Calcium Alpha-Ketoglutarate
Evidence Fact Sheet
CaAKG
Calcium alpha-ketoglutarate (CaAKG) is a calcium salt of the TCA-cycle intermediate alpha-ketoglutarate, marketed as a longevity supplement (e.g. Rejuvant). Human data are open-label/biomarker; the definitive double-blind placebo RCT (ABLE) is ongoing, and a 2026 ITP mouse study found no lifespan benefit. Typical research dose ~1000 mg/day. US DSHEA; no authorized EU/ANVISA/China claim.
Also known as: CaAKG · Calcium AKG · Calcium Alpha-Ketoglutarate · Ca-AKG
Overview
Calcium alpha-ketoglutarate (CaAKG, Ca-AKG) is the calcium salt of alpha-ketoglutarate, an endogenous tricarboxylic-acid (TCA) cycle intermediate that also acts as a co-factor for 2-oxoglutarate-dependent dioxygenases (including TET DNA-demethylases) and is studied for AMPK and OXGR1 signaling in healthy-aging and metabolic research contexts. It is most often used as a longevity / epigenetic-age supplement, with a research-reference dose of roughly 1000 mg/day (the dose used in the Rejuvant open-label study); there is no established RDA or efficacy-validated dose, and it also delivers supplemental calcium. Regulatory status: in the US it is sold as a dietary supplement under DSHEA via a GRAS self-affirmation pathway with no specific FDA-authorized health claim; the EU has no EFSA-authorized claim; ANVISA (Brazil) and China have no specific approval (case-by-case / pending). Educational reference only; not medical advice.
Mechanism of Action
TCA-cycle intermediate / metabolic flux substrate (research-context) · Co-factor for 2-oxoglutarate-dependent dioxygenases incl. TET demethylases (epigenetic-regulation mechanism · preclinical) · AMPK pathway modulation (mechanistic) · OXGR1 receptor signaling (mechanistic) · Calcium-salt delivery vehicle
Body systems: Mitochondrial & Cellular Energy · Cellular Renewal · DNA & Epigenetic · Musculoskeletal
Evidence-Based Benefits
Each benefit below is anchored to a specific PubMed-indexed study. Effect sizes, sample sizes, and p-values are reported as published; no values are inferred. Honest negatives and null results are kept alongside the positive findings, and disease-research populations are described as such — Calcium Alpha-Ketoglutarate is not characterized as a treatment for any disease.
Biological / Epigenetic Age (Open-Label)
RCT supported- 42participants (open-label)
- 8 yearsavg biological-age decrease
- 6.538x10-12p-value
In the most-cited human dataset, a CaAKG-plus-vitamin formulation (Rejuvant, 1 g Ca-AKG/tablet) was associated with an average 8-year decrease in DNA-methylation (epigenetic) biological age after ~7 months. Crucially this was a retrospective, open-label analysis with no placebo control, so it cannot establish causation; the authors themselves call for randomized trials.
Reported effect: n=42; average decrease in biological aging of 8 years; p=6.538x10-12; retrospective, not placebo controlled
“Remarkably, individuals showed an average decrease in biological aging of 8 years (p-value=6.538x10-12)... Primarily, it is not placebo controlled... Future randomized clinical trials will be required.”
Source: PMID 34847066 · Demidenko 2021 · Aging (Albany NY)
Definitive RCT (Ongoing / Feasibility)
RCT supported- 120enrolled (double-blind RCT)
- 467expressed interest
- 66.1 %consent rate
The ABLE trial is the pre-registered double-blind, placebo-controlled RCT designed to test whether 1 g sustained-release CaAKG lowers DNA-methylation age in biologically older, generally healthy adults aged 40-60. This 2025 paper reports only recruitment/feasibility (120 enrolled of 467 interested) and explicitly does NOT yet report efficacy results on biological age — so a properly controlled human efficacy answer is still pending.
Reported effect: 120 enrolled of 467 interested; consent rate 66.1%; recruitment/feasibility only, no efficacy results reported
“Among 467 individuals who expressed interest in participation, 120 participants were enrolled... with a consent rate of 66.1 %... 1 g sustained-release calcium alpha-ketoglutarate versus placebo... double-blind, placebo-controlled randomized trial.”
Source: PMID 40819772 · Lim 2025 · Exp Gerontol
Lifespan in Mice (Rigorous Replication)
Null / no benefit Emerging / indexed- UM-HET3genetically diverse mice
Honest negative: the NIH Interventions Testing Program (ITP), the gold-standard multi-site mouse longevity replication, tested alpha-ketoglutarate in genetically heterogeneous UM-HET3 mice and found it did NOT increase lifespan in either sex. This directly tempers earlier single-lab mouse longevity claims and underscores that the longevity hypothesis remains unconfirmed even in animals.
Reported effect: alpha-ketoglutarate among compounds that did not increase lifespan; none significantly increased lifespan in male or female UM-HET3 mice
“Astaxanthin, meclizine, mitoglitazone, pioglitazone, alpha-ketoglutarate, mifepristone, methotrexate, and atorvastatin-telmisartan do not increase lifespan in UM-HET3 mice... none of the tested compounds significantly increased lifespan in male or female mice.”
Source: PMID 41843349 · Korstanje 2026 · Geroscience
Healthspan / Frailty in Mice (Foundational)
Emerging / indexed- CaAKGcalcium salt, dietary
The foundational preclinical study reported that late-onset dietary CaAKG promoted a longer, healthier life with compressed morbidity and reduced frailty in mice, linked to lower systemic inflammatory cytokines. This is single-lab mouse data and the abstract reports direction rather than extractable headline numbers; the later ITP replication (above) did not confirm a lifespan benefit, so this should be read as hypothesis-generating only.
Effect size: this study reports the direction of the finding but does not state a specific numeric effect size, so none is given here rather than estimated.
“CaAKG promotes a longer, healthier life associated with a decrease in levels of systemic inflammatory cytokines.”
Source: PMID 32877690 · Shahmirzadi 2020 · Cell Metab
Dosage (research context · not a recommendation)
Research-context reference: 1000 mg/day CaAKG was the dose used in the Rejuvant open-label epigenetic-age study (Demidenko 2021); no established RDA or efficacy-validated dose. Educational reference only.
Regulatory Status · 4 Markets
- US · FDA
- GRAS self-affirmation pathway; marketed as a dietary supplement under DSHEA (Rejuvant and other brands legally sold). No specific FDA-authorized health claim.
- EU · EFSA
- Novel Food / EU status: 0 EFSA-authorised and 0 non-authorised health claims (Reg 1924/2006). Some member states permit CaAKG as a food supplement; no EU-level authorized claim.
- CN · China
- Calcium-AKG: AKG not on China's novel-food catalogue; only an unconfirmed calcium-supplement path — no SAMR, common-food, or novel-food approval on record.
- BR · ANVISA
- No specific ANVISA approval; would require case-by-case evaluation under the dietary-supplement framework (RDC 243/2018). No IN 28/2018 Anexo V alegação funcional for CaAKG.
Safety
Long-term tolerability data come largely from dialysis/ICU populations (OKG and CaAKG) with no serious adverse events reported; FDA GRAS self-affirmation pathway. No adequate data in pregnancy/lactation. CaAKG delivers supplemental calcium — total calcium intake should be considered. Long-term safety in healthy aging populations beyond the short open-label/trial durations is not established. Educational information only; not medical advice.
Related
Goals: longevity-stack
Lifestyles: senior-60-plus
References
PubMed-indexed citations anchoring the benefit findings above. Effect sizes are reported as published.
- PMID 34847066 · Demidenko 2021 · Aging (Albany NY) — Biological / Epigenetic Age (Open-Label)
- PMID 40819772 · Lim 2025 · Exp Gerontol — Definitive RCT (Ongoing / Feasibility)
- PMID 41843349 · Korstanje 2026 · Geroscience — Lifespan in Mice (Rigorous Replication)
- PMID 32877690 · Shahmirzadi 2020 · Cell Metab — Healthspan / Frailty in Mice (Foundational)
Frequently Asked Questions
1. Is calcium alpha-ketoglutarate proven to reverse aging in humans?
No. The widely cited 8-year drop in epigenetic biological age (Demidenko 2021, n=42) came from a retrospective, open-label dataset with no placebo control, so it cannot prove cause and effect. The pre-registered double-blind placebo RCT designed to answer this (ABLE, Lim 2025) has enrolled participants but has not yet reported efficacy results. This is an evidence summary, not a recommendation to use it for anti-aging.
2. Did the strong mouse longevity results hold up?
Not in the most rigorous test. While an early single-lab study reported that CaAKG promoted a longer, healthier life in mice, the NIH Interventions Testing Program (Korstanje 2026) tested alpha-ketoglutarate in genetically diverse UM-HET3 mice and found it did not increase lifespan in either sex. That is an important honest negative for the longevity hypothesis.
3. What dose was used in the research?
The open-label epigenetic-age study used a formulation providing about 1000 mg/day of Ca-AKG, and the ongoing ABLE RCT uses 1 g of sustained-release calcium alpha-ketoglutarate. There is no established RDA or efficacy-validated dose, and CaAKG also contributes supplemental calcium, so total calcium intake is a consideration. This page reports research doses only and is not dosing guidance.
4. What is its regulatory status?
In the US, CaAKG is sold as a dietary supplement under DSHEA via a GRAS self-affirmation pathway, with no specific FDA-authorized health claim. The EU has no EFSA-authorized health claim, and Brazil (ANVISA) and China have no specific approval (case-by-case or pending). It is an educational/research-context ingredient, not an approved treatment for any condition.
Last evidence review: 2026-06-13