Melatonin supplementation improves insulin resistance markers but not fasting glucose: a systematic review and meta-analysis of randomized controlled trials.

This study evaluated whether oral melatonin supplementation influences glycemic outcomes in humans through a systematic review and meta-analysis of randomized controlled trials (RCTs). A systematic search of major electronic databases was conducted to identify RCTs evaluating the effects of melatonin supplementation on metabolic outcomes in adults. Studies reporting fasting glucose, glycated hemoglobin (HbA1c), fasting insulin, or homeostatic model assessment of insulin resistance (HOMA-IR) were included. Data were pooled using a random-effects model. Heterogeneity was assessed using the I2 statistic, and meta-regression analyses were performed to explore potential moderators. Statistical analyses were conducted using Jamovi software. Thirty-one RCTs were included in this systematic review. Quantitative synthesis comprised 27 studies reporting fasting glucose, nine studies reporting HbA1c, seven studies reporting fasting insulin, and four studies reporting HOMA-IR. Melatonin doses ranged from 1 to 10 mg/day, with intervention durations between 14 and 365 days. The meta-analysis showed no significant reduction in fasting glucose levels. However, improvements were observed in secondary metabolic outcomes related to glycemic control and insulin resistance, including HbA1c, fasting insulin, and HOMA-IR. Melatonin supplementation did not significantly reduce fasting glucose but may improve markers of glycemic control and insulin sensitivity, suggesting a modulatory role in metabolic regulation.