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Unlocking Better Sleep: The Power of Melatonin and Circadian Rhythms

How Melatonin Works with our Natural Sleep Cycles

by Kyle Perkovich, BS

Sleep determines everything – how we feel throughout the day, our mental and physical performance, and various aspects of our overall health.1 However, an estimated 50 to 70 million Americans struggle with sleep disorders, and one out of every three adults does not get the proper amount of sleep for their health.2 Trouble sleeping can occur for a variety of reasons, such as physiological, psychological, and environmental factors, and it effects all ages.3 This widespread issue is more problematic than feeling groggy during the day; prolonged insufficient sleep is associated with numerous increased health concerns, including anxiety, depression, cardiovascular disease, stroke, and heart attack.4

People today are turning to various methods to get a good night’s sleep. According to a 2022 study by the American Academy of Sleep Medicine,5 64% of Americans use some substance either occasionally or regularly to help with sleep. Reported options included prescription sleeping pills and medications, over-the-counter sleeping aids, herbal supplements, alcohol, and marijuana; however, the largest single category of sleep aids used by American adults was Melatonin, with 27% or respondents indicating its use to help with sleep.5 With the prevalence of melatonin, it is important to dive into this supplement and its effect on our sleep – how does it work, is it safe, and is it effective?

circadian rhythm

Understanding Sleep and our Circadian Rhythm

We spend a third of our lives sleeping, yet do not fully understand how it works. Sleep is a complex process involving different parts of our brains, hormones, chemicals, and internal cycles, all working in unison to regenerate our bodies and remove toxins in our brains that build up during the waking hours.6 Different brain structures play different roles: the hypothalamus functions as a control center affecting sleep and arousal, the brain stem communicates to control the transitioning from waking and sleeping, and the thalamus relays sensations during rapid eye movement (REM) sleep, just to name a few. We go through REM cycles throughout the night, as our brain frequency speeds up and slows down.6

While the actual process is much more complex than this explanation, it is all controlled by two primary internal mechanisms within our bodies – sleep-wake homeostasis and circadian rhythms.6 Sleep-wake homeostasis tells the body when it needs sleep, sending reminders (“getting tired”) and regulating sleep intensity. The other mechanism, which has important interactions with melatonin, is our circadian rhythm. This system has a broad range of functions, including regulating daily fluctuations in wakefulness, body temperature, metabolism, and hormone release.

Our circadian rhythm is the biological 24-hour clock for our bodies, working with our brain and internal systems to regulate when we should be sleeping. It can also be a major factor in sleeping dysfunction, as a disruption to this rhythm can lead to poor sleep and therefore health and mood concerns.5 This internal clock can be divided into two major components: the central clock in the suprachiasmatic nucleus (SCN) of the brain and the peripheral clocks located in various tissues in our organ systems.7  Environmental factors play a role in this system, with sensory information fed into the central clock through signals from the eye, which are then converted to chemical signals in the SCN and synchronized with the peripheral systems. Chemical signals travel through our body and help create this rhythm and regulate our sleep; one crucial hormone involved in this process is melatonin.


melatonin sleep hormone pills

Melatonin: The Sleep Hormone

While many think of melatonin as a supplement you buy at your local drug store, it is in fact a natural and ubiquitous molecule present in our bodies that helps regulate our normal sleep cycles.8 Melatonin, a hormonal signal of our body’s circadian clock, is secreted at night by the pineal gland.9 It is released as part of the circadian cycle into our bloodstream to regulate sleep, increasing in concentration as light begins to fade and our circadian rhythm signals for it1. Along with other hormones, neurotransmitters, and genetic factors, melatonin is part of a complex chemical dance taking place every night, which can be easily disrupted and create the sleeping disorders seen so prevalently today.

Melatonin promotes sleep and tiredness, increasing our sleep propensity at night and helping us get a good night’s rest.10 This effect is attributed to melatonin’s action on the MT1 and MT2 melatonin receptors in the SCN of the hypothalamus. It is believed that when melatonin binds to these receptors, SCN neuronal activity is decreased, slowing brain function and creating the feeling of tiredness.10

Within our natural circadian rhythm, increasing melatonin lowers our brain activity and tell our bodies that it is time to sleep. It is generally a well-oiled machine; however, with modern day stressors, increased screen time, and other factors, it is easy to get off this rhythm and have difficulty falling asleep. One cause of prevalent issues with sleep quality may be attributed to the fact that although melatonin is endogenous in the body, some individuals may have deficient amounts or lack the ability to sufficiently release melatonin for proper sleep.1 Bolstering our natural melatonin with supplements has been shown in clinical studies to promote falling and staying asleep.1

Melatonin as a Supplement: Clinically Effective and Safe

Melatonin use is not just a popular trend—it is a method for sleep improvement with strong clinical evidence. A 2020 meta-analysis,11 analyzing the results of 23 randomized controlled trials, found statistically significant results for the use of melatonin correlating positively with sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI). Similarly, a 2022 meta-analysis12 on 34 randomized controlled trials found positive effects of melatonin versus placebo in both adult populations and child/adolescent populations. Compared to the placebo in these studies, melatonin was shown to significantly improve sleep onset latency and total sleep time in adults with delayed sleep phase disorder and in children/adolescents with a variety of neurodevelopmental disorders. These results were echoed in a 2013 meta-analysis of 19 clinical studies,13 which concluded that melatonin significantly decreased sleep onset latency, increased total sleep time, and improved sleep quality over placebos.

Numerous other studies have looked into melatonin’s effectiveness in promoting quality sleep, finding that melatonin supplementation can aid disrupted circadian cycles,14 decrease daytime sleepiness,15 improve sleep quality for secondary sleep disorders,16 and improve sleep-wake rhythm and endogenous melatonin rhythm.17 The studies are prevalent on this common supplement, with many displaying significant results highlighting the benefits of melatonin for sleep. In addition to its effectiveness, multiple studies have noted that melatonin is generally well-tolerated and does not have a high potential for dependence or pineal atrophy.1,11,12

A Well-Researched and Natural Solution for Better Sleep

Given melatonin’s part in the natural regulation of our circadian rhythms and role in promoting our day-to-day sleepiness, it appears logical that boosting our natural reserves through supplements would be a solution for getting better sleep. This assumption is backed by research, with clinical trials and meta-analyses producing significant results demonstrating the use of exogenous melatonin helping people fall and stay asleep better. Given the sleep issues millions of people experience, along with the scientific evidence for melatonin’s effectiveness and tolerability, it is no wonder that melatonin is the leading solution to help regulate our circadian rhythms and get a well-deserved night’s rest.


  1. Vasey C et al. Circadian rhythm dysregulation and restoration: The role of melatonin. 2021;13(10):3480.
  2. National Heart Lung and Blood Institute. Sleep Health. Accessed Feb 19, 2024.
  3. Nelson K et al. Sleep quality: An evolutionary concept analysis. Nurs Forum. 2022;57(1):144-151.
  4. Lane JM et al. Genetics of circadian rhythms and sleep in human health and disease. Nat Rev Genet. 2023;24(1):4-20.
  5. American Academy of Sleep Medicine. Accessed Feb 19, 2024.
  6. National Institute of Neurological Disorders and Stroke. Accessed Feb 19, 2024.
  7. Richards J et al. Mechanism of the circadian clock in physiology. Am J Physiol Regul Integr Comp Physiol. 2013;304(12):R1053-R1064.
  8. Cipolla-Neto J et al. Melatonin as a hormone: new physiological and clinical insights. Endocr Rev. 2018;39(6):990-1028.
  9. Pevet P et al. Melatonin and the circadian system: Keys for health with a focus on sleep. Handb Clin Neurol. 2021;179:331-343.
  10. Srinivasan V et al. Melatonin and melatonergic drugs on sleep: possible mechanisms of action. Int J Neurosci. 2009;119:6,821-846.
  11. Fatemeh G et al. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials. J Neurol. 2022;269(1):205-216.
  12. Salanitro M et al. Efficacy on sleep parameters and tolerability of melatonin in individuals with sleep or mental disorders: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2022;139:104723.
  13. Ferracioli-Oda E et al. Meta-analysis: melatonin for the treatment of primary sleep disorders. PLOS One. 2013;8(5):e63773.
  14. Baandrup L et al. Circadian rest-activity rhythms during benzodiazepine tapering covered by melatonin versus placebo add-on: data derived from a randomized clinical trial. BMC Psychiatry. 2016;16(1):348.
  15. Baglioni C et al. A systematic review and network meta-analysis of randomized controlled trials evaluating the evidence base of melatonin, light exposure, exercise, and complementary and alternative medicine for patients with insomnia disorder. J Clin Med. 2020;9(6):1949.
  16. Li T et al. Exogenous melatonin as a treatment for secondary sleep disorders: A systematic review and meta-analysis. Front Neuroendocrinol. 2019;52:22-28.
  17. Van Geijlswijk IM et al. The use of exogenous melatonin in delayed sleep phase disorder: A meta-analysis. Sleep. 2010;33(12):1605-1614.


Kyle Perkovich is a medical writer with a background in clinical research and leading medical writing teams in the completion of clinical reports to get products approved for global sale. He graduated from the University of California, Santa Barbara with a degree in microbiology and a minor in professional science writing, while writing for the university newspaper and completing a technical writing internship with the Vandenberg Air Force Base. Kyle has helped manage documentation for large-scale clinical studies of medical devices and has been involved in various clinical and scientific research studies. He hopes to educate healthcare practitioners and consumers on the science behind the world of supplements and vitamins to help people better understand the complexities of nutrition and live healther lives.

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