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Melatonin Supplementation and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Randomized Trials
Song Peng Ang1, Jia Ee Chia2, Umabalan Thirupathy3
1Division of Cardiology, Sarver Heart Center, University of Arizona, Tucson, AZ 85724, USA.
Journal of Clinical Medicine
|May 13, 2026
Summary
Melatonin supplementation improved left ventricular ejection fraction (LVEF) change in cardiovascular patients, especially after coronary artery bypass grafting. However, consistent benefits were not observed for final LVEF, troponin levels, or infarct size.
Area of Science:
- Cardiology
- Pharmacology
- Biochemistry
Background:
- Melatonin possesses antioxidant and anti-inflammatory properties.
- Potential to mitigate ischemia-reperfusion injury in cardiovascular disease.
- Existing randomized trial data on melatonin's cardiovascular effects are inconsistent.
Purpose of the Study:
- To systematically evaluate the association between melatonin supplementation and cardiovascular outcomes.
- Meta-analysis of randomized trials to synthesize evidence on melatonin's efficacy.
- Focus on key cardiovascular endpoints and biomarkers.
Main Methods:
- Systematic review and meta-analysis of 14 randomized controlled trials (1027 participants).
- Searched PubMed, Embase, and CENTRAL databases up to January 1, 2026.
- Used random-effects models with Hartung-Knapp-Sidik-Jonkman confidence intervals.
Main Results:
- Melatonin significantly improved the change in left ventricular ejection fraction (LVEF) (mean difference: 3.95 percentage points; p < 0.001).
- The most significant LVEF change improvement was observed in coronary artery bypass grafting studies (mean difference: 4.65 percentage points).
- No significant reduction in troponin levels; final LVEF was numerically higher but not statistically significant. Mixed results for infarct size and positive trends for heart failure symptoms.
Conclusions:
- Melatonin supplementation is associated with improved LVEF change, particularly in the context of coronary artery bypass grafting.
- Benefits were not consistently demonstrated across all evaluated outcomes, including final LVEF, troponin, and infarct size.
- Further research may be needed to clarify melatonin's role in specific cardiovascular conditions and optimize its application.
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