Effects of exogenous melatonin supplementation on health outcomes: An umbrella review of meta-analyses based on randomized controlled trials

Various melatonin supplementations have been developed to improve health outcomes in various clinical con-ditions. Thus, we sought to evaluate and summarize the effect of melatonin treatments in clinical settings for health outcomes. We searched PubMed/Medline, Embase, and Cochrane Libr a r y from inception to 4 Februa r y 2021. We included meta-analyses of randomized controlled trials investigating the melatonin intervention for any health outcome. Based on the different effect sizes of each meta-analysis, we calculated random models' standardized mean differences or risk ratios. We observed robust evidence supported by statistical significance with non-considerable heterogeneity between studies for sleep-related problems, cancer, surgical patients, and pregnant women. Patients with sleep disorder, sleep onset latency (SM D 0.33, 95% CI: 0.10 - 0.56, P < 0.01) were significantly improved whereas no clear evidence was shown with sleep efficiency (1.10, 95% CI:-0.26 to 2.45). The first analgesic requirement time (SMD 5.81, 95% CI: 2.57-9.05, P < 0.001) of surgical patients was distinctly improved . Female patients under artificial reproductive technologies had significant increase in the top-quality embryos (SM D 0.53, 95% CI: 0.27 - 0.79, P < 0.001), but no statistically clear evidence was found in the live bi r t h rate (SM D 1.20, 95% CI: 0.83 - 1.72). Survival at one year (RR 1.90, 95% CI: 1.28 - 2.83, P < 0.005) significantly increased with cancer patients. Research on melatonin interventions to treat clinical symptoms and sleep problems among diverse health conditions was identified and provided considerable evi-dence. Future well-designed randomized clinical trials of high quality and subgroup quantitative analyses are essential.