Alpha ketoglutarate

non-nutrient/non-botanicalOctyl .alpha.-ketoglutarate

What is it

Alpha-ketoglutarate (AKG, also called alpha-ketoglutaric acid or 2-oxoglutarate) is a central intermediate in the Krebs cycle of cellular energy metabolism. It is also a key precursor and cofactor in amino acid metabolism, epigenetic regulation, and oxygen sensing pathways.

How it works

AKG plays multiple critical roles in cellular biochemistry. As a Krebs cycle intermediate, it is converted to succinyl-CoA, producing NADH for energy generation. As the keto-acid related to glutamate, it is central to nitrogen handling and amino acid metabolism throughout the body. Research suggests AKG is also an essential substrate for alpha-ketoglutarate-dependent dioxygenase enzymes, including TET enzymes (DNA demethylation), Jumonji-domain histone demethylases (gene regulation), and prolyl hydroxylases (oxygen sensing via HIF-1alpha). Through these enzyme families, AKG influences gene expression, cellular responses to stress and hypoxia, and epigenetic state. AKG declines with age in many tissues. Animal studies show that supplementing AKG can extend lifespan, improve healthspan biomarkers, support bone density, and reduce systemic inflammation. Human clinical evidence is much more limited, with one open-label study suggesting effects on epigenetic aging markers and limited evidence in other clinical applications including critical care nitrogen support.

Evidence for 5 uses

AI-assisted evidence assessment — talk to your doctor before relying on any single supplement.

Critical care nitrogen support

Grade C

Moderate evidence

Ornithine alpha-ketoglutarate (OKG) has been used clinically in malnutrition and critical illness to support nitrogen retention with moderate evidence.

Muscle and recovery

Grade D

Mixed evidence

Limited evidence for muscle protein synthesis effects; AAKG is marketed for athletic use but evidence is mixed.

Bone health

Grade D

Mixed evidence

Animal evidence for bone density effects; limited human evidence beyond calcium contribution of calcium AKG.

Healthy aging biomarkers

Grade F

Limited evidence

One small open-label trial reported reductions in epigenetic age markers with calcium AKG. No rigorous controlled human trials.

Lifespan

Grade F

Limited evidence

Strong animal evidence; no human evidence for lifespan extension.

4 commercial forms

Calcium alpha-ketoglutarate

Common form; provides both AKG and calcium.

The form used in published longevity research.

Sodium alpha-ketoglutarate

Sodium salt alternative.

Used in research and supplements when avoiding extra calcium.

Arginine alpha-ketoglutarate (AAKG)

Provides arginine plus AKG; marketed for performance.

Common in pre-workout supplements with limited supporting evidence.

Ornithine alpha-ketoglutarate (OKG)

Clinical nutrition application.

Used in some clinical nutrition formulas for nitrogen support.

Dosage

Typical supplement doses are 1-3 grams per day. Calcium AKG used in the published human aging trial was 1 gram per day. Clinical research has used widely varying doses. There is no established RDA.

When and how to take it

Take with meals to reduce GI upset. Splitting daily doses (morning and evening) provides more consistent levels. Effects on long-term outcomes like aging biomarkers may take months to assess. Short-term applications (recovery, athletic) may show effects within weeks if any.

Food sources

Food	Amount	%DV
Most foods	AKG is endogenously produced; specific dietary intakes are not typically targeted	—

Safety

AKG supplements appear well tolerated based on available human use. Common side effects are mild and include gastrointestinal upset, headache, and occasional flushing. Salt-specific considerations apply: calcium AKG adds to calcium intake; sodium AKG to sodium intake. Long-term safety data are limited.

Who should be cautious

Pregnancy and breastfeeding safety is not established. People with cancer should consult their oncologist due to AKG's role in many cellular processes. People with kidney disease, severe liver disease, or specific salt-related conditions should consult a clinician. People taking chemotherapy should not start AKG without oncologist approval.

Interactions

Salt-specific interactions are most relevant: calcium AKG with calcium-binding medications (tetracyclines, bisphosphonates), sodium AKG with sodium-restricted regimens. AKG itself has limited well-characterized drug interactions. Theoretical interactions with chemotherapy, particularly agents affecting epigenetic regulation or hypoxia pathways.

Frequently asked questions

What is alpha-ketoglutarate used for?⌄

AKG is used as a longevity supplement (especially calcium AKG), an athletic performance supplement (AAKG), and in clinical nutrition for nitrogen support (OKG). Evidence varies considerably across applications.

Does AKG really extend lifespan?⌄

Animal studies show extended healthspan and lifespan with AKG supplementation. Human clinical evidence is limited to one small trial showing reductions in epigenetic age markers - lifespan effects in humans have not been demonstrated.

How is this different from the other AKG entry?⌄

This is an alternate database entry for alpha-ketoglutarate. The compound, applications, and evidence base are the same.

Is AKG safe?⌄

Limited human use suggests good tolerability at typical doses. Long-term safety beyond a year or two is not well established. Salt-specific considerations apply.

Which form is best?⌄

Depends on application. Calcium AKG for longevity-focused use, AAKG for athletic performance, OKG for clinical nitrogen support. Choose based on goals and tolerance for salt form.

References

PubChem: Alpha-ketoglutarate — PubChem link
Wikidata: Alpha-ketoglutarate — Wikidata link

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Disclaimer: These statements have not been evaluated by the FDA. This page is educational, not a substitute for personalized medical advice. Evidence grades are AI-assisted assessments — talk to your doctor before starting any new supplement, especially if you're pregnant, breastfeeding, on medications, or managing a chronic condition.