Human life obeys a certain biological rhythm, through which the precise regulation of the work of various organs and systems is carried out. In the complex system of regulation of this rhythm, a fundamental role is played by melatonin, which is secreted in the brain and influences sleep.
Melatonin is a hormone that is strongly influenced by “dark” and “light” therapy and can be used as a sleep-enhancing agent. It is preferred over some medications because it is not addictive.
What is melatonin?
Melatonin (5-methoxy-N-acetyltryptamine) is a peptide hormone and neutrotransmitter present in the bodies of all living creatures (from algae to humans) in levels that change in a daily cycle. In higher animals, it is produced by pinealocytes (a type of cell) in the pineal gland (located in the brain) and also by the retina and gastrointestinal tract. It is synthesized from the amino acid tryptophan by the synthesis of serotonin by the enzyme 5-hydroxyindole-O-methyltransferase.
Melatonin is produced in the pineal gland (a small gland in the brain) under the guidance of serotonin (one of the most important neurotransmitters). Like a vampire, melatonin appears in the blood only at night and disappears during the day. At twilight, the pineal gland begins to gradually increase melatonin secretion, which reaches its maximum in complete darkness.
In the morning, light activates the optic nerve, and the impulse generated travels through the spinal column and higher conducting tracts to reach the pineal gland, which blocks melatonin synthesis and secretion. Like a metronome regulating the activity of the central nervous system.
Receiving continuous impulses through the optic nerve, the pineal gland is probably able to regulate the activity of various organs and systems and stimulate the switch to “economy mode” when it is dark, thereby reducing the body’s energy expenditure considerably. A key element in this regulatory mechanism is also melatonin.
Melatonin is found naturally in a number of plants in sufficiently bioactive doses. Among the best sources of melatonin are:
- olive oil;
- raw cow’s milk;
How does melatonin work?
It has been found that the synthesis of melatonin in the human body plays an extremely important role in the control of the 24-hour wake-sleep rhythm and with the associated changes in the secretion of various hormones (cortisol, testosterone, growth hormone).
Melatonin is a fundamental regulator of the cyclic rhythms of the human body. It shows a 24-hour pattern of synthesis and release. Its natural biological availability for an extended period of time (5-6 hours) during the night melatonin also determines the effect on the cyclic system of the biological rhythms.
As I already mentioned, melatonin regulates the wake-sleep cycle and synchronizes biorhythms. This precise rhythm, individual to each person, can be impaired if there are disturbances in melatonin secretion. When in sufficient quantity, melatonin slightly lowers a person’s body temperature – thus also reducing energy consumption and speeding up the regeneration of cells that are inactive during the sleep phase.
It is supposed that melatonin is also one of the most powerful antioxidants, acting both at the level of the cell membrane and inside the cell itself.
In the evolution process, humans have lost the ability to produce some powerful antioxidants such as beta-carotene and vitamin C in their bodies, but have retained other antioxidants (such as melatonin) that inactivate free radicals (a major threat to the body) and in this way melatonin creates a powerful defense system against them.
For example, the brain, composed of 50% fat tissue, 1/3 of which is unsaturated fatty acids, is very sensitive to free radicals. Located at the base of the brain, the pineal gland synthesizes melatonin, which represents the “last line” against free radicals attacking the brain.
Melatonin also lowers the level of “bad” LDL-cholesterol, protects against some types of cancer, and stimulates the immune system.
Serum levels and metabolism
In studies on a number of models associated with insomnia or difficulty falling asleep, small doses of 0.3 or 0.5 mg were found to be as effective as doses ten times higher. A large dose of 20 mg was also found to have less effect than the generally accepted dosage.
Establishing serum melatonin peaks is extremely difficult, varying from study to study. At different dosages there is not much difference, but in all cases serum melatonin concentrations increase several fold compared to any physiological concentration. Doses of 3 to 5 mg increase the concentration more and delay the half-life.
The half-life of melatonin is only 24 minutes, and its blood levels remain stable for up to 150 minutes after ingestion. Half-lives do not differ between small and large doses. The same applies to the occurrence of serum peaks, which occur after 45-75 minutes of intake.
There is a research that suggests, that nasal spray intake of melatonin may be far more effective compared to standard oral intake.
Melatonin is metabolized and eliminated from the body quickly. Its metabolism is accelerated by aromatization and certain habits, such as smoking, speed up melatonin elimination from the body.
Melatonin and age
Peripheral blood melatonin levels are different in young and elderly individuals. It has been shown that with age, the circadian systems in the human body “are disrupted”. As it is in the case with most hormones, melatonin levels drop dramatically with aging – in 80-year-old person, for example, serum levels are only 10% of those in a 20-year-old.
The consequence of this is a significant change in a number of vital parameters. Especially that the sleep-wake cycle is negatively affected, at night the temperature of adults does not drop, which means that the regenerative processes of tissues and organs cannot occur.
Scientifically proven and potential benefits in humans
Sleep and relaxation
Melatonin is best known for its qualities in improving sleep and treating insomnia. For this reason, it is used as a reference substance for testing others like it. The most used dose is 3 mg with a gradual release.
The primary mechanism of action is associated with shortening the time to fall asleep, with melatonin also exhibiting benefits in fully healthy individuals. In some studies, melatonin is even claimed to improve sleep quality, but this is not proven in healthy individuals. However, the same is not true for elderly people and children suffering from insomnia, in whom melatonin also positively affects sleep quality. It also applies to individuals who suffer from migraines or subjective tinnitus (noise in one or both of your ears) in which there is no external source, as well as in schizophrenics.
The influence of melatonin on lowering body temperature has also been shown to have its benefits in facilitating falling asleep.
Melatonin shows greatest effect in individuals over 55 or suffering from insomnia.
Melatonin also improves sleep in cases where there are external or internal factors for its poor quality. The external factors are day and night cycles, and the internal factor is the internal clock of each individual. When the internal or external factors are not properly “set,” melatonin helps bringing balance.
One of the most valuable benefits of melatonin is for people who travel a lot, and it is expressed in the ability to regulate circadian rhythms on long trips in different time zones. This is proven in a huge meta-analysis of ten different studies. Taken before travel or in tailored hourly doses, melatonin regulates the circadian rhythm and avoids specific state of fatigue and difficulty falling asleep when crossing multiple time zones. Even more impressive is the fact that this phenomenon also applies to night shifts.
The action of melatonin on sleep is also often related to light exposure. Melatonin works best with exposure to bright light in the first part of the day, but it does not combine well with exposure to bright light right before falling asleep.
Some of the most impressive effects of melatonin are associated with stomach function.
Melatonin successfully increases serum levels of gastrin, low levels of which occur in individuals with stomach ulcers, which is associated with melatonin’s healing properties in this regard.
All studies to date have shown that melatonin has strong protective properties against ulcers, and the effect also occurs independently, with results demonstrating complete recovery. Melatonin has a protective effect against the harmful effects of certain bacteria and aspirin.
Taking melatonin before sleep lowers the symptoms of gastroesophageal reflux disease (GERD), as does heart palpitations when reflux occurs.
Melatonin affects certain neurotransmitters in the body. For example, it restrains the increase in adrenaline and noradrenaline levels in stressful situations, but does not completely eliminate them. In non-stressful situations, melatonin also reduces adrenaline levels.
Melatonin reduces blood flow to the brain and is thought to be beneficial in migraines, although this effect is controversial and not fully proven. It is suggested that melatonin may have its benefits, mostly in improving sleep quality in people suffering from migraine.
There is a theory that melatonin may help with some depressive conditions, especially those associated with changes in daylight during the winter. Melatonin together with light therapy helps normalizing the circadian rhythm in winter and improving the depressive state.
The neurological benefits of melatonin are also associated with memory improvement. It is possible that melatonin may help improve memory markers in the elderly, but so far the data are based only on combinations with other substances. However, melatonin alone improves memory in young individuals under stressful situations.
Small doses of 1-2 mg of melatonin lower blood pressure dramatically in men and women, which is associated with a decrease in adrenaline. The degree of blood pressure lowering differs with activity and inactivity, and it is assumed that such lowering may not be relevant in every situation. In one study on individuals with metabolic syndrome, melatonin successfully lowered diastolic and systolic blood pressure, and this lowering was not correlated with body weight.
Melatonin has been shown to improve blood flow and possess vasorelaxant (reduction of vascular tension) properties. In this case, it affects blood flow to the extremities and kidneys, but not cerebral blood flow.
In relation to triglycerides and cholesterol in the blood, melatonin does not have a positive effect, but an interesting effect has been found when melatonin is taken before exercise, in which situation the peptide hormone enhances the lowering of triglycerides.
Peripheral organs (eyes and ears)
Melatonin has a positive effect on blood pressure in the eyes via the melatonin receptor. This effect is also associated with lowering in adrenaline. A significant reduction is noted up to two hours after oral intake.
The benefits of melatonin for the eyes do not end there. Melatonin levels in the eyes of glaucoma (a common eye condition where the optic nerve, which connects the eye to the brain, becomes damaged) patients have been found to be significantly lower in the evening, with melatonin in this case helping to improve the condition, or at least stop it from getting worse.
As previously mentioned, melatonin also has benefits for the condition of subjective tinnitus. Although it improves falling asleep and the quality of sleep in patients with this disease, it does not directly influence the treatment.
Impact on fat metabolism
So far, there is no research that supports the direct effects of melatonin on the amount of body fat and body composition. However, there is a human study that found that melatonin, when taken for more than a week, increased circulating levels of the hormone leptin (help regulate the long-term balance between your body’s food intake and energy use expenditure) without dietary changes. This increase persisted after the third week of use, and in individuals with “fatty” livers, the increase was even more significant. Leptin secretion was found to be insulin-dependent and this process was stimulated by melatonin.
The same results are confirmed in tests on rats. The percentages differ significantly because of the relationship of leptin to circadian rhythm. Tests on animals go even further, where fat loss is also found. The mechanism is not clear, assuming that this may be through direct fat burning or through suppression of lipogenesis (the synthesis of fatty acids from nonlipid precursors). These findings have no practical benefit so far in healthy individuals, but melatonin intake improves to a small extent the body mass index in individuals with metabolic syndrome. It is possible that melatonin promotes fat burning in certain circumstances, most notably sleep-related abnormalities or because of its positive effects on blood pressure and antioxidant activity.
Impact on physical activity
Melatonin has no physical effects on exercise, but it can have neural effects.
Evening intake of melatonin has been found to have no negative effect on training in the morning, but intake of melatonin up to 3 hours before physical activity resulted in sedation and increased reaction time without negatively affecting endurance and power during aerobic training activity.
Pre-exercise melatonin intake increases antioxidant activity and reduces blood triglyceride rise (type of fat that circulates in our blood) and lipid peroxidation (lipid degradation).
Melatonin and hormones
Although a link between melatonin and female sex hormones has been established, tests on women after undergoing breast cancer surgery found no effect on estrogen, and more specifically on “bad” estrogen. However, melatonin does affect aromatization. We can conclude that this influence is more in relation to ageing, in which a deficiency of melatonin is associated with increased aromatisation, and this process can be regulated. However, melatonin cannot be used as a therapy to regulate aromatization and estrogen.
Melatonin does not particularly affect male sex hormones. Although it suppresses testosterone in rat testes, it has no similar effect in humans and does not affect testosterone and luteinizing hormone levels in healthy men. The only benefits of melatonin in this regard are that its regular intake can reduce testosterone drops after prolonged exercise activity.
Melatonin has a positive effect on steady-state prolactin levels, but only after regular use within 5 days. Unlike other hormones, prolactin is not affected by melatonin when taken once.
Regular intake of melatonin in the evening increases intra-day cortisol levels to a small extent in healthy and young men. Cortisol is more strongly affected than melatonin when taken in high doses in the morning by women who have undergone breast cancer surgery. In these cases, cortisol increases significantly in the evening, and then its levels are suppressed by high estrogen levels.
Among the hormones, melatonin has the strongest effect on the growth hormone. A single dose between 0.5-5 mg successfully increases growth hormone levels by 16-17% within 150 minutes. This effect has been noted in the resting state in healthy men. Analyses suggest that melatonin does not directly increase hormone levels, but exacerbates the pituitary’s sensitivity to its action.
Data on the effects of melatonin on growth hormone after exercise are mixed. Two studies found that melatonin significantly increases growth hormone after exercise, but a third study found that it has the opposite effect. So far, there is no clear answer.
Impact on cancer metabolism
One meta-analysis concluded that one year of melatonin use lowers the risk of death in patients with solid breast tumors. The risk was lowered by nearly 25%.
Melatonin provides a general protective effect and reduces deaths. One hypothesis is that disrupted circadian rhythm as well as low levels of melatonin in the body that are part of the causes of breast cancer development. Other suggestions link the action of melatonin to its influence on processes such as aromatisation (the process that converts testosterone into estrogen) and certain intracellular mechanisms.
Melatonin has also been tested in cancers in the intestinal tract, but even in combination with fish oil, it does not directly affect the metabolism of the disease. However, both supplements help with weight gain in sick patients.
Melatonin and the pineal gland are associated with lifespan. With age, melatonin levels in the body decline and it is thought that supplementation may help longevity.
Melatonin use is associated with effects on pro-inflammatory cytokines in heart tissues, which may increase lifespan. A similar protective effect is also seen in pancreatic and liver tissues. Animal tests also found an anti-aging effect on the skin.
Proven and potential benefits in animals and in-vitro
- Successfully inhibits dopamine release in neurons. Has a particularly strong effect when dopamine release results from the effects of beta antagonists such as ephedrine;
- Functions as a neuroprotective agent due to its antioxidant properties, by suppressing beta-amyloid pigmentation and influencing the mTOR mechanism (mechanism, that regulates cellular metabolism and growth);
- Has anti-adrenergic effect in cardiac tissues by reducing AMR (antimicrobial resistance) production by 34%;
- Strong antioxidant effect. It also stimulates certain antioxidants in the body, such as superoxide dismutase (SOD) and catalase. It also protects DNA from mineral damage and its degree of protection is comparable to that of resveratrol, alpha lipoic acid and PirateTea or only Oolong tea;
- Influences on fat, and this can be by directly burning fat or by inhibiting lipogenesis;
- Has a protective effect on the skin because of its antioxidant activity. The benefits have only been studied in vitro;
- By lowering oxidative stress, melatonin may positively influence hair loss caused by the effects of androgen. In vitro studies point to positive results in terms of stimulating hair growth in these cases, but the only human study could not be found online and is controversial;
- Anti-cancer properties through effects on various mechanisms, but the practical relevance in humans is unclear.
Dosage and method of use
Melatonin is not a sleeping pill, there is no habituation to it – it simply synchronizes biorhythms and ensures a restful and prolonged sleep.
Doses between 0.5 mg to 5 mg have been found to work to improve sleep rhythms. Our recommendation is to start with the minimum dose and gradually increase if there is no effect. The benefits of melatonin are not dose dependent, so a higher dose does not mean a stronger effect. Only a higher dose would have benefits for slightly higher growth hormone peaks.
To ensure better action, it is recommended to be administered in a dose of one tablet daily to be taken with a glass of water in the evening up to 30 minutes before bedtime. The tablet should not be chewed. Exceeding the daily dose is not recommended.
Although melatonin is found as a dietary supplement, self-treatment is not recommended before a medical diagnosis!
Side effects and contraindications
Melatonin is one of the safest and non-toxic substances. Shock doses up to 500 mg, whether taken orally or intravenously, have no intoxicating effect. It is non-toxic in elderly people over the age of 60. Doses up to 5 mg daily are also safe for children over 5 years of age, and it is possible for younger children to take it, but only after consulting a pediatrician.
Melatonin is not addictive. Several detailed, large-scale studies have found that even with a constant intake of 6-12 months it is not addictive.
There are hypotheses that a reverse effect may occur when melatonin supplementation is stopped. At this stage it has been shown that doses up to 2 mg should not have such consequences, but it is assumed that with long-term intake of higher doses there could be adverse effects after stopping melatonin. The most well-established hypothesis so far is that a possible cause is not its cessation itself, but the fact that the body reverts to its previous irregular sleeping pattern.
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