The action of melatonin at the cellular level occurs through two distinct regulatory circuits, two of which are of paramount importance. These are G protein-coupled melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2), which is also G protein-coupled.
MT1 influences reproduction (reproduction), metabolism (metabolism) and vasoconstriction (vasoconstriction); MT2 is required for the transmission of circadian signals as well as for retinal (” retina-affecting”) dopamine release and vasodilation (vasodilatation). Furthermore, the activation of MT1 and MT2 receptors by melatonin positively influences antioxidant potential as well as apoptosis (programmed cell death), i.e. melatonin has an antioxidant effect at the cellular level and is thus cell-protective.
In addition to the antioxidant effect of melatonin, an immunomodulatory effect has also been observed. On the one hand, the hormone acts as a radical scavenger and on the other hand, the number of antioxidant enzymes increases.
Melatonin influences the circadian rhythm and transmits information about the day-night rhythm in the body. It has a sleep-promoting effect and, among other things, lowers body temperature at night.In various studies, it was observed that oral intake of melatonin improved various sleep parameters. In a meta-analysis with 19 placebo-controlled intervention studies including 1,683 subjects with sleep disorders, the effect of 2 to 5 mg melatonin was investigated. Within 7 to 28 days, sleep onset time shortened and sleep quality and duration increased. In another meta-analysis with 13 studies, melatonin was also found to have a positive effect on sleep quality in primary insomnia, delayed sleep phase syndrome, the non-24-hour sleep-wake disorder in blind subjects, and REM sleep behavior disorder. In an intervention study of poorly sleeping subjects over 50 years of age, a dose of as little as 0.3 mg of melatonin daily improved sleep quality and plasma melatonin levels normalized. Since elderly people suffer from mild sleep disturbances due to melatonin deficiency, it was observed in the studies by Wade et al. that melatonin is particularly effective in this subpopulation. Over a period of at least 3 weeks, 18 to 80-year-old subjects took 2 mg of melatonin daily. There was an improvement in sleep quality in the older subject collective (55 years and older). Melatonin showed age-associated effects in these studies independent of basal melatonin levels (6-SMT measured in urine).
Note: The bioavailability of melatonin is very low because melatonin undergoes high first-pass metabolism in the liver. The plasma half-life is only about 30 minutes. Melatonin thus appears to have the function of a short pulse, in the sense of a zeitgeber.
