Alpha-Ketoglutarate (AKG)
A natural metabolite in your body's energy cycle that's emerging as a longevity intervention. The mouse data is striking — and human trials are underway.
Alpha-ketoglutarate (AKG) is a metabolite your body naturally produces as part of the TCA (Krebs) cycle — the central energy pathway in every cell. Levels decline about 10x from age 40 to 60. A landmark 2020 study in Nature Metabolism showed calcium AKG extended median lifespan in mice by 12% and compressed morbidity — meaning the animals were healthier for longer, not just alive longer.
Good for you if: You're interested in longevity science, want to support healthy ageing at the metabolic level, or are building a comprehensive anti-ageing stack.
Dive deeper into the researchCommon side effects
- Mild GI discomfort at higher doses
- Can cause nausea on an empty stomach
- Very few reported side effects overall
What does AKG do?
AKG sits at a critical junction in your metabolism. It's a key intermediate in the TCA cycle (your body's main energy production pathway) and also serves as a co-substrate for a class of enzymes called TET demethylases — which regulate gene expression through epigenetic modifications.
As AKG levels decline with age, two things happen: energy metabolism becomes less efficient, and epigenetic regulation goes awry (genes that should be silenced get activated, and vice versa). Supplementing AKG appears to address both — restoring metabolic efficiency and supporting healthier epigenetic patterns.
What can you expect?
- Better energy and vitality — many users report improved stamina and reduced fatigue
- Younger biological age — preliminary human data shows epigenetic age reversal of ~8 years
- Improved bone and muscle health — AKG supports collagen synthesis and bone mineral density
- Reduced inflammatory burden — modulates IL-10 and other anti-inflammatory pathways
- Healthier hair, skin, nails — anecdotally reported, likely via collagen and metabolic support
How to take it
300–1,000 mg of calcium alpha-ketoglutarate (CaAKG) per day with food. The calcium salt form is what was used in the landmark study. Start at 300 mg and increase based on tolerance.
Rejuvant (LifeAKG) is the branded form with the most human data. Take in the morning with breakfast.
Why calcium AKG: The calcium salt provides stability and better absorption compared to free AKG. It also provides a small amount of supplemental calcium.
Track your biological age alongside AKG supplementation
eterni logs your epigenetic clock results, vitality markers, and supplement stacks — so you can see if AKG is truly turning back the clock.
Get early accessFrequently Asked Questions
Does AKG really extend lifespan?
In mice, calcium AKG extended median lifespan by 12% and significantly compressed morbidity — the animals stayed healthier for longer. A small human pilot showed an average 8-year reversal in epigenetic age (TruAge clock) after 7 months of supplementation. These results are promising but preliminary — large-scale human lifespan data doesn't exist yet.
AKG vs NMN — which is better for longevity?
They target different mechanisms. AKG works on the TCA cycle and epigenetic regulation (TET enzymes), while NMN boosts NAD+ for sirtuin activity and DNA repair. They are complementary, not competing. Many longevity-focused people take both as part of a comprehensive anti-ageing stack.
How much AKG should I take?
Most studies and practitioners recommend 300–1,000 mg of calcium AKG per day. The mouse study used a dose equivalent to roughly 1,000 mg/day in humans. Start at 300 mg and increase if tolerated well. There is no strong evidence that doses above 1,000 mg provide additional benefit.
Is AKG the same as glutamine?
No, but they're related. AKG can be converted to glutamate and then glutamine in the body. However, supplemental AKG has distinct effects on the TCA cycle and epigenetic enzymes that glutamine doesn't share. They're different supplements with different primary benefits.
How it works in your body
AKG is a five-carbon dicarboxylic acid that sits at a metabolic crossroads. In the TCA cycle, it's converted to succinyl-CoA by alpha-ketoglutarate dehydrogenase, generating NADH for ATP production. But AKG also serves as an obligate co-substrate for 2-oxoglutarate-dependent dioxygenases — a large enzyme family that includes TET DNA demethylases and Jumonji histone demethylases.
These epigenetic enzymes use AKG to remove methyl groups from DNA and histones, regulating gene expression. As AKG declines with age, these enzymes become less active, leading to hypermethylation patterns associated with ageing (the epigenetic clock). Restoring AKG levels may partially reverse these age-related epigenetic changes.
What the studies show
- Lifespan: CaAKG extended median lifespan by 12% in female mice and reduced frailty index by 46% (Nature Metabolism, 2020)
- Epigenetic age: A 7-month human pilot showed an average 8-year reduction in biological age (TruAge epigenetic clock) in middle-aged adults
- Bone health: AKG stimulated bone formation and reduced age-related bone loss in animal models
- Inflammation: Modulated IL-10 and reduced chronic low-grade inflammation in ageing mice
- Morbidity compression: The mouse study showed not just longer life, but dramatically healthier old age — less hair loss, better posture, preserved activity
Side effects & safety
AKG is a naturally occurring metabolite with an excellent safety profile:
- GI discomfort — The most common side effect at higher doses. Taking with food prevents this for most people.
- Nausea — Occasionally reported on an empty stomach.
- No serious adverse events — Neither the animal studies nor the human pilots reported significant safety concerns.
Who should be cautious: People with kidney disease (AKG is cleared renally), anyone on dialysis, and people with calcium metabolism disorders (CaAKG provides supplemental calcium). Otherwise, AKG is broadly safe.
Which labs to check
- Epigenetic age test (TruAge, GrimAge, DunedinPACE) — the most relevant marker for AKG's mechanism
- hsCRP — to track anti-inflammatory effects
- Bone density (DEXA) — if interested in bone health effects
- Basic metabolic panel — kidney function and calcium levels
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eterni connects your lab results, supplements, and retests — so you can see the trajectory, not just a snapshot.
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