Zarezadeh · European journal of nutrition 2020 · systematic review and meta-analysis · n=749

Melatonin supplementation and pro-inflammatory mediators: a systematic review and meta-analysis of clinical trials.

Cited 93 times in the scientific literature.

Level 1 - systematic review of randomized trials

Systematic review and meta-analysis of clinical trials

PubMed 31679041 · doi:10.1007/s00394-019-02123-0 · record verified 2026-08-30

What was done

A systematic review and random-effects meta-analysis of clinical trials was conducted to evaluate the effect of melatonin supplementation on inflammatory biomarkers (TNF-α, IL-6, and CRP). Databases including PubMed, Scopus, Cochrane Library, Embase, and Google Scholar were searched up to April 2019. Subgroup analysis, sensitivity analysis, and meta-regression were also conducted.

What was found

Thirteen eligible studies with 22 datasets and 749 total participants were analyzed: - Melatonin supplementation significantly decreased TNF-α levels (WMD = -2.24 pg/ml; 95% CI: -3.45 to -1.03; P < 0.001; I² = 96.7%). - Melatonin supplementation significantly decreased IL-6 levels (WMD = -30.25 pg/ml; 95% CI: -41.45 to -19.06; P < 0.001; I² = 99.0%). - Melatonin had a marginal, non-significant effect on CRP levels (WMD = -0.45 mg/L; 95% CI: -0.94 to 0.03; P = 0.06; I² = 96.6%).

Why it matters

This review provides quantitative clinical trial evidence that melatonin can reduce specific circulating pro-inflammatory cytokines, supporting its proposed anti-inflammatory role.

Limits

Statistical heterogeneity across studies was extremely high (I² ≥ 96.6% for all outcomes). Total sample size across 13 trials was small (749 participants). Participant characteristics, clinical conditions, melatonin dosages, intervention durations, and risk of bias are not reported in the abstract.

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