Melatonin 101: What You Need to Know About this Popular Hormone and Sleep Aid

Melatonin, often called the “sleep hormone”, plays a crucial role in regulating our sleep-wake cycle. As a result, melatonin supplements have become increasingly popular as an unregulated, over-the-counter sleep aid. So popular, in fact, that nearly 20% of kids and teens have used melatonin supplements in the past month (Hartstein et al., 2023). In this context, we will explore the nature of melatonin, the potential benefits and risks associated with melatonin supplements, and possible alternatives to melatonin supplements, with the hopes of increasing awareness of melatonin’s properties and helping families and young people make informed decisions about their psychological health.

Melatonin: It’s Not Just a “Sleep Hormone”

Melatonin (N-acetyl-5-methoxytryptamine) was discovered in 1917 and is found in humans, animals, plants, and microbes (Chen, Fichna, Bashashati, Li, & Storr, 2011). Melatonin plays a critical role in human development and is synthesized or produced by multiple parts of the body, including the pineal gland, which is responsible for producing and distributing it across the entire body system, as well as the retina, gastrointestinal tract, bone marrow, skin, reproductive organs, liver, kidneys, and immune cells, which are all responsible for producing and distributing it within same or nearby cells or organs. What’s more, is that melatonin receptors are widely distributed across the body and exist in each of our 11 biological systems (Ekmekcioglu, 2006; Ng, Leong, Lian, and Paxinos, 2017).

As an example, the digestive system, and specifically the gastrointestinal tract, is the largest source of melatonin in our body. Here, it functions independent of light or the circadian rhythm to regulate digestion, gut motility, immune function, and the microbiome. As another example, the integumentary system, and specifically the skin, also produces melatonin. Here, it functions as an antioxidant, protects us against UV radiation, and plays a critical role in cell repair. And as a last example, the skeletal system, and specifically bone marrow, also produces melatonin. Here, it functions to strengthen bone density, thereby improving skeletal integrity, and regulating the immune system, thereby reducing inflammation and toxic free-radicals (i.e., unstable molecules that damage other cells). In short, melatonin is more than just a “sleep hormone”, it impacts the entire body, is implicated in numerous biological functions, and is likely critical to our overall survival.

But when it comes to sleep, as our eyes process light, nerve signals from the retina are transmitted to the suprachiasmatic nucleus (SCN), an area of the hypothalamus that functions as the body’s master biological clock. In response to darkness, the SCN signals the pineal gland to synthesize melatonin by converting the amino acid tryptophan into serotonin. This is transformed into melatonin via the enzymes arylalkylamine N-acetyltransferase and hydroxyindole-O-methyltransferase, also known as acetylserotonin O-methyltransferase (Hardeland et al., 2006). Once synthesized, melatonin is released directly into the bloodstream and cerebrospinal fluid, where it spreads to every major organ system in the body, a process that peaks between 3:00 am and 4:00 am, and decreases gradually thereafter (Khullar, 2012).

Melatonin: One Hormone in a Sea of Sleepy Hormones

Although melatonin has been branded as the “sleep hormone”, the reality is that sleep is shaped by several other hormones. One of the most important is cortisol, the main stress hormone. Cortisol normally rises in the morning to help us wake up and stays low at night so the body can fall asleep and recover. When stress, bright light, or irregular routines keep cortisol levels high at night, sleep often becomes lighter and more fragmented (Ricketts et al., 2022; Hadwin et al., 2019). Other systems in the brain, such as those that use noradrenaline, acetylcholine, and histamine, help keep us alert during the day but need to quiet down at night for restful sleep. The sleep drive, which builds up as we stay awake, also plays a role. It is partly controlled by a chemical called adenosine that increases during the day and tells the brain it is time to rest. Napping too long or having caffeine late in the day can reduce this signal and delay sleep.

Several metabolic and growth-related hormones are also active during sleep. Growth hormone and prolactin increase during deep sleep and help with tissue repair, growth, and immune function. Hormones that regulate hunger and metabolism, such as leptin and ghrelin, are also linked to sleep quality and energy balance (Paruthi et al., 2016). Finally, sex hormones influence sleep throughout life, whereby progesterone tends to promote relaxation and steadier breathing, estrogen affects temperature control and sleep quality (especially during puberty or menstrual changes), and testosterone is closely tied to sleep depth and consistency, with poor sleep leading to lower levels and lower levels, in turn, contributing to fatigue (Carmona et al., 2024). So taken together, although melatonin is often crowned as the “sleep hormone”, in reality, it is only one of many, so-called sleep hormones.

Melatonin Production Across the Lifespan

Infants, children, adolescents, and adults differ in their production of melatonin. In-utero, babies receive their melatonin directly through the bloodstream and placenta, and once born, begin to produce melatonin from their pineal gland at around 3 months of age (Shenoy et al., 2024). Until then, much of their melatonin comes through breastmilk. For children, the production of melatonin occurs at a higher level than in adolescents and adults, resulting in longer and earlier sleep durations. During puberty, melatonin secretion shifts to later in the evening, which results in the desire to stay up later and sleep in longer. In adulthood, melatonin production gradually declines, which weakens the body’s natural sleep-wake signals and contributes to earlier awakenings and less consolidated sleep. In addition, age-related changes in brain physiology reduce the amount of deep slow-wave sleep, leading to lighter and more fragmented sleep as we get older.

Environmental and Individual Factors that Affect Melatonin Production

While dozens of factors impact melatonin production, to understand why this might be, we should consider the lengthy process of human evolution. That is, research in genetics and molecular anthropology suggests that we split away from the lineage that led to humans and chimpanzees at least 7 million years ago and possibly as early as 13 million years ago. Modern humans, in the form of Homo Sapiens, have roamed this planet for at least 300,000 years. In this context, due to the relatively recent advent of accessible electricity and drastic changes to lifestyle, a gap has emerged between the modern environment, and the one that we have evolved in and adapted to. For example, in our modern world, under exposure to natural daylight, low levels of physical activity, high levels of sedentary activity, irregular schedules, circadian misalignment, night-time noise exposure, ultra-processed foods, exposure to blue light emitted by screens, all significantly suppress or dysregulate melatonin production in the entire body, and therefore, impact sleep.

In addition to environmental factors, individual factors such as neurodiversity also impact the body’s production of melatonin. For example, children and adolescents who present with neurodevelopmental disorders such as autism spectrum disorder and attention-deficit/hyperactivity disorder, commonly exhibit disruptions in melatonin production, a biochemical mechanism that may help explain why neurodiversity is often associated with difficulties initiating and maintaining sleep (Rzepka-Migut & Paprocka, 2020).

Other common individual factors that interfere with melatonin production include chronic stress and anxiety, both of which elevate cortisol levels and disrupt sleep-wake regulation. Recent research, for example, highlights that melatonin and cortisol maintain an inverse relationship that is central to the regulation of the sleep–wake cycle. Melatonin secretion increases in response to darkness, promoting sleepiness, while cortisol peaks shortly after waking, supporting alertness and metabolic activation. Disruption of this balance through stress, irregular light exposure, or delayed sleep schedules can suppress evening melatonin and elevate nighttime cortisol, leading to difficulties initiating and maintaining sleep (Ricketts et al., 2022; Hadwin et al., 2019; Futenma et al., 2023).

Melatonin Supplements: Potential Benefits

To mitigate potential effects of sleep issues and promote healthier sleep patterns, melatonin supplements are often used as a sleep aid and are available in various dosages and formulations, including pills, gummies, and liquid drops. However, when it comes to potential benefits, the existing body of research paints a complex picture. For example, research suggests that among adults, melatonin produces modest improvements in sleep, generally reducing sleep onset latency by roughly 4 to 12 minutes and increasing total sleep time by roughly 8 to 18 minutes overall, with somewhat larger benefits reported in some samples of people who experience insomnia (Brzezinski et al., 2005; Ferracioli-Oda et al. 2013). When it comes to healthy children and adolescents, however, limited research seems to exist and marks a significant gap in the literature. But overall, should one extrapolate the findings from the adult literature, it would seem that kids and teens who do not experience significant sleep disturbances would understandably gain few benefits from supplementing with melatonin.

In contrast, some solid research has investigated the effectiveness of melatonin supplements with young people who experience significant sleep disturbances, such as insomnia, or alternatively, sleep disturbances that are secondary to a neurodevelopmental or mental health disorder. For example, recent systematic reviews and meta-analyses report that melatonin supplements significantly improve sleep onset, total sleep time, and overall sleep quality in youth with insomnia (Bruni et al., 2022; Edemann-Callesen et al., 2023; Wei et al., 2020), AD/HD (Rzepka-Migut and Paprocka, 2020), ASD (Gringras et al., 2017), anxiety, mood, or trauma-related disorders (Hadwin et al., 2019), with some noting no evidence of pubertal or growth delays and with good overall tolerability (Boafo et al., 2019). Practically, what this means is that for these groups, depending on the study and characteristics of the sample included, research suggests an improvement in sleep onset of approximately 20 to 40 minutes, and total sleep time of approximately 20 to 60 minutes.

Additionally, because melatonin has neuroprotective, anti-oxidant, and anti-inflammatory functions, among others, melatonin supplements have been used to target more than just sleep. For example, melatonin supplements have shown considerable promise in the treatment of cancerous cells, muscle injuries, inflammatory conditions such as rheumatoid arthritis (Kostoglou-Athanassiou, 2013), migraines (Gonçalves et al., 2016), and atopic dermatitis (Chang et al., 2016), although research in some of these areas is preliminary.

Melatonin Supplements: Potential Risks

Although melatonin supplements are generally considered safe and certainly preferred over pharmaceutical agents, they may still carry significant risks, particularly for children and adolescents who are undergoing immense developmental changes. Afterall, melatonin is critically implicated in processes associated with cell proliferation, and therefore, is key to overall human development, as early as the embryonic stage.

To begin, in response to multiple international reports of adverse side effects, Health Canada (2025) conducted a safety review of melatonin supplements in 2015, and since then, multiple health advisories have been published (American Academy of Sleep Medicine, 2016; National Institutes of Health, 2023), and Health Canada has taken steps to regulate melatonin supplements by adding them to the Prescription Drug List.

Studies of melatonin use in children and adolescents find mild and transient side effects, most commonly morning drowsiness, sedation, nightmares, vivid dreams, enuresis, headaches, dizziness, diarrhea, rash, and hypothermia (Esposito et al., 2019; Van der Heijden et al., 2007; Gringras et al., 2017; Edemann-Callesen et al., 2023; Shenoy et al., 2024). More serious adverse effects are generally rare, although reports of unintentional ingestions, overdoses, drug-related interactions leading to hospitalization, and death, do exist (Shenoy et al., 2024), and in general, seem to be increasing over the years. For example, a recent analysis published in Morbidity and Mortality Weekly Report indicates that the annual pediatric ingestions of melatonin have risen from 8,337 in 2012 to 52,563 in 2021, and 15% of children with overdoses were hospitalized. Furthermore, the annual number of pediatric melatonin ingestions increased by 530% from 2012 to 2021, with the rise in hospitalizations and more serious outcomes occurring primarily because of unintentional ingestions among children aged 5 years and younger (Lelak et al., 2022).

Further, many studies that look at the safety of melatonin supplements are fraught with methodological and statistical shortcomings, including small sample sizes, short time-frames, use of change scores, and a focus on a select number of factors (e.g., sleep-onset, sleep-duration, and few common adverse effects). At the same time, these studies generally do not systematically examine non-specific factors such as cognitive development, emotional regulation, onset of puberty, physical maturation, skeletal development, or immune system functioning. Furthermore, existing studies assess adverse effects quite differently, with most assessing for “treatment-emergent signs and symptoms” or “adverse events” in such a way that requires the participant to spontaneously detect and report subjective symptoms, where they are the only source of information. To do so accurately, however, requires a considerable amount of insight from the person participating in the intervention, and when it comes to research with children and adolescent, this leaves room for considerable measurement error. As such, it may be the case that when it comes to the safety of melatonin supplements for children and adolescents, we simply do not know what we do not know. In other words, if researchers do not ask participants specific questions about specific symptoms, then underreporting of adverse events is likely.

In the case of puberty and physical maturation, there are concerns that long-term use might delay children’s sexual maturation, possibly by disrupting the decline in nocturnal melatonin levels that occur at the onset of puberty. Many of these concerns emerged from our general understanding of melatonin’s role in the body, but more specifically, from various animal studies. For example, Chen et al. (2022) noted that melatonin interacts with the hypothalamic-pituitary-gonadal (HPG) axis in female mice, which regulates reproductive hormones, and found that melatonin administration resulted in delayed vaginal opening and suppressed ovarian development, showing a direct influence on pubertal timing. Others found that melatonin can directly suppress androgen in male Syrian hamsters (Frungieri et al., 2005). Obviously, humans are not hamsters, so it is difficult to extrapolate those findings to our species. But we are generally lacking these types of studies with humans, and as a result, it will likely be critical for future research to rigorously examine the impact that melatonin supplements have on every developing biological system in the short- and long-term (i.e., 10- or 20-year span).

Melatonin Supplements: Potential Alternatives

Although melatonin supplements are often considered a safer alternative to prescription sleep medication, experts consistently emphasize that non-pharmacological strategies, such as cognitive-behavioral and lifestyle-based interventions, should be the first-line approach. Various studies, reviews, and clinical guidelines highlight that interventions that focus on consistent bedtime routines, limits on evening screen time, and exposure to natural sunlight, physical activity, and a healthy diet, can be as effective in targeting sleep, have fewer side effects, and produce a host of other benefits because they target the root cause of disrupted sleep (CADTH, 2022; Edemann-Callesen et al., 2023). As a result, experts generally advise that melatonin supplements should not be a primary or first-line intervention, but rather, should be considered only with careful professional monitoring and after cognitive-behavioral and lifestyle-based interventions have proven ineffective.

Final Remarks

Taken together, research suggests that melatonin supplements have a limited effect on sleep among healthy children, adolescents, and adults, although they can be used with some effectiveness among those who experience insomnia or sleep-related disturbances due to another condition (e.g., AD/HD, ASD, PTSD). Still, the existing body of research highlights some safety concerns associated with melatonin use, is fraught with statistical and methodological shortcomings, and generally does not address the effect that melatonin supplements might have on broader biological systems over time, particularly during sensitive developmental periods. In this context, given that cognitive-behavioural and lifestyle-based interventions have been demonstrated to have at-least an equal effect on sleep, these types of interventions should likely be prioritized and may include strategies outlined in our adjacent paper, “The Art of Better Sleep”.

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