Melatonin Supplementation in the Management of Irritable Bowel Syndrome: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction characterized by recurrent abdominal pain and altered bowel habits, with substantial effects on quality of life and healthcare utilization. Melatonin has been proposed as a potential adjunctive therapy because of its effects on visceral sensitivity, gastrointestinal motility, and gut-brain signaling. We conducted an updated systematic review and meta-analysis of randomized placebo-controlled trials evaluating melatonin supplementation in adults with IBS. METHODS: PubMed, Web of Science, Cochrane CENTRAL, Scopus, and Embase were searched from inception to April 13, 2026. Randomized, double-blind, placebo-controlled trials evaluating oral or sublingual melatonin in adults with IBS were included. Parallel-group trials were quantitatively synthesized, while crossover trials were narratively summarized when outcome reporting was unsuitable for pooling. Risk of bias was assessed using RoB 2. RESULTS: Seven randomized trials involving 391 participants were included; four contributed to quantitative synthesis and three were narratively reviewed. Melatonin significantly reduced moderate-to-severe IBS symptoms versus placebo (RR = 0.52, 95% CI = 0.39-0.71, p < 0.0001), improved pain frequency (SMD = 0.59, 95% CI = 0.27-0.92, p = 0.0003) and improved frequency of defecation (SMD = 0.42, 95% CI = 0.12-0.72, p = 0.0056). No significant differences were observed for overall quality of life or global sleep quality. Abdominal distension and abdominal pain intensity numerically favored melatonin without reaching statistical significance. Reported adverse effects were mild and infrequent. CONCLUSION: Melatonin may improve overall IBS symptom severity, pain-related outcomes, and bowel habit measures, with an acceptable short-term safety profile. Larger, high-quality trials are needed to confirm long-term efficacy.