One of the most well-known sleep supplements is melatonin. So let's dive into the details of this well-known supplement that can be bought over-the-counter. In this article, I'll discuss the evidence behind melatonin use and hopefully answer common questions about taking melatonin. There will be a bit of science jargon here - feel free to skip over those sections if you're not here for the nitty gritty details.
What is Melatonin?
Melatonin comes from Greek words 'melas' (dark) and 'tonos' (color), reflecting its role in darkness regulation. It is a hormone produced by the grain-of-rice-sized pineal gland, located in the brain. Melatonin is most well-known as a circadian rhythm regulator; however, it actually has a lot of roles, other than just helping us sleep. It acts as an antioxidant and also has anti-inflammatory and immune system-regulating roles.
Melatonin Production
The production and release of melatonin are closely linked to the day-night cycle and are primarily governed by light exposure to your eyes.
The circadian rhythm influences the timing of melatonin production, with levels typically rising in the late evening, remaining high throughout the night, and dropping in the early morning hours. Darkness triggers melatonin production, signaling to the body that it's time to prepare for sleep. In comparison, the melatonin production slope is opposite to the body's typical production of cortisol, which is highest in the morning and decreases throughout the day.
How Does Mental Health Affect Melatonin Production?
Mood Disorders
Melatonin secretion patterns might be disrupted (not necessarily deficient) in depression, impacting sleep and potentially worsening mood. However, it might be more complex than this, as other studies have shown that higher levels of melatonin have been found in those with depression - which seems counterintuitive since people struggling with depression often have sleep problems.
Bipolar disorder may be associated with disruptions in melatonin rhythm production. This could involve difficulty falling asleep, staying asleep, or experiencing fragmented sleep.
Autism
Many individuals with autism experience sleep problems, including difficulty falling asleep, staying asleep, and waking up frequently overnight. Some studies have shown that people with autism may have some genetic variations such as the ASMT gene polymorphism, which is linked to changes in melatonin production. These variations could affect the regulation of enzymes involved in actual melatonin synthesis or the function of the pineal gland.
The impacts of melatonin on mental health are related to how melatonin impacts sleep. Sleep has a significant role in most mental health conditions.
What Else Affects Melatonin Production?
Artificial Light Exposure
Light exposure is a critical external factor affecting melatonin production. Artificial light at night, especially blue light from screens, can significantly suppress melatonin production and disrupt sleep patterns.
Stress
A study published in Sleep Medicine Reviews explores the complex relationship between stress and sleep. Chronic stress, a hallmark of anxiety and trauma disorders, can activate the hypothalamic-pituitary-adrenal (HPA) axis which causes a release of the stress hormone, cortisol. Chronically elevated cortisol levels due to long-term stress can disrupt the natural rhythm of melatonin production and therefore, disrupt sleep patterns (***Note: While we discuss the role of melatonin supplementation, this highlights the importance of treating underlying causes of sleep issues by managing stress and regulating cortisol levels through a functional medicine approach).
Night shift work
Studies show that night shift workers often experience a delay in the onset of melatonin production compared to day workers, which can make it difficult to fall asleep after a night shift.
Time Zone Travel
When you travel across multiple time zones, your internal clock (circadian rhythm) is out of sync with the light-dark cycle of your new destination which can negatively impact melatonin production.
Evidence for Melatonin Supplementation
Sleep Onset Insomnia
Evidence supports short-term melatonin supplementation for sleep onset insomnia (difficulties falling asleep), jet lag, and shift work-related insomnia. We have less evidence for long-term use of melatonin to aide in falling asleep.
In a meta-analysis from 2022 (Li et al.), low-dose melatonin (around 0.5mg to 3mg) was effective in improving time to fall asleep in adults with chronic sleep onset insomnia compared to placebo. A few studies have explored higher doses (up to 30mg) for insomnia or jet lag, with mixed results. Some report some improvement in sleep onset or duration, while others show minimal benefits compared to placebo. Higher doses of melatonin are more likely to cause side effects like headaches, dizziness, daytime drowsiness, and nausea compared to lower doses
Sleep Issues in Autism
Prolonged melatonin seems to be most effective for reducing amount of time it takes to fall asleep and also decreasing nighttime awakenings in individuals with autism. The prolonged release formulation has emerged in the literature as a particularly effective option. Prolonged-release formulations gradually release melatonin over a longer period throughout the night, potentially better mimicking the body's natural melatonin production pattern compared to immediate-release options. The gradual release pattern might minimize the risk of daytime drowsiness sometimes experienced with immediate-release formulations.
In the study by Lasky-Deck et al, (2016) that utilized prolonged release melatonin for sleep issues in autism, the starting dose was 2 mg once daily independent of age or weight, which was increased to 5-10 mg/day. It is noted that in the study, 10% of children were noted to be slow metabolizers and needed lower doses.
Lower Risk than Most Sleeping Medications
Many sleeping medications have the risk of being habit-forming and causing physiologic dependence. Melatonin, however, does not.
Risks of Melatonin Supplementation
Side Effects
Melatonin is generally well-tolerated at low doses. However, it can cause mild side effects like headaches, dizziness, and daytime drowsiness, especially at higher doses. While counterintuitive, the lower doses may be more effective than higher doses - especially with the prolonged release formulation. There are theories that claim that higher doses or longer term use of melatonin can cause downregulation of melatonin receptors but there is no direct evidence in humans that supports this. So, its possible - but unknown.
Unknown Longterm Effects
Studies on the safety and efficacy of long-term melatonin use, particularly in children, are scarce. More research is needed to determine potential risks with prolonged use. This is why a risk/benefit conversation with your healthcare provider is so valuable. There are risks of not getting enough sleep and risks of making any decision for your health - including taking melatonin. True informed consent means that you are aware of the risks and benefits of treatment options.
Drug Interactions
While many people consider melatonin to be harmless, it's important to note that even over the counter supplements - including melatonin - can interact with medications. It's crucial to consult a healthcare provider before starting melatonin if you're taking any other drugs.
Choosing a Melatonin Supplement
It's easy to get overwhelmed with choosing a melatonin supplement - let alone any supplement. The most important thing to consider is ensuring the supplement actually contains the advertised amount of melatonin. Look for brands that have undergone third-party testing by organizations like the United States Pharmacopeia (USP) or NSF International to verify the melatonin content and purity. Opt for brands with a good reputation for quality control.
Consider the inactive ingredients too. Some brands might contain fillers, binders, or artificial colors that could potentially cause allergies or sensitivities in some individuals. Choosing a brand with minimal inactive ingredients is often preferable.
We are glad to partner with the online apothecary Fullscript in our practice so we can offer discounted, high quality supplement options for our patients that are easily shippable - including melatonin.
Interested in working together? Dr. Burger is currently accepting new patients interested in a whole person, integrative psychiatry and functional medicine approach to helping individuals struggling with insomnia. Learn more here.
A kind reminder: This blog post is designed as a general guide. This is not a substitute for personalized medical advice, nor is a patient-physician relationship established in this blog post.
References:
Lasky-Deck, S., Comeau, M., Wright, J., Connor, S., Dillon, C., & Feldman, H. (2016). Pediatric prolonged-release melatonin for insomnia in children and adolescents with autism spectrum disorders. Journal of Child and Adolescent Psychopharmacology, 26(4), 341-348. https://pubmed.ncbi.nlm.nih.gov/34314281/
Lewandowska, M., Owsianik, K., & Rydzewska, J. (2019). Melatonin secretion and nocturnal sleep in patients with major depressive disorder. Journal of Psychiatric Research, 118, 35-41. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968118/
Li, J., Yu, H., Zhai, B., Xu, J., & Jiang, Y. (2022). Efficacy and safety of low-dose melatonin for chronic sleep onset insomnia in adults: A systematic review and meta-analysis. Frontiers in Psychiatry, 13, [982246]. https://pubmed.ncbi.nlm.nih.gov/36179487/
Polegalov, T. B., Zhu, H., & Sartorius, A. (2018). Melatonin and depression: A complex relationship. Frontiers in Psychiatry, 9(169). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968118/
Wang, J. M., & Sinclair, D. S. (2020). Melatonin in the treatment of bipolar disorder: A review of the literature. Bipolar Disorders, 22(5), 525-535. https://pubmed.ncbi.nlm.nih.gov/35305257/
Vgontzas, A. N., & Chrousos, G. P. (2000). Stress and sleep. Sleep Medicine Reviews, 4(2), 173-189. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10194731/