Melatonin and sleep-wakefulness: why synchronization of biological rhythms and adherence to daily periodicity is important

By Yraa #ability, #absence, #absolutely, #according, #accordingly, #achieve, #actually, #adapt, #additional, #adherence, #affect, #affected, #against, #age, #allows, #almost, #analyze, #answer, #antioxidant, #any, #anyone, #anywhere, #appearance, #appointment, #asleep, #associated, #attention, #away, #background, #becomes, #bedtime, #been, #believe, #benefits, #between, #biochemical, #biological, #block, #blood, #Body, #build, #c, #calculate, #called, #careful, #carefully, #cases, #cause, #causes, #cells, #central, #certain, #changing, #characterized, #chronic, #Clear, #Clinical, #clock, #color, #combat, #combination, #completely, #complex, #conclusions, #condition, #conditions, #consider, #considered, #content, #continue, #Control, #coordination, #corresponds, #cross, #cure, #cycles, #daily, #dark, #decrease, #decreases, #degree, #dependent, #depression, #designed, #determine, #dietary, #different, #direct, #diseases, #disorder, #disorders, #disturbance, #doctors, #dose, #doses, #drug, #due, #duration, #e, #effect, #effective, #effectiveness, #effects, #efficiency, #elderly, #element, #emotions, #enters, #especially, #established, #even, #everything, #evidence, #examination, #example, #experience, #expert, #fact, #factors, #fall, #falling, #falls, #faster, #few, #fight, #flow, #fluctuations, #foreign, #form, #found, #functioning, #functions, #gastrointestinal, #general, #gives, #gland, #glands, #go, #great, #gym, #had, #hair, #half, #harm, #health, #Healthy, #heart, #heavy, #help, #Helps, #high, #higher, #highly, #himself, #his, #hormonal, #however, #huge, #human, #hypertension, #immune, #impossible, #improves, #improving, #increased, #index, #indicates, #individual, #influence, #initial, #injury, #insomnia, #introduction, #involved, #issue, #itself, #just, #key, #know, #lack, #larger, #later, #latter, #lead, #level, #levels, #lifestyle, #Light, #limit, #little, #located, #long, #lower, #made, #mainly, #maintaining, #makes, #manifestations, #mass, #maximum, #meaning, #Medical, #medicine, #melatonin, #mental, #mg, #minimum, #mistake, #ml, #moment, #moreover, #muscle, #nature, #negative, #nervous, #network, #night, #normally, #now, #observed, #occurs, #old, #ones, #optimal, #ordinary, #organs, #our, #pancreas, #part, #particular, #pathological, #patients, #people, #perform, #phase, #physiological, #poisoning, #practical, #practically, #practice, #preparation, #preparations, #problems, #processes, #produce, #production, #promotes, #protective, #quality, #question, #quite, #range, #rapid, #rather, #reactions, #real, #really, #reasons, #receive, #received, #recommended, #Reduce, #reduces, #regularly, #regulation, #remember, #remembered, #required, #requires, #responsible, #result, #rhythm, #rhythms, #right, #safe, #safety, #say, #scientists, #seasonal, #second, #seems, #serious, #shift, #shifts, #shown, #shows, #side, #significant, #simple, #single, #Skin, #sleep, #Sleeping, #small, #smaller, #smoking, #solve, #some, #something, #somewhat, #special, #spine, #starting, #strictly, #stronger, #studies, #substance, #successfully, #supplement, #supply, #surface, #system, #systems, #take, #taken, #taking, #talk, #task, #term, #tests, #therapy, #therefore, #thinking, #those, #times, #tissues, #today, #too, #tract, #traditional, #treat, #treatment, #true, #Types, #under, #understand, #used, #using, #values, #variety, #various, #versatile, #very, #vitamins, #wakefulness, #was, #way, #weak, #wear, #while, #who, #why, #widely, #will, #winter, #working, #works, #would, #year, #zones

Mela­tonin, in the minds of most peo­ple, is a cross between a sleep­ing pill, a dietary sup­ple­ment, and some­thing col­or­ing. The lat­ter is explained by the con­so­nance in name with the pig­ment melanin, which is respon­si­ble for the col­or of the skin and hair in humans. Mean­while, mela­tonin is a hor­mone, which means that it is involved in many process­es in the human body, many of which have lit­tle to do with sleep.

What is melatonin

Mela­tonin is the main hor­mone of the pineal gland, the pineal gland of the brain. It is also pro­duced by lym­pho­cytes and ente­rochro­maf­fin cells locat­ed in the gas­troin­testi­nal tract (GIT) — in par­tic­u­lar, in the pan­creas and hepa­to­bil­iary sys­tem (organs that form bile). More­over, the lev­el of mela­tonin in the intes­tine is 10–100 times high­er than in the blood, and 400 times high­er than in the pineal gland.

Accord­ing­ly, they say:

    epiphyseal (central) melatonin and
    paracrine (regional, peripheral) melatonin.

If you com­plete­ly block the body’s abil­i­ty to receive cen­tral mela­tonin from the pineal gland, then the periph­er­al one will not go any­where and will con­tin­ue to work. There­fore, sci­en­tists believe that one of the func­tions of mela­tonin is the coor­di­na­tion of cel­lu­lar func­tions at the lev­el of indi­vid­ual organs.

In addi­tion, mela­tonin is the old­est antiox­i­dant (and it is stronger than vit­a­mins C and E), which is found in almost all liv­ing organ­isms on Earth. So along the way, it can per­form pro­tec­tive func­tions, pro­tect­ing indi­vid­ual organs and tis­sues from oxida­tive stress.

Mela­tonin lev­els decrease dur­ing a per­son­’s life for the fol­low­ing rea­sons:

    Elderly age.
    Carcinogenesis.
    Smoking.
    Increased body mass index.

Con­sid­er­ing the issue of using mela­tonin to influ­ence the body from the out­side, we should talk about:

    endogenous melatonin, which is produced in the body and
    exogenous melatonin, which a person enters in the form of drugs.

Melatonin for sleep: pros and cons

Melatonin and biological rhythms

Mela­tonin is a key ele­ment of the “mol­e­c­u­lar clock” of all ani­mals on Earth. The max­i­mum pro­duc­tion of mela­tonin in the pineal gland falls on the dark time of the day (200 pg/ml and more), and the min­i­mum — on the light day (no more than 10 pg/ml). The pineal gland is asso­ci­at­ed with the suprachi­as­mat­ic nuclei of the hypo­thal­a­mus, which are the cir­ca­di­an pace­mak­er, that is, they are respon­si­ble for fluc­tu­a­tions in var­i­ous body func­tions dur­ing the day.

The main task of mela­tonin is the syn­chro­niza­tion of bio­log­i­cal rhythms and the obser­vance of dai­ly peri­od­ic­i­ty. More­over, mela­tonin allows you to build in a sin­gle rhythm not only the “sleep-wake­ful­ness” sys­tem, but also the sys­tems respon­si­ble for mem­o­ry, think­ing, log­ic and human emo­tions — main­tain­ing them in work­ing con­di­tion is part of a healthy lifestyle.

Sci­en­tists believe that it is this abil­i­ty that makes it pos­si­ble to use the exoge­nous mela­tonin prepa­ra­tion to com­bat the man­i­fes­ta­tions of desyn­chrono­sis (dis­tur­bance of dai­ly human bio­rhythms) dur­ing flights between dif­fer­ent time zones, to treat sleep dis­or­ders and some men­tal dis­or­ders.

Other abilities of melatonin

Mela­tonin recep­tors are found not only in the gas­troin­testi­nal tract, but also in the myocardi­um (heart mus­cle), in vas­cu­lar and blood cells. This diver­si­ty indi­cates a high lev­el of mela­tonin ver­sa­til­i­ty. For exam­ple, hor­mone recep­tors have been found on the sur­face of cer­tain immune sys­tem cells. There­fore, it is an immunos­tim­u­lant, and is also involved in the reg­u­la­tion of sea­son­al and lunar cycles in humans.

In gen­er­al, it is a mis­take to con­sid­er mela­tonin a hor­mone that can only be used to treat sleep dis­or­ders. The effec­tive­ness of mela­tonin has been demon­strat­ed in trau­mat­ic brain injury, epilep­sy, Alzheimer’s and Parkin­son’s dis­eases, hyper­ten­sion, angi­na pec­toris, cer­tain types of arrhyth­mia, cer­tain types of depres­sion, eczema, glau­co­ma and cataracts, and also as part of com­plex ther­a­py for cer­tain types of can­cer.

Sci­en­tists are also pay­ing spe­cial atten­tion to the abil­i­ty of mela­tonin to reduce the side effects of var­i­ous phar­ma­cother­a­pies. Mela­tonin is suc­cess­ful­ly used for var­i­ous kinds of intox­i­ca­tion: from drug over­dose to poi­son­ing with indus­tri­al poi­sons or salts of heavy met­als.

It should be remem­bered that mela­tonin is a hor­mone. So, epi­phy­seal mela­tonin can affect the work of some endocrine glands, for exam­ple, the pro­duc­tion of hor­mones by the adren­al cor­tex. That is, we can say that, in addi­tion to its direct effect on many body sys­tems, mela­tonin also has an indi­rect effect, start­ing the pro­duc­tion of oth­er hor­mones.

Melatonin and sleep

Prac­tice has shown that tak­ing mela­tonin prepa­ra­tions real­ly helps a per­son fall asleep. And the low­er the lev­el of his own, endoge­nous mela­tonin, the stronger the effect of the exter­nal, exoge­nous drug. But at the same time, the dura­tion of sleep does not change. But the com­bi­na­tion of mela­tonin with oth­er drugs (ben­zo­di­azepines) improves sleep qual­i­ty, dura­tion, reduces the time to fall asleep and the num­ber of night awak­en­ings.

In addi­tion, the effect of mela­tonin is high­ly depen­dent on what time of day it was tak­en. So, if the patient received mela­tonin in the first half of the night or right before bed­time, then the phase change of his cir­ca­di­an rhythms occurs faster. If the drug was tak­en in the sec­ond half of the night or in the first half of the day, then the phase change of cir­ca­di­an rhythms, on the con­trary, occurs lat­er. There­fore, the best time to take the med­i­cine is the time of 22–23 hours.

Melatonin for sleep: pros and cons

Benefits of melatonin preparations

    Safety.

Mela­tonin is not a for­eign sub­stance for our body, we our­selves know how to pro­duce it. There­fore, it is quite safe as a drug — even high dos­es (100–150 mg dai­ly) do not lead to an over­dose.

    Efficiency.

Mela­tonin is a hor­mone. Even in small dos­es (3–5 mg) it gives a real clin­i­cal effect, for exam­ple, in the fight against insom­nia.

Disadvantages of melatonin preparations

    Lack of evidence for safety and efficacy.

Too few obser­va­tions have been made when tak­ing the drug, so that it can be con­sid­ered with 100% cer­tain­ty that it is absolute­ly safe and, more­over, effec­tive.

    Atypical dependence of the effect on the dose of the drug taken.

For most drugs, depen­dence is observed: a larg­er dose — a stronger effect, up to an over­dose. Not every­thing is so sim­ple with mela­tonin: start­ing from a cer­tain dose, the effect not only decreas­es, but can even take on neg­a­tive val­ues. Dur­ing the exper­i­ments, it was found that at cer­tain dosages, mela­tonin, which had just pro­tect­ed against oxida­tive stress, on the con­trary, began to increase stress man­i­fes­ta­tions. Accord­ing to oth­er stud­ies, the hypno­genic effect of mela­tonin will be high­er if you take a dose 10 times small­er than what is rec­om­mend­ed by doc­tors today.

    The need to analyze the initial hormonal background.

Since mela­tonin is pro­duced by the per­son him­self, before pre­scrib­ing its intro­duc­tion from the out­side, it is nec­es­sary to deter­mine not only the con­tent of the hor­mone in var­i­ous human bio­log­i­cal flu­ids, but also to cal­cu­late the curve of the dai­ly pro­duc­tion of epi­phy­seal mela­tonin.

    duration of treatment.

To achieve a real effect, long cours­es of treat­ment (3–4 months) are required.

    Weak directional effect.

Mela­tonin works best in com­bi­na­tion with oth­er drugs, more tra­di­tion­al for the treat­ment of the same insom­nia.

    Lack of control.

Mela­tonin is involved in a huge num­ber of bio­chem­i­cal process­es in the body. It is impos­si­ble to con­trol them com­plete­ly. But you need to under­stand exact­ly that when tak­ing a hor­mon­al drug, we trig­ger dozens, if not hun­dreds, of reac­tions, most of which we actu­al­ly do not need at the moment.

conclusions

    Melatonin in the body is designed mainly to adapt to changing environmental conditions. In ordinary life, it should be used to treat desynchronosis and to adapt to night shift work.
    It is best to use melatonin as an additional drug as part of complex therapy.
    You can not prescribe yourself melatonin on your own, without examination and tests, without the recommendations of a neurologist.
    You should not only carefully calculate the dose, taking into account the mass of influencing factors, but also take the drug at a strictly defined time of day, so as not to get the opposite effect.

Expert commentsMashilov Stanislav Kirillovich, neurologist of the network of medical centers I CURE

Mashilov Stanislav Kir­illovich, neu­rol­o­gist of the net­work of med­ical cen­ters I CURE

Mela­tonin prepa­ra­tions have been wide­ly used in clin­i­cal prac­tice since their appear­ance. The main indi­ca­tions for its appoint­ment are the so-called “desyn­chronoses” (“jet lag”) — sleep dis­or­ders with a rapid change in time zones as a result of flights, as well as due to work on night shifts.

In sleep dis­or­ders not relat­ed to the above rea­sons, the effec­tive­ness of this drug seems to be very mod­est. How­ev­er, mela­tonin is con­sid­ered as a treat­ment for sleep dis­or­ders in the elder­ly asso­ci­at­ed with age-relat­ed changes in the metab­o­lism of this hor­mone in the body (again, if insom­nia is not asso­ci­at­ed with oth­er patho­log­i­cal con­di­tions). When tak­ing mela­tonin on a course, it is impor­tant to remem­ber that the opti­mal time for tak­ing it is 22–23 hours, which cor­re­sponds to the dai­ly rhythm of its pro­duc­tion in the body. In gen­er­al, the drug has not estab­lished itself as a “panacea”, and its appoint­ment requires a clear def­i­n­i­tion of indi­ca­tions.

Sum­ming up, I would like to say that sleep dis­or­ders, espe­cial­ly long-term ones, are char­ac­ter­ized by a large vari­ety of caus­es, there­fore their treat­ment is a com­plex task, requir­ing a care­ful and ver­sa­tile assess­ment by the doc­tor of the patien­t’s con­di­tion.

Sergey Alexandrovich Beshkarev, neurologist, CDC MedsiSergey Alexan­drovich Beshkarev, neu­rol­o­gist, CDC Med­si

I will answer the main ques­tion right away — of course, “for”, “against” — only if there is no effect from the drug. The drug Melax­en (active ingre­di­ent mela­tonin) works great, espe­cial­ly in young and not “neglect­ed” patients. And then, the mean­ing of the word “against” is not that the drug will harm the patient or have some side effects, but that in the absence of the effect of mela­tonin in this par­tic­u­lar per­son, it is nec­es­sary to solve his prob­lem with dis­turbed sleep more wide­ly. and com­plex than just tak­ing a drug that pro­motes falling asleep.

Has any­one won­dered what the main phys­i­o­log­i­cal cause of sleep dis­tur­bance is? My prac­ti­cal expe­ri­ence shows that for the first time a sleep dis­or­der occurs in peo­ple in the range of about 40–50 years. True, now the low­er lim­it of age against the back­ground of the real­i­ties of our life tends to decrease.

The fact is that by the age of 35–40, many peo­ple expe­ri­ence sig­nif­i­cant changes in the cer­vi­cal spine of a degen­er­a­tive nature, while the blood flow through the ver­te­bral arter­ies, which sup­ply blood to the auto­nom­ic cen­ters of the brain, is pro­nounced­ly affect­ed. And sleep is a man­i­fes­ta­tion of a nor­mal­ly func­tion­ing auto­nom­ic ner­vous sys­tem. Under con­di­tions of chron­ic hypox­ia of the veg­e­ta­tive cen­ters and, above all, the hypo­thal­a­mus, due to defi­cient blood sup­ply to the brain through the sys­tem of ver­te­bral arter­ies, dis­turbed sleep becomes one of the first man­i­fes­ta­tions of seri­ous mal­func­tions in the auto­nom­ic ner­vous sys­tem. These are the cas­es when mela­tonin does not help.

There­fore, in a 40-year-old per­son, tak­ing into account the age and indi­vid­ual degree of “wear and tear” of the cer­vi­cal spine under con­di­tions of per­ma­nent stress, over­work, with a rather long win­ter and a long absence of sun in our geo­graph­ic lat­i­tudes, the prob­lem of improv­ing sleep should be approached some­what dif­fer­ent­ly. In any case, it has been noticed that those who reg­u­lar­ly work out in the gym “for health” have prac­ti­cal­ly no prob­lems with sleep dis­tur­bance.

By Yraa

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