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Randomized Controlled Trial
. 2021 Sep;44(9):1263-1271.
doi: 10.1002/clc.23682. Epub 2021 Jun 28.

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

Shervin Ghaffari Hoseini  1   2 , Kiyan Heshmat-Ghahdarijani  3 , Saeid Khosrawi  2 , Mohammad Garakyaraghi  3 , Davood Shafie  3 , Hamidreza Roohafza  4 , Marjan Mansourian  1 , Elham Azizi  4 , Yousof Gheisari  5 , Masoumeh Sadeghi  4
Affiliations
Randomized Controlled Trial

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

Shervin Ghaffari Hoseini et al. Clin Cardiol. 2021 Sep.

Abstract

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.

Keywords: blood pressure; endothelial dysfunction; heart failure with reduced ejection fraction; melatonin; oxidative stress.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

FIGURE 1
FIGURE 1
CONSORT flow diagram of the MeHR trial
FIGURE 2
FIGURE 2
Effect of melatonin supplementation on FMD, MDA, and TAC. Outcomes are expressed as a difference between post‐ and pre‐treatment values. Center bars are medians; box tops and bottoms are interquartile ranges; whiskers are minimum and maximum values; crosses inside boxes are means. FMD, flow‐mediated dilatation; MDA, malondialdehyde; TAC, total antioxidant capacity
FIGURE 3
FIGURE 3
Subgroup analysis of effect of melatonin supplementation on FMD according to the diabetes status. Outcomes are expressed as a difference between post‐ and pre‐treatment values. Center bars are medians; box tops and bottoms are interquartile ranges; whiskers are minimum and maximum values; crosses inside boxes are means. FMD, flow‐mediated dilatation; MDA, malondialdehyde; TAC, total antioxidant capacity
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