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Natural Medicine Journal

July 7, 2021

Low Melatonin and Dyspepsia in Menopause

Results from a randomized, placebo-controlled trial
Treatment with melatonin may help resolve Helicobacter pylori infection, according to a new randomized, placebo-controlled trial.

Reference

Chojnacki C, Mędrek-Socha M, Konrad P, Chojnacki J, Błońska. The value of melatonin supplementation in postmenopausal women with Helicobacter pylori-associated dyspepsia. BMC Womens Health. 2020;20(1):262.

Study Objective

This study aims to assess the cause of chronic dyspepsia in patients with low melatonin (ie, postmenopausal women) and the association of Helicobacter pylori infection.

Design

Randomized, placebo-controlled trial

Participants

All 152 participants were postmenopausal women between the ages of 49 to 64 years. Exclusion criteria included those receiving hormone replacement therapy or with a history of inflammatory, metabolic, allergic, or mental illness.

Participants were categorized into 3 groups:

  • Group 1: No H pylori or dyspepsia symptoms (n=30)
  • Group 2: Asymptomatic H pylori infection (n=60)
  • Group 3: Symptomatic H pylori infection (n=64)
    • Group 3a was the placebo group
    • Group 3b was the melatonin treatment group

Intervention

Only Group 3 received the intervention. Group 3b received 1 mg melatonin in the morning and 3 mg melatonin at bedtime, while Group 3a received matching placebo taken at the same times of day.

Study Parameters Assessed

Researchers performed urea breath test, upper gastrointestinal (GI) endoscopy, and histological assessment at the start to confirm H pylori infection. They repeated the urea breath test again after 3 and 6 months.

They evaluated dyspepsia symptoms using the Visual Analogue Scale.

Researchers assessed other parameters at the start and again at 1-, 3-, and 6-month follow-ups. These included complete blood count (CBC), C-reactive protein, glycosylated hemoglobin, bilirubin, liver enzymes, pancreatic enzymes, urea, creatinine, lipid assay, 17-beta-estradiol, follicle-stimulating hormone, serum melatonin, and urinary 6-sulfatoxymelatonin.

Therapeutic Procedure

All participants in the symptomatic H pylori infection group (Group 3) received an antibiotic protocol: daily pantoprazole (2 x 40 mg), amoxicillin (2 x 1,000 mg), and levofloxacin (2 x 500 mg) for 14 days.

Thereafter, Group 3 was split into 2 equal groups: Group 3a received placebo, 2 tablets per day; Group 3b received melatonin, 1 mg each morning and 3 mg at bedtime for 6 months.

Researchers instructed all participants to adhere to 1,600 calories daily for the 6-month study duration.

Key Findings

Initial observation revealed that women in Group 3 (symptomatic H pylori infection) had lower levels of serum melatonin (5.72 ± 1.42 pg/mL; P<0.001) compared to the Group 1 (12.5 ± 2.72 pg/mL) and Group 2 (10.5 ± 3.73 pg/mL) arms.

At baseline, 24-hour urinary 6-sulfatoxymelatonin levels were lower in women with asymptomatic (P<0.001) and symptomatic (P<0.001) H pylori infection compared to the control group.

There was no statistically significant difference between the 3 groups regarding 17-beta-estradiol (P>0.05), follicle-stimulating hormone (P>0.05), or other lab work parameters.

Per protocol, both groups 3a (placebo) and 3b (melatonin) received H pylori eradication treatments for 2 weeks. Eradication of H pylori trended higher in Group 3b (84.3%) than Group 3a (75%) (P>0.5).

After 6 months, symptoms of dyspepsia resolved in 84.3% of those in Group 3b versus 43.7% of those in Group 3a (P<0.001).

Practice Implications

Melatonin is synthesized from L-tryptophan in the pineal gland in a 4-step process that includes serotonin as an intermediary. Melatonin is most commonly used to treat insomnia due to circadian rhythm abnormalities or jet lag. Also found to be an endogenous antioxidant,1 melatonin supports nearly every system in the body including immune,2 eye,3 and gastrointestinal functions.4,5 As previously reported, after adulthood, melatonin production decreases naturally with age.6 In the current study under review, Chojnacki et al demonstrate that lower melatonin levels are associated with symptoms of dyspepsia as well.

Hormone changes are part of the natural menopause process, but this study implies that low melatonin may be the difference between symptomatic and asymptomatic H pylori infection.

This is not the first study on melatonin and dyspepsia. There have been various studies previously on the effects of melatonin on the gastrointestinal tract.7-9 This study adds to the evidence of the association between gut health and melatonin levels. Chojnacki et al propose that dyspepsia symptoms may be caused by decreased production of melatonin locally, in the gastric mucosa. This is supported by a publication in the Journal of Pineal Research that found an association between gastric luminal melatonin levels and bicarbonate secretion in the GI tract.10 Other hypotheses on mechanisms of melatonin-induced symptom relief include effects on the parasympathetic nervous system11 and stimulation of the migrating motor complex (MMP)12 systems intimately involved in digestion.

This study adds to the evidence on the association between gut health and melatonin levels.

Oral melatonin is well-tolerated. When used for insomnia, melatonin is typically taken 1 to 3 hours before bedtime at doses between 0.1 to 6 mg. Serum melatonin levels peak at about 40 minutes with an elimination half-life of 54 minutes with oral ingestion,13 so researchers used more frequent dosing in this study as a treatment for dyspepsia. The dosing in this study was 1 mg in the morning and 3 mg at bedtime, and only 4 out of 32 women reported fatigue. However, daytime dosing has been shown to cause sleepiness,14 so some caution should be used in dosing any time other than bedtime.

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References

  1. Tan DX, Manchester LC, Esteban-Zubero E, Zhou Z, Reiter RJ. Melatonin as a potent and inducible endogenous antioxidant: synthesis and metabolism. Molecules. 2015;20(10):18886-18906.
  2. Srinivasan V, Maestroni GJ, Cardinali DP, Esquifino AI, Perumal SR, Miller SC. Melatonin, immune function and aging. Immun Ageing. 2005;2:17.
  3. Yi C, Pan X, Yan H, Guo M, Pierpaoli W. Effects of melatonin in age-related macular degeneration. Ann N Y Acad Sci. 2005.
  4. Kandil TS, Mousa AA, El-Gendy AA, Abbas AM. The potential therapeutic effect of melatonin in gastro-esophageal reflux disease. BMC Gastroenterol. 2010;10:7.
  5. Sjöblom M, Flemström G. Melatonin in the duodenal lumen is a potent stimulant of mucosal bicarbonate secretion. J Pineal Res. 2003;34(4):288-293.
  6. Bubenik GA, Konturek SJ. Melatonin and aging: prospects for human treatment. J Physiol Pharmacol. 2011;62(1):13-19.
  7. Bubenik GA. Thirty four years since the discovery of gastrointestinal melatonin. J Physiol Pharmacol. 2008;59 Suppl 2:33-51.
  8. 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.
  9. 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.] [Article in Russian.] Klin Med (Mosk). 2012;90(12):48-52.
  10. Sjöblom M, Flemström G. Melatonin in the duodenal lumen is a potent stimulant of mucosal bicarbonate secretion. J Pineal Res. 2003;34(4):288-293.
  11. Pechanova O, Paulis L, Simko F. Peripheral and central effects of melatonin on blood pressure regulation. Int J Mol Sci. 2014;15(10):17920-17937.
  12. Konturek PC, Brzozowski T, Konturek SJ. Gut clock: implication of circadian rhythms in the gastrointestinal tract. J Physiol Pharmacol. 2011;62(2):139-150.
  13. Andersen LPH, Werner MU, Rosenkilde MM, et al. Pharmacokinetics of oral and intravenous melatonin in healthy volunteers. BMC Pharmacol Toxicol. 17(8):2016. https://doi.org/10.1186/s40360-016-0052-2
  14. Lok R, van Koningsveld MJ, Gordijn MCM, Beersma DGM, Hut RA. Daytime melatonin and light independently affect human alertness and body temperature. J Pineal Res. 2019;67(1):e12583.

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