Calcium alpha-ketoglutarate (Ca-AKG)

Ca-AKG · calcium alpha-ketoglutarate · AKG · alpha-ketoglutarate

A Krebs-cycle intermediate promoted to lower 'biological age'.

TypeSupplement / dietary

The grade answers: What does the human evidence support for: Metabolic / epigenetic aging?

Grade

Limited

The grade rates evidence quality — it is not advice to take or buy.

Class: Metabolic intermediate
Primary use: Metabolic / epigenetic aging
Evidence strength: low
Last reviewed: 2026-07-01

Bottom line

Strong animal data and one small, widely-cited human study on biological-age markers — but the human evidence is thin, early, and partly industry-linked. Interesting, far from proven.

What the evidence says

Alpha-ketoglutarate is a central metabolite in the Krebs cycle and a cofactor for enzymes that regulate the epigenome and collagen synthesis; its levels fall with age. In animals it extended healthspan and, in some models, lifespan. The human story rests largely on a single small study reporting a reduction in an epigenetic 'biological age' clock with a Ca-AKG formulation — promising but preliminary, unblinded in parts, and connected to the product's makers. Grade C: compelling mechanism and animal data, minimal independent human evidence.

Key studies

[1]
Ca-AKG and biological age markers in adults (pilot) · pilot trial
Reported drop in an epigenetic-age clock — small, preliminary.
Open on PubMed ↗
[2]
Alpha-ketoglutarate and healthspan in animals · preclinical
Healthspan/lifespan signals in animal models.
Open on PubMed ↗
[3]
Alpha-ketoglutarate metabolism and aging (review) · review
Explains the epigenetic-cofactor rationale.
Open on PubMed ↗

See all studies on PubMed ↗

Mechanism

Serves as a Krebs-cycle intermediate and as a cofactor for dioxygenase enzymes (including TET and prolyl-hydroxylases) that influence DNA methylation, collagen synthesis and hypoxia signalling.

Safety

Generally well tolerated in the limited human data; longer-term safety is not established. As a supplement it also delivers calcium, which counts toward total intake.

Dosage context

The cited human work used ~1 g/day of a Ca-AKG formulation. No independent dose-finding or replication has established an optimal regimen.

Examples of application

Taken as ~1 g/day of the Ca-AKG form used in the cited study.
Evidence rests on one small biological-age trial — treat as early.
Also adds calcium toward daily intake.

From the field

Ca-AKG rides on one small biological-age study and strong mouse data. We grade it C and are explicit that a single, partly self-interested human trial is a starting point, not a verdict.

Related molecules

NMNB

How we assign grades → Method