Efficacy of exogenous melatonin supplements in patients with inflammatory bowel diseases

Abstract Background Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is frequently complicated by persistent inflammation and sleep disturbance, both of which negatively affect disease control and quality of life. Melatonin, a key regulator of circadian rhythm, also exhibits anti-inflammatory, antioxidant, and immunomodulatory properties. Although several clinical trials have evaluated melatonin as an adjunctive therapy in IBD, its overall efficacy remains unclear. Methods We conducted a systematic review and meta-analysis of randomized controlled trials assessing exogenous melatonin supplementation in patients with IBD. Electronic databases (PubMed, Web of Science, and Scopus) were searched until October 7, 2025. Primary outcomes included changes in disease activity indices and clinical remission. Secondary outcomes included inflammatory biomarkers, patient-reported outcomes, and safety. Random-effects models were used to pool effect estimates. Results Five studies involving a total of 214 patients met the inclusion criteria. Melatonin supplementation was associated with a significant reduction in disease activity compared with standard therapy alone (standardized mean difference −0.96, 95% CI −1.60 to −0.32), although heterogeneity was substantial. Individual trials consistently reported earlier remission, improved maintenance of remission, or greater reductions in clinical activity indices with melatonin. Effects on systemic inflammatory markers such as C-reactive protein and erythrocyte sedimentation rate were variable and not consistently significant, while fecal calprotectin improved in one study. Improvements in sleep quality and selected quality-of-life domains were observed. Melatonin was generally well tolerated, with only mild and infrequent adverse events reported. Conclusions Current evidence suggests that melatonin may be a safe and potentially effective adjunctive therapy for improving clinical disease activity and patient-centered outcomes in IBD. Larger, high-quality randomized trials are required to confirm these findings and define its role in routine clinical practice.