RESEARCH MONOGRAPH · KDC-MN-105

Alpha-Ketoglutarate (AKG)

May 9, 2026 Kodiac biolabs Research Revised May 30, 2026 2 min read

Our opinion on this compound

68/100

Interesting TCA cycle play with one striking mouse longevity paper. Human translation is open

AKG (or 2-oxoglutarate) is the TCA cycle intermediate that got pulled into the aging conversation by the Asadi Shahmirzadi 2020 paper in Cell Metabolism. The Brian Kennedy group at Buck Institute ran calcium AKG in middle-aged mice and saw a roughly 12% median lifespan extension along with reduced frailty and inflammation markers. That's a real geroscience signal from a serious lab, and it kicked off a fair amount of follow-on interest.

Mechanistically AKG sits at multiple interesting nodes. It's a substrate for the α-ketoglutarate-dependent dioxygenases (which include the TET DNA demethylases and the JmjC histone demethylases, plus the prolyl hydroxylases regulating HIF). So you can construct a story where AKG availability tunes epigenetic state, hypoxia signaling, and collagen biology simultaneously. AKG also supports protein synthesis and connects to BCAA metabolism. There's a lot of mechanism to choose from, which is a strength and a weakness.

The human side is much thinner. The Demidenko 2021 retrospective using TruDiagnostic methylation clocks suggested an AKG-containing supplement (Rejuvant) was associated with reduced biological age, but it was observational, non-randomized, and the cohort was self-selected. RCT data is sparse. There's plausible biology, modest preclinical evidence, and very limited human controlled data.

What we like: real cell biology, real mechanism breadth, and the Buck/Kennedy connection means the science is not coming from a bad place. The polyamine-and-AKG-and-spermidine cluster of interventions hitting overlapping autophagy and proteostasis axes is genuinely interesting.

What we dont like is the marketing gap. Rejuvant and friends have pushed AKG as a clinically validated anti-aging molecule, which oversells what's been demonstrated in humans by a wide margin. One mouse paper plus a retrospective is not a clinical case.

Sourcing: calcium AKG (the form used in the Kennedy paper) is widely available and cheap, the molecule is stable, storage is unremarkable. Purity 98%+ is standard. Be aware that some commercial AKG products use arginine AKG or other salts which behave somewhat differently.

Worth keeping an eye on. The mechanism is interesting, the mouse data is real, the human data is genuinely thin, and the marketing is well ahead of the science. Typical longevity supplement situation.

Evidence: 50
Mechanism: 70
Reliability: 55
Safety: 85
Sourcing: 88
Value: 78
Signal: 60
Staying power: 60

Plain-language summary Intrigue 65 / 100

Alpha-ketoglutarate (AKG) is a TCA cycle intermediate that has shown lifespan extension in mouse studies. Calcium AKG (Ca-AKG) is sold as a longevity supplement, popularized by Rejuvant. Not stocked by Kodiac. This monograph is provided for research and educational reference.

Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.

TCA cycle intermediate / 2-oxoglutarate

A TCA cycle intermediate sold as calcium alpha-ketoglutarate (Ca-AKG) for longevity applications based on extension of lifespan in mice and worms.

Abstract

Alpha-Ketoglutarate (AKG, 2-oxoglutarate; CAS 328-50-7; molecular formula C5H6O5; molecular weight 146.10) is a tricarboxylic acid cycle intermediate that declines with age in plasma and tissues. The compound is a substrate for the 2-oxoglutarate-dependent dioxygenase family of enzymes (including DNA and histone demethylases, prolyl hydroxylases, and TET enzymes), placing it at a hub of cellular regulation. AKG supplementation extends lifespan in C. elegans (up to 50 percent) and in mice when given as the calcium salt at 2 percent in chow. The mechanism in mice is incompletely characterized but appears to involve reduced cellular senescence, improved metabolic flexibility, and reduced inflammaging markers. Sold as calcium alpha-ketoglutarate (Ca-AKG, Rejuvant) for supplemental use. Reported research dose ranges in the literature are typically 500 to 2000 mg.

Mechanism of action

TCA cycle intermediate and substrate for 2-oxoglutarate-dependent dioxygenases. Reduces senescence and inflammaging in aged mice.

Reported research dose ranges

500 to 2000 mg (reported research dose ranges in the literature).

References

Asadi Shahmirzadi A, et al. Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice. Cell Metab 2020.

Read the full monograph

The full reference document covers compound identification, discovery and developmental history, mechanism of action, pharmacokinetics, reported research dose ranges, sourcing and quality verification, reconstitution and handling, stack interaction considerations, and a curated reference list. Available as a research-use-only PDF download.

KDC-MN-106

The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.

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FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

Kodiac sells research compounds for investigative use only.

Alpha-Ketoglutarate (AKG)

Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

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Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

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