Calcium Alpha-Ketoglutarate (Ca-AKG)
A calcium-buffered salt of alpha-ketoglutarate, a central Krebs-cycle metabolite that declines with age; developed as a better-absorbed oral form and positioned as a biological-age-lowering longevity compound. Update (September 13, 2026): A peer-reviewed cross-sectional analysis in Aging Cell (Pabis et al., acel.70517) of 4,260 self-selected purchasers of a commercial saliva methylation test tested 84 supplements against a proprietary 9-CpG clock (mean absolute error 5.4 years). Delayed-release calcium-AKG plus vitamins showed the strongest association — an average 1.8-year lower Age Residual, persisting after adjustment for age, sex, smoking and health status. This is observational and industry-adjacent, not randomised: healthy-user and reverse-causation bias are unquantified, the outcome is a commercially owned clock rather than function or events, and the associated difference is far smaller than the ~8-year reduction claimed in the 2021 Rejuvant report. The randomised AKG trials (ABLE, NCT07114536) remain the evidence that would change the picture.
Mechanism of Action
AKG is a rate-limiting TCA-cycle intermediate and co-substrate for TET/JmjC-domain dioxygenases that regulate DNA and histone demethylation; in mice it extended lifespan and reduced frailty, plausibly via epigenetic, mTOR/AMPK, and NF-κB effects.
Dosing Protocol
1,000mg
Standard starting dose based on research
Therapeutic Range
1000
Minimum
2000
Maximum
Split into two doses (morning and evening) with food; sustained-release formulations are preferred because free AKG clears from blood within minutes
Cycling Protocol
No validated cycling protocol; human trials to date used continuous daily dosing for 3–7 months
Dosages are general guidelines. Individual requirements vary based on body weight, health status, and specific goals. Start with lower doses and adjust based on response.
Benefits
Primary Benefits
- Small open-label human trial (n=42, Ca-AKG + vitamins formulation, 1,000mg/day) reported an average 8-year reduction in DNA-methylation biological age (TruAge) after ~7 months (Demidenko et al.)
- Extends lifespan and compresses late-life frailty in aged mice (Shahmirzadi et al., Cell Metabolism 2020) — the primary basis for human interest
- Placebo-controlled human RCTs are underway/completed as of 2026 (the ABLE trial; NCT07114536) directly testing DNA methylation age and functional outcomes
Secondary Benefits
Safety Information
Contraindications
Do not use if any of the following apply:
- •History of hypercalcemia, hyperparathyroidism, or calcium-containing kidney stones
- •Significant renal impairment
- •Pregnancy and breastfeeding — no safety data
Drug/Supplement Interactions
May interact with the following. Consult a healthcare provider before combining:
Potential Side Effects
Some users may experience:
This is not a complete list of interactions or side effects. Individual responses vary. Always start with the lowest effective dose and monitor your response. Report any adverse effects to your healthcare provider.
Quality Markers
Look for these specific quality indicators when sourcing this compound:
- Choose calcium alpha-ketoglutarate (not free-acid AKG) — the form used in published human data
- Sustained-release or divided dosing to counter AKG's minutes-long plasma half-life
- Third-party verified elemental calcium content, especially if combined with other calcium sources
Trusted Certifications
Note: Supplement quality varies dramatically between brands. Cheap supplements often contain fillers, incorrect doses, or contaminants. Investing in quality products from reputable manufacturers is essential for safety and efficacy.
Evidence Profile
Evidence Score
4/10
Emerging/Anecdotal
Limited clinical data, primarily mechanistic studies or user reports
Evidence Scale
8-10
Strong
5-7
Moderate
1-4
Emerging
Sample member
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