Does it prevent our body from making melatonin on its own? Are there withdrawal effects when you stop taking it? These are all great questions we are asked often. To answer them, let’s review what melatonin is, what it is used for, and what the research is saying.
What is melatonin?
Melatonin is a hormone that is produced in response to darkness by the pineal gland. It was once thought that its sole purpose was to regulate our internal circadian rhythm (our internal 24 hour clock) and aid in sleep[1]. However, we are now discovering it has roles far beyond this. We now know melatonin has anti-oxidant, anti-ageing, immunomodulating and anticancer properties as well[2]. Research suggests that melatonin may also play roles in our levels of human growth hormone[3] [4], eye health [5] [6], Gastroesophageal reflux disease (heartburn) treatment [7] [8] [9], anxiety prevention[10] [11], and the treatment (adjunctive) and prevention of cancers such as breast cancer[12] [13].
Here's what the research says:
To date, researchers appear to agree that supplementing melatonin (including doses up to 100mg/day) is well tolerated and is not typically associated with any serious adverse affects[14] [15]. The mild adverse effects that have been reported include drowsiness, headaches and dizziness and nausea[16]. Of these mild adverse effects, research suggests they either resolve spontaneously within a few days with no adjustment in melatonin, or immediately upon withdrawal of treatment[17]. Melatonin has not been found to be addictive in nature nor cause hangover symptoms[18], which is why it has been considered as a possible alternative to many sleep medications. In addition to this, research also suggests that the supplementation of melatonin does not interfere with the bodies internal production of melatonin once treatment has ceased[19] [20]. This makes sense when we consider that the half life (the time it takes for half of a drug to be cleared) of melatonin is only 1-2 hours depending on the formulation. This means that in 1-2 hours 50% of the melatonin will be removed from the body. Therefore, in 5 hours the amount of melatonin in the body is negligible and the body knows start producing a “new batch” of melatonin in the pineal gland as soon as you are exposed to light in the morning. Given that melatonin has a short half life, melatonin only targets sleep onset and not maintenance. Because of the short half life, we see so many prolonged release formulations of melatonin to slow down the absorption into the bloodstream to ensure the levels of melatonin are maintained in blood stream for a longer period to extend its sleep benefits. Prolonged release formulas allow you to maintain higher active levels of melatonin throughout the night if your goal with supplementing melatonin is to prevent nighttime waking.
But what about our more vulnerable populations such as children or elderly people?
In children, research suggests adverse effects of melatonin supplementation were few and mild[21]. Of these adverse effects, fatigue and somnolence were mentioned and were found to resolve with dose reduction. In addition, studies on pediatric populations looking at the long term effects of melatonin supplementation (two, three and four years on average) in doses of 2mg-10mg/day, found no notable long term effects on vitals signs or measures of child growth[22] [23]. In a two year long study assessing sleep, growth and puberty in children taking melatonin, a two week placebo period was implemented after treatment to assess withdrawal effects to which there were no apparent signs of withdrawals (mallow).
A 2022 review article discussing the safety of melatonin use in the elderly found that adverse effects were similar to those found in adult populations such as dizziness, nausea and headaches[24].However, there may be an increased risk of hypothermia if melatonin levels reach above normal physiologic levels as well as fractures in those who are at risk of falling due to the possibility of daytime sedation [25]. In regards to discontinuation, research suggests there is no evidence of withdrawal effects in populations 55 years and older[26].
It is important to note that the above research does not include individuals on medications or health concerns/diagnoses outside the parameters of each individual study. Therefore, it is important to discuss melatonin supplementation with your healthcare provider before taking.
In summary, it is SAFE to say melatonin is SAFE for those who are taking melatonin long term as recommended by their health care provider for one of the many clinical benefits we see with melatonin supplementation.
[1] Ferracioli-Oda E, Qawasmi A, Bloch MH. Meta-analysis: melatonin for the treatment of primary sleep disorders. PLoS One. 2013 May 17;8(5):e63773. doi: 10.1371/journal.pone.0063773. PMID: 23691095; PMCID: PMC3656905.
[2] Bhattacharya S, Patel KK, Dehari D, Agrawal AK, Singh S. Melatonin and its ubiquitous anticancer effects. Mol Cell Biochem. 2019 Dec;462(1-2):133-155. doi: 10.1007/s11010-019-03617-5. Epub 2019 Aug 26. PMID: 31451998.
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[8] Kandil TS, Mousa AA, El-Gendy AA, Abbas AM. The potential therapeutic effect of melatonin in Gastro-Esophageal Reflux Disease. BMC Gastroenterol. 2010 Jan 18;10:7. doi: 10.1186/1471-230X-10-7. PMID: 20082715; PMCID: PMC2821302.
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[13] Yang A, Peng F, Zhu L, Li X, Ou S, Huang Z, Wu S, Peng C, Liu P, Kong Y. Melatonin inhibits triple-negative breast cancer progression through the Lnc049808-FUNDC1 pathway. Cell Death Dis. 2021 Jul 16;12(8):712. doi: 10.1038/s41419-021-04006-x. PMID: 34272359; PMCID: PMC8285388.
[14] Menczel Schrire Z, Phillips CL, Chapman JL, Duffy SL, Wong G, D'Rozario AL, Comas M, Raisin I, Saini B, Gordon CJ, McKinnon AC, Naismith SL, Marshall NS, Grunstein RR, Hoyos CM. Safety of higher doses of melatonin in adults: A systematic review and meta-analysis. J Pineal Res. 2022 Mar;72(2):e12782. doi: 10.1111/jpi.12782. Epub 2021 Dec 30. PMID: 34923676.
[15] Andersen LP, Gögenur I, Rosenberg J, Reiter RJ. The Safety of Melatonin in Humans. Clin Drug Investig. 2016 Mar;36(3):169-75. doi: 10.1007/s40261-015-0368-5. PMID: 26692007.
[16] Savage RA, Zafar N, Yohannan S, et al. Melatonin. [Updated 2021 Aug 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534823/
[17] Besag FMC, Vasey MJ, Lao KSJ, Wong ICK. Adverse Events Associated with Melatonin for the Treatment of Primary or Secondary Sleep Disorders: A Systematic Review. CNS Drugs. 2019 Dec;33(12):1167-1186. doi: 10.1007/s40263-019-00680-w. PMID: 31722088.
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