Osadchuk MA, Sibriaev AA, Kireeva NV, Kvetno IM. The influence of melatonin included in the combined treatment of antichelicobaterial therapy on immunohistochemical characteristics of gastric epitheliocytes from patients with duodenal ulcer. Klin Med (Mosk). 2012;90(12):48-52.
An open clinical trial that added melatonin to a standard protocol for treating Helicobacter pylori infection: Clinical outcomes were compared with matched controls.
The study included 100 patients with duodenal ulcer (DU), 30 with chronic nonatrophic gastritis (CNAG), 30 with chronic atrophic gastritis (CAG), and 12 healthy subjects. All patients with DU and CNAG had morphologically confirmed H pylori infection. The patients with DU were divided into 2 groups, each including age-matched subjects with endoscopically, morphologically, and immunohistochemically identical characteristics.
Study Medication and Dosage
Group 1 patients underwent a conventional 7-day course of treatment for H pylori that included omeprazole (20 mg 2x/d), clarithromycin (500 mg 2x/d), and amoxicillin (1000 mg 2x/d). Group 2 received the same treatment with the addition of melatonin (3 mg before bedtime). Patients in group 1 continued omeprazole, and those in group 2 omeprazole plus melatonin for a total of 2 months. Healthy subjects and patients with CAG served as controls.
All patients underwent fibrogastroduodenoscopy (FGDS) on weeks 2 and 4. Immunohistochemical studies were conducted for endothelin-1 and melatonin-positive cells. Apoptotic activity of mucosal epitheliocytes from gastric antrum was measured before and 6 weeks after the start of therapy.
The addition of melatonin to the standard treatment protocol for H pylori increases efficacy of H pylori elimination and accelerates DU healing. A 2-month therapy of omeprazole plus melatonin is more effective at normalizing markers of healing than treatment with omeprazole alone.
Melatonin should now be considered in the treatment of H pylori, gastric and duodenal ulcers, and gastrointestinal reflux disease.
Many patients are aware that melatonin may improve insomnia, but few are aware of its beneficial impact on the gastrointestinal tract. We think of melatonin only as the hormone produced in the brain by the pineal gland, yet far more melatonin is actually made by enteroendocrine cells that line the digestive tract.
Bowel habits follow clear circadian rhythms, and it is melatonin that regulates this timing. Dietary L-tryptophan increases blood levels of melatonin, even in animals that have had their pineal glands removed. L-tryptophan is converted to serotonin that in turn is converted into melatonin. The nighttime surge in melatonin comes from the pineal gland, but the gastrointestinal tract maintains baseline levels. Melatonin levels in the gut are 10 to 100 times higher than in the blood.1
This is not the first study to report melatonin has benefit in treating H pylori. In 2 studies published in 2011, Celinski et al reported that either melatonin or L-tryptophan helps heal gastric and duodenal ulcers resulting from H pylori infections in humans. They gave all patients omeprazole 20 mg twice a day and then added either melatonin (5 mg 2x/d) or tryptophan (250 mg 2x/d). Both melatonin and tryptophan sped healing compared to omeprazole alone.2,3
A number of reports suggest melatonin may be useful in treating gastroesophageal reflux disease (GERD). This was first brought to our attention by de Souza Pereira who in a May 2006 letter to the editor of the Journal of Pineal Research described a 64-year-old woman whose GERD responded well to a formula containing melatonin (6 mg). Later the same year, de Souza Pereira reported the results of a clinical trial in which 176 patients received this melatonin-containing product and 175 received omeprazole (20 mg). All the patients receiving melatonin supplements “reported a complete regression of symptoms after 40 days of treatment.” Only 65.7% of those receiving omeprazole reported similar improvement.4
Madalinski in 2011 suggested that melatonin might protect against development of “erosive esophagitis . . .esophageal stricture, Barrett’s esophagus and extra-esophageal damage (including the lungs, throat, sinuses, middle ear, and teeth),” all of which are “major risk factors for esophageal carcinoma.”5
The benefits of melatonin aren’t limited to the esophagus and stomach but extend to the pancreas and liver.
Melatonin prevents various forms of gastritis and pancreatitis through the activation of specific MT2-receptors and scavenges reactive oxygen species (ROS). Melatonin counteracts the increase in the ROS-induced lipid peroxidation and preserves, at least in part, the activity of key anti-oxidizing enzymes such as superoxide dismutase.6
In a 2011 study of 75 patients with acute pancreatitis, high levels of endogenous melatonin played a protective role and were associated with a milder course of disease.7
Melatonin may also protect against gallstone formation. It reduces biliary levels of cholesterol by inhibiting cholesterol absorption across the intestinal epithelium and by increasing conversion of cholesterol to bile acids.8 In a study of 45 patients with steatohepatitis, melatonin produced a “statistically significant reduction in GGTP, triglycerides and proinflammatory cytokine levels.”9
The bottom line is simple: In melatonin, we have a potent tool to help protect and heal the gastrointestinal tract. This study just adds further evidence to support its use.
- Bubenik GA. Thirty-four years since the discovery of gastrointestinal melatonin. J Physiol Pharmacol. 2008;59 Suppl 2:33-51.
- Celinski K, Konturek PC, Konturek SJ, et al. Effects of melatonin and tryptophan on healing of gastric and duodenal ulcers with Helicobacter pylori infection in humans. J Physiol Pharmacol. 2011;62(5):521-526.
- Celinski K, Konturek SJ, Konturek PC, et al. Melatonin or L-tryptophan accelerates healing of gastroduodenal ulcers in patients treated with omeprazole. J Pineal Res. 2011;50(4):389-394.
- Pereira Rde S. Regression of gastroesophageal reflux disease symptoms using dietary supplementation with melatonin, vitamins and amino acids: comparison with omeprazole. J Pineal Res. 2006;41(3):195-200.
- Madalinski MH. Does a melatonin supplement alter the course of gastro-esophageal reflux disease? World J Gastrointest Pharmacol Ther. 2011;2(6):50-51.
- Jaworek J, Brzozowski T, Konturek SJ. Melatonin as an organoprotector in the stomach and the pancreas. J Pineal Res. 2005;38(2):73-83.
- Belyaev O, Herzog T, Munding J, et al. Protective role of endogenous melatonin in the early course of human acute pancreatitis. J Pineal Res. 2011;50(1):71-77.
- Koppisetti S, Jenigiri B, Terron MP, et al. Reactive oxygen species and the hypomotility of the gall bladder as targets for the treatment of gallstones with melatonin: a review. Dig Dis Sci. 2008;53(10):2592-2603.
- Cichoz-Lach H, Celinski K, Konturek PC, Konturek SJ, Slomka M. The effects of L-tryptophan and melatonin on selected biochemical parameters in patients with steatohepatitis. J Physiol Pharmacol. 2010;61(5):577-580.