Rankings / Longevity — Supplements

Alpha-ketoglutarate (Ca-AKG)

Longevity · TCA cycle intermediate

Tier B+

Reviewed by Read Off Label · Last reviewed · How we grade

otc
7.1 / 10
Tier B+
Ev 6 Bn 5 Sf 9

Bottom line

Read Off Label grades Alpha-ketoglutarate (Ca-AKG) as B+ (7.1/10) based on moderate evidence, med benefit magnitude, and a low-risk safety profile.

Shahmirzadi 2020 Cell Metab: ~12% lifespan extension in mice started at 18 mo.

Typical use: 1-2 g/day sustained-release Ca-AKG — OTC.

What this is

Shahmirzadi 2020 Cell Metab: ~12% lifespan extension in mice started at 18 mo. Retrospective TruAge study: ~8-year reduction in epigenetic age after ~7 months of Rejuvant. ABLE RCT ongoing. Better human data than most experimental compounds. Pabis 2026 (Aging Cell, Kennedy lab, n=4,260 health-enthusiast cohort, 9-CpG saliva clock): delayed-release Ca-AKG ("Rejuvant") associated with ~1.8-year lower Age Residual after adjustment for age, sex, smoking, health status, and covariates; regular non-dAKG much smaller and non-significant. CoQ10 + dAKG longitudinal subset trended favourable but did not survive multivariate correction. More conservative than the 2022 single-arm TruAge ~8-year estimate above — adjusted real-world data, but cross-sectional with healthy-user bias; ABLE RCT remains the gold-standard pending data point.

Mechanism

Krebs cycle metabolite; epigenetic regulator via TET/JHDM demethylases; substrate for collagen synthesis; nitrogen metabolism; declines ~10x from age 40-80

Dose & route

1-2 g/day sustained-release Ca-AKG

Citations

Links go to the source. If a link is dead or you want something re-checked, let me know.

Common questions

Does Alpha-ketoglutarate (Ca-AKG) work?
Read Off Label rates the evidence for Alpha-ketoglutarate (Ca-AKG) as Moderate and the benefit magnitude as med, producing an overall grade of B+ (7.1/10). Shahmirzadi 2020 Cell Metab: ~12% lifespan extension in mice started at 18 mo.
Is Alpha-ketoglutarate (Ca-AKG) safe?
Alpha-ketoglutarate (Ca-AKG) has a low risk profile in published human data. Legal status: OTC (Rejuvant). This is not medical advice — see the disclaimer.
What is the typical dose for Alpha-ketoglutarate (Ca-AKG)?
1-2 g/day sustained-release Ca-AKG
How does Alpha-ketoglutarate (Ca-AKG) work?
Krebs cycle metabolite; epigenetic regulator via TET/JHDM demethylases; substrate for collagen synthesis; nitrogen metabolism; declines ~10x from age 40-80

This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.