Alpha-Ketoglutarate (AKG)

Lifespan studies in animals

• In a 2014 UCLA study in worms, AKG at 8 mM extended the lifespan of Caenorhabditis elegans by about 50 percent through inhibition of ATP synthase and TOR (PMID: 24828042).
• A 2019 study at Sichuan Agricultural University found that dietary AKG extended fruit fly lifespan, reduced reproduction and activated AMPK while lowering mTOR activity (PMID: 31242135).
• In a 2020 Buck Institute mouse study, C57BL/6 mice were switched at 18 months (540 days) of age to food containing 2 percent Ca-AKG by weight, in two cohorts totaling 182 mice. Counted from the start of feeding, median lifespan in females rose by 16.6 percent in the first cohort and 10.5 percent in the second, and the age at 90 percent mortality rose by 19.7 and 8 percent; in males, median lifespan from the start of feeding rose by 9.6 and 12.8 percent, but the survival difference was not significant in either cohort. Counted from birth, the Interventions Testing Program authors put the female median gains at 6.3 and 3.3 percent (PMID: 38753230). The share of life spent frail fell by 46 percent in females and 41 percent in males (PMID: 32877690). The work was funded in part by a company that sells a Ca-AKG supplement; several authors held shares in it, one sat on its board, and several were named inventors on a related patent application (PMID: 32877690, PMID: 34847066).
• In the NIA Interventions Testing Program's 2020 mouse cohort, genetically heterogeneous UM-HET3 mice were given AKG at 20,000 ppm in food from 18 months of age, the same dose and start age as the Buck Institute study. Median lifespan changed by +0.9 percent in females (p=0.59) and +3.0 percent in males (p=0.58), and the authors wrote that their data fail to confirm the earlier result (PMID: 38753230). A 2025 correction restored two omitted authors and the AKG group omitted from one figure, with no change to the results (PMID: 39004654).
• For its 2022 mouse cohort, the NIA Interventions Testing Program started AKG at 7 months of age at a target dose of 20,000 ppm in food (the paper lists an achieved dose of 3,262 ppm). Pooled across three sites, median lifespan changed by +3.4 percent in 153 males (p=0.43) and -1.6 percent in 132 females (p=0.23) compared with controls, and the authors reported no effect in either sex (PMID: 41843349).
• In a 2020 Sichuan University mouse study, AKG increased bone mass in aged mice, reduced age-related bone loss and sped bone regeneration (PMID: 33154378).

Human studies of aging markers

• In a 2021 retrospective analysis of 42 people by Demidenko and colleagues, customers who had taken a commercial supplement containing calcium AKG plus vitamin A (men) or vitamin D (women) for 4 to 10 months, and who had done a saliva DNA methylation test before and after, had an average fall in estimated biological age of about 8 years. The study had no placebo or control group, the participants were customers of the supplement and of the testing company, which had a service agreement to test the supplement's customers, and six of the seven authors listed the supplement company or the testing company as an affiliation, one of them as a consultant and board member of the supplement company; the authors said a placebo-controlled study is needed (PMID: 34847066).
• Pabis and colleagues (2026) published a cross-sectional study of 4,260 people. Among buyers of a saliva epigenetic test who filled in supplement questionnaires, users of the same commercial delayed-release Ca-AKG and vitamin product had an estimated biological age 1.8 years lower than expected, while people taking ordinary AKG showed a smaller difference that was not statistically significant; in a longitudinal subset the association was not significant after multivariate correction, and the authors named healthy-user and recruitment bias as limits. One author worked for the testing company, and some participants were recruited through the supplement's maker and given a free test (PMID: 42166733).
• ABLE, a randomized double-blind placebo-controlled phase 2 trial at the National University of Singapore, enrolled 120 generally healthy adults aged 40 to 60 whose blood DNA methylation age at screening was higher than their actual age, and gave 1 g of sustained-release Ca-AKG a day or placebo for 6 months, with 3 months of follow-up (PMID: 37217632, PMID: 40819772). The primary outcome is the change in DNA methylation age (PMID: 37217632). Supplement adherence was above 90 percent, and 17 percent of participants dropped out (PMID: 42789532). The ClinicalTrials.gov record (NCT05706389) lists primary completion on 15 August 2025, status active and not recruiting, and no posted results, and a PubMed search on 26 October 2026 found only the protocol, recruitment and device-feasibility papers, with no outcome results.
• A randomized, triple-masked, placebo-controlled trial of the commercial Ca-AKG product in 100 people, sponsored by its maker with C-reactive protein at 9 months as the primary outcome, was completed in February 2022 (ClinicalTrials.gov NCT04821401). A 34-person randomized placebo-controlled trial of Ca-AKG on PhenoAge, sponsored by a Chinese biotechnology company, was completed in November 2025 (ClinicalTrials.gov NCT07114536). Neither record had posted results, and no publication of either was found in PubMed on 26 October 2026. At National University Hospital, Singapore, AKG is being tested against placebo after heart bypass surgery (250 planned, status recruiting, NCT07031128) and colorectal surgery (80 planned, status unknown, NCT06646809).

Older clinical trials

• Karolinska Institute researchers tested AKG in surgical patients. In 21 patients after gallbladder removal, intravenous nutrition with AKG (9 patients) prevented the fall in muscle free glutamine and polyribosomes seen without it (12 patients), and cumulative nitrogen balance was -2.6 g against -9.9 g (p<0.05) (PMID: 1898624, PMID: 1969067). A later randomized trial in 20 patients found that AKG-enriched tube feeding after major abdominal surgery did not improve nitrogen balance, muscle breakdown markers or clinical outcomes (PMID: 12297206).
• In an open crossover trial in 28 hemodialysis patients, calcium ketoglutarate and calcium acetate lowered serum phosphate equally over 12 weeks each, with less high blood calcium on ketoglutarate (PMID: 10383011). In a randomized crossover trial in 19 patients, 10 of whom completed both arms, phosphate and parathyroid hormone did not differ from calcium carbonate, and 5 of 17 patients stopped ketoglutarate because of intolerance (PMID: 9469496). In a before-and-after comparison in 24 malnourished dialysis patients given calcium AKG for one year, plasma arginine rose from 53.6 to 71.1 micromol/L, and phosphate and urea fell (PMID: 8676801).
• In a 2007 randomized double-blind trial from Lublin in 76 postmenopausal women with osteopenia, 6 g of AKG with calcium a day for 6 months lowered serum CTX, a bone breakdown marker, by up to 37.0 percent, with significant differences from calcium alone at 12 and 24 weeks; osteocalcin did not change, and the 0.9 percent difference in spine bone density between groups was not significant (PMID: 17896582).
• A 2021 review from the National University of Singapore group noted that a few human studies published in the 1980s and 1990s suggested possible benefits for muscle growth, wound healing and recovery after surgery, and that no recent studies had shown a role for AKG in aging or age-related disease (PMID: 34952764).

Related salts, which are different compounds

• In 35 resistance-trained men, 12 g a day of arginine alpha-ketoglutarate for 8 weeks improved one-repetition bench press and Wingate peak power compared with placebo, with no change in body composition or aerobic capacity; because the salt also supplies arginine, the results cannot be credited to AKG alone (PMID: 16928472).
• A 2026 systematic review of 15 clinical, animal and laboratory studies in burn care, most from France, reported improved nitrogen balance and wound healing with ornithine alpha-ketoglutarate, and noted that the findings come from small and varied studies (PMID: 41504365).

In 20 patients after major abdominal surgery, tube feeding enriched with AKG lowered serum albumin more than standard feeding and did not improve nitrogen balance or clinical outcomes (PMID: 12297206). The longest human study found lasted 36 months, in 14 hemodialysis patients given calcium AKG as a phosphate binder, in whom serum phosphate and parathyroid hormone fell and serum calcium rose (PMID: 8676818).

Animal data

In the 2020 Buck Institute study, the authors did not detect significant adverse changes in mice fed 2 percent Ca-AKG from 18 months of age (PMID: 32877690). In the Interventions Testing Program's 2022 cohort, median lifespan with AKG differed from controls by +3.4 percent in males and -1.6 percent in females, neither statistically significant (PMID: 41843349).

Gaps

No human data on AKG supplements in pregnancy or breastfeeding were found, and no human pharmacokinetic or drug interaction studies of oral AKG supplements were found.