Tier 2 — strong

Alpha-Ketoglutarate: A Metabolic Regulator of Cellular Homeostasis and Pathophysiology

Devulapalli V, Sathiyamurthi A, Gautam S, Bhattaram P
Biomedicines 2026 14(4):836

Bibliography

PubMed
PMID 42072377
PubMed Central
PMC13113529
DOI
10.3390/biomedicines14040836
Funding
NIH/NIAMS grants R01 AR070736 and R21 AR078463; APC funded by the Department of Orthopaedics, Emory University School of Medicine.
Competing interests
The authors declared no conflicts of interest.

Study snapshot

DesignNarrative mechanistic review.
ModelPublished biochemical, cellular, animal and human literature.
SampleNot applicable — narrative review.
InterventionNot applicable.
DurationNot applicable.
EndpointsAKG metabolism; Epigenetic remodeling; Immune regulation; Inflammation; Mitochondrial function; Lifespan biology; Clinical evidence gaps

What the study showed, in plain terms

This 2026 review provides the freshest broad synthesis in the current Ca-AKG Data Center.

It covers mitochondrial and nuclear AKG pools, epigenetic remodeling, macrophage biology, oxidative stress, inflammation, extracellular-matrix regulation and aging mechanisms.

Crucially, the authors also emphasize the lack of adequate human clinical evidence, uncertain optimal dosing and the need to distinguish different AKG formulations.

Key findings

  • AKG links mitochondrial metabolism to epigenetic and immune signaling.
  • The review summarizes anti-inflammatory, redox and tissue-remodeling mechanisms across experimental systems.
  • The authors explicitly identify human clinical evidence, ideal dosing and formulation-specific effects as unresolved gaps.

What this study can and cannot tell us

  • Narrative review, not a quantitative evidence synthesis.
  • The review spans many diseases and formulations, not specifically retail Ca-AKG.
  • Mechanistic plausibility should not be converted into claims of human longevity benefit.

Citation network

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Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology