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

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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.[12] 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.[1415] 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. Financial support and sponsorship Nil Conflict of interest There are no conflicts of interest.

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