Melatonin supplementation improves N-terminal pro-B-type natriuretic peptide levels and quality of life in patients with heart failure with reduced ejection fraction: Results from MeHR trial, a randomized clinical trial

Clin Cardiol. 2022 Apr;45(4):417-426. doi: 10.1002/clc.23796. Epub 2022 Feb 16.


Background: Melatonin, the major secretion of the pineal gland, has beneficial effects on the cardiovascular system and might advantage heart failure with reduced ejection fraction (HFrEF) by attenuating the effects of the renin-angiotensin-aldosterone and sympathetic system on the heart besides its antioxidant and anti-inflammatory effects.

Hypothesis: We hypothesized that oral melatonin might improve echocardiographic parameters, serum biomarkers, and a composite clinical outcome (including quality of life, hospitalization, and mortality) in patients with HFrEF.

Methods: A placebo-controlled double-blinded randomized clinical trial was conducted on patients with stable HFrEF. The intervention was 10 mg melatonin or placebo tablets administered every night for 24 weeks. Echocardiography and measurements of N-terminal pro-B-type natriuretic peptide (NT-Pro BNP), high-sensitivity C-reactive protein, lipid profile, and psychological parameters were done at baseline and after 24 weeks.

Results: Overall, 92 patients were recruited, and 85 completed the study (melatonin: 42, placebo: 43). Serum NT-Pro BNP decreased significantly in the melatonin compared with the placebo group (estimated marginal means for difference [95% confidence interval]: 111.0 [6.2-215.7], p = .044). Moreover, the melatonin group had a significantly better clinical outcome (0.93 [0.18-1.69], p = .017), quality of life (5.8 [0.9-12.5], p = .037), and New York Heart Association class (odds ratio: 12.9 [1.6-102.4]; p = .015) at the end of the trial. Other studied outcomes were not significantly different between groups.

Conclusions: Oral melatonin decreased NT-Pro BNP and improved the quality of life in patients with HFrEF. Thus it might be a beneficial supplement in HFrEF.

Keywords: brain natriuretic peptide; heart failure; melatonin; quality of life.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Dietary Supplements
  • Heart Failure* / diagnosis
  • Heart Failure* / drug therapy
  • Humans
  • Melatonin* / adverse effects
  • Natriuretic Peptide, Brain
  • Peptide Fragments
  • Quality of Life
  • Stroke Volume


  • Peptide Fragments
  • Natriuretic Peptide, Brain
  • Melatonin