Ketone therapy improves cardiac function and structure in rodents with heart failure: A systematic review and
Tingting Lv1, Chunyan Liu2, Mengfei Ye3
1Department of General Practice, Shaoxing People's Hospital, Shaoxing, PR China; Department of Pharmacology, School of Medicine, Shaoxing University, Shaoxing, Zhejiang, PR China.
Insights
Ketone therapy significantly improved heart function and structure in rodents with heart failure (HF). However, it did not benefit healthy rodents, suggesting potential therapeutic applications for HF.
Area of Science:
- Cardiovascular Research
- Metabolic Science
- Animal Models
Background:
- Heart failure (HF) is a complex condition with significant morbidity and mortality.
- Current therapeutic strategies for HF have limitations.
- Metabolic interventions, such as ketone therapy, are being explored as novel treatment options.
Purpose of the Study:
- To quantitatively assess the effects of ketone intervention on cardiac function and structure in rodent models of heart failure.
- To investigate whether ketone intervention could enhance cardiac function and structure in HF.
Main Methods:
- A systematic meta-analysis of 24 animal studies was conducted.
- Studies were identified through searches of PubMed, Cochrane Library, and Embase databases.
- Ketone therapy included ketogenic diets, ketone esters, medium-chain triglycerides, and β-hydroxybutyrate.
Main Results:
- Ketone therapy significantly improved left ventricular ejection fraction (SMD: 1.31) and cardiac output (SMD: 0.70) in HF rodents.
- It also ameliorated myocardial hypertrophy (SMD: -1.95), fibrosis (SMD: -0.87), and ventricular remodeling.
- Ketone intervention worsened myocardial fibrosis in non-HF rodents and had no significant effect on their cardiac function.
Conclusions:
- Ketone therapy demonstrates significant benefits for cardiac systolic function and structure in rodents with heart failure.
- Ketone intervention showed no positive effects in non-HF rodents.
- Ketone therapy may represent a promising therapeutic strategy for patients with heart failure.
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.
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