Exogenous melatonin supplements can improve overall irritable bowel syndrome (IBS) severity, pain severity, and quality of life (QOL), according to study findings in the Journal of the Formosan Medical Association.
Melatonin secretion is dysregulated in patients with IBS, and previous studies on exogenous melatonin supplements in this population have been inconclusive. Researchers conducted a meta-analysis to determine the efficacy of exogenous melatonin supplements in improving IBS severity.
Sourcing data from PubMed, ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, ScienceDirect, and Web of Science, researchers screened 570 potential articles and reviewed 10 eligible articles. A total of 4 randomized controlled trials (RCTs) with 115 participants were included in the final analysis.
Among the study participants (mean age [SD], 39[24.5-56.1] years; women, 75.6%), 62.9% of patients had IBS with constipation on average (range, 35.0%-100%).
There were 3 studies that excluded concurrent medications that affected gastroenterological symptoms. The dosage and administration schedule of melatonin in these studies included “3 mg at bedtime” and “3 mg in the morning and 5 mg in the evening.”
The population, intervention, comparison, and outcome (PICO) of this meta-analysis were patients with IBS, melatonin supplement, placebo control, and change in IBS severity, respectively.
Inclusion criteria were RCTs investigating changes in IBS severity after melatonin supplementation, RCTs using a placebo control group, and RCTs using ROME criteria to diagnose IBS. The exclusion criteria were studies that did not investigate changes in IBS severity after melatonin supplementation, did not recruit patients with IBS, and were not RCTs.
The primary outcome was measuring the change in IBS severity after melatonin administration, and the safety outcome was the rate of any discomfort events. Secondary outcomes were changes in pain severity, abdominal distension, QOL, and sleep quality.
Researchers used Hedges’ g to assess the main effect sizes of outcome measures, with values of 0.2, 0.5, and 0.8 assigned as small, medium, and large effect sizes, respectively.
To assess the quality of the methodology in these studies, researchers used the Cochrane risk of bias tool, which consists of 7 items: randomization, concealment, blindness of participants, blindness of investigator, attrition bias, reporting bias, and other biases.
Researchers found that 71.4% (20/28 items) had a low risk of bias and 28.6% (8/28 items) had an unclear risk of bias.
The primary outcome revealed that melatonin supplement was associated with improvement in overall IBS severity compared with placebo (k, 4; Hedges’ g, 0.746; 95% CI, 0.401-1.091; P < .001) with no significant heterogeneity (P =.892; I2<0.01%). However, there was significant publication bias shown after inspecting the funnel plots.
The safety endpoint showed that melatonin did not affect the rate of discomfort events compared with placebo (k, 3; odds ratio, 1.487; 95% CI, 0.220-10.056; P =.684).
The secondary outcome indicated that melatonin supplement was associated with improved pain severity (k, 3, Hedges’ g, 0.784; 95% CI, 0.369-1.199; P <.001) and improved QOL compared with placebo (k, 2; Hedges’ g, 0.343; 95% CI, 0.422-1.108; P =.380).
There were no associations between melatonin supplement and changes in abdominal distention (k, 3, Hedges’ g, 0.526; 95% CI, 0.121-1.172; P =.111) and changes in sleep quality compared with placebo (k, 2; Hedges’ g, 0.379; 95% CI, 0.126-0.883; P =.142).
Study limitations include a small number of participants, a wide variety of scales to evaluate outcomes, and the inability to measure melatonin levels in IBS patients prior to administration.
“Although no serious adverse events caused by exogenous melatonin supplementation, such as ileus, have been reported in IBS patients, clinicians should be aware of the potential risk of delayed colonic transit time in patients with IBS-constipation dominant,” the study authors noted.
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. J Formos Med Assoc. Published Online October 15, 2022. doi:10.1016/j.jfma.2022.10.001