Ketone therapy improves cardiac function and structure in rodents with heart failure: A systematic review and meta-analysis

Abstract

This meta-analysis aimed to quantitatively assess the effects of ketone intervention on cardiac function and structure in rodents with heart failure (HF). We hypothesized that ketone intervention could enhance the cardiac function and structure in HF. We systematically searched PubMed, Cochrane Library, and Embase databases for relevant studies up to April 13, 2024. Ketone therapy encompassed a ketogenic diet, ketone esters, medium-chain triglycerides, and β-hydroxybutyrate. The effect measures are mainly expressed as standardized mean difference (SMD) and 95% confidence interval (CI). Our meta-analysis included 24 animal studies. Ketone therapy significantly improved left ventricular ejection fraction (SMD: 1.31, 95% CI: 0.79-1.82, I² = 77%), cardiac output (SMD: 0.70, 95% CI: 0.28-1.11, I² = 0%), and ameliorated myocardial hypertrophy (SMD: −1.95, 95% CI: −2.76 to −1.13, I² = 76%), myocardial fibrosis (SMD: −0.87, 95% CI: −1.60 to −0.15, I² = 68%), and ventricular remodeling in HF rodents. Subgroup analysis indicated that ketone intervention worsened myocardial fibrosis in non-HF rodents (SMD: 0.86, 95% CI: 0.09-1.63, I² = 78%) and had no significant effect on cardiac function. Additionally, further subgroup analysis indicated that ketogenic diet significantly alleviated cardiac hypertrophy and fibrosis, whereas ketone esters did not yield significant effects. The effect of ketone on left ventricular ejection fraction strengthened with the duration of intervention. Our results suggested that ketone therapy significantly improved the cardiac systolic function and structure in rodents with HF, and had no effect in rodents non-HF. Thus, ketone intervention may be a promising treatment for HF patients.