Mouse lifespan data, early human trials, dose guidance and open questions for evidences.
Calcium alpha-ketoglutarate (Ca-AKG) is one of the few metabolites with published evidence for lifespan extension in mammals, but the data come from mice. Human trials are ongoing and early. Ca-AKG is not proven to extend human life, though it has a plausible mechanistic basis and a reassuring short-term safety profile.
Alpha-ketoglutarate (AKG) is a five-carbon intermediary metabolite in the Krebs cycle. It sits at the crossroads of energy production, amino-acid metabolism and epigenetic clocks regulation. Calcium alpha-ketoglutarate (Ca-AKG) is the calcium salt, which is less acidic, better tolerated in the gut and supplies a small amount of elemental calcium.
AKG declines with age in humans and other mammals. It also acts as a substrate for dioxygenase enzymes involved in DNA demethylation and collagen peptides guide hydroxylation, giving it roles in both energy metabolism and tissue maintenance.
The most cited Ca-AKG longevity paper comes from Buck Institute researchers and was published in Cell Metabolism in 2020. Middle-aged female mice given AKG in their drinking water showed:
Importantly, the benefit was seen when treatment started at middle age, not when it began very late in life. Males showed some but not all of the same effects.
"Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice." Landmark study reporting median lifespan extension and reduced frailty in female mice treated from midlife.
View DOIHuman Ca-AKG trials are smaller and newer than the mouse work. As of 2026, completed studies focus on biomarkers rather than lifespan.
Why might AKG affect ageing? Several non-exclusive mechanisms have been proposed:
Most longevity supplements provide 500 mg to 1,000 mg of Ca-AKG per day, split into one or two servings. This range overlaps with amounts used in human biomarker studies. There is no established RDA or upper safe limit from regulators. This is research data, not a recommendation.
Common study dose: Notes
Common study dose: Easy to mix; taste can be tart
Common study dose: Convenient; check elemental AKG vs salt weight
Common study dose: Often combined with calcium HMB or amino acids
When reading labels, check whether the dose refers to the Ca-AKG salt or the elemental AKG. The salt is heavier, so 1,000 mg of Ca-AKG delivers roughly 700–800 mg of free AKG depending on the formulation.
Ca-AKG has a short but reassuring safety record in human trials. The most common side effects are mild and gastrointestinal:
Cautions:
Quality varies. compare:
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"Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice." Median lifespan extension and reduced frailty in female C57BL/6 mice.
View DOI"Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8-year reduction in biological aging after ~7 months in the TruAge DNA methylation test." Open-label human study.
View DOI"Effect of alpha-ketoglutarate supplementation on C-terminal cross-linking telopeptide of type I collagen (CTX) in postmenopausal women with osteopenia." Six-month biomarker study.
View DOIInterventions Testing Program report on alpha-ketoglutarate in genetically heterogeneous mice. This independent lifespan study did not find the same benefit as the 2020 Buck Institute study, highlighting the need for replication.
View DOI"Recruitment evaluation of a gerotherapeutic randomized controlled trial testing alpha-ketoglutarate in biologically older, middle-aged adults." Protocol and feasibility paper for an ongoing-relevant human RCT.
View DOIThere is no published evidence that Ca-AKG extends human lifespan. A 2020 mouse study reported longer median lifespan and compressed morbidity with alpha-ketoglutarate, but human lifespan trials have not been completed.
supplements commonly provide 500 mg to 1,000 mg of Ca-AKG per day, often as two divided servings. Human trials testing biological-age and performance outcomes are using broadly similar amounts, though long-term optimal dosing is unknown. This is research data, not a recommendation.
Short-term safety data are reassuring, with mild gastrointestinal upset the most commonly reported issue. People with kidney disease, those who are pregnant or breastfeeding, and anyone on medication should speak to a clinician before using Ca-AKG.
Calcium alpha-ketoglutarate is the calcium salt of alpha-ketoglutarate. It supplies both AKG and elemental calcium, tends to be better tolerated than the free acid, and is the form used in most longevity supplements and several clinical trials.
Some human trials administer Ca-AKG with meals to reduce stomach upset, but there is no strong evidence that timing changes efficacy. Consistency matters more than exact timing.