Following an analysis of four trials, Taiwan-based researchers noted that melatonin deficiency appeared to be associated with core symptoms of IBS and stated that “based on this rationale, melatonin supplementation would have a theoretically beneficial effect in relieving IBS symptoms”.
Patients with IBS-diarrhoea (IBS-D) and IBS-constipation (IBS-C) showed significantly lower levels of the melatonin metabolite, urinary 6-hydroxxymelatonin sulphate (6-HMS), than healthy controls, wrote the researchers.
However, exogenous supplementation restored melatonin insufficiency and alleviated specific IBS symptoms, including severity and pain, in many patients and indicate therapeutic activity.
“The current meta-analysis provided the evidence for the potential benefit of exogenous melatonin supplementation in IBS management. Further, there was no significant difference in the safety profile,” they wrote in the Journal of the Formosan Medical Association.
“The current meta-analysis served the hint to introduce the potentially beneficial role of melatonin in IBS management to the clinicians.”
The right balance
IBS effects 11% of the global population with predominant symptoms including abdominal distension and pain.
Pharmaceutical medication, such as mixed opioid agonists or antagonists and tricyclic antidepressants, are prescribed to relieve symptom severity but can provoke adverse events, like sedation, arrhythmia, and pancreatitis, and driven demand for alternative treatment.
More recently, experts recognise dysregulation of endogenous melatonin in IBS patients and the importance of maintaining the right balance, said the study authors.
“Endogenous melatonin has an excitatory and inhibitory effect on gut motility through the blockade of nicotinic channels and interaction with CA2+ – activated K+ channels,” they wrote.
“In the animal model, a low dose of melatonin supplement accelerated intestinal transit, while a high dose slowed it.”
Furthermore, they explained that by increasing cholecystokinin (CCK) release and activating corresponding CCK1R/CCK2R receptors, melatonin activates the afferent fibre of the vagal nerve to modulate gastrointestinal motility.
The meta-analysis aimed to summarize current evidence on the role of melatonin in modulating IBS and address its effectiveness in reducing its severity.
Study material was gathered from seven databases, including PubMed, ClinicalKey, Cochrane Central and ScienceDirect, and unpublished papers sourced from ClinicalTrials.gov. The random controlled trials used ROME criteria to diagnose IBS, specifically investigated changes in IBS severity as a result of melatonin supplementation in IBS patients and were placebo-controlled.
Four articles met the full criteria and included a total of 115 participants with an average age of 39 years. Women represented 75.6% of subjects and IBS-C was diagnosed in 62.9% of the population.
Average treatment length was 11.5 weeks and 19 weeks for study duration. Melatonin dosages included 3 mg at bedtime, 3 mg in the morning, and 5 mg in the evening.
The primary outcome was the change in IBS severity following melatonin supplementation, with changes in pain severity, abdominal distension, quality of life, and sleep quality secondary outcomes.
Melatonin significantly improved IBS and pain severity in treated patients, compared to the placebo, with no obvious heterogeneity. Observed benefits remained, even when concurrent medication was excluded.
There was no association between supplementation and changes in abdominal distension or sleep quality, but melatonin did significantly improve quality of life, when compared to the placebo.
The authors surmised that benefits could be attributed to the alteration of mood component / sleep disturbance in IBS patients and the re-stabilisation of melatonin insufficiency.
“Findings suggested that melatonin supplementation would modify IBS severity in ways other than simply changing the mood component/sleep disturbance,” they wrote.
Melatonin supplements achieved the target outcome for IBS-D patients and delayed colonic transit time, however this represented an adverse effect for IBC-C patients, where increased colonic transition was already a major cause of discomfort.
“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,” they said.
Larger studies with longer follow-ups are warranted to support or refute the current meta-analysis, they added.
Source: Journal of the Formosan Medical Association
Published online ahead of print, doi: 10.1016/j.jfma.2022.10.001
‘The efficacy of exogenous melatonin supplement in ameliorating irritable bowel syndrome severity: A meta-analysis of randomized controlled trials’
Authors: K-H. Chen, et al.