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Research · Supplements

Alpha-ketoglutarate

No placebo-controlled results on biological age were located. An uncontrolled review of 42 users of an AKG product reported epigenetic age 8 years lower, and a cross-sectional study linked the same product to 1.8 years lower. Both have ties to the product. In one bone trial, AKG with calcium lowered a bone breakdown marker. Adverse effects are barely studied.

Add to Bio HackChecked 2026-11-09
Status
Dietary supplement in the US.
Also called
AKG, Ca-AKG, calcium alpha-ketoglutarate, alpha-ketoglutaric acid, 2-oxoglutarate, Rejuvant, ornithine alpha-ketoglutarate, OKG
Taken for
slowing aging, longer life, biological age, epigenetic age, bone health, muscle, recovery

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help3

Reported risks2

What people take it for, and what was found

Shown to help3

Limited

Epigenetic age

Limited evidence: product users showed lower epigenetic age on one company's saliva test, in studies with no control group and ties to the seller.

The numbers and sources
Effect
In a retrospective analysis of 42 people taking Rejuvant, an AKG formulation with vitamins, for an average of 7 months, DNA methylation age fell by an average of 8 years (p = 6.5 × 10⁻¹²) [1]. In a cross-sectional study of 4,260 people who bought saliva epigenetic tests, users of a delayed-release calcium AKG plus vitamin product had an average 1.8 years lower age residual. People taking regular AKG showed a smaller difference that was not significant [2].
Population
42 product users with tests before and after use [1]; 4,260 test buyers, 71% using supplements [2].
Sources
[1], [2]
Caveats
Neither study had a control group or randomization. Data in [1] came from the product's users. A corresponding author of [1] is a consultant and board member for Ponce de Leon Health, the product's seller, and the test company had a service agreement with the seller. Two authors of [1] are also authors of [2], and some participants in [2] were recruited through the seller. Both studies used the same company's saliva clock [1][2]. Healthy-user and recruitment bias were noted [2]. A placebo-controlled trial of 1 g a day for 6 months in 120 biologically older adults has finished recruiting [3].
LimitedStudied in women

Bone turnover

One trial found AKG with calcium lowered a bone breakdown marker in postmenopausal women with osteopenia, but bone density did not differ from calcium alone.

The numbers and sources
Effect
Over 24 weeks, the bone breakdown marker CTX fell by up to 37.0% on AKG with calcium, and differed from calcium alone at 12 and 24 weeks. Osteocalcin did not change. Lumbar spine bone density rose 1.6% from baseline on AKG, but the 0.9% difference between groups was not significant [4].
Population
76 postmenopausal women with osteopenia, given 6 g AKG and 1.68 g calcium a day or calcium alone [4].
Sources
[4]
Caveats
One 6-month trial. CTX is a marker, and bone density did not differ between groups [4].
Limited

Recovery after burns (ornithine alpha-ketoglutarate)

Limited evidence: ornithine alpha-ketoglutarate, a different compound given in hospital, improved nitrogen balance and wound closure in small, mixed human and animal studies.

The numbers and sources
Effect
A systematic review of 15 studies found ornithine alpha-ketoglutarate improved nitrogen balance, reduced muscle breakdown and sped wound closure in clinical studies [5].
Population
Clinical, animal and mechanistic studies published 1984 to 2024, mostly from France [5].
Sources
[5]
Caveats
This is a different compound, given enterally in hospital care. The review notes heterogeneity and small cohorts, and mixes human and animal studies [5].

Claimed, not studied in people1

Untested

Longer life

Not studied in people. AKG lengthened life in worms and in one mouse study, but a multi-site mouse program found no longer lifespan.

No study in people. This rests on animal studies.

The numbers and sources
Effect
AKG extended the lifespan of adult C. elegans worms, an effect that required ATP synthase and TOR signaling [6]. In C57BL/6 mice, calcium AKG in the diet gave a longer life with less frailty and lower levels of inflammatory cytokines [7]. In the Interventions Testing Program, AKG given to genetically mixed UM-HET3 mice at three sites did not significantly increase lifespan in males or females [8].
Population
C. elegans worms [6]. C57BL/6 mice [7]. UM-HET3 mice at three US sites [8].
Sources
[6], [7], [8]
Caveats
Lifespan has not been measured in people. The mouse results disagree, and the multi-site program tested a different dose or starting age from earlier work [8]. The epigenetic age studies above do not measure lifespan.

Doses studied

The bone trial used 6 g AKG with 1.68 g calcium a day for 6 months [4]. The registered placebo-controlled trial uses 1 g of sustained-release calcium AKG a day for 6 months [3]. The epigenetic studies did not report a fixed dose in their abstracts [1][2].

Risks

Reported risks2

LimitedHow often is not known

Adverse effects in trials

Limited evidence: in dialysis patients, 5 of 17 stopped calcium AKG within 2 weeks for stomach and bowel upset. Trials of related AKG salts reported them well tolerated.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In 19 hemodialysis patients switched from calcium carbonate, 5 of 17 (29%) were withdrawn from calcium ketoglutarate within 1 to 2 weeks for anorexia, vomiting, diarrhea or general uneasiness. All 5 had stomach or bowel symptoms beforehand, and the other 12 reported no side effects [9]. In 28 hemodialysis patients, high blood calcium occurred in 1 on calcium ketoglutarate and 8 on calcium acetate [10]. In 35 trained men, arginine AKG at 12 g a day for 8 weeks was reported as well tolerated, with clinical blood markers measured against placebo [11].
Population
Adults on hemodialysis [9][10]. 35 resistance-trained men aged 30 to 50 [11].
Sources
[9], [10], [11]
Caveats
The dialysis trials were open label with no placebo, in people with kidney failure, and used AKG as a phosphate binder [9][10]. Arginine AKG is a different salt [11]. No adverse event counts were located for the calcium AKG products sold for aging.
LimitedHow often is not known

Long-term use

One small study: over 36 months on calcium AKG, blood calcium rose and parathyroid hormone fell in 14 dialysis patients. No long-term study in healthy people was located.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In 14 hemodialysis patients given calcium AKG, a mean 4.5 g a day for 36 months, serum phosphate fell from 2.6 to 1.9 mmol/l, serum calcium rose from 2.2 to 2.47 mmol/l, and intact parathyroid hormone fell from 29 to 8 pmol/l [12]. The abstract does not report adverse events [12].
Population
14 adults on hemodialysis [12].
Sources
[12]
Caveats
One uncontrolled study in kidney failure, where the falls in phosphate and parathyroid hormone were the aim of treatment [12]. It does not show what years of use do in healthy people.

Claims tested and not found

  1. That AKG raises bone density. In a 6-month trial, the lumbar spine bone density difference between AKG with calcium and calcium alone was 0.9%, not significant [4].

Sources

  1. Demidenko O, Barardo D, Budovskii V, et al. Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test. Aging. 2021. https://doi.org/10.18632/aging.203736
  2. Pabis K, Wang W, Selvarajoo K, et al. Supplements and Drugs Are Associated With Biological Age in a Cohort of Exceptionally Healthy Individuals. Aging Cell. 2026. https://doi.org/10.1111/acel.70517
  3. Lim ZM, Chew YE, Guan L, et al. Recruitment evaluation of a gerotherapeutic randomized controlled trial testing alpha-ketoglutarate in biologically older, middle-aged adults (ABLE). Experimental Gerontology. 2025. https://doi.org/10.1016/j.exger.2025.112867
  4. Filip RS, Pierzynowski SG, Lindegard B, et al. Alpha-ketoglutarate decreases serum levels of C-terminal cross-linking telopeptide of type I collagen (CTX) in postmenopausal women with osteopenia: six-month study. International Journal for Vitamin and Nutrition Research. 2007. https://doi.org/10.1024/0300-9831.77.2.89
  5. Niederegger T, Munzinger R, Schaschinger T, et al. Metabolic and Immunomodulatory Effects of α-Ketoglutarate in Burn Injuries: A Systematic Review. Journal of Burn Care & Research. 2026. https://doi.org/10.1093/jbcr/irag002
  6. Chin RM, Fu X, Pai MY, et al. The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR. Nature. 2014. https://doi.org/10.1038/nature13264
  7. Asadi Shahmirzadi A, Edgar D, Liao CY, et al. Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice. Cell Metabolism. 2020. https://doi.org/10.1016/j.cmet.2020.08.004
  8. Korstanje R, Strong R, Salmon AB, et al. Astaxanthin, meclizine, mitoglitazone, pioglitazone, alpha-ketoglutarate, mifepristone, methotrexate, and atorvastatin-telmisartan do not increase lifespan in UM-HET3 mice. GeroScience. 2026. https://doi.org/10.1007/s11357-026-02201-2
  9. Bro S, Rasmussen RA, Handberg J, et al. Randomized crossover study comparing the phosphate-binding efficacy of calcium ketoglutarate versus calcium carbonate in patients on chronic hemodialysis. American Journal of Kidney Diseases. 1998. https://doi.org/10.1053/ajkd.1998.v31.pm9469496
  10. Birck R, Zimmermann E, Wassmer S, et al. Calcium ketoglutarate versus calcium acetate for treatment of hyperphosphataemia in patients on maintenance haemodialysis: a cross-over study. Nephrology Dialysis Transplantation. 1999. https://doi.org/10.1093/ndt/14.6.1475
  11. Campbell B, Roberts M, Kerksick C, et al. Pharmacokinetics, safety, and effects on exercise performance of L-arginine alpha-ketoglutarate in trained adult men. Nutrition. 2006. https://doi.org/10.1016/j.nut.2006.06.003
  12. Zimmermann E, Wassmer S, Steudle V. Long-term treatment with calcium-alpha-ketoglutarate corrects secondary hyperparathyroidism. Mineral and Electrolyte Metabolism. 1996. https://pubmed.ncbi.nlm.nih.gov/8676818/

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