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 Table of Contents  
Year : 2022  |  Volume : 9  |  Issue : 2  |  Page : 254-255

How effective is daytime oral exogenous melatonin supplementation in improving sleep quality and duration?

1 Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
2 School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada

Date of Submission30-Jan-2022
Date of Acceptance26-Mar-2022
Date of Web Publication17-Jun-2022

Correspondence Address:
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mgmj.mgmj_7_22

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How to cite this article:
Okechukwu CE, Okechukwu CE. How effective is daytime oral exogenous melatonin supplementation in improving sleep quality and duration?. MGM J Med Sci 2022;9:254-5

How to cite this URL:
Okechukwu CE, Okechukwu CE. How effective is daytime oral exogenous melatonin supplementation in improving sleep quality and duration?. MGM J Med Sci [serial online] 2022 [cited 2022 Jul 6];9:254-5. Available from: http://www.mgmjms.com/text.asp?2022/9/2/254/347693

Dear Editor,

Daytime oral administration of exogenous melatonin or melatonin receptor agonists may induce sleepiness by reducing core body temperature and increasing the distal-proximal skin gradient.[1],[2] Exogenous melatonin has cardioprotective, neuroprotective, and antioxidant properties.[3] Exogenous melatonin supplements are often used for the treatment of insomnia.[3] Melatonin absorption and metabolism are variable in exogenous melatonin formulations. Due to first-pass metabolism, the amount of melatonin entering the systemic circulation reduces after oral ingestion.[3] As a result, the pharmacokinetics and efficacy of the compound are affected. The key to improving present formulations and improving their effect on sleep disorders is to increase melatonin bioavailability.[3] The lack of consistency in effectiveness when treating sleep disorders may be partly explained by inconsistency in the delivery time for oral exogenous melatonin formulations.[4] Besides, exogenous melatonin is well tolerated and has no apparent short-or long-term adverse effects.

Melatonin has been proven to synchronize the circadian rhythms and improve the onset, duration, and quality of sleep.[5] Melatonin plays an important role in circadian rhythm alignment and sleeps regulation. Exogenous melatonin has fewer side effects when compared to benzodiazepine receptor agonists, antidepressants, and anxiolytics, which can induce dependence and addiction.[6] Melatonin administration improved daytime sleep duration (> 7 h) after night shift work among individuals who participated in a simulated night shift work experiment.[7] One study shows that the sleep-inducing effects of exogenous melatonin oral supplementation occur only at high doses (9 mg) when administered during the daytime.[8] The results indicate that melatonin exhibits its restorative effects on circadian sleep disorders via temperature-mediated stimulation of circadian phase-shifting rather than by a direct sedative effect that eventually adjusts the association between sleep and light exposure.[8] There was a significant association between salivary melatonin levels and the timing of increased subjective sleepiness among healthy young men who took a single dose of melatonin (5 mg) during the daytime.[9] After exogenous melatonin administration (at 1300 h and 1800 h), the increase in subjective sleepiness reached significance at 40 min and 90 min respectively and lasted for 3 h (at 1300 h) and 5 h (at 1800 h).[9] One study showed that exogenous melatonin administration (6 mg) in the morning after the night shift and reduction of sunlight exposure significantly increased sleep period and total sleep time among night shift nurses.[10] Some side effects of exogenous melatonin administration are dizziness, headaches, short-term feelings of depression, vivid dreams, cardiovascular effects, stomach cramps, and irritability.[11] Some studies show the effectiveness of exogenous melatonin use and its agonists in the improvement of sleep to reduce the symptoms of shift work sleep disorder.[12] A randomized controlled cross-over trial showed melatonin to be effective in treating nurses on rotating shifts with difficulty initiating sleep, as there was a significant reduction in sleep onset latency with melatonin compared with both placebo and baseline.[13] Some studies suggest that exogenous melatonin improves sleep initiation and maintenance with a shift in the circadian rhythms, without any hangover effects.[14],[15] The absence of hangover effects remarkably differentiates exogenous melatonin from other hypnotics such as benzodiazepine and zopiclone, thereby making it the preferred option among hypnotics.

In conclusion, oral exogenous melatonin supplementation during the day may be a beneficial strategy for improving the duration of daytime sleep, especially among night-shift workers who need a good amount of restorative daytime sleep. In humans, increased melatonin levels from exogenous daytime administration are linked to increased sleepiness and lower core temperature. However, there is a lack of clinical trials supporting the effectiveness of daytime exogenous melatonin supplementation in improving sleep quality and duration during the day. Further randomized controlled trials are needed to examine the efficacy of different formulations and doses of daytime exogenous melatonin in improving daytime sleep quality and duration.

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Conflict of interest

There are no conflicts of interest.

  References Top

Lok R, van Koningsveld MJ, Gordijn MCM, Beersma DGM, Hut RA Daytime melatonin and light independently affect human alertness and body temperature. J Pineal Res 2019;67:e12583.  Back to cited text no. 1
Markwald RR, Lee-Chiong TL, Burke TM, Snider JA, Wright KP Jr. Effects of the melatonin MT-1/MT-2 agonist ramelteon on daytime body temperature and sleep. Sleep 2010;33:825-31.  Back to cited text no. 2
Lim S, Park S, Koyanagi A, Yang JW, Jacob L, Yon DK, et al. Effects of exogenous melatonin supplementation on health outcomes: An umbrella review of meta-analyses based on randomized controlled trials. Pharmacol Res 2022;176:106052.  Back to cited text no. 3
Moroni I, Garcia-Bennett A, Chapman J, Grunstein RR, Gordon CJ, Comas M Pharmacokinetics of exogenous melatonin in relation to formulation, and effects on sleep: A systematic review. Sleep Med Rev 2021;57:101431.  Back to cited text no. 4
Xie Z, Chen F, Li WA, Geng X, Li C, Meng X, et al. A review of sleep disorders and melatonin. Neurol Res 2017;39:559-65.  Back to cited text no. 5
Sharkey KM, Fogg LF, Eastman CI Effects of melatonin administration on daytime sleep after simulated night shift work. J Sleep Res 2001;10:181-92.  Back to cited text no. 6
Mishima K, Satoh K, Shimizu T, Hishikawa Y Hypnotic and hypothermic action of daytime-administered melatonin. Psychopharmacology (Berl) 1997;133:168-71.  Back to cited text no. 7
Cajochen C, Kräuchi K, von Arx MA, Möri D, Graw P, Wirz-Justice A Daytime melatonin administration enhances sleepiness and theta/alpha activity in the waking Eeg. Neurosci Lett 1996;207:209-13.  Back to cited text no. 8
Andersen LP, Gögenur I, Rosenberg J, Reiter RJ The safety of melatonin in humans. Clin Drug Investig 2016;36:169-75.  Back to cited text no. 9
Yoon IY, Song BG Role of morning melatonin administration and attenuation of sunlight exposure in improving adaptation of night-shift workers. Chronobiol Int 2002;19:903-13.  Back to cited text no. 10
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;33:1167-86.  Back to cited text no. 11
Gandolfi JV, Di Bernardo APA, Chanes DAV, Martin DF, Joles VB, Amendola CP, et al. The effects of melatonin supplementation on sleep quality and assessment of the serum melatonin in Icu patients: A randomized controlled trial. Crit Care Med 2020;48:e1286-93.  Back to cited text no. 12
Sadeghniiat-Haghighi K, Aminian O, Pouryaghoub G, Yazdi Z Efficacy and hypnotic effects of melatonin in shift-work nurses: Double-blind, placebo-controlled crossover trial. J Circadian Rhythms 2008;6:10.  Back to cited text no. 13
Sharkey KM, Fogg LF, Eastman CI Effects of melatonin administration on daytime sleep after simulated night shift work. J Sleep Res 2001;10:181-92.  Back to cited text no. 14
Rajaratnam SM, Polymeropoulos MH, Fisher DM, Roth T, Scott C, Birznieks G, et al. Melatonin agonist tasimelteon (Vec-162) for transient insomnia after sleep-time shift: Two randomised controlled multicentre trials. Lancet 2009;373:482-91.  Back to cited text no. 15


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