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Melatonin refers to a stress hormone naturally secreted by the human body’s pineal gland, a small endocrine gland located in the center of the vertebrate brain . The pineal gland is essential for regulating the body’s endogenous circadian cycle . It is also photosensitive, and as sunlight decreases, the gland begins to increase melatonin production, thereby inducing a natural impetus to sleep . During the day, melatonin levels in the brain are virtually undetectable .
Melatonin can be isolated from organic subjects or produced synthetically in a laboratory setting . Given the vital role melatonin plays in regulating the human circadian cycle, it is popularly used as a sleep-regulating supplement for individuals suffering from intermittent insomnia, delayed sleep-wake phase disorder, rapid eye movement sleep behaviour disorder, and other circadian rhythm sleep abnormalities .
Melatonin has also been prescribed for individuals suffering from chronic obstructive pulmonary disease (COPD), endometriosis, tinnitus (or chronic ringing in the ears), fibromyalgia and/or chronic fatigue syndrome, migraine and other chronic headache disorders, irritable bowel syndrome, metabolic syndrome, and a variety of other ailments. Some researchers have spoken highly of the ameliorative capabilities of melatonin in reducing chemotherapy-related negative side effects, including nerve pain and thrombocytopenia .
While there is little or insufficient evidence to verify melatonin’s efficacy in the treatment of headaches, psychiatric disorders such as bipolar disorder or schizophrenia, chronic fatigue syndrome and/or fibromyalgia, chronic gastrointestinal illnesses, metabolic syndromes, age-related memory loss, or tinnitus, there is clinical evidence to indicate melatonin’s ability to relieve sleep-wake cycle disturbances, as well as high blood pressure and possibly a painful uterine disease called endometriosis .
Benefit and Effects
Research indicates that melatonin can have a number of benefits, including:
Much placebo-controlled, clinical research has validated melatonin’s ability to reduce insomnia in healthy adults. In 2013, researchers at Yale University conducted a meta-analysis of melatonin’s use in the treatment of chronic insomnia. Results indicated that, among 1,683 subjects, melatonin decreased latent onset of sleep, improved overall sleep quality, and prolonged total sleeping time. Further, while researchers did note that melatonin was less effective than some current pharmacological alternatives for chronic insomnia, it produced fewer negative side effects .
More recently, a 2017 study of insomnia assessed the role of melatonin synthesis in sleep regulation among patients with autism spectrum disorders (ASD) and co-morbid insomnia. Results yielded that the normal nocturnal increase in melatonin production is reduced in patients with ASD, resulting in frequent sleep disturbances . These findings indicate that melatonin supplementation may be effective in reducing insomnia and insomnia-related anxiety in patients with ASD.
Research has also indicated that melatonin may be effective in improving sleep regulation in postmenopausal women. A 2015 placebo-controlled trial conducted at Aarhus University Hospital in Aarhus, Denmark revealed that, while postural balance and muscle strength were not improved by melatonin supplementation, there was a statistically significant trend toward better quality of sleep in the subgroup of postmenopausal women with identifiable sleep disturbances .
In 2014, the Nutrition Journal published a literature review to verify the existing body of clinical evidence that supports melatonin’s use in treating primary sleep disorders. The researchers assessed various high-quality placebo-controlled trials and confirmed that melatonin is overall effective in alleviating circadian sleep disturbances . In terms of treating long-term, chronic insomnia, its efficacy is mild to moderate in comparison to some current pharmacological benzodiazepines, orexin receptor antagonists, and tricyclic antidepressants. However, its negative side effect profile is comparatively very benign .
Uterine Health and Pelvic Pain Relief
In recent years, attention has been directed towards melatonin’s role in aiding patients suffering from endometriosis. Endometriosis is a uterine disease primarily found in women of childbearing age, in which endometrium tissue grows abnormally outside of the uterus, potentially causing extreme pelvic pain, dysmenorrhea, and infertility . A 2013 study conducted at the Laboratory of Pain & Neuromodulation in Porto Alegre, Brazil found that melatonin improved overall sleep quality in women with endometriosis-associated chronic pelvic pain. Further, melatonin was found to have a managing effect on the secretion of brain-derived neurotrophic factor (BNDF), meaning it may be effective as a pain modulator .
Existing evidence recommends further research into melatonin’s role in the pathophysiology of various ovarian diseases . It has been established that deficient melatonin levels may be reliable indicators of endometrial cancer . Its essential functions in the human ovary indicate that it may serve as a therapeutic agent for conditions such as polycystic ovary syndrome (PCOS) and premature ovarian failure, as well as endometriosis .
Melatonin has been clinically proven to yield a direct impact on cardiovascular health. It has been consistently demonstrated that vertebrates with low melatonin production levels are at higher risk of coronary heart disease, cardiac infarction, and age-related hypercholesterolemia and hypertension .
A 2004 trial published by Hypertension explored the effect of nightly administered melatonin in sixteen men with untreated essential nocturnal hypertension. Results yielded that repeated melatonin supplementation significantly decreased systolic and diastolic nocturnal blood pressure in these patients . A 2005 trial published by the American Journal of Hypertension yielded similar results in a study of eighteen adult women with normal or treated essential hypertension. Repeated melatonin administration significantly decreased nocturnal systolic blood pressure .
Melatonin has also been demonstrated effective in the treatment of hypertensive patients with metabolic syndrome. A 2010 study with thirty patients with metabolic syndrome revealed that systolic and diastolic blood pressure were significantly decreased while antioxidative enzymes were significantly increased after two months of consistent nightly melatonin administration .
How it works
Pineal melatonin is naturally secreted during the night hours, not necessarily to induce sleep, but to stimulate the body’s natural circadian response to environmental stimuli (i.e., darkness) . In other words, melatonin is a sleep regulator as opposed to a sleep instigator. Melatonin also has potential anti-inflammatory, pain-modulating, and antioxidant effects .
Melatonin supplements primarily come in pill or chewable tablet form . In Europe and the United Kingdom, melatonin is a prescription-only supplement . Approved brand-name melatonergic agonists include Agomelatine (received approval form the European Medicines Agency in 2008), Ramelteon (received approval from the U.S. Food and Drug Administration in 2005), and Tasimelteon (received approval from the U.S. Food and Drug Administration in 2014). The melatonergic agonist and serotonergic antagonist TIK-301 is currently under development and research in terms of its efficacy as an antidepressant and a treatment for sleep disorders in the visually impaired .
How long does it take for melatonin to kick in?
As a sleep aid, melatonin works relatively quickly. Most individuals suffering from jet lag or intermittent insomnia opt to take it approximately thirty minutes to an hour before going to bed .
How long does melatonin last?
Melatonin can remain in the body for up to twelve hours, in accordance with the body’s natural circadian rhythms. For this reason, it is inadvisable to take melatonin during the daylight hours .
How much melatonin should I take?
The available melatonin dosage for adults ranges from 0.3 mg to 10 mg. Some sources assert that the max dose of melatonin can reach 20 mg, but researchers and physicians consistently recommend less-is-more approach . Anecdotal evidence indicates a wide variety of individual responses to varying doses depending on health and existing circadian patterns. In general, the most appropriate melatonin dose for sleep ranges from 0.3 mg to 1 mg, and is considered safe for treating intermittent sleep cycle disturbances such as jet lag . Individuals with chronic sleep conditions should consult a physician regarding the appropriate dosage for them.
Can you take melatonin every night?
Evidence suggests that melatonin is safe to use in the short term (for periods of three months or less) . While the supplement is not confirmed to be unsafe over the long-term, a dearth of long-term clinical studies means physicians can’t confirm its safety and efficacy beyond a three-month period  .
Can you overdose on melatonin?
Individuals experiencing melatonin overdose will often suffer from symptoms contradicting the supplement’s initial purpose. Side effects of excessive melatonin supplementation include grogginess during the day and insomnia at night, nausea, dizziness, irritability or unstable mood, gastrointestinal upset, and/or joint pain. Individuals have also reported very vivid “melatonin dreams” after taking an excess of the supplement . However, no cases of severe or life-threatening symptoms have been reported as a result of excess melatonin ingestion .
Melatonin for Children
To date, no studies have been conclusive enough to verify the safety and efficacy of regular melatonin supplementation in children. While some surgeons prescribe a melatonin dosage by weight (typically 0.3 mg per kg of body weight) to alleviate preoperative anxiety in children, most physicians recommend against administering this hormonal supplement to kids without medical supervision. A safe dose of melatonin for adults (1 mg or higher) may induce a seizure in a young child . David Kennaway, director of the Circadian Physiology Lab at the University of Adelaide in Australia, stated in a publication from Science Daily that the increased popularity of the unapproved “use of melatonin to treat children’s sleep disorders” was “alarming” and ill advised .
Melatonin for Pets
Some dog owners have administered melatonin supplements to their pets to alleviate separation anxiety, insomnia, and/or alopecia. It is generally regarded as safe, but it is important to speak to your veterinarian before supplementing, as melatonin can cause digestive upset, elevated heart rate, reproductive disturbances, and insulin resistance in some dogs. Further, some melatonin is manufactured with xylitol, which is poisonous to canines. The appropriate melatonin dosage for dogs is entirely dependent on the individual canine’s medication sensitivity, weight, and size, and should be determined only at the discretion of a veterinarian 
Individuals with psychiatric or seizure disorders, bleeding or coagulation disorders, diabetes, and/or a history of medical transplant should be cautious regarding melatonin supplementation. This is because melatonin can counteract the functions of some hypertensive drugs (such as Nifedipine), immunosuppressants, corticosteroids, selective serotonin reuptake inhibitors, benzodiazepines, diabetes medications, anticoagulants, and anticonvulsants .
Further, melatonin and alcohol are unsafe to take in conjunction . Side effects of melatonin and alcohol consumption may include elevated heart rate, inability to concentrate, flushing, swelling in the ankles or feet, and/or fainting .
Melatonin and birth control are also contraindicated, as melatonin may interfere with the regulatory hormonal mechanisms of oral contraceptives . Pregnant or breastfeeding women should not take melatonin .
Side effects of melatonin supplementation may include headache, gastrointestinal cramps or upset, transient depression, anxiety or irritability, and/or dizziness .
Does melatonin make you gain weight?
Some individuals have also reported unwanted weight gain while taking melatonin. However, research has confirmed a potential weight gain reduction effect and an increase in insulin sensitivity in laboratory rats . Similar weight management activity has been observed with melatonin supplementation in postmenopausal women . It is likely that reported weight gain on melatonin can be contributed to other factors outside of the supplement itself.
Is melatonin addictive?
While no current studies implicate melatonin as physiologically addictive, research indicates that acute supplementation may lead to melatonin tolerance .