Dietary Supplements, Nutraceuticals, and Functional Foods

Dietary Supplements and Their Uses: Melatonin

by Dr. Charles Platkin, PhD, JD, MPH & Editorial Staff
by Dr. Charles Platkin, PhD, JD, MPH & Editorial Staff

Melatonin Brand names: Circadin, Adaflex, Ceyesto, Slenyto, Syncrodin

Description: 

Melatonin is a natural hormone produced by the body that helps regulate the sleep-wake cycle or the body’s internal clock that regulates sleep.1 Melatonin levels tend to increase in the body at night, promoting sleep, and decrease during the day to keep you awake.1

If you have trouble sleeping or have issues with jetlag, you can use a synthetic form of melatonin for short durations.1 Synthetic melatonin supplements the body’s natural melatonin, helping you fall asleep faster and stay asleep through the night.1

Melatonin is typically prescribed for individuals aged 55 and older who have short-term sleep disturbances.1 In some cases, specialists may also recommend it for children and adults dealing with long-term sleep issues.1

Melatonin supplements have demonstrated potential benefits in addressing specific conditions, including jetlag, delayed sleep-wake phase disorder, certain pediatric sleep disorders, and pre- and post-operative anxiety management.1

Origin: 

Melatonin is a remarkable molecule that has been around since the dawn of life. Initially, it likely acted as a defender against harmful free radicals, damaging scavenger molecules in the body.2 It is believed to have originated in bacteria and was present in early life forms.2 As life evolved, complex organisms emerged through a process called endosymbiosis, in which bacteria were absorbed by more complex cells, eventually giving rise to mitochondria and chloroplasts.2 These organelles have maintained the ability to produce melatonin, serving as antioxidants in animals and plants.2 

Melatonin’s role as a sleep regulator, circadian rhythm modulator, immunity enhancer, and more developed later in the evolutionary timeline, primarily through receptor-mediated actions.2 In both animals and plants, melatonin begins its journey from the amino acid tryptophan, with slightly different pathways between the two kingdoms.2 Tryptophan is an amino acid produced in plants that is used to synthesize proteins throughout the body.3 In animals, tryptophan is transformed into melatonin via a series of chemical conversions involving serotonin.2 In plants, tryptophan is converted into melatonin through a pathway that includes tryptamine and serotonin.2 Tryptophan plays diverse and essential roles in the functioning and well-being of both plants and animals.2

Current form of consumption: Melatonin is “widely available in tablet, capsule, liquid, and gummy formulations.”1 Tablets and capsules come in both long- and short-release forms.1

A standard dosage ranges from 2 mg/day to 10 mg/day, but it is recommended to begin with smaller dosages.1 Melatonin takes between 30 minutes and two hours to take effect, and it is typically consumed before bedtime.1 It is normally not recommended to take melatonin for more than 13 weeks at a time unless under the care of a medical doctor.1

It is important to keep in mind that while the Food and Drug Administration (FDA) does regulate dietary supplements, including melatonin, the regulations governing dietary supplements are less stringent than those for prescription or over-the-counter medications.1 This distinction highlights the need for consumers to exercise caution and seek professional guidance when using dietary supplements, especially for long-term or complex health concerns.1

In other areas of the world, melatonin is only available with a prescription and at lower doses.4 In the United Kingdom, prescriptions start at the 2 mg dosage level and are only recommended for consumption for a maximum of 13 weeks.4

History of use as medicine: 

In 1958, Dermatologist Aaron B. Lerner at Yale University School of Medicine first discovered melatonin in the brains of cows.5 While it was first identified in the pineal gland of the brain, it turned out to be present in various parts of vertebrates’ bodies, including the eyes and gastrointestinal tracts.5 

Melatonin earned the nickname ‘hormone of darkness’ because it is produced during the dark phase of the light-dark cycle, regardless of an organism’s habits.5 In 1994, Dr. Richard J. Wurtman, a professor of neuroscience at the Massachusetts Institute of Technology (MIT), released the first research findings that low-dose melatonin pills induced sleep in humans.6 In 1996, Interneuron Inc. secured the inaugural utility patent for melatonin’s application as a low-dose sleep aid known as Melzone.5,7 

Over the past five decades, research has unveiled the vast roles melatonin plays for various physiological functions in animals and humans, including aging, sleep, stress management, and reproduction.5

Current Uses and Scientific Literature Review: 

Melatonin is unique, functioning both as a hormone with receptor-mediated effects and as an antioxidant that does not require receptors.4 Its antioxidant capabilities, a more recent discovery, further enhance its impact on various cells throughout the body.4 In essence, melatonin serves as a conductor, harmonizing and refining the multitude of biological functions that sustain life.5 

It is important to note that melatonin supplements should be used under the guidance of a healthcare professional, especially for individuals with certain medical conditions or those taking medications.1 The appropriate dosage and timing of melatonin supplementation can vary based on individual needs and circumstances.1

Note: Before reviewing the literature, it is important to note that many peer-reviewed studies may be biased because of industry-funded research to promote product sales, and a conflict of interest is not always disclosed (see information from biologist and nutritionist Marion Nestle on sponsored research here). In this article, we have done our best not to include any industry-funded studies. As discussed in the Food as Medicine Report (on page 158, specifically), there is a need for more government funding for food as medicine initiatives. 

Sleep Regulation: Melatonin is often used as a supplement to help people with sleep disorders such as insomnia fall asleep more easily and improve the quality of their sleep.1 It can help reset the body’s circadian rhythm, or its internal clock, making it particularly useful for individuals with irregular sleep schedules.1 Melatonin rises in the evening to promote sleep and decreases in the morning to promote wakefulness.1

  • Insomnia (review): Vecchierini et al. (2021) conducted a review of 11 experiments in which patients with insomnia took melatonin for their symptoms. They concluded melatonin, when taken as a supplement, is safe and has shown benefits for regulating sleep patterns and can improve sleep quality and behavioral issues in these conditions. 
  • Circadian Rhythm Dysregulation (review): Vasey et al. (2021) found melatonin supplementation is safe for long-term usage and shows promising effects when used as a sleep aid. It is particularly effective in the short-term when sleep has been disrupted. Since melatonin supplements do not seem to lead to tolerance or damage to the body in any way, it suggests they could be taken for a long time. 
  • Sleep Disorders (review): Central disorders of hypersomnolence are characterized by excessive daytime sleepiness despite normal nocturnal sleep, with subtypes including narcolepsy, which is extreme daytime sleepiness, and hypersomnia, which is falling asleep during the day. Current treatments mainly address daytime sleepiness using over-the-counter medications which have various side effects and contraindications. However, a recent review conducted by Xie et al. (2017) suggests melatonin could be a promising option. Melatonin has shown positive effects on sleep structure in narcolepsy and can improve circadian rhythm-related sleepiness in shift workers and patients with conditions like Parkinson’s disease (PD), a brain disorder that causes unintentional movement. People with Parkinson’s disease who experience excessive sleepiness often have lower levels of melatonin. Melatonin has been associated with protecting brain cells and preventing cell death in cases of nerve damage or injury. 
  • Melatonin Regulation (review): Melatonin secretion, a key regulator of circadian rhythms, is influenced by external factors, which Xie et al. (2017) set out to explore in their review study. Electronic device use has been associated with reduced melatonin secretion, particularly in adolescents. Electric lighting can delay sleep onset, reduce sleep duration, and disrupt circadian alignment with the natural light-dark cycle. Diminished initial melatonin surges following the dim-light melatonin onset (DLMO) have been observed in delayed sleep phase disorder (DSPD) patients, potentially contributing to DSPD’s onset. These findings underscore the importance of melatonin in circadian regulation and its potential as a therapeutic target for circadian rhythm sleep disorders.
  • Parasomnias (review): Parasomnias are disruptive events occurring during sleep, manifesting as various physical activities, emotions, and perceptions, potentially leading to harm and sleep disturbances. They can cause confusion, injuries, and psychological distress, affecting both patients and their bed partners. REM sleep behavior disorder (RBD) is one such parasomnia, associated with potentially violent actions during REM sleep and often linked to neurodegenerative conditions. Clonazepam is the typical treatment for RBD, but as a drug belonging to the class benzodiazepine, it can have serious side effects including addiction and withdrawal. Per Xie et al.’s (2017) review, melatonin has emerged as an effective and safe alternative for RBD management, reducing injuries and adverse effects of the condition while improving clinical symptoms. Melatonin’s favorable safety profile and limited drug interactions make it a valuable treatment option, particularly for elderly individuals with RBD receiving multiple medications.

Antioxidant, Anti-Inflammatory, and Immune Properties: Melatonin acts as a potent antioxidant, helping to protect cells from oxidative damage caused by free radicals, which can cause a buildup of inflammation in the body.1 This antioxidant effect may have potential benefits for overall health, including reducing the risk of certain chronic diseases.1 However, more research is needed to be certain of the appropriate dosages, effectiveness, and safety of melatonin use in humans to treat the health conditions reviewed below. 

  • Cancer Therapy (review): Moslehi et al. (2022) found that melatonin exhibits low toxicity and promising efficacy for boosting immunity in cancer patients, with clinical trials showing that patients can tolerate safe melatonin doses ranging from 5 to 20 mg per kilogram of bodyweight per day. Melatonin’s immunomodulatory effects make it an intriguing candidate for managing the side effects of cancer treatments and enhancing antitumor immune responses.
  • Multiple Sclerosis (MS) Treatment (review): Researchers Munoz-Jurado et al. (2022) concluded that melatonin can increase antioxidant enzymes and reduce harmful inflammation, particularly in patients suffering from multiple sclerosis (MS), a disease of the central nervous system. Melatonin might also help maintain a healthy balance of gut bacteria, which could be beneficial for conditions like MS.
  • Anti-inflammation Overview (review): Bantounou et al. (2022) reviewed the antioxidant and anti-inflammatory effects of melatonin in the body. Generally speaking, it helps protect cells from damage caused by harmful molecules and reduces inflammation. Melatonin has been studied in animals to improve embryo development and increase the chances of successful pregnancies, thanks to its antioxidant properties. In lab studies of liver cancer, melatonin has shown promise in slowing down the growth of cancer cells and enhancing the effects of other cancer treatments, but more research is needed to confirm this effectiveness in humans. Melatonin has been found to protect against inflammation and preserve testosterone production in studies of infectious diseases affecting the testicles. During the COVID-19 pandemic, melatonin was considered a possible treatment due to its anti-inflammatory and antioxidant properties.
  • Immunity & Neuroinflammation (review): Won et al.’s (2021) review found melatonin has versatile effects on the immune system. Under normal or immunosuppressed conditions, melatonin appears to enhance immune responses by increasing the activity and responsiveness of immune cells and stimulating the production of various immunity-enhancing molecules. Additionally, melatonin has demonstrated immune-boosting effects in situations of extreme bleeding, where it restores impaired immune functions associated with blood loss and high inflammation. In contrast, in states of overactive immune responses, such as high-grade inflammation, melatonin tends to have immune-dampening effects. 
  • Antioxidant Effects (review): Ferlazzo et al. (2020) also explored the antioxidant effects of melatonin. Melatonin may be very useful in the therapeutic management of fertility disorders, osteoporosis, oxidative/inflammatory disorders, and obesity, although some meta-analyses report conflicting results. The combination of melatonin with traditional therapies could increase the efficiency of treatment for infectious disorders, cardiovascular disease, cancer, and neurodegenerative disorders, in addition to reducing long-term side effects of conventional drugs. Further investigation is needed to determine the optimal dose of melatonin supplementation in humans. 
  • Immunity and Cancer Regulation (review): Moradkhani et al. (2019) studied the impact of melatonin on immunity, specifically in cancer patients. Studies have shown a connection between melatonin deficiency, often seen in night shift workers, and an increased risk of cancer. Clinical and animal studies have demonstrated melatonin’s potential to interfere with the development and progression of cancer through various mechanisms. Melatonin also has the unique ability to induce programmed cell death (apoptosis) in cancer cells while protecting normal cells, making it a promising avenue for cancer prevention and treatment when combined with standard therapies.

Neuroprotective Effects: There is ongoing research into the potential neuroprotective effects of melatonin.1 It may have a role in protecting brain cells and reducing the risk of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease.1

  • Parkinson’s Disease (review): Hu et al. (2023) conducted a review on melatonin and its impact on patients suffering from Parkinson’s disease (PD), a brain disorder that causes unintentional movement. Some studies suggest melatonin may improve sleep disorders associated with PD by regulating the body’s internal clock and reducing inflammation. Some clinical trials show positive results in reducing symptoms like REM sleep behavior disorder in PD patients. Although melatonin has shown promise in short-term studies for PD-related sleep issues, there is a lack of long-term data and a need for more human clinical trials.
  • Alzheimer’s Disease (review): Available evidence suggests that melatonin treatment for more than 12 weeks may improve cognitive function in Alzheimer’s disease (AD), a degenerative brain disease, especially in mild cases. A review by Sumsuzzman et al. (2021) showed that daytime melatonin administration improved cognitive function in AD patients, while other measures like reaction time and memory remained unaffected. Melatonin may be a better choice than traditional hypnotics like benzodiazepines for managing circadian disruption and insomnia since it leads to less mental disruption. However, more high-quality studies with larger samples and longer durations are needed before recommending melatonin as an adjuvant therapy or an alternative to traditional hypnotics for cognitive improvement in AD.
  • Lee et al. (2019) also conducted a review of the impacts of melatonin usage for Alzheimer’s patients but found mixed evidence. Recent studies have revealed that melatonin can reduce the production of a specific protein that is associated with AD. In clinical studies, melatonin has shown potential in improving sleep duration for AD patients, but its impact on cognitive abilities remains unclear. Some studies report positive effects on cognitive function, while others have yielded inconclusive results.

Mood and Mental Health: Melatonin may have a mild antidepressant effect and could be useful in managing mood disorders.1 Some studies have suggested that it may improve symptoms of depression and anxiety.1

  • Post-Menopausal Depression (interventional): Parry et al. (2023) aimed to test whether a sleep-light intervention, which shifts the timing of melatonin rhythms, could help improve depression in women who were perimenopausal, menopausal, and postmenopausal. Participants with depression (n = 8) had disrupted melatonin rhythms compared to those without (n = 10). After advancing sleep schedules and using a morning bright light for eight weeks, melatonin rhythms advanced significantly in depressed participants and was linked to mood improvement. These initial findings suggest that adjusting melatonin rhythms through sleep-light interventions might offer a promising, non-pharmaceutical, and well-tolerated approach to treating depression in women who are perimenopausal and older.
  • Fibromyalgia (interventional): Castano et al. (2018) wanted to see how melatonin affected people with fibromyalgia, a condition that heightens sensitivity to pain and often involves mood issues. Participants (n = 97) took different doses of melatonin for 10 days. Researchers measured participants’ mood, pain, anxiety, and quality of life using various tests. Melatonin doses of 9, 12, and 15 mg per day helped improve mood, reduced pain, and lowered cortisol levels. Anxiety levels got better with the 12 mg dose, and pain improved with the 9 mg dose. Quality of life also improved with the 9 mg dose. Melatonin seemed to help people with fibromyalgia feel better overall.

Potential Side Effects for Adults:

A 2015 review revealed that numerous short-term studies involving adults, surgical patients, and critically ill individuals taking melatonin supplements reported only mild adverse effects.1 These mild side effects noted in the studies included:

  • Headache
  • Dizziness
  • Nausea
  • Sleepiness

The potential long-term side effects of melatonin usage remain uncertain.1

It is important to avoid drinking alcohol or smoking when taking melatonin, as it can reduce its effectiveness.1 If you are using melatonin as a sleep aid, avoid taking any herbal remedies that may also affect your sleep, as this can make you excessively drowsy.1

Potential Side Effects for Children: 

Melatonin supplements at typical doses seem to be generally safe for short-term usage in most children. However, the research on melatonin use in children is limited, and information regarding its long-term effects remains scarce.1 Given that melatonin is a hormone, there is a potential that melatonin supplements could influence hormonal development, impacting puberty, menstrual cycles, and the secretion of the hormone prolactin. However, these effects are not definitively understood.1

Reported side effects of melatonin supplements in children typically have been mild and may include:

  • Drowsiness
  • Increased nighttime bedwetting or urination
  • Headache
  • Dizziness
  • Agitation

Potential Negative Effects:

Just like with any dietary supplement, individuals who are currently taking medications should seek advice from their healthcare providers before incorporating melatonin into their routine.1 This is particularly crucial for individuals with epilepsy and those on blood thinners, as they require medical supervision when considering melatonin supplements.1 

There is a possibility of experiencing allergic reactions when using melatonin supplements. Also, there is a notable lack of comprehensive research on the safety of melatonin use in pregnant or breastfeeding women, making it important for this group to exercise caution.1 According to the 2015 guidelines from the American Academy of Sleep Medicine, melatonin use is not recommended for individuals with dementia.1 This is because melatonin might remain active in older individuals for a longer duration than in younger people and potentially lead to daytime drowsiness.1

Cooking: 

Cooking with melatonin is not recommended.8 While, in the past, it has been baked into brownies or added to beverages to aid in relaxation, the doses necessary for consumption in these forms are normally too high to be consumed safely. Melatonin is only recommended in its supplement form.8 

Learn more:

News articles: 

Peer-reviewed articles: 

Sleep Regulation:

Circadian Rhythm:

Antioxidant Properties:

Immunity:

Jet Lag & Shift Work:

Neuroprotective Effects:

Mood and Mental Health:

Books: 

Podcasts:

Documentaries:

Social Media: 

YouTube:

Instagram:

TikTok:

Search Terms:

References:

1. Potential Uses and Benefits of Melatonin. Accessed September 21, 2023. https://www.poison.org/articles/melatonin

2. Melatonin: What You Need To Know. NCCIH. Accessed September 21, 2023. https://www.nccih.nih.gov/health/melatonin-what-you-need-to-know

3. Chowdhury I, Sengupta A, Maitra SK. Melatonin: fifty years of scientific journey from the discovery in bovine pineal gland to delineation of functions in human. Indian J Biochem Biophys. 2008;45(5):289-304. https://www.researchgate.net/publication/23650746_Melatonin_Fifty_Years_of_Scientific_Journey_from_the_Discovery_in_Bovine_Pineal_Gland_to_Delineation_of_Functions_in_Human

4. Melatonin: a hormone used for sleep problems. nhs.uk. Published February 23, 2023. Accessed September 18, 2023. https://www.nhs.uk/medicines/melatonin/

5. Zhao D, Yu Y, Shen Y, et al. Melatonin Synthesis and Function: Evolutionary History in Animals and Plants. Frontiers in Endocrinology. 2019;10. Accessed September 21, 2023. https://www.frontiersin.org/articles/10.3389/fendo.2019.002496. Analysis, Nutrition, and Health Benefits of Tryptophan – PMC. Accessed September 21, 2023. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158605/

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