Resident Physician University Of Alberta Edmonton, Alberta, Canada
Background: Ketone bodies, an emerging class of nutraceuticals, have shown potential to improve cardiac metabolism and function in patients with heart failure (HF). The objective of this study is to evaluate the effects of exogenous ketone-based interventions on cardiac function in patients with HF or related cardiometabolic risk factors.
METHODS AND RESULTS: We conducted a systematic review based on a search of MEDLINE, EMBASE, CINAHL, Cochrane Library, and Scopus. Eligible studies include randomized controlled trials published from inception to January 2025 that examined exogenous ketones including oral ketones and ketone infusions. The population consisted of patients with HF or patients with risk factors for HF including type 2 diabetes mellitus, hypertension, or coronary artery disease. Studies that evaluated healthy participants with no relevant comorbidities and those that used ketogenic diets as the intervention were excluded.
Out of 565 unique records, 22 full-text articles were reviewed, and 8 studies met inclusion criteria. Random effects meta-analysis demonstrated improvements in left ventricular ejection fraction (LVEF: estimate = 3.78%, SE = 0.78, p = 0.0029), cardiac output (CO L/min: 1.04, 0.27, p = 0.0090), heart rate (HR: 4.90 bpm, 1.29, p = 0.0090), and stroke volume (SV: 9.45 mls, 3.01, p = 0.0201). Pulmonary capillary wedge pressure (PCWP) decreased (estimate = -1.13 mmHg, SE = 0.37, p = 0.0289), while mean arterial pressure (MAP) showed no change (estimate = -1.41, SE = 1.07, p = 0.2464).
Conclusion: Exogenous ketone-based therapies are associated with improvements in hemodynamic markers of cardiac function, including increases in LVEF, cardiac output, and stroke volume, along with a reduction in pulmonary capillary wedge pressure. These findings suggest that ketone supplementation may offer clinical benefits for patients with heart failure, or vascular disease.
