Also known as: AKG, Ca-AKG, Calcium alpha-ketoglutarate, 2-oxoglutarate, AAKG
FoundationalEmerging evidence
A citric acid cycle intermediate that has moved from sports nutrition into the longevity category. The animal data is genuinely interesting; the human data has barely started.
Typical dose
1000.0–3000.0 mg per day
Daily with food
What it is
Alpha-ketoglutarate is a molecule sitting in the middle of the citric acid cycle, the pathway that extracts energy from carbohydrate, fat and protein. The body produces it constantly as part of normal metabolism.
It has had two separate lives as a supplement. The older one is arginine alpha-ketoglutarate, or AAKG, which was sold for pump in the 2000s on evidence that did not hold up. The newer one is calcium alpha-ketoglutarate, sold for longevity.
These are not the same product and should not be confused. Ca-AKG is what the longevity research uses, and buying AAKG expecting those effects is a mistake the naming makes easy.
How it works
Beyond its role in energy production, alpha-ketoglutarate is a required cofactor for a large family of enzymes called dioxygenases, which are involved in collagen synthesis, DNA and histone demethylation, and oxygen sensing.
The epigenetic angle is what drives the longevity interest. Those demethylating enzymes influence which genes are switched on, and their activity depends on alpha-ketoglutarate availability, which declines with age.
It also participates in nitrogen handling, accepting an amino group to form glutamate, which is the basis of its older use in ammonia clearance contexts.
What the evidence shows
The animal data is the reason anyone is interested. A well-publicised study reported that calcium alpha-ketoglutarate extended healthspan in mice and compressed the period of ill health at the end of life, which is a more meaningful finding than lifespan alone.
Human evidence is early. Small studies have reported changes in biological age markers, but these are preliminary, often industry-linked, and rely on measures whose meaning is itself debated.
For the older AAKG performance claims, controlled trials in trained individuals generally found no benefit to strength, blood flow or performance. That question is reasonably settled and the answer was no.
Dosing
Longevity protocols typically use 1 to 3 g daily of calcium alpha-ketoglutarate, often in a sustained-release format, based on scaling from the animal work rather than on human dose-finding.
Buy Ca-AKG if the longevity research is your reason. AAKG is a different product with a different and largely negative evidence record.
Take with food. Be clear-eyed about what you are buying: the animal data is genuinely interesting, the human data is thin, and you are paying to participate in an unresolved question rather than to obtain an established benefit.
Rapidly metabolised; sustained-release formats used to extend exposure
Timing
Daily with food
Competition status
Permitted — not on the WADA Prohibited List
Category
Foundational
Safety and side effects
Alpha-ketoglutarate is a normal metabolic intermediate and is well tolerated in the studies conducted. Digestive upset is the main reported effect.
The calcium content of Ca-AKG is worth counting toward your total calcium intake if you also take a calcium supplement or a multivitamin.
Long-term human safety data is limited, as it is for everything in the longevity category. Speak to your doctor before use if you take regular medication or are under medical care.
Who should avoid it
Count the calcium content toward your total if you also take calcium or a multivitamin. Speak to your doctor before use if you take regular medication or are under medical care. Long-term safety data is limited. Not established at supplemental doses in pregnancy or breastfeeding.
This entry is provided for information only. Food supplements should not be used as a substitute for a varied and balanced diet and a healthy lifestyle. Consult a qualified healthcare professional before use if you are pregnant, breastfeeding, taking medication or under medical supervision.
