Melatonin

1. Increases Lower Esophageal Sphincter (LES) Tone

• GERD often happens because the LES (a muscular valve between the esophagus and stomach) is weak or relaxes inappropriately.
• Melatonin has been shown to increase LES pressure, making it less likely for stomach acid to flow back into the esophagus.

2. Enhances Mucosal Protection

• Melatonin stimulates the production of bicarbonate and mucus in the stomach and esophagus.
• These act as protective barriers, shielding the esophagus from corrosive stomach acid.

3. Antioxidant Properties

• GERD causes oxidative stress in the esophageal lining.
• Melatonin is a potent antioxidant, neutralizing free radicals and reducing inflammation in the esophageal tissue.

4. Reduces Acid Secretion

• Some studies suggest melatonin may inhibit gastric acid secretion (though less strongly than drugs like PPIs).
• It also helps regulate nitric oxide pathways that influence acid production.

5. Supports Healing

• Melatonin promotes mucosal blood flow, aiding in tissue repair.
• It also helps modulate inflammatory signaling, supporting healing of esophageal irritation and micro-injuries caused by reflux.

6. Synergistic Effect with Other Treatments

• Trials have shown melatonin can work synergistically with proton pump inhibitors (like omeprazole), sometimes even allowing for lower drug doses while achieving similar symptom control.

In short: Melatonin is effective in treating GERD not just because it helps people sleep better (which can reduce nighttime reflux), but also because it strengthens the LES, protects the esophagus, reduces acid damage, and promotes healing through its antioxidant and anti-inflammatory actions.

How Melatonin Has Been Studied for GERD

Doses used in trials:

• 3 mg at bedtime (most common, sometimes sublingual).
• 6 mg at bedtime (often in functional heartburn or more resistant cases).
• Duration: Typically 4–12 weeks of nightly use.
• Formulations: Standard oral tablets, sublingual forms, and sometimes multi-ingredient supplements (though those make it harder to know melatonin’s independent effect).
• Setting: Either alone or more commonly added to a proton pump inhibitor (PPI) such as omeprazole. Add-on use tends to show stronger benefits.

Suggested Stepwise Approach (to discuss with your doctor)

Baseline: Confirm GERD diagnosis (endoscopy or pH monitoring if needed).

Trial of melatonin:

• Start low (e.g., 3 mg nightly).
• Take 30–60 minutes before bed, which also aligns with melatonin’s sleep-regulating effect.

Evaluate after 4–6 weeks: Track heartburn, regurgitation, and sleep quality.

If tolerated but not effective enough: Some studies increased to 6 mg nightly.

Adjunct to PPI: If you’re already on a PPI, melatonin can sometimes help with residual nighttime reflux symptoms.

Reassess: Discuss with your clinician whether to continue, taper, or stop after a trial period.

Summary: In studies, 3–6 mg of melatonin nightly before bed, for 4–12 weeks, has improved GERD symptoms and quality of life, especially when added to a PPI. But it’s still considered an experimental/adjunctive approach, so it’s best used under medical supervision.

Randomized & Controlled Trials

• 2006 — Single-blind RCT (Brazil): melatonin-based combo vs omeprazole: Adults with GERD received either a nightly supplement containing melatonin 6 mg + L-tryptophan, vitamins B6/B12/folate, methionine, betaine or omeprazole 20 mg for ~40 days. The combo arm reported faster and more complete symptom regression than omeprazole alone. Important caveat: the product had multiple actives, so melatonin’s independent effect can’t be isolated. Journal of Pineal Research (paywalled; abstract/DOI info) Kudos Unbound Medicine
• 2010 — Small randomized study (Egypt): melatonin alone vs omeprazole vs combo: ~36 participants divided into 4 groups (healthy controls, melatonin 3 mg, omeprazole 20 mg, melatonin + omeprazole) for 4–8 weeks. Melatonin (alone and with omeprazole) improved heartburn/epigastric pain and increased LES pressure; omeprazole was superior for acid suppression; combo often performed best for symptom relief/time to improvement. Open-access full text (BMC Gastroenterology). BioMed Central
• 2014 — Pilot RCT in functional heartburn (on PPI background): melatonin vs nortriptyline vs placebo: All patients took omeprazole 20 mg qAM. They were randomized to melatonin 6 mg qHS, nortriptyline 25 mg qHS, or placebo for 3 months. Melatonin produced greater improvements in GERD-HRQOL scores than nortriptyline and placebo, with fewer adverse events. (Open Journal of Gastroenterology; pilot size, single-center.) SCIRP
• 2023 — Double-blind RCT (Iran): add-on sublingual melatonin vs placebo: Omeprazole 20 mg daily + sublingual melatonin 3 mg nightly vs omeprazole + placebo for 4 weeks (n=72 completers). Melatonin add-on led to significantly larger reductions in FSSG symptom scores, heartburn, epigastric pain, and better quality-of-life; adverse events similar between groups; no serious AEs. (Turkish Journal of Gastroenterology; free PDF.) Turkish Journal of Gastroenterology

Reviews & Guidance (what bodies say)

• Narrative/Mechanistic reviews describe plausible actions—increasing LES tone, reducing gastric acid output, antioxidant effects, modulating nitric oxide—and summarize the small clinical studies above; they emphasize the need for larger trials. (MDPI review, 2018.) MDPI
• Systematic review protocol (2019) registered plans for a meta-analysis of melatonin in GERD, underscoring that evidence was limited and heterogeneous at the time. (Medicine/Europe PMC). Europe PMC
• NCCIH (U.S.) overview: acknowledges the 2006 trial but notes that overall evidence is limited and safety of high-dose melatonin is not well characterized; advises discussing with a clinician. NCCIH

Typical dosing & duration used in trials (not medical advice)

• 3–6 mg at bedtime, for 4–12 weeks, either alone or as add-on to a PPI. Add-on use (with omeprazole) has the most consistent positive RCT signal to date. BioMed CentralTurkish Journal of Gastroenterology

Evidence consists of a handful of small randomized trials and one older single-blind trial using a multi-ingredient supplement. Findings suggest melatonin, particularly as an add-on to PPIs, can reduce GERD/heartburn symptoms and may increase LES pressure—but higher-quality, larger RCTs are still needed. Major agencies flag the evidence as preliminary. Turkish Journal of Gastroenterology BioMed Central Kudos NCCIH