Ca-AKG (Calcium Alpha-Ketoglutarate)
A calcium salt of the Krebs-cycle intermediate alpha-ketoglutarate, promoted as a geroprotector after it extended lifespan and compressed morbidity in mice. Human data are limited to a small uncontrolled study reporting a reduction in biological-age (methylation) markers.
01 Overview
Alpha-ketoglutarate (AKG) is a central metabolite of the citric-acid cycle and a substrate for enzymes that regulate epigenetic marks, collagen synthesis, and nitrogen metabolism; its levels fall with age. The calcium salt (Ca-AKG) is the common supplemental form.
Interest surged after a 2020 mouse study in which late-life dietary Ca-AKG extended lifespan modestly and, more strikingly, compressed the period of late-life morbidity while reducing inflammation. In humans the main evidence is a small, uncontrolled 2021 study (using the TruAge/TruDiagnostic methylation clock) reporting an average reduction in DNA-methylation age after several months. Controlled human trials are lacking, and it is well tolerated.
02 Mechanism
Serves as a TCA-cycle intermediate and cofactor for dioxygenases (including TET and prolyl hydroxylases) that regulate DNA/histone methylation, collagen synthesis, and HIF signalling; proposed to reduce systemic inflammation with age.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Common | 1000–2000 mg/day | Oral | Typical supplement range; the human methylation study used ~1 g twice daily. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Compressed late-life morbidity (mice)Late-life Ca-AKG modestly extended lifespan and markedly reduced frailty and inflammation in mice. | modest lifespan, large healthspan | Preclinical | |
| Reduced biological (methylation) ageA small uncontrolled human study reported an average drop in DNA-methylation age; needs controlled confirmation. | ~8 years (uncontrolled) | Observational |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Mild GI upsetGenerally well tolerated; occasional mild digestive complaints. | Mild | Rare | Observational | |
| Weak human evidenceHuman benefit rests on a single uncontrolled study; placebo-controlled outcome data are absent. | Mild | Inherent | Unconfirmed |