Vitamin D - Calciferol, ergosterol, viosterol. Metabolism and modern data on metabolically active forms of vitamin D The effect of vitamin D on metabolism

Ushakova O.V. 1, Polikarova O.V. 2

Department of General Medical Practice and Preventive Medicine of the Regional State Budgetary educational institution additional professional education "Institute for Advanced Training of Healthcare Specialists" of the Ministry of Health of the Khabarovsk Territory 1

Regional state state-financed organization Healthcare "Clinical Diagnostic Center" of the Ministry of Health of the Khabarovsk Territory 2

Metabolism of vitamin D and its practical application in clinical practice

Although new evidence has been regularly published recently indicating a possible link between vitamin D deficiency or insufficiency and an increased risk of developing chronic diseases, reviews and analyzes of aggregate data from studies of varying quality indicate that there is no reliable evidence of such an association. The most studied function of vitamin D is the regulation of calcium metabolism and metabolism in bone tissue. When exposed to sunlight, the skin produces vitamin D 3 (cholecalciferol), which is also found in some foods (for example, high-fat fish, egg yolk and liver). After conversion, it turns into the active form - 1,25(OH)2 D 3. Active vitamin D 3 binds to specific vitamin D receptors in the intestinal mucosa and promotes the absorption of calcium, which, along with phosphorus, is vital for the formation of healthy bones. Vitamin D also stimulates bone mineralization and enhances the reabsorption of calcium in the kidneys. Too much low levels Vitamin D intake can lead to disturbances in the metabolism of calcium and phosphate, and therefore provoke metabolic disorders in bone tissue. As a result of insufficient absorption of calcium in the intestines, there is an increased release of calcium from the bones, which leads to decreased bone density and increases the risk of fractures. Thus, knowledge of vitamin D metabolism has great importance in a doctor's practice.

Key words: ergocalciferol, colecalceferol, vitamin D

Summary:
Although in recent times is regularly updated with new data, suggest-ing a possible Association between deficiency or vitamin D deficiency and an increased risk of developing chronic diseases, reviews and analyzes of aggregate data studies of varying quality test the absence of reliable evidence of such a link. The most studied function of vitamin D is the regulation of calcium metabolism and metabolic bone tissue. Under the influence of solar radiation in the skin produces vitamin D3 (cholecalciferol), which is also found in some foods (for example, high fat fish, egg yolk and liver). After conversion, it is transformed into an active form, 1.25(OH)2 D3. Active vitamin D3 binds to a specific receptor of vitamin D in the intestinal mucosa and promotes the absorption of calcium, which, along with phosphorus, is essential for building healthy bones. Vitamin D stimulates the mineralization of bone tissue and increases re-absorption of calcium in the kidneys. Too low levels of vitamin D can lead to violation of the metabolism of calcium and phosphate, and thus provoke the metabolism of the bone. As a result of insufficient calcium absorption in the intestine observed increased release of calcium from the bones, which leads to lower bone density and increases the risk of fractures. Thus, knowledge of the metabolism of vitamin D is of great importance in the practice of a physician.

Keywords: ergocalciferol, cholecalciferol, vitamin D Vitamin D exists in the form of several compounds that differ in chemical structure and biological activity.

For humans, the active drugs are ergocalciferol (D 2) and colecalceferol (D 3).

Natural products contain mainly provitamin D 2 (ergosterol), and the skin (in dermal form) contains provitamin D 3 (7-dehydrocholesterol).

Vitamin D 2 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 (table).

Vitamin D 3 is formed under the influence of ultraviolet irradiation.

Products
Bakery products and cereals	Bran flakes
	Cornflakes
	Cereals
	Rice flakes
		½ cup
	Soft cheese
	Swiss cheese
Chicken eggs
Cod liver oil
	beef
	Low fat
	Broccoli	½ cup
		½ cup
		½ cup

Vitamin D performs its biological functions in the form of active metabolites formed from it: 1.25 dioxycholecalciferol (1.25 (OH) 2 D 3) and 24.25 dioxycholecalciferol (24.25 (OH) 2 D 3).

The main transport circulating form of all calciferols is 25-hydroxycholecalciferol 25(OH)D.

The level of vitamin D formation in the body of an adult 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 (oxycholecalciferol).

Hydroxylation of vitamin D 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. Partial transport form of 25(OH)D enters 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 1α-hydroxylase, forming 1.25 dioxycholecalciferol (1.25 (OH) 2 D 3).

Regulation of the synthesis of 1,25 dioxycholecalciferol 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 D 3 and the concentration of calcium and phosphorus in the plasma blood. 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.; 1a-hydroxylase inhibitors are 1,25 (OH) 2 D 3 and a number of its synthetic analogues, glucocorticosteroid (GCS) hormones, etc.

All of the listed components of vitamin D metabolism, as well as tissue nuclear receptors for 1,25 dioxycholecalciferol (D-hormone), called vitamin D receptors, are combined into the endocrine system of vitamin D, the functions of which are the ability to generate biological reactions in more than 40 tissues -targets.

The D-endocrine system carries out reactions to maintain mineral homeostasis (primarily within the framework of calcium-phosphorus metabolism), concentration of electrolytes and energy metabolism. In addition, it takes part in maintaining adequate bone mineral density, lipid metabolism, and regulation of blood levels. blood pressure, hair growth, stimulation of cell differentiation, inhibition of cell proliferation, implementation of immunological reactions (immunosuppressive effect).

The most important reactions in which 1,25 dioxycholecalciferol participates as a calcium hormone (D-hormone) are the absorption of calcium into gastrointestinal tract and its reabsorption in the kidneys. In intestinal enterocytes, activation of vitamin D receptors is accompanied by an anabolic effect - an increase in the synthesis of calcium-binding protein, which enters the intestinal lumen, binds Ca 2 + and transports it through the intestinal wall into the lymphatic vessels and then into the 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 term D-hormone deficiency primarily refers to a decrease in the level of formation in the body of 25(OH)D and 1a,25(OH)2D3. There are two main types of D-hormone deficiency, sometimes also called “D-deficiency syndrome”.

The first of them is caused by deficiency/insufficiency of vitamin D 3 - a natural prohormonal form from which active metabolites are 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 covering 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 enrichment of products baby food Vitamin D deficiency in children is relatively rare.

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 an inadequate or unbalanced diet and with low physical activity. It has been shown that people aged 65 years and older have a 4-fold decrease in the ability to form vitamin D in the skin.

Obesity is accompanied by a decrease in the bioavailability of vitamin D. Its deficiency most often manifests itself in morbid obesity. And prescribing therapy in the usual prophylactic doses of 800-1000 units per day does not allow achieving a satisfactory effect.

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)2Д 3 . Именно такой уровень снижения 25(ОН)Д 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)Д в сыворотке крови, необходимый для поддержания нормального уровня образования 1a,25(ОН) 2 Д 3 , неизвестен, его пороговые значения, по–видимому, составляют от 12 до 15 нг/мл (30–35 нмоль/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).

The consequences of this type of vitamin D deficiency are a decrease in the absorption and level of Ca 2 +, as well as an increase in the level of PTH in the blood serum (secondary hyperparathyroidism), disruption of the processes of remodeling and mineralization of bone tissue.

25(OH)D deficiency is considered to be closely related to renal dysfunction and age, including the number of years lived after menopause.

25(OH)D deficiency has also been identified in malabsorption syndrome, Crohn's disease, conditions after subtotal gastrectomy or intestinal bypass operations, insufficient secretion of pancreatic juice, liver cirrhosis, congenital bile duct atresia, 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 increased levels in the blood serum can be observed, but is characterized by a decrease in its reception in tissues, i.e. there is resistance to the hormone, which is seen as a function of age. However, a decrease in the level of 1a,25(OH) 2 D 3 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) 2 D 3 is often observed with osteopoprosis, kidney diseases, in elderly people (>65 years), with deficiency of sex hormones, hypophosphatemic osteomalacia of tumor genesis, with PTH-deficient and PTH-resistant hypoparathyroidism, diabetes mellitus, under the influence of the use of glucocorticosteroids. The development of resistance to 1a,25(OH) 2 D 3 is believed to be due to a decrease in the number of vitamin D receptors in target tissues, primarily in the intestines, kidneys and skeletal muscles. Both types of vitamin D deficiency are essential links in the pathogenesis of osteopoprosis, falls and fractures.

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 taking approximately 200 IU of vitamin D, while repeated exposure to the sun in the nude with the appearance of moderate 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, according to most experts, occurs 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 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 Ca 2+ 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).

Based on their pharmacological activity, vitamin D preparations are divided into two groups.

The first of them combines moderately active native vitamins D 2 (ergocalciferol) and D 3 (colecalciferol), as well as a structural analogue of vitamin D 3 - dihydrotachysterol.

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. Physiological replacement doses of native vitamin D range from 400–800 to 1000–2000 IU/day.

Native vitamins D 2 and D 3 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 D 2 and D 3 in fatty and muscle tissues.

Vitamin D 2 (ergocalciferol) – oily solution for oral administration. 1 ml of solution contains 25,000 IU, 1 drop from an eye pipette – 700 IU. Used for the treatment of rickets, in complex therapy for the treatment of osteoporosis and delayed consolidation of fractures. For the treatment of osteoporosis, it is recommended to use 3000 IU per day for 45 days with a repeat course after three months.

Vitamin D 3 (colecalciferol) – solution for oral administration. 1 ml contains 20,000 IU, one drop of solution from an eye pipette contains 625 IU. For the treatment of osteoporosis, it is recommended to use from 1250 to 3125 IU (2-5 drops, for vitamin D deficiency and malabsorption syndrome from 5 to 8 drops.

The mechanism of action of drugs of both groups is similar to that of natural vitamin D and consists of binding to vitamin D receptors 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 D 2 and D 3 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 reasons stated above, the processes of metabolization of these drugs, as a rule, decrease in elderly people, with different types and forms of primary and secondary osteopoprosis, 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 increase the metabolism of 25(OH)D to inactive derivatives. In addition, doses of vitamins D 2 and D 3 and their analogues in dosage forms (as a rule, 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 allow overcoming its malabsorption in various forms of osteoporosis, causing suppression of the secretion of parathyroid-stimulating hormone, and do not have a clear positive effect on bone tissue.

These disadvantages are absent from preparations containing active metabolites of vitamin D 3 (in recent years they have been used for medicinal purposes much more widely than preparations of native vitamin): 1.25(OH) 2 D 3 (INN - calcitriol; chemically identical to the D hormone itself) and its synthetic 1a derivative – 1a(OH) D 3 (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.

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 reached 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 convert into the active form, after oral administration in doses of 0.25–0.5 mcg causes an increase in intestinal absorption of calcium within 2–6 hours.

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 is that, as already noted, it is converted into the active form, metabolized in the liver to 1a,25(OH)2 D 3, and, unlike preparations of native vitamin D, does not require renal hydroxylation, which allows its use in patients with kidney disease, as well as elderly people with reduced renal function.

However, it has been established that the effect of calcitriol develops faster and is accompanied by a more pronounced hypercalcemic effect than that of alfacalcidol, 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 active metabolites of vitamin D (alfacalcidol and calcitriol) are indicated for both types 1 and 2 D deficiency. The main indications for their use are osteoporosis, incl. postmenopausal, senile, steroid, osteodystrophy in chronic renal failure; hypoparathyroidism and pseudohypoparathyroidism, Fanconi syndrome (hereditary renal acidosis with nephrocalcinosis, late rickets and adiposogenital dystrophy); renal acidosis, hypophosphatemic vitamin D-resistant rickets and osteomalacia; pseudodeficiency (vitamin D-dependent) rickets and osteomalacia.

For all vitamin D preparations, it is necessary to remember careful use in nephrolithiasis, atherosclerosis, chronic heart failure, chronic renal failure, sarcoidosis or other granulomatosis, pulmonary tuberculosis (active form), pregnancy (II-III trimester), in patients with an increased risk of developing hypercalcemia , especially in the presence of kidney stones.

Literature

1. Berezov T.T., Biological chemistry / Berezov T.T., Korovkin B.F. M. Medicine, 1990. - p. 140.

1. Dedov I.I. Violation of vitamin D metabolism in obesity / Dedov I.I., Mazurina I.V., Ogneva N.A., Troshin E.A., Rozhinskaya L.Ya. – Journal of Obesity and Metabolism – 2011 No. 2

1. Rozhinskaya L.Ya. Systemic osteoporosis/Rozhinskaya L.Ya. – Practical guide – 2nd ed. M.: Publisher Mokeev, 2000, –196 p.

1. Schwartz G.Ya. Pharmacotherapy of osteoporosis/Shvarts G.Ya. – M.: Medical Information Agency – 2002. – 368 p.

1. Schwartz G.Ya. Vitamin D and D-hormone/Schwartz G.Ya. – M.: Anaharsis, 2005. – 152 p.

1. Autier P., Gaudini S. Vitamin D supplementation and total mortality / Arch Intern Med, 2007, 167 (16): 1730–1737.

1. Forman J.P., Giovannucci E., Holmes M.D. et al. Plasma 25–hydroxyvitamin D level and risk of incidents hypertension. /Hypertension, 2007; 49:1063–1069.

1. Vervloet M.G., Twisk J.W.R. Mortality reduction by vitamin D receptor activation in end–stage renal disease: a commentary on the robustness of current data. /Nephrol Dial Transplant. 2009; 24:703–706.

1. Olga Vyacheslavovna Ushakova – chief physician of the KGBIZ “CDC”, professor of the department of general medical practice and preventive medicine of the KGBOU DPO IPKZZ,

Address: 680031, st. K. Marx, 109 Email address: [email protected]

1. Polikarova Oksana Valerievna – clinical pharmacologist, general medical practice of the KGBUZ “CDC”;

We acquire it through sunlight or through food. Ultraviolet rays act on skin oils, promoting the formation of this vitamin, which is then absorbed into the body. Vitamin D is formed in the skin from provitamins under the influence of sunlight. Provitamins, in turn, partially enter the body in finished form from plants (ergosterol, stigmasterol and sitosterol), and are partially formed in the tissues of their cholesterol (7-dehydrocholesterol (provitamin D3).

When taken orally, vitamin D is absorbed from fats through the walls of the stomach.

Measured in International Units (IU). The daily dose for adults is 400 IU or 5-10 mcg. After tanning, the production of vitamin D through the skin stops.

Benefit: Properly utilizes calcium and phosphorus, necessary for strengthening bones and teeth. When taken together with vitamins A and C, it helps in the prevention of colds. Helps in the treatment of conjunctivitis.

Diseases caused by vitamin D deficiency: rickets, severe tooth decay, osteomalacia*, senile osteoporosis.

Vitamin D belongs to the group of fat-soluble vitamins with antirachitic effects (D 1, D 2, D 3, D 4, D 5)

Vitamins of group D include:

vitamin D 2 - ergocalciferol; isolated from yeast, its provitamin is ergosterol; vitamin D 3 - cholecalciferol; isolated from animal tissues, its provitamin is 7-dehydrocholesterol; vitamin D 4 - 22, 23-dihydro-ergocalciferol; vitamin D 5 - 24-ethylcholecalciferol (sitocalciferol); isolated from wheat oils; itamin D 6 - 22-dihydroethylcalciferol (stigma-calciferol).

Today, vitamin D refers to two vitamins - D 2 and D 3 - ergocalciferol and cholecalciferol - these are colorless and odorless crystals that are resistant to high temperatures. These vitamins are fat soluble, i.e. soluble in fats and organic compounds and insoluble in water.

They regulate the metabolism of calcium and phosphorus: they participate in the process of calcium absorption in the intestine, interact with parathyroid hormone, and are responsible for bone calcification. In childhood, with vitamin D deficiency, due to a decrease in the content of calcium and phosphorus salts in the bones, the process of bone formation (growth and ossification) is disrupted, and rickets develops . In adults, bone decalcification occurs (osteomalacia).

The German chemist A. Windaus, who studied sterols for more than 30 years, in 1928 discovered ergosterol - provitamin D, which was converted into ergocalciferol under the influence of ultraviolet rays. It was found that under the influence of ultraviolet rays, a certain amount of vitamin D can be formed in the skin, and irradiation can be as solar and using a quartz lamp. . It is estimated that 10 minutes of irradiation of animals has the same effect on the body as introducing 21% fish oil into the diet. In irradiated foods, vitamin D is formed from special fat-like substances (sterols). Recently, ultraviolet irradiation of animals, especially young animals, as well as feed, has been widely used in animal husbandry.

Main sources: fish oil, caviar, liver and meat, egg yolk, animal fats and oils, sardines, herring, salmon, tuna, milk. hay flour, Vitamin D is found in large quantities in egg yolk, yeast, good hay, vegetable oil, grass flour and other products. Plants, as a rule, do not contain the vitamin, but they contain the provitamin ergosterol, which is converted into vitamin D in the body of animals.

Daily requirement 2.5 mcg, for children and pregnant women - 10 mcg. Intestinal and liver disorders and gall bladder dysfunction negatively affect the absorption of vitamin D.

In pregnant and lactating animals, the need for vitamin D increases, because Additional amounts are needed to prevent rickets in children.

Sources

Food sources

• liver, yeast, fatty milk products (butter, cream, sour cream), egg yolk (mainly vitamin D2),
• fish oil, cod liver (vitamin D3).

Synthesis in skin

• is formed (vitamin D3) in the epidermis under ultraviolet irradiation (wavelength 290-315 nm) from 7-dehydrocholesterol.

Daily requirement

Vitamin D requirements can be measured in both micrograms and international units (IU) - 25 mcg of vitamin D corresponds to 1000 IU.

The physiological need for young children is 10 mcg, for older children and adults – 10-20 mcg, for people over 60 years old – 15 mcg.
The upper tolerable intake level is 50 mcg/day.

Exposure to UV radiation inducing skin redness in a minimal erythemal dose for 15-20 minutes can, depending on skin type, induce the production of up to 250 mcg of vitamin D (10,000 IU). However, the conversion of provitamin D3 to inactive metabolites lumisterol And tachisterol balances the skin biosynthesis of vitamin D3 via a feedback mechanism. This mechanism effectively prevents “overdose” of vitamin D3 during UV irradiation.

Vitamin D2, produced by plants and fungi and obtained from grains and dairy products, has been shown to be much more less effective compared to vitamin D3.

Dietary Guidelines for Americans (USA, 2015–2020) recommend daily intake of vitamin D: children and adults of both sexes from 0 to 70 years inclusive – 15 mg, elderly people, starting from the age of 71 – 20 mg

Structure

The vitamin comes in two forms - ergocalciferol And cholecalciferol. Chemically, ergocalciferol differs from cholecalciferol by the presence in the molecule of a double bond between C22 and C23 and a methyl group at C24.

The structure of two forms of vitamin D

After absorption in the intestines or after synthesis in the skin, vitamin D3 is transported to the liver by a specific protein. Here it is hydroxylated at C25 and transported by a transport protein to the kidneys, where it is hydroxylated again, this time at C1. The active form of the vitamin is formed - 1,25-dihydroxycholecalciferol or, in other words, calcitriol.

Structure of calcitriol

The hydroxylation reaction in the kidneys is stimulated by parathyroid hormone, prolactin, growth hormone and is suppressed by high concentrations of phosphates and calcium.

Biochemical functions

The most studied and well-known functions of the vitamin are:

1. Increase concentrations calcium And phosphates in blood plasma.

To achieve this, calcitriol induces synthesis in target cells calcium binding protein and components Ca 2+ -ATPases and as a result:

• increases the absorption of Ca 2+ ions into small intestine,
• stimulates the reabsorption of Ca 2+ ions and phosphate ions in proximal renal tubules.

2. Suppresses secretion parathyroidhormone through increasing the concentration of calcium in the blood, but enhances its effect on the reabsorption of calcium in the kidneys.

3. In bone tissue, the role of vitamin D is twofold:

• stimulates mobilization Ca 2+ ions from bone tissue, as it promotes the differentiation of monocytes and macrophages into osteoclasts, destruction of the bone matrix, reduction in the synthesis of type I collagen by osteoblasts,
• increases mineralization bone matrix, as it increases the production of citric acid, which forms insoluble salts with calcium here.

4. In addition, as shown in the last decade, vitamin D, influencing the work of about 200 genes, is involved in proliferation And differentiation cells of all organs and tissues, including blood cells and immunocompetent cells. Vitamin D regulates immunogenesis and reactions immunity, stimulates the production of endogenous antimicrobial peptides in the epithelium and phagocytes, limits inflammatory processes by regulating the production of cytokines.

Generalized diagram of the effects of calcitriol

Hypovitaminosis D

Currently, vitamin D deficiency is associated with increased risk development

• osteoporosis,
• viral infections (!), usually in the Russian Federation this is the flu,
• arterial hypertension,
• atherosclerosis,
• autoimmune diseases,
• diabetes mellitus,
• multiple sclerosis,
• schizophrenia,
• tumors of the mammary and prostate glands,
• duodenal and colon cancer.

Acquired hypovitaminosis

It often occurs with nutritional deficiency (vegetarianism), with insufficient insolation in people who do not go outside, with national characteristics of clothing.
Hypovitaminosis can also be caused by a decrease in hydroxylation calciferol (diseases liver And kidney) and violation suction and lipid digestion (celiac disease, cholestasis).

Vitamin D deficiency affects 50% of the world's population.
In northern European countries, the prevalence of deficiency reaches 85%.
It has been shown that in winter in the Russian Federation, vitamin D deficiency is found in more than 90% of the population.

Clinical picture

The most famous, “classic” manifestation of vitamin D deficiency is rickets, which develops in children from 2 to 24 months. With rickets, despite being supplied with food, calcium is not absorbed in the intestines and is lost in the kidneys. This leads to a decrease in the concentration of calcium in the blood plasma, impaired mineralization of bone tissue and, as a consequence, osteomalacia (softening of the bone). Osteomalacia is manifested by deformation of the bones of the skull (tuberosity of the head), chest (chicken breast), curvature of the lower leg, rachitic rosary on the ribs, enlargement of the abdomen due to hypotonia of the muscles, delayed teething and overgrowth of the fontanelles.

U adults also observed osteomalacia, i.e. Osteoid continues to be synthesized, but is not mineralized. In addition to bone tissue disorders, there is general hypotension of the muscular system, damage to the bone marrow, gastrointestinal tract, lymphoid system, and atopic conditions.

The influenza virus is detected in the human body all year round, but epidemics of the disease in northern latitudes occur only in winter, when the level of vitamin D in the blood reaches its minimum values. Therefore, a low seasonal supply of vitamin D, rather than an increase in viral activity, is considered by some researchers to be the cause of influenza epidemics during the cold months of the year.

Hereditary hypovitaminosis

IN itamin D-dependent hereditary rickets type I, in which there is a recessive renal defect α1-hydroxylase. Manifested by developmental delay, rachitic skeletal features, etc. Treatment is calcitriol preparations or large doses of vitamin D.

Vitamin D-dependent hereditary rickets type II, in which a defect is observed tissue receptors calcitriol. Clinically, the disease is similar to type I, but additionally alopecia, milia, epidermal cysts, and muscle weakness are noted. Treatment varies depending on the severity of the disease, but large doses of calciferol help.

Hypervitaminosis

Cause

Excessive consumption with drugs (at least 1.5 million IU per day).

Clinical picture

Early signs of vitamin D overdose include nausea, headache, loss of appetite and body weight, polyuria, thirst and polydipsia. There may be constipation, hypertension, and muscle stiffness.

Chronic excess of vitamin D leads to hypervitaminosis, which is characterized by:

• demineralization bones, leading to their fragility and fractures.
• increase ion concentrations calcium And phosphorus in the blood, leading to calcification of blood vessels, lung and kidney tissue.

Dosage forms

Vitamin D– fish oil, ergocalciferol, cholecalciferol, aquadetrim, detrimax, calcium D3-nycomed.

Ergocalciferol (vitamin D2), which forms the basis of some drugs, is not able to maintain the level of the active form of vitamin D in the blood for a long time, and is not suitable for patients with moderate to severe deficiency.

Active forms of vitamin D(1α-hydroxycalciferol, calcitriol) – alfacalcidol, osteotriol, oxydevit, rocaltrol, forcal.

In the 15th century in England, an epidemic of rickets (children with a curved spine, arms and legs) began in large cities. This was due to the lack of sunlight due to the close development of tall buildings and smoke in the air.

In 1928 German scientist Windaus received the Nobel Prize in Chemistry for studying the properties and structure of vitamin D.

What causes vitamin D deficiency?

Vitamin D deficiency in many Russian residents is due to:

• location in the northern temperate zone (above 42 degrees north latitude)
• limited exposure to the sun (office work, driving cars)
• eating meat from animals that have not been exposed to the sun (farm)
• use of sunscreens
• chronic diseases (obesity, intestinal pathology, taking a large number of medications)

For the curious

Vitamin D combines a group of vitamins (D1, D2, D3, D4, D5), of which only two forms (D2 and D3) have important biological significance.

	7DHC(cholesterol)	A precursor to vitamin D, it forms its reserve in the skin.
	D3(cholecalciferol)	In the skin 80% of vitamin D3 is formed from cholesterol under the influence of beta-UV rays. Its 20% enters the body with food of animal origin (fish oil, liver, egg yolk).
	D2(ergocalciferol)	Enters the body only with plant products (bread, etc.)
	25(OH)D3(calcidol)	Then in the liver from both forms, as a result of hydroxylation (addition of an OH group), 25-OH-hydroxy-cholecalciferol (calcidol). This form is depot and transport; it is this form that is determined in the blood to determine the level of vitamin D.
	1.25(OH)D3(calcitriol)	1,25-OH-dihydroxy-CHOLECALCIFEROL (calcitriol). It is calcitriol that provides the main biological effects of vitamin D in the body.

The main biological role of calcitriol(1,25-OH-vitamin D) is to maintain a constant level of calcium in the blood (vitamin D enhances the absorption of calcium in the intestines and, if there is not enough calcium in the blood, ensures the flow of calcium from the bones into the blood).

Over time, receptors for calcitriol, in addition to the intestines and bones, were found in the kidneys, genitals, pancreas, muscles, cells of the immune and nervous systems. Thus, it became clear that vitamin D performs a large number of different functions in the human body:

• regulates the expression of 3% of the human genome (several thousand genes)
• increases the sensitivity of the insulin receptor (prevention of insulin resistance, obesity, diabetes)
• strengthens the skeletal system
• reduces the level of parathyroid hormone in the blood
• promotes the synthesis of sex hormones (testosterone, estrogens, progesterone)
• improves reproductive function
• affects innate and acquired immunity
• prevents the development of tumors, depression, Parkinson's disease

Vitamin D deficiency

A lack of vitamin D in the body can lead to the development of:

• diseases of the cardiovascular system
• immunodeficiency, allergies, psoriasis, bronchial asthma, rheumatoid arthritis
• periodontal disease
• tumors of the large intestine, mammary glands, ovaries, prostate
• chronic fatigue, depression, insomnia
• decreased muscle strength leading to a risk of falls
• decreased motility and number of morphologically normal sperm (male factor infertility)
• risk factor for premature birth, fetopathies (less than 20 ng/ml)

Achieving a vitamin D level of 50 ng/ml (125 nmol/l)reduces the risk of developing:

Ostemalacia (softening of bone tissue)
Cancer in general
Breast cancer
Ovarian cancer
Colon cancer
Kidney cancer
Uterine cancer
Diabetes mellitus type 2
Perelomov
Falls in women
Multiple sclerosis
Myocardial infarction
Vascular diseases
Preeclampsia
Caesarean section
Infertility

Vitamin D is important during pregnancy.

Its deficiency is associated with the risk of developing gestational diabetes mellitus, premature birth, preeclampsia, and various intrauterine developmental defects.

There is not a single case of teratogenic (leading to the development of tumors) effect of vitamin D in the world.

Vitamin D standards

60 - 100 ng/ml

150 - 250 nmol/l

To convert from ng/ml to nmol/l you need ng/ml * 2.5 = nmol/l

Example: 30 ng/ml * 2.5 = 75 nmol/l

Russian Association of Endocrinologists believes optimal concentration vitamin D in the blood of an adult is 30-100 ng/ml, insufficiency 20-30 ng/ml, deficit- less than 20 ng/ml.

According to data presented at the 10th European Congress on Menopause and Andropause (Madrid, 2015), vitamin D levels in obese patients in Russia:

less than 20 ng/ml - 35%

20-30 ng/ml - 30%

more than 30 ng/ml - 35%

Daily Values ​​for Vitamin D according to the recommendation of the American Society of Endocrinology (2011).

Age group		Maximum permissible level of consumption, IU
Infant, 0 - 6 months
Infant, 7 - 12 months
Children 1 - 3 years old
Children 4 - 8 years old
Children 9 - 17 years old
Adults 18 - 70 years old
Adults over 70 years old
Pregnancy and lactation

Prophylactic dose vitamin D (when you can not detect it in the blood and take it calmly) is considered to be 4,000 IU per day.

It is almost impossible to overdose on vitamin D. For example, in Holland, an elderly couple (90 and 95 years old) accidentally took a single dose of cholecalciferol 2,000,000 IU each.

Doctors monitored them for 2 months and did not identify any symptoms of overdose or toxicity. The maximum blood concentration of its form of 25-OH-vitamin D on day 8 was 210 and 170 ng/ml, respectively, which is slightly higher than its target values.

Vitamin D3 dosage calculation

The daily dose of vitamin D is calculated according to the table, based on its initial value.

You should also know that:

25 mcg(vitamin D) = 1000 IU(vitamin D)

Expected level (ng/ml)
(ng/ml)

IR - existing level

For example, to increase the level of vitamin D3 from 15 to 60 ng/ml, you need to take 10,000 IU of vitamin D daily.

In European countries, a dose of ergocalciferol of 50,000 IU is often used to correct deficiency, once a week for 8 weeks.

In obese patients with reduced intestinal absorption syndrome and taking medications that interfere with the absorption of vitamin D, it is advisable to take high doses of cholecalciferol (6,000 - 10,000 IU/day) (Russian Association of Endocrinologists).