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Effects of ketone bodies supplementation in patients with heart failure: A systematic review and meta-analysis

Ahmed K Siddiqi1, Syed S Javaid2, Akash Kumar3

  • 1Division of Cardiothoracic Imaging, Department of Radiology and Imaging Sciences, Emory University, Atlanta 30322, GA, United States.

World Journal of Critical Care Medicine
|June 11, 2026
PubMed

Insights

Ketone body supplementation shows potential for improving cardiac function in heart failure (HF) patients, increasing cardiac output and ejection fraction. However, more extensive research is needed to confirm these benefits and establish clinical guidelines.

Area of Science:

  • Cardiology
  • Metabolic Medicine
  • Pharmacology

Background:

  • Ketone bodies, particularly β-hydroxybutyrate, may enhance hemodynamic outcomes in heart failure (HF).
  • The efficacy of ketone body supplementation for HF patients requires further investigation due to limited randomized evidence.

Purpose of the Study:

  • To systematically review and meta-analyze the impact of ketone body supplementation on cardiac and hemodynamic parameters in HF patients.
  • To assess emerging randomized evidence on ketone supplementation in heart failure.

Main Methods:

  • Systematic search of major databases (PubMed, Scopus, EMBASE, Cochrane) and ClinicalTrials.gov.
  • Inclusion of randomized controlled trials (RCTs) comparing ketone supplementation to placebo in HF patients.
  • Random-effects model meta-analysis of outcomes including cardiac output, LVEF, and systemic vascular resistance.

Main Results:

  • Four RCTs with 94 patients indicated ketone supplementation increased cardiac output (CO) and left ventricular ejection fraction (LVEF).
  • Significant reductions in systemic vascular resistance and pulmonary capillary wedge pressure were observed.
  • Improvements in venous oxygen saturation and an increase in heart rate were noted; however, heterogeneity and small sample sizes limit conclusions.

Conclusions:

  • Ketone body supplementation demonstrated short-term improvements in select hemodynamic and cardiac parameters for HF patients.
  • Findings are limited by small sample sizes, short trial durations, and study designs, precluding definitive clinical recommendations.
  • Larger, longer-term RCTs are necessary to validate the therapeutic role and clinical impact of ketone supplementation in HF management.
Abstract

Keywords:
3-β-hydroxybutyrateCardiac outputHeart failureKetone bodiesLeft ventricular ejection fraction

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