Calcium alpha-ketoglutarate

updated

Calcium alpha-ketoglutarate (Ca-AKG) is the calcium salt of a Krebs cycle intermediate the body makes, sold to support healthy aging and lower biological age. A single-laboratory mouse study with company funding and equity ties found longer female lifespan, but a 2026 NIA Interventions Testing Program paper that names alpha-ketoglutarate among eleven compounds reported that none significantly increased lifespan. No controlled human efficacy trial has been published, and the placebo-controlled ABLE trial had no posted results on 11 October 2026.

Calcium salt of a Krebs cycle intermediate (alpha-ketoglutarate)

  • Ca-AKG is PubChem CID 3018235, C5H4CaO5, 184.16 g/mol, CAS 71686-01-6; on 11 October 2026 no FDA-approved Ca-AKG drug was found.
  • In C57BL/6 mice fed 2% Ca-AKG from 18 months of age, female median lifespan rose 16.6% and 10.5% in two cohorts, and male survival was not significantly improved. Several authors hold shares or roles in Ponce de Leon Health or Gerostate Alpha.
  • A 2026 NIA Interventions Testing Program paper reported that none of eleven compounds, with alpha-ketoglutarate named among them, significantly increased lifespan in UM-HET3 mice of either sex.
  • The 8-year biological-age drop reported in 42 people taking Rejuvant, an AKG and vitamin formulation, came from a retrospective analysis with no control group.
  • In 4,260 adults who bought an epigenetic test, Rejuvant use was associated with a 1.8-year lower Age Residual on a clock with a mean absolute error of 5.4 years.
  • The placebo-controlled ABLE trial (NCT05706389, 120 adults) passed its listed primary completion date of 15 August 2025 and had no posted results on 11 October 2026.

What is calcium alpha-ketoglutarate, and is it an approved drug?

Ca-AKG is the calcium salt of alpha-ketoglutarate, a Krebs cycle intermediate the body makes. On 11 October 2026 no FDA-approved Ca-AKG drug was found. The products studied differ: a calcium salt in mouse feed, a delayed-release Ca-AKG and vitamin formulation (Rejuvant), and sustained-release Ca-AKG in the ABLE trial.

Calcium alpha-ketoglutarate is PubChem CID 3018235, C5H4CaO5, molecular weight 184.16 g/mol, CAS 71686-01-6, with calcium oxoglurate (a WHO drug dictionary name) among the listed synonyms. The free acid, alpha-ketoglutaric acid (2-oxoglutaric acid), is a separate record: CID 51, C5H6O5, 146.10 g/mol, CAS 328-50-7.

The products in the studies are not the same. The 2020 mouse study used a calcium salt in feed, the Rejuvant product is a delayed-release Ca-AKG plus vitamin formulation, and the ABLE trial uses 1 g of sustained-release Ca-AKG. A rat study found that intestinal absorption did not depend on the AKG salt, but no human data compare salts.

On 11 October 2026 openFDA Drugs@FDA queries for alpha-ketoglutarate and calcium oxoglurate returned no match, and a DailyMed search for calcium alpha-ketoglutarate returned no labels. DailyMed searches for alpha-ketoglutarate and ketoglutarate returned three labels, all multi-ingredient sprays containing ornithine alpha-ketoglutarate, a different compound. No FDA-approved Ca-AKG drug was found. FDA GRAS or dietary-supplement status is not established here.

PubChem: Ca-AKG identity; no FDA-approved Ca-AKG drug found, 11 October 2026

Chemical identity record

National Library of Medicine. PubChem compound record CID 3018235 (calcium alpha-ketoglutarate), with the free acid record CID 51. openFDA Drugs@FDA queries and DailyMed searches run on 11 October 2026.

Calcium alpha-ketoglutarate: PubChem CID 3018235, C5H4CaO5, 184.16 g/mol, CAS 71686-01-6, with "calcium oxoglurate" (a WHO drug dictionary name) among the listed synonyms. The free acid, alpha-ketoglutaric acid (2-oxoglutaric acid), is a separate record: CID 51, C5H6O5, 146.10 g/mol, CAS 328-50-7. AKG is a Krebs cycle intermediate the body makes. On 11 October 2026 openFDA Drugs@FDA queries for "alpha-ketoglutarate" and "calcium oxoglurate" returned no match, a DailyMed search for "calcium alpha-ketoglutarate" returned no labels, and searches for "alpha-ketoglutarate" and "ketoglutarate" returned three labels, all multi-ingredient sprays containing ornithine alpha-ketoglutarate, a different compound. No FDA-approved Ca-AKG drug was found.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined calcium salt; free acid and other products separate
Follow-up
Searches run on 11 October 2026
Study design
NLM chemical record plus dated US approval-record search
Funding
not stated in the source

The products studied differ: a calcium salt in mouse feed, a delayed-release Ca-AKG and vitamin formulation, and sustained-release Ca-AKG in the ABLE trial. FDA GRAS or dietary-supplement status is not established here.

Read the original source
Exposure: 6 healthy men in 1990, plus rat absorption data; no supplement-dose pharmacokinetics

Human study

Cynober L et al. J Am Coll Nutr. 1990;9(1):2-12. PMID 2407764.

In 6 fasting healthy men given an oral load of 3.6 g alpha-ketoglutarate as calcium alpha-ketoglutarate, plasma glutamate rose 68% at 60 minutes (p < 0.05 versus baseline). The abstract says the rise in plasma alpha-KG itself was very small, in the sentence describing the ornithine alpha-ketoglutarate and ornithine loads, so it is not clear whether that applies to the calcium salt. In rats, up to 50%, 30% and 20% of gastrically delivered AKG was recovered in the stomach at 0.5, 1 and 2 hours, there was no significant excretion of unmetabolized AKG in urine or feces, 14C label appeared in liver, brain, bone, skin and muscle, up to 70% of the dose at 3 hours, and intestinal absorption did not depend on the AKG salt.

Participants / model
6 healthy men; rats
Treatment
Oral Ca-AKG, 3.6 g AKG load; intragastric and enteral AKG in rats
Follow-up
Single load; up to 3 hours in rats
Study design
Small human study; animal study
Funding
not stated in the source

Plasma pharmacokinetics at the doses sold as supplements were not found. No human data compare AKG salts.

Read the original source
Registered placebo-controlled trials: ABLE (120 adults) and NCT07114536 (34 adults), no posted results

Trial registry record

ClinicalTrials.gov record NCT05706389 (ABLE), read 11 October 2026; ABLE protocol PMID 37217632 and recruitment paper PMID 40819772. ClinicalTrials.gov record NCT07114536.

ABLE (Singapore) randomizes 120 healthy adults aged 40 to 60 with a DNA methylation age above their chronological age to 1 g sustained-release Ca-AKG or placebo for 6 months, with DNA methylation age change as the primary outcome and strength, arterial stiffness and inflammatory markers as secondary outcomes. A recruitment paper reports 467 interested individuals and 120 enrolled over 223 working days. On 11 October 2026 the registry listed ABLE as active, not recruiting, with primary completion 15 August 2025 and no posted results, and no primary results paper was found in PubMed. NCT07114536 (sponsor Shenzhen Hygieia Biotech Co., Ltd) randomized 34 adults aged 40 to 75 to four 0.5 g Ca-AKG tablets daily or starch placebo, with PhenoAge change at week 12 as the primary outcome; it is listed completed (primary completion 30 November 2025) with no posted results.

Participants / model
120 planned and 34 registered adults, middle-aged and older, apparently healthy
Treatment
Oral Ca-AKG, 1 g sustained-release daily (ABLE); four 0.5 g tablets daily (NCT07114536); placebo
Follow-up
6 months (ABLE); 12 weeks (NCT07114536)
Study design
Trial protocol and registry records
Funding
The ABLE protocol and recruitment papers list an author on the Ponce de Leon Health advisory board; NCT07114536 is sponsored by Shenzhen Hygieia Biotech Co., Ltd

Registered trials without results show that a study was registered, not that it works.

Read the original source

Where does the longevity claim come from?

From a 2014 worm study, where alpha-ketoglutarate extended adult lifespan in C. elegans, and a 2020 mouse study, where Ca-AKG in the diet from 18 months of age extended female median lifespan but did not significantly improve male survival. The mouse study comes from a single laboratory and is company-linked.

In the nematode C. elegans, alpha-ketoglutarate extended adult lifespan, bound the beta subunit of ATP synthase, and lowered ATP content and oxygen consumption while raising autophagy in worms and mammalian cells. The lifespan gain required ATP synthase subunit beta and depended on TOR downstream. Alpha-ketoglutarate did not extend the lifespan of dietary-restricted worms, which the authors read as AKG mediating the effect of dietary restriction. This is invertebrate and cell work.

In 2020, C57BL/6 mice were fed 2% calcium alpha-ketoglutarate (w/w) in the diet from 18 months of age, in two independent cohorts of 182 animals in total (about 45 of each sex per cohort). Measured from the start of feeding, female median lifespan and survival (age at 90th percentile mortality) were extended by 16.6% and 19.7% in cohort 1 and by 10.5% and 8% in cohort 2. Male survival was not significantly improved in either cohort, although male median lifespan from the start of treatment was 9.6% and 12.8% longer. A frailty index fell, and the authors propose IL-10 induction as the mechanism in females, with the mechanism absent in males. They list two limitations: the control diet lacked calcium, and the frailty index does not assess cognition or behavior.

Funding came from the Weldon Foundation, Ponce de Leon Health and NIH grants. Several authors are shareholders, co-founders or a board member of Ponce de Leon Health or of Gerostate Alpha, and five are named inventors on a preliminary patent application related to the work. The 2% diet dose has no validated human equivalent in the sources on this page.

Worm lifespan, 2014: AKG extended adult lifespan in C. elegans; no humans

Animal study

Chin RM et al. Nature. 2014;510(7505):397-401. PMID 24828042.

In the nematode C. elegans, alpha-ketoglutarate extended adult lifespan, bound the beta subunit of ATP synthase, and lowered ATP content and oxygen consumption while raising autophagy in worms and mammalian cells. The lifespan gain required ATP synthase subunit beta and depended on TOR downstream, and alpha-ketoglutarate did not extend the lifespan of dietary-restricted animals, which the authors read as AKG mediating the effect of dietary restriction.

Participants / model
C. elegans and mammalian cell lines. No humans
Treatment
AKG added to worm culture; cell exposure
Follow-up
Adult lifespan in worms
Study design
Animal and cell study
Funding
not stated in the source

Invertebrate and cell evidence; it does not show an effect in mammals or people.

Read the original source
Mouse lifespan, 2020: female median lifespan up 16.6% and 10.5%; company-linked

Animal study

Asadi Shahmirzadi A et al. Cell Metab. 2020;32(3):447-456.e6. PMID 32877690.

C57BL/6 mice were fed 2% calcium alpha-ketoglutarate (w/w) in the diet from 18 months of age, in two independent cohorts of 182 animals in total (about 45 of each sex per cohort). Median lifespan and survival (age at 90th percentile mortality) in females were extended by 16.6% and 19.7% in cohort 1 and by 10.5% and 8% in cohort 2, measured from the start of feeding. Male survival was not significantly improved in either cohort, although median lifespan from the start of treatment was 9.6% and 12.8% longer. A frailty index fell, and the authors propose IL-10 induction as the mechanism in females, with the mechanism absent in males. They list limitations: the control diet lacked calcium, and the frailty index does not assess cognition or behavior.

Participants / model
C57BL/6 mice of both sexes, treated from 18 months of age
Treatment
Calcium alpha-ketoglutarate, 2% in feed
Follow-up
From 18 months of age, with lifespan follow-up
Study design
Animal lifespan study in two cohorts, single laboratory
Funding
Weldon Foundation, Ponce de Leon Health and NIH grants. Several authors are shareholders, co-founders or a board member of Ponce de Leon Health or of Gerostate Alpha, and five are named inventors on a preliminary patent application related to the work

Read from the abstract and the open-access full text (PMC8508957). The 2% diet dose has no validated human equivalent in the sources on this page.

Read the original source

Did an independent multi-site mouse program confirm longer lifespan?

No. The NIA Interventions Testing Program tested eleven compounds, with alpha-ketoglutarate named among them, in genetically heterogeneous UM-HET3 mice at three sites and reported that none significantly increased lifespan in either sex. The abstract does not give the AKG dose or start age, so whether that arm matched the 2020 design is not stated.

The 2026 NIA Interventions Testing Program paper evaluated eleven compounds in UM-HET3 mice of both sexes at three sites and reported that none significantly increased lifespan in male or female mice. Its title names alpha-ketoglutarate among the compounds. The authors stress rigorous multi-site testing and say timing and dose are critical variables, and they declare no competing interests.

The abstract does not give the alpha-ketoglutarate dose, start age or lifespan figures, so this page does not compare the two designs. The positive mouse result comes from one laboratory with company funding and equity ties, and the independent multi-site program did not reproduce lifespan extension.

NIA ITP, 2026: none of eleven compounds, AKG among them, extended lifespan

Animal study

Korstanje R et al. Geroscience. 2026;48(3):3821-3830. PMID 41843349.

The NIA Interventions Testing Program evaluated eleven compounds in genetically heterogeneous UM-HET3 mice at three sites and reported that none significantly increased lifespan in male or female mice; the title names alpha-ketoglutarate among the compounds. The authors stress rigorous multi-site testing and say timing and dose are critical variables. The abstract does not give the alpha-ketoglutarate dose, start age or lifespan figures.

Participants / model
UM-HET3 mice of both sexes at three sites
Treatment
AKG in the diet (dose and start age not in the abstract)
Follow-up
Lifespan
Study design
Multi-site animal lifespan study
Funding
The authors declare no competing interests

Whether the AKG arm matched the 2020 single-laboratory design is not stated in the abstract.

Read the original source
Mouse lifespan, 2020: female median lifespan up 16.6% and 10.5%; company-linked

Animal study

Asadi Shahmirzadi A et al. Cell Metab. 2020;32(3):447-456.e6. PMID 32877690.

C57BL/6 mice were fed 2% calcium alpha-ketoglutarate (w/w) in the diet from 18 months of age, in two independent cohorts of 182 animals in total (about 45 of each sex per cohort). Median lifespan and survival (age at 90th percentile mortality) in females were extended by 16.6% and 19.7% in cohort 1 and by 10.5% and 8% in cohort 2, measured from the start of feeding. Male survival was not significantly improved in either cohort, although median lifespan from the start of treatment was 9.6% and 12.8% longer. A frailty index fell, and the authors propose IL-10 induction as the mechanism in females, with the mechanism absent in males. They list limitations: the control diet lacked calcium, and the frailty index does not assess cognition or behavior.

Participants / model
C57BL/6 mice of both sexes, treated from 18 months of age
Treatment
Calcium alpha-ketoglutarate, 2% in feed
Follow-up
From 18 months of age, with lifespan follow-up
Study design
Animal lifespan study in two cohorts, single laboratory
Funding
Weldon Foundation, Ponce de Leon Health and NIH grants. Several authors are shareholders, co-founders or a board member of Ponce de Leon Health or of Gerostate Alpha, and five are named inventors on a preliminary patent application related to the work

Read from the abstract and the open-access full text (PMC8508957). The 2% diet dose has no validated human equivalent in the sources on this page.

Read the original source

What do the studies in people show?

No controlled efficacy result has been published. The headline 8-year biological-age drop comes from 42 people taking Rejuvant, a multi-ingredient product, with no control group, and a cohort of 4,260 test buyers found a 1.8-year association. Long-term use is documented only in small uncontrolled dialysis studies.

A retrospective analysis of DNA methylation age in 42 individuals taking Rejuvant, an alpha-ketoglutarate-based formulation with vitamins, for an average of 7 months found an average 8-year reduction in biological age on the TruAge test (p = 6.538 x 10^-12). There was no control group, and the authors say placebo-controlled testing is required. The conflict statement says TruMe entered a non-exclusive customer service agreement to run methylation tests for Ponce de Leon Health customers taking Rejuvant, denies cross ownership, and lists the last author as a scientific consultant and board member of Ponce de Leon Health. The product is not Ca-AKG alone, and a methylation clock is a biomarker, not a health outcome.

A cross-sectional cohort of 4,260 health enthusiasts who bought a saliva epigenetic test (71% used supplements) used a proprietary 9-CpG clock with a mean absolute error of 5.4 years. Rejuvant was associated with an average 1.8-year lower Age Residual, and the association held after adjustment for age, sex, smoking and health status. People reporting regular AKG showed a smaller, statistically insignificant benefit, and in a longitudinal subset the association was not significant after multivariate correction. The authors name healthy-user and recruitment bias and call for controlled trials. The paper declares no conflicts; its last author, B. K. Kennedy, is declared a board member of Ponce de Leon Health in the 2020 mouse paper and the Rejuvant analysis.

The only long-term human use found is in kidney failure: 14 hemodialysis patients took Ca-AKG as a phosphate binder for 36 months, and 24 malnourished hemodialysis patients took it for 1 year. These are small uncontrolled reports, covered under safety below.

Rejuvant users: 42 people, 8-year TruAge drop, no control group, company-linked

Human study

Demidenko O et al. Aging (Albany NY). 2021;13(22):24485-24499. PMID 34847066.

A retrospective analysis of DNA methylation age in 42 individuals taking Rejuvant, an alpha-ketoglutarate-based formulation with vitamins, for an average of 7 months found an average 8-year reduction in biological age on the TruAge test (p = 6.538 x 10^-12), with no control group. The authors say placebo-controlled testing is required.

Participants / model
42 individuals taking a commercial product (health status and ages not given in the abstract)
Treatment
Oral Rejuvant (alpha-ketoglutarate plus vitamins)
Follow-up
Average 7 months
Study design
Retrospective uncontrolled analysis
Funding
TruMe entered a non-exclusive customer service agreement to run methylation tests for Ponce de Leon Health customers taking Rejuvant and denies cross ownership; the last author is a scientific consultant and board member of Ponce de Leon Health

The product is a multi-ingredient formulation, not Ca-AKG alone, and a methylation clock is a biomarker, not a health outcome.

Read the original source
Cohort of 4,260 test buyers: Rejuvant use linked to a 1.8-year lower Age Residual

Human study

Pabis K et al. Aging Cell. 2026;25(6):e70517. PMID 42166733.

In a cross-sectional cohort of 4,260 health enthusiasts who bought a saliva epigenetic test (71% used supplements), a proprietary 9-CpG clock with a mean absolute error of 5.4 years was used. Rejuvant (delayed-release Ca-AKG plus vitamins) was associated with an average 1.8-year lower Age Residual, and the association held after adjustment for age, sex, smoking and health status. People reporting regular AKG showed a smaller, statistically insignificant benefit. In a longitudinal subset, dAKG was associated with higher odds of a lower Age Residual, but the result was not significant after multivariate correction. The authors name healthy-user and recruitment bias and call for controlled trials.

Participants / model
4,260 supplement-using adults who bought an epigenetic test
Treatment
Self-reported AKG or Rejuvant use
Follow-up
Cross-sectional, with a longitudinal subset
Study design
Cross-sectional observational cohort
Funding
The paper declares no conflicts. Its last author, B. K. Kennedy, is declared a board member of Ponce de Leon Health in the 2020 mouse paper and the Rejuvant analysis

An association in self-selected test buyers, measured on a clock with a 5.4-year mean absolute error. It cannot show cause.

Read the original source
Dialysis: 14 patients for 36 months, serum calcium rose; 24 patients for 1 year

Human study

Zimmermann E et al. Miner Electrolyte Metab. 1996;22(1-3):196-9. PMID 8676818.

Calcium alpha-ketoglutarate, used as a phosphate binder, was given to 14 hemodialysis patients at a mean 4.5 g/day (0.975 g elemental calcium) for 36 months: serum phosphate fell from 2.6 to 1.9 mmol/L (p < 0.001), serum calcium rose from 2.2 to 2.47 mmol/L (p < 0.05), and intact parathyroid hormone fell from 29 to 8 pmol/L (p < 0.001). In 24 malnourished hemodialysis patients, 1 year of Ca-AKG raised plasma arginine from 53.6 to 71.1 micromol/L (p < 0.05).

Participants / model
14 and 24 patients on maintenance hemodialysis
Treatment
Oral Ca-AKG, 4.5 g/day in the first study
Follow-up
36 months and 1 year
Study design
Small uncontrolled clinical studies, 1996
Funding
not stated in the source

Uncontrolled reports in kidney failure, not safety data for healthy people at supplement doses. They show the calcium load is real.

Read the original source

Which placebo-controlled trials are registered, and have they reported?

Two are registered and neither had posted results on 11 October 2026. ABLE randomizes 120 healthy adults aged 40 to 60 to sustained-release Ca-AKG or placebo for 6 months and passed its listed primary completion date of 15 August 2025. NCT07114536 randomized 34 adults aged 40 to 75 for 12 weeks and is listed completed.

ABLE (Singapore, NCT05706389) randomizes 120 healthy adults aged 40 to 60 whose DNA methylation age is above their chronological age to 1 g sustained-release Ca-AKG or placebo for 6 months. The primary outcome is change in DNA methylation age, with strength, arterial stiffness and inflammatory markers as secondary outcomes. A recruitment paper reports 467 interested individuals and 120 enrolled over 223 working days. On 11 October 2026 the registry listed ABLE as active, not recruiting, with primary completion 15 August 2025 and no posted results, and no primary results paper was found in PubMed. The ABLE protocol and recruitment papers list an author on the Ponce de Leon Health advisory board.

NCT07114536, sponsored by Shenzhen Hygieia Biotech Co., Ltd, randomized 34 adults aged 40 to 75 to four 0.5 g Ca-AKG tablets daily or starch placebo, with PhenoAge change at week 12 as the primary outcome. It is listed completed (primary completion 30 November 2025) with no posted results.

Registered trials without results show that a study was registered, not that it works.

Registered placebo-controlled trials: ABLE (120 adults) and NCT07114536 (34 adults), no posted results

Trial registry record

ClinicalTrials.gov record NCT05706389 (ABLE), read 11 October 2026; ABLE protocol PMID 37217632 and recruitment paper PMID 40819772. ClinicalTrials.gov record NCT07114536.

ABLE (Singapore) randomizes 120 healthy adults aged 40 to 60 with a DNA methylation age above their chronological age to 1 g sustained-release Ca-AKG or placebo for 6 months, with DNA methylation age change as the primary outcome and strength, arterial stiffness and inflammatory markers as secondary outcomes. A recruitment paper reports 467 interested individuals and 120 enrolled over 223 working days. On 11 October 2026 the registry listed ABLE as active, not recruiting, with primary completion 15 August 2025 and no posted results, and no primary results paper was found in PubMed. NCT07114536 (sponsor Shenzhen Hygieia Biotech Co., Ltd) randomized 34 adults aged 40 to 75 to four 0.5 g Ca-AKG tablets daily or starch placebo, with PhenoAge change at week 12 as the primary outcome; it is listed completed (primary completion 30 November 2025) with no posted results.

Participants / model
120 planned and 34 registered adults, middle-aged and older, apparently healthy
Treatment
Oral Ca-AKG, 1 g sustained-release daily (ABLE); four 0.5 g tablets daily (NCT07114536); placebo
Follow-up
6 months (ABLE); 12 weeks (NCT07114536)
Study design
Trial protocol and registry records
Funding
The ABLE protocol and recruitment papers list an author on the Ponce de Leon Health advisory board; NCT07114536 is sponsored by Shenzhen Hygieia Biotech Co., Ltd

Registered trials without results show that a study was registered, not that it works.

Read the original source

Does Ca-AKG lower biological age in people?

Not established. The 8-year figure is uncontrolled and company-linked, and a PubMed search on 11 October 2026 returned 16 Ca-AKG or Rejuvant records, none a published randomized placebo-controlled trial of an aging outcome in people. The mouse lifespan result was not reproduced by an independent multi-site program.

Sellers say calcium alpha-ketoglutarate supports healthy aging and lowers biological age in people, building on mouse lifespan work. The 8-year biological-age figure comes from an uncontrolled, company-linked analysis of a multi-ingredient product, and the larger observational cohort shows a 1.8-year association on a clock with a 5.4-year mean absolute error.

A PubMed search on 11 October 2026 for Ca-AKG, calcium alpha-ketoglutarate, CaAKG or Rejuvant returned 16 records, and all 16 titles were reviewed. They were the mouse, cohort, exposure, dialysis and trial-design papers on this page, a 1964 French paper on hyperammonemia, a commentary on the mouse paper, mouse studies of arterial elasticity and synaptic plasticity, a lamb feed study, a yeast production paper and a healthspan review. None reported a published randomized placebo-controlled trial of Ca-AKG on biological age, physical function or any aging outcome in people. A ClinicalTrials.gov search for alpha-ketoglutarate returned further registered studies with no results, including NCT07031128, a surgery trial listed as recruiting.

A 2022 review by authors including a Ponce de Leon Health board member and equity holder states that there are no recently published studies showing AKG treats aging or age-related disease in humans.

PubMed search, 11 October 2026: 16 records, no published controlled human aging trial

PubMed search record

PubMed search run on 11 October 2026: (Ca-AKG[tiab] OR "calcium alpha-ketoglutarate"[tiab] OR "calcium alpha ketoglutarate"[tiab] OR CaAKG[tiab] OR Rejuvant[tiab]). 16 records returned. ClinicalTrials.gov search for "alpha-ketoglutarate" run the same day. The 2022 review cited is PMID 34952764.

The search returned 16 records, and all 16 titles were reviewed. They covered the 2020 mouse lifespan paper, the Rejuvant retrospective analysis, the ABLE protocol and recruitment papers, the 4,260-person cohort, rat and 1990 human exposure studies, two 1996 dialysis papers, a 1964 French paper on hyperammonemia, a 2020 Cell Metab commentary on the mouse paper, mouse studies of arterial elasticity and Alzheimer's-model synaptic plasticity, a lamb feed study, a yeast production paper and a healthspan review. None reported a published randomized placebo-controlled trial of Ca-AKG on biological age, physical function or any aging outcome in people. A ClinicalTrials.gov search for "alpha-ketoglutarate" returned further registered studies with no results, including NCT07031128 (a surgery trial listed as recruiting). A 2022 review by authors including a Ponce de Leon Health board member and equity holder states there are no recently published studies showing AKG treats aging or age-related disease in humans.

Participants / model
Records reviewed, not a population
Treatment
Not applicable
Follow-up
Searches run on 11 October 2026
Study design
Literature search and trial registry
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source
Rejuvant users: 42 people, 8-year TruAge drop, no control group, company-linked

Human study

Demidenko O et al. Aging (Albany NY). 2021;13(22):24485-24499. PMID 34847066.

A retrospective analysis of DNA methylation age in 42 individuals taking Rejuvant, an alpha-ketoglutarate-based formulation with vitamins, for an average of 7 months found an average 8-year reduction in biological age on the TruAge test (p = 6.538 x 10^-12), with no control group. The authors say placebo-controlled testing is required.

Participants / model
42 individuals taking a commercial product (health status and ages not given in the abstract)
Treatment
Oral Rejuvant (alpha-ketoglutarate plus vitamins)
Follow-up
Average 7 months
Study design
Retrospective uncontrolled analysis
Funding
TruMe entered a non-exclusive customer service agreement to run methylation tests for Ponce de Leon Health customers taking Rejuvant and denies cross ownership; the last author is a scientific consultant and board member of Ponce de Leon Health

The product is a multi-ingredient formulation, not Ca-AKG alone, and a methylation clock is a biomarker, not a health outcome.

Read the original source
Cohort of 4,260 test buyers: Rejuvant use linked to a 1.8-year lower Age Residual

Human study

Pabis K et al. Aging Cell. 2026;25(6):e70517. PMID 42166733.

In a cross-sectional cohort of 4,260 health enthusiasts who bought a saliva epigenetic test (71% used supplements), a proprietary 9-CpG clock with a mean absolute error of 5.4 years was used. Rejuvant (delayed-release Ca-AKG plus vitamins) was associated with an average 1.8-year lower Age Residual, and the association held after adjustment for age, sex, smoking and health status. People reporting regular AKG showed a smaller, statistically insignificant benefit. In a longitudinal subset, dAKG was associated with higher odds of a lower Age Residual, but the result was not significant after multivariate correction. The authors name healthy-user and recruitment bias and call for controlled trials.

Participants / model
4,260 supplement-using adults who bought an epigenetic test
Treatment
Self-reported AKG or Rejuvant use
Follow-up
Cross-sectional, with a longitudinal subset
Study design
Cross-sectional observational cohort
Funding
The paper declares no conflicts. Its last author, B. K. Kennedy, is declared a board member of Ponce de Leon Health in the 2020 mouse paper and the Rejuvant analysis

An association in self-selected test buyers, measured on a clock with a 5.4-year mean absolute error. It cannot show cause.

Read the original source
NIA ITP, 2026: none of eleven compounds, AKG among them, extended lifespan

Animal study

Korstanje R et al. Geroscience. 2026;48(3):3821-3830. PMID 41843349.

The NIA Interventions Testing Program evaluated eleven compounds in genetically heterogeneous UM-HET3 mice at three sites and reported that none significantly increased lifespan in male or female mice; the title names alpha-ketoglutarate among the compounds. The authors stress rigorous multi-site testing and say timing and dose are critical variables. The abstract does not give the alpha-ketoglutarate dose, start age or lifespan figures.

Participants / model
UM-HET3 mice of both sexes at three sites
Treatment
AKG in the diet (dose and start age not in the abstract)
Follow-up
Lifespan
Study design
Multi-site animal lifespan study
Funding
The authors declare no competing interests

Whether the AKG arm matched the 2020 single-laboratory design is not stated in the abstract.

Read the original source
Registered placebo-controlled trials: ABLE (120 adults) and NCT07114536 (34 adults), no posted results

Trial registry record

ClinicalTrials.gov record NCT05706389 (ABLE), read 11 October 2026; ABLE protocol PMID 37217632 and recruitment paper PMID 40819772. ClinicalTrials.gov record NCT07114536.

ABLE (Singapore) randomizes 120 healthy adults aged 40 to 60 with a DNA methylation age above their chronological age to 1 g sustained-release Ca-AKG or placebo for 6 months, with DNA methylation age change as the primary outcome and strength, arterial stiffness and inflammatory markers as secondary outcomes. A recruitment paper reports 467 interested individuals and 120 enrolled over 223 working days. On 11 October 2026 the registry listed ABLE as active, not recruiting, with primary completion 15 August 2025 and no posted results, and no primary results paper was found in PubMed. NCT07114536 (sponsor Shenzhen Hygieia Biotech Co., Ltd) randomized 34 adults aged 40 to 75 to four 0.5 g Ca-AKG tablets daily or starch placebo, with PhenoAge change at week 12 as the primary outcome; it is listed completed (primary completion 30 November 2025) with no posted results.

Participants / model
120 planned and 34 registered adults, middle-aged and older, apparently healthy
Treatment
Oral Ca-AKG, 1 g sustained-release daily (ABLE); four 0.5 g tablets daily (NCT07114536); placebo
Follow-up
6 months (ABLE); 12 weeks (NCT07114536)
Study design
Trial protocol and registry records
Funding
The ABLE protocol and recruitment papers list an author on the Ponce de Leon Health advisory board; NCT07114536 is sponsored by Shenzhen Hygieia Biotech Co., Ltd

Registered trials without results show that a study was registered, not that it works.

Read the original source

How is Ca-AKG supposed to work, and what reaches the blood?

In worms, AKG bound ATP synthase, lowered ATP and oxygen consumption, raised autophagy and acted through TOR; in female mice the authors propose IL-10 induction. In 6 healthy men, a 3.6 g oral AKG load as Ca-AKG raised plasma glutamate 68% at 60 minutes, and plasma levels at supplement doses were not found.

The proposed mechanism traces to C. elegans, where alpha-ketoglutarate bound the beta subunit of ATP synthase, lowered ATP content and oxygen consumption and raised autophagy, with the lifespan gain depending on TOR. In the 2020 mouse study, the authors propose IL-10 induction as the mechanism in females and report it absent in males, matching the sex difference in survival.

Human exposure data are old and small. In 6 fasting healthy men given an oral load of 3.6 g alpha-ketoglutarate as calcium alpha-ketoglutarate, plasma glutamate rose 68% at 60 minutes (p < 0.05 versus baseline). The abstract says the rise in plasma alpha-KG itself was very small, but in the sentence describing the ornithine alpha-ketoglutarate and ornithine loads, so it is not clear whether that applies to the calcium salt.

In rats, up to 50%, 30% and 20% of gastrically delivered AKG was recovered in the stomach at 0.5, 1 and 2 hours, with no significant excretion of unmetabolized AKG in urine or feces. Labeled AKG appeared in liver, brain, bone, skin and muscle, up to 70% of the dose at 3 hours, and intestinal absorption did not depend on the AKG salt. Plasma pharmacokinetics at the doses sold as supplements were not found.

Worm lifespan, 2014: AKG extended adult lifespan in C. elegans; no humans

Animal study

Chin RM et al. Nature. 2014;510(7505):397-401. PMID 24828042.

In the nematode C. elegans, alpha-ketoglutarate extended adult lifespan, bound the beta subunit of ATP synthase, and lowered ATP content and oxygen consumption while raising autophagy in worms and mammalian cells. The lifespan gain required ATP synthase subunit beta and depended on TOR downstream, and alpha-ketoglutarate did not extend the lifespan of dietary-restricted animals, which the authors read as AKG mediating the effect of dietary restriction.

Participants / model
C. elegans and mammalian cell lines. No humans
Treatment
AKG added to worm culture; cell exposure
Follow-up
Adult lifespan in worms
Study design
Animal and cell study
Funding
not stated in the source

Invertebrate and cell evidence; it does not show an effect in mammals or people.

Read the original source
Mouse lifespan, 2020: female median lifespan up 16.6% and 10.5%; company-linked

Animal study

Asadi Shahmirzadi A et al. Cell Metab. 2020;32(3):447-456.e6. PMID 32877690.

C57BL/6 mice were fed 2% calcium alpha-ketoglutarate (w/w) in the diet from 18 months of age, in two independent cohorts of 182 animals in total (about 45 of each sex per cohort). Median lifespan and survival (age at 90th percentile mortality) in females were extended by 16.6% and 19.7% in cohort 1 and by 10.5% and 8% in cohort 2, measured from the start of feeding. Male survival was not significantly improved in either cohort, although median lifespan from the start of treatment was 9.6% and 12.8% longer. A frailty index fell, and the authors propose IL-10 induction as the mechanism in females, with the mechanism absent in males. They list limitations: the control diet lacked calcium, and the frailty index does not assess cognition or behavior.

Participants / model
C57BL/6 mice of both sexes, treated from 18 months of age
Treatment
Calcium alpha-ketoglutarate, 2% in feed
Follow-up
From 18 months of age, with lifespan follow-up
Study design
Animal lifespan study in two cohorts, single laboratory
Funding
Weldon Foundation, Ponce de Leon Health and NIH grants. Several authors are shareholders, co-founders or a board member of Ponce de Leon Health or of Gerostate Alpha, and five are named inventors on a preliminary patent application related to the work

Read from the abstract and the open-access full text (PMC8508957). The 2% diet dose has no validated human equivalent in the sources on this page.

Read the original source
Exposure: 6 healthy men in 1990, plus rat absorption data; no supplement-dose pharmacokinetics

Human study

Cynober L et al. J Am Coll Nutr. 1990;9(1):2-12. PMID 2407764.

In 6 fasting healthy men given an oral load of 3.6 g alpha-ketoglutarate as calcium alpha-ketoglutarate, plasma glutamate rose 68% at 60 minutes (p < 0.05 versus baseline). The abstract says the rise in plasma alpha-KG itself was very small, in the sentence describing the ornithine alpha-ketoglutarate and ornithine loads, so it is not clear whether that applies to the calcium salt. In rats, up to 50%, 30% and 20% of gastrically delivered AKG was recovered in the stomach at 0.5, 1 and 2 hours, there was no significant excretion of unmetabolized AKG in urine or feces, 14C label appeared in liver, brain, bone, skin and muscle, up to 70% of the dose at 3 hours, and intestinal absorption did not depend on the AKG salt.

Participants / model
6 healthy men; rats
Treatment
Oral Ca-AKG, 3.6 g AKG load; intragastric and enteral AKG in rats
Follow-up
Single load; up to 3 hours in rats
Study design
Small human study; animal study
Funding
not stated in the source

Plasma pharmacokinetics at the doses sold as supplements were not found. No human data compare AKG salts.

Read the original source

What safety data exist for Ca-AKG?

Safety data for healthy people at supplement doses are absent. The only long-term human use found is in dialysis patients, where Ca-AKG used as a phosphate binder raised serum calcium, so the calcium load is real. No data on cancer, kidney stones or long-term safety in healthy adults were found.

Calcium alpha-ketoglutarate, used as a phosphate binder, was given to 14 hemodialysis patients at a mean 4.5 g/day (0.975 g elemental calcium) for 36 months. Serum phosphate fell from 2.6 to 1.9 mmol/L (p < 0.001), serum calcium rose from 2.2 to 2.47 mmol/L (p < 0.05), and intact parathyroid hormone fell from 29 to 8 pmol/L (p < 0.001). In 24 malnourished hemodialysis patients, 1 year of Ca-AKG raised plasma arginine from 53.6 to 71.1 micromol/L (p < 0.05).

These are uncontrolled 1996 reports in kidney failure, not safety data for healthy people at supplement doses, but they show the calcium load is real. In the 2020 mouse study, the control diet lacked calcium, which the authors list as a limitation.

None of the 16 PubMed records on Ca-AKG or Rejuvant reports controlled safety data in healthy adults, and no data on cancer, kidney stones or long-term safety in healthy adults were found.

Dialysis: 14 patients for 36 months, serum calcium rose; 24 patients for 1 year

Human study

Zimmermann E et al. Miner Electrolyte Metab. 1996;22(1-3):196-9. PMID 8676818.

Calcium alpha-ketoglutarate, used as a phosphate binder, was given to 14 hemodialysis patients at a mean 4.5 g/day (0.975 g elemental calcium) for 36 months: serum phosphate fell from 2.6 to 1.9 mmol/L (p < 0.001), serum calcium rose from 2.2 to 2.47 mmol/L (p < 0.05), and intact parathyroid hormone fell from 29 to 8 pmol/L (p < 0.001). In 24 malnourished hemodialysis patients, 1 year of Ca-AKG raised plasma arginine from 53.6 to 71.1 micromol/L (p < 0.05).

Participants / model
14 and 24 patients on maintenance hemodialysis
Treatment
Oral Ca-AKG, 4.5 g/day in the first study
Follow-up
36 months and 1 year
Study design
Small uncontrolled clinical studies, 1996
Funding
not stated in the source

Uncontrolled reports in kidney failure, not safety data for healthy people at supplement doses. They show the calcium load is real.

Read the original source
Mouse lifespan, 2020: female median lifespan up 16.6% and 10.5%; company-linked

Animal study

Asadi Shahmirzadi A et al. Cell Metab. 2020;32(3):447-456.e6. PMID 32877690.

C57BL/6 mice were fed 2% calcium alpha-ketoglutarate (w/w) in the diet from 18 months of age, in two independent cohorts of 182 animals in total (about 45 of each sex per cohort). Median lifespan and survival (age at 90th percentile mortality) in females were extended by 16.6% and 19.7% in cohort 1 and by 10.5% and 8% in cohort 2, measured from the start of feeding. Male survival was not significantly improved in either cohort, although median lifespan from the start of treatment was 9.6% and 12.8% longer. A frailty index fell, and the authors propose IL-10 induction as the mechanism in females, with the mechanism absent in males. They list limitations: the control diet lacked calcium, and the frailty index does not assess cognition or behavior.

Participants / model
C57BL/6 mice of both sexes, treated from 18 months of age
Treatment
Calcium alpha-ketoglutarate, 2% in feed
Follow-up
From 18 months of age, with lifespan follow-up
Study design
Animal lifespan study in two cohorts, single laboratory
Funding
Weldon Foundation, Ponce de Leon Health and NIH grants. Several authors are shareholders, co-founders or a board member of Ponce de Leon Health or of Gerostate Alpha, and five are named inventors on a preliminary patent application related to the work

Read from the abstract and the open-access full text (PMC8508957). The 2% diet dose has no validated human equivalent in the sources on this page.

Read the original source
PubMed search, 11 October 2026: 16 records, no published controlled human aging trial

PubMed search record

PubMed search run on 11 October 2026: (Ca-AKG[tiab] OR "calcium alpha-ketoglutarate"[tiab] OR "calcium alpha ketoglutarate"[tiab] OR CaAKG[tiab] OR Rejuvant[tiab]). 16 records returned. ClinicalTrials.gov search for "alpha-ketoglutarate" run the same day. The 2022 review cited is PMID 34952764.

The search returned 16 records, and all 16 titles were reviewed. They covered the 2020 mouse lifespan paper, the Rejuvant retrospective analysis, the ABLE protocol and recruitment papers, the 4,260-person cohort, rat and 1990 human exposure studies, two 1996 dialysis papers, a 1964 French paper on hyperammonemia, a 2020 Cell Metab commentary on the mouse paper, mouse studies of arterial elasticity and Alzheimer's-model synaptic plasticity, a lamb feed study, a yeast production paper and a healthspan review. None reported a published randomized placebo-controlled trial of Ca-AKG on biological age, physical function or any aging outcome in people. A ClinicalTrials.gov search for "alpha-ketoglutarate" returned further registered studies with no results, including NCT07031128 (a surgery trial listed as recruiting). A 2022 review by authors including a Ponce de Leon Health board member and equity holder states there are no recently published studies showing AKG treats aging or age-related disease in humans.

Participants / model
Records reviewed, not a population
Treatment
Not applicable
Follow-up
Searches run on 11 October 2026
Study design
Literature search and trial registry
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source

Why does Ca-AKG sit in C tier?

C fits an endogenous metabolite with a plausible mechanism and a positive single-laboratory, company-linked mouse lifespan study that an independent multi-site program did not reproduce. Human data are an uncontrolled 42-person biomarker report, a cross-sectional cohort and old dialysis studies, and the placebo-controlled trials have not posted results.

That places Ca-AKG with NMN, nicotinamide riboside and urolithin A. D is arguable if the biological-age claim is read as hype the data have not caught up to. Safety data for healthy people at supplement doses are absent, and the dialysis record shows a calcium load.

"Lowers biological age" is not established. The 8-year figure is uncontrolled and company-linked, and no controlled human result had been published in the records found on 11 October 2026.

Mouse lifespan, 2020: female median lifespan up 16.6% and 10.5%; company-linked

Animal study

Asadi Shahmirzadi A et al. Cell Metab. 2020;32(3):447-456.e6. PMID 32877690.

C57BL/6 mice were fed 2% calcium alpha-ketoglutarate (w/w) in the diet from 18 months of age, in two independent cohorts of 182 animals in total (about 45 of each sex per cohort). Median lifespan and survival (age at 90th percentile mortality) in females were extended by 16.6% and 19.7% in cohort 1 and by 10.5% and 8% in cohort 2, measured from the start of feeding. Male survival was not significantly improved in either cohort, although median lifespan from the start of treatment was 9.6% and 12.8% longer. A frailty index fell, and the authors propose IL-10 induction as the mechanism in females, with the mechanism absent in males. They list limitations: the control diet lacked calcium, and the frailty index does not assess cognition or behavior.

Participants / model
C57BL/6 mice of both sexes, treated from 18 months of age
Treatment
Calcium alpha-ketoglutarate, 2% in feed
Follow-up
From 18 months of age, with lifespan follow-up
Study design
Animal lifespan study in two cohorts, single laboratory
Funding
Weldon Foundation, Ponce de Leon Health and NIH grants. Several authors are shareholders, co-founders or a board member of Ponce de Leon Health or of Gerostate Alpha, and five are named inventors on a preliminary patent application related to the work

Read from the abstract and the open-access full text (PMC8508957). The 2% diet dose has no validated human equivalent in the sources on this page.

Read the original source
NIA ITP, 2026: none of eleven compounds, AKG among them, extended lifespan

Animal study

Korstanje R et al. Geroscience. 2026;48(3):3821-3830. PMID 41843349.

The NIA Interventions Testing Program evaluated eleven compounds in genetically heterogeneous UM-HET3 mice at three sites and reported that none significantly increased lifespan in male or female mice; the title names alpha-ketoglutarate among the compounds. The authors stress rigorous multi-site testing and say timing and dose are critical variables. The abstract does not give the alpha-ketoglutarate dose, start age or lifespan figures.

Participants / model
UM-HET3 mice of both sexes at three sites
Treatment
AKG in the diet (dose and start age not in the abstract)
Follow-up
Lifespan
Study design
Multi-site animal lifespan study
Funding
The authors declare no competing interests

Whether the AKG arm matched the 2020 single-laboratory design is not stated in the abstract.

Read the original source
Rejuvant users: 42 people, 8-year TruAge drop, no control group, company-linked

Human study

Demidenko O et al. Aging (Albany NY). 2021;13(22):24485-24499. PMID 34847066.

A retrospective analysis of DNA methylation age in 42 individuals taking Rejuvant, an alpha-ketoglutarate-based formulation with vitamins, for an average of 7 months found an average 8-year reduction in biological age on the TruAge test (p = 6.538 x 10^-12), with no control group. The authors say placebo-controlled testing is required.

Participants / model
42 individuals taking a commercial product (health status and ages not given in the abstract)
Treatment
Oral Rejuvant (alpha-ketoglutarate plus vitamins)
Follow-up
Average 7 months
Study design
Retrospective uncontrolled analysis
Funding
TruMe entered a non-exclusive customer service agreement to run methylation tests for Ponce de Leon Health customers taking Rejuvant and denies cross ownership; the last author is a scientific consultant and board member of Ponce de Leon Health

The product is a multi-ingredient formulation, not Ca-AKG alone, and a methylation clock is a biomarker, not a health outcome.

Read the original source
Cohort of 4,260 test buyers: Rejuvant use linked to a 1.8-year lower Age Residual

Human study

Pabis K et al. Aging Cell. 2026;25(6):e70517. PMID 42166733.

In a cross-sectional cohort of 4,260 health enthusiasts who bought a saliva epigenetic test (71% used supplements), a proprietary 9-CpG clock with a mean absolute error of 5.4 years was used. Rejuvant (delayed-release Ca-AKG plus vitamins) was associated with an average 1.8-year lower Age Residual, and the association held after adjustment for age, sex, smoking and health status. People reporting regular AKG showed a smaller, statistically insignificant benefit. In a longitudinal subset, dAKG was associated with higher odds of a lower Age Residual, but the result was not significant after multivariate correction. The authors name healthy-user and recruitment bias and call for controlled trials.

Participants / model
4,260 supplement-using adults who bought an epigenetic test
Treatment
Self-reported AKG or Rejuvant use
Follow-up
Cross-sectional, with a longitudinal subset
Study design
Cross-sectional observational cohort
Funding
The paper declares no conflicts. Its last author, B. K. Kennedy, is declared a board member of Ponce de Leon Health in the 2020 mouse paper and the Rejuvant analysis

An association in self-selected test buyers, measured on a clock with a 5.4-year mean absolute error. It cannot show cause.

Read the original source
Registered placebo-controlled trials: ABLE (120 adults) and NCT07114536 (34 adults), no posted results

Trial registry record

ClinicalTrials.gov record NCT05706389 (ABLE), read 11 October 2026; ABLE protocol PMID 37217632 and recruitment paper PMID 40819772. ClinicalTrials.gov record NCT07114536.

ABLE (Singapore) randomizes 120 healthy adults aged 40 to 60 with a DNA methylation age above their chronological age to 1 g sustained-release Ca-AKG or placebo for 6 months, with DNA methylation age change as the primary outcome and strength, arterial stiffness and inflammatory markers as secondary outcomes. A recruitment paper reports 467 interested individuals and 120 enrolled over 223 working days. On 11 October 2026 the registry listed ABLE as active, not recruiting, with primary completion 15 August 2025 and no posted results, and no primary results paper was found in PubMed. NCT07114536 (sponsor Shenzhen Hygieia Biotech Co., Ltd) randomized 34 adults aged 40 to 75 to four 0.5 g Ca-AKG tablets daily or starch placebo, with PhenoAge change at week 12 as the primary outcome; it is listed completed (primary completion 30 November 2025) with no posted results.

Participants / model
120 planned and 34 registered adults, middle-aged and older, apparently healthy
Treatment
Oral Ca-AKG, 1 g sustained-release daily (ABLE); four 0.5 g tablets daily (NCT07114536); placebo
Follow-up
6 months (ABLE); 12 weeks (NCT07114536)
Study design
Trial protocol and registry records
Funding
The ABLE protocol and recruitment papers list an author on the Ponce de Leon Health advisory board; NCT07114536 is sponsored by Shenzhen Hygieia Biotech Co., Ltd

Registered trials without results show that a study was registered, not that it works.

Read the original source
Dialysis: 14 patients for 36 months, serum calcium rose; 24 patients for 1 year

Human study

Zimmermann E et al. Miner Electrolyte Metab. 1996;22(1-3):196-9. PMID 8676818.

Calcium alpha-ketoglutarate, used as a phosphate binder, was given to 14 hemodialysis patients at a mean 4.5 g/day (0.975 g elemental calcium) for 36 months: serum phosphate fell from 2.6 to 1.9 mmol/L (p < 0.001), serum calcium rose from 2.2 to 2.47 mmol/L (p < 0.05), and intact parathyroid hormone fell from 29 to 8 pmol/L (p < 0.001). In 24 malnourished hemodialysis patients, 1 year of Ca-AKG raised plasma arginine from 53.6 to 71.1 micromol/L (p < 0.05).

Participants / model
14 and 24 patients on maintenance hemodialysis
Treatment
Oral Ca-AKG, 4.5 g/day in the first study
Follow-up
36 months and 1 year
Study design
Small uncontrolled clinical studies, 1996
Funding
not stated in the source

Uncontrolled reports in kidney failure, not safety data for healthy people at supplement doses. They show the calcium load is real.

Read the original source

Studies and sources

PubChem: Ca-AKG identity; no FDA-approved Ca-AKG drug found, 11 October 2026

Chemical identity record

National Library of Medicine. PubChem compound record CID 3018235 (calcium alpha-ketoglutarate), with the free acid record CID 51. openFDA Drugs@FDA queries and DailyMed searches run on 11 October 2026.

Calcium alpha-ketoglutarate: PubChem CID 3018235, C5H4CaO5, 184.16 g/mol, CAS 71686-01-6, with "calcium oxoglurate" (a WHO drug dictionary name) among the listed synonyms. The free acid, alpha-ketoglutaric acid (2-oxoglutaric acid), is a separate record: CID 51, C5H6O5, 146.10 g/mol, CAS 328-50-7. AKG is a Krebs cycle intermediate the body makes. On 11 October 2026 openFDA Drugs@FDA queries for "alpha-ketoglutarate" and "calcium oxoglurate" returned no match, a DailyMed search for "calcium alpha-ketoglutarate" returned no labels, and searches for "alpha-ketoglutarate" and "ketoglutarate" returned three labels, all multi-ingredient sprays containing ornithine alpha-ketoglutarate, a different compound. No FDA-approved Ca-AKG drug was found.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined calcium salt; free acid and other products separate
Follow-up
Searches run on 11 October 2026
Study design
NLM chemical record plus dated US approval-record search
Funding
not stated in the source

The products studied differ: a calcium salt in mouse feed, a delayed-release Ca-AKG and vitamin formulation, and sustained-release Ca-AKG in the ABLE trial. FDA GRAS or dietary-supplement status is not established here.

Read the original source
Worm lifespan, 2014: AKG extended adult lifespan in C. elegans; no humans

Animal study

Chin RM et al. Nature. 2014;510(7505):397-401. PMID 24828042.

In the nematode C. elegans, alpha-ketoglutarate extended adult lifespan, bound the beta subunit of ATP synthase, and lowered ATP content and oxygen consumption while raising autophagy in worms and mammalian cells. The lifespan gain required ATP synthase subunit beta and depended on TOR downstream, and alpha-ketoglutarate did not extend the lifespan of dietary-restricted animals, which the authors read as AKG mediating the effect of dietary restriction.

Participants / model
C. elegans and mammalian cell lines. No humans
Treatment
AKG added to worm culture; cell exposure
Follow-up
Adult lifespan in worms
Study design
Animal and cell study
Funding
not stated in the source

Invertebrate and cell evidence; it does not show an effect in mammals or people.

Read the original source
Mouse lifespan, 2020: female median lifespan up 16.6% and 10.5%; company-linked

Animal study

Asadi Shahmirzadi A et al. Cell Metab. 2020;32(3):447-456.e6. PMID 32877690.

C57BL/6 mice were fed 2% calcium alpha-ketoglutarate (w/w) in the diet from 18 months of age, in two independent cohorts of 182 animals in total (about 45 of each sex per cohort). Median lifespan and survival (age at 90th percentile mortality) in females were extended by 16.6% and 19.7% in cohort 1 and by 10.5% and 8% in cohort 2, measured from the start of feeding. Male survival was not significantly improved in either cohort, although median lifespan from the start of treatment was 9.6% and 12.8% longer. A frailty index fell, and the authors propose IL-10 induction as the mechanism in females, with the mechanism absent in males. They list limitations: the control diet lacked calcium, and the frailty index does not assess cognition or behavior.

Participants / model
C57BL/6 mice of both sexes, treated from 18 months of age
Treatment
Calcium alpha-ketoglutarate, 2% in feed
Follow-up
From 18 months of age, with lifespan follow-up
Study design
Animal lifespan study in two cohorts, single laboratory
Funding
Weldon Foundation, Ponce de Leon Health and NIH grants. Several authors are shareholders, co-founders or a board member of Ponce de Leon Health or of Gerostate Alpha, and five are named inventors on a preliminary patent application related to the work

Read from the abstract and the open-access full text (PMC8508957). The 2% diet dose has no validated human equivalent in the sources on this page.

Read the original source
NIA ITP, 2026: none of eleven compounds, AKG among them, extended lifespan

Animal study

Korstanje R et al. Geroscience. 2026;48(3):3821-3830. PMID 41843349.

The NIA Interventions Testing Program evaluated eleven compounds in genetically heterogeneous UM-HET3 mice at three sites and reported that none significantly increased lifespan in male or female mice; the title names alpha-ketoglutarate among the compounds. The authors stress rigorous multi-site testing and say timing and dose are critical variables. The abstract does not give the alpha-ketoglutarate dose, start age or lifespan figures.

Participants / model
UM-HET3 mice of both sexes at three sites
Treatment
AKG in the diet (dose and start age not in the abstract)
Follow-up
Lifespan
Study design
Multi-site animal lifespan study
Funding
The authors declare no competing interests

Whether the AKG arm matched the 2020 single-laboratory design is not stated in the abstract.

Read the original source
Rejuvant users: 42 people, 8-year TruAge drop, no control group, company-linked

Human study

Demidenko O et al. Aging (Albany NY). 2021;13(22):24485-24499. PMID 34847066.

A retrospective analysis of DNA methylation age in 42 individuals taking Rejuvant, an alpha-ketoglutarate-based formulation with vitamins, for an average of 7 months found an average 8-year reduction in biological age on the TruAge test (p = 6.538 x 10^-12), with no control group. The authors say placebo-controlled testing is required.

Participants / model
42 individuals taking a commercial product (health status and ages not given in the abstract)
Treatment
Oral Rejuvant (alpha-ketoglutarate plus vitamins)
Follow-up
Average 7 months
Study design
Retrospective uncontrolled analysis
Funding
TruMe entered a non-exclusive customer service agreement to run methylation tests for Ponce de Leon Health customers taking Rejuvant and denies cross ownership; the last author is a scientific consultant and board member of Ponce de Leon Health

The product is a multi-ingredient formulation, not Ca-AKG alone, and a methylation clock is a biomarker, not a health outcome.

Read the original source
Cohort of 4,260 test buyers: Rejuvant use linked to a 1.8-year lower Age Residual

Human study

Pabis K et al. Aging Cell. 2026;25(6):e70517. PMID 42166733.

In a cross-sectional cohort of 4,260 health enthusiasts who bought a saliva epigenetic test (71% used supplements), a proprietary 9-CpG clock with a mean absolute error of 5.4 years was used. Rejuvant (delayed-release Ca-AKG plus vitamins) was associated with an average 1.8-year lower Age Residual, and the association held after adjustment for age, sex, smoking and health status. People reporting regular AKG showed a smaller, statistically insignificant benefit. In a longitudinal subset, dAKG was associated with higher odds of a lower Age Residual, but the result was not significant after multivariate correction. The authors name healthy-user and recruitment bias and call for controlled trials.

Participants / model
4,260 supplement-using adults who bought an epigenetic test
Treatment
Self-reported AKG or Rejuvant use
Follow-up
Cross-sectional, with a longitudinal subset
Study design
Cross-sectional observational cohort
Funding
The paper declares no conflicts. Its last author, B. K. Kennedy, is declared a board member of Ponce de Leon Health in the 2020 mouse paper and the Rejuvant analysis

An association in self-selected test buyers, measured on a clock with a 5.4-year mean absolute error. It cannot show cause.

Read the original source
Registered placebo-controlled trials: ABLE (120 adults) and NCT07114536 (34 adults), no posted results

Trial registry record

ClinicalTrials.gov record NCT05706389 (ABLE), read 11 October 2026; ABLE protocol PMID 37217632 and recruitment paper PMID 40819772. ClinicalTrials.gov record NCT07114536.

ABLE (Singapore) randomizes 120 healthy adults aged 40 to 60 with a DNA methylation age above their chronological age to 1 g sustained-release Ca-AKG or placebo for 6 months, with DNA methylation age change as the primary outcome and strength, arterial stiffness and inflammatory markers as secondary outcomes. A recruitment paper reports 467 interested individuals and 120 enrolled over 223 working days. On 11 October 2026 the registry listed ABLE as active, not recruiting, with primary completion 15 August 2025 and no posted results, and no primary results paper was found in PubMed. NCT07114536 (sponsor Shenzhen Hygieia Biotech Co., Ltd) randomized 34 adults aged 40 to 75 to four 0.5 g Ca-AKG tablets daily or starch placebo, with PhenoAge change at week 12 as the primary outcome; it is listed completed (primary completion 30 November 2025) with no posted results.

Participants / model
120 planned and 34 registered adults, middle-aged and older, apparently healthy
Treatment
Oral Ca-AKG, 1 g sustained-release daily (ABLE); four 0.5 g tablets daily (NCT07114536); placebo
Follow-up
6 months (ABLE); 12 weeks (NCT07114536)
Study design
Trial protocol and registry records
Funding
The ABLE protocol and recruitment papers list an author on the Ponce de Leon Health advisory board; NCT07114536 is sponsored by Shenzhen Hygieia Biotech Co., Ltd

Registered trials without results show that a study was registered, not that it works.

Read the original source
Exposure: 6 healthy men in 1990, plus rat absorption data; no supplement-dose pharmacokinetics

Human study

Cynober L et al. J Am Coll Nutr. 1990;9(1):2-12. PMID 2407764.

In 6 fasting healthy men given an oral load of 3.6 g alpha-ketoglutarate as calcium alpha-ketoglutarate, plasma glutamate rose 68% at 60 minutes (p < 0.05 versus baseline). The abstract says the rise in plasma alpha-KG itself was very small, in the sentence describing the ornithine alpha-ketoglutarate and ornithine loads, so it is not clear whether that applies to the calcium salt. In rats, up to 50%, 30% and 20% of gastrically delivered AKG was recovered in the stomach at 0.5, 1 and 2 hours, there was no significant excretion of unmetabolized AKG in urine or feces, 14C label appeared in liver, brain, bone, skin and muscle, up to 70% of the dose at 3 hours, and intestinal absorption did not depend on the AKG salt.

Participants / model
6 healthy men; rats
Treatment
Oral Ca-AKG, 3.6 g AKG load; intragastric and enteral AKG in rats
Follow-up
Single load; up to 3 hours in rats
Study design
Small human study; animal study
Funding
not stated in the source

Plasma pharmacokinetics at the doses sold as supplements were not found. No human data compare AKG salts.

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Dialysis: 14 patients for 36 months, serum calcium rose; 24 patients for 1 year

Human study

Zimmermann E et al. Miner Electrolyte Metab. 1996;22(1-3):196-9. PMID 8676818.

Calcium alpha-ketoglutarate, used as a phosphate binder, was given to 14 hemodialysis patients at a mean 4.5 g/day (0.975 g elemental calcium) for 36 months: serum phosphate fell from 2.6 to 1.9 mmol/L (p < 0.001), serum calcium rose from 2.2 to 2.47 mmol/L (p < 0.05), and intact parathyroid hormone fell from 29 to 8 pmol/L (p < 0.001). In 24 malnourished hemodialysis patients, 1 year of Ca-AKG raised plasma arginine from 53.6 to 71.1 micromol/L (p < 0.05).

Participants / model
14 and 24 patients on maintenance hemodialysis
Treatment
Oral Ca-AKG, 4.5 g/day in the first study
Follow-up
36 months and 1 year
Study design
Small uncontrolled clinical studies, 1996
Funding
not stated in the source

Uncontrolled reports in kidney failure, not safety data for healthy people at supplement doses. They show the calcium load is real.

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Why is Calcium alpha-ketoglutarate in C tier?

C fits an endogenous metabolite with a plausible mechanism, a positive single-laboratory mouse lifespan study with company funding, and an independent multi-site mouse program that did not reproduce lifespan extension. Human data are an uncontrolled 42-person biomarker report, a cross-sectional cohort and old dialysis studies, and the placebo-controlled trials have no published results.