The evidence base for calcium alpha-ketoglutarate

Calcium alpha-ketoglutarate (Ca-AKG) is the calcium salt of α-ketoglutarate, a central tricarboxylic-acid-cycle metabolite with roles in energy metabolism, amino-acid handling, redox biology and α-ketoglutarate-dependent dioxygenases. The evidence base is broad but uneven. A 2020 Ca-AKG mouse study reported longer lifespan and better healthspan in C57BL/6J mice, while two independent National Institute on Aging Interventions Testing Program studies in genetically heterogeneous UM-HET3 mice did not reproduce a lifespan benefit. Human exposure to Ca-AKG and other AKG salts has been studied for decades, including gram-level dosing and multi-year clinical use, but most older studies involved renal, metabolic, surgical or hypercatabolic populations rather than healthy aging. A commonly repeated claim that circulating AKG falls about ten-fold between ages 40 and 80 should not be treated as established human evidence. The historical review from which that statement spread attributes it to unpublished observations, while a published metabolomics study of 146 adults found significantly higher serum AKG in older adults than in young adults. Tissue, circulating and organ-specific AKG biology therefore appears context-dependent. Modern human aging evidence remains limited. Retrospective and cross-sectional biological-age studies cannot establish causality, and the ABLE randomized trial has published its protocol and recruitment analysis but not its efficacy outcomes. Related salts such as arginine-AKG and ornithine-AKG are included here only when they clarify formulation, pharmacology, safety or historical human use; their results are not treated as evidence for Ca-AKG. This Data Center separates direct human Ca-AKG evidence, related-form human evidence, observational aging data, animal intervention studies, mechanistic experiments and reviews so that biological plausibility is not confused with proven human longevity benefit.