Melatonin secretion is related to the daily light exposure. Melatonin tells you when it’s dark and it’s time to sleep. Melanopsin ganglion cells in the retina of the eyes, sense light. They are different from the rod and cone cells that are needed to be able to see. Cone cells sense wavelengths and colors, while rod cells need less light energy than cone cells and enable night vision. The messages of these vision cells run along the optic nerve to the brain.
Melanopsin cells send a message about fluctuations in light and darkness to the brain’s central clock, which is suprachiasmatic nucleus near the pituitary gland. Therefore, blind people can sense dark and light fluctuations if these retinal ganglion cells and neural connection to the central clock are working. From the suprachiasmatic nucleus, the message is transmitted along the sympathetic nervous path through the upper sympathetic neckline, passing through the cranial gland at the back of the brain, which is secreting melatonin. In the sympathetic nerve pathways from the supercasmic nucleus to the pituitary gland, noradrenaline acts as the main neurotransmitter. This may partly explain why, in particular, fat-soluble beta-blockers can sometimes degrade sleep. The beta-blocker in the morning and melatonin taken in the evening can normalize the inverse melatonin rhythm, which is typical of, for example, rare Smith-Magenis syndrome.
The light inhibits melatonin secretion, and in the evening when the twilight arrives, the secretion of melatonin increases. The so-called Dim light melatonin onset (DLMO) increases in adults generally between 20:00 and 21.30, and the peak of secretion is approximately at midnight. In children, the secretion of melatonin begins earlier. In morning people (early birds), the secretion of melatonin begins earlier, and they can also have secretion peak in the evening. On the other hand, in evening people (night owls) melatonin secretion can begin not until in the early hours of the morning. In Delayed Sleep Phase Syndrome (DSPS) the DLMO time of melatonin is clearly delayed, and in Advanced Sleep Phase Disorder (ASPD), it is clearly ahead of time.
In the pituitary gland, tryptophan acts as the starting material for melatonin synthesis. It forms serotonin and further melatonin. Melatonin secretion begins shortly after birth and is at its peak shortly before the onset of puberty. In puberty, the secretion of melatonin first decreases strongly, after which the reduction in secretion continues slowly, so that melatonin is secreted very little since approximately 55 years of age.
Two types of melatonin receptors
There are two types of melatonin receptors in humans: MT1 and MT2 receptors. MT1 receptors are associated with the amplitude of melatonin, i.e. amount, extent, and height of secretion, whereas MT2 receptors are associated with the phase of melatonin, i.e., the excretion time.
Melatonin has many other effects. It is also an antioxidant and affects the body’s defense system. Melatonin secretion is low in the elderly and in patients with Alzheimer’s disease, its secretion is very low. Melatonin has been studied for the onset of memory disorders, and some studies suggest that it may also be beneficial for patients with Alzheimer’s disease and poorly sleeping patients.
Melatonin is now also commonly used in the treatment of behavioral sleep syndrome RBD, or REM sleep disorder.
What is the best time to take melatonin?
Melatonin can make it easier to fall asleep when taken at the right time in the evening. The common short-acting melatonin has a half-life of about 45 minutes, so its effect is rapidly reduced. It is useful for the treatment of mainly just jet lag. Long-acting depot melatonin, in turn, releases melatonin slowly, leaving the blood melatonin level high enough until the early morning. The long-acting melatonin preparation mimics the body’s own physiological secretion of melatonin. The effect of melatonin is most effective when taken regularly at the same time before DLMO (dim light melatonin onset). In almost all adults this means that melatonin is taken between 20 and 21 in the evening preferably at the same time. Melatonin should not be taken after midnight or in the morning after a night shift. The instruction “one hour before bed” in the package of several melatonin preparations is wrong and should not be followed if you go to bed at 23:00 or later.
What are melatonin side effects?
Melatonin has no side effects typical of traditional sleeping pills. Melatonin does not cause addiction or drowsiness. A possible drawback may be the aggravation of restless legs. Some people say they have more dreams and also nightmares when they use melatonin. The adverse effects of melatonin are mostly due to an inappropriate melatonin uptake time, resulting in a delayed sleep period, either too late or too early. In this case, melatonin is taken clearly after the DLMO time or too early in relation to the DLMO time. When taking melatonin at the right time, side effects, including nightmares, are also rare.
Use of melatonin in children and adolescents
Medical products for children and adolescents should only be resorted to if non-medication treatment does not provide sufficient help. Melatonin has proven to be an effective treatment for delayed sleep rhythm. There is evidence of efficacy especially in those with developmental neuropsychiatric disorder (ADHD, autism). In this group, the common problems are often more severe and drug treatment needs to be started more frequently than usual. Long-term use is not recommended due to insufficient research data. It is therefore necessary to refrain from doing so unless the benefits outweigh the disadvantages.
Short-term use seems safe. However, melatonin is also not recommended as a medication, if necessary, because non-medication therapy is a priority in temporary insomnia. When using melatonin, relatively short cycles of treatment (eg 1 to 3 months) should be sought and treatment discontinued when the response appears to be permanent or if there is no clear benefit of the drug. On the other hand, a too short duration of treatment seems to lead a relapse. The dose should be kept to a minimum, because at high doses no additional benefit can be obtained and possibly only aggravate the sleep problem. Often, 0.5 to 1 mg is a sufficient dose, especially for the synchronization of the circadian rhythm.
The sleeping effect is achieved by 1 to 5 mg. It is very important that melatonin is not used as the sole treatment for sleep problems. The physician should always find out the cause of the symptom and give priority to sleep care and behavioral care, as well as follow up. To synchronize the circadian rhythm, e.g. light exposure and exercise can be used. Light therapy can be as effective as melatonin in rhythm transmission
Benefits of melatonin
The sales of melatonin have increased significantly year after year, after the short-acting tablets containing normal melatonin could be sold as a nutritional product. There is evidence from scientific double-blind studies that 0.5-3 milligrams of melatonin can accelerate the time difference adaptation. It can also be used, for example, as a treatment for a delayed sleep period to normalize sleep. For people with disabilities, melatonin is used to improve night sleep, and melatonin seems to improve the sleep of children and adolescents with autism, according to preliminary ongoing studies. The long-term use of long-acting, slowly absorbed melatonin is safe for people over 55 years of age. It will then act as a kind of replacement therapy.
Melatonin is safer than traditional benzodiazepines. However, the potential drawbacks of long-term use of melatonin in children and adolescents are poorly known. Melatonin inhibits the function of sex hormones, and previously it was even thought that melatonin could act as a contraceptive pill. However, the dosages required were very high, over 100 milligrams, and thus drug development was stopped. In theory, however, melatonin can affect children, for example, on the onset of puberty. For this reason, it is difficult to recommend long-term use of melatonin for children.
A variant of melatonin receptor 1 gene (MTNR1B) that is susceptible to type 2 diabetes occurs in some people. They may be at an increased risk of getting type 2 diabetes (adult type diabetes) as a result of long-term use of melatonin, especially if high doses (4 mg or more) are used. There is no strong evidence of a risk of diabetes in small doses of 1 to 2 mg melatonin. In any case, blood glucose levels should be monitored if melatonin is used for a longer time.
Because melatonin is a hormone, it may also have other side effects that are not yet known. Cortisone was considered a miracle cure in the 1950s. However, the disadvantages of cortisone therapy today are well known and are no longer used without clear reasons. The disadvantages of melatonin should be taken into consideration especially in children. It should be remembered that melatonin is not able to replace a small evening meal, fairy tales, an evening prayer or a restful mind, which are still the best sleeping pill for a child.