Published online Jun 9, 2026. doi: 10.5492/wjccm.v15.i2.117717
Revised: January 12, 2026
Accepted: April 13, 2026
Published online: June 9, 2026
Processing time: 158 Days and 12.1 Hours
Ketone bodies, especially β-hydroxybutyrate, have shown the potential to im
To evaluate the impact of ketone body supplementation on cardiac and hemodynamic parameters in patients with HF while accounting for the limited and emerging nature of the available randomized evidence.
A systematic search of PubMed, Scopus, EMBASE, and the Cochrane Central Register of Controlled Trials was conducted from inception to March 2025, with additional screening of ClinicalTrials.gov for unpublished or ongoing trials. Randomized controlled trials (RCTs) comparing ketone body supplementation with placebo in patients with HF were included. Statistical analyses were performed using a random-effects model in RevMan 5.4 to calculate weighted mean differences (MDs) with 95% confidence intervals (CIs). Outcomes assessed included CO, systemic vascular resistance, LVEF, heart rate, venous oxygen saturation, pulmonary capillary wedge pressure, and other cardiac functional indices. Given the small number of included studies, subgroup analyses were considered exploratory.
Four randomized controlled trials involving a total of 94 patients were included. Compared with placebo, ketone supplementation was associated with a significant increase in CO (MD = 1.11, 95%CI: 0.13-2.09, P = 0.03) and a reduction in systemic vascular resistance (MD = -252.61, 95%CI: -475.72 to -29.50, P = 0.03). Improvements were also observed in LVEF (MD = 3.31, 95%CI: 0.39-6.22, P = 0.03), venous oxygen saturation (MD = 3.33, 95%CI: -0.01 to 6.68, P = 0.05), and pulmonary capillary wedge pressure (MD = -1.09, 95%CI: -1.60 to -0.59, P < 0.0001), along with an increase in heart rate (MD = 4.08, 95%CI: 3.00-5.17, P < 0.0001). Subgroup analyses by HF phenotype (HF with reduced ejection fraction vs HF with preserved ejection fraction) suggested differential effects; however, several subgroups included only one study and should be interpreted as hypothesis-generating only. No statistically significant changes were observed in global longitudinal strain, left ventricular end-diastolic volume, or tricuspid annular plane systolic excursion, and substantial heterogeneity and potential small-study effects limit the robustness of pooled estimates.
Ketone body supplementation was associated with short-term improvements in selected hemodynamic and cardiac functional parameters in patients with HF. However, these findings are based on a small number of short-duration trials with limited sample sizes and crossover designs, precluding firm clinical conclusions. Larger, well-powered randomized trials with longer follow-up are required to confirm the therapeutic role, optimal dosing, and clinical impact of ketone supplementation in HF.
Core Tip: Metabolic modulation has emerged as a novel therapeutic strategy in heart failure (HF). This systematic review and meta-analysis of randomized controlled trials demonstrates that ketone body supplementation, particularly β-hydroxybutyrate, significantly improves cardiac output, left ventricular ejection fraction, and key hemodynamic parameters while reducing systemic vascular resistance and pulmonary capillary wedge pressure in patients with HF. These findings highlight the potential role of ketone bodies as an adjunctive metabolic therapy to enhance myocardial efficiency and hemodynamic performance, especially in HF with reduced ejection fraction.