Tier 3 — preclinical

Alpha-ketoglutarate supplementation reduces inflammation and thrombosis in type 2 diabetes by suppressing leukocyte and platelet activation

Agarwal S, Ghosh R, Verma G, Khadgawat R, Guchhait P
Clinical and Experimental Immunology 2023 214(2):197-208

Bibliography

PubMed
PMID 37498307
PubMed Central
PMC10714189
DOI
10.1093/cei/uxad086
Funding
Department of Biotechnology, Government of India (BT/PR22881, BT/PR22985) and Science and Engineering Research Board (CRG/000092).
Competing interests
All authors declared no commercial or financial conflict of interest.

Study snapshot

DesignMouse dietary intervention plus cross-sectional human blood analyses and ex-vivo octyl-AKG experiments.
Modeldb/db mice with type 2 diabetes plus blood samples from people with T2D.
SampleMouse cohorts plus human blood samples; sample counts vary by assay.
InterventionMice received dietary AKG at 8 mg/100 g body weight daily for 7 days; human blood was exposed to octyl-AKG ex vivo.
Duration7-day mouse supplementation; acute ex-vivo human blood exposure.
EndpointsPlatelet activation; Leukocyte activation; Platelet-leukocyte aggregates; Inflammatory cytokines; Lung inflammation and microthrombi; Akt/NF-κB signaling

What the study showed, in plain terms

This study tested AKG in diabetic mice and also examined blood from people with type 2 diabetes.

Seven days of AKG supplementation reduced inflammatory and thrombotic markers in db/db mice. In human samples, octyl-AKG suppressed platelet/leukocyte activation ex vivo, but participants were not given oral AKG.

It is useful mechanistic and translational evidence, but it is not a human Ca-AKG supplementation trial.

Key findings

  • Dietary AKG reduced platelet and leukocyte activation in diabetic mice.
  • Circulating IL-1β, TNF-α and IL-6 and lung inflammatory changes were reduced in the mouse model.
  • Octyl-AKG suppressed aggregation and thrombus formation in T2D human blood ex vivo.

What this study can and cannot tell us

  • The human component was ex vivo, not oral supplementation.
  • Mouse dosing and pharmacology cannot be directly mapped onto commercial Ca-AKG doses.
  • The study concerns type 2 diabetes-related thromboinflammation, not healthy longevity 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