Melatonin Supplementation and Pro-Inflammatory Mediators: A Systematic Review and Meta-Analysis of Clinical Trials

Eur J Nutr. 2019 Nov 2. doi: 10.1007/s00394-019-02123-0. Online ahead of print.


Background: Inflammatory processes are involved in chronic diseases. It has been suggested that melatonin reduces inflammation by its radical scavenging properties; however, the results of the previous studies are inconclusive. The objective of the present meta-analysis is to determine the direction and magnitude of melatonin supplementation effect on inflammatory biomarkers.

Methods: Databases including PubMed, Scopus, Cochran Library, Embase, and Google Scholar were searched up to April 2019. Meta-analysis was performed using random-effect model. Subgroup analysis, sensitivity analysis, and meta-regression were also carried out.

Results: Thirteen eligible studies with 22 datasets with total sample size of 749 participants were included in the meta-analysis. Melatonin supplementation significantly decreased TNF-α and IL-6 levels [(WMD = - 2.24 pg/ml; 95% CI - 3.45, - 1.03; P < 0.001; I2 = 96.7%, Pheterogeneity < 0.001) and (WMD = - 30.25 pg/ml; 95% CI - 41.45, - 19.06; P < 0.001, I2 = 99.0%; Pheterogeneity < 0.001)], respectively. The effect of melatonin on CRP levels was marginal (WMD = - 0.45 mg/L; 95% CI - 0.94, 0.03; P = 0.06; I2 = 96.6%, Pheterogeneity < 0.001).

Conclusion: The results of the present meta-analysis support that melatonin supplementation could be effective on ameliorating of inflammatory mediators.

Keywords: C-Reactive protein; Inflammation; Interleukin-6; Melatonin; Meta-analysis; Tumor necrosis factor-α.

Publication types

  • Review