The effect of exogenous melatonin intake on the production of endogenous melatonin. Melatonin. clinical trial of homeopathic melatonin. Interaction with metals
The question of how to prolong youth worries not only gerontologists and geriatricians, but also cosmetologists, since anti-aging procedures occupy the first place in the list of services that patients expect from cosmetology clinics. Among the latest scientific developments that may be able to slow down the aging process of the skin, experts are considering products containing melatonin.
Over the past decades, in world and domestic cosmetology, the question has increasingly been raised about how biological rhythms (that is, the uniform alternation in time of any state of the body) are responsible for our aging, and what should be done to stop this very aging both internally and and outside.
Sundial of aging
A person lives “to the sounds of an orchestra” - rhythms created by the Earth, Sun, Moon, planets, and space. There are external biological rhythms, which are of a geographical nature and follow cyclical changes in the external environment, and internal (physiological) rhythms of the body. The best known are: circadian (circadian or daily) and seasonal biological rhythms associated with a certain photoperiodicity - the reaction of living organisms to the daily rhythm of illumination, the length of daylight hours and the relationship between dark and light time of day. In humans, about 300 physiological functions depend on external biological rhythms.
“The conductor of our orchestra” is the pineal gland, or pineal gland, an endocrine gland located in the geometric center of the brain.
The attention of world science to the pineal gland was attracted relatively recently, only in the second half of the last century. Previously, this pea-sized organ remained outside the scope of scientific interest, since, due to the fault of evolutionary morphologists, it was considered a vestigial third eye, which, moreover, had almost lost connections with the rest of the brain, and therefore unworthy of the attention of serious researchers.
Meanwhile, the pineal gland has been known to mankind for thousands of years, and in the distant past, oddly enough (considering its extremely modest size), it earned a very respectful attitude. One cannot help but be surprised at the coincidence of views of ancient Indian and ancient Greek philosophers on this gland. The former for some reason considered the pineal gland to be an organ of telepathy and reflection on the reincarnation of the soul, and the latter, without talking to the former, took it as a valve, again regulating the amount of the soul, a structure necessary for establishing mental balance.
The impetus for a truly scientific study of the pineal gland was the seminal work of A. Lerner and his co-authors, who in 1958 described the lightening effect on the skin of frogs of a substance isolated from the gland and called melatonin. 10 years later, thanks to the research of J. Axelrod, it was found that the pineal gland and its hormone melatonin are directly related to the regulation of biological rhythms. Since then, an unprecedented “epiphyseal boom” has begun and continues, literally sweeping modern science.
The secret of longevity from the hormone melatonin
It is now known that melatonin, a photoperiodic hormone, secreted mainly at night, since its release is suppressed by impulses coming from the retina of the eye, which reacts to light.
Only about 30 mcg of melatonin is produced per day. Its secretion is subject to a circadian rhythm and occurs mainly in the dark (70% is synthesized at night; peak production occurs at two o’clock in the morning), and in the light, in the morning and daytime hours, the production of the hormone is sharply suppressed.
There is a seasonal change in melatonin synthesis. The level of melatonin in a person's blood is minimal between May and July, that is, during the period of maximum daylight hours and illumination. During these same months, the amplitude between the minimum (daytime) and maximum (nighttime) melatonin levels during the day reaches its maximum value. Apparently, this is precisely what is associated with seasonal changes in a person’s general activity and emotional state.
As we age, melatonin production decreases. The melatonin curve is quite individual for each person. Moreover, a significant decrease in melatonin production in most people begins after 40 years, while long-livers have a fairly high level of this hormone. Maybe this is where the secret of longevity lies?!
Scientists have also discovered membrane receptors for melatonin (MTNR1A, which are located in the anterior lobe of the pituitary gland, suprachiasmatic nuclei of the hypothalamus and in peripheral organs, and MTNR1B - in the brain, retina, lungs) and nuclear (retinoid) receptors. The sensitivity of these receptors to melatonin decreases with age and varies depending on the time of day.
Main functions of melatonin
What are the main functions of melatonin in the body, if the pineal gland is rightly called the “sundial of aging”? Regulation of the body's circadian and seasonal rhythms, antioxidant and antitumor protection, control of the endocrine, nervous and immune systems - and that's not all!
Melatonin provides a natural sleep structure, adapts the body to changes in climatic and geographical zones and rapid changes in time zones, supports the reproductive system, optimizes cognitive activity of the brain and prevents its disorders, improves perception processes, weakens anxious behavior and feelings of fear, reduces energy costs of the myocardium, inhibits platelet aggregation , normalizes fat-carbohydrate metabolism, blood pressure, motility, rhythm and secretory activity of the stomach and intestines and, most importantly, slows down the aging process.
The level of natural hormone in the blood depends on age (we have already mentioned this), on gender (in women it is higher than in men), and if these parameters are not within our power to change, then the third and, perhaps, the most important component is sleep!
Anything that disrupts the normal alternation of light and darkness and disrupts our circadian rhythms contributes to accelerated aging. First of all, light pollution (lightening the night sky with artificial light sources scattered in the lower layers of the atmosphere), night shift work, constant indoor lighting at night, white nights in northern latitudes, and transmeridial flights are to blame for this.
The advent of electricity, an artificial increase in the length of daylight hours, night work or shift work, the night “rest” of young people - these are the reasons leading to the failure of our internal biological clocks. And their work determines their biological age, which does not always correspond to the calendar age.
Methods for determining biological age are based on measuring so-called biomarkers of aging. Biomarkers of aging are objective physiological indicators of the state of organs and systems of the body, with the help of which the rate of aging is determined, and individual health risks are assessed, including the prognosis of the development of a number of diseases. Biomarkers of aging have certain requirements: they must reflect physiological age, allow monitoring changes in the body, serve as a means of predicting life expectancy, be easily reproducible, be measured in both animals and humans, be non-lethal, non-invasive and minimally traumatic.
How to determine whether there is a lack of melatonin in the body and whether its additional intake is necessary
The most reliable way is to measure the content. Currently developed very sensitive (from 0.5 pg/ml) methods for determining this hormone not only in blood plasma, but also in urine and saliva make its use quite possible and justified. Doses, time and course of administration are determined in each case individually, taking into account the shape of the melatonin curve.
If sleep becomes more shallow and restless, if an unhealthy lifestyle disrupts the sleep-wake cycle, if sleep problems arise, then the likely cause is low levels of melatonin secretion. In this case, two ways to solve the problem are possible: sleeping in absolute darkness to fully produce your own melatonin, or taking exogenous melatonin when the production of this hormone decreases with age.
Maintaining a daily routine, sufficient light exposure during the day, going to bed before midnight, long sleep (seven to eight hours) in complete darkness (thick curtains on the windows, turning off the TV, computer, night light, using a blindfold), food consumption , rich in tryptophan (bananas, turkey, chicken, cheese, nuts, seeds) - these are fairly simple conditions that allow you to maintain the secretion of melatonin at the proper physiological level.
It is advisable to give up medications that reduce melatonin levels and take vitamin and mineral complexes with vitamins B3 and B6, calcium and magnesium in the spring and summer, which increase melatonin production. If you follow all these “precautionary” measures, then melatonin, the “pendulum” of our biological clock, will be produced on time and in the right quantity. It will help us cope with diseases, accelerated aging, and age-related pathologies.
There is also external use of melatonin, introduced into creams or lotions, which have an antioxidant, moisturizing and regenerating effect on the skin. At the same time, there is a reduction in shallow wrinkles, restoration of elasticity and skin tone. Studies have shown that regular use of such cosmetics prevents premature aging of the epidermis.
In addition, the photoprotective effect of melatonin when applied externally was noted (absorbs 27.17 % of UVB rays and 12.29 % of UVA rays). It can also be used in complex cosmetic programs, such as contouring, mesotherapy, and botulinum toxin injections. This allows you to prolong the effect of the main procedure; Cosmetics containing melatonin can be used in pre- and post-peeling care. In aesthetic surgery and permanent makeup, such products promote rapid recovery, prevent the development of secondary infections, and increase local immunity.
But you shouldn’t think that the unfolding “epiphyseal boom” is a panacea for all our troubles and misfortunes. Expanded clinical trials of the use of melatonin or other drugs that stimulate the production of endogenous melatonin are needed, which will allow melatonin replacement therapy to be carried out depending on the cause of the deficiency of this hormone.
The all-powerful face looking down from on high! A. A. Chizhevsky, Space |
 | Anisimov Vladimir Nikolaevich - head of the department of carcinogenesis and oncogerontology of the Research Institute of Oncology named after. prof. N.N. Petrova Roszdrav, professor, doctor of medical sciences, president of the Gerontological Society of the Russian Academy of Sciences, member of the Council of the International Association of Gerontology and Geriatrics, expert of the UN Program on Aging, editor-in-chief of the journal "Advances of Gerontology", author of more than 400 scientific papers, including including 19 monographs, 6 inventions and patents. The main scientific interests are related to the study of the relationship between the aging process and the occurrence of malignant neoplasms, and the experimental development of new approaches to the prevention of cancer and premature aging. |
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Prospects for the use of melatonin in clinical practice
Currently, melatonin preparations are produced in many countries, which are registered either as medicines or as dietary supplements (dietary supplements). World medical practice has already accumulated some experience in the use of melatonin in the treatment of various diseases. Only one melatonin drug is registered in the Russian Federation - Melaxen ® (Unipharm, Inc., USA), numerous clinical studies have been conducted confirming its effectiveness in various fields of medicine.
Sleep disorders and traveler's desynchronosis
To date, certain evidence has been obtained of the effect of melatonin on improving adaptation to time zone changes (level A) and normalizing sleep during insomnia disorders in people of various age groups (level B).
With regard to transmeridian flights, when a sharp change in time zones is accompanied by the development of desynchronosis, a number of specific recommendations have been developed for the preventive use of melatonin in order to eliminate desynchronosis.
Table 7. Dynamics of Sandoz geriatric scale indicators in 30 patients with sleep disorders during treatment with Melaxen at a dose of 3-4.5 mg/day for 4 weeks |
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Symptoms |
Before treatment |
After treatment |
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Clarity | |||
Memory for current events | |||
Anxiety | |||
Emotional lability | |||
Depression | |||
Fatigue | |||
Dizziness | |||
Headache | |||
Contact | |||
Social activity | |||
The effect of melatonin can only be called a hypnotic: it provides a mild sedative effect, promotes general relaxation, reduces reactivity in response to external stimuli, which leads to a smooth fall asleep. Figuratively speaking, melatonin opens the “gates of sleep” (V.M. Kovalzon, A.M. Vein, 2004). The sedative-hypnotic activity of melatonin is comparable to the effect of benzodiazepine drugs, however, the rational dose of melatonin is 2 orders of magnitude lower, and it is free from numerous side effects of traditional synthetic hypnotics and sedatives.
The effectiveness, safety and good tolerability of the drug Melaxen ® in patients with sleep disorders have been demonstrated in a number of studies based on leading Russian neurological clinics, including the Center for Somnological Research (Vein A.M., Levin Ya.I., 1997) and the department nervous diseases MMA named after. I. M. Sechenova, (Yakhno N.N., 1997). In total, as a result of the studies, it was found that in patients with insomnia, taking the drug Melaxen ® in a dosage of 3-4.5 mg once at night improves night sleep - speeds up falling asleep, reduces the number of night awakenings, improves well-being after waking up in the morning. In addition, these studies have shown that in addition to the normalizing effect on sleep, Melaxen ® has a positive effect on intellectual-mnestic functions and the emotional-personal sphere (Table 7).
Improvement in the emotional-personal sphere and in intellectual-mental functions in patients with insomnia during therapy with melaxen was expressed in a decrease in emotional lability and anxiety, improved mood, increased clarity of consciousness, improved memory for current events, reduced feelings of fatigue, increased social activity and contact. . Studies conducted at the Federal Center for Somnological Research also showed the effectiveness of Melaxen ® therapy in patients with acute cerebrovascular accident. 15 patients were treated in the acute period of stroke (12 of them with ischemic stroke) and insomnia with sleep cycle inversion (with wakefulness at night and drowsiness during the day). During basic therapy, patients received Melaxen ® 3 mg 30 minutes before bedtime at night for 14 days. As a result of the study, it was found that during therapy with Melaxen ®, according to questionnaires, the quality of sleep improves, the total score of night sleep increases and daytime sleepiness disappears; according to polysomnography, the duration of sleep increases, the time to fall asleep decreases, and the number of awakenings from sleep decreases. In addition, the study showed that Melaxen ® combines well with other medications. The researchers conclude that Melaxen ® is the drug of choice for the treatment of sleep disorders in patients with cerebrovascular accidents.
Cardiovascular pathology: arterial hypertension and coronary heart disease
Specific receptors for melatonin are found in smooth muscle cells and the endothelium of blood vessels. Melatonin inhibits platelet aggregation and provides a cardioprotective effect during reperfusion (restoration of blood circulation in the coronary vessels after dry heart surgery).
Currently, there is no doubt that there is a violation of the temporal organization of hemodynamics, manifested by the phenomenon of internal and external desynchronization of circadian and circaseptan rhythms of hemodynamic parameters in patients with arterial hypertension (AH). When using melatonin preparations in patients with essential hypertension, the effect of reducing the level of diastolic blood pressure by an average of 30 mm Hg is noted. Art. A similar effect, but much less pronounced, is observed in healthy volunteers. It is obvious that the pharmacological effect of melatonin directly depends on the initial vascular tone.
A number of hypotheses regarding the mechanism of the hypotensive effect of melatonin are considered. Melatonin, thanks to its synchronizing properties, is able to eliminate the mismatch of circadian rhythms. Secondly, in a number of patients with hypertension, there is hyperreactivity of the pituitary-adrenal system, the function of which is limited by melatonin. In addition, melatonin activates dopaminergic and GABAergic mechanisms, which may be weakened in hypertension. Thirdly, a decrease in the production of PGE2 and other depressants plays a role in the development of hypertension. And melatonin has the property of stimulating the synthesis of PGE2, prostacyclin. And finally, melatonin controls the activity of Ca 2+ channels, the disruption of which is considered one of the key points in the pathogenesis of hypertension.
Few clinical studies have been devoted to the study of melatonin levels in patients with coronary artery disease. These studies indicate that in patients with angina, nocturnal melatonin production is significantly reduced. Moreover, the more severe the form of IHD, the lower the melatonin level. Melatonin levels are especially low in patients with a high risk of myocardial infarction and death. Giroffi L. et al. (2000) studied the level of melatonin in urine in patients with coronary heart disease in comparison with healthy individuals. The results of the study showed that patients with coronary artery disease have low melatonin production compared to healthy individuals. In addition, melatonin levels were lower in the group with unstable angina, i.e. The higher the risk of myocardial infarction, the lower the level of melatonin in the urine. Other studies also show that melatonin levels drop to low levels when near myocardial infarction. The authors determined the level of melatonin in urine at night in patients with angiographically confirmed coronary disease, and also examined the effect of beta-blockers (BAB) on melatonin levels. It was taken into account that most patients receive beta-blockers and there are studies indicating a decrease in melatonin levels under the influence of beta-blockers. Zakotnik et al., (1999) showed that melatonin production in patients with coronary artery disease decreases, however, as these researchers argue, a decrease in melatonin may be a predisposing factor for the occurrence of coronary heart disease, or coronary artery disease itself contributes to a decrease in melatonin synthesis. However, this issue remains controversial.
Melaxen ® in the treatment of arterial hypertension .
Russian researchers Z.M. Zaslavskaya et al. For a number of years, studies have been conducted to study the effectiveness of melatonin in the form of monotherapy and in complex treatment with melatonin with antihypertensive and antianginal drugs in patients with arterial hypertension and coronary heart disease.
In the subjects with arterial hypertension, there was no daily rhythm in a number of the studied hemodynamic parameters (DBP, heart rate, DP); attention was drawn to the shift in the average acrophases of SBP and BP avg. for the night hours. These data indicated a disturbance in the temporary organization of blood circulation with phenomena of internal and external desynchronosis in the subjects examined. Melaxen ® in a dose of 3 mg was prescribed to these patients once a day at 22.00. Before and after a 10-day course of melatonin therapy, the daily profile of blood pressure (BP), heart rate (HR), double product (DP), and central hemodynamic parameters were studied. As a result of the study, it was found that the average daily level of systolic blood pressure (SBP) under the influence of treatment decreased from 161.4 ± 7.9 to 1 35.02 ± 5.9 mm Hg, diastolic blood pressure (DBP) decreased from 90.1 ± 6.6 to 76.1 ± 5.5 mm Hg (R<0,05). Среднее артериальное давление (АД ср.) снизилось со 112.6±6.9 до 95.7±4.4 мм рт.ст. (р<0.05). ЧСС уменьшилось с 71.5±3.3 до 63.4±4.7 ударов в 1 минуту (р<0.05). Общее периферическое сопротивление сосудов статистически достоверно снизилось с 1845.5±196.5 до 1477.9±111.2 дин/сек/см-5 (р<0.05). Удельное периферическое сопротивление сосудов (УПСС) имело тенденцию к снижению. Работа сердца (А) уменьшилась с 0.12±0.003 до 0.105±0.004 Дж (р<0.05). Двойное произведение (ДП) снизилось со 132.5±9.96 до 88.4±7.96 усл.ед. (р<0.05).
These data indicate the hypotensive effect of melatonin, provided by a decrease in total peripheral resistance (TPR). It should also be noted that there is a negative chronotropic effect and a significant reduction in myocardial energy expenditure, as evidenced by a decrease in cardiac function and double abduction. A persistent hypotensive effect occurred on average on day 5 (5.7±0.3). In addition, the study found that Melaxen at a dose of 3 mg normalizes previously disturbed circadian hemodynamics. Thus, rhythms that were absent before exposure to melatonin appear under the influence of treatment (DBP, heart rate, DP), and signs of internal and external desynchronosis are eliminated, synchronization of circadian hemodynamic rhythms is restored. Similar results were obtained when using higher dosages of Melaxen ® in patients with hypertension (Melaxen 6 mg once at night for 10 days). The same researchers revealed an increase in the effectiveness of hypertension therapy in elderly patients in the case of a combination of standard antihypertensive drugs (captopril, enalapril, moxinidine, losartan) with Melaxen ® (3-6 mg/day) compared with monotherapy with standard antihypertensive drugs.
Thus, the inclusion of melatonin in treatment regimens for hypertension in elderly patients allows not only to enhance the effectiveness of therapy with standard antihypertensive drugs, but also to normalize impaired circadian hemodynamics. In addition, this therapy can effectively eliminate sleep disorders, which are often present in patients with hypertension, especially in old age.
Melaxen ® in the complex treatment of coronary heart disease (CHD) .
It is known that not only intracardiac hemodynamics play a major role in the disturbance of myocardial metabolism, but also the activation of lipid peroxidation (LPO), as well as the depletion and then inhibition of antioxidant defense (AOD) and, as a consequence, an imbalance in the oxidant system /antioxidants with the development of oxidative stress. Melatonin is a strong and quite effective free radical inactivator. It interacts with highly toxic hydroxyl radicals, protecting cells from hydroxyl damage. Like indole derivatives of tryptophan, melatonin, as an electron donor and acceptor, is involved in their transfer and, due to the detoxification of free radicals, limits the intensity of peroxidase processes.
A number of authors, in experimental studies on isolated rat hearts, have shown that melatonin leads to a decrease in the amount of free radicals, protecting the myocardium during post-ischemic reperfusion, reduces the size of myocardial infarction and shortens the duration of ventricular tachycardia, and also has an almost neutral effect on hemodynamic parameters and coronary blood flow.
In addition, melatonin affects lipid peroxidation and the activity of antioxidant (AO) enzymes, reducing the level of malondialdehyde and increasing the activity of Cu, Zn-superoxide dismutase and glutathione content.
As part of a study of the effect of melatonin on the course of coronary artery disease and its complications, R.M. Zaslavskaya et al. We studied a group of elderly patients with coronary artery disease, stable angina pectoris class II-III (SS), who had myocardial infarction and suffering from heart failure (HF) class II-III according to the MUNA classification. All patients in this group received standard therapy in combination with Melaxen ® . As a result of the study, it was found that Melaxen ® in daily doses of 3 and 6 mg against the background of standard treatment (nitrates, β-blockers, ACE inhibitors, antiplatelet agents and diuretics) in elderly patients with coronary artery disease, stable angina II-III class, who had a heart attack myocardium and those suffering from class II-III heart failure, has pronounced antianginal and anti-ischemic effects, significantly improving clinical symptoms, reduces the number of episodes of depression and ST segment elevation almost to their complete disappearance.
A higher dose of Melaxen - 6 mg significantly improves the systolic function of the left ventricle, which does not occur when taking Melaxen ® at a dose of 3 mg. In addition, the effect of Melaxen ® in doses of 3 mg and 6 mg on LPO is manifested by a significant decrease in MDA levels.
The authors conclude that, taking into account the wide range of biological activity of melatonin, including its antioxidant, pro-antioxidant, anti-stress effects, as well as its normalizing effect on the chronostructure of hemodynamic parameters and vasodilating effect, the inclusion of melatonin in the complex therapy of patients with coronary artery disease seems appropriate.
Diseases of the gastrointestinal tract
The presence of melatonin has been found throughout the gastrointestinal tract; moreover, as we mentioned above, the synthesis of this hormone occurs in some cells. Melatonin affects the motility of the digestive system, microcirculation and proliferation of mucosal cells. Severe disturbances in the circadian rhythm of melatonin production were revealed in patients with peptic ulcer disease. And, probably, it is no coincidence that exacerbation of peptic ulcer disease occurs most often in the spring season. This period is characterized not only by possible vitamin deficiency, but also by a restructuring of the light regime, which inevitably affects the activity of the pineal gland.
Within the framework of the scientific theme of the laboratory "Chronomedicine and new technologies in the clinic of internal diseases" MMA named after. THEM. Sechenov has been working for more than 10 years to study the role of melatonin in the pathogenesis and clinical picture of internal diseases, including duodenal ulcer (DU) and irritable bowel syndrome (IBS). Researchers (Malinovskaya N.K., Rapoport S.I., Kvetnoy I.M., Raikhlin I.M.) found that during exacerbation of DU, combination therapy with proton pump blockers (omeprazole) in combination with the drug melatonin (Melaxen ® ) provides a more pronounced clinical effect compared to omeprazole monotherapy.
Combination therapy significantly reduces the degree of activity and severity of antral gastritis with the restoration of the ratio of cells producing gastrin and somatostatin and the intracellular content of these hormones to almost control values, which indicates the achievement of deeper remission with combination therapy in the same time frame as with omeprazole monotherapy. With deep remission (almost complete recovery), the circadian rhythms of melatonin production are restored.
Encouraging results were obtained by the same researchers studying the effectiveness of exogenous melatonin in the treatment of irritable bowel syndrome (IBS). Treatment of IBS using Melaxen ® turned out to be more effective than other treatment regimens, which was confirmed by histological and electron microscopic examination of the colon mucosa. It was determined that basic therapy + Melaxen ® is more effective than basic therapy + psychotropic drugs and only basic therapy in terms of normalizing stool and improving sleep in patients with IBS.
Basic therapy + Melaxen ® is comparable in effectiveness to basic therapy + psychotropic drugs in relieving pain and dyspeptic syndromes in patients with IBS, normalizing their mental status, and improving the quality of life.
Prevention of aging
If the pineal gland is the body's sundial, then, obviously, any changes in the length of daylight hours should significantly affect its functions and, ultimately, the rate of aging. A number of studies have shown that disruption of photoperiodicity can lead to a significant decrease in life expectancy.
American researchers M. Hard and M. Ralph discovered that golden hamsters with a special mutation in the gene responsible for the generation of rhythmic signals in the suprachiasmatic nucleus of the hypothalamus (namely, these signals set the rhythm of melatonin production) had a 20% shorter life expectancy than controls . When hypothalamic cells from the fetuses of healthy hamsters were implanted into the brains of old mutant hamsters, restoration of normal life expectancy was noted (Fig. 7).
Destruction of the suprachiasmatic nuclei leads to a reduction in the lifespan of animals. In these nuclei, a whole set of already mentioned genes, called “clock” genes or circadian rhythm genes, exhibit their activity. Disruption of the function of one of the circadian genes, Per2, causes premature aging and increases the sensitivity of mice to the development of tumors. Mutations in another circadian rhythm gene, Clock, in mice lead to the development of obesity and metabolic syndrome, as well as premature disruption of the ovulatory cycle and decreased fertility.
Numerous studies have shown the ability of melatonin to slow down the aging process and increase the lifespan of laboratory animals - fruit flies, flatworms, mice, rats.
Some optimism is caused by publications on the ability of melatonin to increase resistance to oxidative stress and reduce the manifestations of some age-associated diseases in people, such as macular degeneration of the retina, Parkinson's disease, Alzheimer's disease, and diabetes mellitus.
Further comprehensive clinical trials of melatonin are needed, which we believe will significantly expand its use for the treatment and prevention of age-related diseases and, ultimately, premature aging.
Physiological doses of melatonin are 0.1-0.5 mg. Taking them in the evening ensures an increase in the level of the hormone in the blood to a normal physiological level.
The currently accepted therapeutic doses of melatonin in medications and dietary supplements are 3-5 mg. When administered orally, the peak concentration of the hormone is observed after an hour, and a fairly high level in the blood plasma remains for 3-7 hours. Most clinical studies have been conducted using these dosages.
Table 6. Risk groups when taking melatonin
Melatonin may stimulate tumor development
Numerous studies have confirmed the lack of toxic effects of melatonin. However, this does not serve as a guarantee against the side effects of its long-term use in large doses (3-5 mg or more). In this regard, such daily doses of the drug should be taken in courses lasting no more than 3-4 weeks.
In addition to possible disruption of the circadian rhythm when taking the drug outside of normal hours, in this case serious endocrine disturbances may occur.
It should not be forgotten that excess melatonin production causes hypogonadism in men and amenorrhea in women. Children are especially sensitive to the effects of melatonin.
It is also necessary to remember about the possible interaction of melatonin with other drugs that share metabolic pathways with it. Melatonin inactivation occurs in the liver with the participation of microsomal oxidases and cytochrome P450. Any drug that inhibits or activates this system will have an effect on circulating melatonin levels, and vice versa.
How to increase and harmonize the production of your own melatonin?
(R. J. Reiter, J. Robinson, 1995)
- Make time every day to spend time in the sun (in the light). If this is not possible, create an optimal regime of artificial daylight.
- Don't stay at the computer or TV past midnight. The duration of sleep at night should be sufficient to feel alert and rested in the morning. For many this takes more than 8 hours.
- Do not turn on the lights in the bedroom at night; hang thick curtains on the windows to block out light from the street. As a last resort, you can wear a blindfold made of fabric that does not transmit light.
- If possible, avoid night work and long transmeridian flights.
- Quit smoking, limit alcohol consumption.
- If possible, avoid taking medications that reduce melatonin levels.
- Include foods rich in antioxidants, calcium, magnesium, niacin and pyridoxine in your diet or take vitamin and mineral complexes.
- Eat a banana, a piece of turkey, chicken, soft cheese, a handful of pumpkin seeds, and almonds at night. All of these foods are rich in tryptophan (a precursor to melatonin).
- Set aside time every day for meditation, auto-training or a walk.
Provides adequate sleep restoration of the human body, strengthens his health, increases efficiency. All life processes are subject to biorhythms. Sleep and wakefulness are a manifestation of circadian (daily) surges and declines in the physiological activity of the body.
A good night's sleep is ensured by the hormone melatonin, which is also called the hormone of youth and longevity. If a person has no problems falling asleep, he sleeps in sufficient quantities, the body has a much greater chance of efficiently producing complex biochemical, synthetic reactions aimed at the full restoration of all structures.
General information
Melatonin is the main hormone of the pineal gland, regulator of circadian rhythms. The sleep hormone has been known to the world since 1958; its discovery belongs to the American professor, Aaron Lerner.
Melatonin molecules are small and highly soluble in lipids, which allows them to easily penetrate cell membranes and influence many reactions, such as protein synthesis. In newborns, melatonin begins to be produced only at three months. Before that, they get it through their mother's milk. In the first years of a child’s life, the concentration of the hormone is maximum and gradually begins to decrease over the years.
During the day, the hormone of happiness is active, and with the arrival of darkness it is replaced by the hormone of sleep. There is a biochemical connection between melatonin and serotonin. From approximately 23:00 to 5:00 the highest concentration of the hormone in the body.
Functions of melatonin
Hormone functions are not limited to just managing the processes of sleep and wakefulness. Its activity is manifested in providing other important functions; it has a healing effect on the body:
- ensures cyclical circadian rhythms;
- helps to resist stress;
- slows down the aging process;
- is a powerful antioxidant;
- strengthens immune defense;
- regulates blood pressure and has a beneficial effect on blood circulation;
- controls the functioning of the digestive organs;
- neurons containing melatonin live much longer and ensure full functioning of the nervous system;
- resists the development of malignant neoplasms (research by V. N. Anisimov);
- influences the processes of fat and carbohydrate metabolism, maintains body weight within normal limits;
- influences the synthesis of other hormones;
- reduces pain from headaches and toothaches.
Such actions are provided endogenous melatonin(a hormone produced in the body). Pharmacologists, using knowledge about the therapeutic effect of the sleep hormone, have created drugs containing artificially synthesized (exogenous) melatonin. They are prescribed for the treatment of insomnia, chronic fatigue, migraines, and osteoporosis.
Such medications are used by blind people to normalize sleep. They are prescribed to children with serious developmental disabilities (autism, cerebral palsy, mental retardation). Melatonin is used in complex therapy for those who have decided to quit smoking (the craving for nicotine is reduced). The hormone is prescribed to reduce side effects after chemotherapy.
How and when the hormone is produced
With the onset of darkness, melatonin production begins, by 21:00 its growth is observed. This is a complex biochemical reaction that occurs in the pineal gland (pineal gland). During the day, a hormone is actively formed from the amino acid tryptophan. And at night, under the influence of special enzymes, the joy hormone turns into a sleep hormone. Thus, serotonin and melatonin are connected at the biochemical level.
These two hormones are necessary to ensure the functioning of the body. Melatonin is produced at night; from approximately 11 p.m. to 5 a.m., 70% of the daily amount of the hormone is synthesized.
To avoid disrupting melatonin secretion and sleep, It is recommended to go to bed no later than 10 pm. In the period after 0 and before 4 o'clock you need to sleep in a dark room. If it is impossible to create absolute darkness, it is recommended to use a special eye mask and close the curtains tightly. If you need to stay awake during the active synthesis of a substance, it is better to create dim lighting in the room.
Melatonin is produced in the dark. The detrimental effect of lighting on hormone production.
There are products that catalyze the production of the hormone. The diet should contain foods rich in vitamins (especially B vitamins) and calcium. It is important to balance your intake of complex carbohydrates and proteins.
How it affects the body
Normal concentrations of melatonin ensure easy falling asleep and full, deep sleep. In winter, in cloudy weather, when the amount of light is insufficient, the hormone has a depressing effect on the body. There is lethargy and drowsiness.
In Europe, the Life Extension Foundation is conducting clinical trials using melatonin in the treatment of cancer. The foundation claims that cancer cells produce chemicals similar to pineal hormones. If you influence them with a combination of thyroid hormones and melatonin, the body begins to actively produce cells for immune defense.
To treat depression and prevent many mental disorders, it is enough to sleep or take medications that contain melatonin. It is also important to be in the sun during the daytime.
Experiments on mice
Mice of the same age, to which the cancer gene was introduced, were divided into 2 groups.
One part of the animals was kept in natural conditions; the group had daylight and darkness at night.
The second group was illuminated around the clock. After a while, the experimental mice from the second group began to develop malignant tumors. Studies were carried out on various indicators and it was revealed that:
- accelerated aging;
- excess insulin;
- atherosclerosis;
- obesity;
- high incidence of tumors.
Melatonin deficiency and excess
Consequences of long-term melatonin deficiency:
- at the age of 17, primary signs of aging appear;
- the number of free radicals increases 5 times;
- within six months, weight gain ranges from 5 to 10 kg;
- at the age of 30, women experience menopause;
- the risk of breast cancer increases by 80%.
Causes of lack of sleep hormone:
- chronic fatigue;
- night work;
- puffiness under the eyes;
- sleep disorders;
- anxiety and irritability;
- psychosomatic pathologies;
- vascular diseases;
- stomach ulcer;
- dermatoses;
- schizophrenia;
- alcoholism.
Symptoms of an excess of the hormone are:
- increased heart rate;
- lack of appetite;
- increased blood pressure;
- slow reactions;
- contraction of facial muscles, twitching of shoulders and head.
Excess melatonin causes seasonal depression.
Melatonin tests and norms
The daily norm of the sleep hormone in an adult is 30 mcg. Its concentration by one in the morning is 30 times higher than during the day. In order to provide this amount, eight hours of sleep is required. In the morning, the normal concentration of the hormone is 4-20 pg/ml, at night – up to 150 pg/ml.
The amount of melatonin in the body depends on age:
- up to 20 years of age there is a high level;
- up to 40 years – average;
- after 50 – low, in older people it decreases to 20% and below.
Melatonin does not decrease in centenarians
As a rule, the analysis is performed only by large medical institutions, since it is not among the common laboratory tests.
Biomaterial samples are taken at short intervals, recording the time of day. The analysis requires special preparation:
- 10-12 hours in advance you should not consume medications, alcohol, tea, coffee;
- It is better to donate blood on an empty stomach;
- For women, the day of the menstrual cycle is important, so you should first consult with a gynecologist;
- You should donate blood before 11:00;
- It is not advisable to subject the body to other medical manipulations and procedures before analysis.
The sleep hormone melatonin does not accumulate. It is impossible to get enough sleep or compensate for the lack of sleep. Disruption of natural daily biorhythms leads to disruption of the synthesis of the substance, and this causes not only insomnia, but also exposes the body to the development of diseases.
The lack of sunlight triggers the body's natural production of melatonin for sleep, disrupting this process and disrupting an important human biological clock.
Melatonin- the main hormone of the pineal gland, regulator of circadian rhythms.It is taken in tablets to facilitate falling asleep, in order to correct the “internal clock” during long journeys (see jet lag).
Available in tablets, it is considered a dietary supplement in the USA. In Russia it is available as a drug under the names Melaxen, Melapur, Melaton, Yukalin, Circadin. Also available in sports nutrition stores, most often under the name Melatonin.
Main functions
Regulates the activity of the endocrine system, blood pressure, sleep frequency
Regulates seasonal rhythms in many animals
Slows down the aging process
Enhances the effectiveness of the immune system
Has antioxidant properties
Affects adaptation processes when changing time zones
In addition, melatonin is involved in the regulation
blood pressure,
functions of the digestive tract,
work of brain cells.
Effect on the secretion of other hormones and neurotransmitters
Circadian rhythm and sleep
One of the main actions of melatonin is to regulate sleep. Melatonin is the main component of the body's pacemaker system. It takes part in the creation of the circadian rhythm: it directly affects cells and changes the level of secretion of other hormones and biologically active substances, the concentration of which depends on the time of day. The effect of the light cycle on the rhythm of melatonin secretion is shown in observations of blind people. Most of them exhibit rhythmic secretion of the hormone, but with a freely varying period that differs from the daily cycle (25-hour cycle compared to 24-hour daily). That is, in humans, the rhythm of melatonin secretion has the form of a circadian melatonin wave, “freely running” in the absence of a change in light-dark cycles. A shift in the rhythm of melatonin secretion also occurs when flying across time zones.
The role of the pineal gland and epiphyseal melatonin in the daily and seasonal rhythms, sleep-wake patterns seems undeniable today. In diurnal (daytime) animals (including humans), the secretion of melatonin by the pineal gland coincides with the usual hours of sleep. Studies have shown that an increase in melatonin levels is not a mandatory signal for the onset of sleep. In most subjects, taking physiological doses of melatonin caused only a mild sedative effect and reduced reactivity to common environmental stimuli. There is a hypothesis that melatonin plays a role in opening the so-called sleep gates, in inhibiting wakefulness, and not in directly influencing somnogenic structures of the brain. According to physiologists-somnologists, the opening of the “sleep gate” is preceded by a period of increased human activation - a “forbidden period” (“forbidden zone”) for sleep, which quite abruptly gives way to the “opening of the gate.”
With age, the activity of the pineal gland decreases, so the amount of melatonin decreases, sleep becomes superficial and restless, and insomnia is possible. Melatonin helps eliminate insomnia, prevents disruption of the body's daily routine and biorhythm. Insomnia and lack of sleep give way to healthy and deep sleep, which relieves fatigue and irritability. During calm, deep sleep, the functioning of all internal organs and systems in the body is normalized, muscles relax, the nervous system rests, and the brain has time to process the information accumulated during the day. As a result, the person feels cheerful and healthy.
Anti-stress effect
After experiments and direct clinical observations, the concept was formulated that the pineal gland and its hormone melatonin are part of the body's defense system against adverse effects. The pineal gland and melatonin play a nonspecific role, but pineal gland support is provided at all levels of stress management. In the case of a prolonged stressful situation, a two-phase reaction is observed: an initial decline in epiphyseal activity in the resistant phase of stress with a further sharp rise. In experiments on rats, it was shown that melatonin is able to change a negative emotional state and reduce anxiety, which is provoked by various stressors. According to numerous observations, the hormone stabilizes the activity of various endocrine systems disorganized by stress, including eliminating excess stress adrenal hypercortisolism.
Immunostimulating effect
An important consequence of long-term stress is stress-induced immunodeficiency. Melatonin helps normalize immunological parameters.
Melatonin and other epiphyseal hormones can be classified as geroprotective. A connection has been established between the degree of age-related involution of the pineal gland and tissue deterioration. It is known that with aging, the degree of immunological protection decreases, and melatonin, as has been repeatedly indicated, has immunomodulatory activity.
Melatonin stimulates the immune system (immunostimulant) as it participates in the regulation of thymus and thyroid function, increasing the activity of T cells and phagocytes, which is a warning for a number of diseases and, as laboratory studies show, slows the growth of seven types of cancer cells, including cancer cells mammary and prostate glands.
Lack of melatonin in the body
Experiments on laboratory animals showed that with a lack of melatonin caused by the removal of receptors, the animals began to age faster: menopause began earlier, free radical cell damage accumulated, insulin sensitivity decreased, obesity and cancer developed.
Antitumor effect
In the early stages of embryonic development, biogenic amines, including melatonin, play the role of specialized cell signaling molecules that regulate cellular renewal processes. It has been established that melatonin can suppress cell proliferation, and the strength of its effect is not inferior to the powerful cytotoxic agent colchicine. In a number of studies on laboratory animals and in tumor tissue culture systems, it was found that melatonin has an antitumor, oncostatic effect. The mechanisms of melatonin's effect on tumor growth are diverse: it can influence the synthesis and secretion of pituitary and sex hormones, can modulate the immune response in the presence of tumor cells and have a direct cytotoxic effect. There are suggestions that melatonin may enhance the expression of adhesion molecules and thereby prevent tumor growth, since it is known that in most malignant tumors there are disturbances in cell adhesion and defects in functional intercellular connections.
Melatonin metabolite significantly positively correlates with a reliable marker of proliferative activity of tumor cells - proliferating cell nuclear antigen (PCNA). This indicator reflects the degree of tumor progression, that is, melatonin metabolites can serve as a reliable diagnostic factor. Under the influence of melatonin, in some forms of cancer (breast, ovarian, prostate, etc.), a decrease in the proliferative capacity of cells was observed and an increase in the number of cells dying in the form of apoptosis (oncostatic effect). Nuclear receptors of cancer cells can serve as a target for the implementation of the antitumor effects of melatonin.
In vitro, melatonin was shown to suppress the growth of melanoma cells, although the effect of the hormone depended on the intensity of tumor proliferation: growth was inhibited at moderate, but not at high cell proliferative activity. The effects of melatonin were dose-dependent, but the mechanism of oncostatic action is currently still not fully understood. Epidemiological data indicate that women working night shifts, aviation employees (flight attendants, air traffic controllers), radio and telegraph operators have an increased risk of developing breast cancer, while in women who are primarily blind (that is, having light deprivation), this risk is 2 times less.
Antioxidant effect
Melatonin neutralizes the destructive effects of oxidative processes, which are the main cause of aging and aging of the skin. The most important function of melatonin is antioxidant activity, which manifests itself throughout the body, since melatonin penetrates into all organs and tissues. The mechanism of antioxidant action is manifested in the fact that melatonin has a pronounced ability to bind free radicals, including hydroxyl radicals formed during lipid peroxidation, and exogenous carcinogens; it also activates glutathione peroxidase, a factor that protects the body from free radical damage. The main functions of the antioxidant action of melatonin are aimed at protecting DNA. To a lesser extent on the protection of proteins and lipids.
Melatonin is the most powerful endogenous free radical scavenger known. In recent years, evidence has emerged that melatonin can be localized not only in plasma, but also in cell nuclei and protect nuclear macromolecules from oxidative damage in all subcellular structures.
