Tier 3 — preclinical

α-Ketoglutarate promotes amino acid depletion and suppresses B-cell lymphoma growth and development

Jaafar C, Ethiraj P, Qiu Z, Lin AP, Ferrari PSSM, Aguiar RCT
Blood 2025 146(18):2217-2228

Bibliography

PubMed
PMID 40700634
PubMed Central
PMC12983001
DOI
10.1182/blood.2024028069
Funding
Supported by academic hematology/oncology research funding reported in Blood.
Competing interests
Complete conflict disclosures are reported in the Blood article; no retail Ca-AKG longevity product was tested.

Study snapshot

DesignMechanistic in-vitro and in-vivo B-cell lymphoma study.
ModelB-cell lymphoma cell systems and animal lymphoma models.
SampleMultiple cell and animal cohorts; group sizes varied by experiment.
InterventionExogenous AKG used to alter amino-acid metabolism in lymphoma models.
DurationStudy-specific cell and tumor-growth protocols.
EndpointsAmino-acid pools; mTORC1 activity; Lymphoma proliferation; Tumor growth; Lymphoma development

What the study showed, in plain terms

This 2025 Blood paper provides a second, independent cancer context in which exogenous AKG suppressed malignant growth.

AKG drove depletion of several amino acids, including leucine and other branched-chain amino acids, which suppressed mTORC1 activity and inhibited B-cell lymphoma growth in vitro and in vivo.

The findings are preclinical and cancer-specific; they do not justify taking Ca-AKG as cancer prevention or treatment.

Key findings

  • AKG caused rapid and sustained amino-acid depletion in lymphoma models.
  • Leucine depletion altered mTORC1 localization and activity.
  • AKG inhibited B-cell lymphoma growth and development in preclinical models.

What this study can and cannot tell us

  • No human supplementation trial.
  • Cancer-cell metabolism differs substantially by malignancy and microenvironment.
  • Therapeutic exposures cannot be assumed from commercial Ca-AKG doses.

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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