Effect of melatonin supplementation on endothelial function in heart failure with reduced ejection fraction: A randomized, double‐blinded clinical trial

BACKGROUND: This study aimed to investigate the effect of melatonin supplementation on endothelial function in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: This is an analysis of the MeHR trial, a randomized double‐blinded placebo‐controlled clinical trial with two parallel arms of 1:1. Oral 10 mg melatonin tablets or placebo was administered for 24 weeks. Deference in the percentage of flow‐mediated dilatation (FMD) after the intervention was the primary outcome. RESULTS: Ninety‐two patients were included in the study (age: 62.7±10.3 years, 87.0% male, ejection fraction (EF): 28.6±8.1). After adjustment for baseline FMD and age, a statistically significant difference in post‐treatment FMD in favor of the melatonin group was seen (estimated marginal means [95%CI], melatonin: 7.84% [6.69–8.98], placebo: 5.98% [4.84–7.12], p = .027). There was no significant difference in the mean of post‐treatment systolic/diastolic blood pressure, serum total antioxidant capacity, and serum malondialdehyde (MDA) between groups. Subgroup analysis showed significant improvement in FMD and MDA in the melatonin group in nondiabetic patients, while no difference was seen between study groups in diabetic patients. CONCLUSIONS: Melatonin supplementation in HFrEF might improve endothelial function; however, this beneficial effect might not be seen in diabetic patients.