Key result
Ketone ester lowers plasma glucose appearance by ~0.24 mg/kg/min and reduces LV filling pressures in HFpEF.
Why the study?
Exercise intolerance in HFpEF has a multifactorial etiology with several contributing pathways that may be improved by ketone ester.
Does ketone ester improve exercise tolerance in patients with heart failure with preserved ejection fraction?
RCT
Does ketone ester improve exercise tolerance in patients with heart failure with preserved ejection fraction?
Effect estimate: Difference -0.24 mg/kg/min
p-value: p=<0.001
Exogenous ketone ester alters metabolic substrate utilization and lowers estimated left ventricular filling pressures during exercise in patients with HFpEF.
May lower exercise filling pressures in HFpEF; extends RCT evidence for ketone modulation to preserved EF.
BACKGROUND: The etiology of exercise intolerance in heart failure with preserved ejection fraction (HFpEF) is multifactorial. Several contributing pathways may be improved by ketone ester (KE). OBJECTIVES: This study aims to determine whether KE improves exercise tolerance in HFpEF. METHODS: ) during incremental cardiopulmonary exercise testing and time to exhaustion during an additional constant-intensity exercise (75% peak workload) bout. RESULTS: -glucose infusions during constant-intensity exercise, plasma glucose appearance rate before and during exercise was lower with KE (-0.24 mg/kg/min; P < 0.001). During both exercise protocols, KE lowered: 1) respiratory exchange ratios, demonstrating decreased systemic carbohydrate use; 2) nonesterified fatty acids and glucose; and 3) estimated left ventricular filling pressures (E/e'). CONCLUSIONS: or constant-intensity exercise in HFpEF. (Ketogenic Exogenous Therapies in HFpEF [KETO-HFpEF]; NCT04633460).
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Selvaraj et al. (2025) conducted an RCT in Heart failure with preserved ejection fraction (HFpEF). Ketone ester (KE) was evaluated on Plasma glucose appearance rate before and during exercise (Difference -0.24 mg/kg/min, p=<0.001). Ketone ester lowered plasma glucose appearance rate before and during exercise by 0.24 mg/kg/min (P<0.001) and decreased estimated left ventricular filling pressures in patients with HFpEF.
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