Melatonin overuse has become a very common phenomenon in the United States.
In a recent interview with the Journal of the American Medical Association (JAMA), Judith Owens, MD, MPH, director of the Center for Pediatric Sleep Disorders at Boston Children’s Hospital, said an increasing number of children are taking melatonin. Some pediatricians recommend melatonin to parents, who give their children melatonin in an attempt to solve their sleep problems. According to Dr. Owens, melatonin is not a panacea for the problem, and many of these children eventually end up in a sleep clinic.
In 2020, 933 American parents participated in an online survey that showed that 38 percent of their children had sleeping difficulties (pdf). Among these children, 44 percent were given melatonin products by their parents.
The use of melatonin has been growing rapidly, not only among children, but also among American adults. There has been a five-fold increase in use over the past two decades, from 0.4 percent in the 1999–2000 period to 2.1 percent in the 2017–2018 period according to data from the National Health and Nutrition Examination Survey (NHANES). Its whirlwind rise is also evidenced by the rapid increase in sales of melatonin products, from an estimated $339 million in 2017 to $825 million in 2020 and $1.26 billion in 2021.
In the United States, melatonin is an over-the-counter health supplement that people can purchase without a prescription. And Americans are taking ever-increasing doses of melatonin.
In the 2005–2006 NHANES, no respondents reported taking a daily melatonin dose of more than 5 milligrams (mg), which is tens to hundreds of times the normal amount secreted by the human body each night; even insomnia patients don’t need to take that much.
However, by 2018, one in eight respondents took more than 5 mg daily. Some of the melatonin supplements available even come in the form of a single 10 mg dose.
Melatonin Naturally Secreted by the Human Body Helps Improve Sleep
Melatonin is a hormone mainly secreted by the pineal gland. When it was first discovered, the substance was named “melatonin” due to its ability to alter the melanin pigment of tadpoles, making them almost transparent.
One of the roles played by melatonin in humans is to encourage sleep. At night, melatonin conveys the message to the brain and body that it’s bedtime. This is accompanied by drowsiness and drops in body temperature, pulse rate, and blood pressure.
Melatonin synthesis and secretion is inhibited by light; therefore, it is also known as the hormone of darkness. Melatonin levels in humans vary as the sun rises and sets. Secretion of melatonin increases after nightfall, reaches a peak between 2 a.m. and 4 a.m., and decreases gradually during the second half of the night.
Nearly 80 percent of melatonin is synthesized at night, with serum concentrations reaching 80 to 120 pg/mL (picograms per milliliter), while only 10–20 pg/mL is produced during daylight hours.
Melatonin secretion is affected not only by changes in light, but also by age. Melatonin levels are high in childhood, begin to decline after puberty, and continue to decline throughout middle age, with an average drop of 10–15 percent per decade. By old age, plasma melatonin concentrations have usually dropped to very low levels.
Melatonin naturally secreted by the human body can regulate circadian rhythm, promote sleep, affect human blood pressure and autonomic cardiovascular regulation, enhance immunity, reduce inflammation, resist oxidation, inhibit tumor growth, and protect the brain and nerves. In addition, melatonin has effects on energy expenditure, body weight, and bone mass.
Melatonin also regulates gonadotropin-releasing hormone (GnRH), which affects reproduction and sexual maturation. Variations in melatonin convey information about circadian rhythms and seasonal changes to the body, which affect reproductive hormone levels and reproductive activity in humans.
Oral melatonin can improve the symptoms of some conditions, including insomnia, jet lag, shift work sleep disorders, and neurodegenerative disorders.
Melatonin has also been used in clinical research on diseases including cancer, metabolic disorders, cardiovascular disorders, gastrointestinal conditions, neurodegenerative disorders, pain syndromes, and reproductive dysfunctions, although firm conclusions are not yet established.
Common Side Effects and Potential Long-Term Risks of Melatonin
Melatonin is generally well tolerated when taken orally, but not entirely risk-free. Common side effects of oral melatonin include daytime sleepiness, headache, and dizziness. Other side effects are transient depression, mild tremor, mild anxiety, abdominal cramps, irritability, reduced alertness, confusion, nausea, vomiting, and low blood pressure.
A systematic analysis of 37 short-term (less than four weeks to 29 weeks) randomized, placebo-controlled trials found that oral melatonin administered for insomnia treatment can produce adverse events (AEs). The most frequently reported AEs are daytime sleepiness (1.66 percent), headache (0.74 percent), other sleep-related AEs (0.74 percent), dizziness (0.74 percent), and hypothermia (0.62 percent).
Melatonin overdose can potentially bring serious health problems, especially long-term side effects on which there haven’t yet been definitive studies.
1. Effects on endocrine and reproductive functions
Melatonin can affect neuroendocrine function, and can cause an increase or decrease in plasma growth hormone concentrations. Long-term administration of excessive levels of melatonin will likely have a negative influence on the body’s growth and development.
Furthermore, taking melatonin may be detrimental to gonadal development. Abnormally elevated melatonin plasma concentrations can lead to amenorrhea (an abnormal absence of menstruation) and ovulation suppression in women, and decreased semen quality in men.
With very limited human experimental data available, there is no clear conclusion regarding whether melatonin delays puberty. However, evidence from animal studies strongly demonstrates its influence on reproductive cycles.
2. Association with diabetes and insulin resistance
Abnormalities in melatonin levels have long been found to be associated with insulin sensitivity, glucose tolerance, lipid metabolism, and antioxidant capacity. However, as a hormone that regulates biological rhythm, the association between melatonin and metabolic disorders in humans remains unclarified, although some experts have suggested that metabolic disorders can be treated with melatonin.
Some studies have shown that taking melatonin contributes to impaired glucose tolerance and inhibited insulin secretion; however, this association hasn’t been shown in other studies.
3. Exacerbating autoimmune diseases and elevating blood pressure
The immunomodulatory effects of melatonin may contribute to certain rheumatic diseases, such as exacerbating rheumatoid arthritis.
There are also cases of insomnia patients developing autoimmune hepatitis after being treated with melatonin.
Some children experience mild hypothermia after melatonin administration. For instance, a pediatric patient’s body temperature dropped to 34°C (93.2°F) half an hour after administration of a 3 mg dose of melatonin, and the hypothermia continued for two days.
In addition, studies have mentioned the risks of increased heart rate and blood pressure as a result of melatonin administration.
Proper Ways to Supplement With Melatonin
Most people take melatonin for insomnia. However, changing one’s behavior and habits to improve sleep is far safer than resorting to using drugs or supplements, and often solves the problem of insomnia. For instance, some insomnia is triggered by an irregular bedtime schedule, a stressful life, or the intake of other medications.
There are some simple ways to help elevate natural melatonin levels in the body:
1. Ensure regular sleep and diet, and avoid caffeine and nicotine.
2. Avoid watching TV and using computers, smartphones, or other electronic devices before bedtime because their blue light suppresses melatonin secretion.
3. Expose yourself to the sun in the morning and work out at night to overcome jet lag.
Oral melatonin is recommended to improve sleep, using as low a dose as possible to best simulate the normal circadian rhythm of melatonin and to avoid prolonged excess melatonin levels in the blood.
The human body naturally produces approximately 0.01 to 0.08 mg of melatonin each night. In general, doses of melatonin from 0.1 to 0.3 mg per day (mg/d) are used for physiological clock synchronization, while doses ranging from 0.6 to 5 mg/d are used for sleep disorders, depending on the condition.
In 2019, a systematic analysis of 25 studies found that, depending on individual conditions, doses of melatonin between 1 mg and 6 mg appear to be effective for improving sleep in older adults. However, the analysis also found that further research is needed to find the optimal minimum effective dose.
Patients are advised to discuss melatonin dose and administration methods with their doctor. For some individuals, the optimal frequency of administration is not every night, but two to three times a week.
There are several things to keep in mind when choosing a melatonin product. First, choose high-quality or pharmaceutical-grade melatonin. In some countries, including the U.S., melatonin is an over-the-counter health product instead of a prescription drug. This implies that the specific levels and purity of melatonin may not have been strictly reviewed, and some products may also contain other substances.
A 2017 study conducted tests on 31 melatonin products on the market and found that the melatonin content of the products ranged from –83 percent to +478 percent of the labeled content. Among them, nearly one-third of the products contained serotonin, which should be strictly controlled.
Second, pay attention to dosage and timing of melatonin administration.
Oral melatonin supplements are available in immediate-release formulations and slow-release formulations. Immediate-release formulations are usually taken 45 minutes to one hour before bedtime to reach maximal melatonin plasma levels by bedtime.
Slow-release formulations simulate the gradual release of melatonin into the body at night. The administration time of slow-release formulations should follow the supplement instructions because they may take a few hours to take effect. It is advisable to take the entire tablet, instead of crushing or chewing it.