Alternatives to Alpha-Ketoglutarate (AKG): https://www.bodyhackguide.co/alternatives-to/alpha-ketoglutarate-akg

### 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 alpha-ketoglutarate (AKG)?

Alpha-ketoglutarate (AKG) is an intermediate of the tricarboxylic acid cycle that cells make from isocitrate and from glutamate (PMID: 24828042). Alpha-ketoglutarate is also a co-substrate for 2-oxoglutarate-dependent oxygenases, enzymes that act in collagen formation, gene regulation and DNA and RNA modification (PMID: 29494239). In the US, alpha-ketoglutarate is sold in products labeled as dietary supplements, and its calcium salt (Ca-AKG) is the form used in the main aging studies (NIH Dietary Supplement Label Database; PMID: 32877690).

Does AKG extend lifespan in animals?

Alpha-ketoglutarate extended the lifespan of the worm Caenorhabditis elegans by about 50 percent and also extended fruit fly lifespan (PMID: 24828042, PMID: 31242135). In a 2020 Buck Institute study, female mice fed calcium alpha-ketoglutarate from 18 months of age lived longer and both sexes had lower frailty scores (PMID: 32877690). The US National Institute on Aging's Interventions Testing Program found no lifespan gain in either sex when it gave alpha-ketoglutarate to genetically heterogeneous mice from 18 months at the same dose, or from 7 months at a lower achieved dose (PMID: 38753230, PMID: 41843349).

Has AKG been shown to slow aging in people?

No randomized trial of alpha-ketoglutarate and human aging had posted or published results by 26 October 2026; this includes the 120-person ABLE trial of calcium alpha-ketoglutarate in Singapore (ClinicalTrials.gov NCT05706389; PMID: 37217632). A 2021 report of an 8-year average fall in DNA methylation age in 42 people taking a calcium alpha-ketoglutarate and vitamin product had no placebo group and was based on customers of the product and of the testing company, and six of its seven authors listed the supplement company or the testing company as an affiliation (PMID: 34847066). A 2026 cross-sectional study of 4,260 epigenetic test buyers linked the same calcium alpha-ketoglutarate product to a 1.8-year lower estimated biological age, but found no significant difference for ordinary alpha-ketoglutarate (PMID: 42166733).

What does the ABLE trial of AKG test?

The ABLE trial at the National University of Singapore randomized 120 healthy adults aged 40 to 60, whose DNA methylation age at screening exceeded their actual age, to 1 g of sustained-release calcium alpha-ketoglutarate or placebo for 6 months (PMID: 37217632, PMID: 40819772). The primary outcome of the ABLE alpha-ketoglutarate trial is the change in DNA methylation age, with blood, strength, arterial stiffness and fitness measures as secondary outcomes (PMID: 37217632).

What did older human trials of AKG find?

In 21 patients after gallbladder surgery, intravenous nutrition with alpha-ketoglutarate preserved muscle free glutamine and improved nitrogen balance compared with nutrition without it (PMID: 1898624). A 2002 randomized trial found that alpha-ketoglutarate-enriched tube feeding did not improve nitrogen balance or outcomes after major abdominal surgery (PMID: 12297206). In 76 postmenopausal women with osteopenia, alpha-ketoglutarate with calcium lowered a bone breakdown marker over 6 months, but the spine bone density difference was not significant (PMID: 17896582). In dialysis patients, calcium alpha-ketoglutarate lowered serum phosphate about as well as calcium acetate (PMID: 10383011).

Is AKG safe?

Of 17 patients in a dialysis trial, 5 stopped calcium alpha-ketoglutarate within 2 weeks because of vomiting, anorexia, diarrhea or general uneasiness, and all 5 had stomach or bowel symptoms beforehand (PMID: 9469496). The longest human study of alpha-ketoglutarate found lasted 36 months, in 14 hemodialysis patients given calcium alpha-ketoglutarate as a phosphate binder (PMID: 8676818). In mice fed 2 percent calcium alpha-ketoglutarate from 18 months of age, the authors detected no significant adverse changes (PMID: 32877690).

What is AKG's regulatory status in the US?

Alpha-ketoglutarate is not an FDA-approved drug, and a search of Drugs@FDA through the openFDA API on 26 October 2026 found no product containing it. Alpha-ketoglutarate is sold in the US 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). A search of the FDA's GRAS Notice Inventory on 26 October 2026 found no GRAS notice for alpha-ketoglutarate or its salts.

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      "mechanismOfAction": "What AKG is Alpha-ketoglutarate is an intermediate of the tricarboxylic acid (TCA) cycle (PMID: 24828042). Cells make it from isocitrate through the enzyme isocitrate dehydrogenase, and from glutamate through glutamate dehydrogenase or transamination reactions (PMID: 24828042). AKG is the carbon skeleton that corresponds to glutamine, and surgical researchers in Stockholm tested it as a precursor for muscle glutamine synthesis after operations (PMID: 1898624, PMID: 1969067); see BodyHackGuide's L-glutamine guide. A co-substrate for 2-oxoglutarate-dependent oxygenases A large family of enzymes, the 2-oxoglutarate-dependent oxygenases, uses AKG to carry out hydroxylations and demethylations; in animals these enzymes act in collagen formation, regulation of gene transcription, modification and repair of DNA and RNA, and fatty acid metabolism (PMID: 29494239). In human cells their activity responds to the supply of oxygen, iron and 2-oxoglutarate itself (PMID: 32985654). BodyHackGuide's vitamin C and collagen guides cover the collagen-hydroxylating members of this family. Worms: ATP synthase and TOR At the University of California, Los Angeles, AKG extended the lifespan of the worm Caenorhabditis elegans by about 50 percent, with the largest effect at 8 mM (PMID: 24828042). AKG bound and inhibited the beta subunit of ATP synthase (complex V of the mitochondrial electron transport chain), which lowered ATP content and oxygen use and increased autophagy in worms and in mammalian cells; the lifespan gain required ATP synthase subunit beta and depended on TOR signaling (PMID: 24828042). Worm AKG levels rose during starvation, and AKG did not further extend the lifespan of worms on dietary restriction (PMID: 24828042). Flies In fruit flies, AKG added to the diet extended lifespan but reduced reproduction, improved climbing, and increased resistance to heat stress but not to oxidative stress or starvation; treated flies had a lower ATP/ADP ratio, more autophagy, AMPK activation and lower mTOR activity (PMID: 31242135). Mice: inflammation rather than TOR In the 2020 Buck Institute mouse study, three months of Ca-AKG did not lower mTORC1 signaling in the tissues tested; instead, treated female mice largely did not show the age-related rise in most systemic inflammatory cytokines, and T cells from treated female mice made more of the anti-inflammatory cytokine IL-10 (PMID: 32877690). A study in aged mice found that AKG increased bone mass, reduced age-related bone loss and sped bone regeneration, and lowered the histone marks H3K9me3 and H3K27me3 in bone marrow stem cells (PMID: 33154378). How the body handles oral AKG No human pharmacokinetic study of oral AKG supplements was found. In pigs, AKG was absorbed better from the upper small intestine than from lower sections, and AKG infused into the portal vein left the blood with a half-life of less than 5 minutes (PMID: 16401194). In three growing pigs, only about 4 percent of AKG given in feed could be accounted for in the portal vein, and the authors concluded that oral AKG has low availability to the rest of the body (PMID: 15379910). A radiolabeling study in healthy volunteers, done to develop AKG as an oral cyanide antidote, found that splitting 20 g of oral AKG into two 10 g doses taken with 300 mL of water raised measured bioavailability to 40 percent, compared with a single 20 g dose (PMID: 20572756).",
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        "acceptedAnswer": {
          "@type": "Answer",
          "text": "In 21 patients after gallbladder surgery, intravenous nutrition with alpha-ketoglutarate preserved muscle free glutamine and improved nitrogen balance compared with nutrition without it (PMID: 1898624). A 2002 randomized trial found that alpha-ketoglutarate-enriched tube feeding did not improve nitrogen balance or outcomes after major abdominal surgery (PMID: 12297206). In 76 postmenopausal women with osteopenia, alpha-ketoglutarate with calcium lowered a bone breakdown marker over 6 months, but the spine bone density difference was not significant (PMID: 17896582). In dialysis patients, calcium alpha-ketoglutarate lowered serum phosphate about as well as calcium acetate (PMID: 10383011)."
        }
      },
      {
        "@type": "Question",
        "name": "Is AKG safe?",
        "acceptedAnswer": {
          "@type": "Answer",
          "text": "Of 17 patients in a dialysis trial, 5 stopped calcium alpha-ketoglutarate within 2 weeks because of vomiting, anorexia, diarrhea or general uneasiness, and all 5 had stomach or bowel symptoms beforehand (PMID: 9469496). The longest human study of alpha-ketoglutarate found lasted 36 months, in 14 hemodialysis patients given calcium alpha-ketoglutarate as a phosphate binder (PMID: 8676818). In mice fed 2 percent calcium alpha-ketoglutarate from 18 months of age, the authors detected no significant adverse changes (PMID: 32877690)."
        }
      },
      {
        "@type": "Question",
        "name": "What is AKG's regulatory status in the US?",
        "acceptedAnswer": {
          "@type": "Answer",
          "text": "Alpha-ketoglutarate is not an FDA-approved drug, and a search of Drugs@FDA through the openFDA API on 26 October 2026 found no product containing it. Alpha-ketoglutarate is sold in the US 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). A search of the FDA's GRAS Notice Inventory on 26 October 2026 found no GRAS notice for alpha-ketoglutarate or its salts."
        }
      }
    ]
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