Ca-AKG
Also known as: Calcium Alpha-Ketoglutarate, CaAKG, Calcium 2-oxoglutarate, Ca-AKG, Rejuvant
Lower numbers = closer to natural. Higher numbers = more enhanced.
Why this rating?
Calcium alpha-ketoglutarate is the calcium salt of an endogenous TCA-cycle (Krebs cycle) intermediate the body already makes. It is taken as a longevity/healthspan supplement, not a performance enhancer. It does not build muscle, alter hormones, or improve athletic performance. The strongest data are in mice and worms; human evidence is thin and uncontrolled. Not WADA prohibited. Rated 1 as a dietary-supplement-tier longevity compound with no ergogenic effect.
Overview
A calcium salt of alpha-ketoglutarate (AKG), a central intermediate of the TCA/Krebs cycle that also serves as a co-substrate for a large family of dioxygenase enzymes (including DNA and histone demethylases). Endogenous AKG levels fall with age, which is the rationale for supplementation. It is marketed as a longevity/biological-age supplement (e.g. Rejuvant). Be clear-eyed: the headline lifespan and 'biological age reversal' findings come from mouse studies and a small uncontrolled human dataset, not rigorous human trials.
Purpose & Use Cases
Longevity / Healthspan
The core use case. In aging mice, late-life calcium AKG extended median lifespan and, more consistently, compressed morbidity (more healthy, less frail time). Human longevity use is extrapolated from this.
Epigenetic / Biological Age
Because AKG fuels DNA/histone demethylases, it is promoted for favourable shifts on DNA-methylation 'aging clocks.' The human signal here is from a small retrospective, uncontrolled dataset, suggestive, not proven.
Inflammation & Connective Tissue
AKG suppresses inflammatory signalling in animal models and, as a prolyl-hydroxylase co-substrate, supports collagen synthesis, the basis for interest in bone and connective-tissue health.
Benefits
- Replenishes an endogenous metabolite that declines with age
- Extended lifespan / compressed morbidity in aging mice
- Supports epigenetic-enzyme function (DNA/histone demethylases)
- Anti-inflammatory signalling in preclinical models
- Non-hormonal, inexpensive, well tolerated
Good to Know
The evidence is mostly animal
The lifespan/healthspan data (Shahmirzadi et al., Cell Metabolism 2020) are in mice: late-life CaAKG raised median lifespan in females (~16%) and compressed frailty in both sexes, with weaker/non-significant lifespan effects in males. Worm data preceded it. This is genuinely promising basic science, not proof of a human benefit.
The human "8-year age reversal" study is weak evidence
The widely-cited Rejuvant/TruAge result (an average ~8-year drop in a DNA-methylation age estimate) was a small, retrospective, uncontrolled, non-placebo analysis using a saliva-based clock without an independently validated public algorithm. Self-selected duration and placebo effect are unaddressed. Treat it as a hypothesis, not a demonstrated outcome.
It is a metabolite you already make
AKG is a normal TCA-cycle intermediate and a co-substrate for the enzymes that demethylate DNA and histones and hydroxylate collagen/HIF. Supplementation is a 'top-up' of a molecule that declines with age, which is why the safety profile is benign.
Not performance-enhancing
Despite older marketing (arginine-AKG was sold as a pump/N.O. product), calcium AKG does not build muscle, raise testosterone, or improve strength/endurance in trained humans. It belongs in the longevity bucket, not the ergogenic one.
Calcium salt vs other forms
Most longevity research and products use the calcium salt (CaAKG) for stability. Arginine-AKG (AAKG) is a different, older pre-workout ingredient with its own (unimpressive) performance literature. Do not conflate the two.
Dosage Guidelines
| Experience Level | Dosage Range |
|---|---|
| Beginner | 300 – 1000 mg/day |
| Intermediate | 1000 – 1000 mg/day |
| Advanced | 1000 – 2000 mg/day |
The most-cited human protocol (Rejuvant) uses ~1g/day of a sustained-release calcium AKG. Doses are taken continuously as a longevity supplement rather than 'cycled.' Note the calcium content adds to daily calcium intake, factor it into your total (excess calcium is not benign for arteries), and separate from thyroid meds/some minerals. There is no established 'optimal' human dose; 1g/day is a convention, not a validated target.
Circulating AKG is rapidly consumed by metabolism (free plasma half-life well under 5 minutes in pharmacokinetic studies); commercial products (e.g. Rejuvant) use a patented controlled-release tablet coating over the CaAKG core to slow absorption, but it is not a drug with a meaningful steady-state half-life.
Side Effects
GI Upset
uncommonMild nausea, stomach discomfort, or loose stools, usually at higher doses or on an empty stomach.
Take with food; split the dose or lower it.
Excess Calcium Load
uncommonAs a calcium salt, 1g CaAKG contributes meaningful elemental calcium. Chronically high total calcium intake is not harmless (vascular calcification concern).
Count it toward total daily calcium; do not stack blindly on top of high-dose calcium supplements.
General Mitigation Strategies
Generally very well tolerated in the short human data available. Take with food to avoid GI upset, and account for the calcium content in your overall intake. The bigger 'risk' is opportunity cost and marketing hype. The impressive numbers are from mice and an uncontrolled human dataset, so calibrate expectations accordingly.
Post Cycle Therapy (PCT)
Not hormonal. No PCT required.
How It Works
AKG sits at the crossroads of energy metabolism and epigenetic regulation. As a TCA-cycle intermediate it feeds ATP production and amino-acid/nitrogen metabolism. Just as importantly, it is the obligatory co-substrate for alpha-ketoglutarate-dependent dioxygenases, TET enzymes (DNA demethylation), Jumonji-domain histone demethylases, and prolyl hydroxylases (which regulate HIF and collagen). Through these it influences the epigenome, hypoxia signalling, and connective-tissue synthesis. In animal work it also suppresses chronic inflammation (raising IL-10) and has been linked to reduced mTOR/ATP-synthase activity. AKG declines with age, and restoring it is proposed to partially normalise these pathways.
Fundamentals
Reference on the practices relevant to Ca-AKG: how they are done and where they go wrong. Not a recommendation to use it.
WADA Status
Calcium alpha-ketoglutarate is an endogenous metabolite sold as a dietary supplement and is not listed on the WADA Prohibited List.