February 2023
Chen KH, Zeng BY, Zeng BS, et al. The efficacy of exogenous melatonin supplement in ameliorating irritable bowel syndrome severity: A meta-analysis of randomized controlled trials [published online ahead of print, 2022 Oct 15]. J Formos Med Assoc. 2022;S0929-6646(22)00385-0. doi:10.1016/j.jfma.2022.10.001
Overview
This meta-analysis of 4 randomized control trials (RCTs) reported a significant improvement in overall irritable bowel syndrome (IBS) severity, (P<0.001) pain severity (p<0.001), and quality of life (p=0.007) when supplementation of exogenous melatonin was used at doses of 3 mg daily for an average of 19 weeks. The study also revealed a similar safety profile of melatonin to placebo.
Our clinical takeaways from the article
This article supports the emerging literature on melatonin’s mechanism of action through the GI tract, along with its antioxidant activities. Enterochromaffin cells in the gut contain approximately 400 times more melatonin than what is produced in the pineal gland. This release of melatonin in the gut increases gastric mucosa and gut motility and has been shown to have a protective effect on the GI tract via its antioxidant activities.
The data from the 4 RCTs provide a foundation to consider melatonin as a therapy for patients with IBS. A clinician should carefully assess the individual and make recommendations according to their personalized needs. Three of the four studies included the dose of 3 mg melatonin at bedtime, which aligns with other studies reported in a review article.
Article summary
This manuscript followed PRISMA guidelines for completing the meta-analysis, with clear PICO (population, intervention, comparison, outcome) settings, inclusion and exclusion criteria, validated questionnaires, and Cochrane risk of bias tool. The primary outcome was to see the change in IBS severity following melatonin supplementation. The populations studied included IBS-D and IBS-C. Secondary outcomes include changes in pain severity, abdominal distention, quality of life, and sleep quality following melatonin supplementation.
Details of the studies included:
The diagnosis of IBS was confirmed by Rome III criteria and was present for at least 3 months.
Studies were 2-24 weeks in length.
Melatonin doses included in the 4 RCTs
3 mg in the morning and 5 mg at bedtime OR
3 mg at bedtime
Further, melatonin was not associated with a significant difference in the safety profile compared to placebo.
The authors proposed two hypotheses as to the reason melatonin would be beneficial for IBS:
Alteration in mood and sleep patterns: However, improvements in IBS were noted to be independent of sleep parameters in the RCTs included, and sleep quality was not statistically significantly different in the groups.
Restabilization of melatonin insufficiency: It has been reported that individuals with IBS have lower urinary 6-hydroxymelatonin levels compared to healthy controls. “Melatonin deficiency was believed to be associated with the core symptoms of IBS.” This is likely due to melatonin’s impact on regulating smooth muscle motility and delaying gastric emptying.
The authors noted that melatonin might delay colon transit time in IBS patients. The authors stress the clinical importance of this effect for patients with IBS with constipation (IBS-C), though no serious adverse events have been reported.
Limitations noted by the author(s)
Limited to 4 RCTs with 115 participants (62.9% presented with IBS-C)
A variety of scales are used to measure the primary and secondary outcomes
Endogenous melatonin levels were not monitored in the studiesSome p-values were relatively small in the reviewed studies
Variations in the average study and treatment times
The average study was 19 weeks, with a range of 2 weeks to 56 weeks
The average treatment time was 11.5 weeks, with a range of 2 weeks to 24 weeks
Other limitations noted in this review
While sleep was not a primary outcome, the authors did not provide a possible explanation for why sleep parameters did not improve in these participants, despite the extensive literature available on melatonin’s efficacy for sleep.
Additionally, the melatonin dose used was inconsistent among the studies included.
One study by Chojnacki et al. administered 3 mg of melatonin in the morning and 5 mg at bedtime. The clinical reasoning for administering melatonin in the morning was not provided.
Diet and other lifestyle factors that can impact IBS symptoms were not addressed.
Article review completed by Kim Ross,DCN
Content reviewed by Deanna Minich, PhD
February 14, 2023