Heart failure & cardiomyopathiesRandomised controlled trial
Crossover Trial of Exogenous Ketones on Cardiometabolic Endpoints in Heart Failure With Preserved Ejection Fraction
- Randomised controlled trial
- crossover
- placebo-controlled
Authors' conclusion
Despite robust ketosis, shifting substrate use away from carbohydrates, and decreasing estimated left ventricular filling pressures, acute KE supplementation did not improve peak VO2 or constant-intensity exercise in HFpEF.
Study context
- Population
- Symptomatic heart failure with preserved ejection fraction (HFpEF)
- Participants
- 20 participants
- Comparison
- Acute ketone ester vs placebo
- Primary endpoint
- Coprimary: peak VO2 during incremental cardiopulmonary exercise testing; time to exhaustion during constant-intensity exercise (75% peak workload)
Primary result
As reported in the abstract
| Group | Peak VO2 | Constant-intensity exercise endurance |
|---|---|---|
| Ketone ester (KE) | 10.4 ± 3.6 mL/kg/min | 9.7 ± 7.3 minutes |
| Placebo | 10.5 ± 4.0 mL/kg/min | 8.7 ± 4.4 minutes |
- KE vs Placebo: P = 0.75 — peak VO2
- KE vs Placebo: P = 0.51 — constant-intensity exercise endurance
Further findings
| Outcome | difference (L/min) (95% CI) | P value | |
|---|---|---|---|
| Resting haemodynamics · At rest — KE vs Placebo · cardiac output | 0.6 (0.3–1.0) | ||
| −0.500.511.5Difference, L/min (linear scale) |
| Outcome | difference (WU) (95% CI) | P value | |
|---|---|---|---|
| Resting haemodynamics · At rest — KE vs Placebo · total peripheral resistance | −3.2 (−5.2 to −1.2) | ||
| −10−505Difference, WU (linear scale) |
| Outcome | difference (mL of O2/dL blood) (95% CI) | P value | |
|---|---|---|---|
| Resting haemodynamics · At rest — KE vs Placebo · arteriovenous oxygen content difference | −0.7 (−1.2 to −0.2) | ||
| −1.5−1−0.500.5Difference, mL of O2/dL blood (linear scale) |
| Outcome | difference (mg/kg/min) | P value |
|---|---|---|
| Plasma glucose appearance rate (6 participants with 6,6-2H2-glucose infusions) · before and during constant-intensity exercise | −0.24 | P < 0.001 |
Resting haemodynamics · At rest
- Heart rate and biventricular systolic function greater with KE; differences mostly disappeared during incremental exercise
Respiratory exchange ratio, NEFA and glucose, estimated LV filling pressures (E/e') · during both exercise protocols
- Lowered with KE
Original publication
Crossover Trial of Exogenous Ketones on Cardiometabolic Endpoints in Heart Failure With Preserved Ejection Fraction. JACC Heart Fail. Published 29 March 2025. doi:10.1016/j.jchf.2025.03.002
Summarised from the published abstract; every number is checked against it