Leukocyte telomere length as a compensatory mechanism in vitamin D metabolism.

Vitamin D deficiency is common among postmenopausal women. Telomere length can be a potential protective mechanism for age-related diseases. The objective of our study is to examine the association of vitamin D supplementation on leukocyte telomere length (LTL) in healthy postmenopausal women with vitamin D deficiency. The study was designed as a placebo-controlled study to investigate the short-term effects of vitamin D supplementation and seasonal changes on vitamin D related parameters, including 25(OH)D, 1,25(OH)2D parathormone (PTH), Vitamin D binding protein (VDBP), vitamin D receptor (VDR), and telomere length in a cohort of postmenopausal women (n = 102). The group was divided as supplementation (n = 52) and placebo groups (n = 50). All parameters were measured before and after treatment. Serum VDBP levels were measured by ELISA method and VDR, GC (VDBP) gene expressions and relative telomere lengths were measured in peripheral blood mononuclear cells (PBMC) using a quantitative real-time PCR method. The results demonstrate that baseline levels were similar between the groups. After vitamin D supplementation 25(OH)D, 1,25(OH)2D, PTH and VDBP levels were changed significantly compared to the placebo group. At the end of the study period, LTL levels were significantly increased in both groups and this change was more prominent in placebo group. The change in GC expression was significant between treatment and placebo groups but VDR expression remained unchanged. Even though the study was designed to solely assess the effects of vitamin D supplementation, LTL was significantly increased in the whole study group in summer months suggesting that LTL levels are affected by sun exposure and seasonal changes rather than supplementation. The study displayed the short-term effect of Vitamin D supplementation on vitamin D, PTH levels, LTL and vitamin D associated gene expressions. The relation between Vitamin D and LTL is not linear and could be confounded by several factors such as the population differences, regional and seasonal changes in sun exposure.

The relationships of vitamin D, vitamin D receptor gene polymorphisms, and vitamin D supplementation with Parkinson's disease.

In recent years, many studies have investigated the correlations between Parkinson's disease (PD) and vitamin D status, but the conclusion remains elusive. The present review focuses on the associations between PD and serum vitamin D levels by reviewing studies on the associations of PD with serum vitamin D levels and vitamin D receptor (VDR) gene polymorphisms from PubMed, Web of Science, Cochrane Library, and Embase databases. We found that PD patients have lower vitamin D levels than healthy controls and that the vitamin D concentrations are negatively correlated with PD risk and severity. Furthermore, higher vitamin D concentrations are linked to better cognitive function and mood in PD patients. Findings on the relationship between VDR gene polymorphisms and the risk of PD are inconsistent, but the FokI (C/T) polymorphism is significantly linked with PD. The occurrence of FokI (C/T) gene polymorphism may influence the risk, severity, and cognitive ability of PD patients, while also possibly influencing the effect of Vitamin D3 supplementation in PD patients. In view of the neuroprotective effects of vitamin D and the close association between vitamin D and dopaminergic neurotransmission, interventional prospective studies on vitamin D supplementation in PD patients should be conducted in the future.

Impact of Vitamin D and Vitamin D Receptor on Risk of Cardiovascular Diseases in Children and Adolescents with Obesity in Sichuan, China: A Cross-Sectional Study.

BACKGROUND: Previous studies have demonstrated the close relationship between vitamin D, vitamin D receptor (VDR), and obesity. Nevertheless, few studies have reported wherther the relationship among these is associated with the risk of cardiovascular diseases (CVDs) in Chinese children and adolescents. OBJECTIVE: The present study aimed to reveal the effects of obesity, serum vitamin D levels, and VDR FokI genotype on the risk of CVDs in children and adolescents in Sichuan, China. METHODS: Children and adolescents were recruited into a cross-sectional study. Serum vitamin D levels, serum lipid levels, and VDR FokI gene polymorphisms were measured in the laboratory. The selected lipid factors were used as biomarkers of CVD risk. The impact of obesity, vitamin D levels and VDR FokI genotype on CVD risk factors were investigated. RESULTS: Higher lipid levels were observed in children and adolescents in the obese group, when compared to the nonobese group. In the obese group, the C allele carriers had significantly lower concentrations of lipids, when compared to the TT genotype. C allele carriers who were vitamin D deficient had lower levels of total cholesterol (TC), triglycerides (TG), apolipoprotein B (Apo-B), total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C), low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C), and triglycerides/high-density lipoprotein cholesterol (TG/HDL-C), when compared to those with the TT genotype in obese children and adolescents. For vitamin D-insufficient obese children and adolescents, the TC, Apo-B, and TC/HDL-C in the C allele carriers were significantly lower, when compared to those in the TT genotype in obese children and adolescents. CONCLUSION: Obese children with low vitamin D levels, who are carriers of the C allele of the FokI gene, have lower levels of several biochemical markers of CVD risk, when compared to those who were TT homozygous. Obese children and adolescents may benefit from vitamin D supplementation, terms of lowering their CVD risk, particularly when they are carriers of the C allele of the FokI gene.

Status of vitamin D and the associated host factors in pulmonary tuberculosis patients and their household contacts: A cross sectional study.

Innate immunity plays an important role in pathophysiology of tuberculosis which is influenced by various host factors. One such factor is vitamin D which, along with its associated molecule, can alter the host defense against Mycobacterium Tuberculosis (M.Tb.) via altered production of cathelicidin and nitric oxide, both having bactericidal effect. Therefore, assessment of vitamin D and its associated molecules in tuberculosis patients and household contacts as compared to healthy controls were done and the implication of these findings in susceptibility to tuberculosis (TB) was studied. 80 active TB patients, 75 household contacts and 70 healthy controls were included. Vitamin D receptor (VDR), vitamin D binding protein (VDBP) and inducible nitric oxide synthase (iNOS) mRNA levels were studied using quantitative PCR. Serum VDR, cathelicidin, and iNOS levels were measured using ELISA. Vitamin D and NO levels were measured in serum using chemiluminescence based immunoassay and greiss reaction based colorimetry kit respectively. Decreased serum levels of vitamin D were observed in active TB patients as compared to healthy controls (p < 0.001). VDR and iNOS mRNA levels were found to be significantly lower in active TB patients compared to household contacts and healthy controls (p < 0.0001 and 0.005 respectively). VDBP mRNA expression was found to be lower in active TB group as compared to household contacts and healthy controls however the difference was not found to be significant (p > 0.21). Although, mRNA expression of VDR, VDR protein and iNOS along with vitamin D levels were significantly (p < 0.05) higher in household contacts compared to active TB group. However, levels of iNOS, NO and cathelicidin were found to be higher in TB patients as compared to household contacts and healthy controls (p < 0.01, 0.05 and 0.01 respectively). Higher levels of Vitamin D along with VDR and iNOS expression in household contacts as compared to active TB patients suggest vitamin D might have a protective role against TB plausibly decreasing disease susceptibility. Low vitamin D levels in active TB patients warrants further studies to determine the role of vitamin D supplementation in prevention and treatment of TB.

Effects of vitamin D supplementation on liver fibrogenic factors in non-alcoholic fatty liver patients with steatohepatitis: study protocol for a randomized clinical trial.

BACKGROUND: It has been suggested that vitamin D and its receptors involve in suppressing fibrogenic signaling in non-alcoholic fatty liver disease (NAFLD). However, the effect of vitamin D supplementation on fibrogenic factors has not been investigated in NAFLD individuals with steatohepatitis. This study was designed to examine the effects on vitamin D supplementation on serum levels of vitamin D receptor (VDR), fibrogenic factors, and fibrogenic microRNAs (MiR) in NAFLD patients. METHODS: Forty-six NAFLD patients will be recruited in this study. After block matching for sex and BMI, they will be randomly assigned to receive 4000 IU/day vitamin D or placebo for 12 weeks. Weight, height, and waist circumference will be measured. Determination of serum fibrogenic MiRs, laminin, collagen type IV, hyaluronic acid, vitamin D, VDR, calcium, blood glucose, serum insulin, lipid profile, liver markers (ALT, AST, total, direct, and indirect bilirubin) will be done at study baseline and at the end of the trial. Insulin resistance and insulin sensitivity will be determined using the HOMA-IR and QUICKI equation. DISCUSSION: This is the first randomized controlled trial that will determine the effect of vitamin D supplementation on serum levels of VDR, fibrogenic factors, and fibrogenic MiRs in NAFLD patients. The results of this trial will provide clinical evidence on the effectiveness of vitamin D supplementation in controlling liver fibrosis in NAFLD patients. TRIAL REGISTRATION: Iranian Registry of Clinical Trials, IRCT201405251485N13 . Registered on 14 March 2017.

Role of Vitamin D and Its Receptors in the Pathophysiology of Chronic Rhinosinusitis.

OBJECTIVES: Chronic rhinosinusitis (CRS) is a disease that represents a challenging therapeutic problem. Vitamin D and its receptors (VDR) are involved in the regulation of the immune system and may play role in CRS. Objectives of this study were to assess the relationships between the total concentration of vitamin D (25VD3) in sera, vitamin D receptor (VDR) expression, 1α-hydroxylase expression, and clinical data, including age, gender, Sino-Nasal Outcome Test (SNOT-22), computerized tomography (CT) scan, allergy status, and vitamin D supplementation in CRS patients with (CRSwNP) and without nasal polyps (CRSsNP), and in a control group. METHODS: The studied group comprised 52 patients with CRS without nasal polyps (sNP), 55 with CRS with nasal polyps (wNP), and 59 in the control group. The endpoints were determined by appropriate methods. We conducted immunohistochemical staining of gathered tissue from the ostiomeatal complex for determination of VDR and 1α-hydroxylase. Analytical results were compared with clinical data as already noted. RESULTS: A decrease in VDR nuclear staining occurred in CRS patients as compared to controls. Insignificant differences were observed in 1α-hydroxylase, expression in all studied groups, while VDR and cytochrome CYP27B1 protein expression (1α-hydroxylase) correlated with clinical data. CONCLUSIONS: The data provide evidence that indicates that vitamin D and its receptor and enzymes may play a role in CRS.

Autophagy, apoptosis, vitamin D, and vitamin D receptor in hepatocellular carcinoma associated with hepatitis C virus.

The aims of this study were to investigate the interplay between autophagy and apoptosis and to investigate the association between both of autophagy and apoptosis and vitamin D and its receptor in hepatitis C virus (HCV) viral infection and its implication in the progression into hepatocellular carcinoma (HCC).A cross-sectional study where serum levels of microtubule-associated protein 1A/1B-light chain 3 (LC3); marker of autophagy, caspase-3; marker of apoptosis, vitamin D3 and vitamin D receptor (VDR) were measured in healthy subjects as well as HCV and HCV-HCC patients using enzyme-linked immunosorbent assay technique.Collectively, the liver profile revealed hepatic dysfunctions in HCV patients with or without HCC. A significant reduction in the serum concentration levels LC3 and caspase-3 were observed referring to the down regulation of autophagy and host-mediated apoptosis in HCV patients with or without HCC. Deficiency of vitamin D and decreased levels of its receptor were observed in HCV and HCV-HCC patients.The perturbation in vitamin D/VDR axis, which modulates both of autophagy and apoptosis in HCV infection, may point out to its involvement and implication in the pathogenesis of HCV infection and the development of HCV-related HCC. Therefore, supplementation with vitamin D may not be the only solution to restore the vital biological functions of vitamin D but VDR-targeted therapy may be of great importance in this respect.

Prevalence, determinants and clinical correlates of vitamin D deficiency in patients with Chronic Obstructive Pulmonary Disease in London, UK.

Vitamin D deficiency is common in patients with chronic obstructive pulmonary disease (COPD), yet a comprehensive analysis of environmental and genetic determinants of serum 25-hydroxyvitamin D (25[OH]D) concentration in patients with this condition is lacking. We conducted a multi-centre cross-sectional study in 278 COPD patients aged 41-92 years in London, UK. Details of potential environmental determinants of vitamin D status and COPD symptom control and severity were collected by questionnaire, and blood samples were taken for analysis of serum 25(OH)D concentration and DNA extraction. All participants performed spirometry and underwent measurement of weight and height. Quadriceps muscle strength (QS) was measured in 134 participants, and sputum induction with enumeration of lower airway eosinophil and neutrophil counts was performed for 44 participants. Thirty-seven single nucleotide polymorphisms (SNP) in 11 genes in the vitamin D pathway (DBP, DHCR7, CYP2R1, CYP27B1, CYP24A1, CYP27A1, CYP3A4, LRP2, CUBN, RXRA, and VDR) were typed using Taqman allelic discrimination assays. Linear regression was used to identify environmental and genetic factors independently associated with serum 25(OH)D concentration and to determine whether vitamin D status or genetic factors independently associated with % predicted forced expiratory volume in one second (FEV1), % predicted forced vital capacity (FVC), the ratio of FEV1 to FVC (FEV1:FVC), daily inhaled corticosteroid (ICS) dose, respiratory quality of life (QoL), QS, and the percentage of eosinophils and neutrophils in induced sputum. Mean serum 25(OH)D concentration was 45.4nmol/L (SD 25.3); 171/278 (61.5%) participants were vitamin D deficient (serum 25[OH]D concentration <50nmol/L). Lower vitamin D status was independently associated with higher body mass index (P=0.001), lower socio-economic position (P=0.037), lack of vitamin D supplement consumption (P<0.001), sampling in Winter or Spring (P for trend=0.006) and lack of a recent sunny holiday (P=0.002). Vitamin D deficiency associated with reduced % predicted FEV1 (P for trend=0.060) and % predicted FVC (P for trend=0.003), but it did not associate with FEV1:FVC, ICS dose, QoL, QS, or the percentage of eosinophils or neutrophils in induced sputum. After correction for multiple comparisons testing, genetic variation in the vitamin D pathway was not found to associate with serum 25(OH)D concentration or clinical correlates of COPD severity. Vitamin D deficiency was common in this group of COPD patients in the UK, and it associated independently with reduced % predicted FEV1 and FVC. However, genetic variation in the vitamin D pathway was not associated with vitamin D status or severity of COPD.

Prevalence, determinants and clinical correlates of vitamin D deficiency in adults with inhaled corticosteroid-treated asthma in London, UK.

Vitamin D deficiency is common in children with asthma, and it associates with poor asthma control, reduced forced expiratory volume in one second (FEV1) and increased requirement for inhaled corticosteroids (ICS). Cross-sectional studies investigating the prevalence, determinants and clinical correlates of vitamin D deficiency in adults with asthma are lacking. We conducted a multi-centre cross-sectional study in 297 adults with a medical record diagnosis of ICS-treated asthma living in London, UK. Details of potential environmental determinants of vitamin D status, asthma control and medication use were collected by questionnaire; blood samples were taken for analysis of serum 25(OH)D concentration and DNA extraction, and participants underwent measurement of weight, height and fractional exhaled nitric oxide concentration (FeNO), spirometry and sputum induction for determination of lower airway eosinophil counts (n=35 sub-group). Thirty-five single nucleotide polymorphisms (SNP) in 11 vitamin D pathway genes (DBP, DHCR7, RXRA, CYP2R1, CYP27B1, CYP24A1, CYP3A4 CYP27A1, LRP2, CUBN, VDR) were typed using Taqman allelic discrimination assays. Linear regression was used to identify environmental and genetic factors independently associated with serum 25(OH)D concentration, and to determine whether vitamin D status was independently associated with Asthma Control Test (ACT) score, ICS dose, FeNO, forced vital capacity (FVC), FEV1 or lower airway eosinophilia. Mean serum 25(OH)D concentration was 50.6nmol/L (SD 24.9); 162/297 (54.5%) participants were vitamin D deficient (serum 25(OH)D concentration <50nmol/L). Lower vitamin D status was associated with higher body mass index (P=0.014), non-White ethnicity (P=0.036), unemployment (P for trend=0.012), lack of vitamin D supplement use (P<0.001), sampling in Winter or Spring (P for trend <0.001) and lack of a recent sunny holiday abroad (P=0.030), but not with potential genetic determinants. Vitamin D status was not found to associate with any marker of asthma control investigated. Vitamin D deficiency is common among UK adults with ICS-treated asthma, and classical environmental determinants of serum 25(OH)D operate in this population. However, in contrast to studies conducted in children, we found no association between vitamin D status and markers of asthma severity or control.

Cholecalciferol decreases inflammation and improves vitamin D regulatory enzymes in lymphocytes in the uremic environment: A randomized controlled pilot trial.

It has been reported that vitamin D regulates the immune system. However, whether vitamin D repletion modulates inflammatory responses in lymphocytes from dialysis patients is unclear. In the clinical trial, thirty-two (32) dialysis patients with 25 vitamin D ≤ 20ng/mL were randomized to receive either supplementation of cholecalciferol 100,000 UI/week/3 months (16 patients) or placebo (16 patients). In the in vitro study, B and T lymphocytes from 12 healthy volunteers (HV) were incubated with or without uremic serum in the presence or absence of 25 or 1,25 vitamin D. We evaluated the intracellular expression of IL-6, IFN-γ TLR7, TLR9, VDR, CYP27b1 and CYP24a1 by flow cytometry. We observed a reduction in the expression of TLR7, TLR9, INF-γ and CYP24a1 and an increase in VDR and CYP27b1 expression in patients which were supplemented with cholecalciferol, whereas no differences were found in the placebo group. Uremic serum increased the intracellular expression of IL-6, IFN-γ, TLR7, TLR9, VDR, CYP27b1 and CYP24a1. Treatment with 25 or 1,25 vitamin D decreased IL-6 and TLR9. CYP24a1 silencing plus treatment with 25 and/or 1,25 vitamin D had an additional reduction effect on IL-6, IFN-γ, TLR7 and TLR9 expression. This is the first study showing that cholecalciferol repletion has an anti-inflammatory effect and improves vitamin D intracellular regulatory enzymes on lymphocytes from dialysis patients.

The expression of VDR mRNA but not NF-κB surprisingly decreased after vitamin D treatment in multiple sclerosis patients.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the expression levels of vitamin D receptor (VDR) and NF-κB mRNAs in vitamin D (VD) supplemented multiple sclerosis (MS) patients. METHODS: RRMS patients received 50,000 IU vitamin D3/week as an intra-muscular injection for 2 months. Blood samples were obtained from 30 MS patients before and after VD supplementation and 32 healthy individuals, and then VDR and NF-κB mRNA levels were measured by real time PCR method and analyzed with independent and paired t-tests. Moreover, some correlations were performed between the expression levels of selected genes and some clinical features of MS and control groups. RESULTS: Surprisingly, the expression level of VDR mRNA significantly decreased after 2 months supplementation with VD in our selected patients and in contrast, the level of serum 25(OH) D increased after supplementation. Although, we didn't find any significant difference in the expression level of NF-κB gene before and after treatment with VD, its expression significantly decreased in untreated MS cases compared with healthy controls. CONCLUSION: In conclusion, we found some new evidences from the molecular mechanism of vitamin D effectiveness in MS treatment. Also, we need more functional studies to find the effect of VD on the expression level of VDR mRNA.

Time outdoors, blood vitamin D status and myopia: a review.

BACKGROUND: Myopia is a major public health concern throughout the world and the prevalence has been increasing rapidly in recent years, especially in urban Asia. The "vitamin D hypothesis" has been raised recently because vitamin D may be a link between less time outdoors and increased risk of myopia. METHODS: We reviewed all studies published in English which examined the association of time outdoors and blood vitamin D status with myopia. RESULTS: The protective effect of time spent outdoors on the risk of myopia onset has been well-established with numerous observational studies and three trials published. Five studies reporting the association between the blood vitamin D status and the risk of myopia and two studies examining the variations in the vitamin D receptor as potential risk factors for myopia development were identified. Most of the current evidence was cross-sectional in nature and had not properly controlled important confounders in its analyses. The evidence supporting that vitamin D played a role in myopia development is weak and the mechanisms are unclear. CONCLUSIONS: At the current stage, it is still unclear whether blood vitamin D status regulates the onset or progression of myopia. Blood vitamin D status may only serve as a biomarker of outdoor exposure, which is the real protective factor for myopia.

Successful Conversion From Parenteral Paricalcitol to Pulse Oral Calcitriol for the Management of Secondary Hyperparathyroidism in Hemodialysis Patients.

OBJECTIVE: The management of hyperparathyroidism in hemodialysis patients involves the administration of phosphate binders, vitamin D receptor activators, and calcimimetics. Intravenous paricalcitol has been preferred over oral calcitriol as it may cause less hypercalcemia and hyperphosphatemia. However, there is little data looking at the efficacy and tolerability of oral calcitriol in the calcimimetic era particularly in a real practice-based experience. The University of California, Irvine free-standing dialysis center converted from routine intravenous paricalcitol to oral calcitriol due to pharmacy purchasing preferences. We report the efficacy, safety, and cost of such a change. SUBJECTS: Ninety-three preconversion intravenous paricalcitol and 91 postconversion oral calcitriol. INTERVENTION: Conversion to in-center, pulse, oral calcitriol (0.25 mcg = 1 mcg paricalcitol) 3 times a week from intravenous paricalcitol. Additional dose adjustments were made by the nephrologists based on clinical indications. MAIN OUTCOME MEASURE: Five-month average serum calcium, phosphorous, and intact parathyroid hormone levels and cardiovascular events pretransition and posttransition. RESULTS: There were 93 patients on intravenous paricalcitol between April 2013 and August 2013, of which 74 converted to oral calcitriol and were included in the postconversion group evaluated between October 2013 and February 2014. An additional 17 new patients had initiated calcitriol such that 91 patients were on oral therapy in the postconversion period. Sevelamer use increased from 41 (44.1%) patients preconversion to 48 (52.7%) postconversion, whereas calcium acetate use significantly dropped from 62 (66.7%) to 46 (50.5%) (P = .026). Cinacalcet use dropped slightly from 37 (39.7%) patients preconversion to 35 (38.4%) postconversion. Average serum calcium, phosphorus, and intact parathyroid hormone levels remained unchanged after conversion. Percent of values within Kidney Disease Outcome Quality Initiative guidelines were similarly maintained. Estimated vitamin D cost savings were $564 per person/year. No increase in the incidence of cardiovascular events was observed. CONCLUSIONS: We conclude that in-center distributed pulse oral calcitriol may be an effective, safe, and economical treatment option for the management of hyperparathyroidism in hemodialysis patients.

Weight Status and Alcohol Intake Modify the Association between Vitamin D and Breast Cancer Risk.

BACKGROUND: Mechanistic hypotheses suggest that vitamin D may contribute to the prevention of breast cancer. However, epidemiologic evidence is inconsistent, suggesting a potential effect modification by individual factors. OBJECTIVE: Our objective was to perform exploratory analyses on the prospective associations between the plasma 25-hydroxyvitamin D [25(OH)D] concentration, polymorphisms of genes encoding for the vitamin D receptor (VDR) and vitamin D-binding protein (also known as gc-globulin or group-specific component, GC), and breast cancer risk, along with 2 potential modifiers: body mass index (BMI; in kg/m(2)) and alcohol intake. METHODS: A nested case-control study was set up in the SUpplémentation en VItamines et Minéraux Anti-oXydants (SU.VI.MAX) cohort (1994-2007), involving 233 women with breast cancer and 466 matched controls (mean ± SD age: 49 ± 6 y). The plasma total 25(OH)D concentration and gene polymorphisms were assessed on samples obtained at baseline. Conditional logistic regression models were computed. RESULTS: A higher plasma 25(OH)D concentration was associated with a decreased risk of breast cancer for women with a BMI < the median of 22.4 [OR quartile (Q)4 compared with Q1: 0.46; 95% CI: 0.23, 0.89; P-trend = 0.01, P-interaction = 0.002], whereas it was associated with an increased risk for women with a BMI ≥ the median (OR Q4 compared with Q1: 2.45; 95% CI: 1.13, 5.28; P-trend = 0.02, P-interaction = 0.002). A plasma 25(OH)D concentration ≥ 10 ng/mL was associated with a decreased risk of breast cancer for women with alcohol intakes ≥ the median of 7.1 g/d (OR ≥10 compared with <10 ng/mL: 0.50; 95% CI: 0.26, 0.95; P = 0.03, P-interaction = 0.03). The genetic analyses were consistent with the results observed with plasma 25(OH)D. CONCLUSION: In this prospective study, BMI and alcohol intake modified the association between vitamin D [plasma 25(OH)D and vitamin D-related gene polymorphisms] and breast cancer risk. These effect modifications suggest explanations for discrepancies in results of previous studies. This trial was registered at clinicaltrials.gov as NCT00272428.

Oral vitamin D supplementation has a lower bioavailability and reduces hypersecretion of parathyroid hormone and insulin resistance in obese Chinese males.

OBJECTIVE: To examine the vitamin D status, SNP of the vitamin D receptor gene (VDR) and the effects of vitamin D supplementation on parathyroid hormone and insulin secretion in adult males with obesity or normal weight in a subtropical Chinese city. DESIGN: An intervention trial. SETTING: Shenzhen City, Guangdong Province, China. SUBJECTS: From a cross-sectional survey conducted from June to July, eighty-two normal-weight and ninety-nine obese males (18-69 years) were screened to analyse their vitamin D status and for five SNP of VDR. From these individuals, in the same season of a different year, obese and normal-weight male volunteers (twenty-one per group) were included for an intervention trial with oral vitamin D supplementation at 1250 µg/week for 8 weeks. RESULTS: For the survey, there was no significant difference (P>0·05) in baseline circulating 25-hydroxyvitamin D concentrations or in the percentages of participants in different categories of vitamin D status between the two groups. The VDR SNP, rs3782905, was significantly associated with obesity (P=0·043), but none of the examined SNP were correlated with serum 25-hydroxyvitamin D when adjusted for age, BMI and study group. After vitamin D supplementation, serum 25-hydroxyvitamin D concentration, hypersecretions of parathyroid hormone and insulin, and insulin resistance in the obese were changed beneficially (P<0·05); however, the increase in serum 25-hydroxyvitamin D was less than that of the normal-weight men. CONCLUSIONS: For obese and normal-weight men of subtropical China, the summer baseline vitamin D status was similar. However, oral vitamin D supplementation revealed a decreased bioavailability of vitamin D in obese men and ameliorated their hypersecretion of parathyroid hormone and insulin resistance.

Influence of single nucleotide polymorphisms of vitamin D receptor-gene on the level of osteoassociated hormones linkage with postmenopausal osteoporosis.

The levels of osteoassociated hormones, macroelements, interleukines, cyclic nucleotides and activity of alkaline phosphatase were being detected in the blood plasma of 74 postmenopausal women with and without osteoporosis (OP). Bone mineral density (BMD) and the metacarpal index were being assessed according to the results of densitometry. The allele polymorphisms vitamin D receptor gene (VDR) Cdx2 (rs11568820) and TaqI (rs731236) were being identified with the help of the polymerase chain reaction. The major genotype CC TaqI was found in the group without OP 3.4 times more often than with OP, while the minor genotype TT was found 3.4 times more often with the presence of OP. The presence of the genotype CC TaqI decreased the risk of OP progress by 5.5 times, and the genotype TT TaqI increased by 5.4 times. The presence of the minor allele T was associated with the higher levels of interleukin 1ß, BMD and lower testosterone blood level. The major homozygote AA Cdx2 was found in women without OP 2.9 times more often, while the minor genotype GG - 5.4 times more often with the presence of OP. The presence of the major homozygote decreased the risk of OP progress by more than 5.3 times, while the minor homozygote increased the risk by 8 times. The presence of the minor allele G in the genotype was associated with the increase of parathyroid hormone, phosphorus, magnesium, alkaline phosphatase activity in blood, BMD and with the decrease of testosterone, progesterone and calcium blood levels.

Vitamin D supplementation promotes macrophages' anti-mycobacterial activity in type 2 diabetes mellitus patients with low vitamin D receptor expression.

The increasing number of people with type 2 diabetes (DM2) is alarming and if it is taken into account that the relative odds of developing tuberculosis in diabetic patients ranges from 2.44 to 8.33 compared with non-diabetic patients, thus in developing countries where these two diseases are encountering face to face, there is a need for prophylaxis strategies. The role of vitamin D has been widely implicated in growth control of Mycobacterium tuberculosis (Mtb) during primary infection mainly through the induction of certain antimicrobial peptides (AMPs). In this study we evaluated the vitamin D serum levels, CYP27B1-hydroxylase enzyme, vitamin D receptor (VDR) and AMPs gene expression in Healthy donors, DM2 and TB patients. Results showed that DM2 group has lower VDR and AMPs expression levels. When Monocytes Derived Macrophages (MDM) from DM2 patients with low VDR expression were supplemented with vitamin D, MDMs eliminate efficiently M. tuberculosis. This preliminary study suggests the use of vitamin D as prophylaxis for tuberculosis in high DM2 endemic countries.

Vitamin D in heart failure.

Evidence linking vitamin D to cardiovascular (CV) health has accumulated in recent years: numerous epidemiologic studies report deficiency as a significant CV risk factor, and rodent models suggest that active vitamin D can modulate critical remodeling processes, including cardiac hypertrophy and extracellular matrix remodeling. The presence of vitamin D signaling machinery within the human heart implies a direct role for this hormone in cardiac physiology and may explain associations between vitamin D status and CV outcomes. Heart failure (HF) represents a growing social and economic burden worldwide. Myocardial remodeling is central to HF development, and in the context of emerging evidence supporting mechanistic involvement of vitamin D, this review provides critical appraisal of scientific literature related to the role of vitamin D in CV disease, including data from epidemiologic and supplementation studies, as well as novel findings from animal models and in vitro work. Although associative data linking vitamin D and CV outcomes and evidence supporting a role for vitamin D in relevant pathogenic processes are both substantial, there are limited mechanistic data to indicate vitamin D supplementation as a viable therapeutic adjunct for the prevention of HF development following myocardial injury.

The pleiotropic effects of vitamin D in bone.

A current controversial question related to vitamin D supplementation is what level of serum 25-hydroxyvitamin D3 (25(OH)D3) is required to reduce the incidence of osteoporotic fractures. The reasoning behind vitamin D supplementation has been mostly derived from the role of vitamin D to promote intestinal calcium absorption and reduce bone resorption. While minimum 25(OH)D3 levels of 20nmol/L are required for sufficient intestinal calcium absorption to prevent osteomalacia, the mechanistic details of how higher 25(OH)D3 levels, well beyond that required for optimal calcium absorption, are able to prevent fractures and increase bone mineral density is unclear. Substantial evidence has arisen over the past decade that conversion of 25(OH)D3 to 1,25(OH)2D3via the 1-alpha hydroxylase (CYP27B1) enzyme in osteoblasts, osteocytes, chondrocytes and osteoclasts regulates processes such as cell proliferation, maturation and mineralization as well as bone resorption, which are all dependent on the presence the of the vitamin D receptor (VDR). We and others have also shown that increased vitamin D activity in mature osteoblasts by increasing levels of VDR or CYP27B1 leads to improved bone mineral volume using two separate transgenic mouse models. While questions remain regarding activities of vitamin D in bone to influence the anabolic and catabolic processes, the biological importance of vitamin D activity within the bone is unquestioned. However, a clearer understanding of the varied mechanisms by which vitamin D directly and indirectly influences mineral bone status are required to support evidence-based recommendations for vitamin D supplementation to reduce the risk of fractures. This article is part of a Special Issue entitled 'Vitamin D workshop'.