Anti-inflammatory effects of melatonin: A systematic review and meta-analysis of clinical trials

•This meta-analysis demonstrates anti-inflammatory effects of melatonin.•Exogenous melatonin reduces levels of IL-1, IL-6, IL-8, and TNF.•Melatonin, with few side effects, may be useful for inflammatory disease prevention. Chronic inflammation contributes to multiple diseases including cardiovascular diseases, autoimmune disorders, metabolic disorders, and psychiatric conditions. Melatonin, a hormone responsible for circadian rhythm, plays a complex role within the immune system, including having an anti-inflammatory effect. While there are numerous animal studies demonstrating this effect, few human clinical trials have been conducted. This systematic review of clinical trials examined whether exogenous melatonin reduces levels of inflammatory markers in humans. We searched PubMed, Embase, Cochrane Library, Scopus, and PsycINFO, and the references of the identified articles for randomized and non-randomized placebo-controlled trials. Data were extracted from the articles and meta-analyses were conducted using a random effects model to calculate standardized mean differences (SMDs, i.e., Cohen’s d). From an initial search result of 4548 references, 31 studies met the inclusion criteria and were included involving 1517 participants. Melatonin had significant anti-inflammatory effects on interleukin (IL)-1 (SMD −1.64; 95% confidence interval [CI] −2.86, −0.43; p = 0.008), IL-6 (-3.84; −5.23, −2.46; p