Melatonin

High local gut levels & gut source: the gastrointestinal mucosa (enterochromaffin cells) makes a lot of melatonin — the gut is a major extra-pineal source — so melatonin acts locally in the GI tract. This provides a plausible biological basis for a GI effect. Oxford Academic

Modulation of GI motility & visceral sensitivity: experimental and clinical data show melatonin affects smooth-muscle motility and can reduce visceral (rectal) pain sensitivity — mechanisms include modulation of serotonin signalling, smooth-muscle function and sensory pathways. That combination can reduce abdominal pain and alter bowel habit. jpp.krakow.pl Gut

Anti-inflammatory / mucosal effects & microbiota links: studies report altered mucosal melatonin in IBS and possible links to immune modulation and microbiota — these effects could help symptom generation in some IBS subtypes. Oxford Academic

Sleep and brain–gut axis: melatonin improves sleep and circadian regulation. Since sleep disturbance and central pain sensitization worsen IBS for many patients, improving sleep can indirectly improve IBS symptoms. Several trials enrolled patients with sleep problems or measured sleep/QoL as outcomes. BioMed Central Gut

These are trial-based regimens (what the evidence used), not universal clinical guidelines — talk to your clinician before starting.

Common trial regimens:

• 3 mg once nightly at bedtime — used in several randomized trials (short courses like 2 weeks to longer). Example: a 2-week randomized trial used 3 mg at bedtime and reported decreased abdominal pain and improved rectal pain sensitivity. Gut
• 6 mg/day split dosing (3 mg morning + 3 mg bedtime) for 8 weeks — used in a recent larger RCT (BMC Gastroenterology, 2023) that found improvements in IBS symptom score and quality of life. BioMed Central
• Sublingual 3 mg has been trialed in some studies to improve absorption variability (some investigators prefer SL for more reliable bioavailability). Brieflands

Typical durations in studies:

• Short trials: 2 weeks (pain and rectal sensitivity endpoints). Gut
• Medium trials: 6–8 weeks or more. Recent trials used 8 weeks; meta-analyses include studies averaging up to ~19 weeks follow-up across trials. BioMed Central Phytomelatonin

Suggested, pragmatic approach used in research (example template):

• Start: 3 mg at bedtime (or 3 mg SL) for 4–8 weeks to assess symptom change (pain, global IBS score, QoL). If partial effect and tolerated, clinician may consider continuation or alternative dosing (some trials used 6 mg/day split).
• Assess: symptom scales (IBS-SSS or global IBS score), sleep, daytime sleepiness, and any interactions/side effects.
• Stop or adjust if daytime drowsiness, interactions, or no benefit after a reasonable trial (often 8–12 weeks in clinical practice).

Important: these are the doses that appear in RCTs — OTC melatonin formulations vary widely in dose and quality. Use a reliable product and review with your prescribing clinician (especially if you are on other medicines). ScienceDirect NICE

1. Gut (2005) — Melatonin improves abdominal pain in IBS patients with sleep disturbance (randomized, double-blind, placebo-controlled).
2. Summary: 40 IBS patients with sleep disturbance randomized to 3 mg bedtime vs placebo for 2 weeks; melatonin reduced abdominal pain and rectal pain sensitivity.
3. Link: Gut article (journal page). Gut
4. BMC Gastroenterology (2023) — Randomized double-blind placebo-controlled trial, 136 patients (Rome IV IBS): 6 mg/day (3 mg fasting + 3 mg bedtime) for 8 weeks; showed improvement in IBS scores and QoL (improvements in sleep parameters among those with baseline sleep disturbance).
5. Link (Open access): BMC Gastroenterology 2023 RCT. BioMed Central
6. Meta-analysis / systematic review (2022) — analysis of RCTs showing that exogenous melatonin (commonly 3 mg/day) improved overall IBS severity, pain severity and quality of life versus placebo (average trial lengths variable; pooled effects supportive but heterogenous). (Referenced summary and DOI in reviews).
7. Link / review summary: ScienceDirect / journal review (meta-analysis). ScienceDirect Phytomelatonin
8. Mechanistic / mucosal studies — increased expression of colonic mucosal melatonin and experimental papers showing melatonin’s role in motility and interaction with serotonin systems in the gut (supporting biological plausibility).
9. Link examples: studies on colonic mucosal melatonin and GI motility reviews. Oxford Academic jpp.krakow.pl
10. Clinical summaries and patient-facing overviews (synthesis of the above): MedicalNewsToday and other evidence summaries — useful for plain-language interpretation but not a substitute for the primary studies. Medical News Today

Bottom line from the evidence: multiple small-to-moderate RCTs and at least one pooled analysis show statistically significant improvement in overall IBS severity and abdominal pain with melatonin vs placebo, typically at doses of ~3 mg nightly (some studies used higher/split doses). Results are promising but not yet uniform enough to make melatonin a universal first-line therapy; it’s best considered when standard IBS treatments are insufficient or when sleep disturbance coexists. Gut BioMed Central ScienceDirect