Tier 3 — preclinical

Alpha-ketoglutarate ameliorates pressure overload-induced chronic cardiac dysfunction in mice

An D, Zeng Q, Zhang P, Ma Z, Zhang H, Liu Z, Li J, Ren H, Xu D

Redox Biology 2021 46:102088

Bibliography

PubMed: PMID 34364218
PubMed Central: PMC8353361
DOI: 10.1016/j.redox.2021.102088
Funding: Supported by the Science and Technology Planning Project Foundation of Guangzhou (201707020012) and the National Natural Science Foundation of China (81970336, 81670367).
Competing interests: The authors declared no competing interests.

Design	Controlled mouse pressure-overload study with cardiomyocyte mechanistic experiments.
Model	Transverse-aortic-constriction mice and cultured cardiomyocytes.
Sample	Multiple mouse and cell cohorts; group sizes varied by endpoint.
Intervention	AKG supplementation in pressure-overload mice plus cell-culture AKG treatment.
Duration	Chronic pressure-overload model with study-specific treatment periods.
Endpoints	Left-ventricular systolic function; Cardiac hypertrophy and fibrosis; ROS; Mitophagy; Mitochondrial membrane potential; Apoptosis

This study tested AKG in a mouse model of pressure-overload heart failure rather than normal aging.

AKG reduced hypertrophy and fibrosis and improved systolic function while restoring aspects of mitochondrial quality control and mitophagy.

The findings add cardiovascular and mitochondrial plausibility but do not show that Ca-AKG prevents heart failure or cardiovascular events in humans.

AKG improved systolic dysfunction in pressure-overloaded mice.
Cardiac hypertrophy, fibrosis and ROS were reduced.
Mitophagy and mitochondrial membrane potential were improved in the experimental systems.

Preclinical disease model only.
No oral human Ca-AKG trial or cardiovascular outcomes.
Pressure-overload heart failure is not equivalent to normal cardiovascular aging.

Editorial review

Last verified 20 September 2026