Tier 3 — preclinical

Toxicity of alpha-ketoglutarate following 14-days repeated oral administration in Wistar rats

Bhattacharya R, Gujar N, Singh P, Rao P, Vijayaraghavan R
Cellular and Molecular Biology 2011 57 Suppl:OL1543-OL1549

Bibliography

PubMed
PMID 21791173
DOI
10.1170/178
Funding
Conducted at India's Defence Research and Development Establishment; specific grant information is not stated in the PubMed record.
Competing interests
No commercial longevity-supplement product was evaluated.

Study snapshot

DesignRepeated-dose oral toxicity study with recovery follow-up.
ModelMale and female Wistar rats.
SampleRodent toxicology cohorts across three AKG dose levels plus controls.
InterventionOral AKG at 1, 2 or 4 g/kg/day for 14 days.
Duration14 days treatment plus 7-day recovery.
EndpointsClinical toxicity; Body weight; Hematology; Organ weights; Histopathology; NOAEL

What the study showed, in plain terms

This is one of the most useful dedicated oral-AKG safety studies in the preclinical literature.

Rats received very high doses of 1, 2 or 4 g/kg/day for 14 days. Diarrhea appeared at 4 g/kg, with additional hematologic and organ-weight changes at higher doses; the authors identified 1 g/kg/day as the no-observed-adverse-effect level in this model.

Rat NOAEL values cannot be converted directly into a recommended human supplement dose, but the study provides a real repeated-dose toxicity anchor.

Key findings

  • The reported rat NOAEL was 1 g/kg/day.
  • Diarrhea occurred at 4 g/kg/day in both sexes.
  • Higher doses produced reversible anemia in females and some delayed hematologic/organ-weight changes in males without corresponding major histopathology.

What this study can and cannot tell us

  • Rat toxicology study, not human safety evidence.
  • Doses were far above common retail supplement exposures.
  • The study used alpha-ketoglutarate for antidote-development toxicology, not calcium-AKG longevity supplementation.

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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