Circadian rhythm science is revealing the importance of living in harmony with the rhythms established by nature. Modern living disrupts the natural rhythms and has been connected to numerous diseases, including gastrointestinal (GI), inflammatory, and metabolic conditions. An excellent recent review in the journal Gastroenterology explains how factors such as shift work, light pollution, social jetlag, and eating at the wrong time disrupt natural cycles, contributing to abnormal GI function.
Melatonin is a sleep hormone that helps regulate the body’s circadian rhythm. Intestinal melatonin levels are 400 times higher than in systemic circulation, playing a major role in gut health. It has anxiolytic, anti-inflammatory, antioxidant, and motility-regulating effects. Human studies have shown that supplementation improves motility, visceral sensitivity, and symptoms seen in IBS, gastroesophageal reflux disease (GERD), and inflammatory bowel disease (IBD). Newer studies continue to support the benefit of melatonin with IBS.
The Studies
A 2025 double-blind randomized clinical trial recruited 76 patients from gastroenterology clinics who met the Rome IV criteria for IBS. Patients were randomized to receive either 3 mg sublingual melatonin daily or a placebo for eight weeks. All IBS classes were represented, including diarrhea-predominant, constipation-predominant, and other subtypes.
Participants completed 3 questionnaires to monitor GI symptoms, sleep, and quality of life: IBS-Severity Symptom Scale (IBS-SSS), IBS Quality of Life-34 (IBS-QOL34), and Pittsburgh Sleep Quality Index (PSQI). Questionnaires were completed at baseline, before beginning supplementation, and again at the end of the eight weeks.
The IBS-SSS showed that IBS symptoms were significantly lower in the melatonin group compared to the placebo group after 8 weeks. The IBS-QOL34 showed improved quality of life in the melatonin group compared to placebo. However, the PSQI scores showed no sleep difference between the two arms at baseline or after eight weeks.
Regarding safety, melatonin was well-tolerated with no serious adverse reactions reported in this study and other similar studies. Despite concurrent use of numerous medications by patients, no adverse reactions due to drug interactions were observed at this dose.
Details about when the melatonin was administered (i.e., before bed) were not mentioned. The authors also concluded, “We recommend the administration of sublingual melatonin at a dose of 3 mg twice daily for IBS patients to optimize QoL and alleviate IBS symptoms.” However, the methods section only mentioned 3 mg daily.
Another 2023 randomized placebo-controlled trial included 136 IBS patients and gave 3 mg melatonin fasted and at bedtime for a total of 6 mg daily for 8 weeks. The same questionnaires were used as in the previous study. Significant improvement was noted in IBS symptom scores and quality of life in melatonin recipients compared to those receiving placebo. In this study, they observed that among IBS patients with sleep issues, there was significant improvement in sleep parameters in the melatonin group, while those without sleep concerns did not experience sleep improvement.
Conclusions
These studies support previous studies on melatonin’s benefits for IBS. More clinical trials will help elucidate appropriate dosing and timing to align with circadian biology. Melatonin concentrations are disrupted in IBS patients, and while exogenous melatonin may benefit, it is essential to address the underlying factors that disrupt healthy circadian biology.
More on IBS — Click Here
