Alpha-ketoglutarate

The case for AKG comes from animals, and it is mixed. AKG extended the lifespan of adult worms [1]. In mice given calcium AKG from 18 months of age, median lifespan rose by 10.5% to 16.6% in females across two cohorts, males gained less, and both sexes were less frail, with lower inflammation [2]. When the multi-site Interventions Testing Program tested AKG in genetically mixed mice, it found no lifespan gain in either sex, whether started at 18 months or at 7 months [3].

In people, the evidence is thin. A retrospective analysis of 42 people taking Rejuvant, an AKG and vitamin formula, reported an average 8-year drop on a DNA methylation clock, but it had no control group and was run by the testing company and the supplement maker [4]. Small studies from the 1980s and 1990s looked at AKG for muscle and recovery after surgery [5], for example adding it to intravenous feeding after an operation to preserve muscle protein synthesis [6].

The ABLE trial is testing 1 g of sustained-release calcium AKG a day against placebo for 6 months in 120 middle-aged adults whose DNA methylation age is older than their real age [7]. Until trials like it report, whether AKG slows aging in people is unknown. AKG is not an approved medicine for any aging use.

• Calcium AKG is sold as a dietary supplement. It is not an approved medicine for aging, and no published placebo-controlled trial shows that it slows aging in people.
• Each 2 g of calcium AKG supplies about 400 mg of calcium, which adds to calcium from food and other supplements.
• Safety in pregnancy, breastfeeding and children is not established; Bryan Johnson's protocol lists it among supplements to avoid during pregnancy.
• Several researchers behind the main AKG studies, including Brian Kennedy, have held board seats, equity or advisory roles at Ponce de Leon Health, which sells an AKG supplement.