Is Melatonin Safe for Long-Term Use?

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.

[3] Forsling ML, Wheeler MJ, Williams AJ. The effect of melatonin administration on pituitary hormone secretion in man. Clin Endocrinol (Oxf). 1999 Nov;51(5):637-42. doi: 10.1046/j.1365-2265.1999.00820.x. PMID: 10594526.

[4] Valcavi R, Zini M, Maestroni GJ, Conti A, Portioli I. Melatonin stimulates growth hormone secretion through pathways other than the growth hormone-releasing hormone. Clin Endocrinol (Oxf). 1993 Aug;39(2):193-9. doi: 10.1111/j.1365-2265.1993.tb01773.x. PMID: 8370132.

[5] Lundmark PO, Pandi-Perumal SR, Srinivasan V, Cardinali DP. Role of melatonin in the eye and ocular dysfunctions. Vis Neurosci. 2006 Nov-Dec;23(6):853-62. doi: 10.1017/S0952523806230189. PMID: 17266777.

[6] Yi C, Pan X, Yan H, Guo M, Pierpaoli W. Effects of melatonin in age-related macular degeneration. Ann N Y Acad Sci. 2005 Dec;1057:384-92. doi: 10.1196/annals.1356.029. PMID: 16399908.

[7] Pereira Rde S. Regression of gastroesophageal reflux disease symptoms using dietary supplementation with melatonin, vitamins and aminoacids: comparison with omeprazole. J Pineal Res. 2006 Oct;41(3):195-200. doi: 10.1111/j.1600-079X.2006.00359.x. PMID: 16948779.

[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.

[9] Pereira Rde S. Regression of gastroesophageal reflux disease symptoms using dietary supplementation with melatonin, vitamins and aminoacids: comparison with omeprazole. J Pineal Res. 2006 Oct;41(3):195-200. doi: 10.1111/j.1600-079X.2006.00359.x. PMID: 16948779.

[10] Khare A, Thada B, Jain N, Singh D, Singh M, Sethi SK. Comparison of Effects of Oral Melatonin with Oral Alprazolam used as a Premedicant in Adult Patients Undergoing Various Surgical Procedures under General Anesthesia: A Prospective Randomized Placebo-Controlled Study. Anesth Essays Res. 2018 Jul-Sep;12(3):657-662. doi: 10.4103/aer.AER_90_18. PMID: 30283171; PMCID: PMC6157235.

[11] Ghaeli P, Solduzian M, Vejdani S, Talasaz AH. Comparison of the Effects of Melatonin and Oxazepam on Anxiety Levels and Sleep Quality in Patients With ST-Segment-Elevation Myocardial Infarction Following Primary Percutaneous Coronary Intervention: A Randomized Clinical Trial. Ann Pharmacother. 2018 Oct;52(10):949-955. doi: 10.1177/1060028018776608. Epub 2018 May 11. PMID: 29749262.

[12] Li Y, Li S, Zhou Y, Meng X, Zhang JJ, Xu DP, Li HB. Melatonin for the prevention and treatment of cancer. Oncotarget. 2017 Jun 13;8(24):39896-39921. doi: 10.18632/oncotarget.16379. PMID: 28415828; PMCID: PMC5503661.

[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.

[18] Cardinali DP, Srinivasan V, Brzezinski A, Brown GM. Melatonin and its analogs in insomnia and depression. J Pineal Res. 2012 May;52(4):365-75. doi: 10.1111/j.1600-079X.2011.00962.x. Epub 2011 Sep 23. PMID: 21951153.

[19] Matsumoto M, Sack RL, Blood ML, Lewy AJ. The amplitude of endogenous melatonin production is not affected by melatonin treatment in humans. J Pineal Res. 1997 Jan;22(1):42-4. doi: 10.1111/j.1600-079x.1997.tb00301.x. PMID: 9062869.

[20] Hack LM, Lockley SW, Arendt J, Skene DJ. The effects of low-dose 0.5-mg melatonin on the free-running circadian rhythms of blind subjects. J Biol Rhythms. 2003 Oct;18(5):420-9. doi: 10.1177/0748730403256796. PMID: 14582858.

[21] Maras A, Schroder CM, Malow BA, Findling RL, Breddy J, Nir T, Shahmoon S, Zisapel N, Gringras P. Long-Term Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children with Autism Spectrum Disorder. J Child Adolesc Psychopharmacol. 2018 Dec;28(10):699-710. doi: 10.1089/cap.2018.0020. Epub 2018 Oct 11. PMID: 30132686; PMCID: PMC6306655.

[22] Malow BA, Findling RL, Schroder CM, Maras A, Breddy J, Nir T, Zisapel N, Gringras P. Sleep, Growth, and Puberty After 2 Years of Prolonged-Release Melatonin in Children With Autism Spectrum Disorder. J Am Acad Child Adolesc Psychiatry. 2021 Feb;60(2):252-261.e3. doi: 10.1016/j.jaac.2019.12.007. Epub 2020 Jan 23. PMID: 31982581; PMCID: PMC8084705.

[23] Kennaway, D.J. (2015), Melatonin use in paediatrics. J Paediatr Child Health, 51: 584-589. https://doi.org/10.1111/jpc.12840

[24] Zhdanova IV, Wurtman RJ, Regan MM, Taylor JA, Shi JP, Leclair OU. Melatonin treatment for age-related insomnia. J Clin Endocrinol Metab. 2001 Oct;86(10):4727-30. doi: 10.1210/jcem.86.10.7901. PMID: 11600532.

[25] Should Melatonin Be Used as a Sleeping Aid for Elderly People? Can J Hosp Pharm. 2019 Jul-Aug;72(4):327-329. Epub 2018 Aug 31. PMID: 31452545; PMCID: PMC6699865.

[26] Lemoine P, Nir T, Laudon M, Zisapel N. Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. J Sleep Res. 2007 Dec;16(4):372-80. doi: 10.1111/j.1365-2869.2007.00613.x. PMID: 18036082.

MASSAGE THERAPY

Have you ever been on a massage table and feel like you are going to fall asleep or have fallen asleep? You know then how beneficial massage can be for relaxation and for stress reduction. You may also know that the night after receiving a massage treatment you generally sleep better than other nights. 

Many people experience insomnia at some point in time. Insomnia is defined as difficulty falling asleep and staying asleep. If you experience stress or anxiety this can increase your odds of experiencing insomnia. Relaxation massage can help with insomnia by decreasing stress levels in the body. Your massage therapist may also teach you diaphragmatic breathing techniques. Massage therapy can provide benefits with other underlying pain and stress responses, which can sometimes be caused by a specific conditions such as migraines, fibromyalgia, or cancer. 

Massage therapy is not only good for patients with chronic illnesses but can also be helpful for the caregivers of these patients too. In a study done by the National Institute of Health, sleep quality improved for family caregivers of patients with cancer after therapeutic back massage intervention. Read more here: https://www.healthcentral.com/article/improve-your-sleep-with-massage-therapy and https://www.ncbi.nlm.nih.gov/pubmed/26745049

If you experience insomnia, a chronic illness or are going through a difficult time caring for someone affected by cancer, we encourage you to consider massage therapy at our clinic. We currently have two excellent Registered Massage Therapists available and offer several types of massage including relaxation, deep tissue, and myofascial release. Call the office at 306-664-2150 to book your appointment today.