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Melatonin: what is its relation to sleep and biological rhythms?

Melatonin is a hormone present in practically all living organisms and its production occurs in the pineal gland, being then secreted into the blood, and then acting as a hormoneAMARAL; CIPOLLA-NETO, 2018The circadian timing system exerts control over its production, so that, in the presence of light, its production is inhibited and, on the other hand, in the absence of light, its production is stimulated. Thus, its synthesis is aligned with the light-dark cycle. Its effects on the body are diverse and can be observed even when there is no more melatonin present in the body - a factor that makes it difficult to define functions as in other hormonesCIPOLLA-NETO; AMARAL, 2018). For the purpose of this article, the effects that melatonin exerts on sleep and biological rhythms will be addressed, as well as some conditions that can interfere with its synthesis.

Due to its circadian component, the concentration of melatonin increases during the night and decreases during the day, hence the idea that it is a sleep hormone. However, this statement is an error. In nocturnal species, that is, in species whose activity period is concentrated on the dark phase of the day, it is possible to observe that the melatonin curve follows the same pattern as in diurnal species (human beings, for example). Interestingly, melatonin has sleep-inducing effects only in predominantly diurnal speciesCIPOLLA-NETO; AMARAL, 2018; LIU; WEAVER; JIN; SHEARMAN et al., 1997).

When performed during the light phase of the day, when there is not much melatonin in the body, sleep has a more fragmented architecture and is shorter. Furthermore, the same fragmented pattern is observed when blocking melatonin secretion at night - whether through pharmacological or light interventionCAJOCHEN; KRÄUCHI; DANILENKO; WIRZ-JUSTICE, 1998; VAN DEN HEUVEL; REID; DAWSON, 1997Obviously, during day-time sleeping, there are other components that will influence the quality and duration of sleep, such as high core temperature and higher cortisol concentration, but these results demonstrate the potential of melatonin to induce and improve sleep quality. Studies performed with pinealectomized humans reinforce these data. These patients, in general, have rhythms that are out of sync with the 24-hour light-dark cycle, reduced total sleep time, high volume of awakenings during the night, and poor sleep quality. In most cases, these symptoms were reversed with the administration of exogenous melatoninETZIONI; LUBOSHITZKY; TIOSANO; BEN-HARUSH et al., 1996; LEHMANN; COCKERELL; RUDGE, 1996A systematic review conducted by Brzezinski and colleagues sought to assess the effects of exogenous melatonin administration on sleep parameters. The results demonstrate a reduction in sleep onset latency, as well as an increase in total sleep time and sleep efficiencyBRZEZINSKI; VANGEL; WURTMAN; NORRIE et al., 2005Furthermore, as mentioned by Cipolla Neto, most studies standardize the dosage of melatonin used, and this can reduce the size of the observed effectCIPOLLA-NETO; AMARAL, 2018).

Another important function of melatonin is the regulation of the sleep-wake cycle. As a chronobiotic, it can be used for the regulation of rhythm disorders such as delayed/advanced sleep phase syndrome and non-24-hour rhythm. It is necessary to observe the intended objective to then define the time of its ingestion. In its ingestion at the beginning of the night, the sleep phase advances. On the other hand, at the end of the night, there is a delay in the sleep phase. A “dead zone” is also observed, in which rhythm-related adaptations are not observed when ingestion is carried out at this time. This zone is located in the middle of the night, when melatonin acrophase usually occursCIPOLLA-NETO; AMARAL, 2018).

Conditions that cause endogenous melatonin to be reduced

            Some conditions affect the production of melatonin, varying from too much to too little of it. From a clinical point of view, dysfunction in melatonin production can be classified as:

In addition, other conditions can affect melatonin production, such as cervical spinal cord injurySCHEER; ZEITZER; AYAS; BROWN et al., 2006and visual impairment with interruption in light perceptionLOCKLEY; SKENE; JAMES; THAPAN et al., 2000).

Pharmacokinetics and dosage

            Melatonin pharmacokinetics depend on the form of ingestion (oral, fast/slow release, intravenous, nasal spray, anal suppository, among others) and individual absorption, as well as enzymatic activity in the liver. The dose must be adjusted for each individual in a personalized way, in order to avoid daytime drowsiness and nightmares at night.AMARAL; CIPOLLA-NETO, 2018).

Assessment of biological rhythms

            Actigraphy - the gold standard technique for assessing biological rhythms - can be used when the purpose of melatonin intake is to regulate the sleep-wake cycle, as well as to improve aspects of sleep. The CONDOR actigraph has light, movement, and body temperature sensors and, from these sensors, it is possible to analyze sleep-related variables, such as total sleep time, sleep efficiency, latency to sleep onset and awakenings after sleep onset, as well as variables related to biological rhythm, such as cosinor, spectrogram, periodogram and non-parametric analyzes (L5, M10, IV and IS). Thus, it is possible to carry out patient follow-up in an objective and non-invasive way.

Conclusion

Melatonin administration is effective in improving sleep quality, increasing total sleep time, sleep efficiency, and reducing sleep onset latency. In addition, it can also be used to treat biological rhythm disorders. Currently, there are several ways to consume exogenous melatonin, and the option to be used, as well as the dosage applied, must be defined by the doctor.

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