Vitamin D and cardiovascular system: communication
Section 1: Basics of vitamin D
1.1. Chemical structure and forms of vitamin D
Vitamin D, contrary to common belief, is actually not a vitamin in the classical sense, but a run of active steroid hormones. It exists in several forms, the most important of which are vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol).
Vitamin D2 is formed under the influence of ultraviolet radiation on ergosterin contained in mushrooms and yeast. Vitamin D3, on the other hand, is synthesized in the skin of humans and animals from 7-dehydrocholesterol under the influence of ultraviolet radiation type B (UVB).
The chemical structure of vitamin D includes four connected carbon rings that form a steroid core. The presence of a hydroxyl group (-OH) in the C-25 position leads to the formation of 25-hydroxyvitamin D [25(OH)D]which is the main form of vitamin D, measured in the blood to determine its level in the body. Further hydroxylation in the C-1 position leads to the formation of 1.25-dihydroxyvitamin D [1,25(OH)2D]also known as calcitriol, which is a biologically active form of vitamin D.
1.2. Synthesis, metabolism and regulation of vitamin D
The synthesis of vitamin D3 begins in the skin under the influence of UVB radiation. 7-dehydrocholesterol is converted into previtamin D3, which is then is metered into vitamin D3. Synthesized or obtained with food vitamin D3 and vitamin D2 are not biologically active and require further metabolism.
The first stage of metabolism occurs in the liver, where vitamin D3 and D2 are hydroxilized by the enzyme 25-hydroxylase (CYP2R1) up to 25 (OH) D. This process is not adjustable and mainly depends on the concentration of vitamin D in the body. 25 (OH) D is the main circulating form of vitamin D and is used as a marker of its status.
The second stage of metabolism occurs in the kidneys (and in some other tissues), where 25 (OH) D is hydroxilized by the enzyme 1α-hydroxylase (CYP27B1) to 1.25 (OH) 2D, calcitriol. This stage is strictly regulated by parathormone (PTG), calcium and phosphate. The high level of PTH and the low level of calcium and phosphate stimulate the activity of 1α-hydroxylase, increasing the production of calcitriol.
Calcitriol is associated with the vitamin D (VDR) receptor, which is a nuclear receptor belonging to the super family of steroid/thyroid hormonal receptors. The complex of calcitriol and VDR is associated with DNA in specific areas called vitamin-D-sensitive elements (VDRes), and regulates the transcription of genes involved in various physiological processes.
The regulation of vitamin D metabolism is carried out using the feedback mechanism. The high level of calcitriol inhibits the activity of 1α-hydroxylase and stimulates the activity of 24-hydroxylase (CYP24A1), an enzyme that inactivates both 25 (OH) D and 1.25 (OH) 2D.
1.3. Sources of vitamin D (dietary and sunny)
The main sources of vitamin D are:
- Sunlight: Under the influence of UVB radiation, the skin synthesizes vitamin D3. The amount of synthesized vitamin D depends on the geographical latitude, time of year, time of day, cloudiness, air pollution and skin color. People with dark skin synthesize less vitamin D than people with light skin.
- Dietary sources: Vitamin D is contained in a small amount of food, such as fatty fish (salmon, mackerel, tuna), fish oil, egg yolks and liver.
- Enriched products: Some foods, such as milk, yogurt, orange juice and breakfast flakes, are enriched with vitamin D.
- Food additives: Vitamin D is available in the form of food additives, both in the form of vitamin D2 and in the form of vitamin D3.
1.4. Determination of deficiency and sufficiency of vitamin D
The status of vitamin D is usually estimated by measuring level 25 (OH) D in blood serum. There are various recommendations regarding the optimal level 25 (OH) D, but it is generally accepted that:
- Vitamin D deficiency: 25(OH)D < 20 нг/мл (50 нмоль/л)
- Vitamin D failure: 25 (oh) d 20-29 ng/ml (50-75 nmol/l)
- The sufficiency of vitamin D: 25 (oh) d ≥ 30 ng/ml (75 nmol/l)
Some experts believe that for optimal health, level 25 (OH) D should be higher than 30 ng/ml.
Vitamin D risk factors include:
- Limited Sun stay
- Dark skin
- Elderly age
- Obesity
- Some diseases (for example, malabsorption, chronic kidney disease, liver disease)
- Taking some drugs (for example, glucocorticoids, antifungal drugs)
1.5. The role of vitamin D in the human body (outside the cardiovascular system)
Vitamin D plays an important role in maintaining bone health, regulating the level of calcium and phosphate in the blood. It contributes to the absorption of calcium in the intestines and reduces calcium removal by the kidneys. Vitamin D deficiency can lead to rickets in children and osteomination in adults, diseases characterized by weak and fragile bones.
In addition, vitamin D plays role in:
- Immune system: Vitamin D modulates the immune response and can protect against infections.
- Muscle functions: Vitamin D is necessary to maintain strength and function of muscles.
- Cell growth: Vitamin D is involved in the regulation of cellular growth and differentiation.
- Mood regulation: Some studies associate the deficiency of vitamin D with depression and other mood disorders.
- Insulin secretions: Vitamin D can affect insulin secretion and insulin sensitivity.
Section 2: Vitamin D and Cardiovascular System: Exact mechanisms
2.1. Vitamin D (VDR) receptor in the cardiovascular system
The vitamin D (VDR) receptor is expressed in various cells of the cardiovascular system, including cardiomyocytes (cordial muscle cells), endothelial cells (cells lining the inner surface of blood vessels), smooth muscle cells of blood vessels and immune cells involved in inflammatory processes in the vessels.
The presence of VDR in these cells indicates that vitamin D can have a direct effect on the function and structure of the heart and blood vessels. The binding of calcitriol (active form of vitamin D) with VDR triggers a cascade of intracellular signaling tracks, which affect the expression of genes involved in various processes, such as regulation of blood pressure, inflammation, proliferation of cells and apoptosis.
2.2. The effect of vitamin D on blood pressure
Several mechanisms associate vitamin D with the regulation of blood pressure:
- Renin-Actually-Alldosterone Skill Sat (Rae): Calcitriol suppresses the expression of the Renin gene, a key enzyme in RAS. Raas plays an important role in the regulation of blood pressure and blood volume. Excessive RAAS activation can lead to hypertension. A decrease in renin activity under the influence of vitamin D can help reduce blood pressure.
- Endothelial function: Vitamin D helps to improve the endothelial function, stimulating the production of nitrogen oxide (No), powerful vasodilator (expanding vessels). No helps to relax the smooth muscle cells of blood vessels and reduces blood pressure.
- Inflammation: Vitamin D has anti -inflammatory properties. Chronic inflammation in the vessels plays a role in the development of hypertension. A decrease in inflammation under the influence of vitamin D can contribute to the normalization of blood pressure.
- Vascular stiffness: Some studies show that vitamin D can reduce the rigidity of arteries, which also helps to reduce blood pressure. The rigidity of arteries is an independent risk factor for cardiovascular diseases.
2.3. Impact of vitamin D on the function of the endothelium
Endothelium is a single -layer layer of cells lining the inner surface of blood vessels. He plays an important role in the regulation of vascular tone, blood coagulation, inflammation and permeability of blood vessels. The dysfunction of the endothelium, characterized by a decrease in the production of NO and an increase in the production of vasoconstrictors (narrowing blood vessels) and pro-inflammatory substances, is an early sign of atherosclerosis and the risk factor for cardiovascular diseases.
Vitamin D has a positive effect on the function of the endothelium, stimulating the production of NO and suppressing the production of endothelina-1, a powerful vasoconstrictor. In addition, vitamin D has antioxidant properties and can protect endothelial cells from damage to free radicals.
2.4. The influence of vitamin D on inflammation
Inflammation plays a key role in the development and progression of atherosclerosis, the main pathological process that underlies most cardiovascular diseases. Vitamin D has anti -inflammatory properties and can modulate an immune response.
It suppresses the production of pro-inflammatory cytokines, such as the Alpha tumor factor (TNF-α), Interleukin-6 (IL-6) and Interleukin-1 beta (IL-1), and stimulates the production of anti-inflammatory cytokines, such as Interlayykin-10 (IL-10). In addition, vitamin D can regulate the activity of immune cells, such as T-lymphocytes and macrophages, and reduce their infiltration into the vascular wall.
2.5. The effect of vitamin D on glucose metabolism and insulin resistance
Insulin resistance, a condition in which the cells of the body become less sensitive to insulin, plays an important role in the development of type 2 diabetes and metabolic syndrome, which are risk factors for cardiovascular diseases.
Some studies show that vitamin D can improve glucose metabolism and reduce insulin resistance. It can stimulate the secretion of insulin with pancreatic beta-cells and increase sensitivity to insulin in peripheral tissues, such as muscles and adipose tissue. The mechanisms by which vitamin D affects glucose metabolism has not fully studied, but may include the regulation of the expression of genes involved in glucose metabolism and the modulation of inflammation.
2.6. The effect of vitamin D on a lipid profile
Lipid profile, including general cholesterol, low-density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL) and triglycerides, is an important risk factor in cardiovascular diseases. The increased level of LDLC-cholesterol and triglycerides, as well as the low level of HDL-cholesterol, increase the risk of atherosclerosis.
Data on the influence of vitamin D on a lipid profile is ambiguous. Some studies show that vitamin D deficiency is associated with an increased level of total cholesterol, LDL cholesterol and triglycerides, as well as a low level of HDL cholesterol. Other studies do not detect a significant connection between vitamin D level and lipid profile. Further studies are needed to clarify the effect of vitamin D on the lipid profile and its clinical significance.
2.7. Impact of vitamin D on the function of cardiomyocytes
Cardiomyocytes are cells that make up the heart muscle. They are responsible for the contraction of the heart and the provision of blood circulation. Vitamin D can have a direct effect on the function of cardiomyocytes.
VDR is expressed in cardiomyocytes, and the binding of calcitriol with VDR can affect contractility, relaxation and energy metabolism of cardiomyocytes. Some studies show that vitamin D can improve the contractility of cardiomyocytes and protect them from damage caused by ischemia (insufficient blood supply) and reperfusion (restoration of blood supply). In addition, vitamin D can participate in the regulation of calcium homeostasis in cardiomyocytes, which is important for normal heart function.
Section 3: Vitamin D and cardiovascular disease: epidemiological data
3.1. Vitamin D and arterial hypertension
Numerous epidemiological studies have shown the relationship between the low level of vitamin D and the increased risk of arterial hypertension. The meta-analysis of these studies confirm that the deficiency of vitamin D is associated with increased systolic and diastolic blood pressure.
However, the results of interventional studies, which evaluate the effect of vitamin D additives on blood pressure are ambiguous. Some studies show that vitamin D additives can reduce blood pressure in people with vitamin D deficiency and hypertension, while other studies do not detect a significant effect.
3.2. Vitamin D and coronary heart disease (IBS)
Epidemiological studies also associate the deficiency of vitamin D with an increased risk of coronary heart disease, including angina pectoris, myocardial infarction and sudden heart death. The meta-analyzes of these studies show that the low level of vitamin D is associated with an increased risk of development of coronary heart disease and adverse cardiovascular events.
Some studies suggest that vitamin D may reduce the risk of coronary heart disease, improving the endothelium function, reducing inflammation and suppressing RAAS activation. However, the results of interventional studies, which evaluate the effect of vitamin D additives on the risk of coronary heart disease are also ambiguous.
3.3. Vitamin D and heart failure
Heart failure is a condition in which the heart is not able to pump blood enough to meet the needs of the body. Vitamin D deficiency is often found in patients with heart failure and is associated with the worst forecast.
Epidemiological studies show that the low level of vitamin D is associated with an increased risk of heart failure and the progression of the disease. Some studies suggest that vitamin D can improve the function of the heart and reduce the risk of hospitalization and death in patients with heart failure. However, the results of interventional studies, which evaluate the effect of vitamin D additives on the function of the heart and clinical outcomes in patients with heart failure are also ambiguous.
3.4. Vitamin D i stroke
Several epidemiological studies have shown the relationship between the low level of vitamin D and the increased risk of stroke. The meta-analyzes of these studies confirm that the deficiency of vitamin D is associated with an increased risk of developing ischemic and hemorrhagic stroke.
It is assumed that vitamin D can reduce the risk of stroke, improving the function of the endothelium, reducing inflammation and suppressing the formation of blood clots. However, the results of interventional studies, which evaluate the effect of vitamin D additives on the risk of stroke.
3.5. Vitamin D and atherosclerosis
Atherosclerosis is a chronic inflammatory disease characterized by the formation of plaques in the walls of arteries. Vitamin D deficiency can contribute to the development and progression of atherosclerosis.
Some studies show that the low level of vitamin D is associated with an increased risk of atherosclerosis, which is evaluated in the thickness of the intima-media complex (TMKI) of the carotid arteries, the marker of early atherosclerosis. In addition, vitamin D can reduce inflammation and suppress the proliferation of smooth muscle vessels, which can slow down the progression of atherosclerosis.
Section 4: Clinical studies and interventions by vitamin D
4.1. Review of clinical studies on the influence of vitamin D on cardiovascular risk factors
Numerous clinical studies were carried out to assess the effects of vitamin D additives on cardiovascular risk factors, such as arterial pressure, lipid profile, glucose metabolism, endothelium function and inflammation.
The results of these studies are ambiguous. Some studies show that vitamin D additives can improve some cardiovascular risk factors, especially in people with vitamin D deficiency, while other studies do not find a significant effect.
Differences in the results of research can be associated with different doses of vitamin D, duration of treatment, characteristics of the studied populations (for example, the initial level of vitamin D, the presence of cardiovascular diseases), as well as methodological differences in conducting research.
4.2. Intervention studies on the influence of vitamin D on cardiovascular outcomes
Interventional studies, which evaluate the effect of vitamin D additives on cardiovascular outcomes, such as myocardial infarction, stroke and heart failure, also give ambiguous results.
Some studies show that vitamin D additives can reduce the risk of cardiovascular events, especially in people with vitamin D deficiency, while other studies do not find a significant effect.
Large randomized controlled studies with sufficient power are necessary to finally determine the effects of vitamin D additives on cardiovascular outcomes.
4.3. Vitamin D dosages in intervention studies
Vitamin D dosages used in intervention studies vary in a wide range, from 400 IU to 4000 IU per day or more.
The optimal dose of vitamin D to achieve cardiovascular advantages has not been set. The recommended daily dose of vitamin D to maintain bone health is 600-800 IU for adults. However, to achieve the optimal level of vitamin D in the blood and obtain potential cardiovascular advantages, a higher dose may be required.
It is important to note that high doses of vitamin D can be toxic and cause hypercalcemia (increased blood calcium), which can lead to damage to the kidneys and other organs. Therefore, before taking high doses of vitamin D, it is necessary to consult a doctor.
4.4. Safety and side effects of vitamin D additives
In general, vitamin D additives are considered safe when taking recommended doses. However, high doses of vitamin D can cause side effects, such as:
- Hypercalcemia
- Nausea, vomiting, constipation
- Weakness, fatigue
- Kidney damage
People with kidney diseases, hyperparathyroidism and other diseases affecting calcium metabolism should be especially careful when taking vitamin D.
Vitamin D interactions with drugs are rare, but can occur with simultaneous drugs, such as digoxin, thiazide diuretics and some antifungal drugs.
4.5. Existing recommendations for taking vitamin D for the prevention of cardiovascular diseases
Currently, there are no clear recommendations for taking vitamin D especially for the prevention of cardiovascular diseases.
However, many organizations recommend maintaining a sufficient level of vitamin D in the blood for general health, including bone health and immune system.
People with vitamin D deficiency, especially those who have risk factors for cardiovascular diseases, can benefit from taking vitamin D.
The decision to take vitamin D additives should be taken individually, after consulting a doctor, taking into account individual risk factors, vitamin D levels in the blood and other medical indications.
Section 5: Future research areas
5.1. The need for large -scale randomized controlled research
To finally determine the influence of vitamin D on the cardiovascular system, large-scale randomized controlled studies with sufficient power are needed.
These studies should include various populations with various risk factors of cardiovascular diseases and use standardized protocols to assess the level of vitamin D, dosages of vitamin D additives and cardiovascular outcomes.
5.2. Studies aimed at understanding the mechanisms of vitamin D in the cardiovascular system
Further studies are needed for a deeper understanding of vitamin D action mechanisms in the cardiovascular system.
These studies should be aimed at studying the effects of vitamin D on the function of various cells of the cardiovascular system, including cardiomyocytes, endothelial cells and smooth muscle cells of blood vessels, as well as the identification of key signaling paths involved in these processes.
5.3. Study of individual factors affecting the response to vitamin D additives
It is important to study individual factors that can affect the response to vitamin D additives, such as genetic factors, age, gender, ethnicity, concomitant diseases and taking drugs.
This will develop personalized vitamin D strategies for the prevention and treatment of cardiovascular diseases.
5.4. Studies on the study of the influence of vitamin D in combination with other interventions
Studies are necessary to study the effects of vitamin D in combination with other interventions such as diet, physical exercises and drugs, for cardiovascular outcomes.
This will determine the most effective strategies for the prevention and treatment of cardiovascular diseases.
5.5. Development of more accurate methods for assessing vitamin D status
The development of more accurate and reliable methods for assessing the status of vitamin D, taking into account not only the level of 25 (OH) D in the blood, but also other parameters, such as the level of calcitriol and VDR activity, can help in a more accurate assessment of the need for vitamin D and monitoring the effectiveness of additives.
This detailed analysis provides comprehensive information about the relationship between vitamin D and the cardiovascular system, covering the mechanisms of action, epidemiological data, clinical studies and future research.