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Radiolabeling and dose fixation study of oral alpha-ketoglutarate as a cyanide antidote in healthy human volunteers

Mittal G, Singh T, Kumar N, Bhatnagar A, Tripathi RP, Tulsawani R, Vijayaraghavan R, Bhattacharya R
Clinical Toxicology 2010 48(6):509-515

Bibliography

PubMed
PMID 20572756
DOI
10.3109/15563650.2010.496371
Funding
The authors were affiliated with Indian defense and nuclear-medicine research institutions; specific grant funding is not reported in the accessible abstract.
Competing interests
No commercial Ca-AKG supplement intervention was studied; full conflict disclosures were not available in the accessible abstract.

Study snapshot

DesignHuman pharmacoscintigraphy and radiometry study with supporting animal dose/bioabsorption experiments.
ModelHealthy human volunteers plus rat and rabbit pharmacoscintigraphy.
SampleHealthy volunteers received oral AKG; exact human sample count is not stated in the PubMed abstract.
Intervention5-20 g oral free AKG given as single or split doses with varying water volumes.
DurationAcute single-session pharmacokinetic/bioavailability testing.
EndpointsGastric emptying; Apparent oral bioavailability; Dose-splitting effects; Effect of water volume on absorption

What the study showed, in plain terms

This older human study is relevant because it directly examined how orally administered AKG behaves in people.

Using radiolabeled AKG, the researchers found that dose pattern and water intake substantially affected gastric emptying and estimated bioavailability. Two 10 g doses separated by 10 minutes and followed by 300 mL water produced higher estimated bioavailability than a single 20 g dose.

The doses were extremely high and the indication was cyanide-antidote development, so it should not be treated as a dosing study for modern Ca-AKG longevity supplements.

Key findings

  • Oral AKG absorption depended strongly on dose and administration conditions.
  • Splitting a 20 g total dose into two 10 g doses increased estimated bioavailability versus one 20 g dose.
  • Water intake improved gastric emptying and apparent absorption.

What this study can and cannot tell us

  • Free AKG was tested, not calcium alpha-ketoglutarate.
  • Doses of 5-20 g are far above typical longevity-supplement doses.
  • The study evaluated pharmacokinetics in an antidote-development context, not aging outcomes.

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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