Melatonin effectiveness in amelioration of oxidative stress and strengthening of antioxidant defense system: Findings from a systematic review and dose-response meta-analysis of controlled clinical trials.

Background And Aim: Oxidative stress is involved in the development of chronic diseases. It has been suggested that melatonin has a protective role against oxidative stress by activation of antioxidant enzymes and scavenging free-radicals. Present study aimed to investigate the effect of melatonin supplementation on oxidative stress and antioxidant biomarkers such as malondialdehyde (MDA), increased total antioxidant capacity (TAC), superoxide dismutase (SOD), and Glutathione peroxidase (GPx).

Methods: Systematic search was performed to identify relevant studies in PubMed/Medline, SCOPUS, Web of Science and Embase databases and Google Scholar up to September 2020. Meta-analysis was conducted using random-effect model. Subgroup analysis and meta-regression was used to identify sources of heterogeneity. The quality of studies was assessed using Cochrane Collaboration's tool. Publication bias was assessed by visual inspection of funnel plot.

Results: A total number of 16 eligible articles were included in the meta-analysis. The dosages of melatonin varied between 3 and 400 mg/day, with a duration range between 1.42 and 12 weeks. Melatonin supplementation significantly increased serum levels of TAC [SMD: 1.59; 95% CI: 0.89, 2.29; P < 0.001; (I = 93.53%, P < 0.001 No significant effects were observed on MDA [SMD: -3.09; 95% CI: -7.07, 0.89; P = 0.12; (I = 99.57%, P < 0.001)], GPx [SMD: 0.86; 95% CI: -3.46, 5.19; P = 0.61; (I = 98.17%, P < 0.001)] and SOD levels [SMD: 1.92; 95% CI: -3.57, 7.41; P = 0.35; (I = 98.27%, P < 0.001)].

Conclusion: Results of the current meta-analysis showed that melatonin supplementation had a significant impact on attenuating of oxidative stress and enhancing antioxidant performance. Melatonin supplementation could be suggested as a safe complementary approach in amelioration of the chronic diseases.