Calcium alpha-ketoglutarate is a calcium salt of alpha-ketoglutarate (AKG), a central intermediate of the Krebs (TCA) cycle that links carbon, nitrogen, and energy metabolism. It is marketed (notably as Rejuvant) as a longevity supplement intended to support healthy aging via metabolic and epigenetic pathways. Interest is driven by mouse studies showing extended healthspan and a small open-label human trial reporting reductions in DNA-methylation biological age, though rigorous controlled human evidence remains preliminary.
Investigated for support of muscle and physical function in aging7
What to watch for
Generally well tolerated in short-term studies
Mild gastrointestinal upset, nausea, or bloating
Possible constipation from the calcium content
Hypercalcemia or conditions predisposing to high calcium levels1,5
History of calcium-containing kidney stones (use caution)1,5
The bottom line
Evidence rating emerging. Most-documented uses: may support healthy aging and reduce biological (epigenetic) age markers, provides bioavailable calcium for bone and muscle support, supports cellular energy metabolism as a tca-cycle intermediate. 8 sources indexed (2007–2021), with 5 interaction records on file.
The science
How it works, mechanistically.
Core mechanism
Alpha-ketoglutarate sits at a metabolic crossroads in the TCA cycle, where it is generated from isocitrate and converted to succinyl-CoA, feeding cellular ATP production and amino acid metabolism via transamination reactions. Beyond bioenergetics, AKG is an obligate co-substrate for the 2-oxoglutarate-dependent dioxygenase family of enzymes, which includes prolyl hydroxylases (regulating HIF and collagen), TET DNA demethylases, and Jumonji-domain histone demethylases. Through these enzymes AKG influences DNA and histone methylation states, providing a proposed link to epigenetic 'reprogramming' of biological age. Proposed downstream effects include modulation of mTOR signaling, reduced systemic inflammation, support of collagen and bone matrix synthesis, and improved mitochondrial efficiency, with the bound calcium also contributing mineral intake.2,1
Class
Longevity / Metabolic Intermediate
Found in food
Alpha-ketoglutarate is produced endogenously in the TCA cycle and is not a notable dietary nutrient, Trace amounts arise from metabolism of dietary glutamate and glutamine, Dairy and leafy greens provide the calcium component
Low-status signs
Not an essential nutrient, so there is no defined alpha-ketoglutarate deficiency syndrome, Inadequate calcium intake can contribute to reduced bone density and muscle cramps
Absorption
Water-soluble; take with food
Dosing
Dosing & protocol.
Common range
1000-3000 mg per day of calcium alpha-ketoglutarate, often split into two doses (the Rejuvant protocol uses about 1000 mg twice daily)
Recommended form
Calcium alpha-ketoglutarate powder in capsules; sustained or divided dosing is commonly used
Water-soluble; taking with food can reduce gastrointestinal discomfort and aid calcium absorption. Separate from supplements or medications whose absorption is impaired by calcium (for example certain antibiotics, levothyroxine, and iron) by several hours. Calcium intake should be split across the day for better uptake.1,2
The calcium salt of alpha-ketoglutarate is water-soluble and dissociates in the gut to release free AKG and calcium. AKG itself is a small, polar dicarboxylic acid that is rapidly absorbed but also rapidly metabolized as a Krebs-cycle intermediate, so systemic exposure of intact AKG is brief; much of an oral dose is consumed by enterocytes and the liver on first pass. Take with or without food; some users split the dose to reduce GI upset. Each ~1,000 mg of Ca-AKG provides roughly 200 mg of elemental calcium, which should be counted toward total daily calcium intake.
Mid1,000 mg Ca-AKG once or twice daily (used as ~1,000 mg/day in the Rejuvant human pilot)
Calcium alpha-ketoglutarate powder
Pharmacologically equivalent to the capsule; dissolving the powder first may speed dissociation but does not meaningfully change the rapid first-pass metabolism of AKG. Has a sharp, sour taste. Mix into water or a small amount of food. Acidic taste; can be buffered by taking with a meal. Same elemental-calcium consideration as capsules.
Budget1,000 to 2,000 mg/day measured by scale; titrate from a lower dose to assess GI tolerance
Arginine alpha-ketoglutarate (AAKG) - distinct, NOT calcium salt
A different AKG salt marketed mainly for exercise/nitric-oxide support. Listed only to flag the common label confusion: AAKG is not the calcium form used in the longevity research and contributes no calcium. Provides arginine plus AKG rather than calcium plus AKG; ergogenic evidence is mixed and modest.
BudgetPer product label for sports use; not a substitute for Ca-AKG longevity dosing
Cost
What it actually costs.
Real-world pricing across three quality tiers. Assumes Calcium alpha-ketoglutarate capsules.
BudgetBest value
$9 /mo
$0.30 per dose
Mid
$24 /mo
$0.80 per dose
Premium
$60 /mo
$2.00 per dose
Effective dose assumed at ~1,000 mg/day. Budget tier reflects generic bulk Ca-AKG powder or commodity capsules; mid tier reflects standard branded capsule products; premium reflects branded longevity products such as Rejuvant, which carry a substantial markup over the cost of the underlying ingredient. Prices are approximate US retail and vary with formulation and pack size. Updated 2026-06-04.
Goals
Goal-based dosing.
Longevity / Healthy Aging
Dose: 1,000 mg Ca-AKG per day (range 1,000 to 2,000 mg/day in practice)7
Timing: Once daily, with or without food; consistent daily timing for adherence
Evidence is preliminary. Mouse data show extended lifespan and compressed morbidity with Ca-AKG, and a small open-label human pilot (Rejuvant, ~1,000 mg/day Ca-AKG) reported reductions in DNA-methylation biological age. There are no large randomized controlled trials confirming a lifespan or hard clinical-outcome benefit in humans, so claims should be framed as emerging and unproven.
Timing: Once daily, taken consistently; effects in the pilot were assessed over several months
The signal for reduced epigenetic-clock age comes from a small uncontrolled pilot study with no placebo arm, so regression-to-the-mean and selection effects cannot be excluded. Treat any biological-age change as a research hypothesis, not a validated outcome.
Bone / Skeletal Support (secondary, hypothesis-stage)
Preclinical work suggests AKG may support bone density via osteoblast activity, and the form delivers some elemental calcium. Human bone-outcome evidence is lacking, so this should not replace established osteoporosis therapy or a dedicated calcium plus vitamin D regimen where indicated.
Lab work
Markers to track.
What to test, the optimal window inside the conventional range, and how long a response takes.
Serum Calcium Ca
Generally neutral; Ca-AKG adds dietary calcium that is normally homeostatically buffered, so serum calcium should stay within range. Monitor for any rise if combined with other calcium or vitamin D sources.1,5
Optimal
9–10 mg/dL
Conventional
8.6–10.2 mg/dL
Responds in
Serum calcium is tightly regulated and typically unchanged; recheck at 8 to 12 weeks if total calcium intake is high.
8.6optimal10.2
Use a fasting morning draw; correct for albumin. Ca-AKG contributes to total daily elemental calcium intake, so account for it when assessing calcium status and avoid stacking with high-dose calcium supplements without monitoring.
Alpha-ketoglutarate is a tricarboxylic acid (TCA) cycle intermediate that declines with age and serves as a substrate for energy metabolism and a cofactor for alpha-ketoglutarate-dependent dioxygenases involved in epigenetic regulation. Supplementation has extended median lifespan and reduced frailty markers in aged mice, and a small open-label human study reported a reduction in DNA-methylation-estimated biological age.8,1
MetabolicEmerging evidenceCalcium alpha-ketoglutarate (sustained-release, e.g. Rejuvant)
Human evidence is limited to small, uncontrolled or single-arm trials; the lifespan and frailty data are strongest in mice. Effects on subjective vitality are not established and should not be overstated.
Provides elemental calcium (roughly 20-25 percent by weight) plus alpha-ketoglutarate, which in animal and limited human studies has been associated with reduced bone resorption and improved calcium retention. The contribution to bone health is partly attributable to the calcium content itself.1,8
BoneEmerging evidenceCalcium alpha-ketoglutarate, taken with adequate vitamin D and vitamin K2
Count the elemental calcium toward total daily calcium intake to avoid exceeding the tolerable upper limit. AKG-specific bone benefit beyond the calcium is not well established.
As a TCA-cycle anaplerotic substrate, alpha-ketoglutarate can feed mitochondrial oxidative metabolism and supports amino acid (glutamate/glutamine) and ATP production. Whether this translates to a measurable improvement in clinical fatigue in humans has not been demonstrated.3
Mechanistically plausible but no controlled human fatigue data. Rule out and address common reversible causes of fatigue (iron, B12, thyroid, sleep) first.
Safety
Full safety detail.
Side effects
Generally well tolerated in short-term studies
Mild gastrointestinal upset, nausea, or bloating
Possible constipation from the calcium content
Hypercalcemia risk if total calcium intake is excessive
Contraindications
Hypercalcemia or conditions predisposing to high calcium levels1,5
History of calcium-containing kidney stones (use caution)1,5
Severe renal impairment (impaired calcium and mineral handling)
Hyperparathyroidism or sarcoidosis without medical supervision
Pregnancy and breastfeeding (insufficient safety data for supplemental use)
Calcium alpha-ketoglutarate delivers a meaningful amount of elemental calcium (approximately 20-25 percent by weight). Combining it with a separate calcium supplement can push total elemental calcium intake above the tolerable upper intake level (2,000-2,500 mg/day for adults), increasing risk of hypercalcemia, constipation, and possibly kidney stones.
Recommendation: Add the elemental calcium from the Ca-AKG product to your other calcium sources and keep total supplemental plus dietary calcium within recommended limits. Reduce or omit a standalone calcium supplement if combined intake is high.
The calcium delivered by Ca-AKG can inhibit absorption of non-heme iron when taken together, an effect well documented for calcium supplements generally.
Recommendation: Separate Ca-AKG from oral iron supplements by at least 2 hours. Take iron on an empty stomach with vitamin C when possible.
High doses of calcium can modestly reduce zinc absorption, so taking the calcium from Ca-AKG together with a zinc supplement may slightly lower zinc uptake.
Recommendation: Separate Ca-AKG and zinc supplements by 1-2 hours if zinc status is a concern, particularly at higher calcium doses.
Vitamin D3 increases intestinal calcium absorption, complementing the calcium and bone-supportive aims of Ca-AKG. Adequate vitamin D status helps direct absorbed calcium toward useful physiological roles.
Recommendation: Maintain adequate vitamin D status alongside Ca-AKG, but monitor total calcium intake, since enhanced absorption plus high calcium load can raise hypercalcemia risk in susceptible individuals.
Vitamin K2 activates osteocalcin and matrix Gla protein, helping incorporate calcium into bone and limit vascular calcium deposition, which complements the calcium content of Ca-AKG in a bone-health context.
Recommendation: Pairing vitamin K2 (and vitamin D) with the calcium from Ca-AKG is reasonable for bone goals. No timing separation needed.
Numbered references. Citations throughout the page link here.
Randomized controlled trials
1
1Calcium alpha-ketoglutarate in the treatment of postmenopausal osteoporosisNeeds sourceNo linkFilip RS et al. · Endocrine Regulations · 2007
Supplementation with calcium alpha-ketoglutarate was associated with improvements in bone mineral density compared with control in postmenopausal women.
Reviews & position papers
3
2Alpha-ketoglutarate supplementation and skeletal and metabolic effects in humans and animal models: a systematic reviewNeeds sourceNo linkBayliak MM, Lushchak VI · Ageing Research Reviews · 2021
3Alpha-ketoglutarate: physiological functions and applicationsNeeds sourceNo linkWu N et al. · Biomolecules and Therapeutics · 2016
AKG serves as a required co-substrate for 2-oxoglutarate-dependent dioxygenases including TET DNA demethylases and Jumonji histone demethylases, providing a mechanistic link between cellular metabolism and epigenetic state.
4Alpha-ketoglutarate as a molecule with pleiotropic activity: from metabolism to epigenetic regulationNeeds sourceNo linkWu N, Yang M, Gaur U, Xu H, Yao Y, Li D · Aging and Disease · 2016
Observational studies
2
5Reversal of biological age in subjects taking calcium alpha-ketoglutarate (Rejuvant)Needs sourceNo linkDemidenko O et al. · Aging (Albany NY) · 2021
In 42 participants taking calcium-AKG, average DNA-methylation age decreased by roughly 8 years over about 7 months of use; uncontrolled design limits causal interpretation.
7Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging miceNeeds sourceNo linkShahmirzadi AA et al. · Cell Metabolism · 2020
Calcium alpha-ketoglutarate supplementation begun in mid-to-late life decreased frailty and markers of inflammation and extended healthspan, with a modest effect on lifespan.
8Alpha-ketoglutarate prevents age-related bone loss and stimulates osteoblast differentiationNeeds sourceNo linkRadzki RP, Bienko M, Filip R, et al. · Journal of Bone and Mineral Metabolism · 2012
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