{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:09:49Z","timestamp":1790359789751,"version":"4.1.0"},"reference-count":27,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Melatonin has antioxidant and anti-inflammatory properties that may attenuate ischemia-reperfusion injury, but randomized cardiovascular trial data remain inconsistent. Objectives: This study sought to evaluate the association of melatonin supplementation with cardiovascular outcomes across randomized trials. Methods: We performed a systematic review and meta-analysis of randomized trials comparing melatonin with placebo, usual care, or no melatonin in patients with cardiovascular disease. PubMed, Embase, and CENTRAL were searched from inception to 1 January 2026. Random-effects models with Hartung\u2013Knapp\u2013Sidik\u2013Jonkman confidence intervals were used. Prespecified outcomes included left ventricular ejection fraction (LVEF), change in LVEF, troponin, infarct size by cardiac magnetic resonance, heart failure outcomes, inflammatory and oxidative stress biomarkers, and adverse events. Results: A total of 14 randomized controlled trials involving 1027 participants were included. Melatonin significantly improved change in LVEF from baseline to follow-up (mean difference: 3.95 percentage points; 95% CI: 1.70\u20136.20; p &lt; 0.001), with the most consistent signal in coronary artery bypass grafting studies (mean difference: 4.65 percentage points; 95% CI: 2.56\u20136.74). Final LVEF was numerically higher with melatonin but not statistically significant. Troponin reduction was not significant. Narrative synthesis suggested lower inflammatory and oxidative stress markers after coronary artery bypass grafting and improvement in heart failure symptoms and quality of life, whereas infarct size findings in ST-segment elevation myocardial infarction were mixed and timing-dependent. Conclusions: Melatonin was associated with improved LVEF change, particularly in coronary artery bypass grafting settings, but benefit was not consistently demonstrated across final LVEF, troponin, or infarct size outcomes.<\/jats:p>","DOI":"10.3390\/jcm15093444","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T12:20:25Z","timestamp":1777551625000},"page":"3444","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Melatonin Supplementation and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Randomized Trials"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8557-9880","authenticated-orcid":false,"given":"Song Peng","family":"Ang","sequence":"first","affiliation":[{"name":"Division of Cardiology, Sarver Heart Center, University of Arizona, Tucson, AZ 85724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia Ee","family":"Chia","sequence":"additional","affiliation":[{"name":"Department of Medicine, Texas Tech University Health Science Center, El Paso, TX 79905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2227-2803","authenticated-orcid":false,"given":"Umabalan","family":"Thirupathy","sequence":"additional","affiliation":[{"name":"Cheshire Medical Center, Keene, NH 03431, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison","family":"Laezzo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2021-1660","authenticated-orcid":false,"given":"Vikash","family":"Jaiswal","sequence":"additional","affiliation":[{"name":"Endeavor Health Cardiovascular Institute, University of Chicago Pritzker School of Medicine, Chicago, IL 60026, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7622-9974","authenticated-orcid":false,"given":"Joseph","family":"Varon","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Houston College of Medicine, Houston, TX 77004, USA"},{"name":"Independent Medical Alliance, Washington, DC 20036, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Halma","sequence":"additional","affiliation":[{"name":"Independent Medical Alliance, Washington, DC 20036, USA"},{"name":"Open Source Medicine O\u00dc, P\u00e4rnu mnt. 139c, 11317 Tallinn, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3761-576X","authenticated-orcid":false,"given":"Eunseuk","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rutgers Health Community Medical Center, Toms River, NJ 08755, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2186-8730","authenticated-orcid":false,"given":"George","family":"Davidson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rutgers Health Community Medical Center, Toms River, NJ 08755, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7851-0498","authenticated-orcid":false,"given":"Jose","family":"Iglesias","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA"},{"name":"Department of Medicine, Rutgers Health Community Medical Center, Toms River, NJ 08755, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.1016\/j.jacc.2024.02.056","article-title":"Reperfusion Injury in Patients With Acute Myocardial Infarction: JACC Scientific Statement","volume":"83","author":"Welt","year":"2024","journal-title":"J. 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