In plain terms: Calcium Alpha-Ketoglutarate (Ca-AKG) has not yet been tested in a human trial designed to measure the outcome relevant here. The available human research does not yet answer the question.
Calcium Alpha-Ketoglutarate (Ca-AKG)
The evidence as the record states it
Asadi Shahmirzadi et al. (Cell Metabolism, 2020; PMID 32877690): Ca-AKG extended lifespan in MICE. Demidenko et al. (Aging, 2021; PMID 34847066): retrospective, uncontrolled analysis of a DNA methylation age test in 42 customers taking Rejuvant, an alpha-ketoglutarate formulation with added vitamins, for about 7 months; authored in part from Ponce de Leon Health, the company that sells it, and the methylation testing was done under a customer-service agreement with that company. Filip et al. (Int J Vitam Nutr Res, 2007; PMID 17896582): randomized trial of alpha-ketoglutarate calcium at 6 g/day in women with osteopenia; a bone-turnover marker fell; different dose, population and endpoint. Lim et al. (Exp Gerontol, 2025; PMID 40819772): recruitment report of the ABLE placebo-controlled trial of 1 g Ca-AKG; results not yet published. D Route 1: no controlled human trial on an aging outcome.
Why Grade D Route 1 and not Grade C
Grade D Route 1 applies when no qualifying human randomized trial has tested this compound or intervention against the relevant endpoint. Absence confirmed: alpha-ketoglutarate OR Rejuvant AND randomized controlled trial[pt] AND (aging OR biological age) (PubMed, July 2026)
The first qualifying human RCT with a meaningful endpoint would move this to Grade C or higher, depending on what it shows.
What would move this grade
The first qualifying randomized controlled trial in humans, testing this intervention against a meaningful aging-relevant endpoint, would initiate grading. Depending on the result, it could land at any grade from A to D.