Efficacy of Melatonin Treatment on Sleep Quality Improvement in Inflammatory Bowel Disease Patients With Clinical Remission

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract characterized by immune-mediated intestinal inflammation. IBD is broadly classified into two main types: ulcerative colitis (UC) and Crohn's disease (CD). In recent years, the incidence of IBD has been increasing in several countries across Asia.¹ The natural course of IBD is variable, with disease activity that may improve, remain stable, or worsen despite treatment. Patients typically experience alternating periods of disease remission and disease relapse.²-³ Consequently, considerable efforts have been made to investigate new therapeutic approaches aimed at prolonging remission and improving clinical outcomes in patients with IBD.

Previous studies have shown that patients with IBD are more likely to experience sleep disturbances, including increased microarousals during sleep and insomnia, compared with healthy individuals. These findings have been demonstrated using home-based wireless polysomnography and electroencephalographic monitoring.⁴ Furthermore, patients with IBD have been found to have reduced sleep efficiency compared with healthy controls.⁴ Studies evaluating sleep disturbances in IBD patients using sleep quality questionnaires or wrist actigraphy have reported an overall prevalence ranging from 41-88%. Notably, sleep disturbances appear to be more common among patients with active disease, with reported prevalence ranging from 55-100%, compared with 13-77% among patients in disease remission.⁵-⁹ Poor sleep quality has also been associated with increased disease severity, a higher risk of disease relapse, and reduced quality of life.¹⁰-¹¹ Melatonin is a hormone primarily produced by the pineal gland during the nighttime and released into the bloodstream under the regulation of the circadian rhythm. Melatonin plays an important role in regulating sleep by promoting sleep initiation and inhibiting wake-promoting neural signals.¹²-¹³ Previous studies have suggested that patients with IBD, even during remission, may exhibit abnormal melatonin secretion, which may contribute to sleep disturbance.¹⁴ In addition to the pineal gland, melatonin can also be synthesized by enterochromaffin cells in the gastrointestinal tract.¹⁵ Experimental studies in animal models have demonstrated that melatonin may enhance intestinal epithelial barrier function,¹⁶-¹⁷ promote beneficial gut microbiota,¹⁸-²⁰ and exert antioxidant effects.²¹-²² These findings suggest that melatonin may play a protective role in intestinal inflammation. Moreover, melatonin has been shown to modulate both innate and adaptive immune responses, including suppression of pro-inflammatory cytokines and enhancement of anti-inflammatory cytokines.²³-²⁸ Given that decreased melatonin levels may contribute to poor sleep quality in patients with IBD and may potentially exacerbate intestinal inflammation, several studies have investigated the effects of melatonin supplementation in patients with both active disease and disease remission. These studies have suggested that melatonin supplementation may improve sleep quality and quality of life, reduce disease activity,29-30, 32 decrease inflammatory markers,²⁹-³⁰ and may also prolong the duration of disease remission.³¹ However, the available evidence remains limited, as most studies have involved small sample sizes. In particular, only one study evaluating sleep quality and quality of life included 20 patients and was reported as a preliminary study. Therefore, the present study aims to evaluate the effect of melatonin supplementation compared with placebo on sleep quality in IBD patients with clinical remission.