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How does melatonin work?

Sleep disorders present a major issue to public health, especially insomnia – the most prevalent sleep disorder. Inadequate sleep, whether in terms of quality or duration, has been linked to a variety of diseases, such as hypertension and cardiovascular disease. It has also been reported to impair cognition, making it more difficult for a person to focus or be alert. Medication can be prescribed for treating sleeping disorders, however, it is possible that a patient will become dependent on the drug or no longer experience its effect after long-term use. Thus, over-the-counter melatonin supplements are growing in popularity to promote and regulate healthy sleep in clinical populations and healthy populations experiencing minor sleep problems. So, how does melatonin work?

How does melatonin work?

Melatonin is a hormone produced by the body, primarily in the pineal gland – located in the brain. Its secretion is circadian, meaning that its secretion activity changes depending on environmental light-dark cycles. Melatonin production in a healthy individual typically commences after sundown, and will reach its peak secretion level during the night. During daylight hours, there is very little melatonin circulating through the body since light inhibits melatonin secretion. In this way, it helps reinforce our body’s internal clock. The rhythmic production of melatonin based on daily light-dark cycles works to regulate many circadian rhythms – physiological or behavioural conditions that change over a 24-hour cycle. For example, melatonin is best known for regulating sleep-wake cycles; a circadian rhythm in which healthy individuals feel wakeful during the daylight hours and sleep during the dark night. It is sometimes referred to as the sleep hormone for its role in promoting sleep. Circadian rhythms regulated by melatonin also include blood pressure and body temperature cycles. Level of melatonin secretion is known to decrease gradually with age, possibly contributing to sleep problems common in older populations.

Melatonin binds to specific receptors in the brain, MT1 and MT2, to carry out its function of regulating sleep-wake cycles. While melatonin’s mechanism of action is not completely understood, it is thought that the binding of melatonin to MT1 and MT2 receptors in the brain inhibits wake-promoting signals and thus, promotes sleep. A recent study on worms – which sleep similarly to humans – indicates that the binding to the MT1 receptor activates a potassium channel in the brain which limits the release of neurotransmitters (chemical messengers). In the context of promoting sleep, the potassium channel may limit the release of wake-promoting neurotransmitters in the brain. Research on this potassium channel needs to be conducted in other animal models and eventually humans to confirm this mechanism of action.

While melatonin is a natural hormone secreted in the brain, synthetic melatonin supplements can be taken to amplify its short-term effects within the body, promoting sleep. Melatonin supplements can be prescribed for individuals by physicians, but it is widely available for over-the-counter purchase in most drugstores. Typically, melatonin supplements, ranging from doses of 1-10mg, are taken orally a few hours before bedtime. Within an hour of taking the supplement, the concentration of melatonin circulating through the body is 10-100x higher than usual, depending on the dose of melatonin supplement taken. Much like the melatonin naturally produced by the body, melatonin supplements have short-term effects, with the melatonin concentration returning to its typical levels after 4-8 hours of administration into the body.  Melatonin, whether produced by the body or taken as a supplement, does not cause sleep, rather it helps prepare the body for sleeping. The proposed benefit of taking a melatonin supplement is that its normal sleep promoting function is enhanced with the added melatonin circulating throughout the body.

Uses for melatonin supplements

Individuals may take supplemental melatonin for sleep disorder or sleep problem treatment. Supplemental melatonin has a variety of intended uses. For example, it can promote sleep quality, lessen the time to fall asleep, and allow individuals to stay asleep for longer durations.  Specifically, melatonin supplements have shown promise for use in individuals travelling across time zones experiencing jet lag – the disturbance of their internal clock’s regulation of circadian rhythms – to rebalance their sleep-wake cycle. Synthetic melatonin treatment has also been suggested for shift workers who need to be awake during the dark night and asleep during daylight hours; going against the normal daily rhythmic production of melatonin. However, one systematic review reported that research is inconclusive for melatonin’s effectiveness to promote sleep in shift workers. Melatonin also shows potential in improving sleep quality and duration for healthy individuals with sleep problems, however, research indicates its capacity for sleep improvement is limited. Overall, for most suggested uses of melatonin, studies have reported varied results with regards to its effectiveness.

Risks associated with melatonin use

It is important to note that the FDA does not regulate synthetic melatonin tablets or pills since they are considered a dietary supplement. As such, it is possible that the tablets contain less or more melatonin than declared on the label. Despite this, synthetic melatonin supplements are generally considered relatively safe with a low risk of severe adverse events.

Some minor side effects may be experienced by individuals, especially if they are taking a higher dose or an extended-release formulation. For example, side effects such as daytime drowsiness, headaches, or nausea may occur. Daytime administration may cause fatigue and performance impairments that negatively affect the individual. A few reports of neurological side effects of melatonin supplement use in pediatric populations have indicated it should be avoided by children with immune disorders. Further, melatonin supplements are not approved by Health Canada or the US FDA for use in pediatric populations to treat sleep disorders. Thus, no clear guidelines have been provided for its use in children and adolescents. Nor is there long-term data on the safety of melatonin supplements in pediatric populations.

Melatonin supplements are typically considered a short-term treatment to reset an individual’s sleep-wake cycle and/or improve the quality of their sleep. However, a physician’s medical advice may suggest that synthetic melatonin is an acceptable long-term treatment for an individual. Always consult your doctor before taking any supplements.

References:

Costello, R. B., Lentino, C. V., Boyd, C. C., O’Connell, M. L., Crawford, C. C., Sprengel, M. L., & Deuster, P. A. (2014). The effectiveness of melatonin for promoting healthy sleep: A rapid evidence assessment of the literature. Nutrition Journal, 13, 106. https://doi.org/10.1186/1475-2891-13-106

Eurek Alert (2020). Worms reveal why melatonin promotes sleep. Retrieved from https://www.eurekalert.org/pub_releases/2020-11/uoc-wrw111320.php

Janjua, I., & Goldman, R. D. (2016). Sleep-related melatonin use in healthy children. Canadian Family Physician62(4), 315–317.

Savage, R. A., Zafar, N., Yohannan, S., & Miller, J. M. (2020). Melatonin. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK534823/#_NBK534823_pubdet_

Tordjman, S., Chokron, S., Delorme, R., Charrier, A., Bellissant, E., Jaafari, N., & Fougerou, C. (2017). Melatonin: Pharmacology, functions and therapeutic benefits. Current Neuropharmacology15(3), 434–443. https://doi.org/10.2174/1570159X14666161228122115

Worley, S. L. (2018). The extraordinary importance of sleep: The detrimental effects of inadequate sleep on health and public safety drive an explosion of sleep research. Pharmacy & Therapeutics43(12), 758–763.

Zisapel N. (2018). New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation. British Journal of Pharmacology, 175(16), 3190–3199. https://doi.org/10.1111/bph.14116

Image by Kacper Lawiński from Pixabay 

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