Disclaimer: Nothing stated in this post should be construed as an alternative to diagnosis and treatment by a medical professional. I am not qualified to provide medical advice.
If you’re anything like me, you’ve heard of the near miraculous wonders of melatonin supplementation. You may have also heard some of the not so great effects. So, let’s get down to the truth with our dear friend, science.
Use the Navigation links below to jump to sections of interest or read through for all the knowledge.
What is Melatonin and What Does It Do?
Melatonin (5-methoxy-N-acetyltryptamine) is a fat-soluble hormone that confers widespread health benefits and is produced in the pineal gland of the brain as well as by the retina of the eye and by the gastrointestinal tract. Production of endogenous (meaning made by the body) melatonin is triggered by darkness, and it typically peaks between 11 PM and 3 AM. Our bodies’ ability to produce melatonin decreases with age.
Melatonin “plays the role of a universal endogenous synchronizer” which, in addition to helping to maintain the wake-sleep cycle, also influences hemostasis, glucose homeostasis, phosphocalcic metabolism, blood pressure, and antioxidant defenses. In other words, melatonin stabilizes the circadian rhythms in the body, thereby impacting the body’s ability to coagulate blood, maintain normal blood glucose levels and blood pressure, metabolize phosphate and calcium for functions such as bone mineralization, and defend against the damage caused by free radicals.
Exogenous (meaning man-made) melatonin supplements can be made one of two ways. Either from the pineal glands of animals, which can be dangerous due to the potential for viral contamination, or as a synthetic product that is manufactured in a lab. Most commercial supplements are synthetic. Plant-based supplements are in the pipeline and melatonin naturally exists in the foods we eat as forms of it are produced by living organisms from animals to bacteria to algae to plants and beyond.
Melatonin is now being studied for other applications such as fertility support, reduction of the symptoms of endometriosis and PCOS, treatment of certain cancers, treatment of osteoporosis treatment as it may increase bone density, immune support, pain management, improvement in breathing for people with COPD, treatment for Ebola, protection against neurodegenerative diseases, prevention of Type 2 diabetes, and more. While exogenous melatonin appears to be a promising component of treatments across a variety of conditions, little is known about its dose-response relationships.
Back in 1994, Dr. Richard Wurtman, professor of neuroscience at MIT, led a team that confirmed where melatonin was produced in the body and how it functioned. His team discovered that a dose of 0.3 milligrams of melatonin helped older adults fall asleep faster and get back to sleep if they woke up in the night. However, researchers also discovered that commercial melatonin contained 10 times the effective dose, which, when taken regularly, ultimately overwhelms melatonin receptors in the brain, causing them to become unresponsive. At the time, he warned that “People should not self-medicate with melatonin.”
Studies to date have utilized pharmaceutical grade melatonin that is strictly regulated and certified to contain the ingredients in the appropriate proportions as labeled. Under these controlled conditions, substantive support exists for the presence of a plateau effect in adults with doses higher than 0.3 milligrams; the maximum effect being achieved at low doses with decreasing effectiveness in doses exceeding 1 milligram. In addition, there is some evidence that exogenous melatonin requires dosage over the course of a few days to achieve detectible effectiveness, and that it may increase in effectiveness over the course of time until the benefits plateau. The half-life of melatonin is less than one hour, which means that its usefulness from a given dose is short-lived. Some pharmaceutical grade melatonin medications have extended-release formulations to help improve the usefulness of the drug. It is unclear whether or not single doses of melatonin are effective.
High doses of exogenous melatonin have been demonstrated to desensitize receptors in the brain, thereby eventually making supplementation ineffective. However, without clear guidelines on appropriate dosing, the level at which overdose occurs remains unknown. Unfortunately, a 2017 analysis out of Canada found egregious mislabeling of melatonin supplements with counts varying from −83% to +478% of labeled melatonin. Chewable tablets suffered from the highest variability with one tablet containing nearly 9 milligrams of melatonin when it was labeled as 1.5 milligrams. Capsules suffered the greatest variability among lots. And, liquids had the greatest levels of stability, though they too were highly inconsistent. Oral and sublingual tablets with few ingredients proved the least variable of all the options. However, many of the supplements also contained impurities, including serotonin which has known effects and should not be taken by accident.
There is no known safe dose or dosing frequency for children.
In 2017, a task force from the American Academy of Sleep Medicine conducted a systematic review of the available literature to identify randomized controlled trials. Based on the evidence, this task force established recommendations for use by medical professionals. The task force listed 14 types of sleep aids and noted whether they were recommended for use or not. They advised clinicians not to use melatonin as a treatment for sleep onset and sleep maintenance insomnia.
Melatonin supplements may be contraindicated if a person has:
- An allergy to the ingredients
- High or Low Blood Pressure
- Epilepsy or Other Seizure Disorder
- Conditions requiring Immunosuppressants
- An Autoimmune Condition
Or is using:
- Blood Thinners
- Sedatives or Tranquilizers
Also, it is unknown whether melatonin supplements are safe during pregnancy or breastfeeding. High doses of melatonin may present fertility problems by affecting ovulation.
Possible Safety Issues
In 2015, Dr. David Kennaway conducted a review of the evidence for melatonin use in children, which was published in the Australian Journal of Paediatrics and Child Health. He determined that melatonin can produce “small advances in the timing of sleep onset” in both adults and children, but that there have “no appropriate studies to show that melatonin is safe in the long term for children or adults.” Use in children is always an off-label application of this hormone. He noted that, as a hormone, melatonin directly impacts the endocrine system and that long-term use may result in future “endocrine or other abnormalities.” He recommended that melatonin be prescribed only following a “biochemical diagnosis of an underlying sleep timing abnormality and after full disclosure to the carers of information about the known actions of melatonin on reproductive and other systems.”
In the United Stated, melatonin is considered a supplement. Therefore, it is generally unregulated by the Food and Drug Administration (FDA) and consumers have no guarantees regarding the safety of the commercial melatonin they purchase.
When I began to seek out studies, I discovered thousands of papers that mentioned the term “melatonin.” In order to refine the list, I began by excluding studies published before 2009 and including only studies conducted on humans and written in/translated into English. From this list, I sorted by relevance and chose 175 to skim for abstracts. Then, I selected 80 to read in full, which resulted in a final resource list of 23 papers having targeted relevance. These studies involve research in countries around the world. I have grouped them by year for ease in assessing the progression of the research and recommendations.
The effect of prolonged-release melatonin on sleep measures and psychomotor performance in elderly patients with insomnia
OBJECTIVE: To investigate the effects of prolonged-release melatonin 2 mg (PRM) on sleep and subsequent daytime psychomotor performance in patients aged 55 years and older with primary insomnia.
FINDINGS: By the end of the double-blind treatment, the PRM group had significantly shorter sleep onset latency and scored significantly better on a psychomotor performance test than the placebo group.
Melatonin for disordered sleep in individuals with autism spectrum disorders: systematic review and discussion
OBJECTIVE: To provide a systematic review of efficacy and safety of exogenous melatonin for treating disordered sleep in individuals with ASD.
FINDINGS: The literature supports the existence of a beneficial effect of melatonin on sleep in individuals with ASD, with only few and minor side effects. However, these conclusions cannot yet be regarded as evidence-based. Randomized controlled trials and long-term follow-up data are still lacking.
Prolonged release melatonin in the treatment of primary insomnia: evaluation of the age cut-off for short- and long-term response
OBJECTIVE: To evaluate the age cut-off from a previous study for response to PRM and the long-term maintenance of efficacy and safety by looking at the total cohort (age 18-80).
FINDINGS: At 3 weeks, significant differences in favor of PRM vs placebo were found for the 55-80 year population but not the 18-80 year cut-off which included younger patients. Other variables improved significantly with PRM in the 18-80 year population more so than in the 55-80 year age group. No withdrawal symptoms or rebound insomnia were detected.
Melatonin for sleep in children with autism: a controlled trial examining dose, tolerability, and outcomes
OBJECTIVE: To assess dose-response, tolerability, safety, feasibility of collecting actigraphy data, and ability of outcome measures to detect change during 14-week intervention on children aged 3-10 years with a clinical diagnosis of an autism spectrum disorder who were free of psychotropic medications and whose parents reported sleep onset delay of 30 minutes or longer on three or more nights per week.
FINDINGS: Researchers documented an improvement in sleep latency with melatonin treatment. Because the study criteria were designed to enroll children with sleep-onset delay, they could not definitively comment on the effects of melatonin on sleep duration or night wakings.
Optimal dosages for melatonin supplementation therapy in older adults: a systematic review of current literature
OBJECTIVE: To define the optimal dosage of exogenous melatonin administration in disorders related to altered melatonin levels in older adults aged 55 years and above by determining the dose-response effect of exogenous administered melatonin on endogenous levels.
FINDINGS: Based on a systematic review of 16 articles from 1980 to 2013, nine of which were randomized controlled trials, the best applicable dosage for melatonin for older adults still cannot be adequately determined, as endogenous melatonin levels are subject to altered pharmacokinetics and -dynamics. This causes the risk of prolonged and elevated endogenous melatonin levels after exogenous melatonin administration in older adults. The researchers advise the use of the lowest possible oral dose of immediate-release formulation melatonin to best mimic the normal physiological circadian rhythm of melatonin and to avoid prolonged, supra-physiological blood levels.
The effectiveness of melatonin for promoting healthy sleep: a rapid evidence assessment of the literature
OBJECTIVE: To critically assess the available peer-reviewed literature on the use of melatonin in military service members and in healthy subjects to determine whether melatonin might be useful in military populations.
FINDINGS: The use of melatonin by healthy adults shows promise to prevent phase shifts from jet lag and improvements in insomnia, but to a limited extent. For the initiation of sleep and sleep efficacy, the data cannot yet confirm a positive benefit.
Melatonin in children with autism spectrum disorders: endogenous and pharmacokinetic profiles in relation to sleep
OBJECTIVE: To describe overnight endogenous and PK melatonin profiles in children aged 3-8 years with ASD participating in open-label trial of melatonin for sleep onset insomnia.
FINDINGS: In children with ASD and insomnia responsive to treatment with supplemental melatonin, evidence exists for normal endogenous melatonin profiles. Furthermore, despite a relatively short duration of action of supplemental melatonin, night wakings improved in most children with treatment. This raises the possibility that supplemental melatonin may be influencing sleep onset delay and night wakings by mechnanisms other than simply replacing melatonin.
The effect of melatonin treatment on postural stability, muscle strength, and quality of life and sleep in postmenopausal women: a randomized controlled trial
OBJECTIVE: To document the safety of melatonin in postmenopausal women given evidence from previous studies that suggests a protective role of melatonin against osteoporosis through an increase of bone mineral density.
FINDINGS: Melatonin in a daily dose of 1 or 3 mg is safe to use in postmenopausal women with osteopenia. There is no long term hangover effect causing a reduction in balance- and muscle function or quality of life. In women with poor quality of sleep, small doses of melatonin trended towards improving quality of sleep.
Current role of melatonin in pediatric neurology: clinical recommendations
OBJECTIVE: To establish a consensus on the roles of melatonin in children and on treatment guidelines at a conference in Rome in 2014.
FINDINGS: So far, the best evidence for the indication of melatonin treatment in children is for insomnia caused by circadian rhythm sleep disorders. Because insomnia due to other situations and disorders, including bad sleep hygeine, ADHD/ADD, personality disorders and depression, can mimic insomnia caused by circadian rhythm sleep disorders, the diagnosis should only be made after careful clinical assessment and possibly measuring dim light melatonin onset (DLMO). Melatonin can be effective not only for primary sleep disorders but also for sleep disorders associated with several neurological conditions. Controlled studies on melatonin for sleep disturbance in children are needed since melatonin is very commonly prescribed in infants, children and adolescents, and there is a lack of certainty about dosing regimens. The dose of melatonin should be individualized according to multiple factors, including not only the severity and type of sleep problem, but also the associated neurological pathology.
Melatonin Treatment in Children with Developmental Disabilities
OBJECTIVE: To provide a succinct summary to help inform clinical and research practices for children with developmental disabilities (i.e. children with unspecified developmental delays or cognitive impairments and specific disorders/syndromes including ASD, Smith-Magenis syndrom, Angleman’s syndrom, fragile X syndrom, Down syndrom, and Rett syndrome).
FINDINGS: Following a review of a number of studies and a meta-analysis by Braam and associates, researchers determined that melatonin treatment yields beneficial effects with minimal side effects. However, melatonin is not approved by the US Food an Drug Administration and no drug is approved for use in pediatric insomnia (as of the time of this study).
Potential safety issues in the use of the hormone melatonin in paediatrics
OBJECTIVE: To provide information on the documented actions and properties of melatonin outside its ability to alter sleep timing that have been widely ignored but which raise questions about the safety of its use in infants and adolescents.
FINDINGS: Melatonin is increasingly being prescribed off lable for children and adolescents for difficulty in initiating and maintaining sleep. There is extensive evidence from animal and human studies that melatonin acts on multiple physiological systems, including the reproductive, cardiovascula, immune, and metabolic systems. Long-term safety studies on children and adults are lacking. Prescription of melatonin to any child whether severely physically or neurologically disabled or developing normally should be considered only after the biochemical diagnosis of an underlying sleep timing abnormality and after full disclosure to the carers of information about the known actions of melatonin on reproductive and other systems and the disclosure that there is a lack of appropriate studies conducted on children. Should endocrine or other abnormalities appear in the future in children previously treated with melatonin, it will not be tenable to argue that were were surprised.
The Safety of Melatonin in Humans
OBJECTIVE: To present and evaluate the literature concerning the possible adverse effects and safety of exogenous melatonin in humans and provide recommendations concerning the possible risks of melatonin use in specific patient groups.
FINDINGS: A substantial number of both animal and human studies document that short-term use of melatonin is safe, even in extreme doses. No studies indicate that exogenous melatonin possesses any serious adverse effects. Also, randomized clinical studies indicate that long-term administration only induces mild adverse effects comparable to placebo treatment. Due to a lack of human studies, pregnant and breastfeeding women should not take exogenous melatonin. Also, long-term safety of melatonin in children and adolescents requires further investigation.
Melatonin Supplementation for Children With Atopic Dermatitis and Sleep Disturbance: A Randomized Clinical Trial
OBJECTIVE: To evaluate the effectiveness of melatonin supplementation for improving the sleep disturbance and severity of disease in children with AD.
FINDINGS: Sleep-onset latency shortened by 21.4 minutes after melatonin treatment compared with after placebo. Melatonin supplementation is a safe and effective way to improve the sleep-onset latency and disease severity in children with AD.
Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders
OBJECTIVE: To assess the evidence base for the therapeutic effects of exogenous melatonin in treating primary sleep disorders.
FINDINGS: Results from the meta analysis showed the most convincing evidence for exogenous melatonin use was in reducing sleep onset latency in primary insomnia, delayed sleep phase syndrome, and regulating the sleep-wake patterns in blind patients compared with placebo.
Melatonin Natural Health Products and Supplements: Presence of Serotonin and Significant Variability of Melatonin Content
OBJECTIVE: To quantify melatonin in 30 Canadian commercial supplements, comprising different brands and forms and screen supplements for the presence of serotonin.
FINDINGS: Melatonin content was found to range from -83% to +478% of the labeled content. Additionally, lot-to-lot variable within a particular product varied by as much as 465%. This variability did not appear to be correlated with manufacturer or product type. Furthermore, serotonin was identified in eight of the supplements at levels of 1 mg to 75 mg. Melatonin content did not meet label within a 10% margin of the label claim in more than 71% of supplements and an additional 26% were found to contain serotonin. It is important that clinicians and patients have confidence in the quality of supplements used in the treatment of sleep disorders. To address this, manufacturers require increased controls to ensure melatonin supplements meet both their label claim, and also are free from contaminants, such as serotonin.
The use and misuse of exogenous melatonin in the treatment of sleep disorders
OBJECTIVE: To explore the evidence for using exogenous melatonin in the treatment of sleep disorders, both primary and secondary, in children and adults.
FINDINGS: There is evidence for the efficacy of melatonin in the management of insomnia and some intrinsic disorders of circadian rhythm in adults and children as well as in reducing sleep onset latency in jet-lag and shift work disorder in adults. Melatonin is used routinely in the treatment of rapid-eye movement sleep-behaviour disorder despite limited trial evidence. Increasingly, dual melatonin receptor agonists are being trialed in a variety of sleep disorders. Long-term adverse effects are currently not fully identified.
Sleep disorders during childhood: a practical review
OBJECTIVE: To discuss the normal sleep
development and needs in children, and we will provide an
overview of sleep disorders, based on the 3rd edition of the
International Classification of Sleep Disorders [ICSD-3].
FINDINGS: Melatonin is an effective, safe, and well-tolerated agent, particularly in cases of sleep-initiation insomnia caused by circadian factors. Several placebo-controlled studies of melatonin in adults and children (in some studies, as young as 3 years of age) showed that melatonin administered at bedtime reduces sleep-onset latency time and increases total sleep time.
An update on pharmacotherapy of autism spectrum disorder in children and adolescents
OBJECTIVE: To review pharmacological treatment options for children and adolescents with ASD, with emphasis on recently published studies since our previous published update. We focus on randomized double-blind placebo controlled (RDBPC) trials, with at least 10 subjects. We also discuss CAM treatment options used in children
FINDINGS: In addition to its effect on sleep, a few RDBPC trials have shown that melatonin can improve communication, rigidity, and anxiety in children with ASD.
Pharmacological and non-pharmacological interventions for non-respiratory sleep disturbance in children with neurodisabilities: a systematic review
OBJECTIVE: To assess the clinical effectiveness and safety of NHS-relevant pharmacological and non-pharmacological interventions to manage sleep disturbance in children and young people with NDs, who have non-respiratory sleep disturbance.
FINDINGS: It was not possible to draw conclusions about the effectiveness of non-pharmacological interventions for managing sleep disturbance, and although there was some benefit with melatonin the degree of benefit is uncertain. There is some evidence of benefit for melatonin compared with placebo, but the degree of benefit is uncertain. There are various types of non-pharmacological interventions for managing sleep disturbance; however, clinical and methodological heterogeneity, few RCTs, a lack of standardised outcome measures and risk of bias means that it is not possible to draw conclusions with regard to their effectiveness. Future work should include the development of a core outcome, further evaluation of the clinical effectiveness and cost-effectiveness of pharmacological and non-pharmacological interventions and research exploring the prevention of, and methods for identifying, sleep disturbance. Research mapping current practices and exploring families’ understanding of sleep disturbance and their experiences of obtaining help may facilitate service provision development.
Could long-term administration of melatonin to prepubertal children affect timing of puberty? A clinician’s perspective (2018)
OBJECTIVE: To summarize
some of the current knowledge about the potential effects of exogenous melatonin on puberty
FINDINGS: This review suggests that the role of melatonin in sexual maturation and the timing of puberty is understudied in humans. The three human studies that have examined the question have done so as an ancillary research question in small samples of children and youth, some of whom had neurodevelopmental disorders. This limits the generalizability to the general population and is insufficient evidence to draw conclusions for patients with mental health and neurological disorders. Further experimental studies on the impact of melatonin on puberty, notably in non-seasonal mammals, and advances in the research about the intermediary processes between melatonin and kisspeptin activation, could ultimately inform us about the potential influence of exogenous melatonin on puberty.
The effects of melatonin administration on disease severity and sleep quality in children with atopic dermatitis: A randomized, double-blinded, placebo-controlled trial
OBJECTIVE: To determine the effects of melatonin administration on disease severity and sleep quality in children diagnosed with atopic dermatitis (AD).
FINDINGS: Following 6 weeks of intervention, melatonin supplementation significantly improved SCORAD index, serum total IgE levels, and CSHQ scores. Though melatonin had no significant impact on pruritus scores, high sensitivity C-reactive protein, sleep-onset latency, total sleep time, weight and BMI compared with placebo. Overall, melatonin supplementation had beneficial effects on disease severity, serum total IgE levels and CSHQ among children diagnosed with AD.
Exogenous melatonin as a treatment for secondary sleep disorders: A systematic review and meta-analysis
OBJECTIVE: To determine the efficacy of exogenous melatonin versus placebo in managing secondary sleep disorders.
FINDINGS: Meta-analysis of the data from a series of studies with small sample size demonstrates that exogenous melatonin improves the sleep quality of secondary sleep disorders. Based on the current advantages of melatonin in the management of secondary sleep disorders, it is hoped that there will be a tremendous growth in the use of melatonin application worldwide. Besides, little evidence is available regarding the adverse effects of long-term use of melatonin. Clinicians should be alert to these shortcomings but also aware of the potential role of melatonin in clinical psychiatry and sleep medicine.
Advances of Melatonin-Based Therapies in the Treatment of Disturbed Sleep and Mood
OBJECTIVE: To review the role of melatonin in the circadian regulation of sleep and mood and the phase-shifting and sleep-promoting properties of exogenous melatonin and melatonin agonists and outline how melatonin and melatonin agonists might be used for treatment of various sleep and mood disorders.
FINDINGS: The phase-shifting and sleep-promoting effects of melatonin plus additional effects of melatonin agonists on melatonin and serotonin receptors have shown promise for novel treatments for a variety of circadian, sleep and mood disorders. Importantly, the main advantage melatonin and its agonists offer over traditional sleep and depression treatments is that they assist to restore circadian function which is often misaligned in these disorders and which is increasingly thought to be a causal mechanism and part of the aetiology of sleep and mood disorders. Treatments that fail to address the misaligned circadian system present in sleep and mood disorders may not fully address the underlying causes, and for this reason, further investigation on the potential for melatonin-based treatments should be undertaken.
Assessment of the Evidence
Endogenous melatonin provides widespread health benefits for the human body across many functional systems. Exogenous melatonin is strongly evidenced as an effective sleep aid for sleep onset (meaning, falling asleep) and less strongly for night wakings and other other sleep-related applications in adults aged 55 and older.
However, the literature is glaringly lacking in randomized, controlled trials as well as research on younger adults, teenagers, adolescents, children, and infants. Existing studies utilize small subject pools and short- to medium-term time frames for research, most stopping short at 3 months and few-to-none lasting more than one year. There is no evidence yet that consistent long-term use is safe for any age group. Dosing remains a challenge and a standard dosing table does not yet exist, although it has been long established that overdoses cause receptors in the brain to become unresponsive and supplementation to be rendered useless. Given the lack of information about dosing, it is impossible to determine what amount constitutes an overdose without investigative blood work. Melatonin supplements are almost entirely unregulated in the United States, so high doses are regularly consumed. While high doses don’t appear to have extreme deleterious effects on humans, the fatal dose is yet unknown. Future studies are needed to ameliorate concerns about safety, dosage, and pediatric use.
Promoting Better Sleep
While I cannot make any formal recommendations to you about whether or not to give your child melatonin, I can suggest some solutions to help with sleep outside of melatonin supplements.
- Eating lots of fresh fruits, vegetables, whole grains, and low fat protein sources provides plenty of tryptophan as well as group B vitamins, minerals, and unrefined carbohydrates, all of which supports healthy sleep. Reach for things like salmon, poultry, eggs, spinach, seeds, milk, soy products, and nuts to get a good dose of sleep-promoting nutrients. (Source and Source)
- Tart Montmorency cherries contain high levels of phytochemicals including melatonin. Cherry juice is a natural source of plant-based exogenous melatonin and may help support good sleep. (Source)
- Exercise in the mornings can improve the quality of nighttime sleep by “increasing parasympathetic nerve activity.” However, high-intensity exercise in the evening should be avoided. Getting your child out for some fresh air every morning may make your bedtime routine a breeze. (Source)
- Common wisdom says to help your child avoid blue light LED sources like smartphones, tablets, and TVs near bedtime as this type of light may suppress endogenous melatonin. (Source) However, there is also evidence that such recommendations may be misguided. (Source) Use your best judgment as you watch how nighttime blue light stimulation impacts your child.
- In one of the studies referenced in this Guide, a young girl did not respond to melatonin treatments but was later diagnosed with bipolar disorder, medicated with risperidone, and subsequently experienced improved sleep. If your child is really struggling, it may be worthwhile to seek out age-appropriate therapy to rule out other treatable sources of difficulty. (Source)
The Bottom Line
Do melatonin supplements help your child? Unless you’re using pharmaceutical grade supplements under the strict care of a physician, my best answer is maybe. But it’s hard to know what your child really needs in the way of a dose without extensive blood work . The placebo effect is also in play to an extent. If you and your child believe the supplement works, it’ll probably work even better than the actual physiological impact, if there is one to begin with.
Will melatonin supplements seriously harm your child? Probably not, but there’s no guarantee and there are other effective options that don’t involve using unregulated supplements with potentially harmful impurities.
If you discover any errors in my work, please contact me at peacefulmom(at)peaceigive.com.