By: Ken He
Melatonin is a hormone secreted by the pineal gland and can be found in various types of foods, such as tart cherries. It regulates the circadian system and establishes sleep-wake cycles. Darkness stimulates melatonin production, preparing the body for sleep. Light reduces its production, preparing the body for awakening. In Canada, anywhere from 0.3 mg to 5 mg of melatonin, the active ingredient, can be found in melatonin supplements. Melatonin is claimed to protect the body from oxidative damage (excess free radicals) by acting as an antioxidant. Another health claim is that it can treat sleep disorders that prevent an individual from falling and staying asleep, which disturbs diurnal stability. These include insomnia, delayed sleep phase disorder, shift-work disorder, and jet-lag. For example, people who have insomnia often suffer from low levels of melatonin. Supplementing with melatonin is thought to help them fall asleep faster. Melatonin is reported to increase the propensity for sleep and regulate the circadian rhythm. The mechanism of action by which melatonin induces sleepiness is unknown. It is believed that melatonin advances circadian rhythm after evening administration, which acts on the somnogenic structures of the brain and promotes sleepiness. In Canada, anywhere from 0.3 mg to 5 mg of melatonin, the active ingredient, can be found in melatonin supplements. These supplements can be found over-the-counter at pharmacies and health food stores.
Numerous randomized controlled trials (RCTs) and meta-analyses have documented the safety of melatonin for diurnal stability and maintaining the sleep-wake cycle. Melatonin is determined to be safe for short-term use, even at high doses. No studies have shown the presence of serious adverse effects of administering melatonin in any medical setting. In a short-term placebo-controlled clinical study conducted on adolescents, a daily dosage of 10 mg of melatonin was administered orally for 12 weeks to study its role in improving sleep quality. The side effects reported were agitation, dizziness, headache, nausea, and sleepiness. The distribution of these adverse events did not differ in frequency between the melatonin and placebo groups. Furthermore, a meta-analysis looked into the safety of melatonin for primary sleep disorders in the short-term. 17 RCTs with 651 participants showed no evidence of severe adverse effects of melatonin with short-term use of three months or less. Again, the most commonly reported adverse events were headaches, dizziness, nausea, and drowsiness. There was no significant difference in the occurrence of these outcomes compared to the placebo. Several of these studies did not report on the details of the RCTs, such as the formulation of the melatonin product and the methodology. Therefore, there may be discrepancies in the results reported depending on the contents of the melatonin supplement and the dosage administered.
In conclusion, I would not advocate for the use of melatonin for diurnal stability. Several meta-analyses and clinical trial reports have reported that melatonin is ineffective in treating primary sleep disorders and regulating the circadian system. In studies that showed its effectiveness in reducing the time required to fall asleep and total sleep time, the outcomes were modest compared to proven pharmacological treatments. There are minimal effects of exogenous melatonin in treating desynchronization and regulating sleep-wake cycles as they are governed by many internal autonomic neurological pathways. In many of the aforementioned studies, the sample size is too small to draw firm conclusions. The short time frame of these studies means the long-term efficacy and safety of melatonin are unknown. For the treatment of primary sleep disorders and sleep-wake cycles, melatonin use in the short term is determined to be safe. Few mild adverse events have been reported, and they typically include tiredness, headaches, gastrointestinal upset, and nausea. In Canada, melatonin is available over-the-counter in the form of capsules, tablets, and liquids. Since 2011, two natural health products containing melatonin have been licensed for use in Canada for children 12 years and older. Melatonin-containing products are not authorized in products for children under 12 years old. Future research should look into varying the dose, time of administration, and age groups to identify whether melatonin is effective for diurnal stability in the long-term.
Andersen, L. P., Gögenur, I., Rosenberg, J., & Reiter, R. J. (2015). The safety of melatonin in humans. Clinical Drug Investigation, 36(3), 169-175. doi:10.1007/s40261-015-0368-5
Buscemi, N., Vandermeer, B., Hooton, N., Pandya, R., Tjosvold, L., Hartling, L., . . . Baker, G. (2005). Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. Journal of General Internal Medicine, 20(12), 1151-1158. doi:10.1111/j.1525-1497.2005.0243.x.
Ekmekcioglu, C. (2006). Melatonin receptors in humans: biological role and clinical relevance. Pharmacotherapy, 60(3), 97-108. doi:10.1016/j.biopha.2006.01.002
Ferracioli-Oda, E., Qawasmi, A., & Bloch, M. H. (2018). Meta-Analysis: melatonin for the treatment of primary sleep disorders. Focus, 16(1), 113-118. doi:10.1176/appi.focus.1610
Foley, H. M., & Steel, A. E. (2019). Adverse events associated with oral administration of melatonin: a critical systematic review of clinical evidence. Complementary Therapies in Medicine, 42(11), 65-81. doi:10.1016/j.ctim.2018.11.003
Geijlswijk, I. M., Korzilius, H. P., & Smits, M. G. (2010). The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis. Sleep, 33(12), 1605-1614. doi:10.1093/sleep/33.12.1605
Gitto, E., Aversa, S., Reiter, R. J., Barberi, I., & Pellegrino, S. (2010). Update on the use of melatonin in pediatrics. Journal of Pineal Research, 50(1), 21-28. doi:10.1111/j.1600-079x.2010.00814.x
Health Canada (2015, December 11). Government of Canada. Retrieved from https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect -canada/safety-reviews/summary-safety-review-melatonin-acetyl-methoxytryptamine -review-safety-melatonin-children-adolescents.html
Pfeffer, M., Korf, H., & Wicht, H. (2018). Synchronizing effects of melatonin on diurnal and circadian rhythms. General and Comparative Endocrinology, 258(11), 215-221. doi:10.1016/j.ygcen.2017.05.013
Reiter, R. J., Tan, D., Sainz, R. M., Mayo, J. C., & Lopez-Burillo, S. (2002). Melatonin: reducing the toxicity and increasing the efficacy of drugs. Journal of Pharmacy and Pharmacology, 54(10), 1299-1321. doi:10.1211/002235702760345374
Wei, S., Smits, M. G., Tang, X., Kuang, L., Meng, H., Ni, S., . . . Zhou, X. (2020). Efficacy and safety of melatonin for sleep onset insomnia in children and adolescents: a meta-analysis of randomized controlled trials. Sleep Medicine, 68(3), 1-8. doi:10.1016/j.sleep.2019.02.1
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