Cardiovascular diseases (CVD) are an actual problem of the national health service as well as worldwide. Consequently, many countries in the world appear to have vitamin D deficiency/insufficiency, and data of the recent meta-analyses suggest vitamin D to be a new risk factor of CVD. We performed a clinical and diagnostic examination of 135 residents of the Western Region of Belarus with arterial hypertension (39,3%) and is chemic heart disease (IHD) (60,7%), 34 males and 101 females aged 59,65 ± 8,16 years and 28 practically healthy individuals.

Results.
By Holick MF classification vitamin D deficiency was determined in 78% of the examined individuals, vitamin Dinsufficiency – in 17% and sufficiency – in 4,5%. There were no significant differences in frequency of 25(OH)D deficiency/insufficiency depending on the diagnosis. The level of 25(OH)Din blood plasma lower than 17 nmol/l is associated with elevated systolic blood pressure. Inverse correlations were established between the 25 (OH) D plasma level and body mass, body mass index, heart rate, diastolic blood pressure. In the IHD group there was a direct correlation relationship between the 25(OH)D plasma level and the index of endothelium dependent vasodilatation.

Prolonged and severe vitamin D deficiency leads to rickets and osteomalacia. Secondary hyperparathyroidism as a result of vitamin D deficiency is a significant contributing factor forosteoporosis. Because of signs and symptoms of vitamin D deficiency are nonspecific, it often goes unrecognized and untreated.The aim of study was to determined frequency of vitamin D - deficiency and in sufficiency in people of different age, not previously treated with vitamin D, who living in different regions of Ukraine. It was examined 1575 people aged 20–95 yrs. old who lived in different regions of Ukraine. 25(OH)D and iPTH level was evaluated by electrochemiluminescence method (Elecsys 2010, Roche). Vitamin D deficiency was defined as a 25 (OH)D below 20 ng/ml (50 nmol/liter), and vitamin D insufficiency as a 25 (OH) D of 21–29 ng/ml (52.5–72.5 nmol/liter). Vitamin D deficiency was registered in 81.8 % persons, 13.6% examined had vitamin D insufficiency. It was determined negative significant correlation between iPTH and 25(OH) D (r = -0.16, p < 0.0001). Secondary hyperparathyroidism was diagnosed in 11.9 % patients. The mean level of 25(OH) D was significantly higher in southern resident of the country (p<0.001) and during summer (p<0.05). High level of vitamin D deficiency (81.8 %) and secondary hyperparathyroidism (11.9 %) make doctors to research the effective methods of treatment and prophylactics of revealed disorders.

It is now recognized that vitamin D deficiency, defined as a 25-hydroxyvitamin D < 20 ng/mL (50 nmol/l) and insufficiency 21–29 ng/mL (51–74 nmol/l) is a global health problem. Vitamin D deficiency is associated with poor bone development and mineralization during childhood and causes osteopenia, osteoporosis and osteomalacia in adults. In addition there have been a wide variety of association studies linking vitamin D deficiency and insufficiency with increased risk formany chronic illnesses including type 1 diabetes, multiplesclerosis, rheumatoid arthritis, cardio vascular disease, type 2 diabetes, several cancers, infectious diseases and increased mortality. With all of the health benefits should everyone be screened for vitamin D deficiency by measuring their blood level of 25-hydroxyvitamin D? The consensus is that this would be too expensive and not necessary as long as children and adults receive an adequate amount of vitamin D from three sources, i.e. sensible sun exposure, ingestion of foods containing vitamin D and vitamin D supplementation. For those who are at risk for vitamin D deficiency, screening their 25-hydroxyvitamin D followed by appropriate treatment and a follow up 25-hydroxyvitamin D is recommended.

Background.
1α,25-dihydroxyvitamin D [1α,25(OH)2D], an active form of vitamin D, is a member of genome operated hormone superfamily, but the only one , which synthesis is permanently limited by substrate shortage 25(OH)D. Therefore, proper serum 25(OH)D concentration is the primary target, and achievement and maintenance of proper vitamin D statusis crucial for vitamin D effectiveness and health benefits.

Methods.
Systematic literature analysis based on MEDLINE.

Results.
A target range of 30-80 ng/ml serum 25(OH)D concentration is recommended as effective and safe that was evidenced by studies of: a) highly sun exposed study cohort data, b) kinetic data concerning Km = 40 ng for 1-alfa-hydroxylase (CYP27B1). Serum 25(OH)D values below 36 ng/ml were associated with preventable disease, therefore, should be consideredas indicative of vitamin D deficiency. The upper 25(OH)D normal concentration was set at 90 ng/ml, although toxicity incidents were rare below 200 ng/ml. Assessment of serum 25(OH)D level using the automatic systems (detecting both 25(OH)D2 and 25(OH)D3) with inter-assay CV < 8% in labs subjected to the DEQAS system (The International External Quality Assessment Scheme for Vitamin D Metabolites) must be considered as standard and indication of GLP. Because the rate of response to vitamin D supplementation depends on baseline 25(OH)D concentration and body composition factors (body weight, BMI), the concept of tailored intervention was proposed in patients at vitamin D deficiency risk. Skin synthesis of vitamin D should be kept in mind as a natural and safe source of vitamin D.

Conclusion.:
25(OH)D concentration at range of 30-80 ng/ml indicates adequate body provision in vitamin D that assure human body with adequate substrate concentration for endocrine and paracrine 1,25(OH)2D actions that lead to health benefits. Effective screening policy of vitamin D deficiency in defined risk groups of patients seems as an important endocrine issue.

Basic biomedical research has revealed that vitamin D3 is activated first to its main circulating form, 25-hydroxyvitamin D3[25(OH)D3], then to its hormonal form 1,25-dihydroxyvitamin D3 [1α,25(OH)2D3] before its performs its physiological role in the body, which involves regulation of gene expression in awide range of cell types. 1α, 25(OH)2D3 plays key endocrine roles in calcium and phosphate homeostatic loops, as well as other functions in controlling epithelial cell proliferation and differentiation in what could be classified as local autocrine/paracrine actions. Vitamin D has a broad safety range and reported cases of human toxicity are rare. Hypervitaminosis D resulting in symptoms of hypercalciuric and hypercalcemic seems not to result from over-production of 1α,25(OH)2D3 but by overproduction of 25(OH)D3 and its other metabolites which upset the plasma transport processes involving D-binding protein and allow 25(OH)D3 to flood into cells, trigging aberrant gene expression. However, the levels of 25(OH)D3 associated with acute toxicity are above 500 nmol/L (200ng/mL) and these values are unlikely to be reached at dietaryin takes below 25,000 IU/day. Based upon a few epidemiological studies which suggest that vitamin D might have potentially harmful effects, some agencies are raising concerns that chronic administration of moderate doses over extended periods of time might be deleterious. Based upon balancing the benefits/risks of vitamin D administration, the 2011IOM Report recently recommended a tolerable upper limit of4000 IU/day and keeping serum 25(OH)D levels in the 50–125nmol/L (20–50 ng/mL) range for optimal performance.

A large and growing body of literature addresses how solar ultraviolet-B (UVB) doses and vitamin D reduce the risk of cancer incidence and mortality. This evidence comes from ecological, observational, cross-sectional, and laboratory studies, as well as randomized controlled trials (RCTs). Usingthe criteria for causality that A. Bradford Hill established, we can evaluate the scientific evidence. The most appropriate criteria for vitamin D and cancer are strength of association, consistency (repeated findings in different populations), biological gradient, plausibility (mechanisms), and experimental verification. Many geography-based ecological studies have reported strong inverse correlations between indices of solar UVB doses and rates of cancer incidence or mortality. The 13 types of cancer with the strongest evidence – based on number of studies reporting strong inverse correlations – are bladder, female breast, colon, esophageal, gallbladder, gastric, ovarian, pancreatic, prostate, rectal, and renal cancer, as wellas lymphoma (Hodgkin’s and non-Hodgkin’s). Case-control studies of breast and colorectal cancer incidence find pronounce dinverse correlations with serum 25-hydroxyvitamin D [25(OH)D] concentrations, with rapid reductions in risk for increases of 25(OH)D concentration at low values and little change above about 100 nmol/l. Vitamin D reduces the risk of cancer through effects on cellular differentiation and proliferation, epithelial cell binding, metastasis, and angiogenesis around tumors, thus affecting cancer growth at all stages. Experimental verification of the UVB–vitamin D–cancer hypothesis comes from two RCTs, one treatment study, and many “accidental experiments” such as ecological and observational studies. One RCT found a 77% reduction in all-cancer incidence rates for postmenopausal women taking 1100 IU/dof vitamin D3 plus 1450 mg/d of calcium between the ends of the first and fourth years of the study. “Accidental experiments” include the findings that (1) those who develop nonmelanoma skin cancer may have reduced risk of internal cancers, especially if they live in areas warm enough to expose sufficient body surface area to generate adequate amounts ofvitamin D, and (2) that black Americans have lower cancer incidence, survival, and mortality rates, consistent with having about 35% lower serum 25(OH)D concentrations than white Americans. The available evidence indicates that for optimal cancer risk reduction, serum 25(OH)D concentrations shouldbe above 100 nmol/l and that oral intake without significant vitamin D production from solar UVB irradiance should be1000–5000 IU/day of vitamin D3.

This review provide data from recent studies focusing on evaluation of a relationship between vitamin D provision and risk of development of autoimmune diseases.

Vitamin D, apart from maintaining the calcium balance or influencing other body functions, does also affect the immune system, both innate and adaptive. Therefore the etiological association between the vitamin and some allergy disorders is currently being investigated. This study presents results of few clinical inquiries performed to evaluate the vitamin D influence on the occurrence and the course of atopic eczema. The findings suggest that calcitriol plays a role in the development and in the clinical manifestation of the disease. However farther multicentral, randomized, prospective studies on large groups of patients and double blindtrials are still necessary.

Multiple Sclerosis (MS) is a chronic, autoimune demyelinating disease of the central nervous system (CNS). It is common in young adults, but can also affect children and teenagers. The pathogenesis of MS is unclear, but given that the incidence ofMS increases with distance from the equator, the role of vitamin D insufficiency was recently discussed. Vitamin D, acting through its nuclear receptor, is an important regulator of the immune system. Several studies showed that the adequate level of vitamin D may lower the risk of MS. Additionally, vitamin D supplementation in MS patients may ameliorate the course of the disease. This review discusses the role of vitamin D in MS pathogenesis.

Low serum concentrations of 25(OH) vitamin D were found in patients with systemic lupus erythematosus (SLE), rheumatoidarthritis (RA), ankylosing spondylitis, Behçet’s and dermatomyositis. An important role for vitamin D as a modifiable factor in systemic sclerosis, antiphospholipid syndrome and psoriasish as been suggested as well. There is also growing evidence that pathogenesis of autoimmune rheumatic disorders could be, to some extent, associated to vitamin D deficiency. More oversome recent studies indicate negative correlations between serum levels of vitamin D and SLE activity and seasonal flares. Vitamin D [1,25(OH)2D] has many actions in the immune system and generally shows the immunosuppressive properties. It inhibits B cell proliferation and production of antibodies, inhibitsmaturation of monocytes into dendritic cells, decreases the antigen-presenting activity of macrophages, induces activation of natural killer cells, inhibits Th1 profile and stimulates the Th2 dominance. In our group of 92 RA patients we have found vitamin D deficiency in 95,5% of patients however, regarding disease activity or severity we did not observed anyclear associations. So far, there is no consensus if vitamin D supplementation may reduce the prevalence of autoimmune disorders or may protect against flare.

Calcitriol, that is an active form of vitamin D, regulates not only calcium and phosphorus metabolism. 1,25(OH)2D3 modulates also innate and adaptive immune response of monocytes, macrophages, dendritic cells and T and B-lymphocytes. Epidemiological studies link vitamin D deficiency as one of the reason of incidence of autoimmune diseases. This review discuss correlation between calcitriol deficiency and autoimmune diseases, especially in paediatric patients.

Recent evidence suggests a role for vitamin D in pathogenesis and prevention of diabetes mellitus. Active vitamin D,1.25(OH)2D, prevents type 1 diabetes in animal models, and modifies T-cell differentiation, modulates dendritic cell action and induces cytokine secretion, shifting the balance to regulatory T cells. Vitamin D deficiency in pregnancy probably increases the incidence of autoimmune diseases, such as type1 diabetes, in genetically predisposed individuals. High-dose vitamin D supplementation early in life protects against type1 diabetes. Genomic variations of vitamin D metabolism and target cell action predispose to type 1 diabetes. There are several lines of evidence supporting a role for vitamin D inpan creatic beta-cell function. Vitamin D appears to increase the insulin response to glucose stimulation, whereas it does not appear to influence basal insulinemia. Vitamin D may have also a beneficial effect on insulin action, enhancing insulin responsiveness for glucose transport. Observational studies show a relatively consistent association between low vitamin D status, and prevalent type 2 DM or metabolic syndrome. There are also inverse associations with incident type 2 D Mor metabolic syndrome. Evidence from trials with vitamin D and/or calcium supplementation suggests that combined vitamin D and calcium supplementation may have a role inthe prevention of type 2 DM in populations at high risk (i.e.glucose intolerance). The available evidence is limited because most observational studies are cross-sectional and didnot adjust for important confounders, whereas interventionstudies were short in duration, included few subjects, used avariety of formulations of vitamin D and calcium, or did posthoc analyses. However, it could be concluded, that vitaminD insufficiency may negatively influence glycemia, where assupplementation may be beneficial in optimizing glucose metabolism.

Vitamin D is very old and important compound. One of its role in organism (and most widely known) is related to mineral metabolism. Lack of vitamin D could result in manifestation of rickets in growing organism. With change of life, industry development, air pollution, and undernourishment rickets wasa common phenomenon of last two centuries. At present time the high risk group comprises breast-fed, unsupplemented children with dark skin living in northern latitude.

Since the 1970s the interaction between the skeletal and muscular systems was a subject of many studies. It has been demonstrated that vitamin D plays an important role in controlling this interaction by maintaining an adequate level of calcium in muscle cells, thereby regulating the strength and duration of muscle contraction. This mechanism results from transgenic method of regulating the calcium influx into the cell by means of binding vitamin D with the receptor (VDR).A slower mechanism of vitamin D influence, dependent ongene transcription and synthesis of new proteins (CaBP, osteocalcin, ostepontin) stimulates the synthesis of myocytes, their differentiation, and inhibits apoptosis. In case of vitamin D deficiency a reversed phenomenon occurs. It has been clinically verified that there is a correlation between the level of vitamin D and the formation of sarcopenia and various types of myopathies as well as in the lack of effects of physical exercise. It plays a special role in increasing the fall risk. In all these irregularities vitamin D supplementation has a beneficial effect on muscle tissue.

Lipid malabsorption is observed In cystic fibrosis and chronic cholestasis as well as malabsorption associated with inflammatory bowel disease are a significant risk factor of vitamin D deficiency. Thus management guidelines include also vitaminD status monitoring by measurement of 25(OH)D3 and vitamin D supplementation. Observational studies of large cohorts of patients show a high frequency of vitamin D deficiency in these diseases, still we lack sufficient evidence form intervention trials to show clinical effects of vitamin D supplementation like decreased risk of bone fractures.

Recent epidemiologic and experimental evidence suggest that vitamin D plays a crucial role not only in skeletal development and calcium homeostasis, but may also have an important impact on cardiovascular disease, diabetes and immunologic dysfunction. Serum 25(OH)D vitamin level has been shownto have an inverse relationship with the prevalence of hypertension, obesity, diabetes, endothelial dysfunction, peripheral vascular disease and autoimmune disease. The data support the role of vitamin D in maintaining cardio vascular homeostasis through the action on cardio myocytes, circulating hormones and calcium levels. Vitamin D deficiency may lead to vascular smooth muscle cell proliferation, endothelial dysfunction, vascular and myocardial calcification, and increase dinflammation. Even though the majority of recent clinical studies indicating the link between low vitamin D level and cardiovascular disease, there is still insufficient evidence to conclude that supplementation of vitamin D may play a role in the prevention of cardiovascular outcomes.

Deficiency of vitamin D is common in patients with chronic kidney disease (CKD). One must remember that CKD includes wide range of renal diseases, from mild dysfunction to end stagerenal disease, dialysis and renal transplantation. Therefore the demand for vitamin D is diverse in CKD. Different forms of vitamin are used in supplementation, prophylaxis and treatment of bone disease, including oral ergocalciferol, cholecalciferol or calcitriol as well we high dose of calcitriol iv. The largest demand for vitamin D activity is present in dialyzed patients and the lowest in early stage of CKD, with exception of cases with massive proteinuria (additional wayof waste). The specificity of several forms of CKD is the reason of very variable dosing regimens, which follow the current demand and limited effect on target organs in the course of uremia. Therefore the dosage may be high and iv. route of administration is used in selected cases. Prophylaxis with cholecalciferol is recommended in absence of hyperparathyroidism and active vitamin D metabolites/analogs should beused when this problem is present in children with CKD.

It was suggested that supplementation with vitamin D and calcium can increase the risk of kidney stone formation. Numerous studies showed, however, that adequate calcium andvitamin D in take reduced the risk of crystallization of calciumoxalate in the urinary tract. In healthy individuals a diet with normal calcium intake of 1000–1300 mg per day is associated with a reduction in kidney stone formation by approximately 30–50% as compared with a diet containing 400–600 mg calcium daily. Higher dietary calcium intake results in binding of oxalate in the gut, diminished oxalate absorption from the intestine and reduced urinary oxalate excretion. It was shown that additional calcium supplementation was not associated with increased risk of kidney stones unless calciumis taken apart from meals and total calcium intake exceeds 2000 mg per day.It was shown that vitamin D in the doses of up to 10,000 I Uper day given over several months did not result in hypercalcemia, hypercalciuria and kidney stone formation. No cases of confirmed intoxication with vitamin D have been reported if serum 25(OH)D concentrations were below 150 ng/ml. Doses of vitamin D needed to produce such levels are in excess of20,000 IU daily. It should be stressed that the duration of vitamin D exposurein many clinical trials could be too short to form urinary stones.

The reliable measurement of 25(OH)D remains challenging. Whilst the overall accuracy of methods should be improved by the introduction of Reference Measurement Procedures (RMPs) and standard reference materials, the reliability of individual results may still be compromised by other components of the sample matrix. The advised way to judge the performance of 25(OH)D method was for the laboratory to participate in an External Quality Assessment (proficiencytesting) scheme such as DEQAS (Vitamin D External QualityAssessment Scheme. The correct interpretation of 25(OH)D results requires the close co-operation of clinicians and their laboratory colleagues.

1α,25(OH)2D3 is metabolized through the oxidation pathway of B-ring side chain at C-24 into inactive calcitroic acid or at C-23 leading to formation of 1α,25(OH)2D3-26,23-lactone. In the late 90-ties another metabolic pathway has been described – modification of hydroxyl groups configuration of A-ring at C-3 with formation of 3-epimers of 25(OH)D3,1α,25(OH)2D3 and 24,25(OH)2D3. C-3 epimers have been shown to exert slightly weaker biologic activity. C-3 epimers were, so far, detected in the serum of infants, children and adults however, concentrations were the highest in infants. Inspite of different configuration, these isomers play a similar biological role in the cells as their precursors, occuring inthe higher concentrations due to slow metabolism. It has been suggested that 3-epimers may display transcription and anti-proliferative effects as well as regulate cell differentiation and apoptosis. Elevated concentration of 3-epi-25(OH)D3 in the human serum may inter fere with 25(OH)D as say leading to false positive results. Separation of 3-epi-25-hydroxyvitamin D3 requires using of ultraperformance liquid chromatography –tandem mass spectrometry (LC-MS/MS). It is recommended that concentration of 3-epi-25(OH)D3 should be reported while measuring 25(OH)D3 in the serum samples of infants whereas this is not obligatory for children, adolescents and adults. This recommendation is based on the earlier data showing 3-epi-25(OH)D3 had a lower effecton calcemia comparing to nonepimeric forms.

Adequate vitamin D intake and its status are important for bone health, Ca-P metabolism and many others physiological processes. Pregnant and breast feeding women and their offspring are in a group of increased risk of vitamin D deficiency. Percentage of vitamin D deficiency among pregnant women and their newborns is very high despite of wide range of prenatal multivitamin supplementation. Vitamin D deficiency during pregnancy has negative impact not only on women health but also on their offspring health. Vitamin D supplementation at dose 800–1000 IU/d in case of lack of vitamin D endogenous synthesis and/or low consumption from dietis necessary during pregnancy and lactation to keep optimal vitamin D status of mother and offspring. For safety and efficacy,measurement of serum 25(OH)D concentration during supplementation should be considered. Breastfeeding without supplementation is an important risk factor of vitamin D deficiency in infancy. Vitamin D is recommended for infants at a dose of 400IU/d beginning from first day of life.

The vitamin D deficiency prevention in Poland is based on the recommendation of National Consultant in Pediatrics and the expert group for prevention of rickets and osteoporosis from 2009. Although theoretically the supply in vitamin D seems tobe simple, in current publications the deficiency of this vitaminis described in different age groups. This may be due to vitamin D deficient diet, avoiding of supplementation (exceptfor neonatal and infant period) and usage of UV filters. Polish recommendations are founded on the basis of studies on small groups of Polish population and foreign publications. This was the reason to undertake studies to evaluate the vitamin D supply in children from Poland in pubertal period (9–15 years) inmulticentre project (8 centers in Poland). On the basis of conducted studies in this life period in Polish children the vitamin D deficiency was observed, particularly after winter (75–80 %of examined children). Regardless of commonly known recommendations the prevention of vitamin D deficiency is insufficientand increase in vitamin D concentration is observed in Poland more due to the sun exposure in summer than with properly conducted prevention by pediatricians and general practitioners. The dietary recommendations and supplements including vitamin D (cod-liver oil, multivitamin specimens) are primary way to supply vitamin D, but in observed group it was advised in only half of examined children. The dosages for vitaminD deficiency prevention in children and adolescents are established on 400 IU per day and it may be suspected that this is sufficient because the main reason for vitamin D deficiency is avoidance of supplementation and vitamin D rich diet.

The study covers the issues related to source of vitamin D, including skin synthesis, foods as well as factors affecting effectiveness of endogenous vitamin D production and food fortification. The IOM recommendations for vitamin D supplementation and 25(OH)D concentrations were evaluated and discussed.

Vitamin D supplementation should be done for the whole population for the benefit of the “society’s health” according to the recommended guidelines, and for people who have vitamin D deficiency treatment with vitamin D is needed using higher dosages than those used for supplementation. Before treatment of vitamin D deficiency for an individual patient begins, the etiology of the deficiency should be established, appropriate vitamin D dosage should be decided taking into consideration the extent of the deficiency and weight of the patient, the length of treatment and monitoring procedures of the treatment effectiveness should be recognized. Thus, for patients with vitamin D deficiency, treatment should be “custom-made” and individualized.