How important is vitamin D for adults? Data from numerous studies prove that a deficiency of the substance leads to disorders of bone and mineral metabolism, increases the risk of cancer and chronic diseases, and worsens overall health. Well, since residents of modern megacities are not able to maintain calciferol levels naturally, it is necessary to replenish it with a balanced diet and taking nutritional supplements.
This is interesting. Calciferol can manifest itself in the adult body as both a vitamin and a hormone. In the latter role, it affects the functioning of the kidneys, intestines and muscles.
Vitamin D2 is obtained from ergosterol and is used as a food additive. They enrich bread, milk, and infant formula. Cholecalciferol is natural vitamin D3 is synthesized in the skin under the influence of sunlight or enters the body with food. You can read about which foods contain vitamin D.
The main function of calciferols is to maintain the phosphorus-calcium balance in the body, improve the absorption of these microelements in the intestine and further distribution throughout the musculoskeletal structure.
What else is vitamin D responsible for?
- cell growth and reproduction;
- blood sugar level;
- transmission of nerve impulses;
- synthesis of a number of hormones;
- metabolic processes.
Calciferols are a necessary part of the diet. The daily requirement of an adult is 600 IU or 15 mg of the active substance.
Vitamin D, like other fat-soluble compounds, can accumulate in tissues and is gradually consumed. It is quite resistant to high temperatures And long-term storage products.
Why is vitamin D useful for adults?
What does calciferol affect in the body? Its role is not limited to maintaining phosphorus-calcium metabolism and protecting the bone structure. Active substance has a lot of other beneficial properties:
- increases immunity;
- improves blood composition and clotting;
- corrects the functioning of the thyroid gland;
- prevents the development of myasthenia gravis;
- restores the passage of nerve impulses;
- speeds up metabolism;
- eliminates dry skin and hair;
- regulates the functioning of the heart and blood vessels;
- supports blood pressure;
- prevents the development of tumors.
The benefits of vitamin D for adults do not end there. Of particular interest is the ability of calciferol to counteract chronic diseases autoimmune nature: diabetes and arthritis.
The antitumor properties of the substance are of great importance for the body. The vitamin can prevent or slow down the development of such terrible illnesses, such as cancer of the brain, breast, ovaries, prostate. It is also used to fight leukemia.
The ability of calciferol to restore the myelin sheath of nerve fibers is used in the treatment of multiple sclerosis. To treat skin ailments in adults, vitamin D is taken orally or used externally in the form of ointments. For example, for psoriasis, patients are prescribed drugs such as Daivonex, Silkis, Psorkutan, Curatoderm.
How else does calciferol help adults? It is known that in conditions of severe vitamin D deficiency, a person absorbs calcium worse. This is very bad for your teeth. In areas where the sun is a rare visitor, many suffer from caries and other problems associated with a lack of substance.
However, calciferol can bring not only benefits, but also harm. Remember this and don't get carried away with taking vitamin D.
Why do women need vitamin D3?
The increased need of the female body for cholecalciferol is associated primarily with physiological characteristics. Stress at home and at work, pregnancy, breastfeeding, blood loss during menstruation - all this greatly increases the consumption of vitamin D3. This deficit becomes especially obvious after 40 years. According to statistics, it develops in 8 out of 10 representatives of the fairer sex.
The onset of menopause makes the situation even worse. Female body During this period, people are especially susceptible to the development of such painful conditions as diabetes, oncology, obesity, hypertension, and depression. A lack of vitamin D3 plays an important role in the formation of these ailments.
Attention. Cholecalciferol normalizes blood glucose levels and reduces the risk of diabetes mellitus by 30–40%.
Osteoporosis, which affects almost 30% of women after 50 years, is manifested by fragility and brittleness of bones, osteopenia. With a lack of cholecalciferol, calcium residues are washed out of the skeleton, and fractures and cracks become frequent guests.
A sufficient amount of cholecalciferol prevents or slows down the development of these ailments, improves the functioning of the heart and blood vessels, and ensures normal psychological condition representatives of the fair sex.
How to compensate for vitamin D3 deficiency?
How to increase the level of nutrients in the body? Of course, you can reconsider your diet and get out in the sun more often. It is very beneficial for skin and hair. But in the autumn-winter period this is not enough. Food additives that are oil or aqueous solutions cholecalciferol.
However, if used excessively, the drugs will bring not only benefits, but also harm to the woman. An overdose will cause a lot of unpleasant consequences and have a negative impact on health.
It is preferable to start using vitamin-mineral complexes that combine D3 and calcium.
For example, these:
- Natekal D3;
- Complivit calcium D3;
- Multi-tabs vitamin D3;
- Calcium-D3 Nycomed.
Reception complex drugs useful not only for bones, but also for the face. A properly selected combination of vitamins and microelements will eliminate dryness and flaking, reduce the severity of wrinkles, and make the skin young and fresh.
How to take cholecalciferol during menopause? Adult women require a daily vitamin intake of 400–600 IU. You will get some from food and during walks, and the rest should be made up by taking D3-containing supplements.
The course of prophylactic administration should not exceed 30 days. After this, take a month's break and resume use.
Vitamin D: benefits for men
Cholecalciferol is necessary not only for adult women, but also for the stronger sex. Let's see why men need it.
Firstly, vitamin D is actively involved in the formation of sperm, which means it directly affects the ability to fertilize. It has been proven that the quality of ejaculate in men suffering from calciferol deficiency is much lower than in those whose bodies have enough of the substance.
Secondly, vitamin D levels are directly related to prostate diseases. Its deficiency leads to prostate adenoma, contributes to the occurrence of inflammation and cancerous tumors.
Another reason vitamin D is important for men is its connection to muscle growth and fat storage. It is known that a sufficient amount of the substance accelerates the growth muscle mass and promotes the burning of carbohydrates. This ability of calciferol is especially pronounced after working out in the gym.
In addition, there is a known connection between vitamin D and testosterone, which is responsible for sexual desire. Its deficiency leads to abdominal obesity and feminization of the figure, reduces libido and physical activity of an adult man, and impairs vascular conductivity. This causes loss of performance, weakness and drowsiness.
Advice. All men over 40 years old need to take extra vitamin D, but not get carried away with it. The drug can bring not only benefits, but also harm.
Vitamin D for hair
As we already know, cholecalciferol is responsible for the absorption and metabolism of calcium. Its deficiency in the body causes dry and brittle hair and slows down its growth. A sufficient amount of the substance stimulates the maturation of follicles, protects the roots from exhaustion, and makes the curls smooth and shiny.
Moreover, the vitamin improves the condition of the scalp, relieves dandruff and irritation, and normalizes sebum secretion.
If appearance hair has noticeably deteriorated, and you associate this with vitamin D3 deficiency, you can not only take the substance internally, but also apply it externally, adding it to masks, balms or conditioners.
Advice. Cholecalciferol is a fat-soluble compound, so it should only be mixed with oils.
A nutritious mixture of eggs, hot pepper tincture, castor oil and an ampoule of calciferol oil will help with hair loss. To prepare the mask, you only need yolks.
For oily hair A composition of kefir and vitamin D is suitable. The warm mixture is applied to the head and left for half an hour. The mask nourishes and strengthens curls, normalizes greasiness and adds shine. For hair growth and reduction of split ends, you can prepare a composition of yolk, honey, burdock oil and calciferol.
Vitamin D for immunity
Vitamin D is necessary for the full course of immune reactions, both adaptive and genetically inherited. Prophylactic intake of the substance reduces susceptibility to infections, relieves colds and other diseases of the ENT organs, reduces the risk of developing allergic reactions, including asthma.
This is interesting. Not long ago, scientists discovered another property of cholecalciferol - the ability to influence information recorded in genes.
It is especially important to start supplementing with vitamin D during the epidemic season. The substance is used to prevent influenza, ARVI and acute respiratory infections. When it interacts with the mucous membrane of the respiratory organs, a protein is synthesized that prevents the penetration of pathogenic microbes into tissues.
In addition, calciferol reduces the severity inflammatory processes and alleviates the course of the disease. According to medical observations, additional intake of vitamin D for colds and ARVI significantly speeds up recovery and reduces the risk of complications, and also eliminates resistance to certain antibiotics.
Vitamin D in bodybuilding
Additional intake of vitamin D is especially relevant in bodybuilding. This is due to the ability of calciferol to influence testosterone synthesis. Sports doctors have long noticed this pattern and successfully use it to improve the effectiveness of training.
This way of achieving results is much more effective and safer than taking steroid supplements or artificial testosterone. Today, enough is known about the risks associated with the use of synthetic sports nutrition to build muscle mass. By taking calciferol, you completely eliminate the dangers associated with artificial drugs and receive many benefits.
The daily dose of vitamin D in sports is much higher than the norm ordinary person. The maximum allowable dosage for adult bodybuilders may be 50 mcg per day.
This amount of substance often causes allergic reactions: swelling of the face and chest, skin rash, difficulty breathing. If such symptoms occur, you should consult a doctor, since excess vitamin can lead to negative health consequences.
Rules for using supplements in sports:
- taking medications should be orderly and carried out under the supervision of a specialist;
- it is necessary to regularly determine the level of calciferol in the blood;
- the use of supplements should be supplemented by the normalization of hormonal levels and a sufficient supply of micronutrients;
Athletes with impaired gastrointestinal tract activity, chaotic nutrition or diseases of the digestive system require diet correction with the participation of a specialist.
Vitamin D for weight loss
To this day, there is debate about whether calciferol affects weight loss. Many studies have been conducted involving different groups population, as a result of which it has been proven that people with sufficient vitamin D3 get rid of extra pounds and they are gaining more slowly.
Interestingly, in overweight people, vitamin D3 accumulates in belly fat. Accompanying sports loads By taking additional substances, you will get closer to achieving a thin waist. At the same time, in the process of burning fat, the release of the vitamin hidden there will begin, which will further accelerate weight loss.
A special group includes people with abdominal obesity. They should increase their preventive intake of cholecalciferol by 40%, since at first the process of getting rid of extra pounds will be very slow. But as soon as the accumulation of belly fat is saturated with the vitamin, rapid weight loss will begin.
Advice. If you want to lose weight, increase daily dose cholecalciferol up to 800–1000 IU.
Vitamin D for older people
With age, the human body gradually loses the ability to produce vitamin D under the influence of ultraviolet rays. According to the recommendations of doctors, the daily dosage of this substance increases by 25% for women and men after 65 years.
Elderly people may need calciferol more than pregnant women. The vitamin not only protects against hip fractures, but also performs other equally important functions:
- reduces the risk of developing senile dementia;
- fights Parkinson's disease;
- prevents atherosclerosis;
- prevents the occurrence of glaucoma and retinopathy;
- slows down degenerative changes in the retina of the eye.
Often, older people experience short-term, unexplained weakness and muscle pain. One of the reasons for these unpleasant phenomena may be a D-deficient state.
Elderly people living in northern regions, where the sun is an infrequent visitor, cannot do without additional vitamin intake.
How to take vitamin D correctly
How to take calciferol correctly? Experts recommend using the substance in combination with B vitamins, ascorbic acid, tocopherol and retinol. These elements mutually reinforce each other and increase absorption.
When is it better to take calciferol, at what time of day? Vitamin D, like all medications, is recommended to be taken in the morning. If you are using any other medications, it is better not to drink them all at once, but to use them one by one with an interval of 10 minutes.
You can take vitamin D before or after meals. If you experience nausea, burning sensation and discomfort in the stomach, drink the drug after breakfast. If it is in drops, dilute the prescribed amount of medicine in liquid or apply it to a piece of black bread.
How is vitamin D absorbed? When composing your morning diet, pay attention to the fat content in it. For better absorption of calciferol, it should be consumed with oils - butter or vegetable, so prepare porridge or salad for breakfast and season them with oil.
Advice. Do not take your vitamin with coffee or tea. The best option is a glass of warm milk or plain water.
Dose calculation for adults: preventive and therapeutic
Before you start taking vitamin D, you need to determine the optimal daily norm substances. This will allow you to avoid excesses and not harm your health.
The preventative dose of vitamin D for adults is:
- pregnant and lactating women - 500–700 IU;
- postmenopausal women - 600–1000 IU;
- men from 18 to 60 years old - 500–700 IU. To improve sperm quality, it is recommended to increase the dosage to 1000 IU;
- adults over 60 years old - 800 IU.
How to take vitamin D? The instructions for use state that preventive treatment can be carried out for many years, alternating monthly courses of treatment with 4-week breaks.
If diseases of the skeletal system or other symptoms of vitamin D deficiency are present, the prophylactic dosage must be replaced with a therapeutic one. It is determined, as well as the dosage regimen, only by a doctor. But the patient also needs to navigate the permissible portions of the vitamin.
The maximum safe dose of calciferol for adults is:
- pregnant and nursing mothers - 2000–4000 IU;
- adults over 18 years old - 2000–5000 IU.
You should not take the vitamin in such dosages for longer than 4 weeks. After 2 months, the course of therapy can be continued. Contraindications to the prescription of preventive and therapeutic doses may be renal osteodystrophy with developed hyperphosphatemia and calcium nephrourolithiasis.
It's interesting that in countries Western Europe The most popular supplements are those containing 5000 IU per daily serving. Millions of people take such doses without any harm to their health. From this we can conclude that an overdose in adults occurs when calciferol is consumed from 10,000 IU or more daily for several weeks in a row.
Attention. Vitamin D absorption largely depends on the presence of chronic diseases, age and physiological characteristics adult. For some, the substance quickly and completely turns into its active form, while for others it does not.
10 mcg of vitamin D3 is how many units?
This question often arises among those who take drugs from different manufacturers. Moreover, Russian brands indicate the dosage of vitamin D, as a rule, in micrograms (mcg), while foreign brands prefer international units (IU).
Therefore, everyone will need information about the rules for converting mcg into units: 10 mcg of vitamin D3 is 400 IU.
Vitamin D deficiency: symptoms in adults
In people who live in southern latitudes or long time spent in the sun, calciferol deficiency rarely occurs.
Attention. From November to March, the entire territory above the 42nd parallel of northern latitude is at risk of developing diseases associated with vitamin D deficiency.
Older people who spend a lot of time indoors are more prone to substance deficiency. They are in force various reasons They rarely go outside, which means they do not receive additional sunlight and do not synthesize vitamin D3 in the required amounts.
Almost 60% of elderly patients in hospitals with fractures suffer from osteoporosis to one degree or another.
Residents of northern latitudes, as well as pregnant and nursing mothers, are at risk. In adults, vitamin deficiency is manifested by the following symptoms:
- increased fatigue;
- burning in the mouth and throat;
- decreased performance;
- loss of appetite;
- development of osteomalacia:
- frequent fractures with difficult healing;
- insomnia;
- depression.
In men and women clinical picture Vitamin deficiency occurs in different ways. This is due to physiological differences between the sexes.
Signs of vitamin D deficiency in women
How does calciferol deficiency manifest in women? Beautiful ladies are more susceptible to sudden mood swings and depression. They often panic, worry, cry, and start having hysterics. A lack of vitamin D significantly aggravates these conditions, leading to a nervous breakdown.
The most striking symptoms of calciferol deficiency in the body adult woman are:
- mental disorders;
- Bad mood;
- loss of interest in life, work, family;
- lack of desire to do anything;
- blurred vision;
- paleness of the skin;
- poor condition of the dermis and hair;
- infertility.
Night cramps are often observed in calf muscles, tooth decay, caries, slow healing of fractures.
Signs of calciferol deficiency in men
How does vitamin deficiency manifest itself in men? Many representatives of the stronger sex who are not yet old are faced with abdominal obesity, which is one of the symptoms of vitamin deficiency.
Other signs of calciferol deficiency in adult men:
- muscle weakness;
- night cramps;
- fatigue;
- loss of performance;
- loss of sexual desire;
- insomnia;
- male infertility.
Most representatives of the stronger sex with vitamin D deficiency experience disruption of the heart and blood vessels, increased blood pressure, and sugar surges.
A reliable way to determine a lack of calciferol is a blood test for 25-hydroxycholecalciferol (25-OH). How to prepare for the test and take it is described.
What does vitamin D deficiency lead to?
The consequences of calciferol deficiency in adults do not appear immediately. Many weeks pass before the first diseases associated with vitamin deficiency occur.
Severe deficiency of the substance causes frequent colds, the development of myopia, and distorted posture. Over time, the patency of blood vessels is impaired, hypertension occurs, and cancerous tumors. The bones noticeably weaken, fractures occur even after a simple fall, and healing takes a long time and is difficult.
Vitamin D deficiency also causes other serious diseases:
- arthritis, arthrosis, osteoporosis;
- cocygodynia;
- spondylolisthesis;
- multiple sclerosis;
- asthma;
- tuberculosis.
As a rule, a lack of even one vitamin leads to disruption of the functionality of all organs and systems. The functioning of the heart and pancreas is disrupted, the skin begins to peel and dry, hair falls out, and the risk of developing hepatitis and non-alcoholic fatty liver increases.
In severe cases, secondary hyperparathyroidism occurs - damage to the parathyroid gland.
Vitamin D plays an important role in the body of adults. The substance has wide range beneficial properties and is involved in the regulation of most physiological processes. Its deficiency often leads to a number of common diseases. Timely and competent correction of D-deficiency conditions will help to avoid them.
Back in 1936, G. A. Khain, and then V. V. Khvorov, A. V. Rusakov (1937) and others established the effect of vitamin D on the function of the parathyroid glands. Further research its influence on a number of other endocrine glands (adrenal glands, pituitary gland, etc.) was also discovered. In this regard, reports have appeared in the literature that vitamin D in the body manifests itself as a hormone (parathyroid hormone antagonist). For the first time, the mechanism of action of vitamin D was associated with the implementation of hereditary information embedded in the structure of the gene, i.e., the question was raised about the hormonal nature of the mechanism of its action (Zull a. oth., 1966).
The discovery of the metabolite 1,25-dihydroxycholecalciferol, which is formed in the kidneys and exhibits its specific action of absorption in the intestine through the DNA - RNA system (with the formation of a calcium-binding protein in the ribosomes), brought clarity to the study of this issue. It is known that hormones are active biological substances, acting through the genetic apparatus of the cell in negligible quantities. In addition, it is characteristic of hormones that they are produced in some organs, enter the blood and then specifically act in other organs, which are their physiological targets. 1,25-DHCA meets all these conditions, which allowed some authors to classify this compound as a steroid hormone that regulates calcium metabolism in the body (Dambacher, Girarg, 1972; Foradori, 1972). Currently, vitamins of group D can be classified as steroid hormones, which is confirmed by the following data.
1. The synthesis of vitamin D occurs from acetate and cholesterol, similar to the synthesis of steroid hormones.
2. Vitamin D is converted in the body into active metabolites, like steroid hormones.
3. Its mechanism of action is very similar to that of steroid hormones. Vitamin D affects biological membranes and the genetic apparatus of target organ cells that regulate the synthesis of calcium-binding protein. It is excreted from the body in the form of steroid conjugates.
4. Like steroid hormones, vitamin D exerts its effect at a distance from the site of synthesis and has its own target organs and receptor molecules. Distributed in the body like steroid hormones.
5. Lack or excess of vitamin D leads to a shift in the metabolism of other steroids. Thus, vitamin D, synthesized in the body or introduced from the outside, undergoes a number of complex transformations. Vitamin D2 is absorbed most intensively in the duodenum, and the presence of bile is necessary for absorption. Vitamin D initially enters the lymphatic system, then binds to chylomicrons and blood lipoproteins. It enters the liver through the portal vein, where it binds to the α2-globulin fraction. This bond protects the vitamin D molecule from the destructive effects of enzymatic systems. In addition, it plays an important role in the transport of the vitamin to target organ receptors. In the liver, under the influence of 25-hydroxylase, one hydroxyl group is added to the vitamin D molecule to form 25-hydroxycholecalciferol. The latter enters the kidneys, where, with the participation of 1-hydroxylase, a second hydroxyl group is added to form 1,25-dihydroxycholecalciferol. Then most of The newly formed metabolite enters the small intestine (duodenum) through the bloodstream, where the main purpose of vitamin D is the absorption of calcium (Strukov, 1974).
Most researchers believe that the nuclei of cells in the small intestinal mucosa concentrate the bulk of vitamin D metabolites. However, the exact localization of metabolites in the nucleus has not been fully elucidated. According to some authors, most of vitamin D binds directly to chromatin; according to others, to the nuclear membrane containing specific receptors for binding this vitamin. It can be assumed that further study of the intracellular distribution of vitamin D will finally reveal the molecular mechanisms of its action.
What is vitamin D?
Until the mid-1990s, the answer to this question would have been fairly simple: Vitamin D is a fat-soluble vitamin that is essential for preventing a bone disease in children called rickets. Previous research dating back to the early 1800s has found that fish fat may help prevent and treat bone development problems in children. In the early 1900s, a compound called fat-soluble factor D was isolated from fish oil, and this factor turned out to be the vitamin we now call vitamin D. Further Scientific research rickets helped establish the role sunlight in the formation of vitamin D.
However, starting in the mid-1990s, our understanding of vitamin D began to change in dramatic ways. It is no exaggeration to say that the last 15 years have revolutionized our understanding of this vitamin! We now know that vitamin D is not just a fat-soluble vitamin essential for bone health, it also functions as a hormone.
Hormones are found in a wide variety of cell types and are responsible for regulating various physiological processes.
There are two main types of vitamin D:
Ergosterol(egosterol) is the main building block of vitamin D in plants. When exposed to ultraviolet sunlight, plant leaf ergosterol is converted into ergocalciferol, or vitamin D2 ( vitamin D2).
Cholesterol(cholesterol) is the main building block of vitamin D in the human body. Likewise, when ultraviolet radiation hits our skin cells, one form of cholesterol in our skin cells called 7-dehydrocholesterol can be converted into cholecalciferol, a form of vitamin D3 ( vitamin D3).
In plant life, ergocalciferol (a form of vitamin D2) serves most of its intended purposes. In human life, however, cholecalciferol (vitamin D3) is not the final form - further metabolism is required for the development and growth of our body.
Obtaining hormonal forms of vitamin D:
The first step involves converting cholecalciferol to hydroxyvitamin D, also called 25-hydroxyvitamin D or 25(OH)D. Hydroxyvitamin D can be formed in the liver, kidneys, lungs, skin, prostate gland, brain, on the surface of blood vessels and macrophage cells immune system. The formation of hydroxyvitamin D requires the enzyme CYP27A1.
The second step involves the conversion of hydroxyvitamin D to dihydroxyvitamin D (also called 1,25-dihydroxyvitamin D or 25(OH)2D). This second step can occur in the lungs, brain, liver, stomach, spleen, kidneys, colon, thymus gland, lymph nodes, skin, placenta and in dendritic cells of the immune system. The formation of dihydroxyvitamin D requires the enzyme CYP27B1.
The value of vitamin D or The value of vitamin D
Vitamin D plays a radical role in various aspects of our
health:
Vitamin D helps optimize the metabolism of calcium and phosphorus.
Vitamin D helps prevent type 2 diabetes (non-insulin-dependent diabetes), heart attack, congestive heart failure and stroke.
Vitamin D prevents the causes of muscle weakness and helps regulate muscle composition and muscle activity.
Vitamin D helps prevent bone integrity and osteoporosis.
Vitamin D regulates insulin activity and...
Vitamin D plays an important role in regulating the body's immune response.
Vitamin D helps regulate blood pressure
Vitamin D reduces the risk of excessive inflammation and certain bacterial infections.
Vitamin D supports cognitive function and stabilizes mood, especially in older people, and prevents chronic fatigue.
Vitamin D is essential in preventing the following types of cancer: Bladder, breast, colon, ovaries, prostate and rectum
The hormonal functions of vitamin D include regulating bone and muscle health (including skeletal and cardiac muscle), regulating the immune response, regulating insulin and blood sugar, and regulating calcium and phosphorus metabolism.
More details about these functions are provided in the following paragraphs.
Vitamin D in regulating calcium and phosphorus for bone health.
The composition of bones includes many various substances, including collagen proteins, keratin proteins and various minerals: silicon, boron and. Two particularly important components of bones are the minerals calcium and phosphorus. These minerals make up the bulk of a substance called hydroxyapatite, which accounts for more than half of bone composition.
Parathyroid hormone (PTH) in conjunction with vitamin D are the most important regulators of health bone tissue.
When blood calcium levels drop, parathyroid hormone causes calcium to be released from our bones to raise blood calcium levels back to normal. Parathyroid hormone also acts on our kidneys to store more calcium (storing it for our blood) and release more phosphorus (thus helping to create a more favorable calcium to phosphorus ratio in the blood). If too much parathyroid hormone is produced by the parathyroid glands, too much calcium can move from the bone into our blood, causing damage to bone health and of cardio-vascular system. Research has shown that vitamin D deficiency is one of the key factors in the risk of overproduction of parathyroid hormones.
Vitamin D in regulating immune function.
The role of vitamin D in regulating the body's immune function is so great that it is almost impossible to study an autoimmune disease without considering the possible role of vitamin D. This statement is true for diseases such as rheumatoid arthritis, multiple sclerosis, Crohn's disease, systemic lupus erythematosus, and many other autoimmune conditions . Autoimmune conditions are an extremely active area of vitamin D research.
Vitamin D in regulating blood pressure and cardiovascular diseases.
Vitamin D plays a direct role in regulating our blood pressure by inhibiting the activity of the renin-angiotensin system. To help increase blood pressure when it becomes too low, the renin-angiotensin system stores sodium and water in the body, thereby providing more fluid in our blood vessels and, causing our blood vessels shrink and thereby increase the pressure inside them. Optimal levels of vitamin D help keep this system under control. Vitamin D deficiency is a significant risk factor high pressure. During pregnancy, the risk of high blood pressure is associated with maternal vitamin D deficiency.
The role of vitamin D is not limited to regulating blood pressure. Vitamin D also plays a key role in regulating calcium metabolism.
Calcium overload caused by vitamin D deficiency is a problem for heart tissue and increases the likelihood of developing oxidative stress and tissue damage. The effectiveness of heart tissue healing after a heart attack is directly dependent on optimal vitamin D levels.
Vitamin D regulates insulin activity and blood sugar balance.
There is no doubt that vitamin D is involved in the regulation of blood sugar and insulin metabolism; this mechanism has not yet been thoroughly studied.
Vitamin D deficiency is a clear risk factor for the development of type 2 diabetes, and vitamin D levels are associated with insulin secretion by pancreatic beta cells.
Interestingly, with vitamin D deficiency, parathyroid hormone is released in large quantities, and too much calcium accumulates in the cells. Too much calcium in fat cells causes the cells to overproduce cortisol, a hormone that counteracts the effectiveness of insulin. In addition, too much calcium accumulation in our fat and muscle cells may inhibit the formation of the GLUT-4 transporter protein. This protein helps carry sugar (glucose) from our blood into our cells. Without enough vitamin D, too little GLUT-4 is formed and there is not enough insulin to do its job.
Vitamin D regulates muscle composition and activates muscle activity.
Research in this area has advanced greatly in the last ten years, and vitamin D has been shown to play a key role in preventing muscle weakness, especially in older people.
Interestingly, vitamin D deficiency is associated with too much fat accumulation in muscle tissue, so muscle strength is reduced and physical performance is compromised.
Vitamin D and cancer prevention.
The role of vitamin D in cancer prevention is not entirely obvious; work in this direction is being intensively carried out. However, research has already shown great importance vitamin D in the prevention of the following types of cancer: bladder cancer, breast cancer, colon cancer, ovarian cancer, etc. In certain situations, vitamin D functions as an antitumor agent and is used in the treatment of cancer.
Other benefits of vitamin D.
Research is in full swing on the effect of vitamin D on:
- Senile dementia and;
- Cognitive functions (impaired thinking), especially in aging individuals;
- Mood disorders, especially in older people;
- Related autoimmune diseases, such as .
Vitamin D standards
Recommended daily intake of vitamin D (approved by the US National Academy of Sciences in 1997):
Children and adolescents: 5 mg
Men and women, up to 50 years: 5 mg
Men and women, from 51 to 70 years: 10 mg
Men and women, from 71 years: 15 mg
Pregnant and lactating women: 5 mg
Vitamin D deficiency
Lack of sun exposure for any reason, including geographic location, use of sunscreen, or wearing protective clothing may cause vitamin D deficiency.
Vitamin D deficiency can cause:
Muscle pain and muscle weakness
Bone pain, frequent bone fractures, or softening of the bones
Growth retardation in children, rickets
Asthma in children (especially severe forms)
Cognitive impairment, especially among older people
Reduced immunity
Chronic lack of energy and fatigue
, especially among older people
Autoimmune disorders
Exceeding the norm of vitamin D
Excessive intake of vitamin D can be toxic, and vitamin D toxicity can come from any form of plant (D2) or animal (D3) origin. Symptoms of intoxication include loss of appetite, nausea, vomiting, high blood pressure, and kidney problems. However, it is also important to note that vitamin D deficiency poses a much greater risk for the vast majority of people than vitamin D excess. An increase in vitamin D levels from food intake is extremely unlikely.
What medications affect vitamin D?
The use of the following drugs can reduce the level of vitamin D in the body:
Anticonvulsants, including Dilantin, are used to control seizure activity in people with epilepsy and brain cancer, head injury, or stroke. These drugs reduce the activity of vitamin D.
Medicines to lower cholesterol (such as probucol, cholestyramine, clofibrate, colestipol, and gemfibrozil). These drugs may reduce the intestinal absorption of fat-soluble substances. nutrients, including vitamins A, D, E and K.
Cimetidine (Tagamet and Tagamet HB) limits formation of hydrochloric acid in the stomach and is used to treat symptoms associated with the stomach and duodenum. This drug may reduce the accumulation of vitamin D in the liver.
Substitute hormone therapy may increase blood levels of vitamin D.
Corticosteroids are a family of anti-inflammatory drugs, including hydrocortisone and prednisolone, that are commonly used in the treatment of autoimmune and inflammatory diseases such as asthma, rheumatoid arthritis, and ulcerative colitis. These drugs reduce the activity of vitamin D.
Heparin, an anticoagulant used to prevent blood clots after surgery, may interfere with vitamin D activity.
Sources of vitamin D
Food products richest in vitamin D: fatty fish (salmon, sardines), shrimp, milk, cheese, cod liver, eggs, fortified milk. Wild salmon contains significantly more vitamin D than farmed fish.
Human breast milk contains only small amounts of vitamin D.
Since dairy products are important source vitamin D in the United States, there is extensive research data on the stability of vitamin D under exposure to temperature and storage conditions. Researchers have found that virtually no loss of vitamin D is retained when processed cheeses are pasteurized under normal commercial conditions. They also found that about 25-30% of vitamin D is lost when cheese is oven baked at 450°F (232°C) for about 5 minutes.
Research shows that foods (such as pizza cheese) cooked in an oven at 400-450°F (204-232°C) for about 20 minutes lose at least one-quarter of their vitamin D during the reheating process. This percentage of vitamin loss is still relatively low compared to similar losses of other vitamins (especially less heat-stable vitamins like vitamin C).
Storing the cheese over a 9-month period, at temperatures ranging from 39-84°F (4-29°C), showed no loss of vitamin D and also highlighted the relative stability of this vitamin.
Nutritional supplements
Two forms of vitamin D used in dietary supplements: ergocalciferol(vitamin D2) and cholecalciferol(vitamin D3).
Ergocalciferol is sometimes considered a vegetarian source of vitamin D because it plant origin. However, yeast is also widely used as a source of D2, as are other fungi (eg ergot).
Cholecalciferol (a form of vitamin D3) can be obtained from animal or microbial sources. In practice, D3 was found in sheep wool. Sheep (and many other animals) have sebaceous glands in the skin, which secrete a complex of various substances, including cholesterol (in the form of 7-dehydrocholesterol).
The most common form of vitamin D3 is glue capsules containing D3 in liquid form (and often dissolved in flaxseed oil or olive oil). D3 is also available in powder form in D3 capsules, compressed tablets, and liquid form (D3 drops).
For quotation: Schwartz G.Ya. Vitamin D deficiency and its pharmacological correction // Breast Cancer. 2009. No. 7. P. 477
Disturbances in the formation of hormones and their deficiency are important causes of many human diseases. Deficiency of one of them - D-hormone (more often referred to as vitamin D deficiency), which has a wide range of biological properties and is involved in the regulation of many important physiological functions, also has Negative consequences and underlies a number of types pathological conditions and diseases. Below we consider both the characteristics of vitamin D, its deficiency, the role of the latter in the occurrence and development of a number of common diseases, and modern possibilities for the pharmacological correction of D deficiency conditions.
Characteristics of vitamin D, D-hormone and D-endocrine system
The term “vitamin D” combines a group of similar chemical structure(secosteroids) and several forms of vitamin D existing in nature:
– Vitamin D1 (this is the name given to the substance discovered in 1913 by E.V. McCollum in cod liver oil, which is a compound of ergocalciferol and lumisterol in a 1:1 ratio);
– Vitamin D2 – ergocalciferol, formed from ergosterol under the influence of sunlight, mainly in plants; along with vitamin D3, it is one of the two most common natural forms of vitamin D;
– Vitamin D3 – cholecalciferol, formed in the body of animals and humans under the influence of sunlight from 7-dehydrocholesterol; it is considered as the “true” vitamin D, while other representatives of this group are considered modified derivatives of vitamin D;
– Vitamin D4 – dihydrotahysterol or 22,23-dihydroergocalciferol;
– Vitamin D5 – sitocalciferol (formed from 7-dehydrositosterol).
Vitamin D is traditionally classified as a fat-soluble vitamin. However, unlike all other vitamins, vitamin D is not actually a vitamin in the classical sense of the term, since it: a) is not biologically active; b) due to two-stage metabolization in the body, it is converted into an active - hormonal form and c) has a variety of biological effects due to interaction with specific receptors localized in the nuclei of cells of many tissues and organs. In this regard, the active metabolite of vitamin D behaves like a true hormone, which is why it is called D-hormone. At the same time, following historical tradition, in the scientific literature it is called vitamin D.
Vitamin D2 enters the human body in relatively small quantities - no more than 20-30% of the requirement. Its main suppliers are products from cereal plants, fish oil, butter, margarine, milk, egg yolk, etc. (Table 1). Vitamin D2 is metabolized to form derivatives that have similar effects to vitamin D3 metabolites.
The second natural form of vitamin D, vitamin D3, or cholecalciferol, is the closest analogue of vitamin D2, which is little dependent on external intake. Cholecalciferol is formed in the body of vertebrates, including amphibians, reptiles, birds and mammals, and therefore plays a much greater role in human life processes than vitamin D2, which comes in small quantities from food. In the body, vitamin D3 is formed from a precursor located in the dermal layer of the skin - provitamin D3 (7-dehydrocholesterol) under the influence of short-wavelength radiation. ultraviolet irradiation spectrum B (UV-B/sunlight, wavelength 290–315 nm) at body temperature as a result of the photochemical reaction of opening the B ring of the steroid core and thermal isomerization, characteristic of secosteroids.
Vitamin D (coming from food or formed in the body in the process of endogenous synthesis) as a result of two successive reactions of hydroxylation of biologically inactive prehormonal forms is converted into active hormonal forms: the most important, qualitatively and quantitatively significant - 1a,25-dihydroxyvitamin D3 (1a,25 (OH)2D3; also called D-hormone, calcitriol) and minor – 24,25(OH)2D3 (Fig. 1).
Level of D-hormone formation in the adult body healthy person is about 0.3–1.0 mcg/day. The first hydroxylation reaction occurs predominantly in the liver (up to 90%) and about 10% extrahepatically with the participation of the microsomal enzyme 25-hydroxylase with the formation of an intermediate biologically inactive transport form - 25(OH)D (calcidol).
Hydroxylation of vitamin D3 in the liver is not subject to any extrahepatic regulatory influences and is a completely substrate-dependent process. The 25-hydroxylation reaction occurs very quickly and leads to an increase in the level of 25(OH)D in the blood serum. The level of this substance reflects both the formation of vitamin D in the skin and its intake from food, and therefore can be used as a marker of vitamin D status. Partially, the transport form of 25(OH)D enters the adipose and muscle tissue, where it can create tissue depots with an indefinite lifespan. The subsequent reaction of 1a-hydroxylation of 25(OH)D occurs mainly in the cells of the proximal tubules of the renal cortex with the participation of the enzyme 1a-hydroxylase (25-hydroxyvitamin D-1-a-hydroxylase, CYP27B1). To a lesser extent than in the kidneys, 1a-hydroxylation is also carried out by cells of the lymphohemapoietic system, in bone tissue and, as has recently been established, by the cells of some other tissues containing both 25(OH)D and 1a-hydroxylase. Both 25-hydroxylase (CYP27B1 and its other isoforms) and 1a-hydroxylase are classical mitochondrial and microsomal oxidases with mixed functions and are involved in the transfer of electrons from NADP through flavoproteins and ferrodoxin to cytochrome P450. The formation of 1,25-dihydroxyvitamin D3 in the kidneys is strictly regulated by a number of endogenous and exogenous factors.
In particular, the regulation of 1a,25(OH)2D3 synthesis in the kidneys is a direct function of parathyroid hormone (PTH), the concentration of which in the blood, in turn, is influenced by a feedback mechanism by both the level of the most active metabolite of vitamin D3 and the concentration calcium and phosphorus in blood plasma. In addition, other factors have an activating effect on 1a-hydroxylase and the process of 1a-hydroxylation, including sex hormones (estrogens and androgens), calcitonin, prolactin, growth hormone (through IPGF-1), etc.; inhibitors of 1a-hydroxylase are 1a,25(OH)2D3 and a number of its synthetic analogues, glucocorticosteroid (GC) hormones, etc. Fibroblast growth factor (FGF23), secreted in bone cells, causes the formation of a sodium phosphate cotransporter, which acts in cells of the kidneys and small intestine, has an inhibitory effect on the synthesis of 1,25-dihydroxyvitamin D3. Vitamin D metabolism is also influenced by some medicines(Drugs, for example, antiepileptic drugs).
1α,25-dihydroxyvitamin D3 increases the expression of 25-hydroxyvitamin D-24-hydroxylase (24-OHase), an enzyme that catalyzes its further metabolism, which leads to the formation of water-soluble biologically inactive calcitroic acid, which is excreted in the bile.
All of these components of vitamin D metabolism, as well as tissue nuclear receptors for 1α,25-dihydroxyvitamin D3 (D-hormone), called vitamin D receptors (VD), are combined into the endocrine system of vitamin D, the functions of which are the ability to generate biological reactions in more than 40 target tissues due to the regulation of gene transcription by RBDs (genomic mechanism) and rapid extragenomic reactions carried out during interaction with RBDs localized on the surface of a number of cells. Due to genomic and extragenomic mechanisms, the D-endocrine system carries out reactions to maintain mineral homeostasis (primarily within the framework of calcium-phosphorus metabolism), electrolyte concentrations and energy metabolism. In addition, she takes part in maintaining adequate mineral density bones, lipid metabolism, regulation of blood pressure, hair growth, stimulation of cell differentiation, inhibition cell proliferation, implementation of immunological reactions (immunosuppressive effect).
Moreover, only the D-hormone itself and hydroxylating enzymes are active components of the D-endocrine system (Table 2).
The most important reactions in which 1α,25(OH)2D3 participates as a calcium hormone are the absorption of calcium in the gastrointestinal tract and its reabsorption in the kidneys. D-hormone enhances intestinal absorption of calcium in small intestine due to interaction with specific RBD - representing the X-receptor complex of retinoic acid (RVD-XRC), leading to the expression of calcium channels in the intestinal epithelium. These transient (i.e., non-permanently existing) voltage-gated cation channels belong to the 6th member of subfamily V (TRPV6). In intestinal enterocytes, activation of the RVD is accompanied by an anabolic effect - an increase in the synthesis of calbidin 9K - calcium-binding protein (CaBP), which enters the intestinal lumen, binds Ca2+ and transports them through the intestinal wall into lymphatic vessels and then in vascular system. The effectiveness of this mechanism is evidenced by the fact that without the participation of vitamin D, only 10–15% of dietary calcium and 60% of phosphorus are absorbed in the intestine. The interaction between 1α,25-dihydroxyvitamin D3 and RBD increases the efficiency of intestinal Ca2+ absorption to 30–40%, i.e. 2–4 times, and phosphorus – up to 80%. Similar mechanisms of action of D-hormone underlie the reabsorption of Ca2+ in the kidneys under its influence.
In bones, 1α,25(OH)2D3 binds to receptors on bone-forming cells, osteoblasts (OB), causing them to increase their expression of receptor activator of nuclear factor kB ligand (RANKL). Receptor activator of nuclear factor kB (RANK), which is a receptor for RANKL localized on preosteoclasts (preOCs), binds RANKL, which causes rapid maturation of preOCs and their transformation into mature OCs. During the processes of bone remodeling, mature OCs resorb bone, which is accompanied by the release of calcium and phosphorus from the mineral component (hydroxyapatite) and ensures the maintenance of calcium and phosphorus levels in the blood. In turn, adequate levels of calcium (Ca2+) and phosphorus (in the form of phosphate (HPO42–) are necessary for normal skeletal mineralization.
D-deficiency
Under physiological conditions, the need for vitamin D varies from 200 IU (in adults) to 400 IU (in children) per day. It is believed that short-term (10–30 min) sun exposure to the face and open arms is equivalent to approximately 200 IU of vitamin D, while repeated naked sun exposure with mild skin erythema causes an increase in 25(OH)D levels. higher than observed with repeated administration at a dose of 10,000 IU (250 mcg) per day.
Although there is no consensus on the optimal level of 25(OH)D measured in serum, vitamin D deficiency (VD) is considered by most experts to occur when 25(OH)D is below 20 ng/mL (i.e. below 50 nmol/l). The level of 25(OH)D is inversely proportional to the level of PTH within the range when the level of the latter (PTH) reaches the interval between 30 and 40 ng/ml (i.e. from 75 to 100 nmol/l), at which values the PTH concentration begins to decrease (from maximum). Moreover, intestinal Ca2+ transport increased to 45–65% in women when 25(OH)D levels increased from an average of 20 to 32 ng/mL (50 to 80 nmol/L). Based on these data, a 25(OH)D level of 21 to 29 ng/ml (i.e., 52 to 72 nmol/l) can be considered an indicator of relative vitamin D deficiency, and a level of 30 ng/ml or higher can be considered sufficient (i.e. close to normal). Vitamin D toxicity occurs when 25(OH)D levels are greater than 150 ng/mL (374 nmol/L).
Using the results of determination of 25(OH)D obtained in numerous studies and their extrapolation, we can say that, according to available calculations, about 1 billion people on the Earth have VDD or vitamin D deficiency, which reflects both demographic (aging population) and environmental (climate changes, decreased insolation) changes occurring on the planet in recent years. According to several studies, from 40 to 100% of older people in the United States and Europe living in normal conditions(not in nursing homes), have DVDs. More than 50% of postmenopausal women taking drugs to treat AP have suboptimal (insufficient) 25(OH)D levels, i.e. below 30 ng/ml (75 nmol/l).
A significant number of children and young adults are also at potential risk of VDD. For example, 52% of Hispanic and black (African-American) adolescents in the Boston (USA) study and 48% of white adolescent girls in the Maine (USA) study had 25(OH)D levels below 20 ng/ ml. In other late-winter studies, 42% of U.S. black girls and women aged 15 to 49 years had 25(OH)D levels below 20 ng/mL, and 32% of healthy students and doctors at Boston Hospital VDD was detected despite their daily consumption of 1 glass of milk and multivitamins, as well as the inclusion of salmon in their diet at least once a week.
In Europe, where there are very rare species food products artificially fortified with vitamin D, children and adults are at particularly high risk of VDD. People living in the equatorial region with a high level of natural insolation have close normal level 25(OH)D – above 30 ng/ml. However, in the sunniest regions of the Earth, VD is not uncommon due to the wearing of completely covering clothing. In studies conducted in Saudi Arabia, the United Arab Emirates, Australia, Turkey, India and Lebanon, 30 to 50% of children and adults had 25(OH)D levels below 20 ng/mL. Table 3 summarizes the main causes and consequences of VDD.
D-hormone deficiency (more often represented by D-hypovitaminosis or D-vitamin deficiency, since, in contrast to the dramatic decrease in estrogen levels in postmenopause, this term primarily refers to a decrease in the level of formation in the body of 25(OH)D and 1a,25(OH) 2D3), as well as disturbances in its reception, play a significant role in the pathogenesis of not only skeletal diseases (rickets, osteomalacia, osteoporosis), but also a significant number of common extraskeletal diseases (cardiovascular pathology, tumors, autoimmune diseases, etc.).
There are two main types of D-hormone deficiency, sometimes also called “D-deficiency syndrome”. The first of these is caused by deficiency/insufficiency of vitamin D3, a natural prohormonal form from which the active metabolite(s) is formed. This type of vitamin D deficiency is associated with insufficient exposure to the sun, as well as insufficient intake of this vitamin from food, constant wearing of clothing that covers the body, which reduces the formation of natural vitamin in the skin and leads to a decrease in the level of 25(OH)D in the blood serum. A similar situation was observed previously, mainly in children, and was, in fact, synonymous with rickets. Currently, in most industrialized countries of the world, thanks to the artificial fortification of baby food with vitamin D, its deficiency/insufficiency in children is relatively rare. However, due to the demographic situation that changed in the second half of the twentieth century, vitamin D deficiency often occurs in older people, especially those living in countries and territories with low natural insolation (north or south of 40° longitude in the Northern and Southern Hemispheres, respectively), having inadequate or unbalanced diet and low physical activity. People aged 65 years and older have been shown to have a 4-fold decrease in the ability to form vitamin D in the skin. Due to the fact that 25(OH)D is a substrate for the enzyme 1a-hydroxylase, and the rate of its conversion into the active metabolite is proportional to the level of the substrate in the blood serum, a decrease in this indicator<30 нг/мл нарушает образование адекватных количеств 1a,25(ОН)2D3. Именно такой уровень снижения 25(ОН)D в сыворотке крови был выявлен у 36% мужчин и 47% женщин пожилого возраста в ходе исследования (Euronut Seneca Program), проведенного в 11 странах Западной Европы. И хотя нижний предел концентрации 25(ОН)D в сыворотке крови, необходимый для поддержания нормального уровня образования 1a,25(ОН)2D3, неизвестен, его пороговые значения, по–видимому, составляют от 12 до 15 нг/мл (30–35 нмол/л).
Along with the above data, more clear quantitative criteria for D deficiency have appeared in recent years. According to the authors, hypovitaminosis D is defined at a level of 25(OH)D in the blood serum of 100 nmol/l (40 ng/ml), D-vitamin deficiency - at 50 nmol/l, and D-deficiency - at<25 нмол/л (10 нг/мл). Последствием этого типа дефицита витамина D являются снижение абсорбции и уровня Са2+, а также повышение уровня ПТГ в сыворотке крови (вторичный гиперпаратиреоидизм), нарушение процессов ремоделирования и минерализации костной ткани. Дефицит 25(ОН)D рассматривают в тесной связи с нарушениями функций почек и возрастом, в том числе с количеством лет, прожитых после наступления менопаузы. При этом отмечены как географические и возрастные различия в уровне этого показателя, так и его зависимость от времени года, т.е. от уровня солнечной инсоляции/количества солнечных дней (УФ), что необходимо принимать во внимание при проведении соответствующих исследований и анализе полученных данных.
25(OH)D deficiency has also been identified in malabsorption syndrome, Crohn's disease, conditions after subtotal gastrectomy or during bypass operations on the intestine, insufficient secretion of pancreatic juice, liver cirrhosis, congenital atresia of the bile duct, long-term use of anticonvulsant (antiepileptic) drugs, nephrosis.
Another type of vitamin D deficiency is not always determined by a decrease in the production of D hormone in the kidneys (with this type of deficiency, either normal or slightly elevated serum levels may be observed), but is characterized by a decrease in its reception in tissues (hormone resistance), which is considered as a function of age. Nevertheless, a decrease in the level of 1a,25(OH)2D3 in blood plasma during aging, especially in the age group over 65 years, has been noted by many authors. A decrease in renal production of 1a,25(OH)2D3 is often observed in AP, kidney diseases (CKD, etc.), in elderly people (>65 years), with deficiency of sex hormones, hypophosphatemic osteomalacia of tumor genesis, with PTH-deficiency and PTH – resistant hypoparathyroidism, diabetes mellitus, under the influence of the use of corticosteroids, etc. The development of resistance to 1a,25(OH)2D3 is believed to be due to a decrease in the number of RBD in target tissues, and primarily in the intestines, kidneys and skeletal muscles. Both types of vitamin D deficiency are essential links in the pathogenesis of AP, falls and fractures.
Large-scale studies conducted in recent years have revealed a statistically significant correlation between VDD and the prevalence of a number of diseases. At the same time, important information, in particular, was obtained from studying the connections between VDD and cardiovascular and cancer diseases.
Two prospective cohort studies included 613 men from the Health Professionals Follow-Up Study and 1198 women from the Nurses Health Study with measured 25(OH)D levels and 4 to 8 years of follow-up. In addition, 2 prospective cohort studies included 38,338 men and 77,531 women with predicted 25(OH)D levels over a period of 16 to 18 years. During 4 years of follow-up, the multivariate relative risk of incident hypertension among men with measured 25(OH)D levels was<15 нг/мл (т.е. состояние D–дефицита), в сравнении с теми, у кого этот уровень составлял ³30 нг/мл был определен в 6,13 (!) (95% ДИ 1,00 до 37,8). Среди женщин такое же сравнение выявило показатель относительного риска, равный 2,67 (95% ДИ от 1,05 до 6,79). Группировка данных, касающихся общего относительного риска у мужчин и у женщин, у которых был измерен уровень 25(ОН)D, проведенная с использованием модели дисперсии случайных процессов, позволила получить значение этого риска, близкое к 3,18 (95% ДИ от 1,39 до 7,29). Используя данные об уровне 25(ОН)D в больших когортах, многовариантный и относительные риски сравнивали по наиболее низким и наиболее высоким децилям среди мужчин, где он составил 2,31 (95% ДИ от 2,03 до 2,63) и среди женщин – 1,57 (95% ДИ 1,44 до 1,72). Таким ообразом, уровень 25(ОН)D в плазме крови обратно пропорционален риску развития артериальной гипертензии.
16 different types of malignant tumors have been described, the development of which correlates with low insolation/UV exposure, and their prevalence increases with D deficiency/insufficiency. Among them: cancer of the breast, colon and rectum, uterus, esophagus, ovaries, Hodgkin and non-Hodgkin lymphoma, cancer of the bladder, gall bladder, stomach, pancreas and prostate glands, kidneys, testicles and vagina. Data regarding the association between D deficiency/insufficiency and certain types of cancer are obtained from a number of cohort studies or using case-control methodology.
These studies confirmed the existence of a correlation between the prevalence and mortality of malignant tumors of the breast, colon, ovary and prostate gland and the intensity of solar radiation in the place of residence of patients, the duration of their exposure to the sun and the level of vitamin D in the blood serum.
A US study measured plasma 25(OH)D levels in 1095 men participating in the Health Professionals Follow-Up Study and used a linear regression model to estimate 6 individual characteristics (vitamin D intake from food and supplements, race, body mass index, geographic location, physical activity) as predictors of plasma 25(OH)D levels. When analyzing the results, a computer statistical model was used to calculate the level of 25(OH)D in 47,800 men in the cohort and its association with the risk of cancer of any location. The findings suggest that an increase or increase of 25 nmol/L (10 ng/mL) in estimated 25(OH)D levels was associated with a 17% reduction in total cancer incidence (RR=0.83, 95% CI=0.73 to 0 .94) and a 29% reduction in overall mortality due to malignant tumors (RR = 0.71, 95% CI 0.60 to 0.83) with a predominant effect on cases of gastrointestinal cancer. Similar data were obtained in a number of other studies that established a correlation between VDD and the risk of developing type I diabetes mellitus, other autoimmune diseases (multiple sclerosis, rheumatoid arthritis), mortality in chronic renal failure, etc., diseases of the central nervous system (epilepsy, Parkinson's disease, Alzheimer's, etc.), tuberculosis.
All this data is considered by both specialists and health authorities in the United States and Western European countries as a “DVD epidemic” that has serious medical and medical-social consequences.
Pharmacological correction of D deficiency
As shown above, VDD is one of the significant risk factors for a number of chronic human diseases. Completing this deficiency through adequate exposure to the sun or artificial UV irradiation is an important element in the prevention of these diseases. The use of vitamin D preparations, especially its active metabolites, is a promising direction in the treatment of common types of pathology: along with traditional methods of therapy, they open up new opportunities for practical medicine.
Based on their pharmacological activity, vitamin D preparations are divided into two groups. The first of them combines native vitamins D2 (ergocalciferol) and D3 (cholecalciferol) with moderate activity, as well as a structural analogue of vitamin D3 - dihydrotachysterol. Vitamin D2 is most often used in multivitamin preparations for children and adults. In terms of activity, 1 mg of vitamin D2 is equivalent to 40,000 IU of vitamin D. Vitamin D2 is usually produced in capsules or tablets of 50,000 IU (1.25 mg) or in an oil solution for injection of 500,000 IU/ml (12.5 mg) per ampoules. Over-the-counter oral preparations (solutions) contain 8000 IU/ml (0.2 mg) of vitamin D2. In accordance with the content of active substances, drugs in this group are classified as micronutrients (food additives).
The second group includes the active metabolite of vitamin D3 and its analogs: calcitriol, alfacalcidol, etc.
The mechanism of action of drugs of both groups is similar to that of natural vitamin D and consists of binding to RBD in target organs and the pharmacological effects caused by their activation (increased absorption of calcium in the intestine, etc.). Differences in the action of individual drugs are mainly quantitative in nature and are determined by the characteristics of their pharmacokinetics and metabolism. Thus, preparations of native vitamins D2 and D3 undergo 25-hydroxylation in the liver, followed by conversion in the kidneys into active metabolites that have corresponding pharmacological effects. In this regard, and in accordance with the above reasons, the processes of metabolization of these drugs, as a rule, decrease in elderly people, with different types and forms of primary and secondary AP, in patients suffering from diseases of the gastrointestinal tract, liver, pancreas and kidneys (CRF) , as well as while taking, for example, anticonvulsants and other drugs that enhance the metabolism of 25(OH)D to inactive derivatives. In addition, doses of vitamins D2 and D3 and their analogues in dosage forms (usually close to the physiological needs for vitamin D - 200–800 IU / day) are capable of increasing the absorption of calcium in the intestine under physiological conditions, but do not overcome its malabsorption in various forms of OP, causing suppression of PTH secretion, and do not have a clear positive effect on bone tissue.
These disadvantages are absent from preparations containing active metabolites of vitamin D3 (in recent years they have been used for medicinal purposes much more widely than preparations of the native vitamin): 1a,25(OH)2D3 (INN - calcitriol; chemically identical to the D-hormone itself) and its synthetic 1a derivative – 1a(OH)D3 (INN – alfacalcidol). Both drugs are similar in the range of pharmacological properties and mechanism of action, but differ in pharmacokinetic parameters, tolerability and some other characteristics.
There are significant differences in the pharmacokinetics of drugs based on native forms of vitamin D, their active metabolites and derivatives, which largely determine their practical use. Native vitamins D2 and D3 are absorbed in the upper part of the small intestine, entering the lymphatic system, liver and then into the bloodstream as part of chylomicrons. Their maximum concentration in the blood serum is observed on average 12 hours after taking a single dose and returns to the initial level after 72 hours. With long-term use of these drugs (especially in large doses), their elimination from the circulation slows down significantly and can reach months, which is associated with the possibility of depositing vitamins D2 and D3 in adipose and muscle tissues.
Vitamin D is excreted in bile in the form of more polar metabolites. The pharmacokinetics of the active metabolite of vitamin D, calcitriol, has been studied in detail. After oral administration, it is rapidly absorbed in the small intestine. The maximum concentration of calcitriol in the blood serum is achieved after 2–6 hours and decreases significantly after 4–8 hours. The half-life is 3–6 hours. With repeated administration, equilibrium concentrations are achieved within 7 days. Unlike natural vitamin D3, calcitriol, which does not require further metabolization to be converted into the active form, after oral administration in doses of 0.25–0.5 mcg, due to interaction with extranuclear receptors of enterocytes of the intestinal mucosa, causes an increase in intestinal calcium absorption. It is assumed that exogenous calcitriol penetrates from the mother’s blood into the fetal bloodstream and is excreted in breast milk. It is excreted in bile and undergoes enterohepatic circulation. Several calcitriol metabolites have been identified that have vitamin D properties to varying degrees; these include 1a,25-dihydroxy-24-oxocholecalciferol, 1a,23,25-trihydroxy-24-oxocholecalciferol, etc.
Despite the significant similarity in properties and mechanisms of action between the preparations of active vitamin D metabolites, there are also noticeable differences. The peculiarity of alfacalcidol as a prodrug is that, as already noted, it is converted into the active form, metabolized in the liver to 1a,25(OH)2D3, and, unlike native vitamin D preparations, does not require renal hydroxylation, which allows its use in patients with kidney disease, as well as elderly people with reduced renal function. At the same time, it has been established that the effect of calcitriol develops faster and is accompanied by a more pronounced hypercalcemic effect than that of alfacalcidol (the most widely used alfacalcidol drug in Russia is Alpha D3-Teva), while the latter has a better effect on bone tissue. The pharmacokinetics and pharmacodynamics of these drugs determine their dosage regimen and frequency of administration. Thus, since the half-life of calcitriol is relatively short, to maintain a stable therapeutic concentration it should be prescribed at least 2-3 times a day. The effect of alfacalcidol develops more slowly, but after a single administration it lasts longer, which determines its prescription in doses of 0.25–1 mcg 1–2 times a day.
Preparations of native vitamins D2 and D3, as well as their active metabolites, are among the most well-tolerated and safe drugs used for the prevention and treatment of AP. This provision is of great practical importance due to the fact that their use is usually quite long (for many months and even years). Clinical observations indicate that with individual selection of doses of vitamin D preparations based on assessment of calcium levels in the blood plasma, the risk of side effects is minimal. This is due to the inherent wide breadth of therapeutic action inherent in these drugs. However, when using active metabolites of vitamin D, approximately 2-4% of patients may develop a number of side effects, the most common of which are hypercalcemia and hyperphosphatemia, which is associated with one of the main mechanisms of their action - increased intestinal absorption of calcium and phosphorus. Both of these effects can be manifested by malaise, weakness, drowsiness, headaches, nausea, dry mouth, constipation or diarrhea, epigastric discomfort, muscle and joint pain, itchy skin, and palpitations. With an individually selected dose, these side effects are observed quite rarely.
International and domestic experience in the use of drugs of the active metabolite of vitamin D - calcitriol and alfacalcidol for the prevention and treatment of various types and forms of AP, as well as the prevention of falls and fractures, is summarized in the Clinical Guidelines “Osteoporosis. Diagnosis, prevention and treatment" 2008, prepared by the Russian Association of Osteoporosis. The conclusion and recommendations regarding the use of drugs based on active vitamin D metabolites in the treatment of osteoporosis contained in this document are presented in Tables 4 and 5.
Thus, vitamin D preparations represent a group of effective and safe drugs used mainly for diseases in the pathogenesis of which the leading role is played by D deficiency/insufficiency and associated disorders of mineral metabolism. Preparations of native vitamin D, especially in physiological doses, due to the correction of endogenous D deficiency/insufficiency, have a preventive effect in rickets, as well as in relation to the osteoporetic process, can reduce its intensity and prevent the development of fractures. The use of native vitamin D preparations is advisable mainly for type 1 D deficiency, caused by a lack of insolation and vitamin D intake from food. Preparations of active metabolites of vitamin D (alfacalcidol and calcitriol) are indicated for both types 1 and 2 D deficiency. Due to their significantly higher pharmacological activity than that of native vitamin D preparations, they are able to overcome the resistance of tissue RVD to the agonist and do not require metabolization in the kidneys to convert into the active form. Preparations of active metabolites of vitamin D have preventive and therapeutic effects for various types and forms of AP, reduce the risk of falls; they can be used both in monotherapy and in combination with other antiosteoporetic agents (for example, bisphosphonates, HRT agents) and calcium salts. Individual selection of dosages of calcitriol and alfacalcidol allows minimizing the risk of side effects, which, together with preventing the occurrence of new fractures, eliminating pain and improving motor activity, helps improve the quality of life of patients, especially the elderly.
The high level of D deficiency in the population and the establishment of its association with a number of common extraskeletal diseases (cardiovascular, oncological, neurological, etc.) determine the feasibility of further research to establish the possibilities of their treatment with drugs from the group of the active metabolite of vitamin D.
Literature
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Vitamin D as an active metabolic hormone D.
Traditional ideas about vitamin D are associated primarily with its key role in metabolism
phosphorus and calcium in the human body and the effect on bone mineral density.
Vitamin D is a fat-soluble vitamin that is naturally present in
limited amount of food. In the human body it is produced only when
exposure to ultraviolet rays of the sun on the skin.
However, unlike other vitamins, it is not a vitamin in the classical sense.
term, since it enters the body in an inactive form and only then (in the liver and kidneys)
turns into an active hormonal form.
Thus, vitamin D, being necessary for maintaining physiological processes and
optimal health is essentially a powerful steroid hormone D.
Vitamin (hormone) D deficiency is a new pandemic of the 21st century.
Vitamin (hormone) D deficiency is a new non-infectious pandemic of the 21st century among adults
population living north of the 35th parallel and is due to a sharp decrease in time
exposure to the sun.
Russians are at high risk for vitamin (hormone) D deficiency due to
the specified geographical factors. In Russia, like most northern countries, the frequency of shortages
Vitamin D levels among the population are becoming alarming. It is believed that there is a serious shortage
Vitamin (hormone) D is detected at the concentration in blood serum< 10 нг/мл. Уровни 10–30 нг/мл
indicate a deficiency of vitamin (hormone) D. Optimal concentration in the blood
a level of 30–60 ng/ml is considered.
Approximately 50% of Russian men have an undiagnosed vitamin deficiency
(hormone) D, and every third person has a severe deficiency. The most common vitamin deficiency is
(hormone) D in men is detected in obesity, androgen deficiency, infertility and diseases
prostate gland. People at risk for developing vitamin (hormone) D deficiency are:
infants, elderly persons, people with limited sun exposure, patients with dark complexion
skin, obesity, diseases accompanied by impaired fat absorption.
Vitamin (hormone) D deficiency and male infertility
Recently, more and more evidence has emerged confirming the role of vitamin (hormone) D in
the process of formation and maturation of sperm. A relationship has been identified between low levels
vitamin (hormone) D and a decrease in progressive mobility, as well as the amount of morphological
normal sperm. Unlike men with normal levels of vitamin (hormone) D (> 30
ng/ml), in men with vitamin deficiency (< 20 нг/мл) в эякуляте наблюдалось более высокое количество
immobile, dead and pathologically altered forms of sperm.
Vitamin (hormone) D can affect spermatogenesis both directly and indirectly, affecting
the level of testosterone, a key hormone necessary for the proper development of sperm.
Blood testosterone levels in men it also depends from the abundance of sunlight.
It reaches its maximum level in August. But starting from October there is a gradual
a decline and an indicative minimum are observed closer to March.
Vitamin D deficiency and prostate disease
In recent years, a reliable connection has been established between the level of vitamin D in the blood and the frequency
prostate diseases. Thus, blockade of prostatic receptors for vitamin (hormone) D
leads to the development of autoimmune (non-bacterial) chronic prostatitis, which is associated with
the ability of vitamin (hormone) D to provide a pronounced antibacterial and
anti-inflammatory effect. A preventive effect regarding the development of
benign prostatic hyperplasia.
Conclusion
Vitamin D is a unique, versatile and highly metabolically active steroid
a hormone that is reliably associated with other hormonal regulators of male function
body. The range of vital biological effects of vitamin (hormone) D is extremely wide,
and the prevalence of deficiency is high.
That is why compensation for vitamin (hormone) D deficiency is an important preventive and
a therapeutic factor aimed at increasing the quality of life of men.
In addition, this problem is very relevant for andrological practice, since the deficiency
vitamin (hormone) D is actively involved in the development of most genitourinary and
reproductive systems in men. Managing this hormone could be a breakthrough in increasing
the effectiveness of preventive and therapeutic measures for andrological diseases.
