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Sample records for 25oh vitamin d2

  1. Quantitation of 25-OH-Vitamin-D₂ and 25-OH-Vitamin-D₃ in Urine Using LC-MS/MS.

    PubMed

    Carlow, Dean C; Schofield, Ryan C; Denburg, Michelle

    2016-01-01

    Patients with significant proteinuria represent a unique population with respect to vitamin D status due to the urinary losses of vitamin D-binding protein (DBP) to which >99 % of circulating 25-hydroxy vitamin D (25(OH)D) is bound. Low serum concentrations of 25(OH)D have been found in children and adults with nephrotic syndrome (NS). However, previously described assays developed to quantify the magnitude of urinary loss are technically challenging. This chapter describes a simple and sensitive method to quantify 25(OH)D2 and 25(OH)D3 in urine specimens in a single analytical LC-MS/MS analysis. This assay is more sensitive than previously described radioimmunoassays and offers the ability to quantitate both forms of 25-hydroxy vitamin D. The assay involves no chemical derivitization, has a linear measurement range of 20-1500 pg/mL and displays imprecision (CVs) below 7 % at various concentrations across the analytical measurement range.

  2. Low 25-OH vitamin D levels at time of diagnosis and recurrence of ovarian cancer.

    PubMed

    Granato, Teresa; Manganaro, Lucia; Petri, Luca; Porpora, Maria Grazia; Viggiani, Valentina; Angeloni, Antonio; Anastasi, Emanuela

    2016-02-01

    The objective of this study was to evaluate the correlation between 25-OH vitamin D and ovarian cancer as a diagnostic marker or recurrence disease marker. We studied the following: (1) 61 women without gynecologic diseases, (2) 45 women affected by benign ovarian disease, (3) 46 women with recent diagnosis of ovarian cancer, (4) 26 follow-up women with recurrent ovarian cancer, and (5) 32 follow-up women with stable ovarian cancer. The 25-OH vitamin D was quantified with LUMIPULSE® G 25-OH vitamin D on LUMIPULSE® G 1200 (Fujirebio, Japan). As a threshold value, identified by ROC curve analysis, 20.2 ng/mL (sensitivity 73.3 %, specificity 84 %) was chosen corresponding to the limit between sufficient and insufficient 25-OH vitamin D according to the WHO. Low 25-OH vitamin D levels were observed in 26 % of women without gynecologic diseases, in 80 % of women with recent diagnosis of ovarian cancer and in 24 % women affected by benign ovarian diseases (p < 0.001). The follow-up study showed an insufficient level of 25-OH vitamin D in 73 % women with recurrent ovarian cancer and in 47 % women with stable ovarian cancer (p < 0.0003). This study showed that patients with ovarian cancer are often insufficient in 25-OH vitamin D compared to women with benign ovarian diseases. The women with recurrent ovarian cancer presented more often low levels compared to women with stable ovarian cancer. This study suggests that 25-OH vitamin D, due to its antiproliferative properties, can be a good marker for ovarian cancer also.

  3. Low 25 (OH) vitamin D levels are associated with autoimmune thyroid disease in polycystic ovary syndrome.

    PubMed

    Muscogiuri, Giovanna; Palomba, Stefano; Caggiano, Mario; Tafuri, Domenico; Colao, Annamaria; Orio, Francesco

    2016-08-01

    Low 25(OH) vitamin D levels have been associated with several autoimmune diseases and recently with autoimmune thyroid disease (AITD). The aim of the study was to investigate the association of AITD with 25(OH) vitamin D levels in women with polycystic ovary syndrome (PCOS). Fifty women with PCOS were consecutively enrolled and underwent routine health checkups, which included measurements of 25(OH) vitamin D, anti-thyroid peroxidase (TPO-Ab), anti-thyreoglobulin (TG-Ab) antibodies, FT3, FT4, and TSH. Selecting 50 nmol/L as cut-off point, low 25(OH) vitamin D levels were detected in 23 of 50 patients (46 %). AITD was diagnosed when TPO-Ab levels exceeding 80 U/ml and/or TG-Ab levels exceeding 70 U/ml. AITD was detected in 12 of 50 patients (24 %). The levels of 25(OH) vitamin D were significantly lower in women with PCOS and AITD when compared with women with PCOS and without AITD (p = 0.02). In women with AITD no correlation was found between 25(OH) vitamin D and TG-Ab (r = 0.48; p = 0.16), TPO-Ab (r = 0.43; p = 0.21), TSH (r = 0.38; p = 0.27), FT3 (r = -0.40; p = 0.25) and FT4 levels (r = -0.54; p = 0.10). These findings suggest that low levels of 25(OH) vitamin D were significantly associated with AITD in women with PCOS.

  4. Occurrence of Vitamin 25(OH)D3 Insufficiency in Young Women with Metabolic Syndrome

    PubMed Central

    Rogal, Karolina; Mankowska, Aneta

    2011-01-01

    Vitamin D insufficiency is prevalent and may be associated with higher risk for metabolic syndrome. Low serum 25-hydroxyvitamin D3 is known to perturb cellular function in many tissues, including the endocrine pancreas, which are involved in the pathogenesis of obesity and type 2 diabetes. This study examined the vitamin 25(OH)D3 concentration and its relationship with the metabolic syndrome among 52 young women aged 20-40 yrs with overweight and obese. As defined by revised International Diabetes Federation (IDF 2005) criteria, 27 of the 52 women had the metabolic syndrome (52%). Women with MS had significantly lower mean concentration of vitamin 25(OH)D3. Vitamin D insufficiency was more prevalent in women with MS, compared with those who did not fulfill the criteria for this syndrome (63% vs 37%, respectively) as well as among women with metabolic syndrome mild deficiency occurred much more frequently than in without MS (58% vs 26%, respectively). When serum concentrations of 25(OH)D3 were categorized in tertiles, there was a decreasing prevalence of MS in women with increasing concentrations of 25(OH)D3. The study findings suggest that insufficiency of vitamin 25(OH)D3 is more common in women with excessive body weight and metabolic syndrome than in women with excessive body weight without metabolic syndrome.

  5. Performance Evaluation of Siemens ADVIA Centaur and Roche MODULAR Analytics E170 Total 25-OH Vitamin D Assays

    PubMed Central

    Chen, Yu; Kinney, Lois; Božović, Andrea; Smith, Hilary; Tarr, Heather; Diamandis, Eleftherios P.; LeBlanc, Adrien

    2014-01-01

    Objectives To evaluate the newly developed Roche MODULAR Analytics E170 Total Vitamin D and the Siemens ADVIA Centaur® Vitamin D Total assays. Materials and Methods Assays were evaluated using the Clinical and Laboratory Standards Institute protocols. Split patient samples were compared with LC-MS/MS and DiaSorin LIAISON assays (n=79 including 15 specimens with detectable endogenous 25-OH vitamin D2). Assay accuracy was also evaluated using the Vitamin D External Quality Assessment Scheme samples. Results The ADVIA Centaur and E170 assays demonstrated maximum total CVs of 14.1% and 5.9%, respectively. Both showed excellent linearity (R2 >0.99). The ADVIA Centaur assay demonstrated interference with bilirubin at 800 μmol/L, hemolysis at 1.25 g/L, and triglycerides at 2.8 mmol/L. Compared to LC-MS/MS, the ADVIA Centaur assay demonstrated a R2 value of 0.893, average bias of −8.8%; the E170 assay an R2 value of 0.872, average bias of 14.3% with underestimation of 25-OH vitamin D2. Compared to the LIAISON assay, the ADVIA Centaur assay demonstrated an R2 value of 0.781, average bias of −17.3%; the E170 assay an R2 value of 0.823, average bias of 11.4%. The ADVIA Centaur and E170 assays demonstrated a biases of <20% in 10/10 and 8/10 samples, respectively. Conclusions The ADVIA Centaur and E170 vitamin D assays demonstrated acceptable linearity, imprecision, and accuracy. The E170 assay demonstrated consistent underestimation of 25-OH vitamin D2 levels. Compared with LC-MS/MS, the ADVIA Centaur assay demonstrated a higher R2 value and a smaller average bias than the E170 assay. PMID:22705028

  6. Association of serum 25(OH) vitamin D3 concentration with severity of multiple sclerosis

    PubMed Central

    Shahbeigi, Saeed; Pakdaman, Hosein; Fereshtehnejad, Seyed-Mohammad; Nikravesh, Elham; Jalilzadeh, Roghie

    2012-01-01

    Background There is a known inverse association between solar radiation and the prevalence of multiple sclerosis (MS). Some studies have investigated the link between vitamin D and MS. The aim of this study was to investigate the possible association between serum 25(OH) vitamin D3 concentration and the severity of disease in Iranian patients with MS. Methods Patients with relapsing–remitting MS underwent neurological examination, including measurement of Expanded Disability Status Scale (EDSS) score, and were categorized by disease severity into mild (0 ≤ EDSS ≤3), moderate (3.5 ≤ EDSS ≤5.5) and severe (6 ≤ EDSS). Serum concentrations of 25(OH) vitamin D3, calcium, phosphorus, magnesium and parathyroid hormone were also measured. Results A total of 78 (73.1% female) patients with MS were evaluated. The mean (± standard deviation) of age was 33.9 ± 9.2 years. The mean (± standard error) serum concentrations of 25(OH) vitamin D3 were 36.6 ± 5.1 mg/dL, 50.1 ± 12.6 mg/dL and 19.8 ± 6.5 mg/dL in patients with mild, moderate and severe disease, respectively. There was a statistically significant inverse correlation between 25(OH) vitamin D3 concentration and EDSS score (P = 0.016, r= –0.273 by Spearman rank correlation test), which was observed in women only (P = 0.021, r = –0.305). Receiver operating characteristic curve analysis suggested that a serum 25(OH) vitamin D3 concentration cutoff of 16.5 mg/dL could differentiate patients with mild/moderate MS from severe disease with 74.6% accuracy. Conclusion Our findings further support the association between vitamin D and disease severity in MS. PMID:24250862

  7. Reduced 25-OH vitamin D in patients with autoimmune cytopenias, clinical correlations and literature review.

    PubMed

    Fattizzo, Bruno; Zaninoni, Anna; Giannotta, Juri A; Binda, Francesca; Cortelezzi, Agostino; Barcellini, Wilma

    2016-07-01

    Vitamin D deficiency is widespread in Western Countries and has been found related to autoimmune and hematologic disease incidence and clinical course. We evaluated vitamin D levels, vitamin D receptor (VDR) and T helper (Th)1, Th2 and Th17 immunomodulatory cytokines in patients with immune thrombocytopenic purpura (ITP, N=44), primary autoimmune hemolytic anemia (AIHA, n=35), Evans' syndrome (n=5) and chronic idiopathic neutropenia (CIN, n=19) and also tested vitamin D effect on the in vitro production of anti-erythrocyte autoantibodies. 25-OH-vitamin D levels were significantly lower and vitamin D receptor higher in patients than in controls. Among ITP cases, those with very low vitamin D levels displayed reduced platelet counts, irrespective of the bleeding history. In AIHA patients, LDH values negatively correlated with vitamin D levels in mixed forms, and reticulocyte counts were positively related with vitamin D. Considering treatment, AIHA patients who had been treated with 2 therapy lines or more showed lower mean 25-OH-vitamin D levels than those untreated or treated with one line of therapy only. IL-6, IL-10, IL-17 and IFN-γ levels were higher in patients versus controls, whereas TNF-α was significantly reduced. Finally, vitamin D at concentrations of 10, 20, and 40ng/mL reduced the in vitro production of anti-erythrocyte autoantibodies both in pokeweed-stimulated and unstimulated cultures. In conclusion, vitamin D is reduced in autoimmune cytopenias and correlate with disease severity, supporting its possible protective role against the development of autoimmunity. Literature review showed vitamin D deficiency reports both in onco- and in non onco-hematologic diseases with a relationship with disease severity/activity in myeloid and lymphoid neoplasms, as well as in sickle cell disease. Supplementation has produced weak results in autoimmune and hematologic diseases, and further studies are needed.

  8. Effect of 24,25-dihydroxyvitamin D3 on 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) metabolism in vitamin D-deficient rats infused with 1,25-(OH)2D3

    SciTech Connect

    Yamato, H.; Matsumoto, T.; Fukumoto, S.; Ikeda, K.; Ishizuka, S.; Ogata, E.

    1989-01-01

    Previous studies revealed that administration of 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3) to calcium (Ca)-deficient rats causes a dose-dependent reduction in markedly elevated serum 1,25-(OH)2D3 level. Although the results suggested that the metabolism of 1,25-(OH)2D3 was accelerated by 24,25-(OH)2D3, those experiments could not define whether the enhanced metabolism of 1,25-(OH)2D3 played a role in the reduction in the serum 1,25-(OH)2D3 level. In the present study, in order to address this issue more specifically, serum 1,25-(OH)2D3 was maintained solely by exogenous administration through miniosmotic pumps of 1,25-(OH)2D3 into vitamin D-deficient rats. Thus, by measuring the serum 1,25-(OH)2D3 concentration, the effect of 24,25-(OH)2D3 on the MCR of 1,25-(OH)2D3 could be examined. Administration of 24,25-(OH)2D3 caused a dose-dependent enhancement in the MCR of 1,25-(OH)2D3, and 1 microgram/100 g rat.day 24,25-(OH)2D3, which elevated serum 24,25-(OH)2D3 to 8.6 +/- 1.3 ng/ml, significantly increased MCR and suppressed serum levels of 1,25-(OH)2D3. The effect of 24,25-(OH)2D3 on 1,25-(OH)2D3 metabolism developed with a rapid time course, and the recovery of iv injected (1 beta-3H)1,25-(OH)2D3 in blood was significantly reduced within 1 h. In addition, there was an increase in radioactivity in the water-soluble fraction of serum as well as in urine, suggesting that 1,25-(OH)2D3 is rapidly degraded to a water-soluble metabolite(s). Furthermore, the reduction in serum 1,25-(OH)2D3 was associated with a reduction in both serum and urinary Ca levels. Because the conversion of (3H)24,25-(OH)2D3 to (3H)1,24,25-(OH)2D3 or other metabolites was minimal in these rats, 24,25-(OH)2D3 appears to act without being converted into other metabolites. These results demonstrate that 24,25-(OH)2D3 rapidly stimulates the metabolism of 1,25-(OH)2D3 and reduces its serum level.

  9. Changes of 25-OH-Vitamin D during Overwintering at the German Antarctic Stations Neumayer II and III

    PubMed Central

    Steinach, Mathias; Kohlberg, Eberhard; Maggioni, Martina Anna; Mendt, Stefan; Opatz, Oliver; Stahn, Alexander; Tiedemann, Josefine; Gunga, Hanns-Christian

    2015-01-01

    Purpose Humans in Antarctica face different environmental challenges, such as low ultra-violet radiation, which is crucial for vitamin D production in humans. Therefore we assessed changes in 25-OH-vitamin D serum concentration during 13 months of overwintering at the German Stations Neumayer II and III (2007–2012). We hypothesized that (i) 25-OH-vitamin D serum concentration would significantly decrease, (ii) changes would be affected by age, gender, baseline (i.e. pre-overwintering) fat mass, baseline 25-OH-vitamin D serum concentration, and station residence, and (iii) our results would not differ from similar previous studies in comparable high latitudes. Materials & Methods 25-OH-vitamin D serum concentrations were determined before, after, and monthly during the campaigns from venous blood samples of n = 43 participants (28 men, 15 women). Baseline fat mass was determined via bio impedance analysis and body plethysmography. Data were analyzed for change over time, dependency on independent parameters, and after categorization for sufficiency (>50nmol/l), insufficiency (25-50nmol/l), and deficiency (<25nmol/l). Results were compared with data from similar previous studies. Results We found a significant decrease of 25-OH-vitamin D with dependency on month. Age, gender, fat mass, and station residence had no influence. Only baseline 25-OH-vitamin D serum concentrations significantly affected subsequent 25-OH-vitamin D values. Conclusions Overwinterings at the Antarctic German research stations Neumayer II and III are associated with a decrease in 25-OH-vitamin D serum concentrations, unaffected by age, gender, baseline fat mass, and station residence. Higher baseline vitamin D serum concentrations might protect from subsequent deficiencies. Residence at the Neumayer Stations may lead to lower vitamin D serum concentrations than found in other comparable high latitudes. PMID:26641669

  10. Association Between Serum 25(OH) Vitamin D and the Risk of Cognitive Decline in Older Women

    PubMed Central

    Paudel, Misti; Taylor, Brent C.; Ishani, Areef; Rossom, Rebecca; Yaffe, Kristine; Blackwell, Terri; Lui, Li-Yung; Hochberg, Marc; Ensrud, Kristine E.

    2012-01-01

    Background: Results of prospective studies examining the association between 25 hydroxyvitamin D (25[OH]D) levels and cognitive decline have been inconsistent. We tested the hypothesis that lower 25(OH)D levels are associated with a greater likelihood of cognitive impairment and risk of cognitive decline. Methods: The study is a cross-sectional and longitudinal analysis of a prospective cohort of 6,257 community-dwelling elderly women followed for 4 years. Global cognitive function was measured by the Modified Mini-Mental State Examination and executive function was measured by Trail Making Test Part B (Trails B). Cognitive impairment at baseline was defined as a score >1.5 SD below the sample mean; cognitive decline was defined as decline from baseline to follow-up >1 SD from mean change in score. Results: Women with very low vitamin D levels had an increased odds of global cognitive impairment at baseline: odds ratio (95% confidence interval), 1.60 (1.05–2.42) for women with 25(OH)D <10 ng/mL (25 nmol/L) compared with those with 25(OH)D levels ≥30 ng/mL (75 nmol/L). Compared with women with baseline 25(OH)D level ≥30 ng/mL (75 nmol/L), women with lower levels had an increased risk of global cognitive decline: odds ratio (95% confidence interval), 1.58(1.12–2.22) for women with levels <10 ng/mL (25 nmol/L), and 1.31 (1.04–1.64) for those with levels 10–19.9 ng/mL (25–49 nmol/L). Levels of 25(OH)D were not associated with executive cognitive function. Conclusions: Low 25(OH)D levels among older women were associated with a higher odds of global cognitive impairment and a higher risk of global cognitive decline. PMID:22454371

  11. TREM-2 Receptor Expression Increases with 25(OH)D Vitamin Serum Levels in Patients with Pulmonary Sarcoidosis.

    PubMed

    Bucova, Maria; Suchankova, Magda; Tibenska, Elena; Tedlova, Eva; Demian, Juraj; Majer, Ivan; Novosadova, Helena; Tedla, Miroslav

    2015-01-01

    TREM-1 and TREM-2 molecules are members of the TREM transmembrane glycoproteins. In our previous study we identified increased expressions of TREM-1 and TREM-2 receptors in pulmonary sarcoidosis (PS). Only a few studies concerning the association between vitamin D and TREM receptor expression can be found. The aim of our current study was to determine the association between the levels of an inactive form of 25(OH)D vitamin and TREM-1 and TREM-2 receptor expressions. We have detected low levels of 25(OH)D vitamin in 79% of PS patients. Only 21% of patients had normal serum level of 25(OH)D vitamin with values clustered within the low-normal range. The most striking findings were the increased TREM-2 expressions on myeloid cells surfaces in BALF of PS patients with normal 25(OH)D vitamin serum levels compared with those with its decreased levels. The total number of TREM-2 positive cells was 5.7 times higher and the percentage of TREM-2 positive cells was also significantly increased in BALF of PS patients with normal compared to PS patients with low 25(OH)D vitamin serum levels. A significant correlation between total TREM-2 expression and vitamin D levels has been detected too. However, we have not detected similar differences in TREM-1expression and 25(OH)D vitamin serum levels.

  12. TREM-2 Receptor Expression Increases with 25(OH)D Vitamin Serum Levels in Patients with Pulmonary Sarcoidosis

    PubMed Central

    Bucova, Maria; Suchankova, Magda; Tibenska, Elena; Tedlova, Eva; Demian, Juraj; Majer, Ivan; Novosadova, Helena; Tedla, Miroslav

    2015-01-01

    TREM-1 and TREM-2 molecules are members of the TREM transmembrane glycoproteins. In our previous study we identified increased expressions of TREM-1 and TREM-2 receptors in pulmonary sarcoidosis (PS). Only a few studies concerning the association between vitamin D and TREM receptor expression can be found. The aim of our current study was to determine the association between the levels of an inactive form of 25(OH)D vitamin and TREM-1 and TREM-2 receptor expressions. We have detected low levels of 25(OH)D vitamin in 79% of PS patients. Only 21% of patients had normal serum level of 25(OH)D vitamin with values clustered within the low-normal range. The most striking findings were the increased TREM-2 expressions on myeloid cells surfaces in BALF of PS patients with normal 25(OH)D vitamin serum levels compared with those with its decreased levels. The total number of TREM-2 positive cells was 5.7 times higher and the percentage of TREM-2 positive cells was also significantly increased in BALF of PS patients with normal compared to PS patients with low 25(OH)D vitamin serum levels. A significant correlation between total TREM-2 expression and vitamin D levels has been detected too. However, we have not detected similar differences in TREM-1expression and 25(OH)D vitamin serum levels. PMID:26166951

  13. TREM-2 Receptor Expression Increases with 25(OH)D Vitamin Serum Levels in Patients with Pulmonary Sarcoidosis.

    PubMed

    Bucova, Maria; Suchankova, Magda; Tibenska, Elena; Tedlova, Eva; Demian, Juraj; Majer, Ivan; Novosadova, Helena; Tedla, Miroslav

    2015-01-01

    TREM-1 and TREM-2 molecules are members of the TREM transmembrane glycoproteins. In our previous study we identified increased expressions of TREM-1 and TREM-2 receptors in pulmonary sarcoidosis (PS). Only a few studies concerning the association between vitamin D and TREM receptor expression can be found. The aim of our current study was to determine the association between the levels of an inactive form of 25(OH)D vitamin and TREM-1 and TREM-2 receptor expressions. We have detected low levels of 25(OH)D vitamin in 79% of PS patients. Only 21% of patients had normal serum level of 25(OH)D vitamin with values clustered within the low-normal range. The most striking findings were the increased TREM-2 expressions on myeloid cells surfaces in BALF of PS patients with normal 25(OH)D vitamin serum levels compared with those with its decreased levels. The total number of TREM-2 positive cells was 5.7 times higher and the percentage of TREM-2 positive cells was also significantly increased in BALF of PS patients with normal compared to PS patients with low 25(OH)D vitamin serum levels. A significant correlation between total TREM-2 expression and vitamin D levels has been detected too. However, we have not detected similar differences in TREM-1expression and 25(OH)D vitamin serum levels. PMID:26166951

  14. Oral supplementation with 25(OH)D3 versus vitamin D3: effects on 25(OH)D levels, lower extremity function, blood pressure, and markers of innate immunity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To test the effect of 25(OH)D3 (HyD) compared to vitamin D3 on serum 25-hydroxyvitamin D levels (25(OH)D), lower extremity function, blood pressure, and markers of innate immunity. Twenty healthy postmenopausal women with an average 25(OH)D level of 13.23.9 ng/mL (meanSD) and a mean age of 61.57.2 y...

  15. Serum 25(OH) Vitamin D Levels in Polish Women during Pregnancies Complicated by Hypertensive Disorders and Gestational Diabetes

    PubMed Central

    Domaracki, Piotr; Sadlecki, Pawel; Odrowaz-Sypniewska, Grazyna; Dzikowska, Ewa; Walentowicz, Pawel; Siodmiak, Joanna; Grabiec, Marek; Walentowicz-Sadlecka, Malgorzata

    2016-01-01

    Background: An association between the level of vitamin D and the risk of pregnancy-related complications remains unclear. The aim of this study was to examine concentrations of 25(OH) vitamin D in Polish women with normal pregnancies and pregnancies complicated by gestational hypertension, preeclampsia or gestational diabetes mellitus (GDM). Moreover, we analyzed an association between maternal serum 25(OH)D and the risk of gestational hypertension, preeclampsia and GDM. Material and Methods: The study included 207 pregnant women, among them 171 with pregnancy-related complications: gestational hypertension (n = 45), preeclampsia (n = 23) or GDM (n = 103). The control group consisted of 36 women with normal pregnancies. Concentrations of serum 25(OH)D were measured at admission to the hospital prior to delivery Results: Patients with hypertension did not differ significantly from the controls in terms of their serum 25(OH)D concentrations (18.20 vs. 22.10 ng/mL, p = 0.15). Highly significant differences were found in 25(OH)D concentrations of women with preeclampsia and the controls (14.75 vs. 22.10 ng/mL, p = 0.0021). GDM was not associated with significant differences in 25(OH)D concentration. A low level of 25(OH)D turned out to be associated with an increased risk of preeclampsia during pregnancy on both univariate and multivariate regression analysis, and was a significant predictor of this condition on ROC (receiver operating characteristic) analysis (AUC = 0.70, p < 0.01). Conclusions: 25(OH)D deficiency is common among pregnant Polish women. Low concentrations of 25(OH)D may play a role in the etiopathogenesis of preeclampsia. Routine assessment of the 25(OH)D level during pregnancy may be crucial for the identification of women at increased risk of preeclampsia. PMID:27690002

  16. New perspectives on vitamin D food fortification based on a modeling of 25(OH)D concentrations

    PubMed Central

    2013-01-01

    Background In Germany, vitamin D intake from food and synthesis in the skin is low, which leads to low 25(OH)D serum concentrations. In contrast to many other countries, general vitamin D food fortification is still prohibited in Germany, although the European Commission published a regulatory framework to harmonize addition of vitamins to foods. Thus the purpose of our study was to develop a vitamin D fortification model, taking into account all vitamin D sources with the goal to fulfill requirements of intake recommendations or preferable 25(OH)D serum concentrations. Finally, the aim was to assess the suitability of different carriers and associated risks. Methods We developed a mathematical bottom-up model of 25(OH)D serum concentrations based on data about vitamin D sources of the German population such as sunlight, food and supplements for all federal states taking seasonal and geographical variations into account. We used this model to calculate the optimal fortification levels of different vitamin D carriers in two approaches. First we calculated required fortification levels based on fixed intake recommendations from e.g. the IOM or the DGE and second based on achieving certain 25(OH)D serum concentrations. Results To lift 25(OH)D serum concentration in Germany to 75 nmol/L, e.g. 100 g bread has to be fortified with 11.3 μg during winter, resulting in a daily vitamin D intake of 23.7 μg. Bread seems to be a suitable carrier for base supply. However, overdose risk with a single fortified product is higher than the risk with several fortified carriers. Conclusions With the model in hand, it is possible to conceive vitamin D fortification strategies for different foodstuffs and model its impact on 25(OH)D serum concentrations. PMID:24261676

  17. Association between promoter region genetic variants of PTH SNPs and serum 25(OH)-vitamin D level

    PubMed Central

    Al-Daghri, Nasser M; Al-Attas, Omar S; Krishnaswamy, Soundararajan; Yakout, Sobhy M; Mohammed, Abdul Khader; Alenad, Amal M; Chrousos, George P; Alokail, Majed S

    2015-01-01

    Parathyroid hormone (PTH) plays a crucial role in calcium metabolism and skeletal development via altering vitamin D level. Besides, hypersecretion of PTH is implicated in the etiology of osteoporosis. In this study, we analyzed association between promoter region sequence variants of PTH gene and circulating 25-hydroxy-vitamin D (25(OH)D) level. Genotypes of PTH SNPs rs1459015, rs10500783 and rs10500784 and circulating serum 25(OH)D level of healthy adults (N=386) of different nationalities living in Riyadh were determined and relation between the different PTH allelic variants and corresponding mean 25(OH)D values were obtained using Analysis of Variance (ANOVA) and Bonferroni post-hoc test for multiple comparisons. We observed a high prevalence of vitamin D deficiency (<50 nmol/l) among all nationals which ranged from 59% among Indians to 82% among Yemeni. Comparison of the means of 25(OH)D levels corresponding to different genotypes of PTH SNPs indicated that the T allele of SNP rs1459015 was associated with higher 25(OH)D level in the Sudanese (P=0.03), while the T allele of SNP rs10500783 was associated with higher 25(OH)D level in Saudis (P=0.03). Analysis of results also indicated that the Sudanese carriers of the CC genotype of SNP rs1459015 had a higher risk of suffering from vitamin D deficiency (P=0.02). In conclusion, our study indicated significant association between specific PTH gene promoter region variants and altered levels of 25(OH)D and vitamin D deficiency among specific nationals. PMID:26339419

  18. Effects of sun exposure on 25(OH) vitamin D concentration in urban and rural women in Malaysia.

    PubMed

    Nurbazlin, Musa; Chee, Winnie Siew Swee; Rokiah, Pendek; Tan, Alexander Tong Boon; Chew, Yee Yean; Nusaibah, Abd Rahman Siti; Chan, Siew Pheng

    2013-01-01

    Ultraviolet B sunlight exposure is a primary source of vitamin D. There have been reports of low vitamin D status amongst the Malaysian population despite it being a tropical country. This study was conducted to determine the influence of sun exposure on 25(OH)D concentrations in urban and rural women in Malaysia and factors predicting 25(OH)D concentrations. Women aged above 45 years were recruited from urban (n=107) and rural areas (n=293). Subjects were interviewed regarding their outdoor activities and usual outdoor attire over the previous week. 25(OH)D concentrations were analyzed using the vitamin D3 (25-OH) electrochemiluminescence immunoassay. Median (Q1-Q3) age of the participants was 57 (53-61) years old. Median (Q1-Q3) 25(OH)D concentration of rural women was significantly higher [69.5 (59.0-79.1) nmol/L] compared to urban women [31.9 (26.1- 45.5) nmol/L] (p<0.001). Rural women spent more time in the sun compared to urban women (7.83 (3.67-14.7) vs 2.92 (1.17-4.92) hours, p<0.001), although the fraction of body surface area (BSA) exposed to sunlight was significantly higher in the urban group [0.21 (0.21-0.43) vs 0.12 (0.07-0.17), p<0.001]. The calculated sun index (hours of sun exposure per week × fraction of BSA) was significantly higher in rural [0.89 (0.42-1.83)] compared to urban women [0.72 (0.26-1.28)], p=0.018. In the stepwise linear regression, rural dwelling increased the serum 25(OH)D by 31.74 nmol/L and 25(OH)D concentrations increased by 1.93 nmol/L for every unit increment in sun index. Urban women in Malaysia had significantly lower vitamin D status compared to rural women. Rural dwelling and sun index were key factors influencing vitamin D status in Malaysian women.

  19. Effects of vitamin D2-fortified bread v. supplementation with vitamin D2 or D3 on serum 25-hydroxyvitamin D metabolites: an 8-week randomised-controlled trial in young adult Finnish women.

    PubMed

    Itkonen, Suvi T; Skaffari, Essi; Saaristo, Pilvi; Saarnio, Elisa M; Erkkola, Maijaliisa; Jakobsen, Jette; Cashman, Kevin D; Lamberg-Allardt, Christel

    2016-04-14

    There is a need for food-based solutions for preventing vitamin D deficiency. Vitamin D3 (D3) is mainly used in fortified food products, although the production of vitamin D2 (D2) is more cost-effective, and thus may hold opportunities. We investigated the bioavailability of D2 from UV-irradiated yeast present in bread in an 8-week randomised-controlled trial in healthy 20-37-year-old women (n 33) in Helsinki (60°N) during winter (February-April) 2014. Four study groups were given different study products (placebo pill and regular bread=0 µg D2 or D3/d; D2 supplement and regular bread=25 µg D2/d; D3 supplement and regular bread=25 µg D3/d; and placebo pill and D2-biofortified bread=25 µg D2/d). Serum 25-hydroxyvitamin D2 (S-25(OH)D2) and serum 25-hydroxyvitamin D3 (S-25(OH)D3) concentrations were measured at baseline, midpoint and end point. The mean baseline total serum 25-hydroxyvitamin D (S-25(OH)D=S-25(OH)D2+S-25(OH)D3) concentration was 65·1 nmol/l. In repeated-measures ANCOVA (adjusted for baseline S-25(OH)D as total/D2/D3), D2-bread did not affect total S-25(OH)D (P=0·707) or S-25(OH)D3 (P=0·490), but increased S-25(OH)D2 compared with placebo (P<0·001). However, the D2 supplement was more effective than bread in increasing S-25(OH)D2 (P<0·001). Both D2 and D3 supplementation increased total S-25(OH)D compared with placebo (P=0·030 and P=0·001, respectively), but D2 supplementation resulted in lower S-25(OH)D3 (P<0·001). Thus, D2 from UV-irradiated yeast in bread was not bioavailable in humans. Our results support the evidence that D2 is less potent in increasing total S-25(OH)D concentrations than D3, also indicating a decrease in the percentage contribution of S-25(OH)D3 to the total vitamin D pool. PMID:26864127

  20. Effects of vitamin D2-fortified bread v. supplementation with vitamin D2 or D3 on serum 25-hydroxyvitamin D metabolites: an 8-week randomised-controlled trial in young adult Finnish women.

    PubMed

    Itkonen, Suvi T; Skaffari, Essi; Saaristo, Pilvi; Saarnio, Elisa M; Erkkola, Maijaliisa; Jakobsen, Jette; Cashman, Kevin D; Lamberg-Allardt, Christel

    2016-04-14

    There is a need for food-based solutions for preventing vitamin D deficiency. Vitamin D3 (D3) is mainly used in fortified food products, although the production of vitamin D2 (D2) is more cost-effective, and thus may hold opportunities. We investigated the bioavailability of D2 from UV-irradiated yeast present in bread in an 8-week randomised-controlled trial in healthy 20-37-year-old women (n 33) in Helsinki (60°N) during winter (February-April) 2014. Four study groups were given different study products (placebo pill and regular bread=0 µg D2 or D3/d; D2 supplement and regular bread=25 µg D2/d; D3 supplement and regular bread=25 µg D3/d; and placebo pill and D2-biofortified bread=25 µg D2/d). Serum 25-hydroxyvitamin D2 (S-25(OH)D2) and serum 25-hydroxyvitamin D3 (S-25(OH)D3) concentrations were measured at baseline, midpoint and end point. The mean baseline total serum 25-hydroxyvitamin D (S-25(OH)D=S-25(OH)D2+S-25(OH)D3) concentration was 65·1 nmol/l. In repeated-measures ANCOVA (adjusted for baseline S-25(OH)D as total/D2/D3), D2-bread did not affect total S-25(OH)D (P=0·707) or S-25(OH)D3 (P=0·490), but increased S-25(OH)D2 compared with placebo (P<0·001). However, the D2 supplement was more effective than bread in increasing S-25(OH)D2 (P<0·001). Both D2 and D3 supplementation increased total S-25(OH)D compared with placebo (P=0·030 and P=0·001, respectively), but D2 supplementation resulted in lower S-25(OH)D3 (P<0·001). Thus, D2 from UV-irradiated yeast in bread was not bioavailable in humans. Our results support the evidence that D2 is less potent in increasing total S-25(OH)D concentrations than D3, also indicating a decrease in the percentage contribution of S-25(OH)D3 to the total vitamin D pool.

  1. Low 25(OH) Vitamin D3 Levels Are Associated with Adverse Outcome in Newly-Diagnosed Intensively-Treated Adult Acute Myeloid Leukemia Patients

    PubMed Central

    Lee, Hun Ju; Muindi, Josephia R.; Tan, Wei; Hu, Qiang; Wang, Dan; Liu, Song; Wilding, Gregory E.; Ford, Laurie A.; Sait, Sheila N.J.; Block, Annemarie W.; Adjei, Araba A.; Barcos, Maurice; Griffiths, Elizabeth A; Thompson, James E.; Wang, Eunice S.; Johnson, Candace S; Trump, Donald L.; Wetzler, Meir

    2013-01-01

    Background Several studies suggest that low 25(OH) vitamin D3 levels may be prognostic in some malignancies, but no studies have evaluated their impact on treatment outcome in acute myeloid leukemia (AML). Methods VD levels were evaluated in 97 consecutive newly diagnosed, intensively-treated AML patients. MicroRNA-expression profiles and single nucleotide polymorphisms (SNPs) in the 25(OH) vitamin D3 pathway genes were evaluated and correlated with 25(OH) vitamin D3 levels and treatment outcome. Results Thirty-four (35%) patients had normal 25(OH) vitamin D3 levels (32–100 ng/ml), 34 (35%) insufficient (20–31.9 ng/ml) and 29 (30%) deficient levels (<20 ng/ml). Insufficient/deficient 25(OH) vitamin D3 levels were associated with worse relapse-free survival (RFS) compared to normal vitamin D3 levels. In multivariate analyses, deficient 25(OH) vitamin D3, smoking, European LeukemiaNet Genetic Groups and white blood cell count retained their statistical significance for RFS. A number of microRNAs and SNPs were found to be associated with 25(OH) vitamin D3 level, although none remained significant after multiple test corrections; one 25(OH) vitamin D3 receptor SNP, rs10783219, was associated with lower complete remission rate (p=0.0442), shorter RFS (p=0.0058) and overall survival (p=0.0011). Conclusions It remains to be determined what role microRNA and SNP profiles play in contributing to low 25(OH) vitamin D3 level and/or outcome and whether supplementation will improve AML outcome. PMID:24166051

  2. Interlaboratory trial for measurement of vitamin D and 25(OH)D in foods and a dietary supplement using liquid chromatography-mass spectrometry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Assessment of total vitamin D intake from foods and dietary supplements (DSs) may be incomplete if 25-hydroxyvitamin D [25(OH)D] intake is not included. However, 25(OH)D data for such intake assessments are lacking, no food or DS reference materials (RMs) are available, and comparison of laboratory...

  3. Differences in mineral metabolism among nonhuman primates receiving diets with only vitamin D3 or only vitamin D2.

    PubMed

    Marx, S J; Jones, G; Weinstein, R S; Chrousos, G P; Renquist, D M

    1989-12-01

    We tested for differences in aspects of mineral metabolism during the administration of diets with only vitamin D3 or only vitamin D2 in four nonhuman anthropoid primate species [two catarrhini, Macaca fascicularis (crab-eating macaque) and Macaca mulatta (rhesus macaque), and two platyrrhini, Saimiri sciureus (squirrel monkey) and Aotus vociferans (night monkey)]. All four species maintained approximately 2- to 3-fold higher serum 25-hydroxyvitamin D (25OHD) level while receiving vitamin D3 than while receiving similar amounts of vitamin D2. Serum 25OHD in M. mulatta receiving the standard primate dietary supplement of vitamin D3 was high enough (360 +/- 60 vs. 70 +/- 25 nM in vitamin D-supplemented humans; P less than 0.0001) to suggest that this widely used level of vitamin D3 supplementation is excessive for some M. mulatta. Serum 24,25-dihydroxyvitamin D [24,25-(OH)2D] in A. vociferans was uniquely high [P less than 0.01; species mean, 19 +/- 5, 95 +/- 12, and 27 +/- 5 nM in groups receiving diets with 1.5 IU vitamin D3/g, 6.6 IU vitamin D3/g, and 15 IU vitamin D2/g, respectively; mean 24,25-(OH)2D from the other three species pooled across three diets was 7 +/- 5 nM]. We confirmed relative resistance to 1,25-(OH)2D in S. sciureus, manifested by osteomalacia and moderately high serum 1,25-(OH)2D. Serum 1,25-(OH)2D in S. sciureus increased 4-fold (P less than 0.05) when the precursor in serum was changed from 250HD3 to 250HD2, suggesting that this species shows more severe resistance to 1,25-(OH)2D2 than to 1,25-(OH)2D3. In conclusion, we found many differences in vitamin D metabolism among four nonhuman anthropoid primate species. The striking feature in A. vociferans (high, 24,25-(OH)2D without high 25OHD in serum independent of whether diet contained only vitamin D3 or only vitamin D2) should allow determination of whether 24,25-(OH)2D functions as a unique agonist or an inactive metabolite in this species.

  4. 25 (OH) Vitamin D Levels and Renal Disease Progression in Patients with Type 2 Diabetic Nephropathy and Blockade of the Renin-Angiotensin System

    PubMed Central

    Luño, José; Barrio, Vicente; de Vinuesa, Soledad García; Praga, Manuel; Goicoechea, Marian; Lahera, Vicente; Casas, Luisa; Oliva, Jesús

    2013-01-01

    Summary Background and objectives Experimental studies show that 25 (OH) vitamin D is a suppressor of renin biosynthesis and that vitamin D deficiency has been associated with CKD progression. Patients with type II diabetes and CKD have an exceptionally high rate of severe 25 (OH) vitamin D deficiency; however, it is not known whether this deficiency is a risk factor for progression of diabetic nephropathy. This study aimed to investigate whether there is an association of 25 (OH) vitamin D deficiency with disease progression in type II diabetic nephropathy. Design, setting, participants, & measurements 25 (OH) vitamin D levels were measured at baseline and 4 and 12 months in 103 patients included in a multicenter randomized controlled trial to compare the efficacy of combining an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker with the efficacy of each drug in monotherapy to slow progression of established diabetic nephropathy during 2006–2011. The primary composite endpoint was a >50% increase in baseline serum creatinine, ESRD, or death. All study participants were included in the analysis. Results Fifty-three patients (51.5%) had 25 (OH) vitamin D deficiency (<15 ng/ml). After a median follow-up of 32 months, the endpoint was reached by 23 patients with deficiency (43.4%) and 8 patients without (16%). Multivariate Cox regression analysis adjusted for urinary protein/creatinine ratio, estimated GFR, and baseline aldosterone showed that 25 (OH) vitamin D deficiency was associated with the primary endpoint (hazard ratio, 2.88; 95% confidence interval, 1.84 to 7.67; P=0.04). Conclusions These results show that 25 (OH) vitamin D deficiency is independently associated with a higher risk of the composite outcome in patients with type II diabetic nephropathy. PMID:24135218

  5. Vitamin D3 Effects on Lipids Differ in Statin and Non-Statin-Treated Humans: Superiority of Free 25-OH D Levels in Detecting Relationships

    PubMed Central

    Kane, Lynn; Moore, Kelly; Lütjohann, Dieter; Bikle, Daniel

    2013-01-01

    Context: Inverse associations between 25-OH vitamin D levels and cardiovascular morbidity and mortality have been reported. Objectives: Our goals were to 1) investigate effects of correcting inadequate D status on lipids, 2) determine whether free 25-OH D is better correlated with lipids than total 25-OH D. Design: A randomized, double-blind placebo-controlled trial was performed. Setting: Participants resided in the general community. Participants: Adults with inadequate D status were randomized to D3: 14 men, 12 women, age 60 ± 8 years (mean ± SD) or placebo: 12 men, 11 women: 59 ±12 years. Intervention: Responses to 12-week oral vitamin D3 titrated (1000–3000 IU/d) to achieve 25-OH D levels ≥25 ng/mL were compared to placebo. Main Outcome Measures: Measurements were 25-OH D (tandem mass spectometry), free 25-OH D (direct immunoassay), lipids (directly measured triglyceride, cholesterol, and subfractions; plant sterols and cholesterol synthesis precursors), and safety labs before and after 6 and 12 weeks D3 or placebo. Data were analyzed by repeated measures ANOVA and linear regression. Results: Vitamin D3 was titrated to 1000 IU/d in 15/26 (58%), to 2000 IU/d in 10, and 3000 IU/d in one patient. D3 had no effect on cholesterol or cholesterol subfractions except for trends for decreases in atorvastatin-treated patients (cholesterol, P = .08; low-density lipoprotein [LDL] cholesterol, P = .05). Decreased campesterol concentrations (P = .05) were seen with D3 but not placebo in statin-treated patients. Relationships between total 25-OH D and lipids were not detected, but inverse linear relationships were detected between free 25-OH D and triglycerides (P = .03 for all participants [n = 49], P = .03 in all statin-treated [n = 19], and P = .0009 in atorvastatin-treated [n = 11]), and between free 25-OH D and LDL cholesterol (P = .08 overall, P = .02 in all statin-treated, and P = .03 for atorvastatin-treated), and total cholesterol (P = .09 overall; P = .04

  6. A Population-Based Model to Consider the Effect of Seasonal Variation on Serum 25(OH)D and Vitamin D Status

    PubMed Central

    Vuistiner, Philippe; Rousson, Valentin; Henry, Hugues; Lescuyer, Pierre; Boulat, Olivier; Gaspoz, Jean-Michel; Mooser, Vincent; Vollenweider, Peter; Waeber, Gerard; Cornuz, Jacques; Paccaud, Fred; Bochud, Murielle; Guessous, Idris

    2015-01-01

    Background. We elaborated a model that predicts the centiles of the 25(OH)D distribution taking into account seasonal variation. Methods. Data from two Swiss population-based studies were used to generate (CoLaus) and validate (Bus Santé) the model. Serum 25(OH)D was measured by ultra high pressure LC-MS/MS and immunoassay. Linear regression models on square-root transformed 25(OH)D values were used to predict centiles of the 25(OH)D distribution. Distribution functions of the observations from the replication set predicted with the model were inspected to assess replication. Results. Overall, 4,912 and 2,537 Caucasians were included in original and replication sets, respectively. Mean (SD) 25(OH)D, age, BMI, and % of men were 47.5 (22.1) nmol/L, 49.8 (8.5) years, 25.6 (4.1) kg/m2, and 49.3% in the original study. The best model included gender, BMI, and sin-cos functions of measurement day. Sex- and BMI-specific 25(OH)D centile curves as a function of measurement date were generated. The model estimates any centile of the 25(OH)D distribution for given values of sex, BMI, and date and the quantile corresponding to a 25(OH)D measurement. Conclusions. We generated and validated centile curves of 25(OH)D in the general adult Caucasian population. These curves can help rank vitamin D centile independently of when 25(OH)D is measured. PMID:26421279

  7. Strong association between non alcoholic fatty liver disease (NAFLD) and low 25(OH) vitamin D levels in an adult population with normal serum liver enzymes

    PubMed Central

    2011-01-01

    Background Hypovitaminosis D has been recently recognized as a worldwide epidemic. Since vitamin D exerts significant metabolic activities, comprising free fatty acids (FFA) flux regulation from the periphery to the liver, its deficiency may promote fat deposition into the hepatocytes. Aim of our study was to test the hypothesis of a direct association between hypovitaminosis D and the presence of NAFLD in subjects with various degree of insulin-resistance and related metabolic disorders. Methods We studied 262 consecutive subjects referred to the Diabetes and Metabolic Diseases clinics for metabolic evaluation. NAFLD (non-alcoholic fatty liver disease) was diagnosed by upper abdomen ultrasonography, metabolic syndrome was identified according to the Third Report of National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATPIII) modified criteria. Insulin-resistance was evaluated by means of HOMA-IR. Fatty-Liver-Index, a recently identified correlate of NAFLD, was also estimated. Serum 25(OH)vitamin D was measured by colorimetric method. Results Patients with NAFLD (n = 162,61.8%) had reduced serum 25(OH) vitamin D levels compared to subjects without NAFLD (14.8 ± 9.2 vs 20.5 ± 9.7 ng/ml, p < 0.001, OR 0.95, IC 95% 0.92-0.98). The relationship between NAFLD and reduced 25(OH)vitamin D levels was independent from age, sex, triglycerides, high density lipoproteins (HDL) and glycaemia (p < 0.005) and Fatty Liver Index inversely correlated with low 25(OH) vitamin D regardless sex, age and HOMA-IR (p < 0.007). Conclusions Low 25(OH)vitamin D levels are associated with the presence of NAFLD independently from metabolic syndrome, diabetes and insulin-resistance profile. PMID:21749681

  8. Effects of Oxcarbazepine and Levetiracetam on Calcium, Ionized Calcium, and 25-OH Vitamin-D3 Levels in Patients with Epilepsy

    PubMed Central

    Aksoy, Duygu; Güveli, Betül Tekin; Ak, Pelin Doğan; Sarı, Hüseyin; Ataklı, Dilek; Arpacı, Baki

    2016-01-01

    Objective The primary objective of the present study was to further elucidate the effects of oxcarbazepine (OXC) and levetiracetam (LEV) monotherapies on the bone health status of patients with epilepsy. Methods This study included 48 patients who attended our epilepsy outpatient clinic, had a diagnosis of epilepsy, and were undergoing either OXC or LEV monotherapy and 42 healthy control subjects. The demographic and clinical features of the patients, including gender, age, onset of disease, daily drug dosage, and duration of disease, were noted. Additionally, the calcium, ionized calcium, and 25-OH vitamin-D3 levels of the participants were prospectively evaluated. Results The 25-OH vitamin-D3, calcium, and ionized calcium levels of the patients taking OXC were significantly lower than those of the control group. These levels did not significantly differ between the patients taking LEV and the control group, but there was a significant negative relationship between daily drug dose and ionized calcium levels in the LEV patients. Conclusion In the present study, anti-epileptic drugs altered the calcium, ionized calcium, and 25-OH vitamin-D3 levels of epilepsy patients and resulted in bone loss, abnormal mineralization, and fractures. These findings suggest that the calcium, ionized calcium, and 25-OH vitamin-D3 levels of patients with epilepsy should be regularly assessed. PMID:26792043

  9. Ca2(+)-channel agonist BAY K8644 mimics 1,25(OH)2-vitamin D3 rapid enhancement of Ca2+ transport in chick perfused duodenum

    SciTech Connect

    de Boland, A.R.; Nemere, I.; Norman, A.W. )

    1990-01-15

    To further understand the molecular mechanism by which 1,25(OH)2-vitamin D3 (1,25(OH)2D3) rapidly stimulates intestinal calcium transport (termed transcaltachia), the effect of the calcium channel agonist BAY K8644 was studied in vascularly perfused duodenal loops from normal, vitamin D-replete chicks. BAY K8644, 2 mu M, was found to stimulate {sup 45}Ca{sup 2+} transport from the lumen to the vascular effluent to the same extent as physiological levels of 1,25(OH)2D3. The sterol and the Ca{sup 2+} channel agonist both increased {sup 45}Ca{sup 2+} transport 70% above control values within 2 min and 200% after 30 min of vascular perfusion. The effect of the Ca{sup 2+} channel agonist was dose dependent. Also, 1,25(OH)2D3-enhanced transcaltachia was abolished by the calcium channel blocker nifedipine. Collectively, these results suggest the involvement of 1,25(OH)2D3 in the activation of basal lateral membrane Ca{sup 2+} channels as an early effect in the transcaltachic response.

  10. Stimulation of zinc transport Caco2 cells by 1,25(OH) sub 2 vitamin D sub 3

    SciTech Connect

    Fleet, J.C.; Bourcier, M.; Turnbull, A.J.; Wood, R.J. )

    1991-03-15

    Evidence exists which suggests that 1,25(OH){sub 2} vitamin D{sub 3} (D3) may stimulate zinc (Zn) absorption in animals and man. The authors have studied this phenomenon by assessing Zn transport across monolayers of the human adenocarcinoma cell line, Caco2. This model has been used previously to examine Zn transport kinetics in vitro. Cells for 18 d and then treated with 10 nM D3 for 3 d transported more Zn than controls when each were incubated with 100 uM Zn for 60 min. Excess calcium, added during the transport study, inhibited both basal and D3-stimulated Zn transport equally, indicating the additional Zn was not transported through the D3-stimulated calcium pathway. Metallothionein mRNA levels increased slowly and progressively in response to 10 nM D3. Quinacrine, a lysosome disrupting agent, when added to the transport buffer 30 min prior to the transport study, completely inhibited D3-stimulated Zn transport. Basal Zn transport was reduced 60% by quinacrine suggesting a lysosomal component to both basal and D3-stimulated Zn transport. These data demonstrate that D3 stimulates a unique Zn transport system which may involve both lysosomes and metallothionein.

  11. Human Pigmentation, Cutaneous Vitamin D Synthesis and Evolution: Variants of Genes (SNPs) Involved in Skin Pigmentation Are Associated with 25(OH)D Serum Concentration.

    PubMed

    Rossberg, Willi; Saternus, Roman; Wagenpfeil, Stefan; Kleber, Marcus; März, Winfried; Reichrath, Sandra; Vogt, Thomas; Reichrath, Jörg

    2016-03-01

    Vitamin D deficiency is common and associated with higher risk for and unfavourable outcome of many diseases. Limited data exist on genetic determinants of serum 25(OH)D concentration. In a cohort of the LURIC study (n=2974, median 25(OH)D concentration 15.5 ng/ml), we tested the hypothesis that variants (SNPs, n=244) of several genes (n=15) involved in different aspects of skin pigmentation, including melanosomal biogenesis (ATP7A, DTNBP1, BLOC1S5, PLDN, PMEL), melanosomal transport within melanocytes (RAB27A, MYO5A, MLPH); or various melanocyte signaling pathways (MC1R, MITF, PAX3, SOX10, DKK1, RACK1, CNR1) are predictive of serum 25(OH)D levels. Eleven SNPs located in 6 genes were associated (p<0.05) with low or high serum 25(OH)D levels, 3 out of these 11 SNPs reached the aimed significance level after correction for multiple comparisons (FDR). In the linear regression model adjusted for sex, body mass index (BMI), year of birth and month of blood sample rs7565264 (MLPH), rs10932949 (PAX3), and rs9328451 (BLOC1S5) showed a significant association with 25(OH)D. The combined impact on variation of 25(OH)D serum levels (coefficient of determination (R(2))) for the 11 SNPs was 1.6% and for the 3 SNPs after FDR 0.3%. In Cox Regression we identified rs2292881 (MLPH) as having a significant association (advantage) with overall survival. Kaplan-Meier analysis did not show any significant impact of individual SNPs on overall survival. In conclusion, these results shed new light on the role of sunlight, skin pigmentation and vitamin D for human evolution. PMID:26977047

  12. Human Pigmentation, Cutaneous Vitamin D Synthesis and Evolution: Variants of Genes (SNPs) Involved in Skin Pigmentation Are Associated with 25(OH)D Serum Concentration.

    PubMed

    Rossberg, Willi; Saternus, Roman; Wagenpfeil, Stefan; Kleber, Marcus; März, Winfried; Reichrath, Sandra; Vogt, Thomas; Reichrath, Jörg

    2016-03-01

    Vitamin D deficiency is common and associated with higher risk for and unfavourable outcome of many diseases. Limited data exist on genetic determinants of serum 25(OH)D concentration. In a cohort of the LURIC study (n=2974, median 25(OH)D concentration 15.5 ng/ml), we tested the hypothesis that variants (SNPs, n=244) of several genes (n=15) involved in different aspects of skin pigmentation, including melanosomal biogenesis (ATP7A, DTNBP1, BLOC1S5, PLDN, PMEL), melanosomal transport within melanocytes (RAB27A, MYO5A, MLPH); or various melanocyte signaling pathways (MC1R, MITF, PAX3, SOX10, DKK1, RACK1, CNR1) are predictive of serum 25(OH)D levels. Eleven SNPs located in 6 genes were associated (p<0.05) with low or high serum 25(OH)D levels, 3 out of these 11 SNPs reached the aimed significance level after correction for multiple comparisons (FDR). In the linear regression model adjusted for sex, body mass index (BMI), year of birth and month of blood sample rs7565264 (MLPH), rs10932949 (PAX3), and rs9328451 (BLOC1S5) showed a significant association with 25(OH)D. The combined impact on variation of 25(OH)D serum levels (coefficient of determination (R(2))) for the 11 SNPs was 1.6% and for the 3 SNPs after FDR 0.3%. In Cox Regression we identified rs2292881 (MLPH) as having a significant association (advantage) with overall survival. Kaplan-Meier analysis did not show any significant impact of individual SNPs on overall survival. In conclusion, these results shed new light on the role of sunlight, skin pigmentation and vitamin D for human evolution.

  13. Gestational Vitamin 25(OH)D Status as a Risk Factor for Receptive Language Development: A 24-Month, Longitudinal, Observational Study.

    PubMed

    Tylavsky, Frances A; Kocak, Mehmet; Murphy, Laura E; Graff, J Carolyn; Palmer, Frederick B; Völgyi, Eszter; Diaz-Thomas, Alicia M; Ferry, Robert J

    2015-12-01

    Emerging data suggest that vitamin D status during childhood and adolescence can affect neurocognitive development. The purpose of this study was to investigate whether gestational 25(OH)D status is associated with early childhood cognitive and receptive language development. The Conditions Affecting Neurocognitive Development and Learning in Early Childhood Study (CANDLE) study enrolled 1503 mother-child dyads during the second trimester of healthy singleton pregnancies from Shelby County TN. Among 1020 participants of the total CANDLE cohort for whom 25(OH)D levels were available, mean gestational 25(OH)D level during the second trimester was 22.3 ng/mL (range 5.9-68.4), with 41.7% of values <20 ng/dL. Cognitive and language scaled scores increased in a stair-step manner as gestational 25(OH)D levels in the second trimester rose from <20 ng/dL, through 20-29.99 ng/dL, to ≥30 ng/dL. When controlling for socioeconomic status, race, use of tobacco products, gestational age of the child at birth, and age at the 2-year assessment, the gestational 25(OH)D was positively related to receptive language development (p < 0.017), but not cognitive or expressive language. PMID:26633480

  14. Gestational Vitamin 25(OH)D Status as a Risk Factor for Receptive Language Development: A 24-Month, Longitudinal, Observational Study

    PubMed Central

    Tylavsky, Frances A.; Kocak, Mehmet; Murphy, Laura E.; Graff, J. Carolyn; Palmer, Frederick B.; Völgyi, Eszter; Diaz-Thomas, Alicia M.; Ferry, Robert J.

    2015-01-01

    Emerging data suggest that vitamin D status during childhood and adolescence can affect neurocognitive development. The purpose of this study was to investigate whether gestational 25(OH)D status is associated with early childhood cognitive and receptive language development. The Conditions Affecting Neurocognitive Development and Learning in Early Childhood Study (CANDLE) study enrolled 1503 mother-child dyads during the second trimester of healthy singleton pregnancies from Shelby County TN. Among 1020 participants of the total CANDLE cohort for whom 25(OH)D levels were available, mean gestational 25(OH)D level during the second trimester was 22.3 ng/mL (range 5.9–68.4), with 41.7% of values <20 ng/dL. Cognitive and language scaled scores increased in a stair-step manner as gestational 25(OH)D levels in the second trimester rose from <20 ng/dL, through 20–29.99 ng/dL, to ≥30 ng/dL. When controlling for socioeconomic status, race, use of tobacco products, gestational age of the child at birth, and age at the 2-year assessment, the gestational 25(OH)D was positively related to receptive language development (p < 0.017), but not cognitive or expressive language. PMID:26633480

  15. Effect of calcium or 25OH vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60.

    PubMed

    Peacock, M; Liu, G; Carey, M; McClintock, R; Ambrosius, W; Hui, S; Johnston, C C

    2000-09-01

    Dietary supplements that prevent bone loss at the hip and that can be applied safely in the elderly are likely to reduce hip fractures. A daily dietary supplement of 750 mg calcium or 15 microg 25OH vitamin D3 on bone loss at the hip and other sites, bone turnover and calcium-regulating hormones were studied over 4 yr in elderly volunteers using a randomized, double-blind, placebo-controlled trial. Bone mineral density (BMD) was measured by dual x-ray absorptiometry and bone structure by radiographs. Calcium biochemistry and bone turnover markers were measured in blood and urine. The 316 women entering the trial had a mean age of 73.7 yr and the 122 men of 75.9 yr. Baseline median calcium intake was 546 mg/day, and median serum 25OH vitamin D3 was 59 nmol/L. On placebo, loss of BMD at total hip was 2% and femoral medulla expansion was 3% over 4 yr. Calcium reduced bone loss, secondary hyperparathyroidism, and bone turnover. 25OH vitamin D3 was intermediate between placebo and calcium. Fracture rates and drop-out rates were similar among groups, and there were no serious adverse events with either supplement. A calcium supplement of 750 mg/day prevents loss of BMD, reduces femoral medullary expansion, secondary hyperparathyroidism, and high bone turnover. A supplement of 15 microg/day 25OH vitamin D3 is less effective, and because its effects are seen only at low calcium intakes, suggests that its beneficial effect is to reverse calcium insufficiency. PMID:10999778

  16. 1,25(OH) sub 2 D sub 3 and Ca-binding protein in fetal rats: Relationship to the maternal vitamin D status

    SciTech Connect

    Verhaeghe, J.; Thomasset, M.; Brehier, A.; Van Assche, F.A.; Bouillon, R. Institut National de la Sante et de la Recherche Medical )

    1988-04-01

    The autonomy and functional role of fetal 1,25-dihydroxyvitamin D{sub 3} (1,25(OH){sub 2}D{sub 3}) were investigated in nondiabetic and diabetic BB rats fed diets containing 0.85% calcium-0.7% phosphorus or 0.2% calcium and phosphorus and in semistarved rats on the low calcium-phosphorus diet. The changes in maternal and fetal plasma 1,25(OH){sub 2}D{sub 3} were similar: the levels were increased by calcium-phosphorus restriction and decreased by diabetes and semistarvation. Maternal and fetal 1,25(OH){sub 2}D{sub 3} levels were correlated. The vitamin D-dependent calcium-binding proteins (CaBP{sub 9K} and CaBP{sub 28K}) were measured in multiple maternal and fetal tissues and in the placenta of nondiabetic, diabetic, and calcium-phosphorus-restricted rats. The distributions of CaBP{sub 9K} and CaBP{sub 28K} in the pregnant rat were similar to that of the growing rat. The increased maternal plasma 1,25(OH){sub 2}D{sub 3} levels in calcium-phosphorus-restricted rats were associated with higher duodenal CaBP{sub 9K} and renal CaBPs, but placental CaBP{sub 9K} was not different. In diabetic pregnant rats, duodenal CaBP{sub 9K} was not different. In diabetic pregnant rats, duodenal CaBP{sub 9K} tended to be lower, while renal CaBPs were normal; placental CaBP{sub 9K} was decreased. The results indicate that in the rat fetal 1,25(OH){sub 2}D{sub 3} depends on maternal 1,25(OH){sub 2}D{sub 3} or on factors regulating maternal 1,25(OH){sub 2}D{sub 3}. The lack of changes in fetal CaBP in the presence of altered fetal plasma 1,25(OH){sub 2}D{sub 3} levels confirms earlier data showing that 1,25(H){sub 2}D{sub 3} has a limited hormonal function during perinatal development in the rat.

  17. Nasal Levels of Antimicrobial Peptides in Allergic Asthma Patients and Healthy Controls: Differences and Effect of a Short 1,25(OH)2 Vitamin D3 Treatment

    PubMed Central

    Thijs, Willemien; Janssen, Kirsten; van Schadewijk, Annemarie M.; Papapoulos, Socrates E.; le Cessie, Saskia; Middeldorp, Saskia; Melissant, Christian F.; Rabe, Klaus F.; Hiemstra, Pieter S.

    2015-01-01

    Background Allergy is often accompanied by infections and lower levels of antimicrobial peptides (AMPs). Vitamin D has been shown to increase expression of selected AMPs. In this study we investigated whether antimicrobial peptide levels in nasal secretions of allergic asthma patients are lower than in healthy controls, and whether administration of the active form of vitamin D (1,25(OH)2D3) affects these antimicrobial peptide levels. Methods The levels of antimicrobial peptides in nasal secretions were compared between 19 allergic asthma patients and 23 healthy controls. The effect of seven days daily oral treatment with 2 μg 1,25(OH)2D3 on antimicrobial peptides in nasal secretions was assessed in a placebo-controlled cross-over clinical study. Results Levels of neutrophil α-defensins (human neutrophil peptides 1–3; HNP1-3) and lipocalin 2 (LCN2; also known as NGAL) were significantly lower in asthmatics, but no differences in LL-37 and SLPI were detected. Treatment with a short-term 1,25(OH)2D3 caused a small increase in HNP1-3, but not when the asthma and control groups were analyzed separately. LL-37, LCN2 and SLPI did not change after treatment with 1,25(OH)2D3. Conclusion Levels of the antimicrobial peptides HNP1-3 and LCN2 are lower in nasal secretions in asthmatics and are not substantially affected by a short-term treatment with active vitamin D. PMID:26545199

  18. A novel compound heterozygous ROMK mutation presenting as late onset Bartter syndrome associated with nephrocalcinosis and elevated 1,25(OH)(2) vitamin D levels.

    PubMed

    Sharma, Amita; Linshaw, Micheal A

    2011-08-01

    Bartter syndrome (BS) is a rare renal tubular disorder presenting with hypokalemic metabolic alkalosis, which is classified into five types. KCNJ1 mutations usually cause the neonatal form of BS, type II BS (OMIM 241200). However, this report concerns a female patient with a novel, compound heterozygous KCNJ1 mutation that causes late-onset BS. The unique clinical findings of this case include persistently elevated 1,25(OH)(2) vitamin D levels, possibly due to increase prostaglandin E(2) levels, and medullary nephrocalcinosis. Treatment with COX-2 inhibitors resolved her hypercalciuria and improved her height and weight; renal function remains stable and there is no progression of nephrocalcinosis. PMID:21431899

  19. Vitamin D2 supplementation amplifies eccentric exercise-induced muscle damage in NASCAR pit crew athletes.

    PubMed

    Nieman, David C; Gillitt, Nicholas D; Shanely, R Andrew; Dew, Dustin; Meaney, Mary Pat; Luo, Beibei

    2013-12-20

    This study determined if 6-weeks vitamin D2 supplementation (vitD2, 3800 IU/day) had an influence on muscle function, eccentric exercise-induced muscle damage (EIMD), and delayed onset of muscle soreness (DOMS) in National Association for Stock Car Auto Racing (NASCAR) NASCAR pit crew athletes. Subjects were randomized to vitD2 (n=13) and placebo (n=15), and ingested supplements (double-blind) for six weeks. Blood samples were collected and muscle function tests conducted pre- and post-study (leg-back and hand grip dynamometer strength tests, body weight bench press to exhaustion, vertical jump, 30-s Wingate test). Post-study, subjects engaged in 90 min eccentric-based exercise, with blood samples and DOMS ratings obtained immediately after and 1- and 2-days post-exercise. Six weeks vitD2 increased serum 25(OH)D2 456% and decreased 25(OH)D3 21% versus placebo (p<0.001, p=0.036, respectively), with no influence on muscle function test scores. The post-study eccentric exercise bout induced EIMD and DOMS, with higher muscle damage biomarkers measured in vitD2 compared to placebo (myoglobin 252%, 122% increase, respectively, p=0.001; creatine phosphokinase 24 h post-exercise, 169%, 32%, p<0.001), with no differences for DOMS. In summary, 6-weeks vitD2 (3800 IU/day) significantly increased 25(OH)D2 and decreased 25(OH)D3, had no effect on muscle function tests, and amplified muscle damage markers in NASCAR pit crew athletes following eccentric exercise.

  20. 1α,25(OH)2-3-Epi-Vitamin D3, a Natural Physiological Metabolite of Vitamin D3: Its Synthesis, Biological Activity and Crystal Structure with Its Receptor

    PubMed Central

    Molnár, Ferdinand; Sigüeiro, Rita; Sato, Yoshiteru; Araujo, Clarisse; Schuster, Inge; Antony, Pierre; Peluso, Jean; Muller, Christian; Mouriño, Antonio; Moras, Dino; Rochel, Natacha

    2011-01-01

    Background The 1α,25-dihydroxy-3-epi-vitamin-D3 (1α,25(OH)2-3-epi-D3), a natural metabolite of the seco-steroid vitamin D3, exerts its biological activity through binding to its cognate vitamin D nuclear receptor (VDR), a ligand dependent transcription regulator. In vivo action of 1α,25(OH)2-3-epi-D3 is tissue-specific and exhibits lowest calcemic effect compared to that induced by 1α,25(OH)2D3. To further unveil the structural mechanism and structure-activity relationships of 1α,25(OH)2-3-epi-D3 and its receptor complex, we characterized some of its in vitro biological properties and solved its crystal structure complexed with human VDR ligand-binding domain (LBD). Methodology/Principal Findings In the present study, we report the more effective synthesis with fewer steps that provides higher yield of the 3-epimer of the 1α,25(OH)2D3. We solved the crystal structure of its complex with the human VDR-LBD and found that this natural metabolite displays specific adaptation of the ligand-binding pocket, as the 3-epimer maintains the number of hydrogen bonds by an alternative water-mediated interaction to compensate the abolished interaction with Ser278. In addition, the biological activity of the 1α,25(OH)2-3-epi-D3 in primary human keratinocytes and biochemical properties are comparable to 1α,25(OH)2D3. Conclusions/Significance The physiological role of this pathway as the specific biological action of the 3-epimer remains unclear. However, its high metabolic stability together with its significant biologic activity makes this natural metabolite an interesting ligand for clinical applications. Our new findings contribute to a better understanding at molecular level how natural metabolites of 1α,25(OH)2D3 lead to significant activity in biological systems and we conclude that the C3-epimerization pathway produces an active metabolite with similar biochemical and biological properties to those of the 1α,25(OH)2D3. PMID:21483824

  1. Serum 25(OH) Vitamin D levels is not associated with disability in multiple sclerosis patients: A case-control study

    PubMed Central

    Nikanfar, Masoud; Taheri-Aghdam, Ali Akbar; Yazdani, Maria; Shaafi, Sheida; Masoudian, Nooshin; Akbari, Hossein; Youhanaee, Parisa; Abbaszadeh, Hamzeh

    2015-01-01

    Background: It seems that serum vitamin D levels are one of the potential environmental factors affecting the severity of multiple sclerosis (MS). In this study, we aim to evaluate vitamin D levels in MS patients and healthy subjects and assess the relationship between vitamin D level and disability. Methods: In this case-control study, 168 rapid relapsing MS patients and 168 matched healthy controls were randomly included in this study. Demographic characteristics and serum vitamin D levels for patients and controls, as well as expanded disability status scale (EDSS), duration of disease and diagnostic lag for patients were evaluated. We followed up patients for 6 months and relapses were recorded. Results: The mean serum vitamin D levels were 19.16 ± 17.37 inpatients and 25.39 ± 19.67 in controls (P = 0.560). The mean serum vitamin D levels were 12.65 ± 13.3 in patients with relapses and 22.08 ± 18.22 in patients without any relapses (P < 0.001). There was no significant correlation between EDSS score and serum vitamin D levels (r = −0.08, P = 0.280). There was a significant positive correlation between EDSS score and disease duration (r = 0.52, P < 0.001). Conclusion: In conclusion, vitamin D level in patients with MS was significantly lower than the healthy subjects, but no significant relationship was found between vitamin D levels and disability. Our findings did not suggest a protective role for serum vitamin D levels against disability. PMID:25874052

  2. Active vitamin D3, 1,25-(OH)2D3, protects against macrovasculopathy in a rat model of type 2 diabetes mellitus.

    PubMed

    Ma, R; Deng, X L; Du, G L; Li, C; Xiao, S; Aibibai, Y; Zhu, J

    2016-01-01

    To investigate the protective effect of the active form of vitamin D3, 1,25-(OH)2D3, on macrovasculopathy in rats with type 2 diabetes mellitus (T2DM), 8-week-old male Sprague-Dawley rats were randomly divided into control group, T2DM group, and treatment group. The T2DM model was established after 6 weeks by administering an intraperitoneal injection of streptozotocin (30 mg/kg). 1,25-(OH)2D3 was administered by gavage to rats in the treatment group, and an equal volume of peanut oil was administered to rats in the T2DM group. Fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterols were measured in all rats. The morphology of the thoracic aorta was examined, and the expression of tumor necrosis factor alpha (TNF-α), endothelin (ET), endothelial nitric oxide synthase (eNOS), CD54, and CD106 in the thoracic aorta was determined by immunohistochemistry. The expression of FPG, TG, TC, and LDL-C in rats from the T2DM and treatment groups was significantly elevated compared with rats from the control group (P < 0.05). Compared with that in control group, the expression of TNF-α, ET, eNOS, and CD106 was significantly upregulated in the T2DM group and the treatment group, while the expression of CD54 was increased only in the T2DM group (P < 0.05). Moreover, the levels of TNF-α, CD54, and CD106 in rats from the treatment group were lower than those in the T2DM group (P < 0.05). These data suggest that 1,25-(OH)2D3 may protect the macrovessels from injury in T2DM rats by inhibiting the expression of TNF-α, CD54, and CD106. PMID:27323139

  3. 1α,25(OH)2 Vitamin D3 Modulates Avian T Lymphocyte Functions without Inducing CTL Unresponsiveness

    PubMed Central

    Boodhoo, Nitish; Sharif, Shayan; Behboudi, Shahriar

    2016-01-01

    1,25-Dihydroxyvitamin D3 (Vitamin D) is a naturally synthesized fat soluble vitamin shown to have immunomodulatory, anti-inflammatory and cancer prevention properties in human and murine models. Here, we studied the effects of Vitamin D on the functional abilities of avian T lymphocytes using chicken Interferon (IFN)-γ ELISPOT assay, BrdU proliferation assay, Annexin V apoptosis assay and PhosFlow for detecting phosphorylated signalling molecules. The results demonstrate that Vitamin D significantly inhibited the abilities of T lymphocytes to produce IFN-γ and proliferate in vitro (P≤0.05), but retained their ability to undergo degranulation, which is a maker for cytotoxicity of these cells. Similarly, Vitamin D did not inhibit Extracellular signal-Regulated Kinase (ERK) 1/2 phosphorylation, a key mediator in T cell signalling, in the stimulated T lymphocytes population, while reduced ERK1/2 phosphorylation levels in the unstimulated cells. Our data provide evidence that Vitamin D has immuno-modulatory properties on chicken T lymphocytes without inducing unresponsiveness and by limiting immuno-pathology can promote protective immunity against infectious diseases of poultry. PMID:26910045

  4. In vivo production of novel vitamin D2 hydroxy-derivatives by human placentas, epidermal keratinocytes, Caco-2 colon cells and the adrenal gland

    PubMed Central

    Slominski, Andrzej T.; Kim, Tae-Kang; Shehabi, Haleem Z.; Tang, Edith; Benson, Heather A. E.; Semak, Igor; Lin, Zongtao; Yates, Charles R.; Wang, Jin; Li, Wei; Tuckey, Robert C.

    2014-01-01

    We investigated the metabolism of vitamin D2 to hydroxyvitamin D2 metabolites ((OH)D2) by human placentas ex-utero, adrenal glands ex-vivo and cultured human epidermal keratinocytes and colonic Caco-2 cells, and identified 20(OH)D2, 17,20(OH)2D2, 1,20(OH)2D2, 25(OH)D2 and 1,25(OH)2D2 as products. Inhibition of product formation by 22R-hydroxycholesterol indicated involvement of CYP11A1 in 20- and 17-hydroxylation of vitamin D2, while use of ketoconazole indicated involvement of CYP27B1 in 1α-hydroxylation of products. Studies with purified human CYP11A1 confirmed the ability of this enzyme to convert vitamin D2 to 20(OH)D2 and 17,20(OH)2D2. In placentas and Caco-2 cells, production of 20(OH)D2 was higher than 25(OH)D2 while in human keratinocytes the production of 20(OH)D2 and 25(OH)D2 were comparable. HaCaT keratinocytes showed high accumulation of 1,20(OH)2D2 relative to 20(OH)D2 indicating substantial CYP27B1 activity. This is the first in vivo evidence for a novel pathway of vitamin D2 metabolism initiated by CYP11A1 and modified by CYP27B1, with the product profile showing tissue- and cell-type specificity. PMID:24382416

  5. Effect of 25(OH) vitamin D reference method procedure (RMP) alignment on clinical measurements obtained with the IDS-iSYS chemiluminescent-based automated analyzer.

    PubMed

    Simpson, Christine A; Cusano, Anna Maria; Bihuniak, Jessica; Walker, Joanne; Insogna, Karl L

    2015-04-01

    The Vitamin D Standardization Program (VDSP) has identified ID-LC/MS/MS as the reference method procedure (RMP) for 25(OH) vitamin D and NIST Standard SRM2972 as the standard reference material (SRM). As manufacturers align their products to the RMP and NIST standard, a concern is that results obtained in aligned assays will be divergent from those obtained with pre-alignment assays. The Immunodiagnostic Systems Ltd., chemiluminescent, 25(OH) vitamin D iSYS platform assay, was recently harmonized to the RMP. To determine the impact of standardization on results obtained with iSYS reagents, 119 single donor serum samples from eight different disease categories were analyzed in four non-standardized and two standardized iSYS assays. There were strong correlations between the four non-standardized and two standardized assays with Spearman's rank r values between 0.975 and 0.961 and four of the eight r values were >0.97. R(2) values for the eight best-fit linear regression equations ranging between 0.947 and 0.916. None of the slopes were found to be significantly different from one another. Bland-Altman plots showed that the bias was comparable when each of the four non-standardized assays was compared to either of the standardized assays. When the data were segregated in values between 6 and 49ng/mL (15-122nmol/L) or between 50 and 100ng/mL (125-250nmol/L) significant associations remained between results obtained with non-standardized and standardized calibrators regardless of the absolute value. When five recent DEQAS unknowns were analyzed in one non-standardized and one standardized assay the mean percent difference from the NIST target in values obtained using standardized vs. non-standardized calibrators were not significantly different. Finally, strong and statistically significant associations between the results were obtained using non-standardized and standardized assays for six of eight clinical conditions. The only exceptions were hypocalcemia and breast

  6. Effect of 25(OH) vitamin D reference method procedure (RMP) alignment on clinical measurements obtained with the IDS-iSYS chemiluminescent-based automated analyzer.

    PubMed

    Simpson, Christine A; Cusano, Anna Maria; Bihuniak, Jessica; Walker, Joanne; Insogna, Karl L

    2015-04-01

    The Vitamin D Standardization Program (VDSP) has identified ID-LC/MS/MS as the reference method procedure (RMP) for 25(OH) vitamin D and NIST Standard SRM2972 as the standard reference material (SRM). As manufacturers align their products to the RMP and NIST standard, a concern is that results obtained in aligned assays will be divergent from those obtained with pre-alignment assays. The Immunodiagnostic Systems Ltd., chemiluminescent, 25(OH) vitamin D iSYS platform assay, was recently harmonized to the RMP. To determine the impact of standardization on results obtained with iSYS reagents, 119 single donor serum samples from eight different disease categories were analyzed in four non-standardized and two standardized iSYS assays. There were strong correlations between the four non-standardized and two standardized assays with Spearman's rank r values between 0.975 and 0.961 and four of the eight r values were >0.97. R(2) values for the eight best-fit linear regression equations ranging between 0.947 and 0.916. None of the slopes were found to be significantly different from one another. Bland-Altman plots showed that the bias was comparable when each of the four non-standardized assays was compared to either of the standardized assays. When the data were segregated in values between 6 and 49ng/mL (15-122nmol/L) or between 50 and 100ng/mL (125-250nmol/L) significant associations remained between results obtained with non-standardized and standardized calibrators regardless of the absolute value. When five recent DEQAS unknowns were analyzed in one non-standardized and one standardized assay the mean percent difference from the NIST target in values obtained using standardized vs. non-standardized calibrators were not significantly different. Finally, strong and statistically significant associations between the results were obtained using non-standardized and standardized assays for six of eight clinical conditions. The only exceptions were hypocalcemia and breast

  7. 21 CFR 172.381 - Vitamin D2 bakers yeast.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Vitamin D2 bakers yeast. 172.381 Section 172.381... Additives § 172.381 Vitamin D2 bakers yeast. Vitamin D2 bakers yeast may be used safely in foods as a source of vitamin D2 and as a leavening agent in accordance with the following prescribed conditions:...

  8. 21 CFR 172.381 - Vitamin D2 bakers yeast.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Vitamin D2 bakers yeast. 172.381 Section 172.381... CONSUMPTION Special Dietary and Nutritional Additives § 172.381 Vitamin D2 bakers yeast. Vitamin D2 bakers yeast may be used safely in foods as a source of vitamin D2 and as a leavening agent in accordance...

  9. 21 CFR 582.5950 - Vitamin D 2.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Vitamin D 2. 582.5950 Section 582.5950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5950 Vitamin D 2. (a) Product. Vitamin D2. (b) Conditions of use. This substance...

  10. 21 CFR 582.5950 - Vitamin D2.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Vitamin D2. 582.5950 Section 582.5950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5950 Vitamin D2. (a) Product. Vitamin D2. (b) Conditions of use. This substance is...

  11. 21 CFR 582.5950 - Vitamin D2.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Vitamin D2. 582.5950 Section 582.5950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5950 Vitamin D2. (a) Product. Vitamin D2. (b) Conditions of use. This substance is...

  12. 21 CFR 582.5950 - Vitamin D2.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Vitamin D2. 582.5950 Section 582.5950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5950 Vitamin D2. (a) Product. Vitamin D2. (b) Conditions of use. This substance is...

  13. 21 CFR 582.5950 - Vitamin D 2.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Vitamin D 2. 582.5950 Section 582.5950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5950 Vitamin D 2. (a) Product. Vitamin D2. (b) Conditions of use. This substance...

  14. Determinants of Vitamin D Levels in Italian Children and Adolescents: A Longitudinal Evaluation of Cholecalciferol Supplementation versus the Improvement of Factors Influencing 25(OH)D Status.

    PubMed

    Stagi, Stefano; Pelosi, Paola; Strano, Massimo; Poggi, Giovanni; Manoni, Cristina; de Martino, Maurizio; Seminara, Salvatore

    2014-01-01

    Objective. This paper aims to assess 25(OH)D levels in Italian children and adolescents identifying risk factors for 25(OH)D deficiency and to evaluate whether a normal 25(OH)D value can be restored in 25(OH)D-deficient patients. Methods. We evaluated 25(OH)D levels in 679 Italian children and adolescents (≤10, 11-20, 21-30, and >30 ng/mL were defined as severe deficiency, deficiency, insufficiency, and sufficiency, resp.). Of these, 365 25(OH)D-deficient were followed up for 1 year; 205 were treated with cholecalciferol (Arm A: 400 I.U.) and 160 by improving the environmental variables influencing 25(OH)D levels (Arm B). Results. At cross-sectional evaluation, 11.3% showed sufficiency, 30.0% insufficiency, and 58.7% 25(OH)D deficiency. Mean 25(OH)D was 19.08 ± 8.44 ng/mL. At the enrollment time (T 0), no difference was found between Arms A and B with respect to distribution and 25(OH)D levels. At end time (T 1) 26.0% (29.7% in Arm A versus 20.6% in Arm B) showed sufficiency, 38.4% (42.0% versus 34.4%) insufficiency, and 35.6% (28.3% versus 45.0%) 25(OH)D deficiency. Mean 25(OH)D level was 23.71 ± 6.83 ng/mL. Conclusions. Neither changes of lifestyle nor 400 I.U. cholecalciferol supplementation alone appears to be sufficient to restore adequate 25(OH)D levels.

  15. Activation of RAF-1 through Ras and protein kinase Calpha mediates 1alpha,25(OH)2-vitamin D3 regulation of the mitogen-activated protein kinase pathway in muscle cells.

    PubMed

    Buitrago, Claudia Graciela; Pardo, Veronica González; de Boland, Ana R; Boland, Ricardo

    2003-01-24

    We have previously shown that stimulation of proliferation of avian embryonic muscle cells (myoblasts) by 1alpha,25(OH)(2)-vitamin D(3) (1alpha,25(OH)(2)D(3)) is mediated by activation of the mitogen-activated protein kinase (MAPK; ERK1/2). To understand how 1alpha,25(OH)(2)D(3) up-regulates the MAPK cascade, we have investigated whether the hormone acts upstream through stimulation of Raf-1 and the signaling mechanism by which this effect might take place. Treatment of chick myoblasts with 1alpha,25(OH)(2)D(3) (1 nm) caused a fast increase of Raf-1 serine phosphorylation (1- and 3-fold over basal at 1 and 2 min, respectively), indicating activation of Raf-1 by the hormone. These effects were abolished by preincubation of cells with a specific Ras inhibitor peptide that involves Ras in 1alpha,25(OH)(2)D(3) stimulation of Raf-1. 1alpha,25(OH)(2)D(3) rapidly induced tyrosine de-phosphorylation of Ras-GTPase-activating protein, suggesting that inhibition of Ras-GTP hydrolysis is part of the mechanism by which 1alpha,25(OH)(2)D(3) activates Ras in myoblasts. The protein kinase C (PKC) inhibitors calphostin C, bisindolylmaleimide I, and Ro 318220 blocked 1alpha,25(OH)(2)D(3)-induced Raf-1 serine phosphorylation, revealing that hormone stimulation of Raf-1 also involves PKC. In addition, transfection of muscle cells with an antisense oligodeoxynucleotide against PKCalpha mRNA suppressed serine phosphorylation by 1alpha,25(OH)(2)D(3). The increase in MAPK activity and tyrosine phosphorylation caused by 1alpha,25(OH)(2)D(3) could be abolished by Ras inhibitor peptide, compound PD 98059, which prevents the activation of MEK by Raf-1, or incubation of cell lysates before 1alpha,25(OH)(2)D(3) exposure with an anti-Raf-1 antibody. In conclusion, these results demonstrate for the first time in a 1alpha,25(OH)(2)D(3) target cell that activation of Raf-1 via Ras and PKCalpha-dependent serine phosphorylation plays a central role in hormone stimulation of the MAPK-signaling pathway

  16. Relationship between Body Mass Composition, Bone Mineral Density, Skin Fibrosis and 25(OH) Vitamin D Serum Levels in Systemic Sclerosis.

    PubMed

    Corrado, Addolorata; Colia, Ripalta; Mele, Angiola; Di Bello, Valeria; Trotta, Antonello; Neve, Anna; Cantatore, Francesco Paolo

    2015-01-01

    A reduced bone mineral density (BMD) is observed in several rheumatic autoimmune diseases, including Systemic Sclerosis (SSc); nevertheless, data concerning the possible determinants of bone loss in this disease are not fully investigated. The aim of this study is to evaluate the relationship between BMD, body mass composition, skin sclerosis and serum Vitamin D levels in two subsets of SSc patients. 64 post-menopausal SSc patients, classified as limited cutaneous (lcSSc) or diffuse cutaneous (dcSSc) SSc, were studied. As control, 35 healthy post-menopausal women were recruited. Clinical parameters were evaluated, including the extent of skin involvement. BMD at lumbar spine, hip, femoral neck and body mass composition were determined by dual-energy X-ray absorptiometry. Serum calcium, phosphorus, alkaline phosphatase, urine pyridinium cross-links, intact parathyroid hormone and 25-hydroxyvitamin D (25OHD) were measured. BMD at spine, femoral neck and total hip was significantly lower in SSc patients compared to controls. In dcSSc subset, BMD at spine, femoral neck and total hip was significantly lower compared to lcSSc. No differences in both fat and lean mass were found in the three study groups even if patients with dcSSc showed a slightly lower total body mass compared to healthy controls. Total mineral content was significantly reduced in dSSc compared to both healthy subjects and lcSSc group. Hypovitaminosis D was observed both in healthy post-menopausal women and in SSc patients, but 25OHD levels were significantly lower in dcSSc compared to lcSSc and inversely correlated with the extent of skin thickness. These results support the hypothesis that the extent of skin involvement in SSc patients could be an important factor in determining low circulating levels of 25OHD, which in turn could play a significant role in the reduction of BMD and total mineral content. PMID:26375284

  17. Relationship between Body Mass Composition, Bone Mineral Density, Skin Fibrosis and 25(OH) Vitamin D Serum Levels in Systemic Sclerosis

    PubMed Central

    Corrado, Addolorata; Colia, Ripalta; Mele, Angiola; Di Bello, Valeria; Trotta, Antonello; Neve, Anna; Cantatore, Francesco Paolo

    2015-01-01

    A reduced bone mineral density (BMD) is observed in several rheumatic autoimmune diseases, including Systemic Sclerosis (SSc); nevertheless, data concerning the possible determinants of bone loss in this disease are not fully investigated. The aim of this study is to evaluate the relationship between BMD, body mass composition, skin sclerosis and serum Vitamin D levels in two subsets of SSc patients. 64 post-menopausal SSc patients, classified as limited cutaneous (lcSSc) or diffuse cutaneous (dcSSc) SSc, were studied. As control, 35 healthy post-menopausal women were recruited. Clinical parameters were evaluated, including the extent of skin involvement. BMD at lumbar spine, hip, femoral neck and body mass composition were determined by dual-energy X-ray absorptiometry. Serum calcium, phosphorus, alkaline phosphatase, urine pyridinium cross-links, intact parathyroid hormone and 25-hydroxyvitamin D (25OHD) were measured. BMD at spine, femoral neck and total hip was significantly lower in SSc patients compared to controls. In dcSSc subset, BMD at spine, femoral neck and total hip was significantly lower compared to lcSSc. No differences in both fat and lean mass were found in the three study groups even if patients with dcSSc showed a slightly lower total body mass compared to healthy controls. Total mineral content was significantly reduced in dSSc compared to both healthy subjects and lcSSc group. Hypovitaminosis D was observed both in healthy post-menopausal women and in SSc patients, but 25OHD levels were significantly lower in dcSSc compared to lcSSc and inversely correlated with the extent of skin thickness. These results support the hypothesis that the extent of skin involvement in SSc patients could be an important factor in determining low circulating levels of 25OHD, which in turn could play a significant role in the reduction of BMD and total mineral content. PMID:26375284

  18. Assessing novel prognostic serum biomarkers in advanced pancreatic cancer: the role of CYFRA 21-1, serum amyloid A, haptoglobin, and 25-OH vitamin D3.

    PubMed

    Haas, Michael; Kern, Christoph; Kruger, Stephan; Michl, Marlies; Modest, Dominik P; Giessen, Clemens; Schulz, Christoph; von Einem, Jobst C; Ormanns, Steffen; Laubender, Rüdiger P; Holdenrieder, Stefan; Heinemann, Volker; Boeck, Stefan

    2015-04-01

    The present prospective single-center study investigated the prognostic role of novel serum biomarkers in advanced pancreatic cancer (PC). Patients (pts) with locally advanced or metastatic PC treated with first-line palliative chemotherapy were included. Among others, the serum markers CYFRA 21-1, haptoglobin, serum-amyloid A (SAA), and 25-OH vitamin D3 were determined at baseline and categorized by pre-defined cut-offs [median values (MV), upper limits of normal (ULN), lower limits of normal (LLN), or the natural logarithm (ln)] and correlated with overall survival (OS). Among the 59 pts included, pre-treatment CYFRA 21-1 levels showed a strong correlation with OS independent of the applied cut-off (MV 4.9 ng/ml-14.2 vs. 4.2 months, HR 0.18, p = 0.001; ULN 3.3 ng/ml-14.2 vs. 4.4 months, HR 0.28, p = 0.003; [ln] CYFRA 21-1-HR 0.77, p = 0.013). Lower values of haptoglobin were additionally associated with an improvement in OS (categorized by LLN of 2.05 g/l-10.4 vs. 5.5 months, HR 0.46, p = 0.023; [ln] haptoglobin-HR 0.51, p = 0.036). Pts with baseline SAA values below the MV of 22 mg/l also had a prolonged OS (10.4 vs. 5.0 months, HR 0.47, p = 0.036). For 25-OH vitamin D3 levels, no significant correlation with OS was found. In multivariate analyses, pre-treatment CYFRA 21-1 levels (categorized by MV-HR 0.15, p = 0.032) as well as [ln] haptoglobin (HR 0.30, p = 0.006) retained their independent prognostic significance for OS. CYFRA 21-1, haptoglobin, and SAA might provide useful prognostic information in advanced PC. An external multicenter validation of these results is necessary. PMID:25472579

  19. ERK 5/MAPK PATHWAY HAS A MAJOR ROLE IN 1α,25-(OH)2 VITAMIN D3-INDUCED TERMINAL DIFFERENTIATION OF MYELOID LEUKEMIA CELLS

    PubMed Central

    Wang, Xuening; Pesakhov, Stella; Weng, Ashley; Kafka, Michael; Gocek, Elzbieta; Nguyen, Mai; Harrison, Jonathan S.; Danilenko, Michael; Studzinski, George P.

    2013-01-01

    Vitamin D derivatives, including its physiological form 1α,25(OH)2 vitamin D3 (1,25D), have anti-tumor actions demonstrated in cell culture and confirmatory epidemiological associations are frequently reported. However, their promise for use in the cancer clinic is still incompletely fulfilled, suggesting that a better understanding of the molecular events initiated by these compounds is needed for therapeutic advances. While ERK1/2 has been intensely investigated and is known to transmit signals for cell survival, growth, and differentiation, the role of other MAPK pathways has been studied sporadically. Therefore, we utilized acute myeloid leukemia (AML) cells in culture (HL60 and U937), to determine if ERK5 has a role in 1,25D-induced terminal differentiation which is distinct from the previously shown involvement of ERK1/2. We previously found that inhibition of kinase activity of ERK5 by specific pharmacological inhibitors BIX02189 or XMD8-92 results in higher expression of general myeloid marker CD11b, but a lower expression of the monocytic marker CD14. In contrast, the inhibition of the ERK1/2 pathway by PD98059 or U0126 reduced the expression of all differentiation markers studied. We report here for the first time that the differentiation changes induced by ERK5 inhibitors are accompanied by the inhibition of cell proliferation, and this occurs in the both G1 and G2 phases of the cell cycle. Of note, inhibition of ERK5 auto-phosphorylation by XMD8-92 results in a particularly robust cell cycle arrest in G2 phase in AML cells. This study provides a link between the 1,25D-elevated ERK5 pathway and changes in the cell cycle phase transitions in AML cells. Thus, combinations of vitamin D derivatives and ERK5 inhibitors may be more successful in cancer clinics than 1,25D or analogs alone. PMID:24514755

  20. Circadian rhythm of serum 25 (OH) vitamin D, calcium and phosphorus levels in the treatment and management of type-2 diabetic patients.

    PubMed

    Masood, Tariq; Kushwaha, Rajeev S; Singh, Ranjana; Sailwal, Shivani; Pandey, Himanshu; Varma, Amit; Singh, Raj K; Cornelissen, Germaine

    2015-02-01

    The circadian time structure of serum 25 (OH) vitamin D (25-OHD), calcium (Ca) and phosphorus (P) may prove to be helpful in prevention, efficacy and management of diabetes mellitus. Ten newly diagnosed patients with type-2 diabetes mellitus (6 men and 4 women), 30-65 years of age, and 10 age-matched clinically healthy volunteers (7 men and 3 women) were synchronized for one week with diurnal activity from about 06:00 to about 22:00 and nocturnal rest. Breakfast was served around 08:00, lunch around 13:30 and dinner around 20:00. Drugs/nutraceuticals known to affect the vitamin D-calcium metabolism and status were not taken. Blood samples were collected at 6-h intervals for 24 h under standardized, 24-h synchronized conditions. Serum 25-OHD, Ca, P, Ca-P product and Ca-P ratio were determined. A marked circadian variation was demonstrated for 25-OHD in healthy volunteers (p = 0.030) and of borderline statistical significance in the diabetic patients (p = 0.083) by population-mean cosinor analysis. Similarly, healthy volunteers showed borderline significance for serum Ca, P and Ca-P ratio. The circadian acrophase of Ca occurred later in the patients as compared to healthy controls. Mapping the circadian rhythm (an important component of the broader time structure or chronome, which includes a.o., trends with age and extra-circadian components) of vitamin D and calcium is needed for exploring their role as markers in the treatment and management of diabetic patients. PMID:25788054

  1. Vitamin D delays breast cancer progression in the PyVMT transgenic mouse model: local conversion of the precursor 25(OH)D3 into 1,25(OH)2D3 is safer and more effective than systemic administration of 1,25(OH)2D3

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Metabolic activation of 1,25(OH)2D3 occurs at extra renal sites in several organs, including the breast. The purpose of this study was to determine if this local tumoral 25OHD3-1alphahydroxylase expression modulates any or all of the stages of breast tumor progression. For this purpose we used the...

  2. Interactions between 1alpha,25(OH)2D3 and residues in the ligand-binding pocket of the vitamin D receptor: a correlated fragment molecular orbital study.

    PubMed

    Yamagishi, Kenji; Tokiwa, Hiroaki; Makishima, Makoto; Yamada, Sachiko

    2010-07-01

    To provide physicochemical insight into the role of each residue in the ligand-binding pocket (LBP) of the vitamin D receptor (VDR), we evaluated the energies of the interactions between the LBP residues and 1alpha,25(OH)2D3 by using an ab initio fragment molecular orbital (FMO) method at the Møller-Plesset second-order perturbation (MP2) level. This FMO-MP2 method can be used to correctly evaluate both electrostatic and van der Waals dispersion interactions, and it affords these interaction energies separately. We deduced the nature of each interaction and determined the importance of all the LBP residues involved in ligand recognition by the VDR. We previously reported the results of alanine-scanning mutational analysis (ASMA) of all 34 non-alanine residues lining the LBP of the human VDR. The theoretical results in combination with the ASMA results enabled us to assign the role of each LBP residue. We concluded that electrostatic interactions are the major determinant of the ligand-binding activity and ligand recognition specificity and that van der Waals interactions are important for protein folding and, in turn, for cofactor binding.

  3. Hepatocellular carcinoma cells express 25(OH)D-1α-hydroxylase and are able to convert 25(OH)D to 1α,25(OH)₂D, leading to the 25(OH)D-induced growth inhibition.

    PubMed

    Chiang, Kun-Chun; Yen, Cho-Li; Yeh, Chun-Nan; Hsu, Jun-Te; Chen, Li-Wei; Kuo, Sheng-Fong; Wang, Shang-Yu; Sun, Chi-Chin; Kittaka, Atsushi; Chen, Tai C; Yeh, Ta-Sen; Hsu, Shu-Yuan; Juang, Horng-Heng

    2015-11-01

    Hepatocellular carcinoma (HCC) is the most diagnosed liver cancer without effective treatments available for advanced HCC. Vitamin D is getting popular due to its anti-cancer characteristics. However, the clinical application of 1α,25(OH)2D, the active form of vitamin, is hampered by its hypercalcemia side effect. 1α,25(OH)2D is converted from 25(OH)D, the index of serum vitamin D status, by CYP27B1, which is originally found in kidneys but recently detected in non-renal tissues. 25(OH)D has been shown to repress some cancers expressing CYP27B1 due to the local conversion of 25(OH)D to 1α,25(OH)2D, which works in a intra-, auto-, or paracrine manner and thus minimizes the risk of hypercalcemia. In this study, we found CYP27B1 expression in human hepatocyte, HCC, and HepG2 cells. As we treated HepG2 cells with 25(OH)D, the 1α,25(OH)2D target gene CYP24A1 expression was increased and was further upregulated as CYP27B1 transfection or downregulated as CYP27B1 knockdown. Other 1α,25(OH)2D target genes in HepG2 cells, p21 and p27 were also stimulated by 25(OH)D after CYP27B1 transfection. Further, 25(OH)D could inhibit HepG2 cells growth, which was potentiated by CYP27B1 transfection. Collectively, we showed for the first time that HCC expressed CYP27B1 and was able to covert 25(OH)D to 1α,25(OH)2D in vitro, thus responsive to 25(OH)D treatment. Our data justifies the application of 25(OH)D and CYP27B1 gene transfection therapy in further HCC treatment studies.

  4. Vitamin D deficiency in guinea pigs: exacerbation of bone phenotype during pregnancy and disturbed fetal mineralization, with recovery by 1,25(OH)2D3 infusion or dietary calcium-phosphate supplementation.

    PubMed

    Rummens, K; van Bree, R; Van Herck, E; Zaman, Z; Bouillon, R; Van Assche, F A; Verhaeghe, J

    2002-10-01

    Vitamin D (D) deficiency during human pregnancy appears to disturb fetal growth and mineralization, but fetal development is normal in D-deficient rats and vitamin D receptor gene-ablated mice. We used the guinea pig model to investigate maternal and fetal effects of D deficiency. Pregnant (Pr) and nonpregnant (NPr) animals were fed a D-replete (+D) or D-deficient diet (-D) for 8 weeks. We further studied whether the effects of a -D diet are reversed by continuous 1,25(OH)2D3 infusion (-D+1,25) and/or by a lactose-, Ca- and P-enriched D-deficient diet (-D+Ca/P). Bone analyses included histomorphometry of the proximal tibiae, dual-energy X-ray absorptiometry (DXA), and quantitative computed tomography (QCT) of the femora. Depletion of 25(OH)D3 and 1,25(OH)2D3 levels and the D-deficiency syndrome were more severe in pregnant animals. Indeed, Pr/-D but not NPr/-D guinea pigs were hypophosphatemic, and showed robust increases in growth plate width and osteoid surface and thickness; in addition, bone mineral density on DXA was lower in Pr/-D animals only, which was exclusively in cortical bone on QCT. Bone phenotype was partly normalized in Pr/-D+1,25 and Pr/-D+Ca/P animals. Compared with +D fetuses, -D fetuses had very low or undetectable 25(OH)D3 and 1,25(OH)2D3, were hypercalcemic and hypophosphatemic, and had lower osteocalcin levels. In addition, body weight and total body bone mineral content were 10-15% lower; histomorphometry showed hypertrophic chondrocyte zone expansion and hyperosteoidosis. 1,25(OH)2D3 levels were restored in -D+1,25 fetuses, and the phenotype was partially corrected. Similarly, the fetal +D phenotype was rescued in large part in -D+Ca/P fetuses, despite undetectable circulating 25(OH)D3 and 1,25(OH)2D3. We conclude that pregnancy markedly exacerbates D deficiency, and that augmenting Ca and P intake overrides the deleterious effects of D deficiency on fetal development.

  5. Vector-averaged gravity-induced changes in cell signaling and vitamin D receptor activity in MG-63 cells are reversed by a 1,25-(OH)2D3 analog, EB1089

    NASA Technical Reports Server (NTRS)

    Narayanan, R.; Smith, C. L.; Weigel, N. L.

    2002-01-01

    Skeletal unloading in an animal hindlimb suspension model and microgravity experienced by astronauts or as a result of prolonged bed rest causes site-specific losses in bone mineral density of 1%-2% per month. This is accompanied by reductions in circulating levels of 1,25-(OH)(2)D(3), the active metabolite of vitamin D. 1,25-(OH)(2)D(3), the ligand for the vitamin D receptor (VDR), is important for calcium absorption and plays a role in differentiation of osteoblasts and osteoclasts. To examine the responses of cells to activators of the VDR in a simulated microgravity environment, we used slow-turning lateral vessels (STLVs) in a rotating cell culture system. We found that, similar to cells grown in microgravity, MG-63 cells grown in the STLVs produce less osteocalcin, alkaline phosphatase, and collagen Ialpha1 mRNA and are less responsive to 1,25-(OH)(2)D(3). In addition, expression of VDR was reduced. Moreover, growth in the STLV caused activation of the stress-activated protein kinase pathway (SAPK), a kinase that inhibits VDR activity. In contrast, the 1,25-(OH)(2)D(3) analog, EB1089, was able to compensate for some of the STLV-associated responses by reducing SAPK activity, elevating VDR levels, and increasing expression of osteocalcin and alkaline phosphatase. These studies suggest that, not only does simulated microgravity reduce differentiation of MG-63 cells, but the activity of the VDR, an important regulator of bone metabolism, is reduced. Use of potent, less calcemic analogs of 1,25-(OH)(2)D(3) may aid in overcoming this defect. Copyright 2002 Elsevier Science Inc.

  6. Caveolae and caveolin-1 are implicated in 1alpha,25(OH)2-vitamin D3-dependent modulation of Src, MAPK cascades and VDR localization in skeletal muscle cells.

    PubMed

    Buitrago, Claudia; Boland, Ricardo

    2010-07-01

    We previously reported that 1alpha,25(OH)2D3 induces non-transcriptional rapid responses through activation of MAPKs in C2C12 skeletal muscle cells. However, there is little information on the molecular mechanism underlying the initiation of 1alpha,25(OH)2D3 signaling through this pathway. Plasma membrane components have been involved in some non-genomic effects. In this work, we investigated the role of caveolae and caveolin-1 (cav-1) in 1alpha,25(OH)2D3-stimulation of c-Src and MAPKs. When proliferating cells were pretreated with methyl beta cyclodextrin (MbetaCD), a caveolae disrupting agent, under conditions in which cell morphology is not affected and no signs of apoptosis are observed, 1alpha,25(OH)2D3-dependent activation of ERK1/2, p38 MAPK and c-Src was suppressed. Similar results were obtained by siRNA technology whereby silencing of cav-1 expression abolished activation of c-Src and MAPKs induced by the hormone. By confocal immunocytochemistry it was observed that cav-1 colocalizes with c-Src in the periplasma membrane zone at basal conditions. Hormone treatment disrupted the colocalization of these proteins and redistributed them into cytoplasm and nucleus. Co-immunoprecipitation assays corroborated these observations. Changes in VDR localization after 1alpha,25(OH)2D3 exposure were also investigated. Confocal microscopy images showed that the hormone induces VDR translocation to the plasma membrane, and this effect is abolished by MbetaCD. Altogether, these data suggest that caveolae is involved upstream in c-Src-MAPKs activation by 1alpha,25(OH)2D3 and that VDR and cav-1 participate in the rapid signaling elicited by the hormone.

  7. 25(OH)D Is Effective to Repress Human Cholangiocarcinoma Cell Growth through the Conversion of 25(OH)D to 1α,25(OH)2D3

    PubMed Central

    Chiang, Kun-Chun; Yeh, Chun-Nan; Huang, Cheng-Cheng; Yeh, Ta-Sen; S. Pang, Jong-Hwei; Hsu, Jun-Te; Chen, Li-Wei; Kuo, Sheng-Fong; Kittaka, Atsushi; Chen, Tai C.; Juang, Horng-Heng

    2016-01-01

    Cholangiocarcinoma (CCA) is a devastating disease without effective treatments. 1α,25(OH)2D3, the active form of Vitamin D, has emerged as a new anti-cancer regimen. However, the side effect of hypercalcemia impedes its systemic administration. 25(OH)D is biologically inert and needs hydroxylation by CYP27B1 to form 1α,25(OH)2D3, which is originally believed to only take place in kidneys. Recently, the extra-renal expression of CYP27B1 has been identified and in vitro conversion of 25(OH)D to 1α,25(OH)2D3 has been found in some cancer cells with CYP27B1 expression. In this study, CYP27B1 expression was demonstrated in CCA cells and human CCA specimens. 25(OH)D effectively represses SNU308 cells growth, which was strengthened or attenuated as CYP27B1 overexpression or knockdown. Lipocalcin-2 (LCN2) was also found to be repressed by 25(OH)D. After treatment with 800 ng/mL 25(OH)D, the intracellular 1α,25(OH)2D3 concentration was higher in SNU308 cells with CYP27B1 overexpression than wild type SNU308 cells. In a xenograft animal experiment, 25(OH)D, at a dose of 6 μg/kg or 20 μg/kg, significantly inhibited SNU308 cells’ growth without inducing obvious side effects. Collectively, our results indicated that SNU308 cells were able to convert 25(OH)D to 1α,25(OH)2D3 and 25(OH)D CYP27B1 gene therapy could be deemed as a promising therapeutic direction for CCA. PMID:27529229

  8. 25(OH)D Is Effective to Repress Human Cholangiocarcinoma Cell Growth through the Conversion of 25(OH)D to 1α,25(OH)₂D₃.

    PubMed

    Chiang, Kun-Chun; Yeh, Chun-Nan; Huang, Cheng-Cheng; Yeh, Ta-Sen; S Pang, Jong-Hwei; Hsu, Jun-Te; Chen, Li-Wei; Kuo, Sheng-Fong; Kittaka, Atsushi; Chen, Tai C; Juang, Horng-Heng

    2016-01-01

    Cholangiocarcinoma (CCA) is a devastating disease without effective treatments. 1α,25(OH)₂D₃, the active form of Vitamin D, has emerged as a new anti-cancer regimen. However, the side effect of hypercalcemia impedes its systemic administration. 25(OH)D is biologically inert and needs hydroxylation by CYP27B1 to form 1α,25(OH)₂D₃, which is originally believed to only take place in kidneys. Recently, the extra-renal expression of CYP27B1 has been identified and in vitro conversion of 25(OH)D to 1α,25(OH)₂D₃ has been found in some cancer cells with CYP27B1 expression. In this study, CYP27B1 expression was demonstrated in CCA cells and human CCA specimens. 25(OH)D effectively represses SNU308 cells growth, which was strengthened or attenuated as CYP27B1 overexpression or knockdown. Lipocalcin-2 (LCN2) was also found to be repressed by 25(OH)D. After treatment with 800 ng/mL 25(OH)D, the intracellular 1α,25(OH)₂D₃ concentration was higher in SNU308 cells with CYP27B1 overexpression than wild type SNU308 cells. In a xenograft animal experiment, 25(OH)D, at a dose of 6 μg/kg or 20 μg/kg, significantly inhibited SNU308 cells' growth without inducing obvious side effects. Collectively, our results indicated that SNU308 cells were able to convert 25(OH)D to 1α,25(OH)₂D₃ and 25(OH)D CYP27B1 gene therapy could be deemed as a promising therapeutic direction for CCA. PMID:27529229

  9. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Federal Register approves this incorporation by reference in accordance with 5 U.S.C 552(a) and 1 CFR part... isolated from yeast and is purified by crystallization. (b) Vitamin D2 meets the specifications of the...

  10. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Federal Register approves this incorporation by reference in accordance with 5 U.S.C 552(a) and 1 CFR part... isolated from yeast and is purified by crystallization. (b) Vitamin D2 meets the specifications of the...

  11. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Federal Register approves this incorporation by reference in accordance with 5 U.S.C 552(a) and 1 CFR part... isolated from yeast and is purified by crystallization. (b) Vitamin D2 meets the specifications of the...

  12. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Federal Register approves this incorporation by reference in accordance with 5 U.S.C 552(a) and 1 CFR part... isolated from yeast and is purified by crystallization. (b) Vitamin D2 meets the specifications of the...

  13. Effect of 12-Week Vitamin D Supplementation on 25[OH]D Status and Performance in Athletes with a Spinal Cord Injury.

    PubMed

    Flueck, Joelle Leonie; Schlaepfer, Max Walter; Perret, Claudio

    2016-09-22

    (1) BACKGROUND: studies with able-bodied athletes showed that performance might possibly be influenced by vitamin D status. Vitamin D seems to have a direct impact on neuromuscular function by docking on vitamin D receptors in the muscle tissue. Additionally, a high prevalence of vitamin D deficiency was shown not only in infants and in the elderly but also in healthy adults and spinal cord injured individuals. Therefore, the aim of our study was to investigate whether a vitamin D dose of 6000 IU daily over 12 weeks would be sufficient to increase vitamin D status in indoor wheelchair athletes to a normal or optimal vitamin D level and whether vitamin D deficiency is associated with an impairment in muscle performance in these individuals; (2) METHODS: vitamin D status was assessed in indoor elite wheelchair athletes in order to have a baseline measurement. If vitamin D status was below 75 nmol/L, athletes were supplemented with 6000 IU of vitamin D daily over 12 weeks. A vitamin D status over 75 nmol/L was supplemented with a placebo supplement. Vitamin D status, as well as a Wingate test and an isokinetic dynamometer test, were performed at baseline and after six and 12 weeks; (3) RESULTS: 20 indoor elite wheelchair athletes participated in this double-blind study. All of these athletes showed an insufficient vitamin D status at baseline and were, therefore, supplemented with vitamin D. All athletes increased vitamin D status significantly over 12 weeks and reached an optimal level. Wingate performance was not significantly increased. Isokinetic dynamometer strength was significantly increased but only in the non-dominant arm in isometric and concentric elbow flexion; (4) CONCLUSION: a dose of 6000 IU of vitamin D daily over a duration of 12 weeks seems to be sufficient to increase vitamin D status to an optimal level in indoor wheelchair athletes. It remains unclear, whether upper body performance or muscle strength and vitamin D status are associated with each

  14. Modifying broiler diets with phytase and vitamin D metabolite (25-OH D(3)): impact on phosphorus in litter, amended soils, and runoff.

    PubMed

    McGrath, Joshua M; Sims, J Thomas; Maguire, Rory O; Saylor, William W; Angel, Roselina

    2010-01-01

    Adding phytase and 25- hydroxycholecalciferol (25-OH D(3)) to broiler diets has been shown effective at reducing total P concentrations in broiler litter. This study was conducted to determine the impact of field application of broiler litter from modified diets on P solubility in litter-amended soils and P losses in runoff. Five broiler diets and their resulting litters were evaluated: a high P diet, a low P diet, each of those basal diets with phytase added, and a low P diet with phytase and 25-OH D(3) added. A field study was initiated at two sites with each of the five broiler litters and a commercial P fertilizer (triple superphosphate [TSP]) applied at the same total P rate (150 kg P ha(-1)) and a control where no P was applied. Soil P was monitored over time at two depths (0-5 cm and 0-15 cm) soils were collected in the spring and fall to perform rainfall simulation studies. Broiler litter or TSP application increased soil water-soluble P and Mehlich 3-P concentrations relative to the control, however there were no consistent differences detected between litter treatments. Results from the rainfall simulation experiments indicate that diet modification with phytase or 25-OH D(3) does not increase the potential for P losses in runoff from amended soils relative to traditional diets. Moreover, broiler diet modification to reduce excreted P could be a potentially effective method for reducing watershed scale P surpluses in areas of intensive broiler production, without raising concerns over soluble P losses from litter-amended soils. PMID:20048320

  15. Effect of 12-Week Vitamin D Supplementation on 25[OH]D Status and Performance in Athletes with a Spinal Cord Injury.

    PubMed

    Flueck, Joelle Leonie; Schlaepfer, Max Walter; Perret, Claudio

    2016-01-01

    (1) BACKGROUND: studies with able-bodied athletes showed that performance might possibly be influenced by vitamin D status. Vitamin D seems to have a direct impact on neuromuscular function by docking on vitamin D receptors in the muscle tissue. Additionally, a high prevalence of vitamin D deficiency was shown not only in infants and in the elderly but also in healthy adults and spinal cord injured individuals. Therefore, the aim of our study was to investigate whether a vitamin D dose of 6000 IU daily over 12 weeks would be sufficient to increase vitamin D status in indoor wheelchair athletes to a normal or optimal vitamin D level and whether vitamin D deficiency is associated with an impairment in muscle performance in these individuals; (2) METHODS: vitamin D status was assessed in indoor elite wheelchair athletes in order to have a baseline measurement. If vitamin D status was below 75 nmol/L, athletes were supplemented with 6000 IU of vitamin D daily over 12 weeks. A vitamin D status over 75 nmol/L was supplemented with a placebo supplement. Vitamin D status, as well as a Wingate test and an isokinetic dynamometer test, were performed at baseline and after six and 12 weeks; (3) RESULTS: 20 indoor elite wheelchair athletes participated in this double-blind study. All of these athletes showed an insufficient vitamin D status at baseline and were, therefore, supplemented with vitamin D. All athletes increased vitamin D status significantly over 12 weeks and reached an optimal level. Wingate performance was not significantly increased. Isokinetic dynamometer strength was significantly increased but only in the non-dominant arm in isometric and concentric elbow flexion; (4) CONCLUSION: a dose of 6000 IU of vitamin D daily over a duration of 12 weeks seems to be sufficient to increase vitamin D status to an optimal level in indoor wheelchair athletes. It remains unclear, whether upper body performance or muscle strength and vitamin D status are associated with each

  16. Effect of 12-Week Vitamin D Supplementation on 25[OH]D Status and Performance in Athletes with a Spinal Cord Injury

    PubMed Central

    Flueck, Joelle Leonie; Schlaepfer, Max Walter; Perret, Claudio

    2016-01-01

    (1) Background: studies with able-bodied athletes showed that performance might possibly be influenced by vitamin D status. Vitamin D seems to have a direct impact on neuromuscular function by docking on vitamin D receptors in the muscle tissue. Additionally, a high prevalence of vitamin D deficiency was shown not only in infants and in the elderly but also in healthy adults and spinal cord injured individuals. Therefore, the aim of our study was to investigate whether a vitamin D dose of 6000 IU daily over 12 weeks would be sufficient to increase vitamin D status in indoor wheelchair athletes to a normal or optimal vitamin D level and whether vitamin D deficiency is associated with an impairment in muscle performance in these individuals; (2) Methods: vitamin D status was assessed in indoor elite wheelchair athletes in order to have a baseline measurement. If vitamin D status was below 75 nmol/L, athletes were supplemented with 6000 IU of vitamin D daily over 12 weeks. A vitamin D status over 75 nmol/L was supplemented with a placebo supplement. Vitamin D status, as well as a Wingate test and an isokinetic dynamometer test, were performed at baseline and after six and 12 weeks; (3) Results: 20 indoor elite wheelchair athletes participated in this double-blind study. All of these athletes showed an insufficient vitamin D status at baseline and were, therefore, supplemented with vitamin D. All athletes increased vitamin D status significantly over 12 weeks and reached an optimal level. Wingate performance was not significantly increased. Isokinetic dynamometer strength was significantly increased but only in the non-dominant arm in isometric and concentric elbow flexion; (4) Conclusion: a dose of 6000 IU of vitamin D daily over a duration of 12 weeks seems to be sufficient to increase vitamin D status to an optimal level in indoor wheelchair athletes. It remains unclear, whether upper body performance or muscle strength and vitamin D status are associated with each

  17. Effect of a combined therapeutic approach of intensive lipid management, omega-3 fatty acid supplementation, and increased serum 25 (OH) vitamin D on coronary calcium scores in asymptomatic adults.

    PubMed

    Davis, William; Rockway, Susie; Kwasny, Mary

    2009-01-01

    The impact of intensive lipid management, omega-3 fatty acid, and vitamin D3 supplementation on atherosclerotic plaque was assessed through serial computed tomography coronary calcium scoring (CCS). Low-density lipoprotein cholesterol reduction with statin therapy has not been shown to reduce or slow progression of serial CCS in several recent studies, casting doubt on the usefulness of this approach for tracking atherosclerotic progression. In an open-label study, 45 male and female subjects with CCS of > or = 50 without symptoms of heart disease were treated with statin therapy, niacin, and omega-3 fatty acid supplementation to achieve low-density lipoprotein cholesterol and triglycerides < or = 60 mg/dL; high-density lipoprotein > or = 60 mg/dL; and vitamin D3 supplementation to achieve serum levels of > or = 50 ng/mL 25(OH) vitamin D, in addition to diet advice. Lipid profiles of subjects were significantly changed as follows: total cholesterol -24%, low-density lipoprotein -41%; triglycerides -42%, high-density lipoprotein +19%, and mean serum 25(OH) vitamin D levels +83%. After a mean of 18 months, 20 subjects experienced decrease in CCS with mean change of -14.5% (range 0% to -64%); 22 subjects experienced no change or slow annual rate of CCS increase of +12% (range 1%-29%). Only 3 subjects experienced annual CCS progression exceeding 29% (44%-71%). Despite wide variation in response, substantial reduction of CCS was achieved in 44% of subjects and slowed plaque growth in 49% of the subjects applying a broad treatment program. PMID:19092644

  18. Vitamin D2 is much less effective than vitamin D3 in humans.

    PubMed

    Armas, Laura A G; Hollis, Bruce W; Heaney, Robert P

    2004-11-01

    Vitamins D(2) and D(3) are generally considered to be equivalent in humans. Nevertheless, physicians commonly report equivocal responses to seemingly large doses of the only high-dose calciferol (vitamin D(2)) available in the U.S. market. The relative potencies of vitamins D(2) and D(3) were evaluated by administering single doses of 50,000 IU of the respective calciferols to 20 healthy male volunteers, following the time course of serum vitamin D and 25-hydroxyvitamin D (25OHD) over a period of 28 d and measuring the area under the curve of the rise in 25OHD above baseline. The two calciferols produced similar rises in serum concentration of the administered vitamin, indicating equivalent absorption. Both produced similar initial rises in serum 25OHD over the first 3 d, but 25OHD continued to rise in the D(3)-treated subjects, peaking at 14 d, whereas serum 25OHD fell rapidly in the D(2)-treated subjects and was not different from baseline at 14 d. Area under the curve (AUC) to d 28 was 60.2 ng.d/ml (150.5 nmol.d/liter) for vitamin D(2) and 204.7 (511.8) for vitamin D(3) (P < 0.002). Calculated AUC(infinity) indicated an even greater differential, with the relative potencies for D(3):D(2) being 9.5:1. Vitamin D(2) potency is less than one third that of vitamin D(3). Physicians resorting to use of vitamin D(2) should be aware of its markedly lower potency and shorter duration of action relative to vitamin D(3).

  19. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... this incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain... at NARA, call 202-741-6030 or go to: http://www.archives.gov/federal-register/cfr/ibr-locations.html... crystallization. (b) Vitamin D2 meets the specifications of the Food Chemicals Codex, 7th ed. (2010), pp....

  20. Effects of 1,25(OH)2 D3 and 25(OH)D3 on C2C12 Myoblast Proliferation, Differentiation, and Myotube Hypertrophy.

    PubMed

    van der Meijden, K; Bravenboer, N; Dirks, N F; Heijboer, A C; den Heijer, M; de Wit, G M J; Offringa, C; Lips, P; Jaspers, R T

    2016-11-01

    An adequate vitamin D status is essential to optimize muscle strength. However, whether vitamin D directly reduces muscle fiber atrophy or stimulates muscle fiber hypertrophy remains subject of debate. A mechanism that may affect the role of vitamin D in the regulation of muscle fiber size is the local conversion of 25(OH)D to 1,25(OH)2 D by 1α-hydroxylase. Therefore, we investigated in a murine C2C12 myoblast culture whether both 1,25(OH)2 D3 and 25(OH)D3 affect myoblast proliferation, differentiation, and myotube size and whether these cells are able to metabolize 25(OH)D3 and 1,25(OH)2 D3 . We show that myoblasts not only responded to 1,25(OH)2 D3 , but also to the precursor 25(OH)D3 by increasing their VDR mRNA expression and reducing their proliferation. In differentiating myoblasts and myotubes 1,25(OH)2 D3 as well as 25(OH)D3 stimulated VDR mRNA expression and in myotubes 1,25(OH)2 D3 also stimulated MHC mRNA expression. However, this occurred without notable effects on myotube size. Moreover, no effects on the Akt/mTOR signaling pathway as well as MyoD and myogenin mRNA levels were observed. Interestingly, both myoblasts and myotubes expressed CYP27B1 and CYP24 mRNA which are required for vitamin D3 metabolism. Although 1α-hydroxylase activity could not be shown in myotubes, after treatment with 1,25(OH)2 D3 or 25(OH)D3 myotubes showed strongly elevated CYP24 mRNA levels compared to untreated cells. Moreover, myotubes were able to convert 25(OH)D3 to 24R,25(OH)2 D3 which may play a role in myoblast proliferation and differentiation. These data suggest that skeletal muscle is not only a direct target for vitamin D3 metabolites, but is also able to metabolize 25(OH)D3 and 1,25(OH)2 D3 . J. Cell. Physiol. 231: 2517-2528, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

  1. Effect of 1,25(OH)2 vitamin D3 and ionized Ca/sup 2 +/ on /sup 45/Ca uptake by primary cultures of aortic myocytes of spontaneously hypertensive and Wistar Kyoto normotensive rats

    SciTech Connect

    Bukoski, R.D.; Xue, H.; McCarron, D.A.

    1987-08-14

    The effect of several regulators of whole animal Ca/sup 2 +/ homeostasis on /sup 45/Ca uptake by primary cultures of aortic myocytes isolated from spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats was examined. Exposure of confluent cells to 1.0, 1.25 or 1.50 mM ionized Ca/sup 2 +/ in serum-free medium for seven days resulted in increased /sup 45/Ca uptake at the higher concentrations of Ca/sup 2 +/ in cells of the SHR but not the WKY. 1,25 (OH)2 vitamin D3 (1 ng/ml) for 7 days caused enhanced influx in cells from both the SHR and WKY while parathyroid hormone (1-34) (1 ng/ml) was without effect. The data indicate that humoral factors that serve to regulate whole animal Ca/sup 2 +/ homeostasis may also play a role in the regulation of Ca/sup 2 +/ metabolism of the vascular smooth muscle cell.

  2. Measurement of 25-hydroxyvitamin D2&3 and 1, 25-dihydroxyvitamin D2&3 by Tandem Mass Spectrometry: A Primate Multispecies Comparison

    PubMed Central

    Ziegler, Toni E.; Kapoor, Amita; Hedman, Curtis J.; Binkley, Neil; Kemnitz, Joseph W.

    2015-01-01

    Vitamin D metabolites are widely studied for their roles in bone health, immune functions and other potential physiologic roles in humans. However, the optimal blood levels of vitamin D metabolites are still unclear. Various methods for measuring vitamin D metabolites have been used and recently liquid chromatography tandem mass spectroscopy (LC-MS/MS) has been adopted as the gold standard for vitamin D metabolite measurement. Here we report the use of LC-MS/MS to measure 25-hydroxyvitamin D (25(OH)D2&3), and 1,25-dihydroxyvitamin D (1,25(OH)2D2&3), in three laboratory nonhuman primate species: common marmoset (Callithrix jacchus), rhesus macaque (Macaca mulatta), and cynomolgus macaque (Macaca fascicularis), and compare them to humans using the same technique. The nonhuman primates showed blood levels for 25(OH)D3 and 1,25(OH)2D3 significantly higher than human values with marmosets having the highest levels. Marmoset samples showed significantly more variability among individuals than those from macaques for both metabolites, but all three nonhuman primate species exhibited large variation within species for both 25(OH)D2&3 and 1,25(OH)2D2&3. Marmoset females had significantly lower values than the males for 25(OH)D3, while rhesus males showed a significant decrease in 25(OH)D3 with age. The most striking finding is the variation within species for vitamin D levels even in laboratory primates that have a controlled diet, UV exposure, and in some cases, genetic constraints. Similar variation in 25(OH)D responses to a fixed dose of oral vitamin D supplementation has been reported in humans. We suggest that these species can provide primate models for examining the factors influencing variation in the levels of vitamin D necessary for human and nonhuman primate health. PMID:25845705

  3. 1,25-(OH){sub 2}-vitamin D{sub 3} prevents activation of hepatic stellate cells in vitro and ameliorates inflammatory liver damage but not fibrosis in the Abcb4{sup −/−} model

    SciTech Connect

    Reiter, Florian P.; Hohenester, Simon; Nagel, Jutta M.; Wimmer, Ralf; Artmann, Renate; Wottke, Lena; Makeschin, Marie-Christine; Mayr, Doris; Rust, Christian; Trauner, Michael; Denk, Gerald U.

    2015-04-03

    Background/Purpose of the study: Vitamin D{sub 3}-deficiency is common in patients with chronic liver-disease and may promote disease progression. Vitamin D{sub 3}-administration has thus been proposed as a therapeutic approach. Vitamin D{sub 3} has immunomodulatory effects and may modulate autoimmune liver-disease such as primary sclerosing cholangitis. Although various mechanisms of action have been proposed, experimental evidence is limited. Here we test the hypothesis that active 1,25-(OH){sub 2}-vitamin D{sub 3} inhibits activation of hepatic stellate cells (HSC) in vitro and modulates liver-injury in vivo. Methods: Proliferation and activation of primary murine HSC were assessed by BrdU- and PicoGreen{sup ®}-assays, immunoblotting, immunofluorescence-microscopy, quantitative-PCR, and zymography following calcitriol-treatment. Wild-type and ATP-binding cassette transporter b4{sup −/−} (Abcb4{sup −/−})-mice received calcitriol for 4 weeks. Liver-damage, inflammation, and fibrosis were assessed by serum liver-tests, Sirius-red staining, quantitative-PCR, immunoblotting, immunohistochemistry and hydroxyproline quantification. Results: In vitro, calcitriol inhibited activation and proliferation of murine HSC as shown by reduced α-smooth muscle actin and platelet-derived growth factor-receptor-β-protein-levels, BrdU and PicoGreen®-assays. Furthermore, mRNA-levels and activity of matrix metalloproteinase 13 were profoundly increased. In vivo, calcitriol ameliorated inflammatory liver-injury reflected by reduced levels of alanine aminotransferase in Abcb4{sup −/−}-mice. In accordance, their livers had lower mRNA-levels of F4/80, tumor necrosis factor-receptor 1 and a lower count of portal CD11b positive cells. In contrast, no effect on overall fibrosis was observed. Conclusion: Calcitriol inhibits activation and proliferation of HSCs in vitro. In Abcb4{sup −/−}-mice, administration of calcitriol ameliorates inflammatory liver-damage but has

  4. Investigating causality in the association between 25(OH)D and schizophrenia

    PubMed Central

    Taylor, Amy E.; Burgess, Stephen; Ware, Jennifer J.; Gage, Suzanne H.; Richards, J. Brent; Davey Smith, George; Munafò, Marcus R.

    2016-01-01

    Vitamin D deficiency is associated with increased risk of schizophrenia. However, it is not known whether this association is causal or what the direction of causality is. We performed two sample bidirectional Mendelian randomization analysis using single nucleotide polymorphisms (SNPs) robustly associated with serum 25(OH)D to investigate the causal effect of 25(OH)D on risk of schizophrenia, and SNPs robustly associated with schizophrenia to investigate the causal effect of schizophrenia on 25(OH)D. We used summary data from genome-wide association studies and meta-analyses of schizophrenia and 25(OH)D to obtain betas and standard errors for the SNP-exposure and SNP-outcome associations. These were combined using inverse variance weighted fixed effects meta-analyses. In 34,241 schizophrenia cases and 45,604 controls, there was no clear evidence for a causal effect of 25(OH)D on schizophrenia risk. The odds ratio for schizophrenia per 10% increase in 25(OH)D conferred by the four 25(OH)D increasing SNPs was 0.992 (95% CI: 0.969 to 1.015). In up to 16,125 individuals with measured serum 25(OH)D, there was no clear evidence that genetic risk for schizophrenia causally lowers serum 25(OH)D. These findings suggest that associations between schizophrenia and serum 25(OH)D may not be causal. Therefore, vitamin D supplementation may not prevent schizophrenia. PMID:27215954

  5. Mechanical loading and the synthesis of 1,25(OH)2D in primary human osteoblasts.

    PubMed

    van der Meijden, K; Bakker, A D; van Essen, H W; Heijboer, A C; Schulten, E A J M; Lips, P; Bravenboer, N

    2016-02-01

    local vitamin D metabolism in primary human osteoblasts. Our results suggest that 1,25(OH)2D3 and mechanical loading, both stimuli of the differentiation of osteoblasts, interact at the cellular level.

  6. 1,25(OH)2D3 increases membrane associated protein kinase C in MDBK cells.

    PubMed

    Simboli-Campbell, M; Franks, D J; Welsh, J

    1992-01-01

    To determine whether 1,25-dihydroxycholecalciferol [1,25(OH)2D3] affects protein kinase C (PKC) activity in kidney, as has been demonstrated in HL-60 cells we measured 1,25(OH)2D3 binding, PKC activity and PKC immunoreactivity in Madin Darby bovine kidney (MDBK) cells, a normal renal epithelial cell line derived from bovine kidney. Our data demonstrate that MDBK cells exhibit specific high affinity binding for 1,25(OH)2D3, indicating the presence of the vitamin D receptor (VDR). Treatment of MDBK cells with 1,25(OH)2D3 for 24 h increased membrane PKC activity and immunoreactivity. The effect of 1,25(OH)2D3 was dose-dependent, with a peak effect observed at 10(-7)M 1,25(OH)2D3. The 1,25(OH)2D3 induced increase in membrane PKC was paralleled by a comparable decrease in cytosolic PKC activity and amount. Although time course studies were consistent with a VDR mediated effect of 1,25(OH)2D3 on PKC protein synthesis, total PKC activity was not increased by 1,25(OH)2D3, suggesting an effect on PKC translocation or localization. These results suggest that 1,25(OH)2D3 modulates PKC mediated events in kidney, a classic target for this steroid hormone.

  7. 25-Hydroxyvitamin D Can Interfere With a Common Assay for 1,25-Dihydroxyvitamin D in Vitamin D Intoxication

    PubMed Central

    Hawkes, Colin P.; Schnellbacher, Sarah; Singh, Ravinder J.

    2015-01-01

    Context: Vitamin D intoxication is characterized by elevated serum 25-hydroxyvitamin D (25(OH)D) and suppressed serum 1,25-dihydroxvitamin D (1,25(OH)2D). We evaluated two adolescents with hypercalcemia due to vitamin D intoxication; both had elevated serum 1,25(OH)2D by Diasorin RIA, but normal serum 1,25(OH)2D concentrations by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Objective: This study aimed to determine the effect of 25(OH)D2 and 25(OH)D3 on 1,25(OH)2D concentration determined using RIA and LC-MS/MS. Methods: Pools of normal serum and an artificial serum matrix were prepared and aliquots were spiked with >99% pure 25(OH)D2 or 25(OH)D3 (50–700 ng/mL). Samples were maintained at 4°C or heated to 56°C, and the concentrations of vitamin D metabolites were measured by LC-MS/MS and Diasorin RIA. Results: Median 1,25(OH)2D increased by 114% with RIA and 21% with LC-MS/MS with addition of 100 ng/mL 25(OH)D3, and 349% (RIA) and 117% (LC-MS/MS) with 700 ng/mL of 25(OH)D3. Each 1-ng/mL increase in 25(OH)D3 increased 1,25(OH)2D by 0.231 pg/mL (RIA) and 0.121 pg/mL (LC-MS/MS). Spiking with 25(OH)D2 led to similar changes. Heat inactivation of serum, and using an artificial serum matrix, were associated with similar effects of 25(OH)D on 1,25(OH)2D assays. Conclusions: Vitamin D intoxication with high serum levels of 25(OH)D2 or 25(OH)D3 can be associated with elevated levels of 1,25(OH)2D due to interference in a commonly used RIA. A similar but attenuated effect also occurs when 1,25(OH)2D is measured using LC-MS/MS but does not seem to be clinically significant. The basis for this effect on the LC-MS/MS assay is presently uncertain. PMID:26120794

  8. Synthesis of 25-hydroxy-(26,27-/sup 3/H)vitamin D2, 1,25-dihydroxy-(26,27-/sup 3/H)vitamin D2 and their (24R)-epimers

    SciTech Connect

    Sicinski, R.R.; Tanaka, Y.; Phelps, M.; Schnoes, H.K.; DeLuca, H.F.

    1987-02-15

    Synthesis of a C-24-epimeric mixture of 25-hydroxy-(26,27-/sup 3/H)vitamin D2 and a C-24-epimeric mixture of 1,25-dihydroxy-(26,27-/sup 3/H)vitamin D2 by the Grignard reaction of the corresponding 25-keto-27-nor-vitamin D2 and 1 alpha-acetoxy-25-keto-27-nor-vitamin D3 with tritiated methyl magnesium bromide is described. Separation of epimers by high-performance liquid chromatography afforded pure radiolabeled vitamins of high specific activity (80 Ci/mmol). The identities and radiochemical purities of 25-hydroxy-(26,27-/sup 3/H(vitamin D2 and 1,25-dihydroxy-(26,27-/sup 3/H)vitamin D2 D2 were established by cochromatography with synthetic 25-hydroxyvitamin D2 or 1,25-dihydroxyvitamin D2. Biological activity of 25-hydroxy-(26,27-/sup 3/H)vitamin D2 was demonstrated by its binding to the rat plasma binding protein for vitamin D compounds, and by its in vitro conversion to 1,25-dihydroxy-(26,27-/sup 3/H)vitamin D2 by kidney homogenate prepared from vitamin D-deficient chickens. The biological activity of 1,25-dihydroxy-(26,27-/sup 3/H)vitamin D2 was demonstrated by its binding to the chick intestinal receptor for 1,25-dihydroxyvitamin D3.

  9. Dose-Response Effect of Sunlight on Vitamin D2 Production in Agaricus bisporus Mushrooms.

    PubMed

    Urbain, Paul; Jakobsen, Jette

    2015-09-23

    The dose response effect of UV-B irradiation from sunlight on vitamin D2 content of sliced Agaricus bisporus (white button mushroom) during the process of sun-drying was investigated.Real-time UV-B and UV-A data were obtained using a high-performance spectroradiometer. During the first hour of sunlight exposure, the vitamin D2 content of the mushrooms increased in a linear manner, with concentrations increasing from 0.1 μg/g up to 3.9 ± 0.8 μg/g dry weight (DW). At the subsequent two measurements one and 3 h later, respectively, a plateau was reached. Two hours of additional exposure triggered a significant decline in vitamin D2 content. After just 15 min of sun exposure and an UV-B dose of 0.13 J/cm(2), the vitamin D2 content increased significantly to 2.2 ± 0.5 μg/g DW (P < 0.0001), which is equivalent to 17.6 μg (704 IU) vitamin D2 per 100 g of fresh mushrooms and comparable to levels found in fatty fish like the Atlantic salmon.

  10. Effects of vitamin D2 or D3 supplementation on glycaemic control and cardiometabolic risk among people at risk of type 2 diabetes: results of a randomized double‐blind placebo‐controlled trial

    PubMed Central

    Menon, R. K.; Sharp, S. J.; Mannan, N.; Timms, P. M.; Martineau, A. R.; Rickard, A. P.; Boucher, B. J.; Chowdhury, T. A.; Griffiths, C. J.; Greenwald, S. E.; Griffin, S. J.; Hitman, G. A.

    2016-01-01

    Aims To investigate the effect of short‐term vitamin D supplementation on cardiometabolic outcomes among individuals with an elevated risk of diabetes. Methods In a double‐blind placebo‐controlled randomized trial, 340 adults who had an elevated risk of type 2 diabetes (non‐diabetic hyperglycaemia or positive diabetes risk score) were randomized to either placebo, 100 000 IU vitamin D2 (ergocalciferol) or 100 000 IU vitamin D3 (cholecalciferol), orally administered monthly for 4 months. The primary outcome was change in glycated haemoglobin (HbA1c) between baseline and 4 months, adjusted for baseline. Secondary outcomes included: blood pressure; lipid levels; apolipoprotein levels; C‐reactive protein levels; pulse wave velocity (PWV); anthropometric measures; and safety of the supplementation. Results The mean [standard deviation (s.d.)] 25‐hydroxyvitamin D [25(OH)D]2 concentration increased from 5.2 (4.1) to 53.9 (18.5) nmol/l in the D2 group, and the mean (s.d.) 25(OH)D3 concentration increased from 45.8 (22.6) to 83.8 (22.7) nmol/l in the D3 group. There was no effect of vitamin D supplementation on HbA1c: D2 versus placebo: −0.05% [95% confidence interval (CI) −0.11, 0.02] or −0.51 mmol/mol (95% CI −1.16, 0.14; p = 0.13); D3 versus placebo: 0.02% (95% CI −0.04, 0.08) or 0.19 mmol/mol (95% CI −0.46, 0.83; p = 0.57). There were no clinically meaningful effects on secondary outcomes, except PWV [D2 versus placebo: −0.68 m/s (95% CI −1.31, −0.05); D3 versus placebo −0.73 m/s (95% CI −1.42, −0.03)]. No important safety issues were identified. Conclusions Short‐term supplementation with vitamin D2 or D3 had no effect on HbA1c. The modest reduction in PWV with both D2 and D3 relative to placebo suggests that vitamin D supplementation has a beneficial effect on arterial stiffness. PMID:26700109

  11. Determination of 1,25-dihydroxyvitamin D2 and 1,25-dihydroxyvitamin D3 in human serum using liquid chromatography with tandem mass spectrometry.

    PubMed

    Fang, Huiling; Yu, Songlin; Cheng, Qian; Cheng, Xinqi; Han, Jianhua; Qin, Xuzhen; Xia, Liangyu; Jiang, Xiaomei; Qiu, Ling

    2016-08-01

    Vitamin D plays important roles in skeletal metabolism and many other diseases, including chronic renal failure, hypoparathyroidism, sarcoidosis and rickets. 1α,25-dihydroxy vitamin D (1α,25(OH)2D), the active form of vitamin D, exhibits an extremely low serum concentration, which makes its quantification very challenging. High performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) is considered to be the "gold standard" for the determination of these chemicals, which are found in low concentrations in the serum, but conventionally, it needs tedious sample pretreatment procedures, such as solid phase extraction and derivatization. Herein, we describe a simple and rapid HPLC-MS/MS method for the simultaneous quantification of 1α,25-dihydroxy vitamin D3 (1α,25(OH)2D3) and 1α,25-dihydroxy vitamin D2 (1α,25(OH)2D2). The analytes were extracted from the matrix by liquid-liquid extraction, centrifuged to dryness and reconstituted with 75% methanol. Lithium acetate was employed to improve the ionization efficiency of 1α,25(OH)2D. The assay was sensitive with a low limit of quantitation of 10.0pg/mL for both 1α,25(OH)2D3 and 1α,25(OH)2D2 using a 0.5mL sample aliquot. Linearity was obtained over the range of 10.0pg/mL to 500pg/mL. Both the inter-assay and intra-assay precisions were <15%, and the analytical recoveries were within 100±5%. The performance evaluation of this assay demonstrated that it was a practical, sensitive and specific method for measuring the serum 1α,25(OH)2D3 and 1α,25(OH)2D2 concentrations. PMID:27240300

  12. Increase of vitamin D2 by UV-B exposure during the growth phase of white button mushroom (Agaricus bisporus)

    PubMed Central

    Kristensen, Hanne L.; Rosenqvist, Eva; Jakobsen, Jette

    2012-01-01

    Background Mushrooms are the only non-animal food source of vitamin D. Wild mushrooms have naturally high vitamin D2 content, and cultivated mushrooms produce vitamin D2 from ergosterol when exposed to supplementary UV-B during the post-harvest phase. Objectives This study investigated the effects of providing supplementary UV-B during the growth phase on vitamin D2 formation and the interactions with growth of mushrooms, as compared to supplementary UV-B during the post-harvest phase or exposure to sunlight for both cultivated and wild mushrooms. Methods Experiments were carried out with exposure to supplementary UV-B just prior to harvest in the range of 0–2,400 mJ cm−2. Mushrooms grew for 2 days with or without repeated UV-B exposure each day. Vitamin D2 and growth rate were determined. In addition, some mushrooms were post-harvest treated by exposure at 200 mJ cm−2 supplementary UV-B or natural sunlight, prior to vitamin D2 determination. Results The content of vitamin D2 was 0.2–164 µg 100 g−1 fresh weight, and there was a linear relationship between UV-dose up to 1,000 mJ cm−2 and vitamin D2 content. The fast growth rate of the mushrooms diluted the vitamin D2 from 24 to 3 µg 100 g−1 within 2 days of exposure at 200 mJ cm−2. Following repeated UV-B exposure, vitamin D2 increased to 33 µg vitamin D2 100 g−1. Growth was unaffected by UV-B. Post-harvest exposure to supplementary UV-B resulted in a higher vitamin D2 content of 32 µg 100 g−1 compared to the 24 µg 100 g−1 obtained from exposure to UV-B during the growth phase. In contrast, wild and cultivated mushrooms with and without exposure to sunlight had vitamin D2 content in the range of 0.2–1.5 µg vitamin D2 100 g−1. Conclusions This study showed that mushrooms with a well-defined content of vitamin D2 can be obtained by exposure to supplementary UV-B just prior to harvest. PMID:22489222

  13. Relationship of calcium absorption with 25(OH)D and calcium intake in children with rickets.

    PubMed

    Thacher, Tom D; Abrams, Steven A

    2010-11-01

    Nutritional rickets has long been considered a disease caused by vitamin D deficiency, but recent data indicate that inadequate dietary calcium intake is an important cause of rickets, particularly in tropical countries. Children with rickets due to calcium deficiency do not have very low 25(OH)D concentrations, and serum 1,25(OH)(2) D values are markedly elevated. Studies of Nigerian children with rickets demonstrated they have high fractional calcium absorption. A high-phytate diet was demonstrated to increase calcium absorption compared with the fasting state, and enzymatic dephytinization did not significantly improve calcium absorption. When given vitamin D, children with rickets have a marked increase in 1,25(OH)(2) D concentrations without any change in fractional calcium absorption. No positive relationship was found between fractional calcium absorption and serum 25(OH)D concentrations in children on low-calcium diets. More research is needed to understand the interaction between calcium and vitamin D and the role of vitamin D in calcium absorption.

  14. 25(OH)D Status of Elite Athletes with Spinal Cord Injury Relative to Lifestyle Factors

    PubMed Central

    Pritchett, Kelly; Pritchett, Robert; Ogan, Dana; Bishop, Phil; Broad, Elizabeth; LaCroix, Melissa

    2016-01-01

    Background: Due to the potential negative impact of low Vitamin D status on performance-related factors and the higher risk of low Vitamin D status in Spinal Cord Injury (SCI) population, research is warranted to determine whether elite athletes with SCI have sufficient 25(OH)D levels. The purposes of this study were to examine: (1) the seasonal proportion of vitamin D insufficiency among elite athletes with SCI; and (2) to determine whether lifestyle factors, SCI lesion level, and muscle performance/function are related to vitamin D status in athletes with SCI. Methods: Thirty-nine members of the Canadian Wheelchair Sports Association, and the US Olympic Committee Paralympic program from outdoor and indoor sports were recruited for this study. Dietary and lifestyle factors, and serum 25(OH)D concentrations were assessed during the autumn (October) and winter (February/March). An independent t-test was used to assess differences in 25(OH)D status among seasons, and indoor and outdoor sports in the autumn and winter, respectively. Results: Mean ± SD serum 25(OH)D concentration was 69.6 ± 19.7 nmol/L (range from 30 to 107.3 nmol/L) and 67.4 ± 25.5 nmol/L (range from 20 to 117.3 nmol/L)in the autumn and winter, respectively. In the autumn, 15.4% of participants were considered vitamin D deficient (25(OH)D < 50 nmol/L) whereas 51.3% had 25(OH)D concentrations that would be considered insufficient (<80 nmol/L). In the winter, 15.4% were deficient while 41% of all participants were considered vitamin D insufficient. Conclusion: A substantial proportion of elite athletes with SCI have insufficient (41%–51%) and deficient (15.4%) 25(OH)D status in the autumn and winter. Furthermore, a seasonal decline in vitamin D status was not observed in the current study. PMID:27322316

  15. Consumption of vitamin D2 enhanced mushrooms is associated with improved bone health.

    PubMed

    Chen, Shin-Yu; Yu, Hui-Tzu; Kao, Ju-Po; Yang, Chung-Chun; Chiang, Shen-Shih; Mishchuk, Darya O; Mau, Jeng-Leun; Slupsky, Carolyn M

    2015-07-01

    Mushrooms are the best nonanimal food source of vitamin D2. Pulsed irradiation can enhance vitamin D2 in mushrooms quickly. We investigated the effect of supplementing high vitamin D2Pleurotus ferulae mushrooms in a mouse model of osteoporosis. Thirty-two female C57BL/6JNarl mice were divided into four groups including sham, ovariectomized (OVX), OVX+nonpulsed mushroom (NPM) and OVX+pulsed mushroom (PM). After 23 weeks of treatment, serum samples were analyzed for osteoblast and osteoclast indicators, as well as metabolites using NMR spectroscopy. To examine bone density, femurs were analyzed using micro-computed tomography. The NPM and PM treatment mice showed increased bone density in comparison with OVX mice. In addition, the PM mice showed higher osteoblast and lower osteoclast indicators in comparison with OVX mice. Serum metabolomics analysis indicated several metabolites that were different in PM mice, some of which could be correlated with bone health. Taken together, these results suggest that pulsed irradiated mushrooms are able to increase bone density in osteoporotic mice possibly through enhanced bone metabolism. Further studies in humans are needed to show their efficacy in preventing osteoporosis.

  16. Consumption of vitamin D2 enhanced mushrooms is associated with improved bone health.

    PubMed

    Chen, Shin-Yu; Yu, Hui-Tzu; Kao, Ju-Po; Yang, Chung-Chun; Chiang, Shen-Shih; Mishchuk, Darya O; Mau, Jeng-Leun; Slupsky, Carolyn M

    2015-07-01

    Mushrooms are the best nonanimal food source of vitamin D2. Pulsed irradiation can enhance vitamin D2 in mushrooms quickly. We investigated the effect of supplementing high vitamin D2Pleurotus ferulae mushrooms in a mouse model of osteoporosis. Thirty-two female C57BL/6JNarl mice were divided into four groups including sham, ovariectomized (OVX), OVX+nonpulsed mushroom (NPM) and OVX+pulsed mushroom (PM). After 23 weeks of treatment, serum samples were analyzed for osteoblast and osteoclast indicators, as well as metabolites using NMR spectroscopy. To examine bone density, femurs were analyzed using micro-computed tomography. The NPM and PM treatment mice showed increased bone density in comparison with OVX mice. In addition, the PM mice showed higher osteoblast and lower osteoclast indicators in comparison with OVX mice. Serum metabolomics analysis indicated several metabolites that were different in PM mice, some of which could be correlated with bone health. Taken together, these results suggest that pulsed irradiated mushrooms are able to increase bone density in osteoporotic mice possibly through enhanced bone metabolism. Further studies in humans are needed to show their efficacy in preventing osteoporosis. PMID:25792284

  17. 1,25(OH)2D3 dependent overt hyperactivity phenotype in klotho-hypomorphic mice

    PubMed Central

    Leibrock, Christina B.; Voelkl, Jakob; Kuro-o, Makoto; Lang, Florian; Lang, Undine E

    2016-01-01

    Klotho, a protein mainly expressed in kidney and cerebral choroid plexus, is a powerful regulator of 1,25(OH)2D3 formation. Klotho-deficient mice (kl/kl) suffer from excessive plasma 1,25(OH)2D3-, Ca2+- and phosphate-concentrations, leading to severe soft tissue calcification and accelerated aging. NH4Cl treatment prevents tissue calcification and premature ageing without affecting 1,25(OH)2D3-formation. The present study explored the impact of excessive 1,25(OH)2D3 formation in NH4Cl-treated kl/kl-mice on behavior. To this end kl/kl-mice and wild-type mice were treated with NH4Cl and either control diet or vitamin D deficient diet (LVD). As a result, plasma 1,25(OH)2D3-, Ca2+- and phosphate-concentrations were significantly higher in untreated and in NH4Cl-treated kl/kl-mice than in wild-type mice, a difference abrogated by LVD. In each, open field, dark-light box, and O-maze NH4Cl-treated kl/kl-mice showed significantly higher exploratory behavior than untreated wild-type mice, a difference abrogated by LVD. The time of floating in the forced swimming test was significantly shorter in NH4Cl treated kl/kl-mice compared to untreated wild-type mice and to kl/kl-mice on LVD. In wild-type animals, NH4Cl treatment did not significantly alter 1,25(OH)2D3, calcium and phosphate concentrations or exploratory behavior. In conclusion, the excessive 1,25(OH)2D3 formation in klotho-hypomorphic mice has a profound effect on murine behavior. PMID:27109615

  18. Effects of vitamin D supplementation during pregnancy on neonatal vitamin D and calcium concentrations: a systematic review and meta-analysis.

    PubMed

    Yang, Na; Wang, Linlin; Li, Zhixia; Chen, Sen; Li, Nan; Ye, Rongwei

    2015-07-01

    We conducted a meta-analysis to review the effects of vitamin D supplementation during pregnancy on neonatal 25-hydroxyvitamin D (25(OH)D) and calcium concentrations. Randomized controlled trials that supplemented subjects with vitamin D2 or D3 during pregnancy and reported cord blood 25(OH)D or calcium concentrations were included. A random-effect model was used to pool the data. Subgroup analyses were performed to explore the sources of heterogeneity. We searched PubMed, Web of Science, and Cochrane Library for relevant publications. Among 1768 publications identified by our search strategy, 13 studies met our inclusion criteria. Cord blood 25(OH)D concentration was significantly increased by maternal vitamin D supplementation (mean difference, 22.48 nmol/L; 95% confidence interval, 15.90-29.06 nmol/L) with high heterogeneity (I2 = 98.8%, P < .0001). No effects on cord blood calcium concentration was reported (mean difference, 0.05 mmol/L; 95% confidence interval, -0.04-0.13 mmol/L). Supplementation regimens and the different control groups may be the major sources of heterogeneity. Vitamin D supplementation during pregnancy can improve cord blood 25(OH)D concentration in women with low 25(OH)D concentration, but does not affect cord blood calcium concentration. Future researches are needed to evaluate the effect of maternal vitamin D supplementation in women with a normal 25(OH)D concentration and explore the combined effects of vitamin D, calcium, and multivitamins.

  19. Impact on Vitamin D2, Vitamin D4 and Agaritine in Agaricus bisporus Mushrooms after Artificial and Natural Solar UV Light Exposure.

    PubMed

    Urbain, Paul; Valverde, Juan; Jakobsen, Jette

    2016-09-01

    Commercial mushroom production can expose mushrooms post-harvest to UV light for purposes of vitamin D2 enrichment by converting the naturally occurring provitamin D2 (ergosterol). The objectives of the present study were to artificially simulate solar UV-B doses occurring naturally in Central Europe and to investigate vitamin D2 and vitamin D4 production in sliced Agaricus bisporus (button mushrooms) and to analyse and compare the agaritine content of naturally and artificially UV-irradiated mushrooms. Agaritine was measured for safety aspects even though there is no rationale for a link between UV light exposure and agaritine content. The artificial UV-B dose of 0.53 J/cm(2) raised the vitamin D2 content to significantly (P < 0.001) higher levels of 67.1 ± 9.9 μg/g dry weight (DW) than sun exposure (3.9 ± 0.8 μg/g dry DW). We observed a positive correlation between vitamin D4 and vitamin D2 production (r(2) = 0.96, P < 0.001) after artificial UV irradiation, with vitamin D4 levels ranging from 0 to 20.9 μg/g DW. The agaritine content varied widely but remained within normal ranges in all samples. Irrespective of the irradiation source, agaritine dropped dramatically in conjunction with all UV-B doses both artificial and natural solar, probably due to its known instability. The biological action of vitamin D from UV-exposed mushrooms reflects the activity of these two major vitamin D analogues (D2, D4). Vitamin D4 should be analysed and agaritine disregarded in future studies of UV-exposed mushrooms. PMID:27323764

  20. Impact on Vitamin D2, Vitamin D4 and Agaritine in Agaricus bisporus Mushrooms after Artificial and Natural Solar UV Light Exposure.

    PubMed

    Urbain, Paul; Valverde, Juan; Jakobsen, Jette

    2016-09-01

    Commercial mushroom production can expose mushrooms post-harvest to UV light for purposes of vitamin D2 enrichment by converting the naturally occurring provitamin D2 (ergosterol). The objectives of the present study were to artificially simulate solar UV-B doses occurring naturally in Central Europe and to investigate vitamin D2 and vitamin D4 production in sliced Agaricus bisporus (button mushrooms) and to analyse and compare the agaritine content of naturally and artificially UV-irradiated mushrooms. Agaritine was measured for safety aspects even though there is no rationale for a link between UV light exposure and agaritine content. The artificial UV-B dose of 0.53 J/cm(2) raised the vitamin D2 content to significantly (P < 0.001) higher levels of 67.1 ± 9.9 μg/g dry weight (DW) than sun exposure (3.9 ± 0.8 μg/g dry DW). We observed a positive correlation between vitamin D4 and vitamin D2 production (r(2) = 0.96, P < 0.001) after artificial UV irradiation, with vitamin D4 levels ranging from 0 to 20.9 μg/g DW. The agaritine content varied widely but remained within normal ranges in all samples. Irrespective of the irradiation source, agaritine dropped dramatically in conjunction with all UV-B doses both artificial and natural solar, probably due to its known instability. The biological action of vitamin D from UV-exposed mushrooms reflects the activity of these two major vitamin D analogues (D2, D4). Vitamin D4 should be analysed and agaritine disregarded in future studies of UV-exposed mushrooms.

  1. In vitro effects of 1α,25(OH)₂D₃-glycosides from Solbone A (Solanum glaucophyllum leaves extract; Herbonis AG) compared to synthetic 1α,25(OH)₂D₃ on myogenesis.

    PubMed

    Gili, Valeria; Pardo, Verónica Gonzalez; Ronda, Ana C; De Genaro, Pablo; Bachmann, Heini; Boland, Ricardo; de Boland, Ana Russo

    2016-05-01

    The presence of glycoside derivatives of 1α,25(OH)2D3 endows plants to gradual release of the free bioactive form of 1α,25(OH)2D3 from its glycoconjugates by endogenous animal tissue glycosidases. This results in increased half-life of the hormone in blood when purified plant fractions are administered for therapeutic purposes. In this work, we evaluated the role 1α,25(OH)2D3-glycosides enriched natural product (Solbone A) from Solanum glaucophyllum leaf extract compared with synthetic 1α,25(OH)2D3 on myogenic differentiation in C2C12 myoblasts. For these, differentiation markers and myogenic parameters were studied in C2C12 myoblasts. Results showed that Solbone A, likewise the synthetic hormone, increased creatine kinase activity at day 2 after differentiation induction (60%, p<0.05). Solbone A and synthetic 1α,25(OH)2D3 increased vitamin D3 receptor protein expression at 10nM (50% and 30%, respectively) and the transcription factor myogenin (80%, p<0.05). However, tropomyosin expression was not affected by both compounds. In addition, myosin heavy chain (MHC) protein expression was increased 30% at day 2 of differentiation. Solbone A or synthetic 1α,25(OH)2D3 had no effects on myogenin nor MHC cell localization. Cellular mass increased with myogenesis progression, being Solbone A more effective than synthetic 1α,25(OH)2D3. Finally, Solbone A, as well as synthetic 1α,25(OH)2D3, augmented the index fusion of cultured muscle fibers. In conclusion, these results demonstrated that Solbone A exhibit at least equal or greater effects on early myoblast differentiation as synthetic hormone, suggesting that plant glycosides could be an effective, accessible and cheaper substitute for synthetic 1α,25(OH)2D3 to promote muscle growth. PMID:26968127

  2. The Current Recommended Vitamin D Intake Guideline for Diet and Supplements During Pregnancy Is Not Adequate to Achieve Vitamin D Sufficiency for Most Pregnant Women

    PubMed Central

    Field, Catherine J.; Kaplan, Bonnie J.; Rabi, Doreen M.; Maggiore, Jack A.; O’Beirne, Maeve; Hanley, David A.; Eliasziw, Misha; Dewey, Deborah; Weinberg, Amy; Ross, Sue J.

    2016-01-01

    Background The aims of this study were to determine if pregnant women consumed the recommended vitamin D through diet alone or through diet and supplements, and if they achieved the current reference range vitamin D status when their reported dietary intake met the current recommendations. Methods Data and banked blood samples collected in second trimester from a subset of 537 women in the APrON (Alberta Pregnant Outcomes and Nutrition) study cohort were examined. Frozen collected plasma were assayed using LC-MS/MS (liquid chromatography-tandem mass spectrometry) to determine 25(OH)D2, 25(OH)D3, 3-epi-25(OH)D3 concentrations. Dietary data were obtained from questionnaires including a Supplement Intake Questionnaire and a 24-hour recall of the previous day’s diet. Results Participants were 87% Caucasian; mean (SD) age of 31.3 (4.3); BMI 25.8 (4.7); 58% were primiparous; 90% had education beyond high school; 80% had a family income higher than CAN $70,000/year. 25(OH)D2, 25(OH)D3, and 3-epi-25(OH)D3) were identified in all of the 537 plasma samples;3-epi-25(OH)D3 contributed 5% of the total vitamin D. The median (IQR) total 25(OH)D (D2+D3) was 92.7 (30.4) nmol/L and 20% of women had 25(OH)D concentration < 75 nmol/L. The median (IQR) reported vitamin D intake from diet and supplements was 600 (472) IU/day. There was a significant relationship between maternal reported dietary vitamin D intake (diet and supplement) and 25(OH)D and 3-epi-25(OH)D3 concentrations in an adjusted linear regression model. Conclusions We demonstrated the current RDA (600 IU/ day) may not be adequate to achieve vitamin D status >75 nmol/L in some pregnant women who are residing in higher latitudes (Calgary, 51°N) in Alberta, Canada and the current vitamin D recommendations for Canadian pregnant women need to be re-evaluated. PMID:27367800

  3. Serum 25(OH)D seasonality in urologic patients from central Italy.

    PubMed

    Calgani, Alessia; Iarlori, Marco; Rizi, Vincenzo; Pace, Gianna; Bologna, Mauro; Vicentini, Carlo; Angelucci, Adriano

    2016-09-01

    Hypovitaminosis D is increasingly recognized as a cofactor in several diseases. In addition to bone homeostasis, vitamin D status influences immune system, muscle activity and cell differentiation in different tissues. Vitamin D is produced in the skin upon exposure to UVB rays, and sufficient levels of serum 25(OH)D are dependent mostly on adequate sun exposure, and then on specific physiologic variables, including skin type, age and Body Mass Index (BMI). In contrast with common belief, epidemiologic data are demonstrating that hypovitaminosis D must be a clinical concern not only in northern Countries. In our study, we investigated vitamin D status in a male population enrolled in a urology clinic of central Italy. In addition, we evaluated the correlation between vitamin D status and UVB irradiance measured in our region. The two principal pathologies in the 95 enrolled patients (mean age 66years) were benign prostate hypertrophy and prostate carcinoma. >50% of patients had serum 25(OH)D values in the deficient range (<20ng/mL), and only 16% of cases had serum vitamin D concentration higher than 30ng/mL (optimal range). The seasonal stratification of vitamin D concentrations revealed an evident trend with the minimum mean value recorded in April and a maximum mean value obtained in September. UVB irradiance measured by pyranometer in our region (Abruzzo, central Italy) revealed a large difference during the year, with winter months characterized by an UV irradiance about tenfold lower than summer months. Then we applied a mathematical model in order to evaluate the expected vitamin D production according to the standard erythemal dose measured in the different seasons. In winter months, the low available UVB radiation and the small exposed skin area resulted not sufficient to obtain the recommended serum doses of vitamin D. Although in summer months UVB irradiance was largely in excess to produce vitamin D in the skin, serum vitamin D resulted sufficient in

  4. 1α,25(OH)2D3 differentially regulates miRNA expression in human bladder cancer cells

    PubMed Central

    Ma, Yingyu; Hu, Qiang; Luo, Wei; Pratt, Rachel N.; Glenn, Sean T.; Liu, Song; Trump, Donald L.; Johnson, Candace S.

    2014-01-01

    Bladder cancer is the fourth most commonly diagnosed cancer in men and eighth leading cause of cancer-related death in the US. Epidemiological and experimental studies strongly suggest a role for 1α,25(OH)2D3 in cancer prevention and treatment. The antitumor activities of 1α,25(OH)2D3 are mediated by the induction of cell cycle arrest, apoptosis, differentiation and the inhibition of angiogenesis and metastasis. MiRNAs play important regulatory roles in cancer development and progression. However, the role of 1α,25(OH)2D3 in the regulation of miRNA expression and the potential impact in bladder cancer has not been investigated. Therefore, we studied 1α,25(OH)2D3-regulated miRNA expression profiles in human bladder cancer cell line 253J and the highly tumorigenic and metastatic derivative line 253J-BV by miRNA qPCR panels. 253 J and 253J-BV cells express endogenous vitamin D receptor (VDR) which can be further induced by 1α,25(OH)2D3. VDR target gene 24-hydroxylase was induced by 1α,25(OH)2D3 in both cell lines, indicating functional 1α,25(OH)2D3 signaling. The miRNA qPCR panel assay results showed that 253J and 253J-BV cells have distinct miRNA expression profiles. Further, 1α,25(OH)2D3 differentially regulated miRNA expression profiles in 253J and 253 J-BV cells in a dynamic manner. Pathway analysis of the miRNA target genes revealed distinct patterns of contribution to the molecular functions and biological processes in the two cell lines. In conclusion, 1α,25(OH)2D3 differentially regulates the expression of miRNAs, which may contribute to distinct biological functions, in human bladder 253J and 253J-BV cells. PMID:25263658

  5. Early indicators of survival following exposure to mustard gas: Protective role of 25(OH)D.

    PubMed

    Das, Lopa M; Binko, Amy M; Traylor, Zachary P; Duesler, Lori R; Dynda, Scott M; Debanne, Sara; Lu, Kurt Q

    2016-04-25

    The use of sulfur mustard (SM) as a chemical weapon for warfare has once again assumed center stage, endangering civilian and the military safety. SM causes rapid local skin vesication and late-onset systemic toxicity. Most studies on SM rely on obtaining tissue and blood for characterizing burn pathogenesis and assessment of systemic pathology, respectively. However the present study focuses on developing a non-invasive method to predict mortality from high dose skin SM exposure. We demonstrate that exposure to SM leads to a dose dependent increase in wound area size on the dorsal surface of mice that is accompanied by a progressive loss in body weight loss, blood cytopenia, bone marrow destruction, and death. Thus our model utilizes local skin destruction and systemic outcome measures as variables to predict mortality in a novel skin-based model of tissue injury. Based on our recent work using vitamin D (25(OH)D) as an intervention to treat toxicity from SM-related compounds, we explored the use of 25(OH)D in mitigating the toxic effects of SM. Here we show that 25(OH)D offers protection against SM and is the first known demonstration of an intervention that prevents SM-induced mortality. Furthermore, 25(OH)D represents a safe, novel, and readily translatable potential countermeasure following mass toxic exposure. PMID:26940683

  6. Influence of vitamin D mushroom powder supplementation on exercise-induced muscle damage in vitamin D insufficient high school athletes.

    PubMed

    Shanely, R Andrew; Nieman, David C; Knab, Amy M; Gillitt, Nicholas D; Meaney, Mary Pat; Jin, Fuxia; Sha, Wei; Cialdella-Kam, Lynn

    2014-01-01

    Incidence of vitamin D deficiency is increasing worldwide. The purpose of this study was to determine if supplementation with vitamin D2 from Portobello mushroom powder would enhance skeletal muscle function and attenuate exercise-induced muscle damage in low vitamin D status high school athletes. Participants were randomised to Portobello mushroom powder (600 IU/d vitamin D2) or placebo for 6 weeks. Participants then completed a 1.5-h exercise session designed to induce skeletal muscle damage. Blood samples and measures of skeletal muscle function were taken pre-supplementation, post-supplementation/pre-exercise and post-exercise. Six weeks supplementation with vitamin D2 increased serum 25(OH)D2 by 9.9-fold and decreased serum 25(OH)D3 by 28%. Changes in skeletal muscle function and circulating markers of skeletal muscle damage did not differ between groups. In conclusion, 600 IU/d vitamin D2 increased 25(OH)D2 with a concomitant decrease in 25(OD)D3, with no effect on muscular function or exercise-induced muscle damage in high school athletes.

  7. Impact of sulfur and vitamin C on the allergenicity of Mal d 2 from apple (Malus domestica).

    PubMed

    Marzban, Gorji; Kinaciyan, Tamar; Maghuly, Fatemeh; Brunner, Richard; Gruber, Clemens; Hahn, Rainer; Jensen-Jarolim, Erika; Laimer, Margit

    2014-07-30

    Mal d 2 is a minor allergen from apple which shows a high conformational stability due to its eight conserved disulfide bridges. Chemical reduction of disulfide bridges and linearization of Mal d 2 lead to enhanced IgE reactivity in vitro and indicate a higher potential for allergenicity. Since food preservatives such as sulfur and vitamin C are reducing and denaturing agents, their influence on Mal d 2 allergenicity was verified by simulated food processing conditions. The immunoreactivity of purified Mal d 2 was investigated after different treatments in vitro and in vivo using IgG/IgE Western blotting, mediator-releasing cell assay, and skin prick and oral smear tests. The conformational changes of Mal d 2 upon addition of 1% and 5% vitamin C were also monitored by attenuated total reflectance Fourier transform infrared spectroscopy. The results show no positive skin and oral smear test reactivity to native, heated, or vitamin C-treated purified Mal d 2. Furthermore, the results confirm that sulfur in combination with heat treatment can influence the structural integrity and thus the allergenicity of Mal d 2, while vitamin C is too weak as a reducing agent to change allergenicity. PMID:24983674

  8. Impact of sulfur and vitamin C on the allergenicity of Mal d 2 from apple (Malus domestica).

    PubMed

    Marzban, Gorji; Kinaciyan, Tamar; Maghuly, Fatemeh; Brunner, Richard; Gruber, Clemens; Hahn, Rainer; Jensen-Jarolim, Erika; Laimer, Margit

    2014-07-30

    Mal d 2 is a minor allergen from apple which shows a high conformational stability due to its eight conserved disulfide bridges. Chemical reduction of disulfide bridges and linearization of Mal d 2 lead to enhanced IgE reactivity in vitro and indicate a higher potential for allergenicity. Since food preservatives such as sulfur and vitamin C are reducing and denaturing agents, their influence on Mal d 2 allergenicity was verified by simulated food processing conditions. The immunoreactivity of purified Mal d 2 was investigated after different treatments in vitro and in vivo using IgG/IgE Western blotting, mediator-releasing cell assay, and skin prick and oral smear tests. The conformational changes of Mal d 2 upon addition of 1% and 5% vitamin C were also monitored by attenuated total reflectance Fourier transform infrared spectroscopy. The results show no positive skin and oral smear test reactivity to native, heated, or vitamin C-treated purified Mal d 2. Furthermore, the results confirm that sulfur in combination with heat treatment can influence the structural integrity and thus the allergenicity of Mal d 2, while vitamin C is too weak as a reducing agent to change allergenicity.

  9. Vitamin D status predicts reproductive fitness in a wild sheep population

    PubMed Central

    Handel, Ian; Watt, Kathryn A.; Pilkington, Jill G.; Pemberton, Josephine M.; Macrae, Alastair; Scott, Philip; McNeilly, Tom N.; Berry, Jacqueline L.; Clements, Dylan N.; Nussey, Daniel H.; Mellanby, Richard J.

    2016-01-01

    Vitamin D deficiency has been associated with the development of many human diseases, and with poor reproductive performance in laboratory rodents. We currently have no idea how natural selection directly acts on variation in vitamin D metabolism due to a total lack of studies in wild animals. Here, we measured serum 25 hydroxyvitamin D (25(OH)D) concentrations in female Soay sheep that were part of a long-term field study on St Kilda. We found that total 25(OH)D was strongly influenced by age, and that light coloured sheep had higher 25(OH)D3 (but not 25(OH)D2) concentrations than dark sheep. The coat colour polymorphism in Soay sheep is controlled by a single locus, suggesting vitamin D status is heritable in this population. We also observed a very strong relationship between total 25(OH)D concentrations in summer and a ewe’s fecundity the following spring. This resulted in a positive association between total 25(OH)D and the number of lambs produced that survived their first year of life, an important component of female reproductive fitness. Our study provides the first insight into naturally-occurring variation in vitamin D metabolites, and offers the first evidence that vitamin D status is both heritable and under natural selection in the wild. PMID:26757805

  10. [Is daily supplementation with vitamin D2 equivalent to daily supplementation with vitamin D3 in the elderly?].

    PubMed

    Seijo, Mariana; Mastaglia, Silvina; Brito, Graciela; Somoza, Julia; Oliveri, Beatriz

    2012-01-01

    The equivalence of cholecalciferol (D3) and ergocalciferol (D2) as well as their corresponding doses and administration route remain controversial to date. The aim of this study was to compare the effectiveness of daily supplementation with 800 IU of D2 (drops) and D3 (pills) on 25-hydroxivitamin D (25OHD) levels (= 30 ng/ml). Twenty-one ambulatory postmenopausal women from Buenos Aires City with a mean (X ± SD) age of 77.1 ± 6.8 years were included. The participants were randomly assigned to one of the following groups: GD2 (n = 13): 800 IU (drops) and GD3 (n = 8): 800 IU (pills). Serum 25OHD levels were measured (RIA-DIASORIN) at baseline, and at 7, 28 and 45 days. Nineteen out of twenty one women showed deficient levels of 25OHD at baseline (< 20 ng/ml): GD2: 14.0 ± 4.8 ng/ml and GD3: 13.2 ± 4.9 ng/ml (NS). Whereas only GD3 exhibited an increase (≈ 25%) at 7 days, both groups showed a significant increase at the end of the study. However, neither attained adequate 25OHD levels (GD2: 17.4 ± 5.5 vs. GD3:22.9 ± 4.6 ng/ml; p < 0.001). Administration of 800 IU of vitamin D3 during 45 days was more effective than D2 in increasing 25OHD, but both failed to achieve adequate levels of 25OHD (= 30 ng/ml). but neither succeeded in achieving adequate levels of 25OHD (= 30 ng/ml).

  11. Vitamin D2 Formation from Post-Harvest UV-B Treatment of Mushrooms (Agaricus bisporus) and Retention during Storage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objectives of this research were to study the effects of high intensity (0.5, 0.75, and 1.0 mW/cm2), dose (0.5, 1.0, and 1.5 J/cm2), and post-harvest time (1 and 4 days) on the vitamin D2 formation in Portabella mushrooms (Agaricus bisporus) as a result of UV-B exposure, as well as the vitamin D...

  12. Modeling the sssociation between 25[OH]D and all-cause mortality in a representative US population sample

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamin D has been identified as a potential key risk factor for several chronic diseases and mortality. The association between all-cause mortality and circulating levels of 25-ydroxyvitamin D (25[OH]D) has been described as non-monotonic with excess mortality at both low and high levels (1). Howev...

  13. 1,25 (OH)2D3 treatment alters the granulomatous response in M. tuberculosis infected mice

    PubMed Central

    Bhatt, Kamlesh; Rafi, Wasiulla; Shah, Neel; Christakos, Sylvia; Salgame, Padmini

    2016-01-01

    Induction of cathelicidin-mediated antimicrobial pathway against intracellular M. tuberculosis by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D, has been documented in vitro. However, in in vivo studies related to inflammatory disorders, 1,25(OH)2D3 has been demonstrated to induce an anti-inflammatory response. We therefore examined whether in the murine model of tuberculosis, the anti-inflammatory effects of 1,25(OH)2D3 would affect the outcome of M. tuberculosis infection. We show here that administration of 1,25(OH)2D3 to M. tuberculosis infected mice led to a change in lung granuloma architecture, characterized by a marked decrease in B cell lymphocytic aggregates. Consistent with the altered granulomas, 1,25(OH)2D3-treated mice also exhibited significantly higher bacterial burden in the lungs compared to the control group. These findings highlight the need to further investigate the effect of vitamin D on host immunity to M. tuberculosis in the context of the granulomatous response. PMID:27698450

  14. 77 FR 52228 - Food Additives Permitted for Direct Addition to Food for Human Consumption; Vitamin D2

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-29

    ... the Federal Register of December 17, 2009 (74 FR 66979), FDA announced that a food additive petition... rule (74 FR 11019) for the use of vitamin D 2 in soy-based food products. Lallemand concluded that... supplement in soy-based food products (74 FR 11019, March 16, 2009). The three earlier food...

  15. 1α,25(OH)2D3 differentially regulates miRNA expression in human bladder cancer cells.

    PubMed

    Ma, Yingyu; Hu, Qiang; Luo, Wei; Pratt, Rachel N; Glenn, Sean T; Liu, Song; Trump, Donald L; Johnson, Candace S

    2015-04-01

    Bladder cancer is the fourth most commonly diagnosed cancer in men and eighth leading cause of cancer-related death in the US. Epidemiological and experimental studies strongly suggest a role for 1α,25(OH)2D3 in cancer prevention and treatment. The antitumor activities of 1α,25(OH)2D3 are mediated by the induction of cell cycle arrest, apoptosis, differentiation and the inhibition of angiogenesis and metastasis. miRNAs play important regulatory roles in cancer development and progression. However, the role of 1α,25(OH)2D3 in the regulation of miRNA expression and the potential impact in bladder cancer has not been investigated. Therefore, we studied 1α,25(OH)2D3-regulated miRNA expression profiles in human bladder cancer cell line 253J and the highly tumorigenic and metastatic derivative line 253J-BV by miRNA qPCR panels. 253J and 253J-BV cells express endogenous vitamin D receptor (VDR), which can be further induced by 1α,25(OH)2D3. VDR target gene 24-hydroxylase was induced by 1α,25(OH)2D3 in both cell lines, indicating functional 1α,25(OH)2D3 signaling. The miRNA qPCR panel assay results showed that 253J and 253J-BV cells have distinct miRNA expression profiles. Further, 1α,25(OH)2D3 differentially regulated miRNA expression profiles in 253J and 253J-BV cells in a dynamic manner. Pathway analysis of the miRNA target genes revealed distinct patterns of contribution to the molecular functions and biological processes in the two cell lines. In conclusion, 1α,25(OH)2D3 differentially regulates the expression of miRNAs, which may contribute to distinct biological functions, in human bladder 253J and 253J-BV cells. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. PMID:25263658

  16. 1α,25(OH)2D3 differentially regulates miRNA expression in human bladder cancer cells.

    PubMed

    Ma, Yingyu; Hu, Qiang; Luo, Wei; Pratt, Rachel N; Glenn, Sean T; Liu, Song; Trump, Donald L; Johnson, Candace S

    2015-04-01

    Bladder cancer is the fourth most commonly diagnosed cancer in men and eighth leading cause of cancer-related death in the US. Epidemiological and experimental studies strongly suggest a role for 1α,25(OH)2D3 in cancer prevention and treatment. The antitumor activities of 1α,25(OH)2D3 are mediated by the induction of cell cycle arrest, apoptosis, differentiation and the inhibition of angiogenesis and metastasis. miRNAs play important regulatory roles in cancer development and progression. However, the role of 1α,25(OH)2D3 in the regulation of miRNA expression and the potential impact in bladder cancer has not been investigated. Therefore, we studied 1α,25(OH)2D3-regulated miRNA expression profiles in human bladder cancer cell line 253J and the highly tumorigenic and metastatic derivative line 253J-BV by miRNA qPCR panels. 253J and 253J-BV cells express endogenous vitamin D receptor (VDR), which can be further induced by 1α,25(OH)2D3. VDR target gene 24-hydroxylase was induced by 1α,25(OH)2D3 in both cell lines, indicating functional 1α,25(OH)2D3 signaling. The miRNA qPCR panel assay results showed that 253J and 253J-BV cells have distinct miRNA expression profiles. Further, 1α,25(OH)2D3 differentially regulated miRNA expression profiles in 253J and 253J-BV cells in a dynamic manner. Pathway analysis of the miRNA target genes revealed distinct patterns of contribution to the molecular functions and biological processes in the two cell lines. In conclusion, 1α,25(OH)2D3 differentially regulates the expression of miRNAs, which may contribute to distinct biological functions, in human bladder 253J and 253J-BV cells. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

  17. Extract-filter-shoot liquid chromatography/mass spectrometry for analysis of vitamin D2 in a powdered supplement capsule and SRM 3280

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An ‘extract-filter-shoot’ method for analysis of vitamin D2, ergocalciferol, in a dry powdered dietary supplement capsule containing rice flour excipient and in National Institute of Standards and Technology (NIST) standard reference material (SRM) 3280 is reported. Quantification of vitamin D2 was...

  18. Prospective Investigation of 25(OH)D3 Serum Concentration Following UVB Narrow Band Phototherapy in Patients with Psoriasis and Atopic Dermatitis.

    PubMed

    Weinhold, Annett; Obeid, Rima; Vogt, Thomas; Reichrath, Jörg

    2016-03-01

    Vitamin D deficiency represents a major health issue. It is a worldwide endemic and is associated with a broad variety of severe diseases. The skin is a key tissue for the human body's vitamin D endocrine system. It represents a target tissue for biologically active vitamin D metabolites. Approximately 90% of the human body's requirements of vitamin D have to be synthesised in the skin by the action of UVB-radiation. However, individual factors that influence a person's cutaneous synthesis of vitamin D are still not well understood. In our present prospective study we investigated the effect of UVB narrow band (UVBnb, 311 nm) and PUVA phototherapy on 25(OH)D3 serum concentration, in patients with psoriasis, atopic dermatitis and a few cases with other dermatoses (n=41). We found that two weeks of UVBnb treatment resulted in an increase of 25(OH)D3 serum concentration from 11.4 to 20.5 ng/ml (p<0.001), while in contrast PUVA-treatment did not significantly alter vitamin D status. These findings question the hypothesis of a relevant vitamin D metabolizing effect of UVA. Psoriasis patients showed a trend for a stronger increase in 25(OH)D3 serum levels following UVBnb compared to patients with atopic dermatitis. Patients with relatively low baseline serum 25(OH)D3 concentrations had a stronger increase in 25(OH)D3 concentrations compared to patients with relatively high 25(OH)D serum concentrations. In general patients with skin types (Fitzpatrick) I and II (median=14.3 ng/ml) had a higher baseline of 25(OH)D3 serum concentration compared to patients with skin types III (median=11.2 ng/ml) or IV-V (median=12.3 ng/ml), although these differences were not statistically significant (p=0.106). Baseline 25(OH)D3 serum concentrations were correlated with presence of genetic variants (SNPs of VDR, CYP2R1, VDBP/GC) that influence vitamin D status, and with other individual factors such as body mass index, age and gender. We also investigated the effect of phototherapy on

  19. Prospective Investigation of 25(OH)D3 Serum Concentration Following UVB Narrow Band Phototherapy in Patients with Psoriasis and Atopic Dermatitis.

    PubMed

    Weinhold, Annett; Obeid, Rima; Vogt, Thomas; Reichrath, Jörg

    2016-03-01

    Vitamin D deficiency represents a major health issue. It is a worldwide endemic and is associated with a broad variety of severe diseases. The skin is a key tissue for the human body's vitamin D endocrine system. It represents a target tissue for biologically active vitamin D metabolites. Approximately 90% of the human body's requirements of vitamin D have to be synthesised in the skin by the action of UVB-radiation. However, individual factors that influence a person's cutaneous synthesis of vitamin D are still not well understood. In our present prospective study we investigated the effect of UVB narrow band (UVBnb, 311 nm) and PUVA phototherapy on 25(OH)D3 serum concentration, in patients with psoriasis, atopic dermatitis and a few cases with other dermatoses (n=41). We found that two weeks of UVBnb treatment resulted in an increase of 25(OH)D3 serum concentration from 11.4 to 20.5 ng/ml (p<0.001), while in contrast PUVA-treatment did not significantly alter vitamin D status. These findings question the hypothesis of a relevant vitamin D metabolizing effect of UVA. Psoriasis patients showed a trend for a stronger increase in 25(OH)D3 serum levels following UVBnb compared to patients with atopic dermatitis. Patients with relatively low baseline serum 25(OH)D3 concentrations had a stronger increase in 25(OH)D3 concentrations compared to patients with relatively high 25(OH)D serum concentrations. In general patients with skin types (Fitzpatrick) I and II (median=14.3 ng/ml) had a higher baseline of 25(OH)D3 serum concentration compared to patients with skin types III (median=11.2 ng/ml) or IV-V (median=12.3 ng/ml), although these differences were not statistically significant (p=0.106). Baseline 25(OH)D3 serum concentrations were correlated with presence of genetic variants (SNPs of VDR, CYP2R1, VDBP/GC) that influence vitamin D status, and with other individual factors such as body mass index, age and gender. We also investigated the effect of phototherapy on

  20. The Effect of Various Vitamin D Supplementation Regimens in Breast Cancer Patients

    PubMed Central

    Peppone, Luke J.; Huston, Alissa J.; Reid, Mary E.; Rosier, Randy N.; Zakharia, Yousef; Trump, Donald L.; Mustian, Karen M.; Janelsins, Michelle C.; Purnell, Jason Q.; Morrow, Gary R.

    2014-01-01

    Purpose Vitamin D deficiency in patients treated for breast cancer is associated with numerous adverse effects (bone loss, arthralgia, and falls). The first aim of this study was to assess vitamin D status, determined by 25-OH vitamin D levels, among women diagnosed with breast cancer according to demographic/clinical variables and bone mineral density (BMD). The second aim of this study was to evaluate the effect of daily low-dose and weekly high-dose vitamin D supplementation on 25-OH vitamin D levels. Methods This retrospective study included 224 women diagnosed with Stage 0-III breast cancer who received treatment at the James P. Wilmot Cancer Center at the University of Rochester Medical Center. Total 25-OH vitamin D levels (D2 + D3) were determined at baseline for all participants. Vitamin D deficiency was defined as a 25-OH vitamin D level < 20 ng/mL, insufficiency as 20-31 ng/mL, and sufficiency as ≥ 32 ng/mL. BMD was assessed during the period between 3 months prior to and 6 months following the baseline vitamin D assessment. Based on the participants’ baseline levels, they received either no supplementation, low-dose supplementation (1,000 IU/day), or high-dose supplementation (≥ 50,000 IU/week), and 25-OH vitamin D was reassessed in the following 8-16 weeks. Results Approx 66.5% had deficient/insufficient vitamin D levels at baseline. Deficiency/insufficiency was more common among non-Caucasians, women with later-stage disease, and those who had previously received radiation therapy (p<0.05). Breast cancer patients with deficient/insufficient 25-OH vitamin D levels had significantly lower lumbar BMD (p=0.03). Compared to the no supplementation group, weekly high-dose supplementation significantly increased 25-OH vitamin D levels, while daily low-dose supplementation did not significantly increase levels. Conclusions Vitamin D deficiency and insufficiency were common among women with breast cancer and associated with reduced BMD in the spine

  1. The effect of various vitamin D supplementation regimens in breast cancer patients

    PubMed Central

    Huston, Alissa J.; Reid, Mary E.; Rosier, Randy N.; Zakharia, Yousef; Trump, Donald L.; Mustian, Karen M.; Janelsins, Michelle C.; Purnell, Jason Q.; Morrow, Gary R.

    2011-01-01

    Vitamin D deficiency in the patients treated for breast cancer is associated with numerous adverse effects (bone loss, arthralgia, and falls). The first aim of this study was to assess vitamin D status, determined by 25-OH vitamin D levels, among women diagnosed with breast cancer according to demographic/clinical variables and bone mineral density (BMD). The second aim of this study was to evaluate the effect of daily low-dose and weekly high-dose vitamin D supplementation on 25-OH vitamin D levels. This retrospective study included 224 women diagnosed with stage 0–III breast cancer who received treatment at the James P. Wilmot Cancer Center at the University of Rochester Medical Center. Total 25-OH vitamin D levels (D2 + D3) were determined at baseline for all participants. Vitamin D deficiency was defined as a 25-OH vitamin D level < 20 ng/ml, insufficiency as 20–31 ng/ml, and sufficiency as ≥32 ng/ml. BMD was assessed during the period between 3 months before and 6 months following the baseline vitamin D assessment. Based on the participants’ baseline levels, they received either no supplementation, low-dose supplementation (1,000 IU/day), or high-dose supplementation (≥50,000 IU/week), and 25-OH vitamin D was reassessed in the following 8–16 weeks. Approximately 66.5% had deficient/insufficient vitamin D levels at baseline. Deficiency/insufficiency was more common among non-Caucasians, women with later-stage disease, and those who had previously received radiation therapy (P < 0.05). Breast cancer patients with deficient/insufficient 25-OH vitamin D levels had significantly lower lumbar BMD (P = 0.03). Compared to the no-supplementation group, weekly high-dose supplementation significantly increased 25-OH vitamin D levels, while daily low-dose supplementation did not significantly increase levels. Vitamin D deficiency and insufficiency were common among women with breast cancer and associated with reduced BMD in the spine. Clinicians should

  2. Vitamin D2-enriched button mushroom (Agaricus bisporus) improves memory in both wild type and APPswe/PS1dE9 transgenic mice.

    PubMed

    Bennett, Louise; Kersaitis, Cindy; Macaulay, Stuart Lance; Münch, Gerald; Niedermayer, Garry; Nigro, Julie; Payne, Matthew; Sheean, Paul; Vallotton, Pascal; Zabaras, Dimitrios; Bird, Michael

    2013-01-01

    Vitamin D deficiency is widespread, affecting over 30% of adult Australians, and increasing up to 80% for at-risk groups including the elderly (age>65). The role for Vitamin D in development of the central nervous system is supported by the association between Vitamin D deficiency and incidence of neurological and psychiatric disorders including Alzheimer's disease (AD). A reported positive relationship between Vitamin D status and cognitive performance suggests that restoring Vitamin D status might provide a cognitive benefit to those with Vitamin D deficiency. Mushrooms are a rich source of ergosterol, which can be converted to Vitamin D2 by treatment with UV light, presenting a new and convenient dietary source of Vitamin D2. We hypothesised that Vitamin D2-enriched mushrooms (VDM) could prevent the cognitive and pathological abnormalities associated with dementia. Two month old wild type (B6C3) and AD transgenic (APPSwe/PS1dE9) mice were fed a diet either deficient in Vitamin D2 or a diet which was supplemented with VDM, containing 1±0.2 µg/kg (∼54 IU/kg) vitamin D2, for 7 months. Effects of the dietary intervention on memory were assessed pre- and post-feeding. Brain sections were evaluated for amyloid β (Aβ) plaque loads and inflammation biomarkers using immuno-histochemical methods. Plasma vitamin D metabolites, Aβ40, Aβ42, calcium, protein and cholesterol were measured using biochemical assays. Compared with mice on the control diet, VDM-fed wild type and AD transgenic mice displayed improved learning and memory, had significantly reduced amyloid plaque load and glial fibrillary acidic protein, and elevated interleukin-10 in the brain. The results suggest that VDM might provide a dietary source of Vitamin D2 and other bioactives for preventing memory-impairment in dementia. This study supports the need for a randomised clinical trial to determine whether or not VDM consumption can benefit cognitive performance in the wider population. PMID:24204618

  3. Acute vitamin D2 (ergocalciferol) toxicosis in horses: case report and experimental studies.

    PubMed

    Harrington, D D

    1982-04-15

    Acute accidental vitamin D2 (ergocalciferol) toxicosis was diagnosed in a 6-month-old foal with extensive lesions of soft tissue mineralization. In an experimental study, three 18-month-old horses were given ergocalciferol per os at a rate of 9,300, 22,200, or 47,200 IU/kg of body weight/day for 21 days. Clinical signs or lesions were not seen in horses given the low and intermediate doses, whereas the horse receiving the highest dose developed clinical signs and lesions similar to those noted in the foal. Signs included depression, loss of appetite, weakness, limb stiffness with impaired mobility, and cessation of growth or weight loss. Gross and histologic lesions of mineralization of various soft tissues, especially of the endocardium and wall of large blood vessels, were seen in the foal and the horse given the high dose. Marked, persistent, hyperphosphatemia (7.0 to 13.0 mg of P/dl of serum) developed in each horse. The horse given the intermediate dose remained normocalcemic. Horses given the low and high doses became hypercalcemic (13.6 to 14.5 mg of Ca/dl of serum), but serum calcium concentrations varied from day to day and both horses were normocalcemic at necropsy (12.4 to 12.7 mg of Ca/dl of serum). Distal metacarpal bone ash concentrations of calcium, phosphorus, and magnesium of the foal were mg/g of bone ash) 400.5, 180.5, and 5.30, respectively. In the horses, treatment with ergocalciferol also had no significant effect on serum magnesium (1.88 to 2.18 mg/dl of serum) or distal metacarpal bone ash concentrations of calcium (352.5 to 362.5 mg/g of bone ash), phosphorus (182.5 to 184.0 mg/g of bone ash), or magnesium (5.48 to 6.02 mg/g of bone ash).

  4. 1,25(OH)2D3 Alters Growth Plate Maturation and Bone Architecture in Young Rats with Normal Renal Function

    PubMed Central

    Idelevich, Anna; Kerschnitzki, Michael; Shahar, Ron; Monsonego-Ornan, Efrat

    2011-01-01

    Whereas detrimental effects of vitamin D deficiency are known over century, the effects of vitamin D receptor activation by 1,25(OH)2D3, the principal hormonal form of vitamin D, on the growing bone and its growth plate are less clear. Currently, 1,25(OH)2D3 is used in pediatric patients with chronic kidney disease and mineral and bone disorder (CKD-MBD) and is strongly associated with growth retardation. Here, we investigate the effect of 1,25(OH)2D3 treatment on bone development in normal young rats, unrelated to renal insufficiency. Young rats received daily i.p. injections of 1 µg/kg 1,25(OH)2D3 for one week, or intermittent 3 µg/kg 1,25(OH)2D3 for one month. Histological analysis revealed narrower tibial growth plates, predominantly in the hypertrophic zone of 1,25(OH)2D3-treated animals in both experimental protocols. This phenotype was supported by narrower distribution of aggrecan, collagens II and X mRNA, shown by in situ hybridization. Concomitant with altered chondrocyte maturation, 1,25(OH)2D3 increased chondrocyte proliferation and apoptosis in terminal hypertrophic cells. In vitro treatment of the chondrocytic cell line ATDC5 with 1,25(OH)2D3 lowered differentiation and increased proliferation dose and time-dependently. Micro-CT analysis of femurs from 1-week 1,25(OH)2D3-treated group revealed reduced cortical thickness, elevated cortical porosity, and higher trabecular number and thickness. 1-month administration resulted in a similar cortical phenotype but without effect on trabecular bone. Evaluation of fluorochrome binding with confocal microscopy revealed inhibiting effects of 1,25(OH)2D3 on intracortical bone formation. This study shows negative effects of 1,25(OH)2D3 on growth plate and bone which may contribute to the exacerbation of MBD in the CKD pediatric patients. PMID:21695192

  5. Vitamin D Binding Protein Is Not Involved in Vitamin D Deficiency in Patients with Chronic Kidney Disease

    PubMed Central

    Kalousova, Marta; Dusilova-Sulkova, Sylvie; Zakiyanov, Oskar; Kostirova, Milada; Safranek, Roman; Tesar, Vladimir; Zima, Tomas

    2015-01-01

    Objective. This study was designed to evaluate vitamin D status with separate determination of 25-OH D2 and 25-OH D3 and its relationship to vitamin D binding protein (VDBP) in patients with chronic kidney disease (CKD) and long-term haemodialysis patients (HD). Methods. 45 CKD patients, 103 HD patients, and 25 controls (C) were included. Plasma vitamin D concentrations were determined using chromatography and VDBP in serum and urine in CKD using enzyme immunoassay. Results. Plasma vitamin D levels were lower in CKD (30.16 ± 16.74 ng/mL) and HD (18.85 ± 15.85 ng/mL) versus C (48.72 ± 18.35 ng/mL), P < 0.0001. 25-OH D3 was the dominant form of vitamin D. Serum VDBP was higher in CKD (273.2 ± 93.8 ug/mL) versus C (222 ± 87.6 ug/mL) and HD (213.8 ± 70.9 ug/mL), P = 0.0003. Vitamin D/VDBP ratio was the highest in C and the lowest in HD; however, there was no correlation between vitamin D and VDBP. Urinary concentration of VDBP in CKD (0.25 ± 0.13 ug/mL) correlated with proteinuria (r = 0.43, P = 0.003). Conclusions. Plasma levels of vitamin D are decreased in CKD patients and especially in HD patients. 25-OH D3 was the major form of vitamin D. Despite urinary losses of VDBP, CKD patients had higher serum VDBP concentrations, indicating compensatory enhanced production. Vitamin D binding protein is not involved in vitamin D deficiency. PMID:26064917

  6. The effect of vitamin D2 and vitamin D3 on intestinal calcium absorption in Nigerian children with rickets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Children with calcium-deficiency rickets have high 1,25-dihydroxyvitamin D values. The objective of the study was to determine whether vitamin D increased calcium absorption. This was an experimental study. The study was conducted at a teaching hospital. Participants included 17 children with nutrit...

  7. Association of Circulating 25(OH)D and Lower Urinary Tract Symptoms: A Four-Year Prospective Study among Elderly Chinese Men.

    PubMed

    Liu, Zhao-Min; Wong, Carmen Ka Man; Chan, Dicken; Woo, Jean; Chen, Yu-Ming; Chen, Bailing; Tse, Lap-Ah; Wong, Samuel Yeung-Shan

    2016-01-01

    The role of vitamin D in relation to lower urinary tract symptoms (LUTS) remains inconclusive. This four-year longitudinal study aims to explore the association of circulating 25(OH)D and LUTS in elderly Chinese men. Two thousand Chinese men aged 65 and older were recruited from a local community, of which 1998 (99.9%) at baseline and 1564 (78.2%) at four-year follow-up reported data on LUTS, and 988 of the randomly chosen subpopulation were assayed for serum 25(OH)D by radioimmunoassay at baseline. LUTS were evaluated by a validated International Prostate Symptoms Scale (IPSS). Data on demographic characteristics, lifestyle factors, health, and medications were collected. Serum parathyroid and sex steroid hormones and genotypes of vitamin D receptors were assayed. The association of serum 25(OH)D and LUTS was examined by using multivariable regression models. Serum 25(OH)D was not significantly associated with the changes of IPSS or the risk of LUTS in overall participants. However, among men with 25(OH)D ≤ 60 nmol/L, each 10 nmol/L increase of 25(OH)D over 0 nmol/L was significantly associated with 1.3 lower points of IPSS or a 51.6% decreased risk for moderate/severe LUTS four years later. Adjustment for serum androstenedione (p = 0.019) and dehydropiandrosterone (p = 0.037) attenuated the associations. Our study suggested that among individuals with low vitamin D status, the increase of the 25(OH)D level may be associated with a lowered risk of LUTS. PMID:27164139

  8. Association of Circulating 25(OH)D and Lower Urinary Tract Symptoms: A Four-Year Prospective Study among Elderly Chinese Men

    PubMed Central

    Liu, Zhao-Min; Wong, Carmen Ka Man; Chan, Dicken; Woo, Jean; Chen, Yu-Ming; Chen, Bailing; Tse, Lap-Ah; Wong, Samuel Yeung-Shan

    2016-01-01

    The role of vitamin D in relation to lower urinary tract symptoms (LUTS) remains inconclusive. This four-year longitudinal study aims to explore the association of circulating 25(OH)D and LUTS in elderly Chinese men. Two thousand Chinese men aged 65 and older were recruited from a local community, of which 1998 (99.9%) at baseline and 1564 (78.2%) at four-year follow-up reported data on LUTS, and 988 of the randomly chosen subpopulation were assayed for serum 25(OH)D by radioimmunoassay at baseline. LUTS were evaluated by a validated International Prostate Symptoms Scale (IPSS). Data on demographic characteristics, lifestyle factors, health, and medications were collected. Serum parathyroid and sex steroid hormones and genotypes of vitamin D receptors were assayed. The association of serum 25(OH)D and LUTS was examined by using multivariable regression models. Serum 25(OH)D was not significantly associated with the changes of IPSS or the risk of LUTS in overall participants. However, among men with 25(OH)D ≤ 60 nmol/L, each 10 nmol/L increase of 25(OH)D over 0 nmol/L was significantly associated with 1.3 lower points of IPSS or a 51.6% decreased risk for moderate/severe LUTS four years later. Adjustment for serum androstenedione (p = 0.019) and dehydropiandrosterone (p = 0.037) attenuated the associations. Our study suggested that among individuals with low vitamin D status, the increase of the 25(OH)D level may be associated with a lowered risk of LUTS. PMID:27164139

  9. Vitamin D: present and future.

    PubMed

    Varsavsky, M; Alonso, G; García-Martín, A

    2014-10-01

    In recent years has been a growing interest by vitamin D, not only for its important role in the bone mineral metabolism, but also by the extra-osseous effects. Most of the scientific societies consider that deposits are sufficient if the serum concentration of 25-OH vitamin D is above 30ng/ml and are considered deficient if levels are below 20ng/ml. The majority of studies found that supplements of calcium plus vitamin D have a positive effect in reducing the risk of fracture and the risk of falls in the elderly, although several specifies that doses should be 700-1.000 IU daily. The treatment of the deficit can be performed with vitamin D2, D3 as well as calcidiol or the active metabolite calcitriol. In certain pathologies also selective vitamin D receptor activators can be used. PMID:24910024

  10. Vitamin D: present and future.

    PubMed

    Varsavsky, M; Alonso, G; García-Martín, A

    2014-10-01

    In recent years has been a growing interest by vitamin D, not only for its important role in the bone mineral metabolism, but also by the extra-osseous effects. Most of the scientific societies consider that deposits are sufficient if the serum concentration of 25-OH vitamin D is above 30ng/ml and are considered deficient if levels are below 20ng/ml. The majority of studies found that supplements of calcium plus vitamin D have a positive effect in reducing the risk of fracture and the risk of falls in the elderly, although several specifies that doses should be 700-1.000 IU daily. The treatment of the deficit can be performed with vitamin D2, D3 as well as calcidiol or the active metabolite calcitriol. In certain pathologies also selective vitamin D receptor activators can be used.

  11. Method evaluation study of a new generation of vitamin D assays

    PubMed Central

    Kriegshäuser, Gernot; Stolba, Robert; Worf, Elfriede; Halwachs-Baumann, Gabriele

    2015-01-01

    Introduction Recently several diagnostic manufacturers have launched new 25-hydroxy-vitamin D (25[OH]D) assays, which are aligned to the National Institute of Standards and Technology (NIST) Standard Reference Materials (SRM) (NIST, Gaithersburg, Maryland). The aim of this study was to compare the performance of one liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, one enzyme linked immunosorbent assay (ELISA), and one recalibrated and previous version of a chemiluminescence immunoassay (CLIA). Material and methods Serum-aliquots of 198 patient samples from routine 25(OH)D analysis were measured by the ClinMass® LC-MS/MS Complete Kit (RECIPE Chemicals + Instruments GmbH, Munich, Germany), the ORGENTEC 25(OH)D3/D2 ELISA (ORGENTEC Diagnostika GmbH, Mainz, Germany), the recalibrated Immunodiagnostic Systems (IDS)-iSYS 25(OH)DS and the previous used IDS-iSYS 25(OH)D CLIA (Immunodiagnostic Systems Ltd, Boldon, United Kingdom). Bland-Altman and Deming regression analyses were calculated for methods comparison of all tested 25(OH)D assays. The LC-MS/MS method was defined as the reference method. Within-run and between-run precision measurements were performed for all methods with three different concentration levels. Results Compared to the LC-MS/MS method, the new IDS-iSYS 25(OH)DS and ORGENTEC 25(OH)D3/D2 assay demonstrated mean relative biases of 16.3% and 17.8%. The IDS-iSYS 25(OH)D assay showed the lowest mean bias of 1.5%. Deming regression analyses of the recalibrated IDS-iSYS 25(OH)DS and the ORGENTEC 25(OH)D3/D2 assay showed proportional differences, when compared to the reference method. All assays showed a within-run and between-run imprecision of ≤ 20% at each of the evaluated concentration levels. Conclusions The evaluated standardized immunoassays and LC-MS/MS are useful methods for measuring 25(OH)D serum-levels in clinical laboratories. PMID:26110032

  12. FGF23 Regulates Bone Mineralization in a 1,25(OH)2 D3 and Klotho-Independent Manner.

    PubMed

    Murali, Sathish Kumar; Roschger, Paul; Zeitz, Ute; Klaushofer, Klaus; Andrukhova, Olena; Erben, Reinhold G

    2016-01-01

    Fibroblast growth factor-23 (Fgf23) is a bone-derived hormone, suppressing phosphate reabsorption and vitamin D hormone (1,25(OH)2 D3 ) production in the kidney. It has long been an enigma why lack of Fgf23 or of Klotho, the coreceptor for Fgf23, leads to severe impairment in bone mineralization despite the presence of hypercalcemia and hyperphosphatemia. Using Fgf23(-/-) or Klotho(-/-) mice together with compound mutant mice lacking both Fgf23 or Klotho and a functioning vitamin D receptor, we show that in Klotho(-/-) mice the mineralization defect is solely driven by 1,25(OH)2 D3 -induced upregulation of the mineralization-inhibiting molecules osteopontin and pyrophosphate in bone. In Fgf23(-/-) mice, the mineralization defect has two components, a 1,25(OH)2 D3 -driven component similar to Klotho(-/-) mice and a component driven by lack of Fgf23, causing additional accumulation of osteopontin. We found that FGF23 regulates osteopontin secretion indirectly by suppressing alkaline phosphatase transcription and phosphate production in osteoblastic cells, acting through FGF receptor-3 in a Klotho-independent manner. Hence, FGF23 secreted from osteocytes may form an autocrine/paracrine feedback loop for the local fine-tuning of bone mineralization.

  13. Genetic Ancestry, Skin Reflectance and Pigmentation Genotypes in Association with Serum Vitamin D Metabolite Balance

    PubMed Central

    Wilson, Robin Taylor; Roff, Alanna N.; Dai, P. Jenny; Fortugno, Tracey; Douds, Jonathan; Chen, Gang; Grove, Gary L.; Nikiforova, Sheila Ongeri; Barnholtz-Sloan, Jill; Frudakis, Tony; Chinchilli, Vernon M.; Hartman, Terryl J.; Demers, Laurence M.; Shriver, Mark D.; Canfield, Victor A.; Cheng, Keith C.

    2012-01-01

    Background Lower serum vitamin D (25(OH)D) among individuals with African ancestry is attributed primarily to skin pigmentation. However, the influence of genetic polymorphisms controlling for skin melanin content has not been investigated. Therefore, we investigated differences in non-summer serum vitamin D metabolites according to self-reported race, genetic ancestry, skin reflectance and key pigmentation genes (SLC45A2 and SLC24A5). Materials and Methods Healthy individuals reporting at least half African American or half European American heritage were frequency matched to one another on age (+/− 2 years) and sex. 176 autosomal ancestry informative markers were used to estimate genetic ancestry. Melanin index was measured by reflectance spectrometry. Serum vitamin D metabolites (25(OH)D3, 25(OH)D2 and 24,25(OH)2D3) were determined by high performance liquid chromatography (HPLC) tandem mass spectrometry. Percent 24,25(OH)2D3 was calculated as a percent of the parent metabolite (25(OH)D3). Stepwise and backward selection regression models were used to identify leading covariates. Results Fifty African Americans and 50 European Americans participated in the study. Compared with SLC24A5 111Thr homozygotes, individuals with the SLC24A5 111Thr/Ala and 111Ala/Ala genotypes had respectively lower levels of 25(OH)D3 (23.0 and 23.8 nmol/L lower, p-dominant=0.007), and percent 24,25(OH)2D3 (4.1 and 5.2 percent lower, p-dominant=0.003), controlling for tanning bed use, vitamin D/fish oil supplement intake, race/ethnicity, and genetic ancestry. Results were similar with melanin index adjustment, and were not confounded by glucocorticoid, oral contraceptive, or statin use. Conclusions The SLC24A5 111Ala allele was associated with lower serum vitamin 25(OH)D3 and lower percent 24,25(OH)2D3, independently from melanin index and West African genetic ancestry. PMID:23525585

  14. Use of vitamin D in clinical practice.

    PubMed

    Cannell, John J; Hollis, Bruce W

    2008-03-01

    The recent discovery--from a meta-analysis of 18 randomized controlled trials--that supplemental cholecalciferol (vitamin D) significantly reduces all-cause mortality emphasizes the medical, ethical, and legal implications of promptly diagnosing and adequately treating vitamin D deficiency. Not only are such deficiencies common, and probably the rule, vitamin D deficiency is implicated in most of the diseases of civilization. Vitamin D's final metabolic product is a potent, pleiotropic, repair and maintenance, seco-steroid hormone that targets more than 200 human genes in a wide variety of tissues, meaning it has as many mechanisms of action as genes it targets. One of the most important genes vitamin D up-regulates is for cathelicidin, a naturally occurring broad-spectrum antibiotic. Natural vitamin D levels, those found in humans living in a sun-rich environment, are between 40-70 ng per ml, levels obtained by few modern humans. Assessing serum 25-hydroxy-vitamin D (25(OH)D) is the only way to make the diagnosis and to assure treatment is adequate and safe. Three treatment modalities exist for vitamin D deficiency: sunlight, artificial ultraviolet B (UVB) radiation, and vitamin D3 supplementation. Treatment of vitamin D deficiency in otherwise healthy patients with 2,000-7,000 IU vitamin D per day should be sufficient to maintain year-round 25(OH)D levels between 40-70 ng per mL. In those with serious illnesses associated with vitamin D deficiency, such as cancer, heart disease, multiple sclerosis, diabetes, autism, and a host of other illnesses, doses should be sufficient to maintain year-round 25(OH)D levels between 55 -70 ng per mL. Vitamin D-deficient patients with serious illness should not only be supplemented more aggressively than the well, they should have more frequent monitoring of serum 25(OH)D and serum calcium. Vitamin D should always be adjuvant treatment in patients with serious illnesses and never replace standard treatment. Theoretically

  15. Histone Deacetylation Mediates the Rejuvenation of Osteoblastogenesis by the Combination of 25(OH)D3 and Parathyroid Hormone in MSCs from Elders

    PubMed Central

    Zhou, Shuanhu; Geng, Shuo; Glowacki, Julie

    2012-01-01

    Vitamin D metabolites are important effectors of bone and mineral homeostasis. Human bone marrow stromal cells (hMSCs) are targets of 1α,25-dihydroxyvitamin D [1α, 25(OH)2D] action to promote their differentiation to osteoblasts. Osteoblastogenesis is also stimulated by 25-hydroxyvitamin D [25(OH)D], an effect that requires conversion to 1α, 25(OH)2D3 by 25-hydroxyvitamin D3 1α-hydroxylase (CYP27B1). These findings support an autocrine/paracrine role of vitamin D metabolism in osteoblastogenesis of hMSCs. In this study, we assessed whether and by what mechanisms osteoblastogenesis could be rejuvenated with hMSCs from elders. First, knockdown studies with VDR-siRNA showed that both the pro-differentiation and anti-proliferative effects of 1α, 25(OH)2D3 required VDR. Second, 100 nM 25(OH)D3 (p<0.01 vs. control, ANOVA) and 100 nM PTH1-34 (p<0.05) significantly stimulated alkaline phosphatase activity (a measure of osteoblastogenesis), with a synergistic effect when combined (p<0.001). Scriptaid, an inhibitor of histone deacetylase, blocked the effect of 25(OH)D3 and PTH on osteoblastogenesis. Scriptaid alone downregulated VDR in hMSCs. These data demonstrate that histone deacetylation is required for the synergistic effect of 25(OH)D3 and PTH on osteoblastogenesis in hMSCs. Both VDR siRNA and Scriptaid dowregulated VDR mRNA and inhibited osteoblastogenesis. Thus, epigenetic regulation of the VDR may be central to rejuvenating osteoblastogenesis in hMSCs from elders. PMID:22982627

  16. Vitamin D2-Enriched Button Mushroom (Agaricus bisporus) Improves Memory in Both Wild Type and APPswe/PS1dE9 Transgenic Mice

    PubMed Central

    Bennett, Louise; Kersaitis, Cindy; Macaulay, Stuart Lance; Münch, Gerald; Niedermayer, Garry; Nigro, Julie; Payne, Matthew; Sheean, Paul; Vallotton, Pascal; Zabaras, Dimitrios; Bird, Michael

    2013-01-01

    Vitamin D deficiency is widespread, affecting over 30% of adult Australians, and increasing up to 80% for at-risk groups including the elderly (age>65). The role for Vitamin D in development of the central nervous system is supported by the association between Vitamin D deficiency and incidence of neurological and psychiatric disorders including Alzheimer’s disease (AD). A reported positive relationship between Vitamin D status and cognitive performance suggests that restoring Vitamin D status might provide a cognitive benefit to those with Vitamin D deficiency. Mushrooms are a rich source of ergosterol, which can be converted to Vitamin D2 by treatment with UV light, presenting a new and convenient dietary source of Vitamin D2. We hypothesised that Vitamin D2-enriched mushrooms (VDM) could prevent the cognitive and pathological abnormalities associated with dementia. Two month old wild type (B6C3) and AD transgenic (APPSwe/PS1dE9) mice were fed a diet either deficient in Vitamin D2 or a diet which was supplemented with VDM, containing 1±0.2 µg/kg (∼54 IU/kg) vitamin D2, for 7 months. Effects of the dietary intervention on memory were assessed pre- and post-feeding. Brain sections were evaluated for amyloid β (Aβ) plaque loads and inflammation biomarkers using immuno-histochemical methods. Plasma vitamin D metabolites, Aβ40, Aβ42, calcium, protein and cholesterol were measured using biochemical assays. Compared with mice on the control diet, VDM-fed wild type and AD transgenic mice displayed improved learning and memory, had significantly reduced amyloid plaque load and glial fibrillary acidic protein, and elevated interleukin-10 in the brain. The results suggest that VDM might provide a dietary source of Vitamin D2 and other bioactives for preventing memory-impairment in dementia. This study supports the need for a randomised clinical trial to determine whether or not VDM consumption can benefit cognitive performance in the wider population. PMID

  17. Effects of UV-C treatment and cold storage on ergosterol and vitamin D2 contents in different parts of white and brown mushroom (Agaricus bisporus).

    PubMed

    Guan, Wenqiang; Zhang, Jie; Yan, Ruixiang; Shao, Suqin; Zhou, Ting; Lei, Jing; Wang, Zhidong

    2016-11-01

    Effects of ultraviolet-C (UV-C) treatment (0.5, 1.0 and 2.0kJ/m(2)) and cold storage on ergosterol and vitamin D2 content in different parts of white and brown button mushrooms (Agaricus bisporus) were investigated. UV-C treatment did not significantly affect ergosterol content in the caps and stems of the two mushrooms, but ergosterol content increased significantly during 14days cold storage. Vitamin D2 content in the caps and stems of two mushrooms significantly increased as UV-C dose increased, and 2.0kJ/m(2) UV-C showed the best result. During cold storage, vitamin D2 content in the caps of the two mushrooms decreased from day 1 to day 7, and then kept stable until day 14, but vitamin D2 content in the stems of brown mushrooms kept increasing for the whole 14days period. UV-C could increase vitamin D2 contents in both caps and stems of white and brown mushrooms without significantly affecting ergosterol content. PMID:27211630

  18. Analysis of Vitamin D2 and Vitamin D3 in Fortified Milk Powders and Infant and Nutritional Formulas by Liquid Chromatography-Tandem Mass Spectrometry: Single-Laboratory Validation, First Action 2016.05.

    PubMed

    Gill, Brendon D; Abernethy, Grant A; Green, Rebecca J; Indyk, Harvey E

    2016-09-01

    A method for the determination of vitamin D2 and vitamin D3 in fortified milk powders and infant and adult nutritional formulas is described. Samples are saponified at high temperature and lipid-soluble components are extracted into isooctane. A portion of the isooctane layer is transferred and washed, and an aliquot of 4-phenyl-1,2,4-triazoline-3,5-dione is added to derivatize the vitamin D to form a high-molecular-mass, easily ionizable adduct. The vitamin D adduct is then re-extracted into a small volume of acetonitrile and analyzed by RPLC. Detection is by tandem MS, using multiple reaction monitoring. Stable isotope-labeled vitamin D2 and vitamin D3 internal standards are used for quantitation to correct for losses in extraction and any variation in derivatization and ionization efficiencies. A single-laboratory validation of the method using AOAC Stakeholder Panel on Infant Formula and Adult Nutritionals (SPIFAN) kit samples was performed and compared with parameters defined according to the vitamin D Standard Method Performance Requirements (SMPR(®)). Linearity was demonstrated over the range specified in the SMPR, with the LOD being estimated at below that required. Method spike recovery (vitamin D2, 97.0-99.2%; and vitamin D3, 96.0-101.0%) and RSDr (vitamin D3, 1.5-5.2%) were evaluated and compared favorably with limits in the vitamin D SMPR. Acceptable bias for vitamin D3 was demonstrated against both the certified value for National Institute of Standards and Technology 1849a Standard Reference material (P(α = 0.05) = 0.25) and AOAC INTERNATIONAL reference method 2002.05 (P(α = 0.05) = 0.09). The method was demonstrated to meet the requirements of the vitamin D SMPR as defined by SPIFAN, and was recently approved for Official First Action status by the AOAC Expert Review Panel on SPIFAN Nutrient Methods. PMID:27461755

  19. Antiproliferative Activity of Double Point Modified Analogs of 1,25-Dihydroxyvitamin D2 Against Human Malignant Melanoma Cell Lines

    PubMed Central

    Piotrowska, Anna; Wierzbicka, Justyna; Nadkarni, Sharmin; Brown, Geoffrey; Kutner, Andrzej; Żmijewski, Michał A.

    2016-01-01

    Vitamin D is a lipid soluble steroid hormone with pleiotropic biological properties, including regulation of cell proliferation, differentiation and apoptosis. As to these desirable anticancer actions, 1,25-dihydroxyvitamins D and analogs have been reported to inhibit the proliferation and to induce differentiation of a wide variety of cancer cell types, including human malignant melanoma. However, there is a need for novel and more efficacious vitamin D analogs, and how best to design such is still an open issue. A series of double point modified (DPM) analogs of 1,25-dihydroxyvitamin D2 (1,25(OH)2D2) induced differentiation of the vitamin D receptor (VDR) positive A375 and VDR negative SK-MEL 188b human malignant melanoma cell lines. Surprisingly, the dose of 1,25(OH)2D2 required to inhibit the proliferation of the A375 melanoma cell line by was several fold lower than that required in the case of 1,25(OH)2D3. To evaluate the impact of the modification in the side chain (additional 22-hydroxyl) and in the A-ring (5,6-trans modification), the regular side-chain of vitamin D2 or D3 was retained in the structure of our analogs. As expected, 5,6-trans modification was advantageous to enhancing the anti-proliferative activity of analogs, but not as a single point modification (SPM). Very unexpectedly, the additional 22-hydroxyl in the side-chain reduced significantly the anti-proliferative activity of both the natural and 5,6-trans series analogs. Finally, an induction of pigmentation in melanoma SK-MEL 188b cells was observed to sensitized cells to the effect of vitamin D analogs. PMID:26760999

  20. Optimal Dose of Vitamin D3 400 I.U. for Average Adults has A Significant Anti-Cancer Effect, While Widely Used 2000 I.U. or Higher Promotes Cancer: Marked Reduction of Taurine & 1α, 25(OH)2D3 Was Found In Various Cancer Tissues and Oral Intake of Optimal Dose of Taurine 175mg for Average Adults, Rather Than 500mg, Was Found to Be A New Potentially Safe and More Effective Method of Cancer Treatment.

    PubMed

    Omura, Yoshiaki; Lu, Dominic; Jones, Marilyn K; Nihrane, Abdallah; Duvvi, Harsha; Yapor, Dario; Shimotsuura, Yasuhiro; Ohki, Motomu

    2016-01-01

    During the past 10 years, the author had found that the optimal dose of Vitamin D3 400 I.U. has safe & effective anticancer effects, while commonly used 2000-5000 I.U. of Vit. D3 often creates a 2-3 time increase in cancer markers. We examined the concentration of Taurine in normal internal organs and in cancer using Bi-Digital O-Ring Test. We found that Taurine levels in normal tissue are 4-6ng. But, the amount of Taurine of average normal value of 5.0-5.25ng was strikingly reduced to 0.0025-0.0028ng in this study of several examples in adenocarcinomas of the esophagus, stomach, pancreas, colon, prostate, and lung, as well as breast cancer. The lowest Taurine levels of 0.0002-0.0005ng were found in so called Zika virus infected babies from Brazil with microcephaly. While Vitamin D3 receptor stimulant 1α, 25 (OH)2D3 in normal tissues was 0.45-0.53ng, they were reduced to 0.025-0.006ng in cancers (1/100th-1/200th of normal value), particularly in various adenocarcinomas. All of these adenocarcinomas had about 1500ng HPV-16 viral infection. In 500 breast cancers, about 97% had HPV-16. The optimal dose of Taurine for average adult has been found to be about 175mg, rather than the widely used 500mg. In addition, since Taurine is markedly reduced to close to 1/1000th-1/2000th of its normal value in these cancer tissues, we examined the effect of the optimal dose of Taurine on cancer patients. Optimal dose of Taurine produced a very significant decrease in cancer-associated parameters, such as Oncogene C-fosAb2 & Integrin α5β1 being reduced to less than 1/1,000th, and 8-OH-dG (which increases in the presence of DNA mutation) reduced to less than 1/10th. The optimal dose of Taurine 175mg for average adult various cancer patient 3 times a day alone provide beneficial effects with very significant anti-cancer effects with strikingly increased urinary excretion of bacteria, viruses, & funguses, asbestos, toxic metals & other toxic substances. However, optimal doses of

  1. Optimal Dose of Vitamin D3 400 I.U. for Average Adults has A Significant Anti-Cancer Effect, While Widely Used 2000 I.U. or Higher Promotes Cancer: Marked Reduction of Taurine & 1α, 25(OH)2D3 Was Found In Various Cancer Tissues and Oral Intake of Optimal Dose of Taurine 175mg for Average Adults, Rather Than 500mg, Was Found to Be A New Potentially Safe and More Effective Method of Cancer Treatment.

    PubMed

    Omura, Yoshiaki; Lu, Dominic; Jones, Marilyn K; Nihrane, Abdallah; Duvvi, Harsha; Yapor, Dario; Shimotsuura, Yasuhiro; Ohki, Motomu

    2016-01-01

    During the past 10 years, the author had found that the optimal dose of Vitamin D3 400 I.U. has safe & effective anticancer effects, while commonly used 2000-5000 I.U. of Vit. D3 often creates a 2-3 time increase in cancer markers. We examined the concentration of Taurine in normal internal organs and in cancer using Bi-Digital O-Ring Test. We found that Taurine levels in normal tissue are 4-6ng. But, the amount of Taurine of average normal value of 5.0-5.25ng was strikingly reduced to 0.0025-0.0028ng in this study of several examples in adenocarcinomas of the esophagus, stomach, pancreas, colon, prostate, and lung, as well as breast cancer. The lowest Taurine levels of 0.0002-0.0005ng were found in so called Zika virus infected babies from Brazil with microcephaly. While Vitamin D3 receptor stimulant 1α, 25 (OH)2D3 in normal tissues was 0.45-0.53ng, they were reduced to 0.025-0.006ng in cancers (1/100th-1/200th of normal value), particularly in various adenocarcinomas. All of these adenocarcinomas had about 1500ng HPV-16 viral infection. In 500 breast cancers, about 97% had HPV-16. The optimal dose of Taurine for average adult has been found to be about 175mg, rather than the widely used 500mg. In addition, since Taurine is markedly reduced to close to 1/1000th-1/2000th of its normal value in these cancer tissues, we examined the effect of the optimal dose of Taurine on cancer patients. Optimal dose of Taurine produced a very significant decrease in cancer-associated parameters, such as Oncogene C-fosAb2 & Integrin α5β1 being reduced to less than 1/1,000th, and 8-OH-dG (which increases in the presence of DNA mutation) reduced to less than 1/10th. The optimal dose of Taurine 175mg for average adult various cancer patient 3 times a day alone provide beneficial effects with very significant anti-cancer effects with strikingly increased urinary excretion of bacteria, viruses, & funguses, asbestos, toxic metals & other toxic substances. However, optimal doses of

  2. TPA decreases 1,25(OH)2D3 binding and calbindin D-28K in renal (MDBK) cells.

    PubMed

    Simboli-Campbell, M; Gagnon, A M; Franks, D J; Welsh, J

    1992-02-01

    The effect of the phorbol ester TPA (12-O-tetradecanoylphorbol 13-acetate) on vitamin D receptors (VDRs) was studied in MDBK cells, a normal bovine renal epithelial cell line. 24 h treatment of MDBK cells with TPA resulted in down-regulation of VDR number, with no change in the binding affinity for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) or approximate molecular weight determined by fast protein liquid chromatography (FPLC). TPA treatment also reduced the level of calbindin D-28K, a vitamin D-dependent renal protein. 4 alpha-Phorbol 12,13-didecanoate (4 alpha-PDD), an inactive phorbol ester, did not affect either 1,25(OH)2D3 binding or calbindin D-28K levels. TPA elicited a significant decrease in membrane-associated protein kinase C (PKC) activity which coincided with the reduction in VDR number and calbindin D-28K. These data support a link between TPA, PKC activity and vitamin D actions in kidney.

  3. Effects of 1α,25-(OH)2D3 on the formation and activity of osteoclasts in RAW264.7 cells.

    PubMed

    Gu, Jianhong; Tong, Xi-Shuai; Chen, Guo-Hong; Wang, Dong; Chen, Yang; Yuan, Yan; Liu, Xue-Zhong; Bian, Jian-Chun; Liu, Zong-Ping

    2015-08-01

    The hormonally active form of vitamin D3, 1α,25-(OH)2D3, has an important role in bone metabolism. This study examined the effects of 1α,25-(OH)2D3 on the ability of two cytokines, receptor activator of nuclear factor-κB ligand (RANKL) and macrophage-colony stimulating factor (M-CSF), to induce RAW 264.7 cells to form osteoclasts. A TRAP histochemical staining assay and bone resorption analysis were used to identify the rate of formation and activity of osteoclasts. The numbers of osteoclasts formed, and their bone resorption activity, was enhanced by the addition of 1α,25-(OH)2D3. The expression levels of osteoclast-specific proteins that are essential for bone resorption, integrin β3, V-ATPase, CAII, CTSK, TRAP and MMP-9, were detected by western blotting. During 48 h, the expression levels of all these proteins significantly increased. Quantitative real-time polymerase chain reaction was used to determine the expression levels of the transcription factors, c-Fos and NFATcl. The expression levels of c-Fos and NFATc1 also increased 24h after treatment with 1α,25-(OH)2D3. These results suggest that 1α,25-(OH)2D3 can regulate bone metabolism by directly enhancing the formation and maturation of osteoclasts.

  4. Vitamin D and inflammation

    PubMed Central

    Cannell, John J; Grant, William B; Holick, Michael F

    2014-01-01

    Several studies found an inverse relationship between 25-hydroxyvitamin D [25(OH)D] and markers of inflammation. A controversy exists as to whether vitamin D lowers inflammation or whether inflammation lowers 25(OH)D concentrations. Certainly 25(OH)D concentrations fall after major surgery. However, is this due to inflammation lowering 25(OH)D or is 25(OH)D being metabolically cleared by the body to quell inflammation. We searched the literature and found 39 randomized controlled trials (RCT) of vitamin D and markers of inflammation. Seventeen found significantly reduced inflammatory markers, 19 did not, one was mixed and one showed adverse results. With few exceptions, studies in normal subjects, obesity, type 2 diabetics, and stable cardiovascular disease did not find significant beneficial effects. However, we found that 6 out of 7 RCTS of vitamin D3 in highly inflammatory conditions (acute infantile congestive heart failure, multiple sclerosis, inflammatory bowel disease, cystic fibrosis, SLE, active TB and evolving myocardial infarction) found significant reductions. We found baseline and final 25(OH)D predicted RCTs with significant reduction in inflammatory markers. Vitamin D tends to modestly lower markers of inflammation in highly inflammatory conditions, when baseline 25(OH)D levels were low and when achieved 25(OH)D levels were higher. Future inquiries should: recruit subjects with low baseline 25(OH)D levels, subjects with elevated markers of inflammation, subjects with inflammatory conditions, achieve adequate final 25(OH)D levels, and use physiological doses of vitamin D. We attempted to identify all extant randomized controlled trials (RCTs) of vitamin D that used inflammatory markers as primary or secondary endpoints. PMID:26413186

  5. Super pharmacological levels of calcitriol (1,25-(OH)2D3) inhibits mineral deposition and decreases cell proliferation in a strain dependent manner in chicken mesenchymal stem cells undergoing osteogenic differentiation in vitro

    PubMed Central

    Pande, Vivek V.; Chousalkar, Kapil C.; Bhanugopan, Marie S.; Quinn, Jane C.

    2015-01-01

    The biologically active form of vitamin D3, calcitriol (1,25-(OH)2D3), plays a key role in mineral homeostasis and bone formation and dietary vitamin D3 deficiency is a major cause of bone disorders in poultry. Supplementary dietary cholecalciferol (25-hydroxyvitamin D, 25-OH), the precursor of calcitriol, is commonly employed to combat this problem; however, dosage must be carefully determined as excess dietary vitamin D can cause toxicity resulting in a decrease in bone calcification, hypercalcinemia and renal failure. Despite much research on the therapeutic administration of dietary vitamin D in humans, the relative sensitivity of avian species to exogenous vitamin D has not been well defined. In order to determine the effects of exogenous 1,25-(OH)2D3 during avian osteogenesis, chicken bone marrow-derived mesenchymal stem cells (BM-MSCs) were exposed to varying doses of 1,25-(OH)2D3 during in vitro osteogenic differentiation and examined for markers of early proliferation and osteogenic induction. Similar to humans and other mammals, poultry BM-MSCs were found to be highly sensitive to exogenous 1,25-(OH)2D3 with super pharmacological levels exerting significant inhibition of mineralization and loss of cell proliferation in vitro. Strain related differences were apparent, with BM-MCSs derived from layers strains showing a higher level of sensitivity to 1,25-(OH)2D3 than those from broilers. These data suggest that understanding species and strain specific sensitivities to 1,25-(OH)2D3 is important for optimizing bone health in the poultry industry and that use of avian BM-MSCs are a useful tool for examining underlying effects of genetic variation in poultry. PMID:26500277

  6. Simultaneous determination of vitamins D2 and D3 by electrospray ionization LC/MS/MS in infant formula and adult nutritionals: First Action 2012.11.

    PubMed

    Gilliland, Donald L; Black, Charles K; Denison, James E; Seipelt, Charles T; Baugh, Steve

    2013-01-01

    A method was developed for the analysis of vitamins D2 and D3 in a variety of nutritional products. To extract vitamins D2 and D3 from products containing substantial amounts of fat, a saponification with alcoholic potassium hydroxide is required to release the vitamin D. Trideuterium-labeled vitamin D is added to the sample prior to saponification, and quantitation is achieved using linear regression of the ratio of peak response for 2H3-D and vitamin D. Acceptable linearity was achieved between 0.6 and 27 microg/100 g with a correlation requirement of >0.999. The method detection limit of 0.02 microg/100 g was verified by spiking placebo products carried through the saponification and extraction steps of the method. At the quantitation limit (0.12 microg/100 g), the signal was easily distinguished from the background. Vitamin D3 spike recoveries ranged from 107 to 119% at the low level and 104 to 116% at the high-level spike. Vitamin D2 recoveries were 105 to 116% and 91 to 110% for the low- and high-level spikes, respectively. SRM 1849a has a certified concentration of 11.1 +/- 1.7 microg/100 g; using this standard reference material, the range of 9.4 to 12.8 microg/100 g was met on each of the 6 days. Method repeatability, determined in 12 vitamin D3 product matrixes over 6 days, ranged from 3.9 to 48%. The adult nutrition-milk protein sample was the most notable; it failed within-day, as well as day-to-day, precision requirements. There was no attempt to optimize the sample preparation to accommodate any problem matrix.

  7. Prodifferentiation Activity of Novel Vitamin D2 Analogs PRI-1916 and PRI-1917 and Their Combinations with a Plant Polyphenol in Acute Myeloid Leukemia Cells

    PubMed Central

    Nachliely, Matan; Sharony, Ehud; Bolla, Narasimha Rao; Kutner, Andrzej; Danilenko, Michael

    2016-01-01

    1α,25-dihydroxyvitamin D3 (1,25D3) is a powerful differentiation inducer for acute myeloid leukemia (AML) cells. However, 1,25D3 doses required for differentiation of AML cells may cause lethal hypercalcemia in vivo. There is evidence that vitamin D2 is less toxic than vitamin D3 in animals. Here, we determined the differentiation effects of novel analogs of 1α,25-dihydroxyvitamin D2 (1,25D2), PRI-1916 and PRI-1917, in which the extended side chains of their previously reported precursors (PRI-1906 and PRI-1907, respectively) underwent further 24Z (24-cis) modification. Using four human AML cell lines representing different stages of myeloid maturation (KG-1a, HL60, U937, and MOLM-13), we found that the potency of PRI-1916 was slightly higher or equal to that of PRI-1906 while PRI-1917 was significantly less potent than PRI-1907. We also demonstrated that 1,25D2 was a less effective differentiation agent than 1,25D3 in these cell lines. Irrespective of their differentiation potency, all the vitamin D2 derivatives tested were less potent than 1,25D3 in transactivating the DR3-type vitamin D response elements. However, similar to 1,25D3, both 1,25D2 and its analogs could strongly cooperate with the plant polyphenol carnosic acid in inducing cell differentiation and inhibition of G1–S cell cycle transition. These results indicate that the 24Z modification has contrasting effects on the differentiation ability of PRI-1906 and PRI-1907 and that the addition of a plant polyphenol could result in a similar extent of cell differentiation induced by different vitamin D compounds. The enhanced antileukemic effects of the tested combinations may constitute the basis for the development of novel approaches for differentiation therapy of AML. PMID:27399677

  8. Serum 25(OH)D Is a 2-Year Predictor of All-Cause Mortality, Cardiac Death and Sudden Cardiac Death in Chest Pain Patients from Northern Argentina

    PubMed Central

    Naesgaard, Patrycja A.; León De La Fuente, Ricardo A.; Nilsen, Stein Tore; Woie, Leik; Aarsland, Torbjoern; Brede, Cato; Staines, Harry; Nilsen, Dennis W. T.

    2012-01-01

    Background Several studies have shown an association between vitamin D deficiency and cardiovascular risk. Vitamin D status is assessed by determination of 25-hydroxyvitamin D [25(OH)D] in serum. Methods We assessed the prognostic utility of 25(OH)D in 982 chest-pain patients with suspected acute coronary syndrome (ACS) from Salta, Northern Argentina. 2-year follow-up data including all-cause mortality, cardiac death and sudden cardiac death were analyzed in quartiles of 25(OH)D, applying univariate and multivariate analysis. Results There were statistically significant changes in seasonal 25(OH)D levels. At follow-up, 119 patients had died. The mean 25(OH)D levels were significantly lower among patients dying than in long-term survivors, both in the total population and in patients with a troponin T (TnT) release (n = 388). When comparing 25(OH)D in the highest quartile to the lowest quartile in a multivariable Cox regression model for all-cause mortality, the hazard ratio (HR) for cardiac death and sudden cardiac death in the total population was 0.37 (95% CI, 0.19–0.73), p = 0.004, 0.23 (95% CI, 0.08–0.67), p = 0.007, and 0.32 (95% CI, 0.11–0.94), p = 0.038, respectively. In patients with TnT release, the respective HR was 0.24 (95% CI, 0.10–0.54), p = 0.001, 0.18 (95% CI, 0.05–0.60), p = 0.006 and 0.25 (95% CI, 0.07–0.89), p = 0.033. 25(OH)D had no prognostic value in patients with no TnT release. Conclusion Vitamin D was shown to be a useful biomarker for prediction of mortality when obtained at admission in chest pain patients with suspected ACS. Trial registration ClinicalTrials.gov NCT01377402 PMID:22970121

  9. Plant Oils as Potential Sources of Vitamin D.

    PubMed

    Baur, Anja C; Brandsch, Corinna; König, Bettina; Hirche, Frank; Stangl, Gabriele I

    2016-01-01

    To combat vitamin D insufficiency in a population, reliable diet sources of vitamin D are required. The recommendations to consume more oily fish and the use of UVB-treated yeast are already applied strategies to address vitamin D insufficiency. This study aimed to elucidate the suitability of plant oils as an alternative vitamin D source. Therefore, plant oils that are commonly used in human nutrition were first analyzed for their content of vitamin D precursors and metabolites. Second, selected oils were exposed to a short-term UVB irradiation to stimulate the synthesis of vitamin D. Finally, to elucidate the efficacy of plant-derived vitamin D to improve the vitamin D status, we fed UVB-exposed wheat germ oil (WGO) for 4 weeks to mice and compared them with mice that received non-exposed or vitamin D3 supplemented WGO. Sterol analysis revealed that the selected plant oils contained high amounts of not only ergosterol but also 7-dehydrocholesterol (7-DHC), with the highest concentrations found in WGO. Exposure to UVB irradiation resulted in a partial conversion of ergosterol and 7-DHC to vitamin D2 and D3 in these oils. Mice fed the UVB-exposed WGO were able to improve their vitamin D status as shown by the rise in the plasma concentration of 25-hydroxyvitamin D [25(OH)D] and the liver content of vitamin D compared with mice fed the non-exposed oil. However, the plasma concentration of 25(OH)D of mice fed the UVB-treated oil did not reach the values observed in the group fed the D3 supplemented oil. It was striking that the intake of the UVB-exposed oil resulted in distinct accumulation of vitamin D2 in the livers of these mice. In conclusion, plant oils, in particular WGO, contain considerable amounts of vitamin D precursors which can be converted to vitamin D via UVB exposure. However, the UVB-exposed WGO was less effective to improve the 25(OH)D plasma concentration than a supplementation with vitamin D3. PMID:27570765

  10. Plant Oils as Potential Sources of Vitamin D

    PubMed Central

    Baur, Anja C.; Brandsch, Corinna; König, Bettina; Hirche, Frank; Stangl, Gabriele I.

    2016-01-01

    To combat vitamin D insufficiency in a population, reliable diet sources of vitamin D are required. The recommendations to consume more oily fish and the use of UVB-treated yeast are already applied strategies to address vitamin D insufficiency. This study aimed to elucidate the suitability of plant oils as an alternative vitamin D source. Therefore, plant oils that are commonly used in human nutrition were first analyzed for their content of vitamin D precursors and metabolites. Second, selected oils were exposed to a short-term UVB irradiation to stimulate the synthesis of vitamin D. Finally, to elucidate the efficacy of plant-derived vitamin D to improve the vitamin D status, we fed UVB-exposed wheat germ oil (WGO) for 4 weeks to mice and compared them with mice that received non-exposed or vitamin D3 supplemented WGO. Sterol analysis revealed that the selected plant oils contained high amounts of not only ergosterol but also 7-dehydrocholesterol (7-DHC), with the highest concentrations found in WGO. Exposure to UVB irradiation resulted in a partial conversion of ergosterol and 7-DHC to vitamin D2 and D3 in these oils. Mice fed the UVB-exposed WGO were able to improve their vitamin D status as shown by the rise in the plasma concentration of 25-hydroxyvitamin D [25(OH)D] and the liver content of vitamin D compared with mice fed the non-exposed oil. However, the plasma concentration of 25(OH)D of mice fed the UVB-treated oil did not reach the values observed in the group fed the D3 supplemented oil. It was striking that the intake of the UVB-exposed oil resulted in distinct accumulation of vitamin D2 in the livers of these mice. In conclusion, plant oils, in particular WGO, contain considerable amounts of vitamin D precursors which can be converted to vitamin D via UVB exposure. However, the UVB-exposed WGO was less effective to improve the 25(OH)D plasma concentration than a supplementation with vitamin D3. PMID:27570765

  11. Simultaneous quantitative analysis of eight vitamin D analogues in milk using liquid chromatography-tandem mass spectrometry.

    PubMed

    Gomes, Fabio P; Shaw, P Nicholas; Whitfield, Karen; Hewavitharana, Amitha K

    2015-09-01

    Milk is an important source of nutrients for various risk populations, including infants. The accurate measurement of vitamin D in milk is necessary to provide adequate supplementation advice for risk groups and to monitor regulatory compliance. Currently used liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods are capable of measuring only four analogues of vitamin D in unfortified milk. We report here an accurate quantitative analytical method for eight analogues of vitamin D: Vitamin D2 and D3 (D2 and D3), 25-hydroxy D2 and D3, 24,25-dihydroxy D2 and D3, and 1,25-dihydroxyD2 and D3. In this study, we compared saponification and protein precipitation for the extraction of vitamin D from milk and found the latter to be more effective. We also optimised the pre-column derivatisation using 4-phenyl-l,2,4-triazoline-3,5-dione (PTAD), to achieve the highest sensitivity and accuracy for all major vitamin D forms in milk. Chromatography was optimised to reduce matrix effects such as ion-suppression, and the matrix effects were eliminated using co-eluting stable isotope labelled internal standards for the calibration of each analogue. The analogues, 25-hydroxyD3 (25(OH)D3) and its epimer (3-epi-25(OH)D3) were chromatographically resolved, to prevent over-estimation of 25(OH)D3. The method was validated and subsequently applied for the measurement of total vitamin D levels in human, cow, mare, goat and sheep milk samples. The detection limits, repeatability standard deviations, and recovery ranges were from 0.2 to 0.4 femtomols, 6.30-13.5%, and 88.2-105%, respectively.

  12. Simultaneous quantitative analysis of eight vitamin D analogues in milk using liquid chromatography-tandem mass spectrometry.

    PubMed

    Gomes, Fabio P; Shaw, P Nicholas; Whitfield, Karen; Hewavitharana, Amitha K

    2015-09-01

    Milk is an important source of nutrients for various risk populations, including infants. The accurate measurement of vitamin D in milk is necessary to provide adequate supplementation advice for risk groups and to monitor regulatory compliance. Currently used liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods are capable of measuring only four analogues of vitamin D in unfortified milk. We report here an accurate quantitative analytical method for eight analogues of vitamin D: Vitamin D2 and D3 (D2 and D3), 25-hydroxy D2 and D3, 24,25-dihydroxy D2 and D3, and 1,25-dihydroxyD2 and D3. In this study, we compared saponification and protein precipitation for the extraction of vitamin D from milk and found the latter to be more effective. We also optimised the pre-column derivatisation using 4-phenyl-l,2,4-triazoline-3,5-dione (PTAD), to achieve the highest sensitivity and accuracy for all major vitamin D forms in milk. Chromatography was optimised to reduce matrix effects such as ion-suppression, and the matrix effects were eliminated using co-eluting stable isotope labelled internal standards for the calibration of each analogue. The analogues, 25-hydroxyD3 (25(OH)D3) and its epimer (3-epi-25(OH)D3) were chromatographically resolved, to prevent over-estimation of 25(OH)D3. The method was validated and subsequently applied for the measurement of total vitamin D levels in human, cow, mare, goat and sheep milk samples. The detection limits, repeatability standard deviations, and recovery ranges were from 0.2 to 0.4 femtomols, 6.30-13.5%, and 88.2-105%, respectively. PMID:26388380

  13. Maternal Vitamin D Levels and the Autism Phenotype among Offspring

    ERIC Educational Resources Information Center

    Whitehouse, Andrew J. O.; Holt, Barbara J.; Serralha, Michael; Holt, Patrick G.; Hart, Prue H.; Kusel, Merci M. H.

    2013-01-01

    We tested whether maternal vitamin D insufficiency during pregnancy is related to the autism phenotype. Serum 25(OH)-vitamin D concentrations of 929 women were measured at 18 weeks' pregnancy. The mothers of the three children with a clinical diagnosis of autism spectrum disorder had 25(OH)-vitamin D concentrations above the population mean.…

  14. Vitamins

    MedlinePlus

    ... and folate) Vitamin C Vitamin D Vitamin E Vitamin K You can usually get all your vitamins from ... foods you eat. Your body can also make vitamins D and K. People who eat a vegetarian diet may need ...

  15. Effects of intramuscular administration of 1α,25(OH)2D3 during skeletal muscle regeneration on regenerative capacity, muscular fibrosis, and angiogenesis.

    PubMed

    Srikuea, Ratchakrit; Hirunsai, Muthita

    2016-06-15

    The recent discovery of the vitamin D receptor (VDR) in regenerating muscle raises the question regarding the action of vitamin D3 on skeletal muscle regeneration. To investigate the action of vitamin D3 on this process, the tibialis anterior muscle of male C57BL/6 mice (10 wk of age) was injected with 1.2% BaCl2 to induce extensive muscle injury. The bioactive form of vitamin D3 [1α,25(OH)2D3] was administered daily via intramuscular injections during the regenerative phase (days 4-7 postinjury). Physiological and supraphysiological doses of 1α,25(OH)2D3 relative to 1 μg/kg muscle wet weight and mouse body weight were investigated. Muscle samples were collected on day 8 postinjury to examine proteins related to vitamin D3 metabolism (VDR, CYP24A1, and CYP27B1), satellite cell differentiation and regenerative muscle fiber formation [myogenin and embryonic myosin heavy chain (EbMHC)], protein synthesis signaling (Akt, p70 S6K1, 4E-BP1, and myostatin), fiber-type composition (fast and slow MHCs), fibrous formation (vimentin), and angiogenesis (CD31). Administration of 1α,25(OH)2D3 at physiological and supraphysiological doses enhanced VDR expression in regenerative muscle. Moreover, CYP24A1 and vimentin expression was increased, accompanying decreased myogenin and EbMHC expression at the supraphysiological dose. However, there was no change in CYP27B1, Akt, p70 S6K1, 4E-BP1, myostatin, fast and slow MHCs, or CD31 expression at any dose investigated. Taken together, administration of 1α,25(OH)2D3 at a supraphysiological dose decreased satellite cell differentiation, delayed regenerative muscle fiber formation, and increased muscular fibrosis. However, protein synthesis signaling, fiber-type composition, and angiogenesis were not affected by either 1α,25(OH)2D3 administration at a physiological or supraphysiological dose. PMID:27032903

  16. Vitamin D3 supplementation increases fibroblast growth factor-23 in HIV-infected youth treated with tenofovir disoproxil fumarate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tenofovir (TDF) is associated with phosphaturia and elevated 1,25 dihydroxy vitamin D (1,25-OH(2)D). Fibroblast growth factor-23 causes phosphaturia and increases in response to elevated 1,25-OH(2)D. Vitamin D binding proetin (VDBP) binds to 1,25-OH(2)D, decreasing biologic activity, and is elevated...

  17. Administration of exogenous 1,25(OH)2D3 normalizes overactivation of the central renin-angiotensin system in 1α(OH)ase knockout mice.

    PubMed

    Zhang, Wei; Chen, Lulu; Zhang, Luqing; Xiao, Ming; Ding, Jiong; Goltzman, David; Miao, Dengshun

    2015-02-19

    Previously, we reported that active vitamin D deficiency in mice causes secondary hypertension and cardiac dysfunction, but the underlying mechanism remains largely unknown. To clarify whether exogenous active vitamin D rescues hypertension by normalizing the altered central renin-angiotensin system (RAS) via an antioxidative stress mechanism, 1-alpha-hydroxylase [1α(OH)ase] knockout mice [1α(OH)ase(-/-)] and their wild-type littermates were fed a normal diet alone or with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], or a high-calcium, high-phosphorus "rescue" diet with or without antioxidant N-acetyl-l-cysteine (NAC) supplementation for 4 weeks. Compared with their wild-type littermates, 1α(OH)ase(-/-)mice had high mean arterial pressure, increased levels of renin, angiotensin II (Ang II), and Ang II type 1 receptor, and increased malondialdehyde levels, but decreased anti-peroxiredoxin I and IV proteins and the antioxidative genes glutathione reductase (Gsr) and glutathione peroxidase 4 (Gpx4) in the brain samples. Except Ang II type 1 receptor, these pathophysiological changes were rescued by exogenous 1,25(OH)2D3 or NAC plus rescue diet, but not by rescue diet alone. We conclude that 1,25(OH)2D3 normalizes the altered central RAS in 1α(OH)ase(-/-)mice, at least partially, through a central antioxidative mechanism.

  18. VITAMIN D STATUS: MEASUREMENT, INTERPRETATION AND CLINICAL APPLICATION

    PubMed Central

    Holick, Michael F.

    2009-01-01

    Vitamin D, the sunshine vitamin, is now recognized not only for its importance of bone health in children and adults, but also for other health benefits including reducing risk of chronic diseases including autoimmune diseases, common cancer and cardiovascular disease. Vitamin D made in the skin or ingested in the diet is biologically inert and requires two successive hydroxylations first in the liver on carbon 25 to form 25-hydroxyvitamin D [25(OH)D], and then in the kidney for a hydroxylation on carbon 1 to form the biologically active form of vitamin D, 1,25-dihydroxyvitamin D [1,25(OH)2D]. With the identification of 25(OH)D and 1,25(OH)2D, methods were developed to measure these metabolites in the circulation. Serum 25(OH)D is the barometer for vitamin D status. Serum 1,25(OH)2D provides no information about vitamin D status and is often normal or even elevated due to secondary hyperparathyroidism associated with vitamin D deficiency. Most experts agree that 25(OH)D of < 20 ng/ml is considered to be vitamin D deficiency whereas a 25(OH)D of 21-29 ng/ml is considered to be insufficient. The goal should be to maintain both children and adults at a level > 30 ng/ml to take full advantage of all the health benefits that vitamin D provides. PMID:18329892

  19. Vitamin D–Binding Protein Modifies the Vitamin D–Bone Mineral Density Relationship

    PubMed Central

    Powe, Camille E; Ricciardi, Catherine; Berg, Anders H; Erdenesanaa, Delger; Collerone, Gina; Ankers, Elizabeth; Wenger, Julia; Karumanchi, S Ananth; Thadhani, Ravi; Bhan, Ishir

    2011-01-01

    Studies examining the relationship between total circulating 25-hydroxyvitamin D [25(OH)D] levels and bone mineral density (BMD) have yielded mixed results. Vitamin D–binding protein (DBP), the major carrier protein for 25(OH)D, may alter the biologic activity of circulating vitamin D. We hypothesized that free and bioavailable 25(OH)D, calculated from total 25(OH)D, DBP, and serum albumin levels, would be more strongly associated with BMD than levels of total 25(OH)D. We measured total 25(OH)D, DBP, and serum albumin levels in 49 healthy young adults enrolled in the Metabolic Abnormalities in College-Aged Students (MACS) study. Lumbar spine BMD was measured in all subjects using dual-energy X-ray absorptiometry. Clinical, diet, and laboratory information also was gathered at this time. We determined free and bioavailable (free + albumin-bound) 25(OH)D using previously validated formulas and examined their associations with BMD. BMD was not associated with total 25(OH)D levels (r = 0.172, p = .236). In contrast, free and bioavailable 25(OH)D levels were positively correlated with BMD (r = 0.413, p = .003 for free, r = 0.441, p = .002 for bioavailable). Bioavailable 25(OH)D levels remained independently associated with BMD in multivariate regression models adjusting for age, sex, body mass index, and race (p = .03). It is concluded that free and bioavailable 25(OH)D are more strongly correlated with BMD than total 25(OH)D. These findings have important implications for vitamin D supplementation in vitamin D–deficient states. Future studies should continue to explore the relationship between free and bioavailable 25(OH)D and health outcomes. © 2011 American Society for Bone and Mineral Research. PMID:21416506

  20. Cholecalciferol(25-[OH]-Vitamin D) in Treating Patients With Colorectal Cancer

    ClinicalTrials.gov

    2014-01-16

    Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage I Colon Cancer; Stage I Rectal Cancer

  1. Association between vitamin D and hepatitis C virus infection: A meta-analysis

    PubMed Central

    Villar, Livia Melo; Del Campo, José Antonio; Ranchal, Isidora; Lampe, Elisabeth; Romero-Gomez, Manuel

    2013-01-01

    AIM: To evaluate the association between 25-hydroxyvitamin D [25(OH)D] and sustained virological response (SVR) in hepatitis C virus (HCV) infected individuals. METHODS: Relevant studies were identified by systematically searching MEDLINE databases up to March 2012 and abstracts of the European and American Congress of Hepatology conducted in 2011. Studies must provide information on SVR and the levels of 25(OH)D3 and/or 25(OH)D2 [henceforth referred to as 25(OH)D] in sera samples from HCV infected individuals. The inclusion criteria were: clinical studies that included HCV infected patients aged older than 18 years regardless of HCV genotype or ethnic group; provided information on SVR rates; and were reported in the English language as full papers. Due to the heterogeneity of studies in categorizing serum vitamin D levels, a cut-off value of 30 ng/mL of serum 25(OH)D was used. Heterogeneity was assessed using I2 statistics. The summary odds ratios with their corresponding 95%CI were calculated based on a random-effects model. RESULTS: Overall, 11 studies (8 observational and 3 interventional) involving 1575 individuals were included and 1117 HCV infected individuals (71%) showed low vitamin D levels. Most of the studies included mono-infected HCV individuals with the mean age ranging from 38 to 56 years. Four studies were conducted in human immunodeficiency virus/HCV infected individuals. Regarding vitamin D measurement, most of the studies employed radioimmunoassays (n = 5) followed by chemiluminescence (n = 4) and just one study employed high performance/pressure liquid chromatography (HPLC). Basal vitamin D levels varied from 17 to 43 ng/mL in the studies selected, and most of the HCV infected individuals had genotype 1 (1068/1575) with mean viral load varying from log 4.5-5.9 UI/mL. With regard to HCV treatment, most of the studies (n = 8) included HCV individuals without previous treatment, where the pooled SVR rate was 46.4%. High rates of SVR were observed

  2. Vitamin D: calcium and bone homeostasis during evolution

    PubMed Central

    Bouillon, Roger; Suda, Tatsuo

    2014-01-01

    Vitamin D3 is already found early in the evolution of life but essentially as inactive end products of the photochemical reaction of 7-dehydrocholestol with ultraviolet light B. A full vitamin D (refers to vitamin D2 and D3) endocrine system, characterized by a specific VDR (vitamin D receptor, member of the nuclear receptor family), specific vitamin D metabolizing CYP450 enzymes regulated by calciotropic hormones and a dedicated plasma transport-protein is only found in vertebrates. In the earliest vertebrates (lamprey), vitamin D metabolism and VDR may well have originated from a duplication of a common PRX/VDR ancestor gene as part of a xenobiotic detoxification pathway. The vitamin D endocrine system, however, subsequently became an important regulator of calcium supply for an extensive calcified skeleton. Vitamin D is essential for normal calcium and bone homeostasis as shown by rickets in vitamin D-deficient growing amphibians, reptiles, birds and mammals. From amphibians onward, bone is gradually more dynamic with regulated bone resorption, mainly by combined action of PTH and 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the generation and function of multinucleated osteoclasts. Therefore, bone functions as a large internal calcium reservoir, under the control of osteoclasts. Osteocytes also display a remarkable spectrum of activities, including mechanical sensing and regulating mineral homeostasis, but also have an important role in global nutritional and energy homeostasis. Mineralization from reptiles onward is under the control of well-regulated SIBLING proteins and associated enzymes, nearly all under the control of 1,25(OH)2D3. The vitamin D story thus started as inert molecule but gained an essential role for calcium and bone homeostasis in terrestrial animals to cope with the challenge of higher gravity and calcium-poor environment. PMID:24466411

  3. [Vitamin D dependency and its treatment].

    PubMed

    Kitanaka, Sachiko

    2016-02-01

    Vitamin D dependency is classified to vitamin D-dependent rickets type 1 which shows defective 1,25(OH)(2)D production, and vitamin D-dependent rickets type 2 which shows end-organ unresponsiveness to 1,25(OH)(2)D. Recent advance in the molecular analysis of these diseases revealed variety in the presentation and in the inheritance patterns. Molecular diagnosis would be preferable for adequate therapy especially in type 2.

  4. [Vitamin D dependency and its treatment].

    PubMed

    Kitanaka, Sachiko

    2016-02-01

    Vitamin D dependency is classified to vitamin D-dependent rickets type 1 which shows defective 1,25(OH)(2)D production, and vitamin D-dependent rickets type 2 which shows end-organ unresponsiveness to 1,25(OH)(2)D. Recent advance in the molecular analysis of these diseases revealed variety in the presentation and in the inheritance patterns. Molecular diagnosis would be preferable for adequate therapy especially in type 2. PMID:26813508

  5. 25-hydroxy vitamin D test

    MedlinePlus

    25-OH vitamin D test; Calcidiol; 25-hydroxycholecalciferol test ... if you have too much or too little vitamin D in your blood. ... The normal range of vitamin D is measured as nanograms per milliliter (ng/mL). Many experts recommend a level between 20 and 40 ng/mL. ...

  6. Application of dried blood spots to determine vitamin D status in a large nutritional study with unsupervised sampling: the Food4Me project.

    PubMed

    Hoeller, Ulrich; Baur, Manuela; Roos, Franz F; Brennan, Lorraine; Daniel, Hannelore; Fallaize, Rosalind; Forster, Hannah; Gibney, Eileen R; Gibney, Mike; Godlewska, Magdalena; Hartwig, Kai; Kolossa, Silvia; Lambrinou, Christina P; Livingstone, Katherine M; Lovegrove, Julie A; Macready, Anna L; Manios, Yannis; Marsaux, Cyril F M; Martinez, J Alfredo; Celis-Morales, Carlos; Moschonis, George; Navas-Carretero, Santiago; O'Donovan, Clare B; San-Cristobal, Rodrigo; Saris, Wim H M; Surwiłło, Agnieszka; Traczyk, Iwona; Tsirigoti, Lydia; Walsh, Marianne C; Woolhead, Clara; Mathers, John C; Weber, Peter

    2016-01-28

    An efficient and robust method to measure vitamin D (25-hydroxy vitamin D3 (25(OH)D3) and 25-hydroxy vitamin D2 in dried blood spots (DBS) has been developed and applied in the pan-European multi-centre, internet-based, personalised nutrition intervention study Food4Me. The method includes calibration with blood containing endogenous 25(OH)D3, spotted as DBS and corrected for haematocrit content. The methodology was validated following international standards. The performance characteristics did not reach those of the current gold standard liquid chromatography-MS/MS in plasma for all parameters, but were found to be very suitable for status-level determination under field conditions. DBS sample quality was very high, and 3778 measurements of 25(OH)D3 were obtained from 1465 participants. The study centre and the season within the study centre were very good predictors of 25(OH)D3 levels (P<0·001 for each case). Seasonal effects were modelled by fitting a sine function with a minimum 25(OH)D3 level on 20 January and a maximum on 21 July. The seasonal amplitude varied from centre to centre. The largest difference between winter and summer levels was found in Germany and the smallest in Poland. The model was cross-validated to determine the consistency of the predictions and the performance of the DBS method. The Pearson's correlation between the measured values and the predicted values was r 0·65, and the sd of their differences was 21·2 nmol/l. This includes the analytical variation and the biological variation within subjects. Overall, DBS obtained by unsupervised sampling of the participants at home was a viable methodology for obtaining vitamin D status information in a large nutritional study.

  7. Vitamin D expenditure is not altered in pregnancy and lactation despite changes in vitamin D metabolite concentrations

    PubMed Central

    Jones, Kerry S; Assar, Shima; Prentice, Ann; Schoenmakers, Inez

    2016-01-01

    Pregnancy and lactation are associated with changes in vitamin D and calcium metabolism but the impact of these changes on vitamin D expenditure is unknown. We measured plasma 25(OH)D3 half-life with a stable-isotope tracer and investigated relationships with vitamin D metabolites in pregnant, lactating and ‘non-pregnant, non-lactating’ (NPNL) women. Vitamin D metabolites, vitamin D binding protein (DBP), PTH and 25(OH)D3 half-life were measured in third-trimester pregnant women (n22) and repeated during lactation 12 weeks post-partum (n14) and twice in NPNL women (n23 and n10, respectively) in rural Gambia where calcium intakes are low with little seasonality in UVB-exposure. 25(OH)D3 half-life was not significantly different between groups (mean(SD): 20.6(6.8), 22.6(7.7), 18.0(4.7) and 17.7(9.5) days in pregnant, lactating and NPNL women, respectively). Plasma 25(OH)D3, 1,25(OH)2D, and DBP were higher in pregnancy, and calculated free-25(OH)D3 and PTH were lower (P < 0.05). In lactation, 25(OH)D3 and 24,25(OH)2D3 were lower compared to pregnant (P < 0.001, P = 0.02) and NPNL women (P = 0.04, P = 0.07). Significant associations were observed between half-life and 25(OH)D3 (+ve) in pregnancy, and in all groups between 25(OH)D3 and free-25(OH)D3 (+ve) and PTH and 25(OH)D3 (−ve) (P < 0.0001). These data suggest that adaptive changes in pregnancy and lactation occur that prevent pronounced changes in vitamin D expenditure. PMID:27222109

  8. Vitamin D Bioavailability and Catabolism in Pediatric Chronic Kidney Disease

    PubMed Central

    Denburg, Michelle R.; Kalkwarf, Heidi J.; de Boer, Ian H.; Hewison, Martin; Shults, Justine; Zemel, Babette S.; Stokes, David; Foerster, Debbie; Laskin, Benjamin; Ramirez, Anthony; Leonard, Mary B.

    2013-01-01

    Background Vitamin D-binding protein (DBP) and catabolism have not been examined in childhood chronic kidney disease (CKD). Methods Serum vitamin D [25(OH)D, 1,25(OH)2D, 24,25(OH)2D], DBP, intact parathyroid hormone (iPTH), and fibroblast growth factor-23 (FGF23) concentrations were measured in 148 participants with CKD stages 2–5D secondary to congenital anomalies of the kidney/urinary tract (CAKUT), glomerulonephritis (GN), or focal segmental glomerulosclerosis (FSGS). Free and bioavailable 25(OH)D were calculated using total 25(OH)D, albumin and DBP. Results All vitamin D metabolites were lower with more advanced CKD (p<0.001) and glomerular diagnoses (p≤0.002). Among non-dialysis participants, DBP was lower in FSGS vs. other diagnoses (FSGS-dialysis interaction p=0.02). Winter season, older age, FSGS and GN, and higher FGF23 were independently associated with lower free and bioavailable 25(OH)D. Black race was associated with lower total 25(OH)D and DBP, but not free or bioavailable 25(OH)D. 24,25(OH)2D was the vitamin D metabolite most strongly associated with iPTH. Lower 25(OH)D, black race, greater CKD severity, and higher iPTH were independently associated with lower 24,25(OH)2D, while higher FGF23 and GN were associated with greater 24,25(OH)2D. Conclusions Children with CKD exhibit altered catabolism and concentrations of DBP and free and bioavailable 25(OH)D, and there is an important impact of their underlying disease. PMID:23728936

  9. Vitamins

    MedlinePlus

    ... with an illness. Which foods are rich in vitamin C? citrus fruits, like oranges cantaloupe strawberries tomatoes broccoli cabbage kiwi fruit sweet red peppers previous continue Vitamin D No bones about it . . . vitamin D is ...

  10. Seasonal variation in 25(OH)D at Aberdeen (57°N) and bone health indicators--could holidays in the sun and cod liver oil supplements alleviate deficiency?

    PubMed

    Mavroeidi, Alexandra; Aucott, Lorna; Black, Alison J; Fraser, William D; Reid, David M; Macdonald, Helen M

    2013-01-01

    Vitamin D has been linked with many health outcomes. The aim of this longitudinal study, was to assess predictors of seasonal variation of 25-hydroxy-vitamin D (25(OH)D) (including use of supplements and holidays in sunny destinations) at a northerly latitude in the UK (57°N) in relation to bone health indicators. 365 healthy postmenopausal women (mean age 62.0 y (SD 1.4)) had 25(OH)D measurements by immunoassay, serum C-telopeptide (CTX), estimates of sunlight exposure (badges of polysulphone film), information regarding holidays in sunny destinations, and diet (from food diaries, including use of supplements such as cod liver oil (CLO)) at fixed 3-monthly intervals over 15 months (subject retention 88%) with an additional 25(OH)D assessment in spring 2008. Bone mineral density (BMD) at the lumbar spine (LS) and dual hip was measured in autumn 2006 and spring 2007 (Lunar I-DXA). Deficiency prevalence (25(OH)D<25 nmol/L) was reduced in women who went on holiday to sunny destinations 3 months prior to their visit, compared to women who did not go on holidays [5.4% vs. 24.6% in Spring (p<0.001) and 3.8% vs. 25.6% in Winter (p = 0.001), respectively]. Similarly deficiency was lower amongst those who took CLO supplements compared to women that did not consume these supplements [2.0% vs. 23.7% in Spring (p = 0.001) and 4.5% vs. 24.8% in winter (p = 0.005), respectively]. There was no seasonal variation in CTX; 25(OH)D predicted a small proportion (1.8% variation) of LS BMD in spring 2007 [unstandardized β (SE): 0.039 (0.016), p = 0.017]. Seasonal variation of 25(OH)D had little effect on BMD and no effect on CTX. It appears that small increments in vitamin D (e.g. those that can be achieved by cod liver oil supplements of 5 µg/day) are sufficient to ensure that 25(OH)D is above 25 nmol/L for most people throughout the year. Similarly, holidays in sunny destinations show benefit.

  11. Overestimation of the 25(OH)D serum concentration with the automated IDS EIA kit.

    PubMed

    Cavalier, Etienne; Huberty, Véronique; Cormier, Catherine; Souberbielle, Jean-Claude

    2011-02-01

    We have recently observed an increasing number of patients presenting very high serum levels of 25-hydroxyvitamin D [25(OH)D] (> 150 ng/mL), which, in all cases, had been measured with the IDS EIA kit adapted on different "open" automated platforms. We performed a comparison between the IDS EIA kit adapted on two different "open"automated platforms and the DiaSorin RIA. We found a systematic bias (higher levels with the IDS EIA kit) for concentrations more than 50-60 ng/mL that was less obvious when the IDS EIA was used in its manual procedure. We thus suggest to use the IDS EIA kit in its manual procedure rather than to adapt it on an automated platform, and to interpret cautiously a 25(OH)D greater than 100 ng/mL with this kit.

  12. Ion microprobe analysis of bone surface elements: Effects of 1,25(OH)2D3

    SciTech Connect

    Bushinsky, D.A.; Chabala, J.M.; Levi-Setti, R. )

    1989-12-01

    When neonatal mouse calvariae are incubated with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) there is net calcium efflux from the bone into the medium. The effect of this enhanced cell-mediated Ca efflux on the relative concentrations of mineral 23Na, 39K, and 40Ca has not previously been studied. We used an imaging scanning ion microprobe, utilizing secondary ion mass spectrometry, to compare the relative ion concentrations of Na, K, and Ca on the surface, subsurface, and cross-section of cultured bone incubated in the presence of 1,25(OH)2D3 with the ion concentrations in similar regions of bone incubated in unaltered control medium. Changes in mineral ion concentration were correlated with net fluxes of Na, K, and Ca relative to bone. Calvariae incubated in control medium (24 h at pH approximately 7.40) have abundant surface Na and K relative to Ca (Na/Ca, 85 and K/Ca, 68), whereas the subsurface has less Na/Ca (21) and K/Ca (23), and on cross section the ratios of both Na/Ca (2.0) and K/Ca (1.9) decrease further. After incubation with 10(-8) M 1,25(OH)2D3, there is a significant increase in bone surface Na/Ca (154) and K/Ca (141) without a change in these ratios on the subsurface and a small fall in both ratios on cross section. The linear relationship between Na/Ca and K/Ca across the three regions of bone observed in control calvariae did not change with 1,25(OH)2D3 treatment. As determined by flux measurements there is a net efflux of Ca but not Na or K from bone.

  13. Association Between Vitamin D Deficiency and Allergic Diseases

    PubMed Central

    Malinowski, Bartosz; Bergmann, Katarzyna

    2011-01-01

    Vitamin D is important for the regulation of bone and muscle metabolism and other functions in the human body. The hydroxylated forms of vitamin D2 and D3 are the most important, however only 1,25(OH)D2 is a fully active product. This hormone exert its pleiotropic actions via the specific receptor VDR, an important transcription factor. The optimal vitamin D concentration in the blood is >20 ng/mL whereas insufficiency and deficiency are 10-20 ng/mL and <10 ng/mL, respectively. To maintain the optimal vitamin D status the total vitamin D intake in children should be at least 400 IU/day. Several studies have shown the effects of vitamin D on proinflammatory cytokines, regulatory T cells and immune response. Vitamin D is a very important activator of the immune response, and in hypovitaminosis D, T killer cells are not able to fight off serious infections. A negative correlation between IgE and vitamin D concentration and a positive relation between vitamin D and lung function was documented in children and teenagers with asthma. In asthmatic children the vitamin D deficiency is associated with a higher corticosteroid use. Vitamin D supplementation in patients with steroid resistant asthma can potentially increase the glucocorticoid therapeutic response. Recently, a new mediator in allergy pathogenesis was reported - IL-33 and its soluble receptor ST2. IL-33 promotes the Th2 lymphocytes response as well as the activation of both mast cells and eosinophils via the ST2 receptor. “A vitamin is a substance that makes you ill if you don’t eat it.” (Albert Szent-Gyorgyi, Nobel Prize winner in Physiology and Medicine, 1937)

  14. Association Between Vitamin D Deficiency and Allergic Diseases

    PubMed Central

    Malinowski, Bartosz; Bergmann, Katarzyna

    2011-01-01

    Vitamin D is important for the regulation of bone and muscle metabolism and other functions in the human body. The hydroxylated forms of vitamin D2 and D3 are the most important, however only 1,25(OH)D2 is a fully active product. This hormone exert its pleiotropic actions via the specific receptor VDR, an important transcription factor. The optimal vitamin D concentration in the blood is >20 ng/mL whereas insufficiency and deficiency are 10-20 ng/mL and <10 ng/mL, respectively. To maintain the optimal vitamin D status the total vitamin D intake in children should be at least 400 IU/day. Several studies have shown the effects of vitamin D on proinflammatory cytokines, regulatory T cells and immune response. Vitamin D is a very important activator of the immune response, and in hypovitaminosis D, T killer cells are not able to fight off serious infections. A negative correlation between IgE and vitamin D concentration and a positive relation between vitamin D and lung function was documented in children and teenagers with asthma. In asthmatic children the vitamin D deficiency is associated with a higher corticosteroid use. Vitamin D supplementation in patients with steroid resistant asthma can potentially increase the glucocorticoid therapeutic response. Recently, a new mediator in allergy pathogenesis was reported - IL-33 and its soluble receptor ST2. IL-33 promotes the Th2 lymphocytes response as well as the activation of both mast cells and eosinophils via the ST2 receptor. “A vitamin is a substance that makes you ill if you don’t eat it.” (Albert Szent-Gyorgyi, Nobel Prize winner in Physiology and Medicine, 1937) PMID:27683389

  15. Differential response to 1α, 25-dihydroxyvitamin D3 (1α,25(OH)2D3) in non-small cell lung cancer cells with distinct oncogene mutations1

    PubMed Central

    Zhang, Qiuhong; Kanterewicz, Beatriz; Shoemaker, Suzanne; Hu, Qiang; Liu, Song; Atwood, Kristopher; Hershberger, Pamela

    2012-01-01

    We previously demonstrated that non-small cell lung cancer (NSCLC) cells and primary human lung tumors aberrantly express the vitamin D3-catabolizing enzyme, CYP24, and that CYP24 restricts transcriptional regulation and growth control by 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) in NSCLC cells. To ascertain the basis for CYP24 dysregulation, we assembled a panel of cell lines that represent distinct molecular classes of lung cancer: Cell lines were selected which harbored mutually exclusive mutations in either the K-ras or the Epidermal Growth Factor Receptor (EGFR) genes. We observed that K-ras mutant lines displayed a basal vitamin D receptor (VDR)lowCYP24high phenotype, whereas EGFR mutant lines had a VDRhighCYP24low phenotype. A mutation-associated difference in CYP24 expression was also observed in clinical specimens. Specifically, K-ras mutation was associated with a median 4.2-fold increase in CYP24 mRNA expression (p = 4.8 × 10−7) compared to EGFR mutation in a series of 147 primary lung adenocarcinoma cases. Because of their differential basal expression of VDR and CYP24, we hypothesized that NSCLC cells with an EGFR mutation would be more responsive to 1,25(OH)2D3 treatment than those with a K-ras mutation. To test this, we measured the ability of 1,25(OH)2D3 to increase reporter gene activity, induce transcription of endogenous target genes, and suppress colony formation. In each assay, the extent of 1,25(OH)2D3 response was greater in EGFR mutation-positive HCC827 and H1975 cells than in K-ras mutation-positive A549 and 128.88T cells. We subsequently examined the effect of combining 1,25(OH)2D3 with erlotinib, which is used clinically in the treatment of EGFR mutation-positive NSCLC. 1,25(OH)2D3/erlotinib combination resulted in significantly greater growth inhibition than either single agent in both the erlotinib-sensitive HCC827 cell line and the erlotinib-resistant H1975 cell line. These data are the first to suggest that EGFR mutations may

  16. Histochemical examination of the effects of high-dose 1,25(OH)2D3 on bone remodeling in young growing rats.

    PubMed

    Sun, Jing; Sun, Bao; Wang, Wei; Han, Xiuchun; Liu, Hongrui; Du, Juan; Feng, Wei; Liu, Bo; Amizuka, Norio; Li, Minqi

    2016-08-01

    Vitamin D has an anabolic effect on bone developmental processes and is involved in maintaining skeletal integrity. In recent years, pediatric cases of vitamin D intoxication have attracted attention. Therefore, the aim of this study was to investigate the influence of long-term administration of physiologically-high-dose calcitriol (1,25(OH)2D3) on bone remodeling in young developing rats. Neonatal rats received once-daily subcutaneous injection of calcitriol (250 ng/kg body weight), or PBS only as a control, for 3 weeks. At 1, 2 and 4 weeks' post-administration, rats were sacrificed and fixed by transcardial perfusion with 4 % paraformaldehyde, following which tibiae were extracted for histochemical analysis. Compared with the control group, the number of tartrate-resistant acid phosphatase- and Cathepsin K-positive osteoclasts were significantly increased, and the expression of alkaline phosphatase in osteoblasts was decreased in trabecular bone of rats administered high-dose 1,25(OH)2D3, leading to decreased trabecular bone volume. In addition, the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) was increased, while that of osteoprotegerin was weaker in osteoblasts in the experimental group compared with the control group. Moreover, there was weaker immunoreactivity for EphrinB2 in osteoclasts and EphB4 in osteoblasts of trabecular bone in the experimental group compared with the control group. These findings suggest that long-term use of physiologically-high dose calcitriol may result in bone loss through RANKL/RANK/osteoprotegerin and EphrinB2-EphB4 signaling pathways, and that these negative effects could continue after drug withdrawal. Therefore, optimal limits for vitamin D administration need to be established for children and adolescents. PMID:27255234

  17. Vitamins

    MedlinePlus

    ... Vitamin C , also called ascorbic acid, is an antioxidant that promotes healthy teeth and gums. It helps ... of calcium and phosphorus . Vitamin E is an antioxidant also known as tocopherol. It helps the body ...

  18. Development and comparison of three liquid chromatography-atmospheric pressure chemical ionization/mass spectrometry methods for determining vitamin D metabolites in human serum.

    PubMed

    Bedner, Mary; Phinney, Karen W

    2012-06-01

    Liquid chromatographic methods with atmospheric pressure chemical ionization mass spectrometry were developed for the determination of the vitamin D metabolites 25-hydroxyvitamin D₂ (25(OH)D₂), 25-hydroxyvitamin D₃ (25(OH)D₃), and 3-epi-25-hydroxyvitamin-D₃ (3-epi-25(OH)D₃) in the four Levels of SRM 972, Vitamin D in Human Serum. One method utilized a C18 column, which separates 25(OH)D₂ and 25(OH)D₃, and one method utilized a CN column that also resolves the diastereomers 25(OH)D₃ and 3-epi-25(OH)D₃. Both methods utilized stable isotope labeled internal standards for quantitation of 25(OH)D₂ and 25(OH)D₃. These methods were subsequently used to evaluate SRM 909c Human Serum, and 25(OH)D₃ was the only vitamin D metabolite detected in this material. However, SRM 909c samples contained matrix peaks that interfered with the determination of the [²H₆]-25(OH)D₃ peak area. The chromatographic conditions for the C18 column were modified to remove this interference, but conditions that separated the matrix peaks from [²H₆]-25(OH)D₃ on the CN column could not be identified. The alternate internal standard [²H₃]-25(OH)D₃ did not suffer from matrix interferences and was used for quantitation of 25(OH)D₃ in SRM 909c. During the evaluation of SRM 909c samples, a third method was developed using a pentafluorophenylpropyl column that also separates the diastereomers 25(OH)D₃ and 3-epi-25(OH)D₃. The 25(OH)D₃ was measured in SRM 909c using all three methods, and the results were compared.

  19. Defective female reproductive function in 1,25(OH)2D-deficient mice results from indirect effect mediated by extracellular calcium and/or phosphorus.

    PubMed

    Sun, Weiwei; Xie, Hui; Ji, Ji; Zhou, Xiaojie; Goltzman, David; Miao, Dengshun

    2010-12-01

    We used mice with targeted deletion of 25-hydroxyvitamin D 1α-hydroxylase [1α(OH)ase(-/-)] to investigate the effects of calcium and phosphorus on defects in the reproductive system of 1,25-dihydroxyvitamin D [1,25(OH)(2)D]-deficient female mice. The 1α(OH)ase(-/-) mice and their wild-type littermates were fed either a normal diet or a rescue diet (high calcium, phosphate, and lactose) starting from weaning until 3 mo of age. We then determined serum calcium and phosphorus levels, assessed gonadotropin and gonadal hormone production, and evaluated folliculogenesis, corpus luteum formation, ovarian angiogenesis, uterus development, and fertility. Results showed that hypocalcemic and hypophosphatemic female 1α(OH)ase(-/-) mice developed infertility accompanied by decreased estrogen and progestogen levels, elevated follicle-stimulating hormone and luteinizing hormone levels, defects in follicular development and corpus luteum formation, uterine hypoplasia, and decreased ovarian expression of angiogenic factors including vascular endothelial growth factor (VEGF), angiopoietin-1 and -2, and Tie-2. When serum calcium and phosphorus were normalized by the rescue diet, the defective reproductive phenotype in the female 1α(OH)ase(-/-) mice, including the dysfunction in the hypothalamic-pituitary-ovarian axis, and ovarian angiogenesis were reversed. These results indicate that the infertility seen in 1,25(OH)(2)D-deficient mice is not a direct effect of active vitamin D deficiency on the reproductive system but is an indirect effect mediated by extracellular calcium and phosphorus.

  20. Vitamin D in pregnancy at high latitude in Scotland.

    PubMed

    Haggarty, Paul; Campbell, Doris M; Knox, Susan; Horgan, Graham W; Hoad, Gwen; Boulton, Emma; McNeill, Geraldine; Wallace, Alan M

    2013-03-14

    The aims of the present study were to determine compliance with current advice on vitamin D and to assess the influence of season, dietary intake, supplement use and deprivation on vitamin D status in pregnant mothers and newborns in the north of Scotland where sunlight exposure is low. Pregnant women (n 1205) and their singleton newborns were studied in the Aberdeen Maternity Hospital (latitude 57°N) between 2000 and 2006. Plasma 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 were measured at 19 weeks of gestation in mothers and at delivery in newborns. During pregnancy, 21·0 (95 % CI 18·5, 23·5) % of women took vitamin D supplements. The median intake was 5 μg/d and only 0·6 (95 % CI 0·1, 1·0) % took the recommended 10 μg/d. Supplement use, adjusted for season, dietary intake and deprivation, significantly increased maternal 25-hydroxyvitamin D (25(OH)D) by 10·5 (95 % CI 5·7, 15·2) nmol/l (P< 0·001); however, there was no significant effect on cord 25(OH)D (1·4 (95 % CI - 1·8, 4·5) nmol/l). The biggest influence on both maternal and cord 25(OH)D was season of birth (P< 0·001). Compared with the least deprived women (top three deciles), the most deprived pregnancies (bottom three deciles) were characterised by a significantly lower seasonally adjusted 25(OH)D ( - 11·6 (95 % CI - 7·5, - 15·7) nmol/l in the mother and - 5·8 (95 % CI - 2·3, - 9·4) nmol/l in the cord), and a lower level of supplement use (10 (95 % CI 4, 17) v. 23 (95 % CI 20, 26) %). More should be done to promote vitamin D supplement use in pregnancy but the critical importance of endogenous vitamin D synthesis, and known adaptations of fat metabolism specific to pregnancy, suggest that safe sun advice may be a useful additional strategy, even at high latitude.

  1. Single high-dose vitamin D at birth corrects vitamin D deficiency in infants in Mexico.

    PubMed

    Moodley, Amaran; Spector, Stephen A

    2015-05-01

    This study examined the prevalence of vitamin D deficiency in mothers and infants in Tijuana, Mexico and determined the effect of a single oral dose of 50,000 IU vitamin D3 at birth on 25-hydroxyvitamin D (25[OH]D) levels during infancy. Healthy infants were randomized to receive vitamin D3 or placebo at birth. At birth 23% of infants were vitamin D deficient and 77% had vitamin D insufficiency (mean 25[OH]D level 18.9 ng/ml); 10% of mothers were vitamin D deficient and 61% were insufficient. Infants receiving vitamin D3 had higher 25(OH)D levels at two months (N = 29; 33.9 versus 24.2 ng/ml) and six months (N = 21; 36.5 versus 27.4 ng/ml). Exclusively breastfed infants had lower 25(OH)D levels at two months (14.9 versus 33.4 ng/ml). Vitamin D deficiency is common in infants and mothers in Tijuana, Mexico. A single dose of vitamin D3 at birth was safe and significantly increased 25(OH)D levels during infancy.

  2. Vitamin D, steroid hormones, and autoimmunity.

    PubMed

    Cutolo, Maurizio; Paolino, Sabrina; Sulli, Alberto; Smith, Vanessa; Pizzorni, Carmen; Seriolo, Bruno

    2014-05-01

    The endogenous serum metabolite of vitamin D (calcitriol, 1,25(OH)2 D3 ) is considered a true steroid hormone (D hormone), and like glucocorticoids (GCs) and gonadal hormones, may exert several immunomodulatory activities. Serum vitamin D deficiency (25(OH) D), and therefore reduced 1,25(OH)2 D3 availability, is considered a risk factor for several chronic/inflammatory or autoimmune conditions, including infectious diseases, type 1 diabetes, multiple sclerosis, and especially autoimmune rheumatic diseases (ARD). In ARD in particular, 1,25(OH)2 D3 regulates both innate and adaptive immunity, potentiating the innate response (antimicrobial activity) but reducing adaptive immunity (antigen presentation, T and B cell activities). Regarding a possible synergism between vitamin D and GCs, several studies show that 1,25(OH)2 D3 has significant additive effects on dexamethasone-mediated inhibition of human lymphocyte and monocyte proliferation. Conversely, vitamin D deficiency seems to play a role in increasing autoantibody production by B cells, and seasonal vitamin D declines may trigger flares in ARD, as recently shown. Finally, 1,25(OH)2 D3 seems to reduce aromatase activity and limit the negative effects related to increased peripheral estrogen metabolism (cell proliferation, B cell overactivity).

  3. Vitamin D Status of College Students: Implications for Health Leaders

    ERIC Educational Resources Information Center

    Cress, Eileen McKenna

    2014-01-01

    Vitamin D deficiency is considered to be a pandemic with implications for compromised bone health and other chronic diseases. Few studies have examined vitamin D status in college-aged individuals where prevention of future health consequences is still possible. Serum vitamin D 25(OH)D status and vitamin D intake were examined in 98 college…

  4. Association between vitamin D metabolites in fat tissue and serum 25-hydroxy vitamin D in overweight and obese adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cholecalciferol has been measured in human white adipose tissue (WAT), but little is known about the relationship between the other circulating vitamin D metabolites and WAT. We measured concentrations of 25(OH)D and 1,25(OH)2D in subcutaneous fat tissue from 20 overweight and obese subjects partic...

  5. Effects of 25-(OH)D3 on fecal Ca and P excretion, bone mineralization, Ca and P transporter mRNA expression and performance in growing female pigs.

    PubMed

    Regassa, Alemu; Adhikari, Roshan; Nyachoti, Charles M; Kim, Woo Kyun

    2015-01-01

    A study was conducted to examine the effects of 25-hydroxyvitamin D3 (25-(OH)D3) on fecal Ca and P excretion, bone mineralization, performance and the mRNA expression of intestinal transporter genes in growing female pigs. Sixty-day old gilts (n = 24) with an average initial BW of 23.13 ± 1.49 kg were randomly allocated to a control diet (diet 1) containing wheat/corn/soybean meal and 150 IU kg(-1) of Vitamin D3, diet 1 + 50 μg of 25-(OH)D3 kg(-1) (diet 2) and diet 1 + 100 μg of 25-(OH)D3 kg(-1) (diet 3). The pigs were housed in an individual pen and had ad libitum access to feed and water for 42 days, and BWG and feed intake were measured weekly. Measures of bone mineralization and expression of Ca and P transporters mRNA were analyzed using Dual Energy X-Ray Absortiometry (DEXA) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Data were analyzed using GLM procedure of the Statistical Analysis System (SAS Institute version 9.2). Fecal Ca and P concentration were significantly reduced (P ≤ 0.05) in pigs fed diets 2 and 3 compared with the control diet. Supplementation of 25-(OH)D3 did not significantly improve bone mineralization, animal performance and intestinal transporters mRNA expression except for SLC34A1, a sodium-dependent phosphate transporter 1. In conclusion, supplementation of 25-(OH)D3 in swine nutrition may not improve animal performance but has the potential to reduce environmental pollution by increasing dietary Ca and P retention while reducing their excretion.

  6. How to optimize vitamin D supplementation to prevent cancer, based on cellular adaptation and hydroxylase enzymology.

    PubMed

    Vieth, Reinhold

    2009-09-01

    The question of what makes an 'optimal' vitamin D intake is usually equivalent to, 'what serum 25-hydroxyvitamin D [25(OH)D] do we need to stay above to minimize risk of disease?'. This is a simplistic question that ignores the evidence that fluctuating concentrations of 25(OH)D may in themselves be a problem, even if concentrations do exceed a minimum desirable level. Vitamin D metabolism poses unique problems for the regulation of 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations in the tissues outside the kidney that possess 25(OH)D-1-hydroxylase [CYP27B1] and the catabolic enzyme, 1,25(OH)2D-24-hydroxylase [CYP24]. These enzymes behave according to first-order reaction kinetics. When 25(OH)D declines, the ratio of 1-hydroxylase/24-hydroxylase must increase to maintain tissue 1,25(OH)2D at its set-point level. The mechanisms that regulate this paracrine metabolism are poorly understood. I propose that delay in cellular adaptation, or lag time, in response to fluctuating 25(OH)D concentrations can explain why higher 25(OH)D in regions at high latitude or with low environmental ultraviolet light can be associated with the greater risks reported for prostate and pancreatic cancers. At temperate latitudes, higher summertime 25(OH)D levels are followed by sharper declines in 25(OH)D, causing inappropriately low 1-hydroxylase and high 24-hydroxylase, resulting in tissue 1,25(OH)2D below its ideal set-point. This hypothesis can answer concerns raised by the World Health Organization's International Agency for Research on Cancer about vitamin D and cancer risk. It also explains why higher 25(OH)D concentrations are not good if they fluctuate, and that desirable 25(OH)D concentrations are ones that are both high and stable. PMID:19667164

  7. [Vitamin D insufficiency/deficiency:its clinical significance and treatment].

    PubMed

    Okazaki, Ryo

    2016-02-01

    Vitamin D insufficiency/deficiency, a medical condition in which vitamin D store is decreased, is the most frequent cause of decreased action of vitamin D. Severer form vitamin D deficiency can cause hypocalcemia and rickets/osteomalacia. Milder form vitamin D insufficiency also harms bone health via secondary hyperparathyroidism, the increase in fracture risk, and poor responses to anti-osteoporotic medications. Diagnosis can only be made by measuring serum 25(OH)D, which is not currently covered by the Japanese health insurance policy. In Japan, the guideline for the diagnosis vitamin D insufficiency/deficiency is in the process of drafting. According to the current provisional guideline draft that was made in public, vitamin D deficiency would be defined by serum 25(OH)D level less than 20 ng/mL whereas vitamin D insufficiency would refer to the state in which serum 25(OH)D level is between 20 and 30 ng/mL.

  8. Serum vitamin D, vitamin D binding protein, and lung cancer survival

    PubMed Central

    Anic, Gabriella M.; Weinstein, Stephanie J.; Mondul, Alison M.; Männistö, Satu; Albanes, Demetrius

    2014-01-01

    Objectives Vitamin D may prolong cancer survival by inhibiting tumor progression and metastasis, however, there are limited epidemiologic studies regarding the association between circulating 25-hydroxyvitamin D (25(OH)D) and lung cancer survival. The aim of this study was to examine the relationship between serum 25(OH)D and lung cancer specific survival and to evaluate whether vitamin D binding protein (DBP) concentration modified this association. Materials and Methods 25(OH)D and DBP were measured in fasting serum samples from 500 male lung cancer cases in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for lung cancer related death according to quartiles of season-specific 25(OH)D, DBP, and the molar ratio of 25(OH)D:DBP, a proxy for free circulating 25(OH)D. Results Comparing highest to lowest quartiles, serum 25(OH)D (HR=1.18; 95% CI: 0.89–1.56) and DBP (HR=0.95; 95% CI: 0.71–1.26) were not associated with lung cancer survival and DBP concentration did not modify the association with 25(OH)D (p for interaction=0.56). There was suggestion of an association between higher serum 25(OH)D and better survival from adenocarcinoma (HR=0.64; 95% CI: 0.17–2.45) and small cell carcinoma (HR=0.55; 95% CI: 0.21–1.45), but these estimates were based on a relatively small number of cases. Conclusion Serum 25(OH)D was not associated with overall lung cancer survival regardless of DBP concentration, however, these findings should be examined in other studies that include women and subjects with higher 25(OH)D levels. PMID:25456734

  9. The effects of vitamin D2 or D3 supplementation on glycaemic control and related metabolic parameters in people at risk of type 2 diabetes: protocol of a randomised double-blind placebo-controlled trial

    PubMed Central

    2013-01-01

    Background The global prevalence of type 2 diabetes is increasing. Effective strategies to address this public health challenge are currently lacking. A number of epidemiological studies have reported associations between low concentrations of 25-hydroxy vitamin D and the incidence of diabetes, but a causal link has not been established. We investigate the effect of vitamin D supplementation on the metabolic status of individuals at increased risk of developing type 2 diabetes. Methods/design In a randomised double-blind placebo-controlled trial individuals identified as having a high risk of type 2 diabetes (non-diabetic hyperglycaemia or positive diabetes risk score) are randomised into one of three groups and given 4 doses of either placebo, or 100,000 IU Vitamin D2 (ergocalciferol) or 100,000 IU Vitamin D3 (cholecalciferol) at monthly intervals. The primary outcome measure is the change in glycated haemoglobin level between baseline and 4 months. Secondary outcome measures include blood pressure, lipid levels, apolipoproteins, highly sensitive C-reactive protein, parathyroid hormone (PTH) and safety of supplementation. and C-reactive protein. The trial is being conducted at two sites (London and Cambridge, U.K.) and a total of 342 participants are being recruited. Discussion Trial data examining whether supplementation of vitamin D improves glycaemic status and other metabolic parameters in people at risk of developing type 2 diabetes are sparse. This trial will evaluate the causal role of vitamin D in hyperglycaemia and risk of type 2 diabetes. Specific features of this trial include recruitment of participants from different ethnic groups, investigation of the relative effectiveness and safety of vitamin D2 and D3 and an evidence based approach to determination of the dose of supplementation. Trial registration EudraCT2009-011264-11; ISRCTN86515510 PMID:24152375

  10. [Vitamin D, determinant of bone and extrabone health. Importance of vitamin D supplementation in milk and dairy products].

    PubMed

    Navarro Valverde, Cristina; Quesada Gómez, José Manuel

    2015-04-07

    Vitamin D is obtained mainly from ultraviolet irradiation of 7-dehydrocholesterol in the skin to form cholecalciferol (vitamin D3), and minimally from diet, unless vitamin D fortified food is taken, mainly enriched milk. In some countries, vitamin D is added to diet as ergocalciferol (vitamin D2). In the liver, vitamin D3 is hydroxylated to form 25-hydroxyvitamin D3 (marker of body nutritional status of vitamin D). Subsequently, in the kidney, 25OHD3 is hydroxylated to form 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). By VDR stimulation, (1,25)OH)2D3 controls calcium homeostasis and bone health and, what is more, many other cells and tissues including skin, muscle, cardiovascular and immune systems as well as glucose homeostasis. Thus, about 3% of the human genome is regulated by this hormone. Association and recent intervention studies describe beneficial effects on bone, cardiovascular disease, hypertension, diabetes mellitus type 2,colorectal cancer, breast cancer, multiple sclerosis, immune function inflammation etc. A minimum target for public health should be to achieve serum 25OHD levels above 20 ng/ml to ensure optimum status for bone health. However, levels above 30 ng/ml should be reached to achieve other health goals. Paradoxically, inadequacy (or even deficiency) in vitamin D levels is highly prevalent in children and youth in Spain. This deficit persists in adults, as well as in postmenopausal women (osteoporotic or not) and the elderly (especially amongst those institutionalized). Seasonal variation barely normalizes serum 25OHD levels after summer-autumn. Treated postmenopausal osteoporotic women also show high prevalence of inadequate levels of vitamin D, a major contributor to antiresortive treatments failure. A normalization of serum vitamin D enables diet to provide the calcium necessary to achieve a good bone health and an adequate response to antiresortive drugs. Given the difficulty to get adequate levels of vitamin D by UV irradiation and diet, a

  11. Vitamin D insufficiency in internal medicine residents.

    PubMed

    Haney, E M; Stadler, D; Bliziotes, M M

    2005-01-01

    Medical residents may be vulnerable to low vitamin D status because of long work hours and lack of sun exposure. We conducted a prospective cohort study to measure serum 25-hydroxyvitamin D concentrations among internal medicine residents, document seasonal variation in vitamin D status, and assess risk factors for inadequate vitamin D stores. Dietary intake of calcium and vitamin D, lifestyle characteristics, and serum concentrations of 25(OH)-vitamin D and intact parathyroid hormone (iPTH) were measured in 35 resident volunteers before and after the winter season. A total of 63-69% of medical residents consumed <400 IU/day of vitamin D; 61-67% consumed <1000 mg/day of calcium. Twenty-five (74%) had lower serum 25(OH)-vitamin D concentrations and 23 (68%) had higher serum iPTH in the spring than in the fall. Nine (26%) residents had serum concentrations of 25(OH)-vitamin D of <20 ng/mL in the fall; and sixteen (47%) in the spring. Seven residents (20%) had serum concentrations of 25(OH)-vitamin D of <20 ng/mL at both time-periods; Eighteen residents (51.4%) had 25(OH)-vitamin D levels of <20 ng/mL for at least one of the time-periods. Medical residents are at risk for hypovitaminosis D, particularly during the winter months and should be aware of the need to supplement their vitamin D stores. Insufficient vitamin D status and inadequate vitamin D intake may have long-term implications for bone health in these individuals. Increased educational efforts to promote healthy dietary and lifestyle choices that allow attainment and maintenance of skeletal health are appropriate in this population. PMID:15478001

  12. Vitamin D Deficiency in Pediatric Critical Illness

    PubMed Central

    Hebbar, Kiran B.; Wittkamp, Michael; Alvarez, Jessica A.; McCracken, Courtney E.; Tangpricha, Vin

    2014-01-01

    Introduction The potential role for vitamin D in infection has been well described in adults. The objective of our study was to determine the prevalence of vitamin D insufficiency and to evaluate the relationship between vitamin D status and markers of innate immunity and infection in critically ill children. Hypothesis Vitamin D deficiency was highly prevalent in children with critical illness and correlated with the severity of illness and dysfunction in innate immunity. Methods We performed a prospective clinical observational study with both case and control groups in the pediatric intensive care unit (PICU). Vitamin D status was defined as vitamin D sufficient (25-hydroxyvitamin D (25(OH)D≥ 20 ng/mL), vitamin D insufficient (25(OH)D 10 to 20 ng/mL), and vitamin D deficient (25(OH)D <10 ng/mL). Vitamin D status, severity of illness scores, and cathelicidin, and other clinical data were collected. Results Sixty-one PICU patients and 46 control patients were enrolled. Over 60% of the PICU cases were found to be vitamin D insufficient while less than 1/3 of the controls were insufficient (p < 0.0001). No significant correlation was seen between plasma 25(OH)D and any severity of illness scores. Cases with asthma had a significantly lower median level 25(OH)D (16.9 ng/mL) than cases without asthma (18.7 ng/mL). Over 50% of patients hospitalized during the fall and winter were considered vitamin D deficient or insufficient whereas in the sunnier seasons (spring and summer) the prevalence of vitamin D deficiency/insufficiency decreased to about 30% (p = 0.003). Conclusions The overall finding of profound vitamin D deficiency in the pediatric critical care population is an important finding. Significant seasonal differences were noted even in the critically ill. Certain diseases like asthma in critically ill children merit further study. PMID:25580380

  13. 25-Hydroxyvitamin D Concentration, Vitamin D Intake and Joint Symptoms in Postmenopausal Women

    PubMed Central

    Chlebowski, Rowan T.; Johnson, Karen C.; Lane, Dorothy; Pettinger, Mary; Kooperberg, Charles L.; Wactawski-Wende, Jean; Rohan, Tom; Jo O'Sullivan, Mary; Yasmeen, Shagufta; Hiatt, Robert A.; Shikany, James M.; Vitolins, Mara; Khandekar, Janu; Hubbell, F. Allan

    2010-01-01

    Introduction Low 25 hydroxyvitamin D (25(OH) D) concentrations have been associated with radiologic worsening of osteoarthritis in some reports. However, the results are mixed and few studies have evaluated associations between 25(OH) D concentrations and both total vitamin D intake and clinical joint symptoms. Study Design Cross-sectional analyses of information from a subset of 1993 postmenopausal women obtained at baseline entry in the Women's Health Initiative Calcium plus Vitamin D clinical trial. Main Outcome Measures 25(OH) D concentration, total vitamin D intake (diet plus supplements), presence and severity of joint pain and joint swelling. Results The 25(OH) D levels were commonly low with 53% having deficient (< 50 nmol/L) and only 17% having sufficient (> 72 nmol/L) levels. Joint pain (reported by 74%) and joint swelling (reported by 34%) were also commonly reported. 25(OH) D concentrations were modestly correlated with total vitamin D intake (R =0.29, P<0.0001); however, considerable variability in 25(OH) D concentrations for a given vitamin D intake was seen. In adjusted linear regression models, lower serum 25(OH) D concentrations were associated with higher average joint pain score (P=0.01 for trend) with differences most apparent in the lowest 25(OH) D levels sextile. Conclusions Relatively low 25(OH) D levels and a high frequency of joint symptoms were common in this population of postmenopausal women. Total vitamin D intake was only modestly associated with 25(OH) D. Low serum 25(OH) D concentrations were associated with higher joint pain scores. These findings can inform the design of future intervention trials. PMID:21093181

  14. The First Intervention Study in Elder Self-Neglect: A Randomized Clinical Trial to Improve Vitamin D Levels

    NASA Technical Reports Server (NTRS)

    Burnett, Jason; Hochschild, Ann; Smith, Scott M.; Diamond, Pam; Stotts, Angela; Dyer, Carmel

    2011-01-01

    Despite high mortality rates, elder self-neglect is characterized by refusal of medical and social interventions. To date there have been no tested clinical interventions in elders who self-neglect. Previous research from the TEAM Institute has shown significantly low vitamin D levels in this population. This study aimed to determine the feasibility of a clinical intervention. Replacement of vitamin D was chosen because of its ease of administration and favorable safety profile. Methods: A randomized clinical trial using directly observed therapy of vitamin D was conducted using 50 elders, >65 years of age, with Adult Protective Services (APS) validated self-neglect. A staggered intervention with waiting controls was used to maximize statistical power. One-third (n=17) of the group was administered 50,000 IU vitamin D2 (ergocalciferol) monthly and the remainder (n=33) were administered 400 IU monthly. Serum 25-OH vitamin D was assessed at baseline and 5-months. Results: 69% agreed to participate in the study and of those n=40 (80%) remained at 5-months. At baseline, 12% (n=7) were deficient in vitamin D (<30nmol/L) and approximately 38% (n=22) had inadequate vitamin D levels (<50nmol/L). The baseline 25-OH vitamin D level was 59 nmol/L +25 (mean SD), and increased significantly to 72nmol/L +21 nmol/L at 5-months. Conclusion: These data are the first to provide evidence that clinical interventions are feasible in elders who self-neglect. The increase in vitamin D levels confirmed that the study personnel were able to successfully intervene community-dwelling elders with self-neglect. This study sets the precedent for future intervention and prevention studies

  15. Enhancement of antioxidant properties and increase of content of vitamin D2 and non-volatile components in fresh button mushroom, Agaricus bisporus (higher Basidiomycetes) by γ-irradiation.

    PubMed

    Tsai, Shu-Yao; Mau, Jeng-Leun; Huang, Shih-Jeng

    2014-01-01

    Agaricus bisporus is a popular culinary-medicinal mushroom in Taiwan, and γ-irradiation could extend its shelf life. Our objective was to study the content of vitamin D2 and the taste components and antioxidant properties of ethanolic extracts from A. bisporus with various doses of γ-irradiation. After irradiation, the vitamin D2 content of 5-10 kGy irradiated mushrooms was in the range of 5.22-7.90 µg/g, higher than that of the unirradiated control (2.24 µg/g). For all treatments, the total content of soluble sugars and polyols ranged from 113 to 142 mg/g, and the monosodium glutamate-like components ranged from 6.57 to 13.50 mg/g, among which the 2.5 kGy irradiated sample has the highest content of flavor 5'-nucleotide. About antioxidant properties, 10 kGy irradiated samples exhibited lower EC50 values than did other samples. EC50 values were less than 5 mg/mL for ethanolic extracts. Total phenols were the major antioxidant components and the total content was 13.24-22.78 mg gallic acid equivalents/g. Based on the results obtained, γ-irradiation could be used to improve the vitamin D2 content and intensity of umami taste in fresh mushrooms. In addition, γ-irradiation not only maintained the antioxidant properties of mushrooms but also enhanced the antioxidant properties to some extent.

  16. A closer look at evolution: Variants (SNPs) of genes involved in skin pigmentation, including EXOC2, TYR, TYRP1, and DCT, are associated with 25(OH)D serum concentration.

    PubMed

    Saternus, Roman; Pilz, Stefan; Gräber, Stefan; Kleber, Marcus; März, Winfried; Vogt, Thomas; Reichrath, Jörg

    2015-01-01

    Vitamin D deficiency is common in the Caucasian population and is associated with increased incidence and unfavorable outcome of many diseases, including various types of cancer, infectious, cardiovascular, and autoimmune diseases. Individual factors that predispose for a person's vitamin D status, such as skin type, have been identified, but limited data exist on genetic determinants of serum 25-hydroxyvitamin D (25[OH]D) concentration. We have tested the hypothesis that variants of genes (single nucleotide polymorphisms [SNPs]) involved in skin pigmentation are predictive of serum 25(OH)D levels. Serum 25(OH)D and SNPs (n = 960) related to genes with relevance for skin pigmentation (tyrosinase [TYR], TYR-related protein 1 [TYRP1], dopachrome tautomerase [DCT], oculocutaneous albinism II [OCA2], two pore segment channel 2 [TPCN2], solute carrier family 24 A4 [SLC24A4], solute carrier family 45 A2 [SLC45A2], agouti signalling peptide [ASIP], cyclic AMP-dependent transcription factor [ATF1], microphthalmia-associated transcription factor [MITF], proopiomelanocortin [POMC], cAMP-dependent protein kinase catalytic subunit beta [PRKACB], cAMP-dependent protein kinase catalytic subunit gamma [PRKACG], cAMP-dependent protein kinase type I-alpha regulatory subunit [PRKAR1A], cAMP-dependent protein kinase type II-alpha regulatory subunit [PRKAR2A], cAMP-dependent protein kinase type II-beta regulatory subunit [PRKAR2B], tubulin beta-3 chain/melanocortin receptor 1 [TUBB3/MC1R], Cadherin-1 [CDH1], catenin beta 1 [CTNNB1], Endothelin 1 [EDN1], endothelin 3 [EDN3], endothelin receptor type B [EDNRB], fibroblast growth factor 2 [FGF2], KIT, KIT ligand [KITLG], nerve growth factor [NGF], interferon regulatory factor 4 [IRF4], exocyst complex component 2 [EXOC2], and tumor protein 53 [TP53]) were analyzed in a cohort of participants of the Ludwigshafen Risk and Cardiovascular Health Study (n = 2970). A total of 46 SNPs were associated (P <.05) with lower or higher serum 25(OH

  17. A closer look at evolution: Variants (SNPs) of genes involved in skin pigmentation, including EXOC2, TYR, TYRP1, and DCT, are associated with 25(OH)D serum concentration.

    PubMed

    Saternus, Roman; Pilz, Stefan; Gräber, Stefan; Kleber, Marcus; März, Winfried; Vogt, Thomas; Reichrath, Jörg

    2015-01-01

    Vitamin D deficiency is common in the Caucasian population and is associated with increased incidence and unfavorable outcome of many diseases, including various types of cancer, infectious, cardiovascular, and autoimmune diseases. Individual factors that predispose for a person's vitamin D status, such as skin type, have been identified, but limited data exist on genetic determinants of serum 25-hydroxyvitamin D (25[OH]D) concentration. We have tested the hypothesis that variants of genes (single nucleotide polymorphisms [SNPs]) involved in skin pigmentation are predictive of serum 25(OH)D levels. Serum 25(OH)D and SNPs (n = 960) related to genes with relevance for skin pigmentation (tyrosinase [TYR], TYR-related protein 1 [TYRP1], dopachrome tautomerase [DCT], oculocutaneous albinism II [OCA2], two pore segment channel 2 [TPCN2], solute carrier family 24 A4 [SLC24A4], solute carrier family 45 A2 [SLC45A2], agouti signalling peptide [ASIP], cyclic AMP-dependent transcription factor [ATF1], microphthalmia-associated transcription factor [MITF], proopiomelanocortin [POMC], cAMP-dependent protein kinase catalytic subunit beta [PRKACB], cAMP-dependent protein kinase catalytic subunit gamma [PRKACG], cAMP-dependent protein kinase type I-alpha regulatory subunit [PRKAR1A], cAMP-dependent protein kinase type II-alpha regulatory subunit [PRKAR2A], cAMP-dependent protein kinase type II-beta regulatory subunit [PRKAR2B], tubulin beta-3 chain/melanocortin receptor 1 [TUBB3/MC1R], Cadherin-1 [CDH1], catenin beta 1 [CTNNB1], Endothelin 1 [EDN1], endothelin 3 [EDN3], endothelin receptor type B [EDNRB], fibroblast growth factor 2 [FGF2], KIT, KIT ligand [KITLG], nerve growth factor [NGF], interferon regulatory factor 4 [IRF4], exocyst complex component 2 [EXOC2], and tumor protein 53 [TP53]) were analyzed in a cohort of participants of the Ludwigshafen Risk and Cardiovascular Health Study (n = 2970). A total of 46 SNPs were associated (P <.05) with lower or higher serum 25(OH

  18. Vitamin D3 metabolism in dogs.

    PubMed

    Hazewinkel, H A W; Tryfonidou, M A

    2002-11-29

    Plasma concentrations of the main vitamin D(3) metabolites (i.e., 25(OH)D(3), 1,25(OH)(2)D(3), and 24,25(OH)(2)D(3)) were measured in 14 weeks old large- and small-breed dogs (adult body weight 60 kg vs. 6 kg), raised under the same conditions. Levels of 25(OH)D(3) (approx. 22 microg/l) and 1,25(OH)(2)D(3) (approx. 40 ng/l) were similar in both groups, whereas plasma 24,25(OH)(2)D(3) concentrations were lower in large-breed dogs (7 microg/l vs. 70 microg/l, large- vs. small-breed dogs, respectively). The lower plasma 24,25(OH)(2)D(3) concentrations could be explained by the higher plasma GH and IGF-I concentrations in the large- vs. small-breed dogs, and these hormones are known to suppress 24-hydroxylation. Plasma 24,25(OH)(2)D(3) concentrations increased during Ca supplementation in small-breed but not in large-breed dogs (100 microg/l vs. 7 microg/l, respectively). Hypophosphatemia induced by a high dietary Ca content was only seen together with increased plasma 1,25(OH)(2)D(3) concentrations in euparathyroid dogs and not in hypoparathyroid dogs. Hyperparathyroidism due to Ca deficiency was accompanied by increased plasma 1,25(OH)(2)D(3) concentrations and decreased plasma 24,25(OH)(2)D(3) concentrations in both large- and small-breed dogs, together with generalized osteoporosis. Large-breed pups fed on a standard diet supplemented with Ca and P had decreased plasma concentrations of both 25(OH)D(3) and 1,25(OH)(2)D(3), which may indicate an increased clearance of these metabolites; the low plasma concentrations of the di-hydroxylated vitamin D metabolites were considered responsible for the disturbance in cartilage maturation (i.e., osteochondrosis) in these dogs. Even lower concentrations of all vitamin D(3) metabolites were seen in young dogs raised on a vitamin D(3)-deficient diet, and led to disturbed osteoid and cartilage mineralization (i.e., rickets). These studies indicate that there is a hierarchy of factors regulating vitamin D(3) metabolism in dogs

  19. Vitamin D-binding protein and free vitamin D concentrations in acromegaly.

    PubMed

    Altinova, Alev Eroglu; Ozkan, Cigdem; Akturk, Mujde; Gulbahar, Ozlem; Yalcin, Muhittin; Cakir, Nuri; Toruner, Fusun Balos

    2016-05-01

    Free 25-hydroxyvitamin D [25(OH)D] is suggested to be important in the determination of vitamin D deficiency, since vitamin D-binding protein (VDBP) may affect total 25(OH)D levels. There are no data about free 25(OH)D concentrations in acromegaly. We aimed to investigate serum VDBP and total and free 25(OH)D levels in patients with acromegaly in comparison with control subjects. We recruited 54 patients with acromegaly and 32 control subjects who were similar according to age, gender, and body mass index. Serum VDBP levels were found to be increased in patients with acromegaly compared to control subjects [90.35 (72.45-111.10) vs. 69.52 (63.89-80.13) mg/l, p = 0.001]. There was statistically no significant difference in serum total 25(OH)D levels between the patients with acromegaly and control subjects [18.63 (13.35-27.73) vs. 22.51 (19.20-28.96) ng/ml, p = 0.05]. Free 25(OH)D levels were significantly decreased in patients with acromegaly compared to control subjects [14.55 (10.45-21.45) vs. 17.75 (15.30-23.75) pg/ml, p = 0.03]. Free 25(OH)D levels correlated positively with total 25(OH)D (p = 0.0001) and HDL cholesterol (p = 0.04) and negatively with fasting blood glucose (p = 0.04). Our findings indicate that VDBP is increased and free 25(OH)D is decreased in acromegaly, while there is no significant alteration in total 25(OH)D.

  20. Vitamin D and Actigraphic Sleep Outcomes in Older Community-Dwelling Men: The MrOS Sleep Study

    PubMed Central

    Massa, Jennifer; Stone, Katie L.; Wei, Esther K.; Harrison, Stephanie L.; Barrett-Connor, Elizabeth; Lane, Nancy E.; Paudel, Misti; Redline, Susan; Ancoli-Israel, Sonia; Orwoll, Eric; Schernhammer, Eva

    2015-01-01

    Study Objectives: Maintaining adequate serum levels of vitamin D may be important for sleep duration and quality; however, these associations are not well understood. We examined whether levels of serum 25(OH)D are associated with objective measures of sleep in older men. Setting and Participants: Cross-sectional study within a large cohort of community-dwelling older men, the MrOS study. Interventions: Among 3,048 men age 68 years or older, we measured total serum vitamin D. Objective estimates of nightly total sleep time, sleep efficiency, and wake time after sleep onset (WASO) were obtained using wrist actigraphy worn for an average of 5 consecutive 24-h periods. Results: 16.4% of this study population had low levels of vitamin D (< 20.3 ng/mL 25(OH)D). Lower serum vitamin D levels were associated with a higher odds of short (< 5 h) sleep duration, (odds ratio [OR] for the highest (≥ 40.06 ng/mL) versus lowest (< 20.3 ng/mL) quartile of 25(OH)D, 2.15; 95 % confidence interval (CI), 1.21–3.79; Ptrend = 0.004) as well as increased odds of actigraphy-measured sleep efficiency of less than 70% (OR, 1.45; 95% CI, 0.97–2.18; Ptrend = 0.004), after controlling for age, clinic, season, comorbidities, body mass index, and physical and cognitive function. Lower vitamin D levels were also associated with increased WASO in age-adjusted, but not multivariable adjusted models Conclusions: Among older men, low levels of total serum 25(OH)D are associated with poorer sleep including short sleep duration and lower sleep efficiency. These findings, if confirmed by others, suggest a potential role for vitamin D in maintaining healthy sleep. Citation: Massa J, Stone KL, Wei EK, Harrison SL, Barrett-Connor E, Lane NE, Paudel M, Redline S, Ancoli-Israel S, Orwoll E, Schernhammer E. Vitamin D and actigraphic sleep outcomes in older community-dwelling men: the MrOS Sleep Study. SLEEP 2015;38(2):251–257. PMID:25581929

  1. 24-Hydroxylase in Cancer: Impact on Vitamin D-based Anticancer Therapeutics

    PubMed Central

    Luo, Wei; Hershberger, Pamela A.; Trump, Donald L.; Johnson, Candace S.

    2013-01-01

    The active vitamin D hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) plays a major role in regulating calcium homeostasis and bone mineralization. 1,25(OH)2D3 also modulates cellular proliferation and differentiation in a variety of cell types. 24-hydroxylase, encoded by the CYP24A1 gene, is the key enzyme which converts 1,25(OH)2D3 to less active calcitroic acid. Nearly all cell types express 24-hydroxylase, the highest activity being observed in the kidney. There is increasing evidence linking the incidence and prognosis of certain cancers to low serum 25 (OH)D3 levels and high expression of vitamin D 24-hydroxylase supporting the idea that elevated CYP24A1 expression may stimulate degradation of vitamin D metabolites including 25-(OH)D3 and 1,25(OH)2D3. The over expression of CYP24A1 in cancer cells may be a factor affecting 1,25(OH)2D3 bioavailability and anti-proliferative activity pre-clinically and clinically. The combination of 1,25(OH)2D3 with CYP24A1 inhibitors enhances 1,25(OH)2D3 mediated signaling and anti-proliferative effects and may be useful in overcoming effects of aberrant CYP24 expression. PMID:23059474

  2. Circulating Vitamin D3 and 25-hydroxyvitamin D in Humans: An Important Tool to Define Adequate Nutritional Vitamin D Status

    PubMed Central

    Hollis, Bruce W.; Wagner, Carol L.; Drezner, Mark K.; Binkley, Neil C.

    2007-01-01

    Circulating 25-hydroxyvitamin D [25(OH)D] is generally considered the means by which we define nutritional vitamin D status. There is much debate, however, with respect to what a healthy minimum level of circulation 25(OH)D should be. Recent data using various biomarkers such as intact parathyroid hormone (PTH), intestinal calcium absorption, and skeletal density measurements suggest this minimum level to be 80 nmol (32 ng/mL). Surprisingly, the relationship between circulating vitamin D3 and its metabolic product—25(OH)D3 has not been studied. We investigated this relationship in two separate populations: the first, individuals from Hawaii who received significant sun exposure; the second, subjects from a lactation study who received up to 6,400 IU vitamin D3/day for six months. Results: 1) The relationship between circulating vitamin D3 and 25(OH)D in both groups was not linear, but appeared saturable and controlled; 2) Optimal nutritional vitamin D status appeared to occur when molar ratios of circulating vitamin D3 and 25(OH)D exceeded 0.3; at this point, the Vmax of the 25-hydroxylase appeared to be achieved. This was achieved when circulating 25(OH)D exceeded 100 nmol. We hypothesize that as humans live today, the 25-hydroxylase operates well below its Vmax because of chronic substrate deficiency, namely vitamin D3. When humans are sun (or dietary) replete, the vitamin D endocrine system will function in a fashion as do these other steroid synthetic pathways, not limited by substrate. Thus, the relationship between circulating vitamin D and 25(OH)D may represent what “normal” vitamin D status should be. PMID:17218096

  3. 1,25(OH)2D3 and VDR Signaling Pathways Regulate the Inhibition of Dectin-1 Caused by Cyclosporine A in Response to Aspergillus Fumigatus in Human Corneal Epithelial Cells

    PubMed Central

    Xia, Yiping; Zhao, Guiqiu; Lin, Jing; Li, Cui; Cong, Lin; Jiang, Nan; Xu, Qiang; Wang, Qian

    2016-01-01

    Background The objective of this study is to observe whether cyclosporine A (CsA) inhibits the expression of dectin-1 in human corneal epithelial cells infected with Aspergillus fumigatus (A. fumigatus) and to investigate the molecular mechanisms of the inhibition. Methods Immortalized human corneal epithelial cells (HCECs) were pretreated with 1,25(OH)2D3 and VDR inhibitor for 1 h, and then they were pretreated with CsA for 12h. After these pretreatments, the HCECs were stimulated with A. fumigatus and curdlan respectively, and the expression of dectin-1 and proinflammatory cytokines (IL-1β and TNF-α) were detected by RT-PCR, western blot and ELISA. Results Dectin-1 mRNA and dectin-1 protein expression increased when HCECs were stimulated with A. fumigatus or curdlan, and CsA inhibited the dectin-1 expression both in mRNA and protein levels specifically. Dectin-1 and proinflammatory cytokine expression levels were higher when HCECs were pretreated with VDR inhibitor and CsA compared to pretreatment with CsA alone, while dectin-1 and proinflammatory cytokine levels were lower when HCECs were pretreated with 1,25(OH)2D3 and CsA compared to pretreatment with CsA alone. Conclusions These data provide evidence that CsA can inhibit the expression of dectin-1 and proinflammatory cytokines through dectin-1 when HCECs are stimulated by A. fumigatus or curdlan. The active form of vitamin D, 1,25(OH)2D3, and VDR signaling pathway regulate the inhibition of CsA. The inhibition is enhanced by 1,25(OH)2D3, and the VDR inhibitor suppresses the inhibition. PMID:27755569

  4. Vitamin D Test

    MedlinePlus

    ... limited. Home Visit Global Sites Search Help? Vitamin D Tests Share this page: Was this page helpful? Also known as: Ergocalciferol (Vitamin D 2 ); Cholecalciferol (Vitamin D 3 ); Calcidiol (25-hydroxyvitamin ...

  5. Primary vitamin D target genes allow a categorization of possible benefits of vitamin D₃ supplementation.

    PubMed

    Carlberg, Carsten; Seuter, Sabine; de Mello, Vanessa D F; Schwab, Ursula; Voutilainen, Sari; Pulkki, Kari; Nurmi, Tarja; Virtanen, Jyrki; Tuomainen, Tomi-Pekka; Uusitupa, Matti

    2013-01-01

    Vitamin D deficiency has been associated with an increased risk of developing a number of diseases. Here we investigated samples from 71 pre-diabetic individuals of the VitDmet study, a 5-month high dose vitamin D3 intervention trial during Finnish winter, for their changes in serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations and the expression of primary vitamin D target genes in peripheral blood mononuclear cells and adipose tissue. A negative correlation between serum concentrations of parathyroid hormone and 25(OH)D3 suggested an overall normal physiological vitamin D response among the participants. The genes CD14 and thrombomodulin (THBD) are up-regulated primary vitamin D targets and showed to be suitable gene expression markers for vitamin D signaling in both primary tissues. However, in a ranking of the samples concerning their expected response to vitamin D only the top half showed a positive correlation between the changes of CD14 or THBD mRNA and serum 25(OH)D3 concentrations. Interestingly, this categorization allows unmasking a negative correlation between changes in serum concentrations of 25(OH)D3 and the inflammation marker interleukin 6. We propose the genes CD14 and THBD as transcriptomic biomarkers, from which the effects of a vitamin D3 supplementation can be evaluated. These biomarkers allow the classification of subjects into those, who might benefit from a vitamin D3 supplementation, and others who do not.

  6. Extracts from Lentinula edodes (Shiitake) Edible Mushrooms Enriched with Vitamin D Exert an Anti-Inflammatory Hepatoprotective Effect.

    PubMed

    Drori, Ariel; Shabat, Yehudit; Ben Ya'acov, Ami; Danay, Ofer; Levanon, Dan; Zolotarov, Lidya; Ilan, Yaron

    2016-04-01

    Vitamin D has been known for its anti-inflammatory properties. Extracts derived from Lentinula edodes (Shiitake) edible mushroom exert an anti-inflammatory effect. These extracts contain high levels of ergosterol, which converts into ergocalciferol (vitamin D2) following exposure to ultraviolet light, followed by absorption and hydroxylation into the active form 25-hydroxyvitamin D [25(OH)D]. To determine the anti-inflammatory effect of overexpression of vitamin D in edible mushrooms, L. edodes mushrooms were exposed to ultraviolet-B light, freeze-dried, followed by measurement of vitamin D2 contents, in their dry weight. C57B1/6 mice were orally treated with vitamin D2-enriched or nonenriched mushroom extract prior and during concanavalin A-immune-mediated liver injury. Exposure to ultraviolet light increased vitamin D2 content in Shiitake edible mushrooms. Following feeding of vitamin D-enriched mushroom extracts to mice with immune-mediated hepatitis, a significant decrease in liver damage was noted. This was shown by a decrease in alanine aminotransferase and aspartate aminotransferase serum levels, a decrease in proportion of mice with severe liver injury, and by improvement in liver histology. These effects were associated with a decrease in serum interferon gamma levels. A synergistic effect was noted between the anti-inflammatory effect of the mushroom extracts and that of vitamin D. Oral administration of vitamin D-enriched L. edodes edible mushroom exerts a synergistic anti-inflammatory effect in the immune-mediated hepatitis. The data support its potential use as safe immunomodulatory adjuvant for the treatment of HCV and nonalcoholic steatohepatitis. PMID:27027234

  7. 1,25(OH)2D deficiency induces temporomandibular joint osteoarthritis via secretion of senescence-associated inflammatory cytokines.

    PubMed

    Shen, Ming; Luo, Yuqian; Niu, Yuming; Chen, Lulu; Yuan, Xiaoqin; Goltzman, David; Chen, Ning; Miao, Dengshun

    2013-08-01

    1,25-Dihydroxyvitamin D [1,25(OH)(2)D] insufficiency appears to be associated with several age-related diseases. Insufficient levels of serum 25-hydroxyvitamin D has been shown to lead to the progression of osteoarthritis (OA) while underlying biological mechanisms remain largely unknown. In this study, we sought to determine whether 1,25(OH)(2)D deficiency has a direct effect on the process of murine temporomandibular joint (TMJ) OA in 25-hydroxyvitamin D 1α-hydroxylase knockout [1α(OH)ase(-/-)] mice that had been fed a rescue diet (high calcium, phosphate, and lactose) from weaning until 6 or 18 months of age. Our results showed that the bone mineral density and subchondral bone volume were reduced in mandibular condyles, articular surfaces were collapsed, the thickness of articular cartilage and cartilage matrix protein abundance were progressively decreased and eventually led to an erosion of articular cartilage of mandibular condyles. We also found that DNA damage, cellular senescence and the production of senescence-associated inflammatory cytokines were increased significantly in 1α(OH)ase(-/-) mice. This study demonstrates that 1,25(OH)(2)D deficiency causes an erosive TMJ OA phenotype by inducing DNA damage, cellular senescence and the production of senescence-associated inflammatory cytokines. Our results indicate that 1,25(OH)(2)D plays an important role in preventing the development and progression of OA. PMID:23624390

  8. Current Scenario of Prevalence of Vitamin D Deficiency in Ostensibly Healthy Indian Population: A Hospital Based Retrospective Study.

    PubMed

    Shukla, Kirtikar; Sharma, Shikha; Gupta, Aditi; Raizada, Arun; Vinayak, Kamini

    2016-10-01

    25-hydroxy vitamin D [25(OH) vit D] deficiency is a serious public health problem, particularly in the Indian sub-continent. The objective of the present study was to study the prevalence of 25(OH) vit D in different age groups. The data of 25(OH) vit D assay of 26,346 ostensibly healthy individuals, enrolled under executive health checkup at Medanta The Medicity, Gurgaon, over a period of 3 years, were extracted from the hospital information system and reviewed extensively. 25(OH) vit D deficiency (VDD) was defined as 25(OH) vit D < 20 ng/ml, insufficiency (VDI) as 25(OH) vit D between 20 and 40 ng/ml and 25(OH) vit D sufficiency (VDS) as 25(OH) D > 40 ng/mL. 25(OH) vit D deficiency (VDD + VDI) was observed in 93 % of the subject population. Maximum number of the subjects belonged to the age group of 41-60 years. 59 % had frank 25(OH) vit D deficiency when cut off level was <20 ng/mL. Mean value of 25(OH) vit D in our subjects was 21.4 ± 14.4 ng/mL. Significant difference in 25(OH) vit D level was observed in between male and female subjects. Simultaneously 25(OH) vit D levels were significantly lower in the patient visited hospital in winter-spring season than the summer-autumn season (p > 0.001). Our study demonstrates a high prevalence of 25(OH) vit D deficiency in an ostensibly healthy Indian population. There is a need for redefining our reference ranges according to our population and extensively improving the status of vitamin D. PMID:27605743

  9. Current Scenario of Prevalence of Vitamin D Deficiency in Ostensibly Healthy Indian Population: A Hospital Based Retrospective Study.

    PubMed

    Shukla, Kirtikar; Sharma, Shikha; Gupta, Aditi; Raizada, Arun; Vinayak, Kamini

    2016-10-01

    25-hydroxy vitamin D [25(OH) vit D] deficiency is a serious public health problem, particularly in the Indian sub-continent. The objective of the present study was to study the prevalence of 25(OH) vit D in different age groups. The data of 25(OH) vit D assay of 26,346 ostensibly healthy individuals, enrolled under executive health checkup at Medanta The Medicity, Gurgaon, over a period of 3 years, were extracted from the hospital information system and reviewed extensively. 25(OH) vit D deficiency (VDD) was defined as 25(OH) vit D < 20 ng/ml, insufficiency (VDI) as 25(OH) vit D between 20 and 40 ng/ml and 25(OH) vit D sufficiency (VDS) as 25(OH) D > 40 ng/mL. 25(OH) vit D deficiency (VDD + VDI) was observed in 93 % of the subject population. Maximum number of the subjects belonged to the age group of 41-60 years. 59 % had frank 25(OH) vit D deficiency when cut off level was <20 ng/mL. Mean value of 25(OH) vit D in our subjects was 21.4 ± 14.4 ng/mL. Significant difference in 25(OH) vit D level was observed in between male and female subjects. Simultaneously 25(OH) vit D levels were significantly lower in the patient visited hospital in winter-spring season than the summer-autumn season (p > 0.001). Our study demonstrates a high prevalence of 25(OH) vit D deficiency in an ostensibly healthy Indian population. There is a need for redefining our reference ranges according to our population and extensively improving the status of vitamin D.

  10. 1,25(OH)2D3 Deficiency Induces Colon Inflammation via Secretion of Senescence-Associated Inflammatory Cytokines

    PubMed Central

    Zhi, Chunchun; Shen, Ming; Sun, Weiwei; Miao, Dengshun; Yuan, Xiaoqin

    2016-01-01

    Epidemiological studies showed that 1,25-Dihydroxyvitamin D[1,25(OH)2D3] insufficiency appears to be associated with aging and colon cancer while underlying biological mechanisms remain largely unknown. Inflammatory bowel disease is one of the risk factors for colon cancer. In this study, we investigated whether 1,25(OH)2D3 deficiency has an impact on the colon of 25-hydroxyvitamin D 1α-hydroxylase knockout [Cyp27b1−/−] mice fed on a rescue diet (high calcium, phosphate, and lactose) from weaning to 10 months of age. We found that 1,25(OH)2D3 deficient mice displayed significant colon inflammation phenotypes including shortened colon length, thinned and disordered mucosal structure, and inflammatory cell infiltration. DNA damage, cellular senescence and the production of senescence-associated inflammatory cytokines were also increased significantly in the colon of Cyp27b1−/−mice. Furthermore, the levels of ROS in the colon were increased significantly, whereas the expression levels of antioxidative genes were down-regulated dramatically in the colon of Cyp27b1−/−mice. Taken together, our results demonstrated that 1,25(OH)2D3 deficiency could induce colon inflammation, which may result from increased oxidative stress and DNA damage, subsequently, induced cell senescence and overproduction of senescence-associated secretory factors. Therefore, our findings suggest that 1,25(OH)2D3 may play an important role in preventing the development and progression of colon inflammation and colon cancer. PMID:26790152

  11. Vitamin D and Mortality.

    PubMed

    Pilz, Stefan; Grübler, Martin; Gaksch, Martin; Schwetz, Verena; Trummer, Christian; Hartaigh, Bríain Ó; Verheyen, Nicolas; Tomaschitz, Andreas; März, Winfried

    2016-03-01

    In this narrative review, we aim to summarize and discuss the current evidence linking vitamin D and mortality. Low 25-hydroxyvitamin D [25(OH)D] concentrations are associated with an increased risk of mortality. This has been shown in different cohort studies including general populations, as well as various patient cohorts. Some single-study results and meta-analyses indicate that the shape of the relationship between 25(OH)D and mortality follows a U- or a reverse J-shaped curve. Interassay and laboratory differences are, however, a limitation of most previous surveys, and standardization of 25(OH)D measurements is needed for future investigations. Apart from observational data, it has been documented in meta-analyses of randomized controlled trials that vitamin D3 supplementation is associated with a moderate, yet statistically significant, reduction in mortality. This latter finding must be interpreted in light of some limitations such as incomplete follow-up data, but such a reduction of mortality with vitamin D3 supplementation as the finding of meta-analyses of randomized controlled trials strongly argues for the benefits and, importantly, also the safety of vitamin D. PMID:26977039

  12. Dietary vitamin D₂--a potentially underestimated contributor to vitamin D nutritional status of adults?

    PubMed

    Cashman, Kevin D; Kinsella, Michael; McNulty, Breige A; Walton, Janette; Gibney, Michael J; Flynn, Albert; Kiely, Mairead

    2014-07-28

    It has been suggested that vitamin D₂ is not very prevalent in the human food chain. However, data from a number of recent intervention studies suggest that the majority of subjects had measurable serum 25-hydroxyvitamin D₂ (25(OH)D₂) concentrations. Serum 25(OH)D₂, unlike 25(OH)D₃, is not directly influenced by exposure of skin to sun and thus has dietary origins; however, quantifying dietary vitamin D₂ is difficult due to the limitations of food composition data. Therefore, the present study aimed to characterise serum 25(OH)D₂ concentrations in the participants of the National Adult Nutrition Survey (NANS) in Ireland, and to use these serum concentrations to estimate the intake of vitamin D₂ using a mathematical modelling approach. Serum 25(OH)D₂ concentration was measured by a liquid chromatography-tandem MS method, and information on diet as well as subject characteristics was obtained from the NANS. Of these participants, 78.7 % (n 884) had serum 25(OH)D₂ concentrations above the limit of quantification, and the mean, maximum, 10th, 50th (median) and 90th percentile values of serum 25(OH)D₂ concentrations were 3.69, 27.6, 1.71, 2.96 and 6.36 nmol/l, respectively. To approximate the intake of vitamin D₂ from these serum 25(OH)D₂ concentrations, we used recently published data on the relationship between vitamin D intake and the responses of serum 25(OH)D concentrations. The projected 5th to 95th percentile intakes of vitamin D₂ for adults were in the range of 0.9-1.2 and 5-6 μg/d, respectively, and the median intake ranged from 1.7 to 2.3 μg/d. In conclusion, the present data demonstrate that 25(OH)D₂ concentrations are present in the sera of adults from this nationally representative sample. Vitamin D₂ may have an impact on nutritional adequacy at a population level and thus warrants further investigation.

  13. Changes in vitamin D supplement use and baseline plasma 25-hydroxyvitamin D concentration predict 5-y change in concentration in postmenopausal women.

    PubMed

    Kluczynski, Melissa A; Wactawski-Wende, Jean; Platek, Mary E; DeNysschen, Carol A; Hovey, Kathleen M; Millen, Amy E

    2012-09-01

    Few studies have prospectively examined predictors of change in plasma concentrations of 25-hydroxyvitamin D [25(OH)D]. We sought to determine the predictors of 5-y change in 25(OH)D. Plasma 25(OH)D concentrations were assessed at baseline (1997-2000) and 5 y later (2002-2005) in 668 postmenopausal women enrolled in the Osteoporosis and Periodontal Disease Study. Baseline and changes in demographic, dietary, lifestyle, and health-related factors were tested as predictors of change in 25(OH)D concentrations by using multivariable linear regression. The mean 5-y change in 25(OH)D (mean ± SD) was 7.7 ± 0.7 nmol/L (P < 0.001). In our predictive model (n = 643), predictors explained 31% of the variance in change in 25(OH)D concentrations and included baseline 25(OH)D, baseline and change in vitamin D supplementation and physical activity, change in season of blood draw, BMI, whole-body T score, and baseline hormone therapy use. Baseline 25(OH)D and change in vitamin D supplementation explained the most variation (25%) in 25(OH)D. Exploratory analyses showed a borderline significant interaction between tertiles of baseline 25(OH)D and change in vitamin D supplementation over time (P = 0.06). The greatest mean increase in 25(OH)D (22.9 ± 16.8 nmol/L), with adjustment for other statistically significant predictors, occurred in women whose baseline 25(OH)D concentration was ≤51.0 nmol/L (tertile 1) and who increased supplementation use over time. These results confirm the importance of supplementation in increasing 25(OH)D concentrations in aging women, even after other statistically significant predictors are controlled for. These data also suggest that this is especially true among aging women with inadequate 25(OH)D (e.g., <50 nmol/L). PMID:22833661

  14. Vitamin D status in Poland.

    PubMed

    Płudowski, Paweł; Ducki, Czesław; Konstantynowicz, Jerzy; Jaworski, Maciej

    2016-08-01

    INTRODUCTION    Epidemiological data on vitamin D status in the Polish population are limited. OBJECTIVES    The aim of the study was to evaluate the vitamin D status in a representative group of adult inhabitants of 22 Polish cities, based on the analysis of serum 25-hydroxyvitamin D [25(OH)D] levels. PATIENTS AND METHODS    This cross-sectional study included a total of 5775 adult volunteers (4464 women; 1311 men; mean age, 54.0 ±15.9 years; range, 15.6-89.8 years), who were enrolled and examined through late winter and spring 2014. Serum concentrations of 25(OH)D were determined using the Liaison XL system (DiaSorin; CLIA method). Demographic and anthropometric data were also analyzed. RESULTS    The mean 25(OH)D concentration in the studied population was 18.0 ±9.6 ng/ml; 65.8% of the patients had 25(OH)D levels of less than 20 ng/ml; 24.1% had suboptimal levels of 20 to 30 ng/ml; and only 9.1% demonstrated the optimal levels of 30 to 50 ng/ml. In 89.9% of the studied population, 25(OH)D levels of less than 30 ng/ml were found. Obesity, defined as body mass index (BMI) over 30 kg/m2, was associated with lower 25(OH)D levels compared with normal weight (15.8 ±8.5 vs 18.5 ±9.7 ng/ml; P <0.0001). Lower 25(OH)D levels were observed in men, younger individuals, and individuals with excess body weight and higher BMI. CONCLUSIONS    The results of our study, which involved the most representative sample size of Polish adults, support the previously reported data on vitamin D status. The levels of 25(OH)D determined for adults in our study demonstrate that the majority of the Polish population is vitamin D deficient, at least during winter and spring, and that preventive or interventional strategies must be considered to improve the vitamin D status in Poland. PMID:27509842

  15. Determination of vitamins D2 and D3 in selected food matrices by online high-performance liquid chromatography-gas chromatography-mass spectrometry (HPLC-GC-MS).

    PubMed

    Nestola, Marco; Thellmann, Andrea

    2015-01-01

    An online normal-phase liquid chromatography-gas chromatography-mass spectrometry (HPLC-GC-MS) method was developed for the determination of vitamins D2 and D3 in selected food matrices. Transfer of the sample from HPLC to GC was realized by large volume on-column injection; detection was performed with a time-of-flight mass spectrometer (TOF-MS). Typical GC problems in the determination of vitamin D such as sample degradation or sensitivity issues, previously reported in the literature, were not observed. Determination of total vitamin D content was done by quantitation of its pyro isomer based on an isotopically labelled internal standard (ISTD). Extracted ion traces of analyte and ISTD showed cross-contribution, but non-linearity of the calibration curve was not determined inside the chosen calibration range by selection of appropriate quantifier ions. Absolute limits of detection (LOD) and quantitation (LOQ) for vitamins D2 and D3 were calculated as approximately 50 and 150 pg, respectively. Repeatability with internal standard correction was below 2 %. Good agreement between quantitative results of an established high-performance liquid chromatography with UV detection (HPLC-UV) method and HPLC-GC-MS was found. Sterol-enriched margarine was subjected to HPLC-GC-MS and HPLC-MS/MS for comparison, because HPLC-UV showed strong matrix interferences. HPLC-GC-MS produced comparable results with less manual sample cleanup. In summary, online hyphenation of HPLC and GC allowed a minimization in manual sample preparation with an increase of sample throughput.

  16. Calcium and vitamin D metabolism in spontaneously hypertensive rats

    SciTech Connect

    Hsu, Chen Hsing; Yang, Chweishiun; Patel, S.R.; Stevens, M.G. )

    1987-10-01

    The authors have studied the effect of dietary vitamin D restriction on serum levels of vitamin D metabolites, measured by radioreceptor assay and radioimmunoassay in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Both WKY and SHR were fed a vitamin D-deficient or a vitamin D-supplemented diet beginning at 4 wk of age. In vitamin D-supplemented animals, the serum 1,25-dihydroxycholecalciferol (1,25(OH){sub 2}D{sub 3}) concentration of WKY was similar to the level of SHR. Plasma calcium concentration was not different between WKY and SHR. In animals fed a vitamin D-deficient diet, the serum concentration of 1,25-(OH){sub 2}D{sub 3} of SHR was significantly lower than that of WKY. Plasma 25-hydroxycholecalciferol level was markedly decreased in both WKY and SHR. The SHR, but not the WKY, developed hypocalcemia. Despite hypocalcemia, fasting urinary Ca{sup 2+} excretion of SHR exceeded that of WKY. They conclude that the lower 1,25(OH){sub 2}D{sub 3} level in SHR fed a vitamin D-deficient diet may be due to a defect in the synthesis of 1,25(OH){sub 2}D{sub 3}. The low level of 1,25(OH){sub 2}D{sub 3} is associated with renal wasting of calcium and hypocalcemia in SHR.

  17. Tumoral vitamin D synthesis by CYP27B1 1-alpha-hydroxylase delays mammary tumor progression in the PyMT-MMTV mouse model and its action involves NF-kappaB modulation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biologically-active vitamin D (1,25(OH)2D) is synthetized from inactive prohormone 25(OH)D by the enzyme CYP27B1 1-a-hydroxylase in kidney and several extra-renal tissues including breast. While the development of breast cancer has been linked to inadequate vitamin D status, the importance of bioac...

  18. Determinants of changes in vitamin D status postpartum in Swedish women.

    PubMed

    Brembeck, Petra; Winkvist, Anna; Bååth, Mari; Bärebring, Linnea; Augustin, Hanna

    2016-02-14

    Low vitamin D status has been associated with unfavourable health outcomes. Postpartum, it is speculated that maternal vitamin D status decreases due to transfer of vitamin D from mother to child through breast milk. A few studies have investigated changes in maternal vitamin D postpartum and possible determinants. Thus, the aims of the present study were to determine changes in serum concentrations of 25-hydroxyvitamin D (25(OH)D) between 2 weeks and 12 months postpartum in Swedish women and to evaluate lactation and other determinants for changes in 25(OH)D concentration postpartum. In total, seventy-eight women were studied at 2 weeks, 4 months and 12 months postpartum. Data collection included measurements of weight and height as well as information about lactation, sun exposure, use of oestrogen contraceptives and physical activity level. Blood samples were collected and serum 25(OH)D levels were analysed using liquid chromatography-tandem MS. Dietary intake of vitamin D was recorded using 4-d food diaries. For all the women studied, mean serum 25(OH)D did not change between 2 weeks and 12 months postpartum (67 (SD 23) v. 67 (SD 19) nmol/l). No association was found between lactation and changes in serum 25(OH)D concentration postpartum. Significant determinants for postpartum changes in 25(OH)D concentration were use of vitamin D supplements (P=0·003), use of oestrogen contraceptives (P=0·013) and season (P=0·005). In conclusion, no changes were observed in 25(OH)D concentrations during the 1st year postpartum in these women and no association was found between lactation and changes in 25(OH)D concentration postpartum. The main determinants for the variation in changes in 25(OH)D concentrations postpartum were use of vitamin D supplements, use of oestrogen contraceptives and season. PMID:26586446

  19. Supplemental vitamin D increases serum cytokines in those with initially low 25-hydroxyvitamin D: a randomized, double blind, placebo-controlled study.

    PubMed

    Barker, Tyler; Rogers, Victoria E; Levy, Mark; Templeton, Jenna; Goldfine, Howard; Schneider, Erik D; Dixon, Brian M; Henriksen, Vanessa T; Weaver, Lindell K

    2015-02-01

    The purpose of this study was to determine if vitamin D status before supplementation influences the cytokine response after supplemental vitamin D. Forty-six reportedly healthy adults (mean(SD); age, 32(7) y; body mass index (BMI), 25.3(4.5) kg/m(2); serum 25-hydroxyvitamin D (25(OH)D), 34.8(12.2) ng/mL) were randomly assigned (double blind) to one of three groups: (1) placebo (n=15), or supplemental vitamin D (cholecalciferol) at (2) 4000 (n=14) or (3) 8000IU (n=17). Supplements were taken daily for 35days. Fasting blood samples were obtained before (Baseline, Bsl) and 35-days after (35-d) supplementation. Serum 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)D), cytokines, and intact parathyroid hormone with calcium were measured in each blood sample. Supplemental vitamin D increased serum 25(OH)D (4000IU, ≈29%; 8000IU, ≈57%) and 1,25(OH)D (4000IU, ≈12%; 8000IU, ≈38%) without altering intact parathyroid hormone or calcium. The vitamin D metabolite increases in the supplemental vitamin D groups (n=31) were dependent on initial levels as serum 25(OH)D (r=-0.63, p<0.05) and 1,25(OH)D (r=-0.45, p<0.05) at Bsl correlated with their increases after supplementation. Supplemental vitamin D increased interferon (IFN)-γ and interleukin (IL)-10 in subjects that were vitamin D insufficient (serum 25(OH)D<29ng/mL) compared to sufficient (serum 25(OH)D⩾30ng/mL) at Bsl. We conclude that supplemental vitamin D increase a pro- and anti-inflammatory cytokine in those with initially low serum 25(OH)D. PMID:25461390

  20. Vitamin D Intake and Serum 25-Hydroxyvitamin D Levels in Korean Adults: Analysis of the 2009 Korea National Health and Nutrition Examination Survey (KNHANES IV-3) Using a Newly Established Vitamin D Database

    PubMed Central

    Yoo, Kyoungok; Cho, Jinah; Ly, Sunyung

    2016-01-01

    Vitamin D is important for maintaining bone health and may prevent various diseases (i.e., cardiovascular disease and cancer). The aim of this study was to estimate vitamin D intakes of Korean adults using the Korea National Health and Nutrition Examination Survey (KNHANES, 2009) data and a newly established vitamin D database. KNHANES (2009) participants (n = 4541; 2021 men; 2520 women) aged ≥20 years were included. Dietary vitamin D intake, serum 25-hydroxyvitamin D (25(OH)D), and the relationship between vitamin D intake and serum 25(OH)D were evaluated. In men and women, vitamin D intakes were 4.00 ± 0.17 µg/day and 2.6 ± 0.1 µg/day respectively, and serum 25(OH)D concentrations were 19.78 ± 0.33 ng/mL and 17.10 ± 0.26 ng/mL respectively. Serum 25(OH)D concentrations of men aged <50 years and women aged >20 years were under 20 ng/mL. After adjusting for confounding factors, the positive relationship between vitamin D intake and serum 25(OH)D was observed in total subjects (p < 0.05), excluding participants ≥50 years old. The main food sources for vitamin D among Korean adults were fish/shellfish (71.34%) and egg (14.89%). Korean adults should increase their serum 25(OH)D concentrations by increasing vitamin D intake. PMID:27690097

  1. Counter-regulatory paracrine actions of FGF-23 and 1,25(OH)2D in macrophages

    PubMed Central

    Han, Xiaobin; Li, Linqiang; Yang, Jiancheng; King, Gwendalyn; Xiao, Zhousheng; Quarles, Leigh Darryl

    2016-01-01

    Mechanisms underlying the association between fibroblastic growth factor 23 (FGF-23) and inflammation are uncertain. We found that FGF-23 was markedly up-regulated in LPS/INF-γ-induced proinflammatory M1 macrophages and Hyp mouse-derived peritoneal macrophages, but not in IL-4-induced M2 anti-inflammatory macrophages. NF-κB and JAK/STAT1 pathways mediated the increased transcription of FGF-23 in response to M1 polarization. FGF-23 stimulated TNF-α, but not IL-6, expression in M0 macrophages and suppressed Arginase-1 expression in M2 macrophages through FGFR-mediated mechanisms. 1,25(OH)2D stimulated Arginase-1 expression and inhibited FGF-23 stimulation of TNF-α. FGF-23 has proinflammatory paracrine functions and counter-regulatory actions to 1,25(OH)2D on innate immune responses. PMID:26762170

  2. Vitamin D Promotes Odontogenic Differentiation of Human Dental Pulp Cells via ERK Activation

    PubMed Central

    Woo, Su-Mi; Lim, Hae-Soon; Jeong, Kyung-Yi; Kim, Seon-Mi; Kim, Won-Jae; Jung, Ji-Yeon

    2015-01-01

    The active metabolite of vitamin D such as 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) is a well-known key regulatory factor in bone metabolism. However, little is known about the potential of vitamin D as an odontogenic inducer in human dental pulp cells (HDPCs) in vitro. The purpose of this study was to evaluate the effect of vitamin D3 metabolite, 1α,25(OH)2D3, on odontoblastic differentiation in HDPCs. HDPCs extracted from maxillary supernumerary incisors and third molars were directly cultured with 1α,25(OH)2D3 in the absence of differentiation-inducing factors. Treatment of HDPCs with 1α,25(OH)2D3 at a concentration of 10 nM or 100 nM significantly upregulated the expression of dentin sialophosphoprotein (DSPP) and dentin matrix protein1 (DMP1), the odontogenesis-related genes. Also, 1α,25(OH)2D3 enhanced the alkaline phosphatase (ALP) activity and mineralization in HDPCs. In addition, 1α,25(OH)2D3 induced activation of extracellular signal-regulated kinases (ERKs), whereas the ERK inhibitor U0126 ameliorated the upregulation of DSPP and DMP1 and reduced the mineralization enhanced by 1α,25(OH)2D3. These results demonstrated that 1α,25(OH)2D3 promoted odontoblastic differentiation of HDPCs via modulating ERK activation. PMID:26062551

  3. Seasonal variations in serum 25-hydroxy vitamin D levels in a Swedish cohort.

    PubMed

    Klingberg, Eva; Oleröd, Göran; Konar, Jan; Petzold, Max; Hammarsten, Ola

    2015-08-01

    To study seasonal inter-individual and intra-individual variations in serum 25-hydroxy vitamin D (25(OH)D) and to explore parameters associated with 25(OH)D in a healthy Swedish adult population. 540 blood donors (60 % men; mean age 41 ± 13 years) and 75 thrombocyte donors (92 % men, aged 46 ± 11 years) were included. Serum was collected during 12 months and analyzed for 25(OH)D and parathyroid hormone (S-iPTH). The blood donors answered questionnaires concerning vitamin D supplements, smoking, physical activity, sunbed use and sun holidays. Repeated serum samples were collected from the thrombocyte donors to study the intra-individual variations in S-25(OH)D. S-25(OH)D varied greatly over the year correlating with the intensity of the UV-B irradiation (r S = 0.326; p < 0.001). During January-March, a S-25(OH)D level below the thresholds of 50 and 75 nmol/L was observed in 58 and 88 %, respectively, and during July-September in 11 and 50 % (p < 0.001). S-25(OH)D was negatively correlated with body mass index and S-iPTH, but was significantly higher in holiday makers in sunny destinations, sunbed users, non-smokers, and in the physically active. The intra-individual analyses showed a mean increase in S-25(OH)D by 8 nmol/L/month between April and August. Approximately 75 % had serum 25(OH)D values <75 nmol/L during 75 % of the year and 50 % had serum 25(OH)D <50 nmol/L during 50 % of the year. Serum 25(OH)D was strongly associated with parameters related to sun exposure, but only weakly with intake of vitamin D supplements.

  4. Vitamin D deficiency in rheumatoid arthritis: prevalence, determinants and associations with disease activity and disability

    PubMed Central

    2010-01-01

    Introduction The aim of this study was to estimate the prevalence and determinants of vitamin D deficiency in patients with rheumatoid arthritis (RA) as compared to healthy controls and to analyze the association between 25-hydroxyvitamin D (25(OH)D) with disease activity and disability. Methods The study includes 1,191 consecutive RA patients (85% women) and 1,019 controls, not on vitamin D supplements, from 22 Italian rheumatology centres. Together with parameters of disease activity, functional impairment, and mean sun exposure time, all patients had serum 25(OH)D measured in a centralized laboratory. Results A total of 55% of RA patients were not taking vitamin D supplements; the proportion of these with vitamin D deficiency (25(OH)D level <20 ng/ml) was 52%. This proportion was similar to that observed in control subjects (58.7%). One third of supplemented patients were still vitamin D deficient. In non-supplemented RA patients 25(OH)D levels were negatively correlated with the Health Assessment Questionnaire Disability Index, Disease Activity Score (DAS28), and Mobility Activities of daily living score. Significantly lower 25(OH)D values were found in patients not in disease remission or responding poorly to treatment, and with the highest Steinbrocker functional state. Body mass index (BMI) and sun exposure time were good predictors of 25(OH)D values (P < 0.001). The association between disease activity or functional scores and 25(OH)D levels remained statistically significant even after adjusting 25(OH)D levels for both BMI and sun exposure time. Conclusions In RA patients vitamin D deficiency is quite common, but similar to that found in control subjects; disease activity and disability scores are inversely related to 25(OH)D levels. PMID:21114806

  5. High Prevalence of Vitamin D Deficiency among Pregnant Saudi Women.

    PubMed

    Al-Faris, Nora A

    2016-02-04

    Vitamin D deficiency has emerged as a public health problem worldwide due to its important role in health and disease. The present work is intended to examine prevalence of vitamin D deficiency among pregnant Saudi women and related risk factors. A cross-sectional study was carried out at King Fahad Medical City in Riyadh, Saudi Arabia. Serum 25-hydroxy vitamin D (25(OH)D) was measured by enzyme-linked immunosorbent assay in 160 pregnant women during the first trimester of pregnancy. Socio-demographic, lifestyle and maternal characteristics were collected and vitamin D intake was assessed using a 24-h dietary recall. Weight and height were measured using standardized methods. Vitamin D deficiency (25(OH)D < 50 nmol/L) and insufficiency (25(OH)D = 50-74 nmol/L) were reported in 50% and 43.8% of the study sample, respectively. Median serum 25(OH)D concentration was 49.9 nmol/L. Adequate vitamin D intake (≥600 IU/day) was reported among only 8.1% of pregnant women. Age group, educational level, sun exposure frequency and daytime and daily practice of exercise were significantly associated with vitamin D status. Overall, vitamin D deficiency was common among pregnant Saudi women in Riyadh. Steps should be taken to address the current situation, including increased sunlight exposure, consumption of fatty fish, and vitamin D supplements.

  6. High Prevalence of Vitamin D Deficiency among Pregnant Saudi Women

    PubMed Central

    Al-Faris, Nora A.

    2016-01-01

    Vitamin D deficiency has emerged as a public health problem worldwide due to its important role in health and disease. The present work is intended to examine prevalence of vitamin D deficiency among pregnant Saudi women and related risk factors. A cross-sectional study was carried out at King Fahad Medical City in Riyadh, Saudi Arabia. Serum 25-hydroxy vitamin D (25(OH)D) was measured by enzyme-linked immunosorbent assay in 160 pregnant women during the first trimester of pregnancy. Socio-demographic, lifestyle and maternal characteristics were collected and vitamin D intake was assessed using a 24-h dietary recall. Weight and height were measured using standardized methods. Vitamin D deficiency (25(OH)D < 50 nmol/L) and insufficiency (25(OH)D = 50–74 nmol/L) were reported in 50% and 43.8% of the study sample, respectively. Median serum 25(OH)D concentration was 49.9 nmol/L. Adequate vitamin D intake (≥600 IU/day) was reported among only 8.1% of pregnant women. Age group, educational level, sun exposure frequency and daytime and daily practice of exercise were significantly associated with vitamin D status. Overall, vitamin D deficiency was common among pregnant Saudi women in Riyadh. Steps should be taken to address the current situation, including increased sunlight exposure, consumption of fatty fish, and vitamin D supplements. PMID:26861386

  7. Standardizing serum 25-hydroxyvitamin D data from four Nordic population samples using the Vitamin D Standardization Program protocols: Shedding new light on vitamin D status in Nordic individuals.

    PubMed

    Cashman, Kevin D; Dowling, Kirsten G; Škrabáková, Zuzana; Kiely, Mairead; Lamberg-Allardt, Christel; Durazo-Arvizu, Ramon A; Sempos, Christopher T; Koskinen, Seppo; Lundqvist, Annamari; Sundvall, Jouko; Linneberg, Allan; Thuesen, Betina; Husemoen, Lise Lotte N; Meyer, Haakon E; Holvik, Kristin; Grønborg, Ida M; Tetens, Inge; Andersen, Rikke

    2015-11-01

    Knowledge about the distributions of serum 25-hydroxyvitamin D (25(OH)D) concentrations in representative population samples is critical for the quantification of vitamin D deficiency as well as for setting dietary reference values and food-based strategies for its prevention. Such data for the European Union are of variable quality making it difficult to estimate the prevalence of vitamin D deficiency across member states. As a consequence of the widespread, method-related differences in measurements of serum 25(OH)D concentrations, the Vitamin D Standardization Program (VDSP) developed protocols for standardizing existing serum 25(OH)D data from national surveys around the world. The objective of the present work was to apply the VDSP protocols to existing serum 25(OH)D data from a Danish, a Norwegian, and a Finnish population-based health survey and from a Danish randomized controlled trial. A specifically-selected subset (n 100-150) of bio-banked serum samples from each of the studies were reanalyzed for 25(OH)D by LC-MS/MS and a calibration equation developed between old and new 25(OH)D data, and this equation was applied to the entire data-sets from each study. Compared to estimates based on the original serum 25(OH)D data, the percentage vitamin D deficiency (< 30 nmol/L) decreased by 21.5% in the Danish health survey but by only 1.4% in the Norwegian health survey; but was relatively unchanged (0% and 0.2%) in the Finish survey or Danish RCT, respectively, following VDSP standardization. In conclusion, standardization of serum 25(OH)D concentrations is absolutely necessary in order to compare serum 25(OH)D concentrations across different study populations, which is needed to quantify and prevent vitamin D deficiency.

  8. Providing vitamin D to confined sheep by oral supplementation vs ultraviolet irradiation

    SciTech Connect

    Hidiroglou, M.; Karpinski, K.

    1989-03-01

    Serial vitamin D3 (D3) and 25-hydroxyvitamin D3 (25 OH D3) concentrations of plasma were measured in confined, shorn sheep that had either been supplemented with vitamin D3 (50 micrograms/d) or exposed daily to ultraviolet irradiation (UVI). In the sheep administered D3 orally, plasma D3 increased continuously until d 35. This was followed by small fluctuations of the plasma D3 concentrations until a plateau was reached after 56 d of supplementation (.94 ng/ml plasma). Plasma 25 OH D3 concentrations increased continuously and plateaued between d 65 to 75 at about 21 ng/ml plasma. In the UVI sheep, plasma D3 and 25 OH D3 concentrations increased continuously for the first 49 d, then plateaued at 2.03 ng D3 and 29.6 ng 25 OH D3/ml. When a plateau was reached in plasma 25 OH D3 concentrations in both treatment groups, a /sup 3/H-labeled tracer dose of 25 OH D3 was given i.v., and disappearance of the /sup 3/H-labeled 25 OH D3 was followed. The UVI group had a faster decline in specific activities during the first exponential phase but a slower decline during the prolonged terminal elimination phase. These differences are reflected in the intercompartmental transfer rates. Our data indicate that UVI is as effective as oral vitamin D3 supplementation for improving vitamin D status of confined sheep.

  9. The Effects of Fat-soluble Vitamin Administration on Plasma Vitamin Status of Nursing Pigs Differ When Provided by Oral Administration or Injection

    PubMed Central

    Jang, Y. D.; Lindemann, M. D.; Monegue, H. J.; Stuart, R. L.

    2014-01-01

    Four experiments were conducted to investigate the effect of fat-soluble vitamin administration to sows or newborn pigs on plasma vitamin status. In Exp. 1 and 2, a total of 24 and 43 newborn pigs were allotted to control and vitamin treatments (vitamin D3 with variable addition of vitamins A and E) orally or by i.m. injection. In Exp. 3, pigs from Exp. 2 were allotted to 2 treatments (±vitamins D3 and E in drinking water) for 14 d postweaning. In Exp. 4, twenty-four gestating sows were used for 2 treatments (±injection of a vitamin D3/A/E product 2 wk prepartum). In Exp. 1 and 2, when vitamin D3 was administrated orally or by i.m. injection on d 1 of age, pigs had increased plasma 25-hydroxycholecalciferol (25-OH D3) concentration 10 d after administration compared with control pigs (p<0.05). The injectable administration with vitamin D3 and E was able to achieve higher plasma 25-OH D3 (p<0.05) and α-tocopherol (p<0.05) concentrations than oral administration. At weaning, the pigs in the injection group had higher plasma 25-OH D3 concentration than those in the other groups in both studies (p<0.05). In Exp. 3, water supplementation of vitamin D3 and E postweaning increased plasma 25-OH D3 and α-tocopherol concentrations at d 14 postweaning (p<0.01). In Exp. 4, when sows were injected with the vitamin D3 product prepartum, serum 25-OH D3 concentrations of sows at farrowing (p<0.01), and in their progeny at birth (p<0.01) and weaning (p<0.05) were increased. These results demonstrated that fat-soluble vitamin administration to newborn pigs increased plasma 25-OH D3 concentration regardless of administration routes and α-tocopherol concentration by the injectable route, and that water supplementation of vitamin D3 and E to nursery pigs increased plasma 25-OH D3 and α-tocopherol concentrations. Additionally, injecting sows with vitamin D3 prepartum increased 25-OH D3 in sows and their offspring. If continued research demonstrates that the serum levels of 25-OH D

  10. Common genetic determinants of vitamin D insufficiency: the sunlight consortium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Vitamin D is crucial for maintaining musculoskeletal health. Recently, vitamin D insufficiency has been linked to a number of extraskeletal disorders, including diabetes, cancer, and cardiovascular disease. Determinants of circulating 25-hydroxyvitamin D (25-OH D) include sun exposure an...

  11. Vitamin D and the skin: an ancient friend, revisited.

    PubMed

    Reichrath, Jörg

    2007-07-01

    Most vertebrates need vitamin D to develop and maintain a healthy mineralized skeleton. However, 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D(3)], the biologically active vitamin D metabolite, exerts a multitude of important physiological effects independent from the regulation of calcium and bone metabolism. We know today that the skin has a unique role in the human body's vitamin D endocrine system. It is the only site of vitamin D photosynthesis, and has therefore a central role in obtaining a sufficient vitamin D status. Additionally, the skin has the capacity to synthesize the biologically active vitamin D metabolite 1,25(OH)(2)D(3), and represents an important target tissue for 1,25(OH)(2)D(3). In keratinocytes and other cell types, 1,25(OH)(2)D(3) regulates growth and differentiation. Consequently, vitamin D analogues have been introduced for the treatment of the hyperproliferative skin disease psoriasis. Recently, sebocytes were identified as 1,25(OH)(2)D(3)-responsive target cells, indicating that vitamin D analogues may be effective in the treatment of acne. Other new functions of vitamin D analogues include profound effects on the immune system as well as in various tissues protection against cancer and other diseases, including autoimmune and infectious diseases. It can be speculated that the investigation of biological effects of vitamin D analogues will lead to new therapeutic applications that, besides cancer prevention, may include the prevention and treatment of infectious as well as of inflammatory skin diseases. Additionally, it can be assumed that dermatological recommendations on sun protection and health campaigns for skin cancer prevention will have to be re-evaluated to guarantee a sufficient vitamin D status.

  12. Ultraviolet index: a light in atopic dermatitis and vitamin D research?*

    PubMed Central

    Mesquita, Kleyton de Carvalho; Igreja, Ana Carolina de Souza Machado; Costa, Izelda Maria Carvalho

    2016-01-01

    BACKGROUND: The role played by vitamin D in atopic dermatitis is controversial and has been the focus of many studies. The ultraviolet index has not been considered in this type of research. OBJECTIVES: The objectives of the study were to assess 25-hydroxy vitamin D [25(OH)D] serum level in atopic dermatitis patients and control group, to investigate the association between atopic dermatitis clinical severity (using the SCORing Atopic Dermatitis index - SCORAD) and 25(OH)D serum levels, and to evaluate the independent predictors, including Ultraviolet index, SCORAD and 25(OH)D. METHODS: We conducted a cross-sectional study of 106 atopic dermatitis patients. A control group was matched with a subsample of 54 participants with atopic dermatitis. SCORAD index, laboratory tests, and local Ultraviolet index were assessed. RESULTS: The atopic dermatitis patients had serum 25(OH)D levels and mean UVI significantly higher than the control group. Immunoglobulin E and Ultraviolet index were associated with the SCORAD index. Skin type, age and Ultraviolet index were independent predictors of 25(OH)D. CONCLUSIONS: Although statistically significant, the different levels of 25(OH)D between the paired groups may be attributed to the higher mean Ultraviolet index in atopic dermatitis patients. Since Ultraviolet index is an independent predictor of SCORAD index and of 25(OH)D level, it may work as a confounding factor in studies involving atopic dermatitis and 25(OH)D and must be considered in this kind of research. PMID:26982776

  13. Circulating Vitamin D, Vitamin D-related genetic variation, and risk of fatal prostate cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

    PubMed Central

    Shui, Irene M; Mondul, Alison M.; Lindström, Sara; Tsilidis, Konstantinos K.; Travis, Ruth C.; Gerke, Travis; Albanes, Demetrius; Mucci, Lorelei A; Giovannucci, Edward; Kraft, Peter

    2015-01-01

    Background Evidence from animal and cell line experimental studies support a beneficial role for vitamin D in prostate cancer (PCa). While the results from human studies have been mainly null for overall PCa risk, there may be a benefit for survival. We assessed the associations of circulating 25-hydroxyvitamin D [25(OH)D] and common variation in key vitamin D-related genes with fatal PCa. Methods In a large cohort consortium, we identified 518 fatal cases and 2986 controls with 25(OH)D data. Genotyping information for 91 single nucleotide polymorphisms (SNPs) in 7 vitamin D-related genes (VDR, GC, CYP27A1, CYP27B1, CYP24A1, CYP2R1, RXRA) was available for 496 fatal cases and 3577 controls. We used unconditional logistic regression to calculate odd ratios (OR) and 95% confidence intervals (CI) for the associations of 25(OH)D and SNPs with fatal PCa. We also tested for 25(OH)D-SNP interactions among 264 fatal cases and 1169 controls. Results We observed no statistically significant relationship between 25(OH)D and fatal PCa [OR(95% CI)extreme quartiles=0.86(0.65-1.14); p-trend=0.22] or the main effects of the SNPs and fatal PCa. There was suggestive evidence that associations of several SNPs (including 5 related to circulating 25(OH)D) with fatal PCa were modified by 25(OH)D. Individually these associations would not remain significant after considering multiple testing; however the p-value for the set-based test for CYP2R1 was 0.002. Conclusions In our study, we did not observe statistically significant associations for either 25(OH)D or vitamin D-related SNPs with fatal PCa. Effect modification of 25(OH)D associations by biologically plausible genetic variation may deserve further exploration. PMID:25731953

  14. Low maternal serum vitamin D during pregnancy and the risk for postpartum depression symptoms.

    PubMed

    Robinson, Monique; Whitehouse, Andrew J O; Newnham, John P; Gorman, Shelley; Jacoby, Peter; Holt, Barbara J; Serralha, Michael; Tearne, Jessica E; Holt, Pat G; Hart, Prue H; Kusel, Merci M H

    2014-06-01

    Pregnancy is a time of vulnerability for vitamin D insufficiency, and there is an emerging literature associating low levels of 25(OH)-vitamin D with depressive symptoms. However, the link between 25(OH)-vitamin D status in pregnancy and altered risk of postnatal depressive symptoms has not been examined. We hypothesise that low levels of 25(OH)-vitamin D in maternal serum during pregnancy will be associated with a higher incidence of postpartum depressive symptoms. We prospectively collected sera at 18 weeks gestation from 796 pregnant women in Perth (1989-1992) who were enrolled in the Western Australian Pregnancy Cohort (Raine) Study and measured levels of 25(OH)-vitamin D. Women reported postnatal depressive symptoms at 3 days post-delivery. Women in the lowest quartile for 25(OH)-vitamin D status were more likely to report a higher level of postnatal depression symptoms than women who were in the highest quartile for vitamin D, even after accounting for a range of confounding variables including season of birth, body mass index and sociodemographic factors. Low vitamin D during pregnancy is a risk factor for the development of postpartum depression symptoms.

  15. Regulation of Dendritic Cell Function by Vitamin D

    PubMed Central

    Barragan, Myriam; Good, Misty; Kolls, Jay K.

    2015-01-01

    Studies over the last two decades have revealed profound immunomodulatory aspects of vitamin D on various aspects of the immune system. This review will provide an overview of Vitamin D metabolism, a description of dendritic cell subsets, and highlight recent advances on the effects of vitamin D on dendritic cell function, maturation, cytokine production and antigen presentation. The active form of vitamin D, 1,25(OH)2D3, has important immunoregulatory and anti-inflammatory effects. Specifically, the 1,25(OH)2D3-Vitamin D3 complex can affect the maturation and migration of many dendritic cell subsets, conferring a special immunoregulatory role as well as tolerogenic properties affecting cytokine and chemokine production. Furthermore, there have been many recent studies demonstrating the effects of Vitamin D on allergic disease and autoimmunity. A clear understanding of the effects of the various forms of Vitamin D will provide new opportunities to improve human health. PMID:26402698

  16. Vitamin D Metabolism and Action in Human Marrow Stromal Cells: Effects of Chronic Kidney Disease

    PubMed Central

    Zhou, Shuanhu; LeBoff, Meryl S.; Waikar, Sushrut S.; Glowacki, Julie

    2012-01-01

    Human marrow stromal cells (hMSCs) are targets of 1! ,25-dihydroxyvitamin D [1! ,25(OH)2D3] action to promote their differentiation to osteoblasts, but they also participate in vitamin D metabolism by converting 25-dihydroxyvitamin D3 [25(OH)D3] to 1! ,25(OH)2D3 by 1α-hydroxylase (CYP27B1). Chronic kidney disease (CKD) is associated with impaired renal biosynthesis of 1! ,25(OH)2D, low bone mass, and increased fracture risk. We tested whether CKD influences hMSCs' responses to vitamin D3 metabolites. The hMSCs were obtained from tissues discarded during arthroplasty for hip osteoarthrosis, including a subject who had been undergoing hemodialysis for 2+ years. There was a significant positive correlation between in vitro stimulation of osteoblastogenesis (alkaline phosphatase activity) by 1! ,25(OH)2D3 and subjects' estimated glomerular filtration rate (eGFR, r=0.47, p=0.015, n=26, 56–83 years of age). Osteoblastogenesis was stimulated in hMSCs from both the hemodialysis and control subjects by 1! ,25(OH)2D3 (10 ! M), 25(OH)D3 (100 ! M), or D3 (1000 ! M). Thus, vitamin D metabolism may play an autocrine/paracrine role in osteoblast differentiation of hMSCs. These findings suggest that in CKD patients 25(OH)D-sufficiency may play an important role in skeletal health; osteoblastic bone formation in CKD patients may not be optimal unless there is sufficient serum 25(OH)D substrate for the MSCs to synthesize and respond to local 1! ,25(OH)2D. PMID:22989482

  17. Vitamin D supplementation in athletes.

    PubMed

    Larson-Meyer, Enette

    2013-01-01

    It is well recognized that vitamin D is necessary for optimal bone health. Emerging evidence is finding that vitamin D deficiency can have a profound effect on immunity, inflammation and muscle function. Studies in athletes have found that vitamin D status varies among different populations and is dependent on skin color, early- or late-day training, indoor training and geographic location. Although dietary assessment studies have found that athletes worldwide do not meet the dietary intake recommendations for vitamin D, the most probable reason for poor status is inadequate synthesis due to lack of sun exposure. Studies in athletic populations suggest that maintaining adequate vitamin D status may reduce stress fractures, total body inflammation, common infectious illnesses, and impaired muscle function, and may also aid in recovery from injury. Given that compromised vitamin D status can potentially impact an athlete's overall health and training efficiency, vitamin D status should be routinely assessed so that athletes can be coached to maintain serum 25(OH)D concentration of ≥30 and preferably ≥40 ng/ml. Recommendations will be dependent on the athlete's current 25(OH)D concentration, but can include regular safe sun exposure and/or dietary supplementation combined with increased vitamin D intake. PMID:23765355

  18. 19F NMR study on the complex of fluorinated vitamin D derivatives with vitamin D receptor: elucidation of the conformation of vitamin D ligands accommodated in the receptor.

    PubMed

    Morizono, Daisuke

    2011-12-28

    Nuclear receptors mediate allosteric communications where ligand binding initiates a cascade of signal transduction. The interaction of vitamin D with vitamin D receptor (VDR) was investigated by (19)F NMR spectroscopy of the complexes of three fluorinated vitamin D derivatives with the full-length rat VDR-LBD. In the (19)F NMR spectra of the VDR-ligand complexes, the A-ring of 4,4-difluoro-1,25(OH)2D3 was revealed to adopt β-conformation in the VDR in solution, and the spectra were shown to be dependent on the dissociation constant. While the complex of 4,4-difluoro-1,25(OH)2D3 with VDR exhibited a clear distinguishable (19)F NMR spectrum, those of (19)F-1,25(OH)2D3 stereoisomers, which have 10-fold higher VDR affinity than 4,4-difluoro-1,25(OH)2D3, did not. The solid-phase NMR technique was useful for (19)F-1,25(OH)2D3 stereoisomers. The fluorinated vitamin D derivatives showed marked changes in the chemical shift (Δ4-19.7 ppm) upon VDR-complex formation, and the ab initio MO method suggested that van der Waals interactions play a major role in the complex formation.

  19. Impact of pregnancy on vitamin D status: a longitudinal study.

    PubMed

    Zhang, Joy Y; Lucey, Alice J; Horgan, Richard; Kenny, Louise C; Kiely, Mairead

    2014-10-14

    Nutritional requirements for vitamin D during pregnancy have been inadequately described, and there are conflicting data on the impact of gestation on vitamin D status. In the present study, we conducted a longitudinal analysis of total and free (unbound) serum 25-hydroxyvitamin D (25(OH)D), vitamin D-binding protein (DBP) and albumin concentrations in a random sample of thirty women from the Screening for Pregnancy Endpoints Ireland pregnancy cohort study at 15, 20, 24, 28, 32, 36 and 40 weeks of gestation and at 2 months postpartum. Concentrations of serum 25(OH)D, DBP and albumin were determined, and free 25(OH)D was calculated from the concentrations of total 25(OH)D, DBP and albumin. Serum albumin concentration decreased during pregnancy (P< 0·001), with a nadir at 36 weeks (P< 0·005), during which the concentration was approximately 80 % of the postnatal concentration. Serum DBP concentration increased during pregnancy and at 28 weeks of gestation, which was almost double the postnatal level (P< 0·001). Total and free 25(OH)D concentrations decreased (both P< 0·005) as pregnancy progressed, and both were lowest at 36 weeks of gestation. At 15 weeks, 10 and 63 % of the women had serum 25(OH)D concentration < 30 and 50 nmol/l, respectively, which increased to 53 and 80 % at 36 weeks of gestation. The time course of decreasing concentrations of 25(OH)D during gestation among women recruited during May-July, who delivered between October and November, and among those recruited in August-September, who delivered between February and March, was similar. The lower percentage of free 25(OH)D during pregnancy is mainly due to increased DBP.

  20. [The vitamin D endocrine system].

    PubMed

    Castro, Luiz Claudio Gonçalves de

    2011-11-01

    The vitamin D endocrine system comprises a group of 7-dehydrocholesterol-derived secosteroid molecules, including its active metabolite 1,25-dihydroxy-vitamin D (1,25(OH)(2)D), its precursors and other metabolites, its binding protein (DBP) and nuclear receptor (VDR), as well as cytochrome P450 complex enzymes participating in activation and inactivation pathways of those molecules. The biologic effects of 1,25(OH)(2)D are mediated by VDR, a ligand-activated transcription factor which is a member of the nuclear receptors family, spread in almost all human cells. In addition to its classic role in the regulation of calcium metabolism and bone health, evidence suggests that 1,25(OH)(2)D directly or indirectly modulates about 3% of the human genome, participating in the regulation of chief functions of systemic homeostasis, such as cell growth, differentiation and apoptosis, regulation of immune, cardiovascular and musculoskeletal systems, and insulin metabolism. Given the critical influence of the vitamin D endocrine system in many processes of systemic metabolic equilibrium, the laboratory assays available for the evaluation of this system have to present high accuracy and reproducibility, enabling the establishment of cutoff points that, beyond being consensually accepted, reliably express the vitamin D status of the organism, and the respective clinical-metabolic impacts on the global health of the individual.

  1. Vitamin D status among postmenopausal Malaysian women.

    PubMed

    Rahman, Suriah A; Chee, W S S; Yassin, Zaitun; Chan, S P

    2004-01-01

    Serum levels of 25-hydroxyvitamin D (25 (OH) D) were determined in 276 (103 Malays and 173 Chinese) postmenopausal women, aged 50 to 65 years. The level of 25 (OH) D was significantly lower in the postmenopausal Malay women (44.4 +/-10.6 nmol/L) compared to the Chinese women (68.8 +/- 15.7 nmol/L) (P<0.05). There were 27% Malay women with serum 25 (OH) D in the range of 50 - 100 nmol/L (defined as lowered vitamin D status, or hypovitaminosis D) and 71% with levels in the range of 25 - 50 nmol/L (defined as vitamin D insufficiency) compared to 87% and 11% Chinese women respectively. Serum 25 (OH) D was found to significantly correlate with BMI, fat mass and PTH level. Multivariate analyses showed that race has a strong association with vitamin D status. The high prevalence of inadequate levels of serum vitamin D found in our study may have important public health consequences and warrants the development of a strategy to correct this problem in the older adult Malaysian population. PMID:15331337

  2. 1,25(OH)2D3-enhanced hypercalciuria in genetic hypercalciuric stone-forming rats fed a low-calcium diet

    PubMed Central

    Asplin, John R.; Krieger, Nancy S.; Culbertson, Christopher D.; Asplin, Daniel M.; Bushinsky, David A.

    2013-01-01

    The inbred genetic hypercalciuric stone-forming (GHS) rats exhibit many features of human idiopathic hypercalciuria and have elevated levels of vitamin D receptors (VDR) in calcium (Ca)-transporting organs. On a normal-Ca diet, 1,25(OH)2D3 (1,25D) increases urine (U) Ca to a greater extent in GHS than in controls [Sprague-Dawley (SD)]. The additional UCa may result from an increase in intestinal Ca absorption and/or bone resorption. To determine the source, we asked whether 1,25D would increase UCa in GHS fed a low-Ca (0.02%) diet (LCD). With 1,25D, UCa in SD increased from 1.2 ± 0.1 to 9.3 ± 0.9 mg/day and increased more in GHS from 4.7 ± 0.3 to 21.5 ± 0.9 mg/day (P < 0.001). In GHS rats on LCD with or without 1,25D, UCa far exceeded daily Ca intake (2.6 mg/day). While the greater excess in UCa in GHS rats must be derived from bone mineral, there may also be a 1,25D-mediated decrease in renal tubular Ca reabsorption. RNA expression of the components of renal Ca transport indicated that 1,25D administration results in a suppression of klotho, an activator of the renal Ca reabsorption channel TRPV5, in both SD and GHS rats. This fall in klotho would decrease tubular reabsorption of the 1,25D-induced bone Ca release. Thus, the greater increase in UCa with 1,25D in GHS fed LCD strongly suggests that the additional UCa results from an increase in bone resorption, likely due to the increased number of VDR in the GHS rat bone cells, with a possible component of decreased renal tubular calcium reabsorption. PMID:23926184

  3. Vitamin D status in Egyptian patients with juvenile-onset systemic lupus erythematosus.

    PubMed

    Garf, Kamal El; Marzouk, Huda; Farag, Yomna; Rasheed, Laila; Garf, Ayman El

    2015-09-01

    There are scanty data on the prevalence of vitamin D deficiency and its relation to disease activity among patients with juvenile-onset systemic lupus erythematosus (JoSLE) in the Middle East and North Africa, an area known to be endemic for vitamin D deficiency and insufficiency. The aim of this study was, therefore, to study vitamin D status and its relation to disease activity and parameters in Egyptian patients with JoSLE. Serum levels of 25(OH) D3 in 70 JoSLE patients were compared to 40 age-, sex-, and body mass index-matched healthy controls. The 25(OH) D3 was determined by enzyme-linked immunosorbent assay. Information regarding the medical history, clinical symptoms, and signs was registered at the time of serum sampling. Disease activity of SLE was evaluated according to the SLEDAI score. The mean level of serum 25(OH) D3 was 12 ± 3.7 in JoSLE patients compared to 21 ± 3.5 ng/mL in normal controls (p < 0.001). Forty percent (28/70) of the JoSLE patients has severe 25(OH) D3 deficiency (≤10 ng/mL), and 60 % of the JoSLE patients has 25(OH) D3 insufficiency (≤30 ng/mL). None of the JoSLE patients has 25(OH) D3 level >30 ng/mL. There was no significant correlation between serum levels of 25(OH) D3 and the demographic data, medication used, and some laboratory data of patients with JoSLE. Disease activity score in our patients was insignificantly correlated with serum levels of 25(OH) D3. In spite of vitamin D supplementation in Egyptian JoSLE patients and the presence of vitamin D insufficiency in the control group, there are still significantly lower levels of vitamin D in JoSLE compared to normal controls.

  4. Vitamin D deficiency is associated with insulin resistance in nondiabetics and reduced insulin production in type 2 diabetics.

    PubMed

    Esteghamati, A; Aryan, Z; Esteghamati, Ar; Nakhjavani, M

    2015-04-01

    It is not known whether the association of serum 25-hydroxyvitamin D [25(OH)D] with glycemic measurements of individuals without diabetes is similar to those with diabetes or not. This study is aimed to investigate the association of serum 25(OH)D with glycemic markers of diabetics, nondiabetics, and prediabetics. A case-control study was conducted on age and sex matched 1,195 patients with type 2 DM, 121 prediabetics, and 209 healthy controls. Anthropometric variables, lipid profile, glycemic measurements, and serum 25(OH)D levels were recorded. Serum insulin and C-peptide levels were also measured. All glycemic measurements were compared between diabetics and nondiabetics and prediabetics at different vitamin D status. Patients with DM had lower serum 25(OH)D compared to prediabetics and healthy controls. Endogenous insulin production in response to food intake and in fasting was significantly lower in vitamin D deficient patients with DM compared to those with serum 25(OH)D>40 ng/ml. Diabetic women with serum 25(OH)D<20 ng/ml had lower beta cell function as estimated by lower HOMA-B compared to their counterparts with serum 25(OH)D>40 ng/ml. Healthy individuals with serum 25(OH)D<20 ng/ml had signs of insulin resistance as estimated by significant increase of HOMA-IR, HbA1c, and fasting plasma glucose (FPG). In addition, we found that serum 25(OH)D was inversely associated with insulin resistance. Vitamin D deficiency is associated with insulin resistance in nondiabetics, which is independent of obesity. Furthermore, vitamin D deficiency is associated with reduced insulin production in type 2 diabetics, which was mainly observed in men. Accordingly, a gender disparity also exists in association of serum 25(OH)D with glycemic measurements. PMID:25230322

  5. Development and Validation of a Vitamin D Status Prediction Model in Danish Pregnant Women: A Study of the Danish National Birth Cohort

    PubMed Central

    Bjørn Jensen, Camilla; Thorne-Lyman, Andrew L.; Vadgård Hansen, Linda; Strøm, Marin; Odgaard Nielsen, Nina; Cohen, Arieh; Olsen, Sjurdur Frodi

    2013-01-01

    Vitamin D has been hypothesized to reduce risk of pregnancy complications such as preeclampsia, gestational diabetes mellitus, and preterm delivery. However, many of these outcomes are rare and require a large sample size to study, representing a challenge for cohorts with a limited number of preserved samples. The aims of this study were to (1) identify predictors of serum 25-hydroxy-vitamin D (25(OH)D) among pregnant women in a subsample (N = 1494) of the Danish National Birth Cohort (DNBC) and (2) develop and validate a score predicting 25(OH)D-status in order to explore associations between vitamin D and maternal and offspring health outcomes in the DNBC. In our study sample, 42.3% of the population had deficient levels of vitamin D (<50 nmol/L 25(OH)D) and average levels of 25(OH)D-status were 56.7(s.d. 24.6) nmol/L. A prediction model consisting of intake of vitamin D from diet and supplements, outdoor physical activity, tanning bed use, smoking, and month of blood draw explained 40.1% of the variance in 25(OH)D and mean measured 25(OH)D-level increased linearly by decile of predicted 25(OH)D-score. In total 32.2% of the women were placed in the same quintile by both measured and predicted 25(OH)D-values and 69.9% were placed in the same or adjacent quintile by both methods. Cohen's weighted kappa coefficient (Κ = 0.3) reflected fair agreement between measured 25(OH)D-levels and predicted 25(OH)D-score. These results are comparable to other settings in which vitamin D scores have shown similar associations with disease outcomes as measured 25(OH)D-levels. Our findings suggest that predicted 25(OH)D-scores may be a useful alternative to measured 25(OH)D for examining associations between vitamin D and disease outcomes in the DNBC cohort, but cannot substitute for measured 25(OH)D-levels for estimates of prevalence. PMID:23326380

  6. Optimal vitamin D status and serum parathyroid hormone concentrations in African American women123

    PubMed Central

    Aloia, John F; Talwar, Sonia A; Pollack, Simcha; Feuerman, Martin; Yeh, James K

    2009-01-01

    Background Optimal vitamin D status for the prevention of osteoporosis has been inferred from examinations of the serum 25-hydroxyvitamin D [25(OH)D] concentration below which there is an increase in serum parathyroid hormone (PTH). Objective The objectives of the study were to ascertain whether a threshold for serum 25(OH)D exists below which serum PTH increases and whether persons with 25(OH)D above this threshold have lower rates of bone loss than do persons with 25(OH)D below the threshold. Design The relation of serum 25(OH)D to serum PTH was analyzed in 208 African American women studied longitudinally for 3 y. These healthy women in midlife were randomly assigned to receive placebo or 800 IU vitamin D3/d; after 2 y, the vitamin D3 supplementation was increased to 2000 IU/d. Both groups received calcium supplements to ensure an adequate calcium intake. A systematic literature review found a wide range of threshold values in part due to varied calcium intake. Results A Loess plot suggested a breakpoint between 40 and 50 nmol/L for serum 25(OH)D. A line-line model was fitted to the data, and it showed a spline knot at 44 nmol/L. A heuristic approach verified that PTH does not decline as rapidly when the serum concentration of 25(OH)D is >40 nmol/L as when it is <40 nmol/L. We found no significant difference in rates of bone loss between persons with 25(OH)D concentrations above and below 40 nmol/L. Conclusion Although a threshold for 25(OH)D can be identified, we suggest that it should not be used to recommend optimal vitamin D status. PMID:16960175

  7. Vitamin D Status during Pregnancy in a Multi-Ethnic Population-Representative Swedish Cohort

    PubMed Central

    Bärebring, Linnea; Schoenmakers, Inez; Glantz, Anna; Hulthén, Lena; Jagner, Åse; Ellis, Joy; Bärebring, Mattias; Bullarbo, Maria; Augustin, Hanna

    2016-01-01

    There is currently little information on changes in vitamin D status during pregnancy and its predictors. The aim was to study the determinants of change in vitamin D status during pregnancy and of vitamin D deficiency (<30 nmol/L) in early pregnancy. Blood was drawn in the first (T1) and third trimester (T3). Serum 25-hydroxyvitamin D (25(OH)D) (N = 1985) was analysed by liquid chromatography tandem-mass spectrometry. Season-corrected 25(OH)D was calculated by fitting cosine functions to the data. Mean (standard deviation) 25(OH)D was 64.5(24.5) nmol/L at T1 and 74.6(34.4) at T3. Mean age was 31.3(4.9) years, mean body mass index (BMI) was 24.5(4.2) kg/m2 and 74% of the women were born in Sweden. Vitamin D deficiency was common among women born in Africa (51%) and Asia (46%) and prevalent in 10% of the whole cohort. Determinants of vitamin D deficiency at T1 were of non-North European origin, and had less sun exposure, lower vitamin D intake and lower age. Season-corrected 25(OH)D increased by 11(23) nmol/L from T1 to T3. The determinants of season-corrected change in 25(OH)D were origin, sun-seeking behaviour, clothing style, dietary vitamin D intake, vitamin D supplementation and recent travel <35° N. In conclusion, season-corrected 25(OH)D concentration increased during pregnancy and depended partly on lifestyle factors. The overall prevalence of vitamin D deficiency was low but common among women born in Africa and Asia. Among them, the determinants of both vitamin D deficiency and change in season-corrected vitamin D status were fewer, indicating a smaller effect of sun exposure. PMID:27782070

  8. Vitamin D status is associated with grip strength in centenarians.

    PubMed

    Haslam, Alyson; Johnson, Mary Ann; Hausman, Dorothy B; Cress, M Elaine; Houston, Denise K; Davey, Adam; Poon, Leonard W

    2014-01-01

    Low serum concentrations of 25-hydroxyvitamin D (25(OH)D) have been associated with poor physical function in older adults, but few, if any, studies have examined this relationship in the very old. Therefore, the purpose of this study is to examine this relationship in the very old. Serum 25(OH)D concentrations were obtained from 194 centenarians and near centenarians (98 years and older). The associations between 25(OH)D concentrations and measures of physical function were evaluated with unadjusted and adjusted regression models. We found that 35% of centenarians had 25(OH)D concentrations less than 50 nmol/L. Adjusted mean grip strength was lower for centenarians with 25(OH)D concentrations less than 75 nmol/L than for centenarians with higher concentrations (P<0.05). However, there were no differences in the Georgia Centenarian Study (GCS) Composite Scale, a global measure of physical function, between those with higher and lower 25(OH)D concentrations. We conclude that low 25(OH)D concentrations are associated with poor grip strength, but not GCS Composite Scale, in the very old. Considering the high burden of poor physical function in older adults, understanding the relationship between vitamin D and different measures of physical function, including strength, becomes increasingly important.

  9. Factors Affecting 25-Hydroxyvitamin D Concentration in Response to Vitamin D Supplementation

    PubMed Central

    Mazahery, Hajar; von Hurst, Pamela R.

    2015-01-01

    Sun exposure is the main source of vitamin D. Due to many lifestyle risk factors vitamin D deficiency/insufficiency is becoming a worldwide health problem. Low 25(OH)D concentration is associated with adverse musculoskeletal and non-musculoskeletal health outcomes. Vitamin D supplementation is currently the best approach to treat deficiency and to maintain adequacy. In response to a given dose of vitamin D, the effect on 25(OH)D concentration differs between individuals, and it is imperative that factors affecting this response be identified. For this review, a comprehensive literature search was conducted to identify those factors and to explore their significance in relation to circulating 25(OH)D response to vitamin D supplementation. The effect of several demographic/biological factors such as baseline 25(OH)D, aging, body mass index(BMI)/body fat percentage, ethnicity, calcium intake, genetics, oestrogen use, dietary fat content and composition, and some diseases and medications has been addressed. Furthermore, strategies employed by researchers or health care providers (type, dose and duration of vitamin D supplementation) and environment (season) are other contributing factors. With the exception of baseline 25(OH)D, BMI/body fat percentage, dose and type of vitamin D, the relative importance of other factors and the mechanisms by which these factors may affect the response remains to be determined. PMID:26121531

  10. Isolated Vitamin D Deficiency Is Not Associated with Nonthyroidal Illness Syndrome, but with Thyroid Autoimmunity

    PubMed Central

    Sayki Arslan, Muyesser; Topaloglu, Oya; Ucan, Bekir; Karakose, Melia; Karbek, Basak; Tutal, Esra; Caliskan, Mustafa; Ginis, Zeynep; Cakal, Erman; Sahin, Mustafa; Ozbek, Mustafa; Delibasi, Tuncay

    2015-01-01

    Aim. This study aimed to compare thyroid functions, thyroid autoantibodies, and the existence of nonthyroidal illness syndrome (NTIS) according to vitamin D level. Materials and Methods. The study included age- and BMI-matched healthy volunteers with and without vitamin D deficiency. In addition, the nonthyroidal illness syndrome status was evaluated. Results. Anti-TPO positivity was significantly more common in those with severe and moderate vitamin D deficiency, as compared to those with a normal 25(OH)D level. Furthermore, TSH levels were significantly lower in those with severe and moderate vitamin D deficiency than in those with a normal 25(OH)D level. In addition, there was a significant weak inverse correlation between anti-TPO positivity and the 25(OH)D level and a positive correlation between the TSH level and 25(OH)D level. Only 1 thyroid function test result was compatible with NTIS among the participants with moderate vitamin D deficiency; therefore the difference was not significant. Conclusions. The prevalence of thyroid autoantibody positivity was higher in those with severe and moderate vitamin D deficiency than in those with a normal 25(OH)D level. Additional large-scale studies must be conducted to determine if vitamin D deficiency plays a causal role in the pathogenesis of Hashimoto's thyroiditis and NTIS. PMID:25654127

  11. [Updates on rickets and osteomalacia: vitamin D dependency].

    PubMed

    Kitanaka, Sachiko

    2013-10-01

    Vitamin D dependency was first termed for patients resembling vitamin D-deficiency but require high doses of vitamin D administration. Now this disease is known to be caused by defective conversion of 25OHD to 1,25 (OH) 2D, which is termed vitamin D-dependent rickets type 1 or 1α-hydroxylase deficiency, or by end-organ unresponsiveness to 1,25 (OH) 2D, which is called vitamin D-dependent rickets type 2 or hereditary vitamin D-resistant rickets. Recent advance in the molecular analysis of these diseases revealed variety in the presentation and in the inheritance patterns. Molecular diagnosis would be preferable for some atypical cases for adequate therapy.

  12. Vitamin D status and sun exposure in southeast Asia

    PubMed Central

    Nimitphong, Hataikarn; Holick, Michael F.

    2013-01-01

    Vitamin D deficiency is more common in South Asia and Southeast Asia than is appreciated. Most studies defined 25-hydroxyvitamin D levels [25(OH)D] levels of less than 50 nmol/L (20 ng/mL) as vitamin D deficiency. With this cut-off level, the prevalence of vitamin D deficiency was about 70% or higher in South Asia and varied from 6–70% in Southeast Asia. The determinants for the variation of vitamin D status are skin pigmentation, aging, the sun protection behaviors such as application of a sunscreen, religious, lifestyle and nutritional differences. Advanced age is a known risk factor for vitamin D deficiency. Interestingly, elderly in countries such as Korea and Thailand, had higher 25(OH)D levels when compared with young people. This widespread vitamin D deficiency problem especially in the young generation is an urgent health issue that needs to be remedied. PMID:24494040

  13. Effect of vitamin D status on pharmacological treatment efficiency

    PubMed Central

    Karczmarewicz, Elżbieta; Czekuć-Kryśkiewicz, Edyta; Płudowski, Paweł

    2013-01-01

    At least 80% of the whole Polish population, including prepubertal children and adolescents, adults and seniors, are vitamin D deficient, defined as 25(OH)D < 50 nmol/L. 83% of Polish newborns start their lives at the state of vitamin D deficiency because 78% of their mothers are also deficient. It was observed that treating patient vitamin D deficiency to vitamin D status serum 25(OH)D) 75–100 nmol/L increased effectiveness of therapies in infectious diseases (chronic hepatitis C, tuberculosis), osteoporosis, multiple sclerosis, epilepsy, Chronic Kidney Diseases and atopic dermatitis. . For these reasons doctors should take special attension to vitamin D status in patients suffering for these diseases properly implementing recent vitamin D recommendation. PMID:24494037

  14. Effect of vitamin D status on pharmacological treatment efficiency

    PubMed Central

    Karczmarewicz, Elzbieta; Czekuc-Kryskiewicz, Edyta; Płudowski, Paweł

    2013-01-01

    At least 80% of the whole Polish population, including prepubertal children and adolescents, adults and seniors, are vitamin D deficient, defined as 25(OH)D < 50 nmol/L. 83% of Polish newborns start their lives at the state of vitamin D deficiency because 78% of their mothers are also deficient. It was observed that treating patient vitamin D deficiency to vitamin D status serum 25(OH)D) 75–100 nmol/L increased effectiveness of therapies in infectious diseases (chronic hepatitis C, tuberculosis), osteoporosis, multiple sclerosis, epilepsy, Chronic Kidney Diseases and atopic dermatitis. . For these reasons doctors should take special attention to vitamin D status in patients suffering for these diseases properly implementing recent vitamin D recommendation. PMID:24194969

  15. Vitamin D₃ metabolites enhance the NLRP3-dependent secretion of IL-1β from human THP-1 monocytic cells.

    PubMed

    Tulk, Sarah E; Liao, Kuo-Chieh; Muruve, Daniel A; Li, Yan; Beck, Paul L; MacDonald, Justin A

    2015-05-01

    Vitamin D3 has emerged as an important regulator of the immune system. With metabolic enzymes for vitamin D3 activation and vitamin D receptors (VDR) now identified in a variety of immune cells, the active vitamin D3 metabolite 1,25(OH)2D3, is thought to possess immunomodulatory properties. We examined whether 1,25(OH)2D3 might also enhance the NLRP3-dependent release of mature IL-1β from macrophages. PMA-differentiated THP-1 cells were stimulated with vitamin D3 metabolites and assessed for CYP27, CYP24, NLRP3, ASC, pro-caspase-1 expression by western blot and real-time qPCR as well as inflammasome activation with pro-inflammatory cytokine IL-1β release measured by ELISA. Exposure to 1,25(OH)2D3 had no effect on the basal expression levels of VDR; however, CYP27A1 transcript was suppressed and CYP24A1 transcript was substantively elevated. Both 1,25(OH)2D3 - and 25(OH)D3 induced IL-1β release from THP-1 cells, and these effects were blocked with application of the caspase-1 inhibitor YVAD and the NLRP3 inhibitors glyburide and Bay 11-7082. Interestingly, 1,25 (OH)2D3 exposure reduced NLRP3 protein expression but had no effect on ASC or pro-caspase-1 protein levels. The increase in mature IL-1β elicited by 1,25(OH)2D3 was modest compared to that found for ATP or C. difficile toxins. However, co-treatment of THP-1 cells with ATP and 1,25(OH)2D3 resulted in more IL-1β secretion than ATP or 1,25(OH)2D3 alone. PMID:25639477

  16. Vitamin D₃ metabolites enhance the NLRP3-dependent secretion of IL-1β from human THP-1 monocytic cells.

    PubMed

    Tulk, Sarah E; Liao, Kuo-Chieh; Muruve, Daniel A; Li, Yan; Beck, Paul L; MacDonald, Justin A

    2015-05-01

    Vitamin D3 has emerged as an important regulator of the immune system. With metabolic enzymes for vitamin D3 activation and vitamin D receptors (VDR) now identified in a variety of immune cells, the active vitamin D3 metabolite 1,25(OH)2D3, is thought to possess immunomodulatory properties. We examined whether 1,25(OH)2D3 might also enhance the NLRP3-dependent release of mature IL-1β from macrophages. PMA-differentiated THP-1 cells were stimulated with vitamin D3 metabolites and assessed for CYP27, CYP24, NLRP3, ASC, pro-caspase-1 expression by western blot and real-time qPCR as well as inflammasome activation with pro-inflammatory cytokine IL-1β release measured by ELISA. Exposure to 1,25(OH)2D3 had no effect on the basal expression levels of VDR; however, CYP27A1 transcript was suppressed and CYP24A1 transcript was substantively elevated. Both 1,25(OH)2D3 - and 25(OH)D3 induced IL-1β release from THP-1 cells, and these effects were blocked with application of the caspase-1 inhibitor YVAD and the NLRP3 inhibitors glyburide and Bay 11-7082. Interestingly, 1,25 (OH)2D3 exposure reduced NLRP3 protein expression but had no effect on ASC or pro-caspase-1 protein levels. The increase in mature IL-1β elicited by 1,25(OH)2D3 was modest compared to that found for ATP or C. difficile toxins. However, co-treatment of THP-1 cells with ATP and 1,25(OH)2D3 resulted in more IL-1β secretion than ATP or 1,25(OH)2D3 alone.

  17. 1α,25(OH)2D3 Suppresses the Migration of Ovarian Cancer SKOV-3 Cells through the Inhibition of Epithelial–Mesenchymal Transition

    PubMed Central

    Hou, Yong-Feng; Gao, Si-Hai; Wang, Ping; Zhang, He-Mei; Liu, Li-Zhi; Ye, Meng-Xuan; Zhou, Guang-Ming; Zhang, Zeng-Li; Li, Bing-Yan

    2016-01-01

    Ovarian cancer is the most lethal gynecological malignancy due to its high metastatic ability. Epithelial-mesenchymal transition (EMT) is essential during both follicular rupture and epithelium regeneration. However, it may also accelerate the progression of ovarian carcinomas. Experimental studies have found that 1α,25-dihydroxyvitamin-D3 [1α,25(OH)2D3] can inhibit the proliferation of ovarian cancer cells. In this study, we investigated whether 1α,25(OH)2D3 could inhibit the migration of ovarian cancer cells via regulating EMT. We established a model of transient transforming growth factor-β1(TGF-β1)-induced EMT in human ovarian adenocarcinoma cell line SKOV-3 cells. Results showed that, compared with control, 1α,25(OH)2D3 not only inhibited the migration and the invasion of SKOV-3 cells, but also promoted the acquisition of an epithelial phenotype of SKOV-3 cells treated with TGF-β1. We discovered that 1α,25(OH)2D3 increased the expression of epithelial marker E-cadherin and decreased the level of mesenchymal marker, Vimentin, which was associated with the elevated expression of VDR. Moreover, 1α,25(OH)2D3 reduced the expression level of transcription factors of EMT, such as slug, snail, and β-catenin. These results indicate that 1α,25(OH)2D3 suppresses the migration and invasion of ovarian cancer cells by inhibiting EMT, implying that 1α,25(OH)2D3 might be a potential therapeutic agent for the treatment of ovarian cancer. PMID:27548154

  18. 1α,25(OH)₂D₃ Suppresses the Migration of Ovarian Cancer SKOV-3 Cells through the Inhibition of Epithelial-Mesenchymal Transition.

    PubMed

    Hou, Yong-Feng; Gao, Si-Hai; Wang, Ping; Zhang, He-Mei; Liu, Li-Zhi; Ye, Meng-Xuan; Zhou, Guang-Ming; Zhang, Zeng-Li; Li, Bing-Yan

    2016-01-01

    Ovarian cancer is the most lethal gynecological malignancy due to its high metastatic ability. Epithelial-mesenchymal transition (EMT) is essential during both follicular rupture and epithelium regeneration. However, it may also accelerate the progression of ovarian carcinomas. Experimental studies have found that 1α,25-dihydroxyvitamin-D3 [1α,25(OH)₂D₃] can inhibit the proliferation of ovarian cancer cells. In this study, we investigated whether 1α,25(OH)₂D₃ could inhibit the migration of ovarian cancer cells via regulating EMT. We established a model of transient transforming growth factor-β1(TGF-β1)-induced EMT in human ovarian adenocarcinoma cell line SKOV-3 cells. Results showed that, compared with control, 1α,25(OH)₂D₃ not only inhibited the migration and the invasion of SKOV-3 cells, but also promoted the acquisition of an epithelial phenotype of SKOV-3 cells treated with TGF-β1. We discovered that 1α,25(OH)₂D₃ increased the expression of epithelial marker E-cadherin and decreased the level of mesenchymal marker, Vimentin, which was associated with the elevated expression of VDR. Moreover, 1α,25(OH)₂D₃ reduced the expression level of transcription factors of EMT, such as slug, snail, and β-catenin. These results indicate that 1α,25(OH)₂D₃ suppresses the migration and invasion of ovarian cancer cells by inhibiting EMT, implying that 1α,25(OH)₂D₃ might be a potential therapeutic agent for the treatment of ovarian cancer. PMID:27548154

  19. Relationship between vitamin D status and vascular complications in patients with type 2 diabetes mellitus.

    PubMed

    Jung, Chan-Hee; Kim, Kyu-Jin; Kim, Bo-Yeon; Kim, Chul-Hee; Kang, Sung Koo; Mok, Ji-Oh

    2016-02-01

    We aimed to investigate the association between serum 25-hydroxyvitamin D (25[OH]D) and microvascular complications in type 2 diabetes mellitus (T2DM) patients. It was hypothesized that lower 25(OH)D would be associated with increased microvascular complications in T2DM. A total of 257 T2DM patients (111 men, 146 women) who underwent diabetic microvascular complication (peripheral neuropathy, nephropathy, retinopathy) studies were recruited. Patients were categorized into 3 groups according to vitamin D status: vitamin D sufficient (n = 41, 25[OH]D ≥ 20 ng/mL), vitamin D insufficient (n = 132, 10 ≤ 25[OH]D < 20 ng/mL), and vitamin D deficient (n = 84, 25[OH]D < 10 ng/mL). In men, the prevalence of diabetic peripheral neuropathy (DPN) was significantly higher in patients with vitamin D deficiency than in those with insufficiency or sufficiency (38%, 11.7%, and 10%, respectively; P = .005). In addition, the prevalence of diabetic nephropathy (DN) was significantly higher in women with vitamin D deficiency than in the other 2 groups (40%, 20.6%, and 0%; P = .007). Compared with men in the vitamin D-sufficient group (reference), men in the vitamin D-deficient group had an increased risk of DPN after adjusting for confounding factors (odds ratio, 7.79; 95% confidence interval, 1.52-40.05). For women, when the vitamin D-sufficient group was used as a reference, those in the vitamin D-deficient group had an increased risk of DN after adjusting for confounding factors (odds ratio, 4.27; 95% confidence interval, 1.58-11.56). This present study found that a serum 25(OH)D level less than 10 ng/mL is independently associated with increased DPN in male patients and increased DN in female patients with T2DM.

  20. The Relationship between Vitamin D Status and Allergic Diseases in New Zealand Preschool Children

    PubMed Central

    Cairncross, Carolyn; Grant, Cameron; Stonehouse, Welma; Conlon, Cath; McDonald, Barry; Houghton, Lisa; Eyles, Darryl; Camargo, Carlos A.; Coad, Jane; von Hurst, Pamela

    2016-01-01

    Recent research on vitamin D in young children has expanded from bone development to exploring immunomodulatory effects. Our aim was to investigate the relationship of vitamin D status and allergic diseases in preschool-aged children in New Zealand. Dried capillary blood spots were collected from 1329 children during late-winter to early-spring for 25(OH)D measurement by LC-MS/MS. Caregivers completed a questionnaire about their child’s recent medical history. Analysis was by multivariable logistic regression. Mean 25(OH)D concentration was 52(SD19) nmol/L, with 7% of children <25 nmol/L and 49% <50 nmol/L. Children with 25(OH)D concentrations ≥75 nmol/L (n = 29) had a two-fold increased risk for parent-report of doctor-diagnosed food allergy compared to children with 25(OH)D 50–74.9 nmol/L (OR = 2.21, 1.33–3.68, p = 0.002). No associations were present between 25(OH)D concentration and presence of parent-reported eczema, allergic rhinoconjunctivitis or atopic asthma. Vitamin D deficiency was not associated with several allergic diseases in these New Zealand preschool children. In contrast, high 25(OH)D concentrations were associated with a two-fold increased risk of parental-report food allergy. This increase supports further research into the association between vitamin D status and allergic disease in preschool children. PMID:27258306

  1. The Relationship between Vitamin D Status and Allergic Diseases in New Zealand Preschool Children.

    PubMed

    Cairncross, Carolyn; Grant, Cameron; Stonehouse, Welma; Conlon, Cath; McDonald, Barry; Houghton, Lisa; Eyles, Darryl; Camargo, Carlos A; Coad, Jane; von Hurst, Pamela

    2016-06-01

    Recent research on vitamin D in young children has expanded from bone development to exploring immunomodulatory effects. Our aim was to investigate the relationship of vitamin D status and allergic diseases in preschool-aged children in New Zealand. Dried capillary blood spots were collected from 1329 children during late-winter to early-spring for 25(OH)D measurement by LC-MS/MS. Caregivers completed a questionnaire about their child's recent medical history. Analysis was by multivariable logistic regression. Mean 25(OH)D concentration was 52(SD19) nmol/L, with 7% of children <25 nmol/L and 49% <50 nmol/L. Children with 25(OH)D concentrations ≥75 nmol/L (n = 29) had a two-fold increased risk for parent-report of doctor-diagnosed food allergy compared to children with 25(OH)D 50-74.9 nmol/L (OR = 2.21, 1.33-3.68, p = 0.002). No associations were present between 25(OH)D concentration and presence of parent-reported eczema, allergic rhinoconjunctivitis or atopic asthma. Vitamin D deficiency was not associated with several allergic diseases in these New Zealand preschool children. In contrast, high 25(OH)D concentrations were associated with a two-fold increased risk of parental-report food allergy. This increase supports further research into the association between vitamin D status and allergic disease in preschool children.

  2. Determination of optimal vitamin D3 dosing regimens in HIV-infected paediatric patients using a population pharmacokinetic approach

    PubMed Central

    Foissac, Frantz; Meyzer, Candice; Frange, Pierre; Chappuy, Hélène; Benaboud, Sihem; Bouazza, Naïm; Friedlander, Gérard; Souberbielle, Jean-Claude; Urien, Saïk; Blanche, Stéphane; Tréluyer, Jean-Marc

    2014-01-01

    Aims To investigate 25-hydroxycholecalciferol [25(OH)D] population pharmacokinetics in children and adolescents, to establish factors that influence 25(OH)D pharmacokinetics and to assess different vitamin D3 dosing schemes to reach sufficient 25(OH)D concentrations (>30 ng ml−1). Methods This monocentric prospective study included 91 young HIV-infected patients aged 3 to 24 years. Patients received a 100 000 IU vitamin D3 supplementation. A total of 171 25(OH)D concentrations were used to perform a population pharmacokinetic analysis. Results At baseline 28% of patients had 25(OH)D concentrations below 10 ng ml−1, 69% between 10 and 30 ng ml−1 and 3% above 30 ng ml−1. 25(OH)D pharmacokinetics were best described by a one compartment model with an additional production parameter reflecting the input from diet and sun exposure. The effects of skin phototype and bodyweight were significant on 25(OH)D production before any supplementation. The basal level was 27% lower in non-white skin phototype patients and was slightly decreased with bodyweight. No significant differences in 25(OH)D concentrations were related to antiretroviral drugs. To obtain concentrations between 30 and 80 ng ml−1, patients with baseline concentrations between 10 and 30 ng ml−1 should receive 100 000 IU per 3 months. However, vitamin D deficient patients (<10 ng ml−1) would need an intensive phase of 100 000 IU per 2 weeks (two times) followed 2 weeks later by a maintenance phase of 100 000 IU per 3 months. Conclusions Skin phototype and bodyweight had an influence on the basal production of 25(OH)D. According to 25(OH)D baseline concentrations, dosing schemes to reach sufficient concentrations are proposed. PMID:24902982

  3. High prevalence of vitamin D deficiency and insufficiency in patients with manifest Huntington disease: An explorative study.

    PubMed

    Chel, Victor Gm; Ooms, Marcel E; van der Bent, Jessie; Veldkamp, Fleur; Roos, Raymund Ac; Achterberg, Wilco P; Lips, Paul

    2013-06-01

    Vitamin D deficiency and insufficiency are common in older institutionalized people and known to be associated with muscle weakness, impaired balance and increased fall risk. Falls and balance problems are common in people with Huntington disease (HD). Despite this, the prevalence of vitamin D deficiency in patients with manifest HD has never been investigated. Serum 25(OH)D levels were measured in routinely drawn blood samples from 28 Dutch institutionalized patients with manifest Huntington disease. Mean serum 25(OH)D level was 33 nmol/l (SD 15). Twenty-five subjects (89%) were vitamin D deficient or insufficient (25(OH)D < 50 nmol/L). A positive association was found between serum 25(OH)D levels and Functional Ambulation Classification (FAC) scores (p = 0.023). PMID:24516688

  4. Different doses of supplemental vitamin D maintain interleukin-5 without altering skeletal muscle strength: a randomized, double-blind, placebo-controlled study in vitamin D sufficient adults

    PubMed Central

    2012-01-01

    Background Supplemental vitamin D modulates inflammatory cytokines and skeletal muscle function, but results are inconsistent. It is unknown if these inconsistencies are dependent on the supplemental dose of vitamin D. Therefore, the purpose of this study was to identify the influence of different doses of supplemental vitamin D on inflammatory cytokines and muscular strength in young adults. Methods Men (n = 15) and women (n = 15) received a daily placebo or vitamin D supplement (200 or 4000 IU) for 28-d during the winter. Serum 25-hydroxyvitamin D (25(OH)D), cytokine concentrations and muscular (leg) strength measurements were performed prior to and during supplementation. Statistical significance of data were assessed with a two-way (time, treatment) analysis of variance (ANOVA) with repeated measures, followed by a Tukey's Honestly Significant Difference to test multiple pairwise comparisons. Results Upon enrollment, 63% of the subjects were vitamin D sufficient (serum 25(OH)D ≥ 30 ng/ml). Serum 25(OH)D and interleukin (IL)-5 decreased (P < 0.05) across time in the placebo group. Supplemental vitamin D at 200 IU maintained serum 25(OH)D concentrations and increased IL-5 (P < 0.05). Supplemental vitamin D at 4000 IU increased (P < 0.05) serum 25(OH)D without altering IL-5 concentrations. Although serum 25(OH)D concentrations correlated (P < 0.05) with muscle strength, muscle strength was not changed by supplemental vitamin D. Conclusion In young adults who were vitamin D sufficient prior to supplementation, we conclude that a low-daily dose of supplemental vitamin D prevents serum 25(OH)D and IL-5 concentration decreases, and that muscular strength does not parallel the 25(OH)D increase induced by a high-daily dose of supplemental vitamin D. Considering that IL-5 protects against viruses and bacterial infections, these findings could have a broad physiological importance regarding the ability of vitamin D sufficiency to mediate the immune systems protection

  5. Association Between Vitamin D Status and Weaning From Prolonged Mechanical Ventilation in Survivors of Critical Illness

    PubMed Central

    Verceles, Avelino C; Weiler, Bethany; Koldobskiy, Dafna; Goldberg, Andrew P; Netzer, Giora; Sorkin, John D

    2015-01-01

    BACKGROUND In this study, we examined the association between 25-hydroxyvitamin D (25(OH)D) concentration and successful weaning from mechanical ventilation in a cohort of ICU survivors requiring prolonged mechanical ventilation. METHODS This was a retrospective cohort study of ICU survivors admitted to a long-term acute care hospital. Demographic data were extracted from medical records, including 25(OH)D concentrations drawn on admission. Subjects were divided into 2 groups based on their 25(OH)D concentrations (deficient, < 20 ng/mL; not deficient, ≥ 20 ng/mL), and associations between 25(OH)D concentration and successful weaning were calculated. RESULTS A total of 183 subjects were studied. A high prevalence of 25(OH)D deficiency was found (61%, 111/183). No association was found between 25(OH)D concentration and weaning from mechanical ventilation. Increased comorbidity burden (Charlson comorbidity index) was associated with decreased odds of weaning (odds ratio of 0.50, 95% CI 0.25– 0.99, P = .05). CONCLUSIONS Vitamin D deficiency is common in ICU survivors requiring prolonged mechanical ventilation. Surprisingly, there was no significant relationship between 25(OH)D concentration and successful weaning. This finding may be due to the low 25(OH)D concentrations seen in our subjects. Given what is known about vitamin D and lung function and given the low vitamin D concentrations seen in patients requiring long-term ventilatory support, interventional studies assessing the effects of 25(OH)D supplementation in these patients are needed. PMID:25715347

  6. 1,25 (OH)2D3 enhances PTH-induced Ca2+ transients in preosteoblasts by activating L-type Ca2+ channels

    NASA Technical Reports Server (NTRS)

    Li, W.; Duncan, R. L.; Karin, N. J.; Farach-Carson, M. C.

    1997-01-01

    We previously demonstrated electrophysiologically that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] shifts the activation threshold of L-type Ca2+ channels in osteoblasts toward the resting potential and prolongs mean open time. Presently, we used single-cell Ca2+ imaging to study the combined effects of 1,25(OH)2D3 and parathyroid hormone (PTH) during generation of Ca2+ transients in fura 2-loaded MC3T3-E1 cells. Pretreatment with 1,25(OH)2D3 concentrations, which alone did not produce Ca2+ transients, consistently enhanced Ca2+ responses to PTH. Enhancement was dose dependent over the range of 1 to 10 nM and was blocked by pretreatment with 5 microM nitrendipine during pretreatment. A 1,25(OH)2D3 analog that activates L-type channels and shifts their activation threshold also enhanced PTH responses. In contrast, an analog devoid of membrane Ca2+ effects did not enhance PTH-induced Ca2+ transients. The PTH-induced Ca2+ transient involved activation of a dihydropyridine-insensitive cation channel that was inhibited by Gd3+. Together, these data suggest that 1,25(OH)2D3 increases osteoblast responsiveness to PTH through rapid modification of L-type Ca2+ channel gating properties, whose activation enhances Ca2+ entry through other channels such as the PTH-responsive, Gd(3+)-sensitive cation channel.

  7. Inverse Correlation between Vitamin D and C-Reactive Protein in Newborns

    PubMed Central

    Tao, Rui-Xue; Zhou, Qi-Fan; Xu, Zhi-Wei; Hao, Jia-Hu; Huang, Kun; Mou, Zhe; Jiang, Xiao-Min; Tao, Fang-Biao; Zhu, Peng

    2015-01-01

    Some studies suggested that adequate vitamin D might reduce inflammation in adults. However, little is known about this association in early life. We aimed to determine the relationship between cord blood 25-hydroxyvitamin D (25(OH)D) and C-reactive protein (CRP) in neonates. Cord blood levels of 25(OH)D and CRP were measured in 1491 neonates in Hefei, China. Potential confounders including maternal sociodemographic characteristics, perinatal health status, lifestyle, and birth outcomes were prospectively collected. The average values of cord blood 25(OH)D and CRP were 39.43 nmol/L (SD = 20.35) and 6.71 mg/L (SD = 3.07), respectively. Stratified by 25(OH)D levels, per 10 nmol/L increase in 25(OH)D, CRP decreased by 1.42 mg/L (95% CI: 0.90, 1.95) among neonates with 25(OH)D <25.0 nmol/L, and decreased by 0.49 mg/L (95% CI: 0.17, 0.80) among neonates with 25(OH)D between 25.0 nmol/L and 49.9 nmol/L, after adjusting for potential confounders. However, no significant association between 25(OH)D and CRP was observed among neonates with 25(OH)D ≥50 nmol/L. Cord blood 25(OH)D and CRP levels showed a significant seasonal trend with lower 25(OH)D and higher CRP during winter-spring than summer-autumn. Stratified by season, a significant linear association of 25(OH)D with CRP was observed in neonates born in winter-spring (adjusted β = −0.11, 95% CI: −0.13, −0.10), but not summer-autumn. Among neonates born in winter-spring, neonates with 25(OH)D <25 nmol/L had higher risk of CRP ≥10 mg/L (adjusted OR = 3.06, 95% CI: 2.00, 4.69), compared to neonates with 25(OH)D ≥25 nmol/L. Neonates with vitamin D deficiency had higher risk of exposure to elevated inflammation at birth. PMID:26569292

  8. Inverse Correlation between Vitamin D and C-Reactive Protein in Newborns.

    PubMed

    Tao, Rui-Xue; Zhou, Qi-Fan; Xu, Zhi-Wei; Hao, Jia-Hu; Huang, Kun; Mou, Zhe; Jiang, Xiao-Min; Tao, Fang-Biao; Zhu, Peng

    2015-11-01

    Some studies suggested that adequate vitamin D might reduce inflammation in adults. However, little is known about this association in early life. We aimed to determine the relationship between cord blood 25-hydroxyvitamin D (25(OH)D) and C-reactive protein (CRP) in neonates. Cord blood levels of 25(OH)D and CRP were measured in 1491 neonates in Hefei, China. Potential confounders including maternal sociodemographic characteristics, perinatal health status, lifestyle, and birth outcomes were prospectively collected. The average values of cord blood 25(OH)D and CRP were 39.43 nmol/L (SD = 20.35) and 6.71 mg/L (SD = 3.07), respectively. Stratified by 25(OH)D levels, per 10 nmol/L increase in 25(OH)D, CRP decreased by 1.42 mg/L (95% CI: 0.90, 1.95) among neonates with 25(OH)D <25.0 nmol/L, and decreased by 0.49 mg/L (95% CI: 0.17, 0.80) among neonates with 25(OH)D between 25.0 nmol/L and 49.9 nmol/L, after adjusting for potential confounders. However, no significant association between 25(OH)D and CRP was observed among neonates with 25(OH)D ≥50 nmol/L. Cord blood 25(OH)D and CRP levels showed a significant seasonal trend with lower 25(OH)D and higher CRP during winter-spring than summer-autumn. Stratified by season, a significant linear association of 25(OH)D with CRP was observed in neonates born in winter-spring (adjusted β = -0.11, 95% CI: -0.13, -0.10), but not summer-autumn. Among neonates born in winter-spring, neonates with 25(OH)D <25 nmol/L had higher risk of CRP ≥10 mg/L (adjusted OR = 3.06, 95% CI: 2.00, 4.69), compared to neonates with 25(OH)D ≥25 nmol/L. Neonates with vitamin D deficiency had higher risk of exposure to elevated inflammation at birth. PMID:26569292

  9. Vitamin D status of older adults of diverse ancestry living in the greater Toronto area

    PubMed Central

    2013-01-01

    Background Physiological and lifestyle factors put older adults at an increased risk of vitamin D insufficiency and resulting negative health outcomes. Here we explore the vitamin D status in a sample of community dwelling older adults of diverse ancestry living in the Greater Toronto area (GTA). Methods Two hundred and twenty-four (224) adults over 60 years of age were recruited from the Square One Older Adult Centre, in Mississauga, Ontario. Circulating 25-hydroxyvitamin D (25(OH)D) concentrations were measured from dried blood spot cards. Dietary and supplemental intakes of vitamin D were assessed via questionnaires. Skin pigmentation was assessed quantitatively by measuring melanin levels using a reflectometer. Results The mean 25(OH)D concentration in the total sample was 82.4 nmol/L. There were no statistically significant differences in serum 25(OH)D concentrations, supplemental or dietary vitamin D intakes between the three major ancestral groups (East Asians, Europeans and South Asians). Females had significantly higher 25(OH)D concentrations than males (84.5 nmol/L vs. 72.2 nmol/L, p = 0.012). The proportion of participants with 25(OH)D concentrations below 50 nmol/L and 75 nmol/L were 12.1%, and 38.8%, respectively. The mean daily supplemental intake of vitamin D was 917 IU/day. Vitamin D intake from supplements was the major factor determining 25(OH)D concentrations (p < 0.001). Conclusions Mean concentration of 25(OH)D in a sample of older adults of diverse ancestry living in the GTA exceeded 80 nmol/L, and there were no significant differences in 25(OH)D levels between ancestral groups. These results sharply contrast with our recent study focused on young adults of diverse ancestry living in the same geographic area, in which we found substantially lower 25(OH)D concentrations (mean 39.5 nmol/L), low supplemental vitamin D intake (114 IU/day), and significant differences in 25(OH)D levels between ancestral groups. High daily intake

  10. Vitamin D status among preterm and full-term infants at birth

    PubMed Central

    Burris, Heather H.; Van Marter, Linda J.; McElrath, Thomas F.; Tabatabai, Patrik; Litonjua, Augusto A.; Weiss, Scott T.; Christou, Helen

    2015-01-01

    Background Risk factors for maternal vitamin D deficiency and preterm birth overlap but the distribution of 25-hydroxyvitamin D (25(OH)D) levels among preterm infants is not known. We aimed to determine associations between 25(OH)D levels and gestational age. Methods We measured umbilical cord plasma levels of 25(OH)D from 471 infants born at Brigham and Women’s Hospital in Boston. We used generalized estimating equations to determine whether preterm (<37 weeks’ gestation) or very preterm (<32 weeks’ gestation) infants had greater odds of 25(OH)D levels < 20 ng/ml than more mature infants. We adjusted for potential confounding by season of birth, maternal age, race, marital status and singleton or multiple gestation. Results Mean cord plasma 25(OH)D level was 34.0 ng/ml (range 4.1 to 95.3, and SD 14.1). Infants born before 32 weeks’ gestation had increased odds of 25(OH)D levels < 20 ng/ml in unadjusted (OR 2.2, 95% CI 1.1, 4.3) and adjusted models (OR 2.4, 95% CI 1.2, 5.3) compared to more mature infants. Conclusion Infants born < 32 weeks’ gestation are at higher risk than more mature infants for low 25(OH)D levels. Further investigation of the relationships between low 25(OH)D levels and preterm birth and its sequelae is thus warranted. PMID:24121425

  11. Meta-Analysis of the Association between Vitamin D and Autoimmune Thyroid Disease

    PubMed Central

    Wang, Jiying; Lv, Shishi; Chen, Guo; Gao, Chenlin; He, Jianhua; Zhong, Haihua; Xu, Yong

    2015-01-01

    Although emerging evidence suggests that low levels of vitamin D may contribute to the development of autoimmune disease, the relationship between vitamin D reduction and autoimmune thyroid disease (AITD), which includes Graves’ disease (GD) and Hashimoto thyroiditis (HT), is still controversial. The aim was to evaluate the association between vitamin D levels and AITD through systematic literature review. We identified all studies that assessed the association between vitamin D and AITD from PubMed, Embase, CENTRAL, and China National Knowledge Infrastructure (CNKI) databases. We included studies that compared vitamin D levels between AITD cases and controls as well as those that measured the odds of vitamin D deficiency by AITD status. We combined the standardized mean differences (SMD) or the odds ratios (OR) in a random effects model. Twenty case-control studies provided data for a quantitative meta-analysis. Compared to controls, AITD patients had lower levels of 25(OH)D (SMD: −0.99, 95% CI: −1.31, −0.66) and were more likely to be deficient in 25(OH)D (OR 2.99, 95% CI: 1.88, 4.74). Furthermore, subgroup analyses result showed that GD and HT patients also had lower 25(OH)D levels and were more likely to have a 25(OH)D deficiency, suggesting that low levels of serum 25(OH)D was related to AITD. PMID:25854833

  12. Vitamin D–Binding Protein Levels Do Not Influence The Effect of Vitamin D Repletion on Serum PTH and Calcium: Data From a Randomized, Controlled Trial

    PubMed Central

    McGee, David; Breslow, Jan L.

    2014-01-01

    Context: Vitamin D deficiency, defined by the total serum 25-hydroxyvitamin D [25(OH)D] level, is common and more prevalent among Blacks than whites. Vitamin D–binding protein (DBP) levels vary with race and may modulate “bioavailable” levels of 25(OH)D. Objective: To determine the effect of DBP levels on the functional response to vitamin D. Setting and Design: A randomized, placebo-controlled trial of vitamin D repletion for 2 mo, which took place at an outpatient research unit. Participants included 150 vitamin D–deficient (25(OH)D <20 ng/mL) adults. Participants were randomly assigned to receive either 50,000 IU of vitamin D3 or placebo weekly for 8 weeks. This is a post-hoc analysis using DBP, 25(OH)D, PTH, and calcium levels. Results: Blacks had lower total 25(OH)D (12 vs 15 ng/mL, P < .001) and DBP levels (119 vs 234 μg/mL, P < .001) than non-Blacks. DBP levels were similar before and after vitamin D3 or placebo treatment (r = 0.98, P < .001). Baseline total 25(OH)D levels were a significant determinant of baseline PTH levels (P < .001). The change in total 25(OH)D was associated with the change in PTH (P < 0.001) and calcium levels (P < .05). In contrast, DBP levels were not a determinant of baseline PTH (P = .57) nor significantly related to changes in either PTH (P = .53) or calcium levels (P = .88). Conclusions: DBP levels are stable in Blacks and non-Blacks, and do not change with correction of vitamin D deficiency. Even for individuals with total 25(OH)D levels < 20 ng/mL, Blacks have significantly lower DBP levels than non-Blacks. However, within this range of total 25(OH)D, DBP levels do not influence the effect of vitamin D repletion on PTH or calcium levels. PMID:24712573

  13. Vitamin D and Breast Cancer

    PubMed Central

    Klein, Paula; Grossbard, Michael L.

    2012-01-01

    In addition to its role in calcium homeostasis and bone health, vitamin D has also been reported to have anticancer activities against many cancer types, including breast cancer. The discovery that breast epithelial cells possess the same enzymatic system as the kidney, allowing local manufacture of active vitamin D from circulating precursors, makes the effect of vitamin D in breast cancer biologically plausible. Preclinical and ecologic studies have suggested a role for vitamin D in breast cancer prevention. Inverse associations have also been shown between serum 25-hydroxyvitamin D level (25(OH)D) and breast cancer development, risk for breast cancer recurrence, and mortality in women with early-stage breast cancer. Clinical trials of vitamin D supplementation, however, have yielded inconsistent results. Regardless of whether or not vitamin D helps prevent breast cancer or its recurrence, vitamin D deficiency in the U.S. population is very common, and the adverse impact on bone health, a particular concern for breast cancer survivors, makes it important to understand vitamin D physiology and to recognize and treat vitamin D deficiency. In this review, we discuss vitamin D metabolism and its mechanism of action. We summarize the current evidence of the relationship between vitamin D and breast cancer, highlight ongoing research in this area, and discuss optimal dosing of vitamin D for breast cancer prevention. PMID:22234628

  14. Vitamin D deficiency in Malawian adults with pulmonary tuberculosis: risk factors and treatment outcomes

    PubMed Central

    Mwandumba, H. C.; Kamdolozi, M.; Shani, D.; Chisale, B.; Dutton, J.; Khoo, S. H.; Allain, T. J.; Davies, G. R.

    2015-01-01

    SUMMARY SETTING: Vitamin D deficiency is common in African adults with tuberculosis (TB), and may be exacerbated by the metabolic effects of anti-tuberculosis drugs and antiretroviral therapy (ART). It is unclear whether vitamin D deficiency influences response to anti-tuberculosis treatment. OBJECTIVES: To describe risk factors for baseline vitamin D deficiency in Malawian adults with pulmonary TB, assess the relationship between serum 25-hydroxy vitamin D (25[OH]D) concentration and treatment response, and evaluate whether the administration of anti-tuberculosis drugs and ART is deleterious to vitamin D status during treatment. DESIGN: A prospective longitudinal cohort study. RESULTS: The median baseline 25(OH)D concentration of the 169 patients (58% human immunodeficiency virus [HIV] infected) recruited was 57 nmol/l; 47 (28%) had vitamin D deficiency (<50 nmol/l). Baseline 25(OH)D concentrations were lower during the cold season (P < 0.001), with food insecurity (P = 0.034) or in patients who consumed alcohol (P = 0.019). No relationship between vitamin D status and anti-tuberculosis treatment response was found. 25(OH)D concentrations increased during anti-tuberculosis treatment, irrespective of HIV status or use of ART. CONCLUSIONS: Vitamin D deficiency is common among TB patients in Malawi, but this does not influence treatment response. Adverse metabolic effects of drug treatment may be compensated by the positive impact of clinical recovery preventing exacerbation of vitamin D deficiency during anti-tuberculosis treatment. PMID:26162355

  15. Vitamin D status and nutrition in Europe and Asia.

    PubMed

    Lips, P

    2007-03-01

    Vitamin D status is highly different in various countries of Europe, the Middle East and Asia. For this review, vitamin D deficiency is defined as serum 25-hydroxyvitamin D (25(OH)D) <25 nmol/l. Within European countries, serum 25(OH)D is <25 nmol/l in 2-30% of adults, increasing in the elderly and institutionalized to more than 80% in some studies. A north-south gradient was observed for serum 25(OH)D in the Euronut and MORE studies with higher levels in Scandinavia and lower levels in Italy and Spain and some Eastern European countries. This points to other determinants than sunshine, e.g. nutrition, food fortification and supplement use. Mean vitamin D intake in Scandinavia is 200-400IU/d, twice that in other European countries. Very low serum 25(OH)D levels have been reported in the Middle East, e.g. Turkey, Lebanon, Jordan and Iran. In these countries serum 25(OH)D was lower in women than in men and associated with clothing habits. In a Lebanese survey, vitamin D deficiency was observed in the majority and occurred mainly in veiled women. In India, vitamin D deficiency was observed in more than 30%, vitamin D status being poor in school children, pregnant women and large cities. Vitamin D status was much better in Malaysia and Singapore, but lower serum 25(OH)D was observed in Japan and China. Rickets and osteomalacia appear quite common in India, but precise data are lacking. Immigrants in Europe from the Middle East and Asia carry a high risk for vitamin D deficiency, pregnant women being especially at risk. Comparison of vitamin D status between countries is hampered by interlaboratory variation of serum 25(OH)D measurement. In addition, there is a need of population-based data. In conclusion, vitamin D deficiency is common in Southern Europe, the Middle East, India, China and Japan. It is less common in Northern Europe and Southeast Asia. Risk groups are young children, the elderly, pregnant women and non-western immigrants in Europe. Important

  16. Role of vitamin D receptor activation in racial disparities in kidney disease outcomes.

    PubMed

    Essien, Utibe; Goel, Narender; Melamed, Michal L

    2013-09-01

    African Americans have lower 25-hydroxyvitamin D (25(OH)D) levels compared with whites. African Americans also have a higher risk of developing albuminuria and end-stage renal disease but a lower risk of death once they commence hemodialysis compared with whites. Vitamin D levels have been associated with multiple outcomes including albuminuria, progression to end-stage renal disease, and all-cause and cardiovascular mortality. In this review, we examine the evidence linking 25(OH)D to outcomes and the possibility that differential 25(OH)D may explain certain racial differences in outcomes.

  17. Comparative kinetics of the turnover rates of vitamin D/sub 2/ and vitamin D/sub 3/ and their metabolites in chick plasma

    SciTech Connect

    Hoy, D.A.; Horst, R.L.

    1986-01-01

    Studies regarding the discrimination between vitamin D/sub 2/ and vitamin D/sub 3/ by chickens have led to conflicting conclusions. To investigate this problem in more detail the authors administered radiolabeled vitamin D and vitamin D metabolites, which allowed them to determine their relative plasma clearance rates. The study involved 3 groups of adult male chickens (5/group). Group I received (/sup 3/H)-vitamin D/sub 2/ (1.2 Ci/mmole) and (/sup 3/H)-vitamin D/sub 3/ (1.2 Ci/mmole). Group II received (/sup 3/H)-25-OHD/sub 2/ (90 Ci/mmole) and (/sup 3/H)-25-OHD/sub 3/ (90 Ci/mmole). Group III received (/sup 3/H)-1,25-(OH)/sub 2/D/sub 3/ (90 Ci/mmole) and (/sup 3/H)-1,25-(OH)/sub 2/D/sub 2/ (90 Ci/mmole). The (/sup 3/H)-sterols were co-dosed within each group. The results indicated that the turnover rates of (/sup 3/H)-vitamin D/sub 2/ and (/sup 3/H)-vitamin D/sub 3/ were not significantly different. However, the plasma turnover of the 25 hydroxylated metabolites differed, with (/sup 3/H)-25-OHD/sub 2/ clearing faster (2-4X) than (/sup 3/H)-25-OHD/sub 3/. The largest difference appeared in the 1,25-(OH)/sub 2/D turnover rates with 1,25-(OH)/sub 2/D/sub 2/ clearing approximately 10X faster than (/sup 3/H)-1,25-(OH)/sub 2/D/sub 3/. These data, therefore, indicate that discrimination against vitamin D/sub 2/ sterols in the chick occurs primarily between steps in the metabolism of vitamin D and not at the point of the parent vitamin.

  18. Vitamin D and UV exposure in chronic kidney disease

    PubMed Central

    Krause, Rolfdieter

    2013-01-01

    With loss of renal function and decreasing glomerula filtration rate the serum levels of 25-hydroxyvitamin D [25(OH)D] as well as 1,25-dihydroxyvitamin D [1,25 (OH)2 D] often decrease simultaneously. In representative groups of German patients on renal replacement therapy (hemodialysis, peritoneal dialysis, kidney transplantation) our group retrospectively analyzed the vitamin D status over a period of 12 y (1995‒2006). Only 11% of patients had a serum level of 25(OH)D that was > 30 ng/ml, more than 70% had a level of 25(OH)D < 20 ng/ml. In clinical trials we used sun-simulating artificial lamps to produce vitamin D3 in the skin. Partial-body irradiation (15% of body surface) was used during the routine hemodialysis treatment. Whole-body UV exposure was done in a standing position three times a week before the hemodialysis treatment. With both procedures we observed an increase of the serum level of 25(OH)2D3 by approx. 35–50% over a period of 2‒3 mo, maintenance of trabecular bone mineral density and a normalization of systolic and diastolic blood pressure. Heart rate variability improved during the whole-body radiation intervention period by 20‒25%. Patients who continued the whole-body irradiation regularly two or three times before starting the routine hemodialysis session had maintained normal levels of circulating 25(OH)D3 and of 1,25(OH)2D3. Therefore, from our data it can be recommended that intermittent suberythemal UVB exposure with a sun-simulation spectrum is effective to treat and/or protect against vitamin D deficiency in chronic and end-stage kidney disease patients. PMID:24494043

  19. Effects of vitamin D metabolites on healing of low phosphate, vitamin D-deficient induced rickets in rats.

    PubMed

    Atkin, I; Pita, J C; Ornoy, A; Agundez, A; Castiglione, G; Howell, D S

    1985-01-01

    A model of low-phosphate, vitamin D-deficient rachitic rats was used to compare the effects of 1 alpha(OH)D3, 1,25(OH)2D3, and 24,25(OH)2D3 on cartilage and bone. The rats were maintained for 3 weeks on a high-calcium, low-phosphate, vitamin D-deficient diet, during which period they developed severe rickets. The rachitic rats were injected for 2 or 3 consecutive days with a physiologic dose of either metabolite. Other littermates were given a single dose of 50,000 IU of cholecalciferol in combination with a normal diet. Samples of cartilage fluid (Cfl) and of blood were removed prior to sacrifice for biochemical studies of some parameters of calcification. These parameters were correlated with the results of light and electron microscopic studies of the growth plate cartilage and bone. Treatment with 1 alpha (OH)D3 or with 1,25(OH)2D3, in spite of increasing Ca and P levels in the Cfl, induced only partial healing of the rickets. In contrast, 24,25(OH)2D3 or vitamin D with a normal diet resulted in complete morphologic and biochemical healing of the rickets. Transmission electron microscopic (TEM) studies have shown partial mineralization of the wide hypertrophic zone of the growth plate following treatment with 1 alpha(OH)D3 or with 1,25(OH)2D3. Mineralization was more complete with 24,25(OH)2D3 treatment. The results of this study emphasize the importance of 24,25(OH)2D3 for normal endochondral bone formation and mineralization.

  20. Kidney-specific upregulation of vitamin D3 target genes in ClC-5 KO mice.

    PubMed

    Maritzen, T; Rickheit, G; Schmitt, A; Jentsch, T J

    2006-07-01

    Mutations in ClC-5 cause Dent's disease, a disorder associated with low molecular weight proteinuria, hyperphosphaturia, and kidney stones. ClC-5 is a Cl(-)/H(+)-exchanger predominantly expressed in the kidney, where it facilitates the acidification of proximal tubular endosomes. The reduction in proximal tubular endocytosis resulting from a lack of ClC-5 raises the luminal concentration of filtered proteins and peptides like parathyroid hormone (PTH). The increase in PTH may explain the hyperphosphaturia observed in Dent's disease. Expression profiling, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and hormone measurements were used to investigate whether the disruption of ClC-5 affects other signalling pathways. Although the upregulation of 25(OH)(2)-vitamin D(3) 1alpha-hydroxylase and downregulation of vitamin D(3) 24-hydroxylase suggested an increased formation of 1,25(OH)(2)-vitamin D(3), the concentration of this active metabolite was reduced in the serum of ClC-5 knockout (KO) mice. However, target genes of 1,25(OH)(2)-vitamin D(3) were upregulated in KO kidneys. Expression analysis of intestine and bone revealed that the upregulation of 1,25(OH)(2)-vitamin D(3) target genes was kidney intrinsic and not systemic. In spite of reduced serum levels of 1,25(OH)(2)-vitamin D(3) in ClC-5 KO mice, 1,25(OH)(2)-vitamin D(3) is increased in later nephron segments as a consequence of impaired proximal tubular endocytosis. This leads to a kidney-specific stimulation of 1,25(OH)(2)-vitamin D(3) target genes that may contribute to the pathogenesis of Dent's disease. The activation of genes in distal nephron segments by hormones that are normally endocytosed in the proximal tubule may extend to other pathways like those activated by retinoic acid.

  1. Modulation of 1alpha,25-dihydroxyvitamin D3-membrane associated, rapid response steroid binding protein expression in mouse odontoblasts by 1alpha,25-(OH)2D3.

    PubMed

    Teillaud, Christophe; Nemere, Ilka; Boukhobza, Florine; Mathiot, Claire; Conan, Nicole; Oboeuf, Martine; Hotton, Dominique; Macdougall, Mary; Berdal, Ariane

    2005-01-01

    The rapid, nongenomic effects of 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3 have been related to a 1,25D3-membrane associated, rapid response steroid binding protein or 1,25D3-[MARRS]bp, with a molecular weight of 65 kDa, in several tissues and species. Currently, no information is available concerning the nongenomic responses to 1alpha,25-(OH)2D3 in dental tissues. In order to investigate the expression of 1,25D3-[MARRS]bp in dental cells, in the presence or absence of 1alpha,25-(OH)2D3, we have used rabbit polyclonal antibodies directed against the N-terminus of the 1,25D3-[MARRS]bp (Ab099) that recognizes the 1alpha,25-(OH)2D3 binding protein in chick intestinal basolateral membranes and a mouse odontoblast-like cell line (MO6-G3). Western blotting and flow cytometric analyses with Ab099 specifically detected 1,25D3-[MARRS]bp in MO6-G3 cells. Moreover, 1,25D3-[MARRS]bp was up-regulated, in vivo, in differentiated dental cells. Electron microscopic analysis confirmed the plasma membrane localization of this binding protein and also showed its intracellular presence. Incubation of MO6-G3 cells with different doses of 1alpha,25-(OH)2D3 for 36 h resulted in an inhibition of 1,25D3-[MARRS]bp expression with a maximal effect at 50 nM steroid. In addition, the culture media of MO6-G3 cells contains immunoreactive 1,25D3-[MARRS]bp. Immunogold positive membrane vesicle-like structures are present in the extracellular matrix of MO6-G3 cells. Altogether, these results indicate that the 1,25D3-[MARRS]bp expression in MO6-G3 cells is modulated by 1alpha,25-(OH)2D3. In conclusion, this 1alpha,25-(OH)2D3 binding protein could play an important role in the rapid, nongenomic responses to 1alpha,25-(OH)2D3 in dental cells.

  2. A Randomized Trial of Vitamin D3 Supplementation in Children: Dose-Response Effects on Vitamin D Metabolites and Calcium Absorption

    PubMed Central

    Laing, E. M.; Hill Gallant, K. M.; Hall, D. B.; McCabe, G. P.; Hausman, D. B.; Martin, B. R.; Warden, S. J.; Peacock, M.; Weaver, C. M.

    2013-01-01

    Context: Changes in serum vitamin D metabolites and calcium absorption with varying doses of oral vitamin D3 in healthy children are unknown. Objective: Our objective was to examine the dose-response effects of supplemental vitamin D3 on serum vitamin D metabolites and calcium absorption in children living at two U.S. latitudes. Design: Black and white children (n = 323) participated in a multisite (U.S. latitudes 34° N and 40° N), triple-masked trial. Children were randomized to receive oral vitamin D3 (0, 400, 1000, 2000, and 4000 IU/d) and were sampled over 12 weeks in winter. Serum 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured using RIA and intact PTH (iPTH) by immunoradiometric assay. Fractional calcium absorption was determined from an oral stable isotope 44Ca (5 mg) in a 150-mg calcium meal. Nonlinear and linear regression models were fit for vitamin D metabolites, iPTH, and calcium absorption. Results: The mean baseline 25(OH)D value for the entire sample was 70.0 nmol/L. Increases in 25(OH)D depended on dose with 12-week changes ranging from −10 nmol/L for placebo to 76 nmol/L for 4000 IU. Larger 25(OH)D gains were observed for whites vs blacks at the highest dose (P < .01). Gains for 1,25(OH)2D were not significant (P = .07), and decreases in iPTH were not dose-dependent. There was no dose effect of vitamin D on fractional calcium absorption when adjusted for pill compliance, race, sex, or baseline 25(OH)D. Conclusion: Large increases in serum 25(OH)D with vitamin D3 supplementation did not increase calcium absorption in healthy children living at 2 different latitudes. Supplementation with 400 IU/d was sufficient to maintain wintertime 25(OH)D concentrations in healthy black, but not white, children. PMID:24092833

  3. The effect of a single, large bolus of vitamin D in healthy adults over the winter and following year: a randomized, double-blind, placebo-controlled trial

    PubMed Central

    Kearns, MD; Binongo, JNG; Watson, D; Alvarez, JA; Lodin, D; Ziegler, TR; Tangpricha, V

    2014-01-01

    BACKGROUND/OBJECTIVES Although single, high doses of vitamin D effectively maintain vitamin D sufficiency in several populations, no studies have evaluated healthy adults over winter, during which vitamin D status declines. This study investigated whether high-dose vitamin D3 given once to healthy adults before winter will (1) prevent the wintertime decline in vitamin D status, (2) promote vitamin D sufficiency 1 year following the dose and (3) prevent the rise of parathyroid hormone (PTH) concentrations. SUBJECTS/METHODS In this double-blind, placebo-controlled trial, we assessed plasma 25(OH)D and PTH concentrations at baseline, 5, 90 and 365 days after drug administration in 28 healthy adults. In all, >80% of subjects returned at each time point. RESULTS At baseline, the young, healthy participants had a mean plasma 25(OH)D concentration of 17.5 ± 6.1 ng/ml. Only two subjects exhibited plasma 25(OH)D concentrations >30 ng/ml. At 5 days, subjects randomized to vitamin D3 had a higher mean plasma 25(OH)D concentration compared with the placebo group (39.1 vs 19.1 ng/ml, P<0.001). Plasma 25(OH)D concentrations returned to baseline at 90 and 365 days in the vitamin D3 group and remained unchanged in the placebo group. PTH and calcium concentrations were unrelated to changes in 25(OH)D levels and similar between groups over time. CONCLUSIONS A dose of 250 000 IU of vitamin D3 given once in November resulted in a robust increase in plasma 25(OH)D after 5 days, but it was unable to sustain this increase after 90 days. A larger or more frequent dosing regimen may be needed for long-term vitamin D sufficiency. PMID:25271011

  4. Vitamin D deficiency is prevalent in girls and women with rett syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The aim of the study was to determine the prevalence of vitamin D deficiency and identify the relation between 25-hydroxyvitamin D (25-(OH)D) levels and the consumption of dietary sources of vitamin D or exposure to anticonvulsants in girls and women with Rett syndrome (RTT). Retrospective review of...

  5. Determination of Reference Intervals for Serum Total Calcium in the Vitamin D-Replete Pediatric Population

    PubMed Central

    Roizen, Jeffrey D.; Shah, Vipul; Levine, Michael A.

    2013-01-01

    Context: Widespread vitamin D insufficiency raises concerns regarding the reliability of reference intervals for serum calcium. Objective: We sought to determine the reference intervals for serum total calcium in pediatric subjects without vitamin D [25-hydroxyvitamin D [25(OH)D

  6. Effect of lowered vitamin D binding protein levels on the biological activity and metabolism of 1,25-dihydroxyvitamin D/sub 3/

    SciTech Connect

    Kost, S.B.; Londowski, J.; Audran, M.; Kumar, R.

    1986-03-01

    The authors studied the effect of lowered vitamin D binding protein levels on the biological activity and metabolism of 1,25-dihydroxyvitamin D/sub 3/ (1,25(OH)/sub 2/D/sub 3/) in vivo. Estrogen administration to vitamin D-deficient rats resulted in decrease of plasma vitamin D binding protein concentrations by about 20%. The authors administered graded doses of 1,25(OH)/sub 2/D/sub 3/ (5 - 5000 pmol intravenously) to vitamin D-deficient rats given estrogen or vehicle, and studied the biological response in intestine and bone. Intestinal calcium transport, following the administration of 1,25(OH)/sub 2/D/sub 3/, was similar in the estrogen or vehicle-treated groups. Serum calcium concentrations were lower in the estrogen-treated rats when compared to rats given vehicle. Serum calcium in both groups, however, increased the same amount over the range of 1,25(OH)/sub 2/D/sub 3/ given. The uptake of (/sup 3/H) 1,25(OH)/sub 2/D/sub 3/ by the intestine and bone 8 hours after the administration of (/sup 3/H) 1,25(OH)/sub 2/D/sub 3/ was similar in estrogen- and vehicle-treated rats. The amount of (/sup 3/H) 1,25(OH)/sub 2/D/sub 3/ in plasma of estrogen-treated rats was the same as in vehicle-treated rats. The authors conclude that in estrogen-treated rats, lowered vitamin D binding protein levels do not alter the effect of 1,25(OH)/sub 2/D/sub 3/ on intestine or bone and do not alter the metabolism of 1,25(OH)/sub 2/D/sub 3/.

  7. Cyclic changes of vitamin D and PTH are primarily regulated by solar radiation: 5-year analysis of a German (50 degrees N) population.

    PubMed

    Reusch, J; Ackermann, H; Badenhoop, K

    2009-05-01

    Cutaneous vitamin D precursor production depends on UV-exposure and is ineffective in most regions above latitudes of 50 degrees in winter. We hypothesized whether the cyclic course of vitamin D levels can be modelled with sunshine duration and would affect parathyroid hormone concentrations, but not calcium in a large patient population. We investigated 13330 blood samples from 6099 in- and out patients for 25(OH)D3, 1,25(OH)2D3, PTH, and total Ca in Frankfurt, Germany over 6.5 years. Vitamin D deficiency [25(OH)D3 <10 ng/ml] was found in 12.23% and vitamin D insufficiency [25(OH)D3 <20 ng/ml] in 40.62% of all the blood samples and more frequently during winter. We observed a significant difference between men and women, children and adults, migrants and local residents. Cycling of the curve was significantly related to Julian day for 25(OH)D3 and parathyroid hormone (PTH), but not for 1,25(OH)2D3 and Ca. The peak concentration of 25(OH)D3 was found at Aug 16th and correlated well with the length of day whereas PTH is inversely related with 25(OH)D (3). Seasonal cycling of 25(OH)D3-levels correlated significantly with Julian Day and inversely with PTH. This tight feed back ensures stable Ca concentrations within narrow limits. We conclude that changes in vitamin D levels are mainly regulated by solar radiation and to a lesser degree by other factors such as nutrition. PMID:19241329

  8. Vitamin D status and recommendations to improve vitamin D status in Canadian youth.

    PubMed

    Mark, Sean

    2010-10-01

    Little is known regarding the vitamin D status of Canadian youth. Our objectives were (i) to describe the vitamin D status of Quebec youth using a representative sample; (ii) to examine the relative contributions of diet, physical activity, and fat mass to the variance in plasma 25-hydroxyvitamin D(25(OH)D), the best biomarker of vitamin D status; and (iii) to examine the influence of household income and food insecurity on the intakes of dietary vitamin D, calcium, and dairy foods. To describe vitamin D status, we used data from the Quebec Child and Adolescent Health and Social Survey (QCAHS), which is a cross-sectional survey representative of Quebec youth aged 9, 13, and 16 years. For the second objective, 159 youth, aged 8 to 11 years, whose parents (at least one) were obese or had the metabolic syndrome, were used for cross-sectional analysis in the Quebec Adipose and Lifestyle InvesTigation in Youth (QUALITY). Fat mass was measured using dual X-ray absorptiometry (DXA), and physical activity was assessed by an accelerometer. Finally, we analyzed data from the Canadian Community Health Survey (CCHS), which collected data from 9 to 18 year olds (N = 8960), and was representative of Canadian youth. From this survey a single 24-h dietary recall, measured height and weight, sociodemographic, and food insecurity information were available. In both the QUALITY and QCAHS study, >90% of youth had suboptimal vitamin D levels (plasma 25(OH)D < 75 nmol L(-1)) at the end of winter and beginning of spring. In the QCAHS study, older youth had a higher prevalence of vitamin D deficiency (25(OH)D < 27.5 nmol L(-1)) (>10%) than younger youth, and girls from low-income households had lower plasma 25(OH)D concentrations. In the QUALITY study, milk consumption and physical activity had modest associations with plasma 25(OH)D, corresponding to 2.9 nmol L(-1) and 2.1 nmol L(-1) higher plasma 25(OH)D per standard deviation increase in these exposures, respectively. In the CCHS study

  9. Assessing the vitamin D status of the US population.

    PubMed

    Yetley, Elizabeth A

    2008-08-01

    This article describes the information currently available in the National Nutrition Monitoring System that is relevant to assessing the vitamin D status of US population groups, the strengths and limitations of this information, and selected results of vitamin D nutritional status assessments. The National Health and Nutrition Examination Survey (NHANES) provides information on vitamin D intakes only from 1988 to 1994. NHANES collected information on supplement use and circulating 25-hydroxyvitamin D [25(OH)D] concentrations from 1988 through current surveys. The National Nutrient Database for Standard Reference started providing limited data on the vitamin D content of foods in 2002 and continues to update these values. The Food Label and Package Survey provides 2006-2007 label information on vitamin D fortification of marketed foods. Despite limitations in the available data and controversies about appropriate criteria for evaluating vitamin D status among population groups, we can make some useful comparisons of vitamin D status among life-stage groups. In general, males have higher vitamin D intakes and 25(OH)D concentrations than do females. Children tend to have higher vitamin D status than adults. The increasing use of multivitamin-mineral dietary supplements in younger to older adults is not associated with a corresponding increase in serum 25(OH)D concentrations. In general, leaner individuals have higher circulating concentrations of 25(OH)D and supplement use than do heavier individuals. Finally, non-Hispanic whites tend to have higher vitamin D status than do non-Hispanic blacks and Mexican Americans.

  10. Urban and rural comparison of vitamin D status in Pakistani pregnant women and neonates.

    PubMed

    Anwar, S; Iqbal, M P; Azam, I; Habib, A; Bhutta, S; Soofi, S B; Bhutta, Z A

    2016-01-01

    We undertook a cross-sectional study in rural Jehlum and urban Karachi to evaluate the prevalence of vitamin D deficiency in Pakistani pregnant women and neonates and to assess any association of serum 25(OH) vitamin D [25(OH)D] concentration with vitamin D binding protein (Gc) genotypes. Altogether, 390 women and 266 neonates were recruited from urban and rural sites, respectively. Serum 25(OH)D was measured by an immunoassay, while Gc genotypes were identified using polymerase chain reaction followed by restriction fragment length polymorphism or PCR-RFLP. One-way analysis of variance or ANOVA and linear regression were used for statistical analysis. In urban Karachi, 99.5% of women and 97.3% of neonates were vitamin D deficient (< 50 nmol/L), while 89% of women and 82% of neonates were deficient in rural Jehlum. Gc genotypes were not associated with serum 25(OH)D concentrations in both women and their neonates. We conclude that vitamin D deficiency is highly prevalent in Pakistani women and their neonates, and Gc genotypes are not associated with serum 25(OH)D concentrations.

  11. Analysis of vitamin D status at two academic medical centers and a national reference laboratory: result patterns vary by age, gender, season, and patient location

    PubMed Central

    2013-01-01

    Background Testing for 25-hydroxyvitamin D [25(OH)D] has increased dramatically in recent years. The present report compares overall utilization and results for 25(OH)D orders at two academic medical centers - one in New York and one in Iowa – in order to characterize the vitamin D status of our inpatient and outpatient populations. Results are also compared to those from a national reference laboratory to determine whether patterns at these two institutions reflect those observed nationally. Methods Retrospective data queries of 25(OH)D orders and results were conducted using the laboratory information systems at Weill Cornell Medical College / New York Presbyterian Hospital (WCMC), University of Iowa Hospitals and Clinics (UIHC), and ARUP Laboratories (ARUP). Chart review was conducted for cases with very high or low serum 25(OH)D levels in the WCMC and UIHC datasets. Results The majority of tests were ordered on females and outpatients. Average serum 25(OH)D levels were higher in female versus male patients across most ages in the WCMC, UIHC, and ARUP datasets. As expected, average serum 25(OH)D levels were higher in outpatients than inpatients. Serum 25(OH)D levels showed seasonal periodicity, with average levels higher in summer than winter and correlating to regional UV index. Area plots demonstrated a peak of increased 25(OH)D insufficiency / deficiency in adolescent females, although overall worse 25(OH)D status was found in male versus female patients in the WCMC, UIHC, and ARUP datasets. Surprisingly, improved 25(OH)D status was observed in patients starting near age 50. Finally, chart review of WCMC and UIHC datasets revealed over-supplementation (especially of ≥ 50,000 IU weekly doses) in the rare cases of very high 25(OH)D levels. General nutritional deficiency and/or severe illness was found in most cases of severe 25(OH)D deficiency. Conclusions 25(OH)D status of patients seen by healthcare providers varies according to age, gender, season

  12. Serum Vitamin D Is Significantly Inversely Associated with Disease Severity in Caucasian Adults with Obstructive Sleep Apnea Syndrome

    PubMed Central

    Kerley, Conor P.; Hutchinson, Katrina; Bolger, Kenneth; McGowan, Aisling; Faul, John; Cormican, Liam

    2016-01-01

    Study Objectives: To evaluate vitamin D (25(OH)D) levels in obstructive sleep apnea syndrome (OSAS) and possible relationships to OSAS severity, sleepiness, lung function, nocturnal heart rate (HR), and body composition. We also aimed to compare the 25(OH)D status of a subset of OSAS patients compared to controls matched for important determinants of both OSAS and vitamin D deficiency (VDD). Methods: This was a cross-sectional study conducted at an urban, clinical sleep medicine outpatient center. We recruited newly diagnosed, Caucasian adults who had recently undergone nocturnal polysomnography. We compared body mass index (BMI), body composition (bioelectrical impedance analysis), neck circumference, sleepiness (Epworth Sleepiness Scale), lung function, and vitamin D status (serum 25-hydrpoxyvitamin D (25(OH)D) across OSAS severity categories and non-OSAS subjects. Next, using a case-control design, we compared measures of serum 25(OH)D from OSAS cases to non-OSAS controls who were matched for age, gender, skin pigmentation, sleepiness, season, and BMI. Results: 106 adults (77 male; median age = 54.5; median BMI = 34.3 kg/m2) resident in Dublin, Ireland (latitude 53°N) were recruited and categorized as non-OSAS or mild/moderate/severe OSAS. 98% of OSAS cases had insufficient 25(OH)D (< 75 nmol/L), including 72% with VDD (< 50 nmol/L). 25(OH)D levels decreased with OSAS severity (P = 0.003). 25(OH)D was inversely correlated with BMI, percent body fat, AHI, and nocturnal HR. Subsequent multivariate regression analysis revealed that 25(OH)D was independently associated with both AHI (P = 0.016) and nocturnal HR (P = 0.0419). Our separate case-control study revealed that 25(OH)D was significantly lower in OSAS cases than matched, non-OSAS subjects (P = 0.001). Conclusions: We observed widespread vitamin D deficiency and insufficiency in a Caucasian, OSAS population. There were significant, independent, inverse relationships between 25(OH)D and AHI as well as

  13. [Updates on rickets and osteomalacia: vitamin D deficiency : its pathophysiology and treatment].

    PubMed

    Okazaki, Ryo

    2013-10-01

    Vitamin D deficiency is a common cause of rickets/osteomalacia. Milder decrease in vitamin D store, vitamin D insufficiency, does not lead to clinical rickets/osoteomalacia but could result in mineralization defect and an increased fracture risk. Vitamin D store is easily assessed by serum 25 (OH) D concentration : less than 20 ng/mL is generally considered vitamin D deficiency whereas between 20 and 30 ng/mL vitamin D insufficiency. In the management of bone and mineral disorders including rickets/osteomalacia, it is a common practice in many countries to measure serum 25 (OH) D, and if deficiency/insufficiency is present, which would be corrected by native vitamin D. However, in Japan, serum 25 (OH) D is not routinely measured because it is not covered by national health insurance policy, thus vitamin D deficiency/insufficiency is often overlooked and even misdiagnosed. There has been no native vitamin D that can be prescribed in Japan, thus patients with vitamin D deficiency/insufficiency have been prescribed active instead of native vitamin D. These circumstances must be changed to increase the awareness of vitamin D deficiency/insufficiency.

  14. Vitamin D Intake and Status in 6-Year-Old Icelandic Children Followed up from Infancy.

    PubMed

    Thorisdottir, Birna; Gunnarsdottir, Ingibjorg; Steingrimsdottir, Laufey; Palsson, Gestur I; Birgisdottir, Bryndis E; Thorsdottir, Inga

    2016-02-04

    High serum 25-hydroxyvitamin D (25(OH)D) levels have been observed in infants in Nordic countries, likely due to vitamin D supplement use. Internationally, little is known about tracking vitamin D status from infancy to childhood. Following up 1-year-old infants in our national longitudinal cohort, our aims were to study vitamin D intake and status in healthy 6-year-old Icelandic children (n = 139) and to track vitamin D status from one year of age. At six years, the mean 25(OH)D level was 56.5 nmol/L (SD 17.9) and 64% of children were vitamin D sufficient (25(OH)D ≥ 50 nmol/L). A logistic regression model adjusted for gender and breastfeeding showed that higher total vitamin D intake (Odds ratio (OR) = 1.27, 95% confidence interval (CI) = 1.08-1.49), blood samples collected in summer (OR = 8.88, 95% CI = 1.83-43.23) or autumn (OR = 5.64, 95% CI = 1.16-27.32) compared to winter/spring, and 25(OH)D at age one (OR = 1.02, 95% CI = 1.002-1.04) were independently associated with vitamin D sufficiency at age six. The correlation between 25(OH)D at age one and six was 0.34 (p = 0.003). Our findings suggest that vitamin D status in infancy, current vitamin D intake and season are predictors of vitamin D status in early school age children. Our finding of vitamin D status tracking from infancy to childhood provides motivation for further studies on tracking and its clinical significance.

  15. Dietary diallyl disulfide supplementation attenuates ethanol-mediated pulmonary vitamin D speciate depletion in C57Bl/6 mice

    PubMed Central

    McCaskill, Michael L.; Hottor, Henry T.; Sapkota, Muna; Wyatt, Todd A.

    2016-01-01

    Background Slightly more than 5 % of the United States population heavily consumes ethanol, i.e., more than 14 drinks for men and 7 drinks for women a week. Chronic ethanol consumption can result in increased liver disease, reduced recovery from burn injury, and more frequent and severe respiratory infections. Chronic ethanol over-consumption also leads to vitamin D dysmetabolism and depletion. Vitamin D is a fat-soluble pro-hormone that regulates musculoskeletal health, cellular proliferation/differentiation, and innate and adaptive immune response. Methods In this study, C57BL/6 mice were fed 20 % ethanol in their water ad libitum for 7 weeks. Some mice were fed either a standard chow or a modified diet containing 0.15 μg/day of diallyl disulfide (DADS). Whole blood, lung tissue, and bronchial alveolar lavage fluid (BALF) were collected at sacrifice and analyzed for 25(OH) D3, 1,25 (OH)2D3, vitamin D receptor VDR, CYP2E1, and CYP27B1 levels. Results Ethanol reduced 25(OH) D3 and 1,25 (OH)2D3 in lung tissue and BALF on average 31 %. The largest ethanol-mediated reduction was in the 1,25 (OH)2D3 (42 %) measured in the BALF. Dietary supplementation of DADS restored BALF and lung tissue protein of 25(OH) D3 and 1,25(OH)2D3 to control levels. Chronic ethanol consumption also resulted in tissue increases of vitamin D response (VDR) protein, Cyp2E1, and reductions in vitamin D-activating enzyme CYP27B1. All three of these effects were attenuated by dietary supplementation of DADS. Conclusions In conclusion, the pulmonary metabolic disturbances mediated by chronic ethanol consumption as measured by 1,25(OH)2D3 protein levels, epithelial lining fluid, and lung tissue can be ameliorated by dietary supplementation of DADS in C57BL/6 mice. PMID:27536382

  16. Regulation of calcitonin gene transcription by vitamin D metabolites in vivo in the rat.

    PubMed Central

    Naveh-Many, T; Silver, J

    1988-01-01

    Calcitonin is secreted by the C cells of the thyroid in response to a raised serum calcium, and acts on bone to lower serum calcium. The C cells have specific receptors for the dihydroxymetabolite of vitamin D3, 1,25(OH)2D3. Moreover, calcitonin stimulates the synthesis of 1,25(OH)2D3 in the kidney. Parathyroid hormone (PTH), the third calciotrophic hormone, is also trophic to the renal synthesis of 1,25(OH)2D3, and in turn 1,25(OH)2D3 inhibits PTH gene transcription and synthesis. We report here the marked inhibition of calcitonin gene transcription by the injection of physiologically relevant doses of 1,25(OH)2D3 to normal rats that did not raise serum calcium. Calcitonin mRNA levels after 100 pmol 1,25(OH)2D3 decreased to 6% of basal at 6 h and 4% at 48 h, and a dose response showed a marked effect even after 12.5 pmol 1,25(OH)2D3, with no appreciably greater effect with larger doses (up to 200 pmol). Control genes, actin, thyroglobulin (thyroid follicular cells), somatostatin (thyroid C-cells) were not affected by 1,25(OH)2D3. Gel blots showed that 1,25(OH)2D3 decreased calcitonin mRNA levels without any change in its size. In vitro nuclear transcription showed that 1,25(OH)2D3-treated (100 pmol) rats' calcitonin transcription was 10% of control, while thyroglobulin and actin were 100%. We propose that calcium is the major regulator of PTH and calcitonin secretion, while 1,25(OH)2D3 is an important regulator of PTH and calcitonin gene transcription. We believe this to be the first demonstration of an effect of 1,25(OH)2D3 on the C cells thereby establishing a new target organ and site of action of vitamin D. Calcitonin is trophic to 1,25(OH)2D3 synthesis, which in turn inhibits calcitonin synthesis, which are the components of a new endocrinological feedback loop. Images PMID:2891728

  17. High serum vitamin D levels reduce the risk for nonalcoholic fatty liver disease in healthy men independent of metabolic syndrome.

    PubMed

    Rhee, Eun-Jung; Kim, Mee Kyoung; Park, Se Eun; Park, Cheol-Young; Baek, Ki Hyun; Lee, Won-Young; Kang, Moo Il; Park, Sung-Woo; Kim, Sun-Woo; Oh, Ki Won

    2013-01-01

    Recent studies suggest an association of vitamin D with obesity, diabetes and cardiovascular diseases. We analyzed the association of serum vitamin D level assessed by 25-hydroxyvitamin D3 {25(OH)D3 } with nonalcoholic fatty liver disease (NAFLD) in apparently healthy men. We performed a cross-sectional study of 6,567 Korean men who participated in a health screening program, evaluating the association of serum 25(OH)D3 levels with the risk of NAFLD assessed by abdominal ultrasonogram. Of the participants, 43.6% had NAFLD and 21.1% had metabolic syndrome. Age, serum calcium, and aspartate aminotransferase levels showed weak but significant positive correlations with 25(OH)D3 level; total cholesterol, triglycerides, low-density lipoprotein cholesterol and fasting insulin level showed weak but significant negative correlations with 25(OH)D3 level. The mean 25(OH)D3 level was significantly lower in participants with NAFLD than in those without (38.7 ± 9.0 vs. 39.7 ± 9.7 nmol/L, p < 0.001). When participants were divided into tertiles based on mean 25(OH)D3 level, the proportion with NAFLD significantly increased as mean 25(OH)D3 level decreased (40.0, 45.0 and 45.9%, p for linear trend < 0.001). Multiple logistic regression analyses with NAFLD as the dependent variable showed that the tertiles with lower 25(OH)D3 levels had a significantly increased risk for NAFLD compared with the highest tertile, even after adjusting for body mass index and metabolic syndrome (OR 1.247 and 1.408 vs. the highest tertile, p < 0.001). Thus, participants with higher serum 25(OH)D3 showed a significantly reduced risk for NAFLD compared with the low 25(OH)D3 groups, independent of obesity and metabolic syndrome.

  18. Vitamin D and sunlight: strategies for cancer prevention and other health benefits.

    PubMed

    Holick, Michael F

    2008-09-01

    Vitamin D deficiency is a worldwide health problem. The major source of vitamin D for most humans is sensible sun exposure. Factors that influence cutaneous vitamin D production include sunscreen use, skin pigmentation, time of day, season of the year, latitude, and aging. Serum 25-hydroxyvitamin D [25(OH)D] is the measure for vitamin D status. A total of 100 IU of vitamin D raises blood level of 25(OH)D by 1 ng/ml. Thus, children and adults who do not receive adequate vitamin D from sun exposure need at least 1000 IU/d vitamin D. Lack of sun exposure and vitamin D deficiency have been linked to many serious chronic diseases, including autoimmune diseases, infectious diseases, cardiovascular disease, and deadly cancers. It is estimated that there is a 30 to 50% reduction in risk for developing colorectal, breast, and prostate cancer by either increasing vitamin D intake to least 1000 IU/d vitamin D or increasing sun exposure to raise blood levels of 25(OH)D >30 ng/ml. Most tissues in the body have a vitamin D receptor. The active form of vitamin D, 1,25-dihydroxyvitamin D, is made in many different tissues, including colon, prostate, and breast. It is believed that the local production of 1,25(OH)(2)D may be responsible for the anticancer benefit of vitamin D. Recent studies suggested that women who are vitamin D deficient have a 253% increased risk for developing colorectal cancer, and women who ingested 1500 mg/d calcium and 1100 IU/d vitamin D(3) for 4 yr reduced risk for developing cancer by >60%. PMID:18550652

  19. Blood vitamin D(3) metabolite concentrations of adult female bearded dragons (Pogona vitticeps) remain stable after ceasing UVb exposure.

    PubMed

    Oonincx, D G A B; van de Wal, M D; Bosch, G; Stumpel, J B G; Heijboer, A C; van Leeuwen, J P T M; Hendriks, W H; Kik, M

    2013-07-01

    Vitamin D deficiency can lead to several health problems collectively called metabolic bone disease (MBD). One commonly kept reptile species prone to develop MBD if managed incorrectly is the bearded dragon (Pogona vitticeps). This study aimed to determine the extent to which adult female bearded dragons fed a diet low in vitamin D can use stored vitamin D and its metabolites to maintain plasma 25(OH)D(3) and 1,25(OH)(2)D(3) concentrations after discontinuing UVb exposure. Blood samples of healthy adult female bearded dragons, exposed to UVb radiation for over 6 months were collected (day 0) after which UVb exposure was discontinued for 83 days and blood was collected. Blood plasma was analysed for concentrations of total Ca, total P, ionized Ca, uric acid, 25(OH)D(3) and 1,25(OH)(2)D(3). There was no significant change in plasma 25(OH)D(3) and 1,25(OH)(2)D(3) concentrations during the study. While total Ca and P in whole blood was found to significantly decrease over time (P < 0.0088 and 0.0016, respectively), values were within the reference range. Plasma ionized Ca tended (P = 0.0525) to decrease during the study. Adult female bearded dragons, previously exposed to UVb, are able to maintain blood vitamin D metabolite concentrations when UVb exposure is discontinued for a period of up to 83 days. PMID:23648288

  20. Blood vitamin D(3) metabolite concentrations of adult female bearded dragons (Pogona vitticeps) remain stable after ceasing UVb exposure.

    PubMed

    Oonincx, D G A B; van de Wal, M D; Bosch, G; Stumpel, J B G; Heijboer, A C; van Leeuwen, J P T M; Hendriks, W H; Kik, M

    2013-07-01

    Vitamin D deficiency can lead to several health problems collectively called metabolic bone disease (MBD). One commonly kept reptile species prone to develop MBD if managed incorrectly is the bearded dragon (Pogona vitticeps). This study aimed to determine the extent to which adult female bearded dragons fed a diet low in vitamin D can use stored vitamin D and its metabolites to maintain plasma 25(OH)D(3) and 1,25(OH)(2)D(3) concentrations after discontinuing UVb exposure. Blood samples of healthy adult female bearded dragons, exposed to UVb radiation for over 6 months were collected (day 0) after which UVb exposure was discontinued for 83 days and blood was collected. Blood plasma was analysed for concentrations of total Ca, total P, ionized Ca, uric acid, 25(OH)D(3) and 1,25(OH)(2)D(3). There was no significant change in plasma 25(OH)D(3) and 1,25(OH)(2)D(3) concentrations during the study. While total Ca and P in whole blood was found to significantly decrease over time (P < 0.0088 and 0.0016, respectively), values were within the reference range. Plasma ionized Ca tended (P = 0.0525) to decrease during the study. Adult female bearded dragons, previously exposed to UVb, are able to maintain blood vitamin D metabolite concentrations when UVb exposure is discontinued for a period of up to 83 days.

  1. Vitamin D Levels Are Associated with Expression of SLE, but Not Flare Frequency

    PubMed Central

    Squance, Marline L.; Reeves, Glenn E. M.; Tran, Huy A.

    2014-01-01

    This study explores links between vitamin D deficiency (25(OH)D = 50 nmol/L) and serological autoimmunity (ANA > 1 : 80) and frequency of self-reported flares (SRF) in participants with clinical autoimmunity (SLE). 25(OH)D levels of 121 females were quantified and compared. The cohort consisted of 80 ACR defined SLE patients and 41 age and sex matched controls. Association analysis of log2 (25(OH)D) levels and ANA 80 positivity was undertaken via two-sample t-tests and regression models. Significant differences were found for 25(OH)D levels (mean: control 74 nmol/L (29.5 ng/ml); SLE 58 nmol/L (23.1 ng/ml), P = 0.04), 25(OH)D deficiency (P = 0.02). Regression models indicate that, for a twofold rise in 25(OH)D level, the odds ratio (OR) for ANA-positivity drops to 36% of the baseline OR. No link was found between SRF-days and 25(OH)D levels. Our results support links between vitamin D deficiency and expression of serological autoimmunity and clinical autoimmunity (SLE). However, no demonstrable association between 25(OH)D and SRF was confirmed, suggesting independent influences of other flare-inducing factors. Results indicate that SLE patients have high risk of 25(OH)D deficiency and therefore supplementation with regular monitoring should be considered as part of patient management. PMID:25506363

  2. Photoaffinity labeling of the rat plasma vitamin D binding protein with (26,27-3H)-25-hydroxyvitamin D3 3 beta-(N-(4-azido-2-nitrophenyl)glycinate)

    SciTech Connect

    Ray, R.; Holick, S.A.; Hanafin, N.; Holick, M.F.

    1986-08-26

    It is well recognized that the vitamin D binding protein (DBP) is important for the transport of vitamin D, 25-hydroxyvitamin D (25-OH-D), and its metabolites. In an attempt to better understand the molecular-binding properties of this ubiquitous protein, we designed and synthesized a photoaffinity analogue of 25-OH-D3 and its radiolabeled counterpart. This analogue, 25-hydroxyvitamin D3 3 beta-(N-(4-azido-2-nitrophenyl)glycinate) (25-OH-D3-ANG), was recognized by the rat DBP and was about 10 times less active than 25-OH-D3 in terms of binding. Incubation of (/sup 3/H)25-OH-D3 or (/sup 3/H)25-OH-D3-ANG with rat DBP revealed that both compounds were specifically bound to a protein with a sedimentation coefficient of 4.1 S. Each was displaced with a 500-fold excess of 25-OH-D3. When (/sup 3/H)25-OH-D3-ANG was exposed to UV radiation in the presence of rat DBP followed by the addition of a 500-fold excess of 25-OH-D3, there was no displacement of tritium from the 4.1S peak. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiographic analysis of (/sup 3/H)25-OH-D3-ANG exposed to UV radiation in the presence of rat DBP followed by the addition of a 500-fold excess of 25-OH-D3 revealed one major band with a molecular weight of 52 000. These data provide strong evidence that (/sup 3/H)25-OH-D3-ANG was covalently linked to the rat DBP. This photoaffinity probe should provide a valuable tool for the analysis of the binding site on this transport protein.

  3. Serum Vitamin D, Vitamin D Binding Protein, and Risk of Colorectal Cancer

    PubMed Central

    Anic, Gabriella M.; Weinstein, Stephanie J.; Mondul, Alison M.; Männistö, Satu; Albanes, Demetrius

    2014-01-01

    Background We previously reported a positive association between serum 25-hydroxyvitamin D (25(OH)D) and colorectal cancer risk. To further elucidate this association, we examined the molar ratio of 25(OH)D to vitamin D binding protein (DBP), the primary 25(OH)D transport protein, and whether DBP modified the association between 25(OH)D and colorectal cancer risk. Methods In a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, controls were 1∶1 matched to 416 colorectal cancer cases based on age and date of blood collection. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for quartiles of 25(OH)D, DBP, and the molar ratio of 25(OH)D:DBP, a proxy for free, unbound circulating 25(OH)D. Results Comparing highest to lowest quartiles, DBP was not associated with colorectal cancer risk (OR = 0.91; 95% CI: 0.58, 1.42, p for trend  = 0.58); however, a positive risk association was observed for the molar ratio of 25(OH)D:DBP (OR = 1.44; 95% CI: 0.92, 2.26, p for trend  = 0.04). In stratified analyses, the positive association between 25(OH)D and colorectal cancer was stronger among men with DBP levels above the median (OR = 1.89; 95% CI: 1.07, 3.36, p for trend  = 0.01) than below the median (OR = 1.20; 95% CI: 0.68, 2.12, p for trend  = 0.87), although the interaction was not statistically significant (p for interaction  = 0.24). Conclusion Circulating DBP may influence the association between 25(OH)D and colorectal cancer in male smokers, with the suggestion of a stronger positive association in men with higher DBP concentrations. This finding should be examined in other populations, especially those that include women and non-smokers. PMID:25036524

  4. Vitamin D status among immigrant mothers from Pakistan, Turkey and Somalia and their infants attending child health clinics in Norway.

    PubMed

    Madar, Ahmed A; Stene, Lars C; Meyer, Haakon E

    2009-04-01

    High prevalences of vitamin D deficiency have been reported in non-Western immigrants moving to Western countries, including Norway, but there is limited information on vitamin D status in infants born to immigrant mothers. We aimed to describe the vitamin D status and potentially correlated factors among infants aged 6 weeks and their mothers with Pakistani, Turkish or Somali background attending child health clinics in Norway. Eighty-six healthy infants and their mothers with immigrant background were recruited at the routine 6-week check-up at nine centres between 2004 and 2006. Venous or capillary blood was collected at the clinics from the mother and infant, and serum separated for analysis of 25-hydroxyvitamin D (s-25(OH)D) and intact parathyroid hormone (s-iPTH). The mean maternal s-25(OH)D was 25.8 nmol/l, with 57 % below 25 nmol/l and 15 % below 12.5 nmol/l. Of the mothers, 26 % had s-iPTH>5.7 pmol/l. For infants, mean s-25(OH)D was 41.7 nmol/l, with 47 % below 25 nmol/l and 34 % below 12.5 nmol/l. s-25(OH)D was considerably lower in the thirty-one exclusively breast-fed infants (mean 11.1 nmol/l; P < 0.0001). Use of vitamin D supplements and education showed a positive association with maternal s-25(OH)D. There was no significant association between mother's and child's s-25(OH)D, and no significant ethnic or seasonal variation in s-25(OH)D for mothers or infants. In conclusion, there is widespread vitamin D deficiency in immigrant mothers and their infants living in Norway. Exclusively breast-fed infants who did not receive vitamin D supplements had particularly severe vitamin D deficiency.

  5. Vitamin D: the iceberg nutrient.

    PubMed

    Armas, Laura A G; Heaney, Robert P

    2011-03-01

    The understanding of vitamin D's role in human health has recently expanded. It is now recognized as more than a hormone activated in the kidney only for calcium homeostasis. It is metabolized and used by virtually every cell in the body. Patients with chronic kidney disease have a deficit in their kidney production of 1,25(OH)(2)D and have classically been treated with calcitriol or its active analogues. Despite often having lower systemic levels of 1,25(OH)(2)D, patients with chronic kidney disease retain the capability of extra renal production of 1,25(OH)(2)D. This has far reaching implications for their health. This review examines clinical trials and observations in 3 areas that impact chronic kidney disease patients. Cancer, cardiovascular disease and infections are responsible for much of the morbidity and mortality in this patient population. We will discuss vitamin D's role in these disease states with a focus on the chronic kidney disease patient.

  6. Association of Urinary Calcium Excretion with Serum Calcium and Vitamin D Levels

    PubMed Central

    Rathod, Anita; Bonny, Olivier; Guessous, Idris; Suter, Paolo M.; Conen, David; Erne, Paul; Binet, Isabelle; Gabutti, Luca; Gallino, Augusto; Muggli, Franco; Hayoz, Daniel; Péchère-Bertschi, Antoinette; Paccaud, Fred

    2015-01-01

    Background and objectives Population-based data on urinary calcium excretion are scarce. The association of serum calcium and circulating levels of vitamin D [25(OH)D2 or D3] with urinary calcium excretion in men and women from a population-based study was explored. Design, settings, participants, & measurements Multivariable linear regression was used to explore factors associated with square root–transformed 24-hour urinary calcium excretion (milligrams per 24 hours) taken as the dependent variable with a focus on month-specific vitamin D tertiles and serum calcium in the Swiss Survey on Salt Study. Results In total, 624 men and 669 women were studied with mean ages of 49.2 and 47.0 years, respectively (age range=15–95 years). Mean urinary calcium excretion was higher in men than in women (183.05 versus 144.60 mg/24 h; P<0.001). In adjusted models, the association (95% confidence interval) of square root urinary calcium excretion with protein–corrected serum calcium was 1.78 (95% confidence interval, 1.21 to 2.34) mg/24 h per milligram per deciliter in women and 0.59 (95% confidence interval, −0.11 to 1.29) mg/24 h per milligram per deciliter in men. Men in the third 25(OH)D3 tertile had higher square root urinary calcium excretion than men in the first tertile (0.99; 95% confidence interval, 0.36 to 1.63 mg/24 h per nanogram per milliliter), and the corresponding association was 0.32 (95% confidence interval, −0.22 to 0.85) mg/24 h per nanogram per milliliter in women. These sex differences were more marked under conditions of high urinary sodium or urea excretions. Conclusions There was a positive association of serum calcium with urinary calcium excretion in women but not men. Vitamin 25(OH)D3 was associated with urinary calcium excretion in men but not women. These results suggest important sex differences in the hormonal and dietary control of urinary calcium excretion. PMID:25518946

  7. Longitudinal associations between lifestyle and vitamin D: A general population study with repeated vitamin D measurements.

    PubMed

    Skaaby, Tea; Husemoen, Lise Lotte Nystrup; Thuesen, Betina Heinsbæk; Pisinger, Charlotta; Hannemann, Anke; Jørgensen, Torben; Linneberg, Allan

    2016-02-01

    Several lifestyle factors have been found to be associated with vitamin D status in cross-sectional studies, but it is not clear whether a change in these factors can actually affect the vitamin D level. We investigated the association between repeated measurements of physical activity, body mass index (BMI), diet, alcohol consumption, and smoking habits, and corresponding levels of vitamin D during 5 years of follow-up of a large general population sample. We included 4185 persons who participated and had vitamin D (serum-25-hydroxyvitamin D, 25-OH-D) measurements in the Inter99 study at baseline (1999-2001) and 5-year follow-up. In a subsample, 25-OH-D was also measured at 1- and 3-year follow-ups. We used mixed models to examine the association between repeated measurements of lifestyle factors and 25-OH-D levels. In multivariable analyses of repeated measurements, the difference in 25-OH-D was -0.32 ng/ml (95 % CI -0.37, -0.28) per 1 kg/m(2) increase in BMI; 4.50 ng/ml (95 % CI 3.84, 5.15) for persons moderately/vigorously physically active versus sedentary; 1.82 ng/ml (95 % CI 1.09, 2.56) for persons with healthy versus unhealthy dietary habits; 0.05 ng/ml (95 % CI 0.03, 0.07) per 1 standard drink/weak increase in alcohol consumption; and 0.86 ng/ml (95 % CI 0.36, 1.35) for never smokers versus daily smokers. Our study shows that lower BMI, a higher level of physical activity, a healthier diet and possibly a higher alcohol intake, and not smoking, are associated with higher 25-OH-D levels.

  8. A pilot randomized, controlled trial of vitamin D repletion to determine if endothelial function improves in patients with systemic lupus erythematosus

    PubMed Central

    Kamen, Diane L; Oates, Jim

    2015-01-01

    The endothelium is important not only in regulating vascular tone but also in modulating inflammation. Patients with systemic lupus erythematosus (SLE) have deficits in these endothelial functions. Vitamin D is a nuclear hormone that regulates vascular endothelial nitric oxide synthase activity and expression. Many SLE patients have insufficient levels of vitamin D. The effect of this hormone on vascular endothelial function in SLE patients is not known. This study was designed to determine the effect size of repleting vitamin D levels on endothelial function in patients with SLE and vitamin D deficiency. SLE patients with 25(OH) vitamin D (25(OH)D) levels < 20 ng/ml were randomized to oral vitamin D3 (D3) doses that did or did not raise 25(OH)D levels to ≥ 32 ng/ml. Endothelial function was measured with flow-mediated dilation (FMD) before and after 16 weeks of vitamin D3 supplementation. Half of those who achieved 25(OH)D levels of ≥32 ng/ml experienced increases in FMD, while none of those with continued low 25(OH)D levels did. Those with increases in FMD had significantly higher final 25(OH)D levels. Using the effect size from this study, future studies designed to test the effect of repleting 25(OH)D on FMD in vitamin D deficient SLE patients will require 35 patients in each group. These results suggest a potential role for vitamin D in SLE-related endothelial dysfunction and that an adaptive multi-arm treat-to-target serum level trial design may increase the efficiency and likelihood of success of such a study. PMID:26351776

  9. Association between serum vitamin D levels and subclinical coronary atherosclerosis and plaque burden/composition in young adult population

    PubMed Central

    Satilmis, Seckin; Celik, Omer; Biyik, Ismail; Ozturk, Derya; Celik, Kubra Asik; Akın, Fatih; Ayca, Burak; Yalcin, Burce; Dagdelen, Sinan

    2015-01-01

    Evidence suggests that low 25-OH vitamin D 25(OH)D concentrations may increase the risk of several cardiovascular diseases such as hypertension, peripheral vascular disease, diabetes mellitus, obesity, myocardial infarction, heart failure and cardiovascular mortality. Recent studies suggested a possible relationship between vitamin D deficiency and increased carotid intima-media wall thickness and vascular calcification. We hypothesized that low 25(OH)D may be associated with coronary atherosclerosis and coronary plaque burden and composition, and investigated the relationship between serum vitamin D levels and coronary atherosclerosis, plaque burden or structure, in young adult patients by using dual-source 128x2 slice coronary computed tomography angiography (CCTA). We included 98 patients with coronary atherosclerosis and 110, age and gender matched, subjects with normal findings on CCTA examinations. Patients with subclinical atherosclerosis had significantly higher serum total cholesterol, triglycerides, hs-CRP, uric acid, HbA1c and creatinine levels and lower serum 25(OH)D levels in comparison with controls. There was no significant correlation between 25(OH)D and plaque morphology. There was also a positive relationship between 25(OH)D and plaque burden of coronary atherosclerosis. In multivariate analysis, coronary atherosclerosis was associated high hs-CRP (adjusted OR: 2.832), uric acid (adjusted OR: 3.671) and low 25(OH)D (adjusted OR: 0.689). Low levels of 25(OH)D were associated with coronary atherosclerosis and plaque burden, but there was no significant correlation between 25(OH)D and plaque morphology. PMID:25725147

  10. Vitamin D and diabetes mellitus.

    PubMed

    Harinarayan, Chittari Venkata

    2014-01-01

    The vitamin D endocrine system in now recognized as subserving a wide range of fundamental biological functions in cell differentiation, inhibition of cell growth as well as immunomodulation. Both forms of immunity, namely adaptive and innate, are regulated by 1,25(OH)2D3. The immune-modulatory properties of vitamin D suggest that it could play a potential therapeutic role in prevention of type 1 diabetes mellitus (T1DM). It is postulated that large doses of vitamin D supplementation may influence the pattern of immune regulation and subsequent progression to T1DM in a genetically susceptible individual. More studies are required to substantiate the relation between T1DM and vitamin D/vitamin D analogues in the pattern of immune regulations in susceptible individuals. In type 2 diabetes mellitus (T2DM), vitamin D may influence both insulin secretion and sensitivity. An inverse relationship between T2DM and vitamin D is postulated from cross-sectional and prospective studies, though conclusive proof is as yet lacking. Available studies differ in their design and in the recommended daily allowances (RDA) of vitamin D in non-skeletal diseases and β-cell function. Large, well designed, controlled, randomized interventional studies on the potential role of vitamin D and calcium in prevention and management of T2DM are required to clarify the relationship between vitamin D and glucose homeostasis in T2DM.

  11. What is the role of vitamin D in autism?

    PubMed

    Cannell, John J; Grant, William B

    2013-01-01

    A growing body of literature suggests that higher serum 25-hydroxyvitamin D [25(OH)D] concentrations, either in utero or in early life, may reduce the risk of autism. For example, an ecological study in the companion paper inversely correlated solar UV-B doses in the United States with prevalence of autism among those aged 6-17 y. That study proposed that vitamin D deficiency during pregnancy could account for this finding, although the findings are also consistent with childhood vitamin D deficiency contributing to the condition. Also, in a recent study, children with autism had lower serum 25(OH)D concentrations than did control subjects (19 vs. 33 ng/ml), despite parents of each group reporting the same amount of sun exposure. The same study found highly significant inverse correlations between 25(OH)D and autism rating scales and between 25(OH)D and levels of an antineuronal antibody. This finding indicates that higher serum 25(OH)D concentrations may reduce the symptoms of established autism. Because activated vitamin D, a secosteroid, upregulates DNA-repair genes, vitamin D deficiency during development may inhibit the repair of de novo DNA mutations in fetuses and infants and thus contribute to risk of autism. Vitamin D might also reduce the risk or severity of autism through its anti-inflammatory actions, antiautoimmune effects, increasing seizure threshold, increasing T-regulatory cells, protecting the mitochondria, and upregulating glutathione, which scavenges oxidative by-products and chelates (captures and excretes) heavy metals. Vitamin D deficiency during pregnancy and childhood is a widespread and growing epidemic.

  12. Low Maternal Vitamin D Status during the Second Trimester of Pregnancy: A Cross-Sectional Study in Wuxi, China

    PubMed Central

    Xiao, Jian-Ping; Zang, Jia; Pei, Jing-Jing; Xu, Fei; Zhu, Yan; Liao, Xiang-Peng

    2015-01-01

    Background Vitamin D deficiency is common in pregnant women, but an optimal serum vitamin D level during pregnancy has not been determined and remains an area of active research. Vitamin D data from large populations of pregnant Chinese women are still limited. Objective To evaluate the vitamin D status of women in Eastern China during the second trimester of pregnancy. Methods A hospital-based, cross-sectional, observational study. Serum 25-hydroxyvitamin D [25(OH)D] concentration was measured in samples from 5823 pregnant women in Wuxi City, China (latitude: 31.5o N), from January 2011 to June 2012. Results The median serum 25(OH)D concentration was 34.0 nmol/L [2.5 nmol/L 25(OH)D = 1 ng/mL 25(OH)D]. Vitamin D deficiency [defined as 25(OH)D < 30 nmol/L according to the Institute of Medicine (National Academy of Sciences, Washington, D.C., USA)] or inadequacy [25(OH)D of 30–49.9 nmol/L] was identified in 40.7% and 38.0% of the women, respectively. Only 0.9% had a 25(OH)D level ≥ 80.0 nmol/L, which is the concentration recommended as adequate by the Endocrine Society (Washington, D.C., USA). Compared with older women, younger women were more likely to be deficient in vitamin D. There were significant differences in the 25(OH)D levels according to season. The 25(OH)D levels reached peak values in September and were correlated with (r = 0.337, P < 0.001), and fluctuated with, average monthly air temperatures. Conclusions There is a high prevalence of Vitamin D deficiency among pregnant Chinese women, and 25(OH)D levels varied according to season and air temperature. The results of this study also suggest that currently there is a big gap between the levels of Vitamin D detected in pregnant Chinese women and the levels recommended by the Endocrine Society. PMID:25659105

  13. Modulation of peritoneal macrophage antimicrobial activity by peritoneal dialysis fluid, Ca++, and 1,25(OH)2D3 in CAPD patients.

    PubMed

    Carozzi, S; Nasini, M G; Schelotto, C; Caviglia, P M; Barocci, S; Cantaluppi, A; Salit, M

    1990-01-01

    Previous in vitro studies showed that Ca++ and 1,25(OH)2D3 modulate peritoneal macrophage (PM0) antimicrobial activity in CAPD patients. Twenty-four CAPD patients were evaluated in vivo (12 who had never had peritonitis, and 12 with an overall peritonitis incidence of more than one episode per 8 patient/months), for the effects of different peritoneal dialysis fluids (PDF) and Ca++ concentrations (1.25, 1.75, and 2.25 mmol/L) on PM0: cytoplasmic Ca++ concentration; superoxide generation; leukotriene B4 (LTB4) release; and bacterial killing for Staphylococcus epidermidis. The same parameters were also evaluated after adding 1,25(OH)2D3 (0.25 microgram/L) to the PDF. Results showed a direct correlation between the PDF Ca++ concentration and PM0 Ca++ levels, superoxide and LTB4 generation, and bacterial killing such that, with 2.25 mmol/L of Ca++, these values were significantly higher than those seen with 1.75 mmol/L. The addition of 1,25(OH)2D3 potentiated the Ca(++)-induced effects. On the other hand, with PDF Ca++ levels of 1,25 mmol/L, an inhibition of the aforementioned parameters was seen. However, this effect was reversed by the addition of 1,25(OH)2D3. These in vivo results confirm the importance of Ca++ and 1,25(OH)2D3 in PM0 antibacterial function in CAPD patients, and may be useful in determining the prophylaxis and therapy of peritonitis.

  14. A Randomized Trial of Vitamin D Supplementation in Two Community Health Center Networks in South Carolina

    PubMed Central

    WAGNER, Carol L.; MCNEIL, Rebecca; HAMILTON, Stuart A.; WINKLER, Joyce; COOK, Carolina Rodriguez; WARNER, Gloria; BIVENS, Betty; DAVIS, Deborah J.; SMITH, Pamela G.; MURPHY, Martha; SHARY, Judy; HOLLIS, Bruce W.

    2015-01-01

    Objective To determine whether 4000 IU vitamin D3/day (vs. 2000 IU/day) during pregnancy is safe and improves maternal/neonatal 25(OH)D in a dose-dependent manner. Study Design 257 pregnant women 12–16 weeks’ gestation were enrolled. Randomization to 2000- vs. 4000 IU/day followed one-month run-in at 2000 IU/day. Participants were monitored for hypercalciuria, hypercalcemia and 25(OH)D status. Results Maternal 25(OH)D (n=161) increased from 22.7(SD 9.7) at baseline to 36.2(SD 15) and 37.9(SD 13.5) in the 2000- and 4000 IU groups, respectively. While maternal 25(OH)D change from baseline did not differ between groups, 25(OH)D monthly increase differed between groups (p<0.01). No supplementation-related adverse events occurred. Mean cord blood 25(OH)D (ng/mL) was 22.1±10.3 in 2000- and 27.0±13.3 in 4000 IU group (p=0.024). After controlling for race and study site, preterm birth and labor were inversely associated with pre-delivery- and mean 25(OH)D, but not baseline 25(OH)D,. Conclusions Maternal supplementation with 2000 and 4000 IU vitamin D/day during pregnancy improved maternal/neonatal vitamin D status. Evidence of risk reduction in infection, preterm labor and preterm birth was suggestive, requiring additional studies powered for these endpoints. PMID:23131462

  15. Vitamin D status in early pregnancy and risk of preeclampsia

    PubMed Central

    Achkar, Madonna; Dodds, Linda; Giguère, Yves; Forest, Jean-Claude; Armson, B. Anthony; Woolcott, Christy; Agellon, Sherry; Spencer, Anne; Weiler, Hope A.

    2016-01-01

    OBJECTIVE We sought to examine the association between maternal serum 25-hydroxyvitamin D (25[OH]D) concentration in early pregnancy and the subsequent diagnosis of preeclampsia (PE). STUDY DESIGN This was a nested case-control study from 2 prospective Canadian cohorts conducted in Quebec City, Quebec, and Halifax, Nova Scotia, from 2002 through 2010. Participants were pregnant women (n=169 cases with PE and 1975 controls). Maternal serum was drawn <20 weeks of gestation, and 25(OH)D measurement was performed. Cases were ascertained from medical records. Logistic regression analysis was used to estimate adjusted odds ratios with 95% confidence intervals. RESULTS Women who developed PE had a significantly lower 25(OH)D concentration at a mean gestational age of 14 weeks compared with women in the control group (mean ± SD 25[OH]D 47.2 ± 17.7 vs 52.3 ± 17.2 nmol/L, P < .0001). Women with 25(OH)D <30 nmol/L compared to those with at least 50 nmol/L had a greater risk of developing PE (adjusted odds ratio, 2.23; 95% confidence interval, 1.29–3.83) after adjustment for prepregnancy body mass index, maternal age, smoking, parity, season and year of blood collection, gestational week at blood collection, and cohort site. Exploratory analysis with cubic splines demonstrated a dose-response relationship between maternal 25(OH)D and risk of PE, up to levels around 50 nmol/L, where the association appeared to plateau. CONCLUSION Maternal vitamin D deficiency early in pregnancy defined as 25(OH)D<30 nmol/L may be an independent risk factor for PE. The relevance of vitamin D supplementation for women of child-bearing age should be explored as a strategy for reducing PE and for promoting a healthier pregnancy. PMID:25446694

  16. Chemotherapy is linked to severe vitamin D deficiency in patients with colorectal cancer

    PubMed Central

    Fakih, Marwan G.; Trump, Donald L.; Johnson, Candace S.; Tian, Lili; Muindi, Josephia; Sunga, Annette Y.

    2009-01-01

    Background Preclinical and clinical evidence support an association between vitamin D deficiency and an increased risk of colorectal cancer. Normal vitamin D status has been linked to favorable health outcomes ranging from decreased risk of osteoporosis to improved cancer mortality. We performed a retrospective study to assess the impact of metastatic disease and chemotherapy treatment on vitamin D status in patients with colorectal cancer residing in Western New York. Materials and methods Patients, 315, with colorectal cancer treated in a single institute were assayed for 25-OH vitamin D. The association of age, gender, primary disease site and stage, body mass index, and chemotherapy with vitamin D status was investigated. Results Vitamin D deficiency was common among participants with a median 25-OH vitamin D level of 21.3 ng/ml (optimal range 32–100 ng/ml). Primary site of disease and chemotherapy status were associated with very low 25-OH vitamin D levels (≤15 ng/ml) on multivariate analysis. Patients receiving chemotherapy and patients with a rectal primary were fourfold and 2.6-fold more likely to have severe vitamin D deficiency on multivariate analysis than nonchemotherapy patients and colon cancer primary patients, respectively. Conclusions Chemotherapy is associated with a significant increase in the risk of severe vitamin D deficiency. Patients with colorectal cancer, especially those receiving chemotherapy, should be considered for aggressive vitamin D replacement strategies. PMID:18830610

  17. Assessment of the effect of esterified propoxylated glycerol (EPG) on the status of fat-soluble vitamins and select water-soluble nutrients following dietary administration to humans for 8 weeks.

    PubMed

    Davidson, Michael H; Bechtel, David H

    2014-12-01

    This double-blind, randomized, controlled study assessed the effect of esterified propoxylated glycerol (EPG) on fat-soluble vitamins and select nutrients in human subjects. For 8 weeks, 139 healthy volunteers consumed a core diet providing adequate caloric and nutrient intakes. The diet included items (spread, muffins, cookies, and biscuits) providing EPG (10, 25, and 40 g/day) vs. margarine alone (control). EPG did not significantly affect circulating retinol, α-tocopherol, or 25-OH D2, but circulating β-carotene and phylloquinone were lower in the EPG groups, and PIVKA-II levels were higher; 25-OH D3 increased but to a lesser extent than the control. The effect might be related to EPG acting as a lipid "sink" during gastrointestinal transit. No effects were seen in secondary endpoint measures (physical exam, clinical pathology, serum folate, RBC folate, vitamin B12, zinc, iron, calcium, phosphorus, osteocalcin, RBP, intact PTH, PT, PTT, cholesterol, HDL-C, LDL-C, triglycerides). Gastrointestinal adverse events (gas with discharge; diarrhea; oily spotting; oily evacuation; oily stool; liquid stool; soft stool) were reported more frequently by subjects receiving 25 or 40 g/day of EPG. In general, the incidence and duration of these symptoms correlated directly with EPG dietary concentration. The results suggest 10 g/day of EPG was reasonably well tolerated. PMID:25497998

  18. Assessment of the effect of esterified propoxylated glycerol (EPG) on the status of fat-soluble vitamins and select water-soluble nutrients following dietary administration to humans for 8 weeks.

    PubMed

    Davidson, Michael H; Bechtel, David H

    2014-12-01

    This double-blind, randomized, controlled study assessed the effect of esterified propoxylated glycerol (EPG) on fat-soluble vitamins and select nutrients in human subjects. For 8 weeks, 139 healthy volunteers consumed a core diet providing adequate caloric and nutrient intakes. The diet included items (spread, muffins, cookies, and biscuits) providing EPG (10, 25, and 40 g/day) vs. margarine alone (control). EPG did not significantly affect circulating retinol, α-tocopherol, or 25-OH D2, but circulating β-carotene and phylloquinone were lower in the EPG groups, and PIVKA-II levels were higher; 25-OH D3 increased but to a lesser extent than the control. The effect might be related to EPG acting as a lipid "sink" during gastrointestinal transit. No effects were seen in secondary endpoint measures (physical exam, clinical pathology, serum folate, RBC folate, vitamin B12, zinc, iron, calcium, phosphorus, osteocalcin, RBP, intact PTH, PT, PTT, cholesterol, HDL-C, LDL-C, triglycerides). Gastrointestinal adverse events (gas with discharge; diarrhea; oily spotting; oily evacuation; oily stool; liquid stool; soft stool) were reported more frequently by subjects receiving 25 or 40 g/day of EPG. In general, the incidence and duration of these symptoms correlated directly with EPG dietary concentration. The results suggest 10 g/day of EPG was reasonably well tolerated.

  19. Vitamin D in epilepsy: vitamin D levels in epilepsy patients, patients on antiepileptic drug polytherapy and drug-resistant epilepsy sufferers.

    PubMed

    Nagarjunakonda, S; Amalakanti, S; Uppala, V; Rajanala, L; Athina, S

    2016-01-01

    The objective of this study was to assess vitamin D levels in epileptic patients and to compare its serum levels in patients on antiepileptic monotherapy and polytherapy. We analyzed the serum 25-hydroxy (25-OH) vitamin D levels in 98 consecutive subjects (43 epileptic patients and 55 non-epileptics). Factors influencing its serum levels such as degree of sun exposure, physical activity and dietary intake were taken into consideration. Overall, 41% had deficient, 49% had insufficient and 9% had sufficient levels of serum vitamin D. Elderly individuals (>60 years) and people employed in offices and schools had lower blood vitamin D levels. Across both the sexes, epileptic patients and non-epileptics, epileptic patients on monotherapy and polytherapy and patients with drug-responsive and -resistant seizures, there were no significant differences in serum 25-OH vitamin D levels. Our study shows that people with epilepsy suffer with vitamin D deficiency along with their normal peers.

  20. Optimal vitamin D levels in Crohn's disease: a review.

    PubMed

    Raftery, Tara; O'Sullivan, Maria

    2015-02-01

    Vitamin D deficiency is common among patients with Crohn's disease. Serum 25-hydroxyvitamin D (25(OH)D) is the best measure of an individual's vitamin D status and current cut-off ranges for sufficiency are debatable. Several factors contribute to vitamin D deficiency in Crohn's disease. These include inadequate exposure to sunlight, inadequate dietary intake, impaired conversion of vitamin D to its active metabolite, increased catabolism, increased excretion and genetic variants in vitamin D hydroxylation and transport. The effects of low 25(OH)D on outcomes other than bone health are understudied in Crohn's disease. The aim of the present review is to discuss the potential roles of vitamin D and the possible levels required to achieve them. Emerging evidence suggests that vitamin D may have roles in innate and adaptive immunity, in the immune-pathogenesis of Crohn's disease, prevention of Crohn's disease-related hospitalisations and surgery, in reducing disease severity and in colon cancer prevention. The present literature appears to suggest that 25(OH)D concentrations of ≥75 nmol/l may be required for non-skeletal effects; however, further research on optimal levels is required.

  1. Vitamin D and Mammographic Findings

    PubMed Central

    Riedel, J.; Straub, L.; Wissing, J.; Artmann, A.; Schmidmayr, M.; Kiechle, M.; Seifert-Klauss, V. R.

    2016-01-01

    Introduction: Pleiotropic immune-modulatory and anti-proliferative effects of vitamin D and hopes to stop cancerogenesis have led to an increased interest in possible reduction of breast cancer with higher vitamin D levels. Mammographic density is an established risk factor for breast cancer risk, and its association with serum vitamin D is complex, as recent studies have shown. Patients and Methods: In this cross-sectional study, 1103 participants were recruited in the breast diagnostic unit of the Klinikum rechts der Isar, TU Munich. A standardised questionnaire and blood samples for 25-OH-vitamin D were taken on the day of mammography. Histologic results of biopsies in suspicious mammographies were documented. Results: In the 1090 data-sets analysed, vitamin D-deficiency was common among women under 40. Highest vitamin D values were observed in participants aged 60–69 years, but average values for all age cohorts were below 20 ng/ml of vitamin D. 15.6 % of all participants had very low vitamin D values (< 10 ng/ml), 51.3 % were vitamin D-deficient (10–19 ng/ml) and only 5.7 % were above 30 ng/ml, i.e. showed sufficient vitamin D. Patients with malignant results had vitamin D < 10 ng/ml more often (16.9 %; p = 0.61), and only 3.4 % in this group had sufficient vitamin D supply (> 30 ng/ml). There were no significant differences in vitamin D-levels between density groups according to the American College of Radiology (ACR) criteria. Conclusion: Vitamin D values were lower than in comparable US women. Up to now, there is no direct clinical evidence for a relationship between the risk for breast cancer and a specific vitamin D value. PMID:27239067

  2. The Vitamin D Status of Prison Inmates

    PubMed Central

    Nwosu, Benjamin Udoka; Maranda, Louise; Berry, Rosalie; Colocino, Barbara; Flores Sr., Carlos D.; Folkman, Kerry; Groblewski, Thomas; Ruze, Patricia

    2014-01-01

    Introduction There is no comprehensive, systematic analysis of the vitamin D status of prisoners in the scientific literature. Objective To investigate the vitamin D status and its determinants in US prison inmates. Hypothesis Given the uniformity of dietary intake amongst inmates, vitamin D status will be determined by non-dietary factors such as skin pigmentation, security level-, and the duration of incarceration. Subjects and Methods A retrospective study of 526 inmates (males, n = 502, age 48.6±12.5 years; females, n = 24, age 44.1±12.2) in Massachusetts prisons. Vitamin D sufficiency, insufficiency, and deficiency were respectively defined as a 25(OH)D concentration 75 nmol/L; 50 to 75 nmol/L; and <50 nmol/L. The Massachusetts Department of Correction Statement of Nutritional Adequacy stated that each inmate received the recommended daily allowance of vitamin D daily. Security level of incarceration was designated as minimum, medium, and maximum. Racial groups were categorized as Black, white, Asian, and Others. Results Serum 25(OH)D levels peaked in summer and autumn, and decreased in winter and spring. Vitamin D deficiency occurred in 50.5% of blacks, 29.3% of whites, and 14.3% of Asian inmates (p = 0.007). Black inmates had significantly lower serum 25(OH)D level than white inmates at the maximum security level (p = 0.015), medium security level (p = 0.001), but not at the minimum security level (p = 0.40). After adjusting for covariates black inmates at a maximum security level had a four-fold higher risk for vitamin D deficiency than white inmates at the same security level (OR 3.9 [95% CI 1.3–11.7]. Conclusions The vitamin D status of prison inmates is determined by skin pigmentation, seasons, and the security level of incarceration. PMID:24598840

  3. Racial differences in the relationship between vitamin D, bone mineral density, and parathyroid hormone in the National Health and Nutrition Examination Survey

    PubMed Central

    Farwell, W. R.; Kermah, D.; Taylor, E. N.

    2011-01-01

    Summary It is unclear whether optimal levels of 25-hydroxyvitamin D (25(OH)D) in whites are the same as in minorities. In adult participants of NHANES, the relationships between 25(OH)D, bone mineral density (BMD), and parathyroid hormone (PTH) differed in blacks as compared to whites and Mexican-Americans, suggesting that optimal 25(OH)D levels for bone and mineral metabolism may differ by race. Introduction Blacks and Hispanics have lower 25-hydroxyvitamin D concentrations than whites. However, it is unclear whether 25(OH)D levels considered “optimal” for bone and mineral metabolism in whites are the same as those in minority populations. Methods We examined the relationships between 25(OH)D and parathyroid hormone in 8,415 adult participants (25% black and 24% Mexican-American) in the National Health and Nutrition Examination Surveys 2003–2004 and 2005–2006; and between 25(OH)D and bone mineral density in 4,206 adult participants (24% black and 24% Mexican-American) in the 2003–2004 sample. Results Blacks and Mexican-Americans had significantly lower 25(OH)D and higher PTH concentrations than whites (P<0.01 for both). BMD significantly decreased (P<0.01) as serum 25(OH)D and calcium intake declined among whites and Mexican-Americans, but not among blacks (P=0.2). The impact of vitamin D deficiency (25 (OH)D≤20 ng/ml) on PTH levels was modified by race/ethnicity (P for interaction, 0.001). Whereas inverse relationships between 25(OH)D and PTH were observed above and below a 25(OH)D level of 20 ng/ml in whites and Mexican-Americans, an inverse association between 25(OH)D and PTH was only observed below this threshold in blacks, with the slope of the relationship being essentially flat (P=0.7) above this cut-point, suggesting that PTH may be maximally suppressed at lower 25(OH)D levels in blacks than in whites or Mexican-Americans. Conclusions The relationships between 25(OH)D, BMD, and PTH may differ by race among US adults. Whether race

  4. Evolution and function of vitamin D.

    PubMed

    Holick, Michael F

    2003-01-01

    It is remarkable that phytoplankton and zooplankton have been producing vitamin D for more than 500 million years. The role of vitamin D in lower non-vertebrate life forms is not well understood. However, it is critically important that most vertebrates obtain an adequate source of vitamin D, either from exposure to sunlight or from their diet, in order to develop and maintain a healthy mineralized skeleton. Vitamin D deficiency is an unrecognized epidemic in most adults who are not exposed to adequate sunlight. This can precipitate and exacerbate osteoporosis and cause the painful bone disease osteomalacia. Once vitamin D is absorbed from the diet or made in the skin by the action of sunlight, it is metabolized in the liver to 25-hydroxyvitamin D [25(OH)D] and then in the kidney to 1,25-dihydroxyvitamin D [1,25(OH)2D]. 1,25(OH)2D interacts with its nuclear receptor (VDR) in the intestine and bone in order to maintain calcium homeostasis. The VDR is also present in a wide variety of other tissues. 1,25(OH)2D interacts with these receptors to have a multitude of important physiological effects. In addition, it is now recognized that many tissues, including colon, breast and prostate, have the enzymatic machinery to produce 1,25(OH)2D. The insights into the new biological functions of 1,25(OH)2D in regulating cell growth, modulating the immune system and modulating the renin-angiotensin system provides an explanation for why diminished sun exposure at higher latitudes is associated with increased risk of dying of many common cancers, developing type 1 diabetes and multiple sclerosis, and having a higher incidence of hypertension. Another calciotropic hormone that is also produced in the skin, parathyroid hormone-related peptide, is also a potent inhibitor of squamous cell proliferation. The use of agonists and antagonists for PTHrP has important clinical applications for the prevention and treatment of skin diseases and disorders of hair growth. PMID:12899511

  5. Vitamin D and diabetes mellitus: an update 2013.

    PubMed

    Griz, Luiz Henrique Maciel; Bandeira, Francisco; Gabbay, Mônica Andrade Lima; Dib, Sergio Atala; Carvalho, Eduardo Freese de

    2014-02-01

    Vitamin D deficiency and diabetes mellitus are two common conditions and they are widely prevalent across all ages, races, geographical regions, and socioeconomic conditions. Epidemiologic studies have shown association of vitamin D deficiency and increased risk of chronic diseases, such as cancer, cardiovascular disease, type 2 diabetes, and autoimmune diseases, such as multiple sclerosis and type 1 diabetes mellitus. The identification of 1,25(OH)2D receptors and 1-α-hydroxilase expression in pancreatic beta cells, in cells of the immune system, and in various others tissues, besides the bone system support the role of vitamin D in the pathogenesis of type 2 diabetes. Observational studies have revealed an association between 25(OH) D deficiency and the prevalence of type 1 diabetes in children and adolescents. This review will focus on the concept of vitamin D deficiency, its prevalence, and its role in the pathogenesis and risk of diabetes mellitus and cardiovascular diseases.

  6. Association between Serum Vitamin D Level and Glycemic and Inflammatory Markers in Non-obese Patients with Type 2 Diabetes

    PubMed Central

    Haidari, Fatemeh; Zakerkish, Mehrnoosh; Karandish, Majid; Saki, Azadeh; Pooraziz, Sakineh

    2016-01-01

    Background: Low serum 25-hydroxy vitamin D (25(OH)D) has been shown to correlate with an increased risk of type 2 diabetes mellitus (T2DM). The objective of this study was to investigate the association between serum 25(OH)D and glycemic and inflammatory markers in non-obese patients with T2DM. Methods: Eighty-four non-obese patients with T2DM were recruited in this cross-sectional study. Demographic, anthropometric, and dietary information was obtained from all the participants. The serum concentrations of glucose, HbA1C, insulin, 25(OH)D, and inflammatory markers including tumor necrosis factor-alpha (TNF-α) and high sensitive C-reactive protein (hs-CRP) were measured. A homeostatic model of insulin resistance (HOMA-IR) was also evaluated. Results: The mean serum concentration of 25(OH)D was 11.01±5.55 ng/mL. Severe deficiency, deficiency, and insufficiency of vitamin D were detected in 60.71%, 35.72%, and 3.57% of the participants, respectively. The results showed that those in the lowest group of serum 25(OH)D had significantly higher TNF-α than did those in the highest group (P=0.026). Although the association between serum 25(OH)D and fasting blood sugar and TNF-α was statistically significant (P=0.049 and P=0.044, respectively), the other glycemic markers and hs-CRP did not have any significant relationships with 25(OH)D. Conclusion: According to the high prevalence of vitamin D deficiency in the diabetic patients and the inverse relationship between serum 25(OH)D and fasting blood sugar and TNF-α in this study, vitamin D status may be a determining factor of systemic inflammation in patients with T2DM. Further studies with larger sample sizes are suggested in this regard. PMID:27582585

  7. In vivo activation of the intracrine vitamin D pathway in innate immune cells and mammary tissue during a bacterial infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is an important regulator of immune function. The enzyme that synthesizes 1,25(OH)2D3 from 25-hydroxyvitamin D3 is 1alpha-hydroxylase (1alpha-OHase; CYP27B1). Several in vitro studies have shown that TLR signaling induces expre...

  8. Mechanisms regulating osteoblast response to surface microtopography and vitamin D

    NASA Astrophysics Data System (ADS)

    Bell, Bryan Frederick, Jr.

    A comprehensive understanding of the interactions between orthopaedic and dental implant surfaces with the surrounding host tissue is essential in the design of advanced biomaterials that better promote bone growth and osseointegration of implants. Dental implants with roughened surfaces and high surface energy are well known to promote osteoblast differentiation in vitro and promote increased bone-to-implant contact in vivo. In addition, increased surface roughness increases osteoblasts response to the vitamin D metabolite 1alpha,25(OH)2D3. However, the exact mechanisms mediating cell response to surface properties and 1alpha,25(OH)2D3 are still being elucidated. The central aim of the thesis is to investigate whether integrin signaling in response to rough surface microtopography enhances osteoblast differentiation and responsiveness to 1alpha,25(OH)2D3. The hypothesis is that the integrin alpha5beta1 plays a role in osteoblast response to surface microtopography and that 1alpha,25(OH) 2D3 acts through VDR-independent pathways involving caveolae to synergistically enhance osteoblast response to surface roughness and 1alpha,25(OH) 2D3. To test this hypothesis the objectives of the studies performed in this thesis were: (1) to determine if alpha5beta 1 signaling is required for osteoblast response to surface microstructure; (2) to determine if increased responsiveness to 1alpha,25(OH)2D 3 requires the vitamin D receptor, (3) to determine if rough titanium surfaces functionalized with the peptides targeting integrins (RGD) and transmembrane proteoglycans (KRSR) will enhance both osteoblast proliferation and differentiation, and (4) to determine whether caveolae, which are associated with integrin and 1alpha,25(OH)2D3 signaling, are required for enhance osteogenic response to surface microstructure and 1alpha,25(OH)2D 3. The results demonstrate that integrins, VDR, and caveolae play important roles in mediating osteoblast response to surface properties and 1alpha,25

  9. Comparison of Vitamin D Levels in Patients with and without Acne: A Case-Control Study Combined with a Randomized Controlled Trial

    PubMed Central

    Ha, Jeong-Min; Lee, Young-Ho; Lee, Young; Seo, Young-Joon; Kim, Chang-Deok; Lee, Jeung-Hoon; Im, Myung

    2016-01-01

    Background Vitamin D plays an important role in the immune system, and its deficiency has been implicated in various skin diseases, including atopic dermatitis and psoriasis. Acne is a common inflammatory skin disease; however, the association with vitamin D remains unclear. Objectives We evaluated vitamin D levels in patients with acne to determine the effect of vitamin D supplementation. Methods This study included 80 patients with acne and 80 healthy controls. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured, and demographic data were collected. Vitamin D-deficient patients were treated with oral cholecalciferol at 1000 IU/day for 2 months. Results Deficiency in 25(OH)D was detected in 48.8% of patients with acne, but in only 22.5% of the healthy controls. The level of 25(OH)D was inversely associated with the severity of acne, and there was a significant negative correlation with inflammatory lesions. In a subsequent trial, improvement in inflammatory lesions was noted after supplementation with vitamin D in 39 acne patients with 25(OH)D deficiency. Limitations Limitations of the study include the small number of patients in the supplementation study and the natural fluctuation of acne. Conclusions Vitamin D deficiency was more frequent in patients with acne, and serum 25(OH)D levels were inversely correlated with acne severity, especially in patients with inflammatory lesions. PMID:27560161

  10. Vitamin D and Gestational Diabetes Mellitus

    PubMed Central

    Burris, Heather H.; Camargo, Carlos A.

    2014-01-01

    Gestational diabetes mellitus (GDM) complicates 7–14% of pregnancies in the United States. Vitamin D deficiency also is common in pregnancy. Emerging evidence suggests that Vitamin D administration can improve insulin sensitivity and glucose tolerance, but whether vitamin D supplementation can prevent GDM is unknown. Observational studies provide conflicting evidence as to whether low serum 25-hydroxyvitmain D (25(OH)D) levels are associated with GDM. Two recent systematic reviews concluded that vitamin D deficiency is associated with a higher risk of GDM. However, these reviews are limited by the observational and diverse nature of the included studies. Of greatest concern is the inability to understand how important confounding variables such as race/ethnicity and adiposity might affect the association. Randomized controlled trial data remain limited but are critical to understanding whether supplementation with vitamin D beyond what is contained in routine prenatal vitamins will prevent GDM or improve glucose tolerance for women with GDM. PMID:24277676

  11. [Down-regulation of p38 MAPK and collagen by 1, 25-(OH)2-VD3 in rat models of diabetic nephropathy].

    PubMed

    Xie, Xianhui; Li, Zhengsheng; Pi, Mingjing; Wu, Jing; Zeng, Wen; Zuo, Li; Zha, Yan

    2016-07-01

    Objective To investigate the effect of 1, 25-(OH)2-VD3 on collagen type III (Col3), collagen type IV (Col4) and p38 mitogen-activated protein kinase (p38 MAPK) in rat models of type 2 diabetic nephropathy, and explore the relationships of p38MAPK with Col3 and Col4. Methods Rat models of type 2 diabetic nephropathy were induced by streptozocin (STZ, 30 mg/kg) combined with high-glucose-and-fat diet. Sixty rats were randomly divided into control group, model group, 1, 25-(OH)2-VD3 treatment group [given 1, 25-(OH)2-VD3 6 ng/(100 g.d) after modeling] and insulin group (given 2-3 U insulin after modeling). After 8 weeks' intervention, serum creatinine (Scr), blood urea nitrogen (BUN) and 24-hour proteinuria were detected in all groups. Periodic acid-Schiff (PAS) staining was used to observe the kidney pathological changes, and immunohistochemical staining and Western blotting were performed to determine p38 MAPK Col3 and Col4 expressions in rat renal interstitium. Spearman method was applied to the correlation analysis. Results Compared with the model group, blood glucose, Scr, BUN, 24-hour proteinuria and impaired renal interstitial area were all reduced in the 1, 25-(OH)2-VD3 treatment group and the insulin group. Compared with the control group, the expressions of Col3, Col4 and p38 MAPK were higher in the model group, and lower in the 1, 25-(OH)2-VD3 treatment group and the insulin group. Correlation analysis showed that 24-hour proteinuria was positively related with p38 MAPK, Col3, Col4 and immunohistochemical results; p38MAPK was positively correlated with Col3 and Col4 expressions. Conclusion Col3, Col4 and p38MAPK are up-regulated in rat models of type 2 diabetic nephropathy. The 1, 25-(OH)2-VD3 might attenuates the progression of renal interstitial fibrosis via down-regulating p38 MAPK, Col3 and Col4. PMID:27363275

  12. Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up

    PubMed Central

    Schoindre, Yoland; Jallouli, Moez; Tanguy, Marie-Laure; Ghillani, Pascale; Galicier, Lionel; Aumaître, Olivier; Francès, Camille; Le Guern, Véronique; Lioté, Frédéric; Smail, Amar; Limal, Nicolas; Perard, Laurent; Desmurs-Clavel, Hélène; Thi Huong, Du Le; Asli, Bouchra; Kahn, Jean-Emmanuel; Sailler, Laurent; Ackermann, Félix; Papo, Thomas; Sacré, Karim; Fain, Olivier; Stirnemann, Jérôme; Cacoub, Patrice; Leroux, Gaëlle; Cohen-Bittan, Judith; Hulot, Jean-Sébastien; Lechat, Philippe; Musset, Lucile; Piette, Jean-Charles; Amoura, Zahir; Souberbielle, Jean-Claude; Costedoat-Chalumeau, Nathalie

    2014-01-01

    Objectives Growing evidence suggests that vitamin D plays a key role in the pathogenesis and progression of autoimmune diseases, including systemic lupus erythematosus (SLE). Recent studies have found an association between lower serum 25-hydroxyvitamin D (25(OH)D) levels and higher SLE activity. We studied the relationship between 25(OH)D levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and we assessed for the first time the role of vitamin D in predicting SLE flare-ups. Methods Serum 25(OH)D levels were measured in 170 patients with SLE who were prospectively followed up for 6 months (Plaquenil LUpus Systemic study, ClinicalTrials.gov number NCT00413361). Results The mean SLEDAI score was 2.03±2.43 and 12.3% patients had active disease (SLEDAI ≥6). The mean 25(OH)D level was 20.6±9.8 ng/mL. Deficiency (25(OH)D <10 ng/mL) was observed in 27 (15.9%), insufficiency (10≤25(OH)D<30) in 112 (65.9%) and optimal vitamin D status (25(OH)D≥30) in 31 (18.2%) patients. In multivariate analysis, female gender (p=0.018), absence of defined antiphospholipid syndrome (p=0.002) and higher creatinine clearance (p=0.004) were predictive of lower 25(OH)D levels. In multivariate analysis, lower 25(OH)D levels were associated with high SLE activity (p=0.02). Relapse-free survival rate was not statistically different according to the vitamin D status during the 6-month follow-up (p=0.22). Conclusions We found a low vitamin D status in the majority of patients with SLE, and a modest association between lower 25(OH)D levels and high disease activity. There was no association between baseline 25(OH)D levels and relapse-free survival rate. PMID:25379192

  13. A systems-based investigation into vitamin D and skeletal muscle repair, regeneration, and hypertrophy.

    PubMed

    Owens, Daniel J; Sharples, Adam P; Polydorou, Ioanna; Alwan, Nura; Donovan, Timothy; Tang, Jonathan; Fraser, William D; Cooper, Robert G; Morton, James P; Stewart, Claire; Close, Graeme L

    2015-12-15

    Skeletal muscle is a direct target for vitamin D. Observational studies suggest that low 25[OH]D correlates with functional recovery of skeletal muscle following eccentric contractions in humans and crush injury in rats. However, a definitive association is yet to be established. To address this gap in knowledge in relation to damage repair, a randomised, placebo-controlled trial was performed in 20 males with insufficient concentrations of serum 25(OH)D (45 ± 25 nmol/l). Prior to and following 6 wk of supplemental vitamin D3 (4,000 IU/day) or placebo (50 mg of cellulose), participants performed 20 × 10 damaging eccentric contractions of the knee extensors, with peak torque measured over the following 7 days of recovery. Parallel experimentation using isolated human skeletal muscle-derived myoblast cells from biopsies of 14 males with low serum 25(OH)D (37 ± 11 nmol/l) were subjected to mechanical wound injury, which enabled corresponding in vitro studies of muscle repair, regeneration, and hypertrophy in the presence and absence of 10 or 100 nmol 1α,25(OH)2D3. Supplemental vitamin D3 increased serum 25(OH)D and improved recovery of peak torque at 48 h and 7 days postexercise. In vitro, 10 nmol 1α,25(OH)2D3 improved muscle cell migration dynamics and resulted in improved myotube fusion/differentiation at the biochemical, morphological, and molecular level together with increased myotube hypertrophy at 7 and 10 days postdamage. Together, these preliminary data are the first to characterize a role for vitamin D in human skeletal muscle regeneration and suggest that maintaining serum 25(OH)D may be beneficial for enhancing reparative processes and potentially for facilitating subsequent hypertrophy. PMID:26506852

  14. Vitamin D Status Is Negatively Correlated with Insulin Resistance in Chinese Type 2 Diabetes.

    PubMed

    Zhang, Jie; Ye, Jianhong; Guo, Gang; Lan, Zhenhao; Li, Xing; Pan, Zhiming; Rao, Xianming; Zheng, Zongji; Luo, Fangtao; Lin, Luping; Lin, Zhihua; Xue, Yaoming

    2016-01-01

    Objectives. Vitamin D deficiency plays a role in insulin resistance and the pathogenesis of type 2 diabetes mellitus. Little information is available about the association between vitamin D status and insulin resistance in the Chinese population. Currently, vitamin D status is evaluated by the concentrations of serum 25-hydroxyvitamin D [25(OH)D]. This study explores the relationship between insulin resistance and serum 25-hydroxyvitamin D concentrations in Chinese patients with type 2 diabetes mellitus. Subjects and Methods. This study included 117 patients with type 2 diabetes. The following variables were measured: 25-hydroxyvitamin D [25(OH)D], glycosylated hemoglobin A1c (HbA1c), fasting blood glucose (FBS), fasting blood insulin (FINS), fasting blood C-peptide, serum creatinine (SCr), glomerular filtration rate (eGFR), body mass index (BMI), and homeostatic model estimates of insulin resistance (HOMA-IR). Results. The cases were divided into three groups: Group 1 (G1) with 25(OH)D ≤ 20 ng/mL [≤50 nmol/L], Group 2 (G2) with 25(OH)D values from 20 ng/mL [50 nmol/L] to 30 ng/mL [75 nmol/L], and Group 3 (G3) with 25(OH)D ≥ 30 ng/mL [≥75 nmol/L], with 52.6%, 26.3%, and 21.1% of subjects in Groups 1-3, respectively. There was a negative correlation between 25(OH)D and HOMA-IR (β = -0.314, p = 0.001) adjusted by age, BMI, and eGFR. Conclusion. Better vitamin D status may be protective of glucose homeostasis since 25(OH)D was negatively associated with insulin resistance in Chinese patients with type 2 diabetes. PMID:27413370

  15. Vitamin D Status Is Negatively Correlated with Insulin Resistance in Chinese Type 2 Diabetes

    PubMed Central

    Zhang, Jie; Ye, Jianhong; Guo, Gang; Lan, Zhenhao; Li, Xing; Pan, Zhiming; Rao, Xianming; Luo, Fangtao; Lin, Luping; Lin, Zhihua; Xue, Yaoming

    2016-01-01

    Objectives. Vitamin D deficiency plays a role in insulin resistance and the pathogenesis of type 2 diabetes mellitus. Little information is available about the association between vitamin D status and insulin resistance in the Chinese population. Currently, vitamin D status is evaluated by the concentrations of serum 25-hydroxyvitamin D [25(OH)D]. This study explores the relationship between insulin resistance and serum 25-hydroxyvitamin D concentrations in Chinese patients with type 2 diabetes mellitus. Subjects and Methods. This study included 117 patients with type 2 diabetes. The following variables were measured: 25-hydroxyvitamin D [25(OH)D], glycosylated hemoglobin A1c (HbA1c), fasting blood glucose (FBS), fasting blood insulin (FINS), fasting blood C-peptide, serum creatinine (SCr), glomerular filtration rate (eGFR), body mass index (BMI), and homeostatic model estimates of insulin resistance (HOMA-IR). Results. The cases were divided into three groups: Group 1 (G1) with 25(OH)D ≤ 20 ng/mL [≤50 nmol/L], Group 2 (G2) with 25(OH)D values from 20 ng/mL [50 nmol/L] to 30 ng/mL [75 nmol/L], and Group 3 (G3) with 25(OH)D ≥ 30 ng/mL [≥75 nmol/L], with 52.6%, 26.3%, and 21.1% of subjects in Groups 1–3, respectively. There was a negative correlation between 25(OH)D and HOMA-IR (β = −0.314, p = 0.001) adjusted by age, BMI, and eGFR. Conclusion. Better vitamin D status may be protective of glucose homeostasis since 25(OH)D was negatively associated with insulin resistance in Chinese patients with type 2 diabetes. PMID:27413370

  16. Circulating Vitamin D, Supplement Use, and Cardiovascular Disease Risk: The MrOS Sleep Study

    PubMed Central

    Bajaj, Archna; Stone, Katie L.; Peters, Katherine; Parimi, Neeta; Barrett-Connor, Elizabeth; Bauer, Doug; Cawthon, Peggy M.; Ensrud, Kristine E.; Hoffman, Andrew R.; Orwoll, Eric

    2014-01-01

    Context: Evidence suggests an inverse association between circulating 25(OH) vitamin D and cardiovascular disease (CVD). Objective: To determine the association between serum 25(OH) vitamin D and risk for CVD events. Setting and Design: From March 2000 to April 2002, participants were recruited for the Osteoporotic Fractures in Men (MrOS) study. Between December 2003 and March 2005, members of the MrOS cohort were invited to participate in the MrOS Sleep Study. Participants were recruited from 6 clinical centers across the United States and followed for a mean of 5.9 years. Three-thousand-one-hundred-thirty-five men ages 65 and older were included from the MrOS cohort, of whom 116 were excluded for missing vitamin D or CVD data. Participants were divided into two groups based on serum 25(OH) vitamin D levels, <20 ng/mL and ≥20 ng/mL. Participants were followed for CVD endpoints including coronary heart disease (CHD) and cerebrovascular events. Age- and multivariable-adjusted hazard ratios were calculated and stratified by use of vitamin D containing supplements. Results: We observed no significant association between circulating 25(OH) vitamin D and risk of CVD event (HR, 0.91; 95% confidence interval (CI), 0.73–1.13) and CHD event (HR, 0.81; 95% CI, 0.61–1.07). For cerebrovascular events, men with vitamin D deficiency exhibited a higher risk (HR, 1.44; 95% CI, 1.00–2.08) using the minimally adjusted model and after excluding supplement users (HR, 1.70; 95% CI, 1.02–2.83). Conclusions: 25(OH) vitamin D was not associated with risk of CVD and CHD events. However, vitamin D deficiency may be associated with an increased risk of cerebrovascular events. PMID:24670083

  17. A Survey of Vitamin D Status in Patients with Degenerative Diseases of the Spine

    PubMed Central

    Zolfaghari, Farid; Faridmoayer, Alireza; Soleymani, Bahram; Mahabadi, Maryam

    2016-01-01

    Study Design Descriptive cross-sectional study. Purpose To determine the prevalence of vitamin D deficiency in patients with degenerative diseases of the spine about to undergo spinal surgery and the relations between such deficiency and potential risk factors. Overview of Literature Vitamin D has a major role in musculoskeletal system health maintenance. Recently, studies on degenerative diseases of the spine have shown a high prevalence of vitamin D deficiency in patients undergoing spine surgery. Methods Serum levels of 25(OH)D were determined by an electrochemiluminescence detection assay. The other variables were determined through relevant questionnaires, and the data was analyzed through analysis of variance, t-test, chi-square and multivariate logistic regression analysis. Results A total of 110 patients were enrolled in the study. The mean serum level of 25(OH)D was 27.45±18.75 ng/mL, and 44.5% of patients showed vitamin D deficiency (25(OH)D<20 ng/mL), with an additional 17.3% of patients having a serum level of 25(OH)D that was insufficient (20≤25(OH)D<30 ng/mL). The prevalence of vitamin D deficiency was significantly higher in the younger age group compared to the older age group (p<0.001) and the ones without a history of taking vitamin D supplements (p=0.013). Compared to men, women showed significantly higher levels of vitamin D (p=0.029). Conclusions A high prevalence of vitamin D deficiency is seen in patients with degenerative diseases of the spine. On the other hand, the conventional risk factors such as old age or female sex alone did not seem to be sufficient in determining the likelihood of deficiency. Thus, it is recommended that vitamin D deficiency prevention strategies comprise a broader spectrum of the population through which such degenerative diseases and their consequences may be prevented or delayed. PMID:27790310

  18. Prospective study on food fortification with vitamin D among adolescent females in Finland: minor effects.

    PubMed

    Lehtonen-Veromaa, Marjo; Möttönen, Timo; Leino, Aila; Heinonen, Olli J; Rautava, Essi; Viikari, Jorma

    2008-08-01

    Vitamin D insufficiency is common particularly during winter time. After the recommendation by the Ministry of Social Affairs and Health, Finnish fluid milks and margarines have been fortified with vitamin D since February 2003. The aims of the present study were to examine the impact of vitamin D fortification of food supplies on serum 25-hydroxyvitamin D (S-25(OH)D) concentrations and on daily dietary vitamin D intake among adolescent females. One hundred and forty-two girls of Caucasian ethnicity aged 12-18 years completed semi-quantitative FFQ from which the dietary vitamin D and Ca intakes were calculated. S-25(OH)D was measured by radioimmunoassay. The study was performed from February-March 2000 to February-March 2004, one year after the initiation of fortification. The mean dietary intake of vitamin D was < 7.5 microg in 91.5 % of the adolescent girls in 2000 and 83.8 % in 2004. The midwinter mean S-25(OH)D concentration did not change significantly during the follow-up period (48.3 v. 48.1 nmol/l, NS). The proportion of participants who had S-25(OH)D concentration < 50 nmol/l was 60.6 % in 2000 and 65.5 % in 2004. Only 7.0 % of the participants had an adequate S-25(OH)D ( >or= 75 nmol/l) level in 2000 or 4 years later. The vitamin D fortification of fluid milks and margarines was inadequate to prevent vitamin D insufficiency. There are numerous adolescent girls and women who are not reached by the current fortification policy. Therefore new innovative and feasible ways of improving vitamin D nutrition are urged. PMID:18275625

  19. Vitamin D is associated with cardiopulmonary exercise capacity: results of two independent cohorts of healthy adults.

    PubMed

    Kaul, A; Gläser, S; Hannemann, A; Schäper, C; Nauck, M; Felix, S B; Bollmann, T; Ewert, R; Friedrich, N

    2016-02-14

    Vitamin D has an important role in calcium homeostasis and is known to have various health-promoting effects. Moreover, potential interactions between vitamin D and physical activity have been suggested. This study aims to investigate the relationship between 25-hydroxyvitamin D (25(OH)D) and exercise capacity quantified by cardiopulmonary exercise testing (CPET). For this, 1377 participants from the Study of Health in Pomerania (SHIP-1) and 750 participants from the independent SHIP-TREND cohort were investigated. Standardised incremental exercise tests on a cycle ergometer were performed to assess exercise capacity by VO2 at anaerobic threshold, peakVO2, O2 pulse and peak power output. Serum 25(OH)D levels were measured by an automated chemiluminescence immunoassay. In SHIP-1, 25(OH)D levels were positively associated with all considered parameters of cardiopulmonary exercise capacity. Subjects with high 25(OH)D levels (4th quartile) showed an up to 25% higher exercise capacity compared with subjects with low 25(OH)D levels (1st quartile). All associations were replicated in the independent SHIP-TREND cohort and were independent of age, sex, season and other interfering factors. In conclusion, significant positive associations between 25(OH)D and parameters of CPET were detected in two large cohorts of healthy adults.

  20. Vitamin D nutritional policy needs a vision for the future.

    PubMed

    Norman, Anthony W; Bouillon, Roger

    2010-09-01

    Historically vitamin D is known to be essential for normal bone growth and quality, and thus appropriate dietary vitamin D supplementation can eliminate vitamin D deficiency childhood rickets and adult osteomalacia. In spite of many government and medical associations' worldwide guidelines for the reference daily intake (RDI) of vitamin D, scientists and nutritionists from many countries agree that at present about half of elderly North Americans and Western Europeans and probably also of the rest of the world are not receiving enough vitamin D to maintain healthy bone. In addition, over the past decade there has been a dramatic increase in our understanding of the many biological actions that result from vitamin D acting through its daughter steroid hormone, 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] in collaboration with its cognate vitamin D receptor (VDR). Consequently, evidence has accumulated that beside intestine and bone, there are five additional physiological systems where the VDR with 1alpha,25(OH)(2)D generates biological responses. These include the immune system (both the innate and adaptive), pancreas and metabolic homeostasis, heart-cardiovascular, muscle and brain systems as well as the control of the cell cycle, and thus of the disease process of cancer. Acting through the VDR, 1alpha,25(OH)(2)D(3) can produce a wide array of favorable biological effects that collectively are projected to contribute to the improvement of human health. Responsible medicine demands that worldwide vitamin D nutritional guidelines reflect current scientific knowledge about vitamin D's spectrum of activities. Thus, worldwide vitamin D nutritional policy is now at a crossroads. This paper presents several proposed policy changes with regard to the amount of vitamin D daily intake that if implemented will maximize vitamin D's contribution to reducing the frequency of many diseases, which would then increase the quality and longevity of life and significantly

  1. Evaluation of fall Sun Exposure Score in predicting vitamin D status in young Canadian adults, and the influence of ancestry.

    PubMed

    Sham, Lauren; Yeh, E Ann; Magalhaes, Sandra; Parra, Esteban J; Gozdzik, Agnes; Banwell, Brenda; Hanwell, Heather E

    2015-04-01

    Query of sun-related habits or ancestry could help screen for risk of vitamin D insufficiency (serum 25-hydroxyvitamin D<75nmol/L). We evaluated the association between Sun Exposure Score (calculated from recall of Time Exposed to Sun and Skin Exposed to Sun in the previous week), demographics and anthropometrics (including self-reported ancestry and skin melanin reflectometry), and serum 25(OH)D levels in healthy young Canadian adults in the Greater Toronto Area (GTA; 43°N) during fall. 310 adults (67% female) of European, East Asian, and South Asian ancestries were evaluated. The median (interquartile range) 25(OH)D level was 49.7nmol/L (36.7-70.3) and 80% of participants were vitamin D insufficient. The vast majority of those of East and South Asian ancestry were vitamin D insufficient (91% and 97%, respectively), as were 55% of those of European ancestry. Sun Exposure Score and 25(OH)D concentrations were not associated after accounting for confounders. A multivariable model showed ancestry, recent summer sun exposure, sex, melanin, vitamin D intake, age and year of study significantly predicted 25(OH)D concentration; ancestry was the strongest independent predictor (adjusted R(2)=43%). Although Sun Exposure Score was not a significant predictor of serum 25(OH)D levels, inquiry of ancestry has potential use in screening for vitamin D insufficiency.

  2. The Associations of Serum Lipids with Vitamin D Status

    PubMed Central

    Liu, Junli; Wang, Zongye; Jia, Haiying; Feng, Kai; Sun, Lili

    2016-01-01

    Aims Vitamin D deficiency has been associated with some disorders including cardiovascular diseases. Dyslipidemia is a major risk factor for cardiovascular diseases. However, data about the relationships between vitamin D and lipids are inconsistent. The relationship of vitamin D and Atherogenic Index of Plasma (AIP), as an excellent predictor of level of small and dense LDL, has not been reported. The objective of this study was to investigate the effects of vitamin D status on serum lipids in Chinese adults. Methods The study was carried out using 1475 participants from the Center for Physical Examination, 306 Hospital of PLA in Beijing, China. Fasting blood samples were collected and serum concentrations of 25(OH)D, total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were measured. AIP was calculated based on the formula: log [TG/HDL-C]. Multiple linear regression analysis was used to estimate the associations between serum 25(OH)D and lipids. The association between the occurrences of dyslipidemias and vitamin D levels was assessed by multiple logistic regression analysis. Confounding factors, age and BMI, were used for the adjustment. Results The median of serum 25(OH)D concentration was 47 (27–92.25) nmol/L in all subjects. The overall percentage of 25(OH)D ≦ 50 nmol/L was 58.5% (males 54.4%, females 63.7%). The serum 25(OH)D levels were inversely associated with TG (β coefficient = -0.24, p < 0.001) and LDL-C (β coefficient = -0.34, p < 0.001) and positively associated with TC (β coefficient = 0.35, p < 0.002) in men. The associations between serum 25(OH)D and LDL-C (β coefficient = -0.25, p = 0.01) and TC (β coefficient = 0.39, p = 0.001) also existed in women. The serum 25(OH)D concentrations were negatively associated with AIP in men (r = -0.111, p < 0.01) but not in women. In addition, vitamin D deficient men had higher AIP values than vitamin D sufficient men

  3. Placental amino acid transport may be regulated by maternal vitamin D and vitamin D-binding protein: results from the Southampton Women's Survey.

    PubMed

    Cleal, J K; Day, P E; Simner, C L; Barton, S J; Mahon, P A; Inskip, H M; Godfrey, K M; Hanson, M A; Cooper, C; Lewis, R M; Harvey, N C

    2015-06-28

    Both maternal 25-hydroxyvitamin D (25(OH)D) concentrations during pregnancy and placental amino acid transporter gene expression have been associated with development of the offspring in terms of body composition and bone structure. Several amino acid transporter genes have vitamin D response elements in their promoters suggesting the possible linkage of these two mechanisms. We aimed to establish whether maternal 25(OH)D and vitamin D-binding protein (VDBP) levels relate to expression of placental amino acid transporters. RNA was extracted from 102 placental samples collected in the Southampton Women's Survey, and gene expression was analysed using quantitative real-time PCR. Gene expression data were normalised to the geometric mean of three housekeeping genes, and related to maternal factors and childhood body composition. Maternal serum 25(OH)D and VDBP levels were measured by radioimmunoassay. Maternal 25(OH)D and VDBP levels were positively associated with placental expression of specific genes involved in amino acid transport. Maternal 25(OH)D and VDBP concentrations were correlated with the expression of specific placental amino acid transporters, and thus may be involved in the regulation of amino acid transfer to the fetus. The positive correlation of VDBP levels and placental transporter expression suggests that delivery of vitamin D to the placenta may be important. This exploratory study identifies placental amino acid transporters which may be altered in response to modifiable maternal factors and provides a basis for further studies.

  4. 25-hydroxy-vitamin D demography and the risk of vitamin D insufficiency in the South East Asian Nutrition Surveys (SEANUTS).

    PubMed

    Poh, Bee Koon; Rojroongwasinkul, Nipa; Nguyen, Bao Khanh Le; Sandjaja; Ruzita, Abd Talib; Yamborisut, Uruwan; Hong, Truong Nguyen; Ernawati, Fitrah; Deurenberg, Paul; Parikh, Panam

    2016-01-01

    The South East Asian Nutrition Surveys (SEANUTS) were conducted in 2010/2011 in Indonesia, Malaysia, Thailand and Vietnam in country representative samples totalling 16,744 children aged 0.5 to 12 years. Information on socio-demographic and behavioural variables was collected using questionnaires and anthropometric variables were measured. In a sub-sample of 2016 children, serum 25-hydroxy-vitamin D (25(OH)D) was determined. Data were analysed using SPSS complex sample with weight factors to report population representative data. Children were categorized as deficient (<25 nmol/L), insufficient (<50 nmol/L), inadequate (<75 nmol/L) or desirable (>=75 nmol/L). In Malaysia and Thailand, urban children had lower 25(OH)D than rural children. In all countries, except Vietnam, boys had higher 25(OH)D levels and older children had lower 25(OH)D. Regional differences after correcting for age, sex and area of residence were seen in all countries. In Thailand and Malaysia, 25(OH)D status was associated with religion. The percentage of children with adequate 25(OH)D (>=75 nmol/L) ranged from as low as 5% (Indonesia) to 20% (Vietnam). Vitamin D insufficiency (<50 nmol/L) was noted in 40 to 50% of children in all countries. Logistic regression showed that girls, urban area, region within the country and religion significantly increased the odds for being vitamin D insufficient. The high prevalence of vitamin D insufficiency in the (sub) tropical SEANUTS countries suggests a need for tailored approach to successfully combat this problem. Promoting active outdoor livestyle with safe sunlight exposure along with food-based strategies to improve vitamin D intake can be feasible options.

  5. 25-hydroxy-vitamin D demography and the risk of vitamin D insufficiency in the South East Asian Nutrition Surveys (SEANUTS).

    PubMed

    Poh, Bee Koon; Rojroongwasinkul, Nipa; Nguyen, Bao Khanh Le; Sandjaja; Ruzita, Abd Talib; Yamborisut, Uruwan; Hong, Truong Nguyen; Ernawati, Fitrah; Deurenberg, Paul; Parikh, Panam

    2016-01-01

    The South East Asian Nutrition Surveys (SEANUTS) were conducted in 2010/2011 in Indonesia, Malaysia, Thailand and Vietnam in country representative samples totalling 16,744 children aged 0.5 to 12 years. Information on socio-demographic and behavioural variables was collected using questionnaires and anthropometric variables were measured. In a sub-sample of 2016 children, serum 25-hydroxy-vitamin D (25(OH)D) was determined. Data were analysed using SPSS complex sample with weight factors to report population representative data. Children were categorized as deficient (<25 nmol/L), insufficient (<50 nmol/L), inadequate (<75 nmol/L) or desirable (>=75 nmol/L). In Malaysia and Thailand, urban children had lower 25(OH)D than rural children. In all countries, except Vietnam, boys had higher 25(OH)D levels and older children had lower 25(OH)D. Regional differences after correcting for age, sex and area of residence were seen in all countries. In Thailand and Malaysia, 25(OH)D status was associated with religion. The percentage of children with adequate 25(OH)D (>=75 nmol/L) ranged from as low as 5% (Indonesia) to 20% (Vietnam). Vitamin D insufficiency (<50 nmol/L) was noted in 40 to 50% of children in all countries. Logistic regression showed that girls, urban area, region within the country and religion significantly increased the odds for being vitamin D insufficient. The high prevalence of vitamin D insufficiency in the (sub) tropical SEANUTS countries suggests a need for tailored approach to successfully combat this problem. Promoting active outdoor livestyle with safe sunlight exposure along with food-based strategies to improve vitamin D intake can be feasible options. PMID:27440689

  6. Vitamin D and adipose tissue—more than storage

    PubMed Central

    Mutt, Shivaprakash J.; Hyppönen, Elina; Saarnio, Juha; Järvelin, Marjo-Riitta; Herzig, Karl-Heinz

    2014-01-01

    The pandemic increase in obesity is inversely associated with vitamin D levels. While a higher BMI was causally related to lower 25-hydroxyvitamin D (25(OH)D), no evidence was obtained for a BMI lowering effect by higher 25(OH)D. Some of the physiological functions of 1,25(OH)2D3 (1,25-dihydroxycholecalciferol or calcitriol) via its receptor within the adipose tissue have been investigated such as its effect on energy balance, adipogenesis, adipokine, and cytokine secretion. Adipose tissue inflammation has been recognized as the key component of metabolic disorders, e.g., in the metabolic syndrome. The adipose organ secretes more than 260 different proteins/peptides. However, the molecular basis of the interactions of 1,25(OH)2D3, vitamin D binding proteins (VDBPs) and nuclear vitamin D receptor (VDR) after sequestration in adipose tissue and their regulations are still unclear. 1,25(OH)2D3 and its inactive metabolites are known to inhibit the formation of adipocytes in mouse 3T3-L1 cell line. In humans, 1,25(OH)2D3 promotes preadipocyte differentiation under cell culture conditions. Further evidence of its important functions is given by VDR knock out (VDR−/−) and CYP27B1 knock out (CYP27B1 −/−) mouse models: Both VDR−/− and CYP27B1−/− models are highly resistant to the diet induced weight gain, while the specific overexpression of human VDR in adipose tissue leads to increased adipose tissue mass. The analysis of microarray datasets from human adipocytes treated with macrophage-secreted products up-regulated VDR and CYP27B1 genes indicating the capacity of adipocytes to even produce active 1,25(OH)2D3. Experimental studies demonstrate that 1,25(OH)2D3 has an active role in adipose tissue by modulating inflammation, adipogenesis and adipocyte secretion. Yet, further in vivo studies are needed to address the effects and the effective dosages of vitamin D in human adipose tissue and its relevance in the associated diseases. PMID:25009502

  7. Vitamin D and adipose tissue-more than storage.

    PubMed

    Mutt, Shivaprakash J; Hyppönen, Elina; Saarnio, Juha; Järvelin, Marjo-Riitta; Herzig, Karl-Heinz

    2014-01-01

    The pandemic increase in obesity is inversely associated with vitamin D levels. While a higher BMI was causally related to lower 25-hydroxyvitamin D (25(OH)D), no evidence was obtained for a BMI lowering effect by higher 25(OH)D. Some of the physiological functions of 1,25(OH)2D3 (1,25-dihydroxycholecalciferol or calcitriol) via its receptor within the adipose tissue have been investigated such as its effect on energy balance, adipogenesis, adipokine, and cytokine secretion. Adipose tissue inflammation has been recognized as the key component of metabolic disorders, e.g., in the metabolic syndrome. The adipose organ secretes more than 260 different proteins/peptides. However, the molecular basis of the interactions of 1,25(OH)2D3, vitamin D binding proteins (VDBPs) and nuclear vitamin D receptor (VDR) after sequestration in adipose tissue and their regulations are still unclear. 1,25(OH)2D3 and its inactive metabolites are known to inhibit the formation of adipocytes in mouse 3T3-L1 cell line. In humans, 1,25(OH)2D3 promotes preadipocyte differentiation under cell culture conditions. Further evidence of its important functions is given by VDR knock out (VDR(-/-)) and CYP27B1 knock out (CYP27B1 (-/-)) mouse models: Both VDR(-/-) and CYP27B1(-/-) models are highly resistant to the diet induced weight gain, while the specific overexpression of human VDR in adipose tissue leads to increased adipose tissue mass. The analysis of microarray datasets from human adipocytes treated with macrophage-secreted products up-regulated VDR and CYP27B1 genes indicating the capacity of adipocytes to even produce active 1,25(OH)2D3. Experimental studies demonstrate that 1,25(OH)2D3 has an active role in adipose tissue by modulating inflammation, adipogenesis and adipocyte secretion. Yet, further in vivo studies are needed to address the effects and the effective dosages of vitamin D in human adipose tissue and its relevance in the associated diseases. PMID:25009502

  8. Vitamin D Insufficiency: Disease or No Disease?

    PubMed Central

    Hansen, Karen E; Jones, Andrea N; Lindstrom, Mary J; Davis, Lisa A; Engelke, Jean A; Shafer, Martin M

    2008-01-01

    Vitamin D insufficiency (VDI) is widely reported. In patients with normal PTH, the diagnosis rests on increases in fractional calcium absorption (FCA) when 25(OH)D increases above 30 ng/ml. However, estimates of increased FCA after correction of VDI vary dramatically, depending on study methods. We used a dual stable calcium isotope to clarify the impact of vitamin D repletion on FCA in postmenopausal women with VDI. We hypothesized that FCA would increase with vitamin D repletion. We studied postmenopausal women with VDI [25(OH)D = 16–24 ng/ml] and an estimated calcium intake ≤1100 mg daily. Exclusion criteria included hypercalcemia, hypercalciuria, renal insufficiency, nephrolithiasis, gastrointestinal disorders, osteomalacia, prior adult fragility fracture, baseline T-score < −3.0, and use of medications known to interfere with vitamin D or calcium metabolism. Each woman underwent inpatient FCA studies before and after correction of VDI. We used ergocalciferol 50,000 IU/d for 15 days to achieve vitamin D repletion. During each study, women consumed their typical diet. They ingested 44Ca orally with breakfast and received 42Ca intravenously. We collected urine for 24 h and measured its calcium isotope content by mass spectrometry. Eighteen women completed the study; all but two had normal PTH. During the first and second FCA studies, their mean 25(OH)D level was 22 ± 4 and 64 ± 21 ng/ml, respectively (p < 0.001). Subjects' average FCA was 24 ± 7% initially and 27 ± 6% after vitamin D repletion (p = 0.04). Thus, FCA increased by 3 ± 1% with correction of VDI. Postmenopausal women with VDI experience small FCA increments with vitamin D therapy. In existing literature, this small change in FCA does not associate with lower fracture rates or consistently higher bone mass. Future studies should ascertain whether small FCA increments favorably affect the skeleton. PMID:18302509

  9. Vitamin D Status and Its Consequences for Health in South Africa

    PubMed Central

    Norval, Mary; Coussens, Anna K.; Wilkinson, Robert J.; Bornman, Liza; Lucas, Robyn M.; Wright, Caradee Y.

    2016-01-01

    In this review, reports were retrieved in which vitamin D status, as assessed by serum 25-hydroxyvitamin D [25(OH)D] levels, was measured in South African population groups with varied skin colours and ethnicities. Healthy children and adults were generally vitamin D-sufficient [25(OH)D level >50 nmol/L] but the majority of those aged above 65 years were deficient. A major role for exposure to solar ultraviolet radiation (UVR) in determining 25(OH)D levels was apparent, with the dietary contribution being minor. Limited data exist regarding the impact of recent changes in lifestyles on vitamin D status, such as urbanisation. With regard to disease susceptibility, 11 of 22 relevant publications indicated association between low 25(OH)D levels and disease, with deficiency most notably found in individuals with tuberculosis and HIV-1. Information on the relationship between vitamin D receptor variants and ethnicity, disease or treatment response in the South African population groups demonstrated complex interactions between genetics, epigenetics and the environment. Whether vitamin D plays an important role in protection against the range of diseases that currently constitute a large burden on the health services in South Africa requires further investigation. Only then can accurate advice be given about personal sun exposure or dietary vitamin D supplementation. PMID:27763570

  10. High Prevalence of Vitamin D Deficiency in Patients With Basal Cell Nevus Syndrome

    PubMed Central

    Tang, Jean Y.; Wu, Angela; Linos, Eleni; Parimi, Neeta; Lee, Wayne; Aszterbaum, Michelle; Asgari, Maryam M.; Bickers, David R.; Epstein, Ervin H.

    2011-01-01

    Objectives To evaluate vitamin D status in patients with basal cell nevus syndrome (BCNS) who practice photo-protection because of their genetic predisposition to skin cancer and to determine risk factors for deficiency. Design Retrospective cohort study. Setting Academic medical centers. Patients Forty-one ambulatory patients with BCNS who participated in a 2-year chemoprevention clinical trial. Population-based controls (n=360) were selected and matched by age, sex, Fitzpatrick skin type, and season/geography. Main Outcome Measures Levels of 25-hydroxy-vitamin D (25[OH]D) and vitamin D deficiency (defined as a 25[OH]D level of ≤20 ng/mL). Results Twenty-three patients with BCNS (56%) were vitamin D deficient. Patients with BCNS had mean 25(OH)D levels below those of the general population (−3 ng/mL; P=.02) and were 3 times more likely to be vitamin D deficient (56% vs 18%; P<.001). Levels of 25(OH)D were lower in patients who were overweight (−3.0 ng/mL; P=.04) and who had blood collected in the winter compared with the summer (−7.1 ng/mL; P<.001). Conclusion Patients with BCNS may be at increased risk for vitamin D deficiency, depending on their adherence to photoprotection practices. PMID:20956641

  11. Vitamin D deficiency in reproductive age Mongolian women: a cross sectional study.

    PubMed

    Ganmaa, Davaasambuu; Holick, Michael F; Rich-Edwards, Janet W; Frazier, Lindsay A; Davaalkham, Dambadarjaa; Ninjin, Boldbaatar; Janes, Craig; Hoover, Robert N; Troisi, Rebecca

    2014-01-01

    Vitamin D production is critical not only for rickets prevention but for its role in several chronic diseases of adulthood. Maternal vitamin D status also has consequences for the developing fetus. This study assessed the prevalence of vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D]<20ng/ml) and insufficiency [25(OH)D=20-29ng/ml] in spring, among reproductive age Mongolian women. Blood was drawn in March and April, 2009 from 420 Mongolian women, 18-44 years of age. Serum 25(OH)D concentrations were measured, anthropometric measurements were performed and information was collected by interview on lifestyle, dietary and reproductive factors. Logarithm-transformed 25(OH)D levels were compared across risk factor categories by analysis of variance. Linear regression analysis was used to assess the independent associations of factors with vitamin D status. Cutaneous vitamin D3 synthesis was assessed between December and July using a standard 7-dehydrocholesterol ampoule model. The vast majority of women 415 (98.8%) had serum 25(OH)D<20ng/ml (50nmol/l) with an additional 4 women (<1%) in the insufficient range (20-29ng/ml); only one women (0.2%) had sufficient levels (>30ng/ml or 75nmol/l). 25(OH)D concentrations were positively and independently associated with educational status and use of vitamin D supplements, but not with other demographic, lifestyle, reproductive, or anthropometric factors. 25(OH)D levels were not associated with dietary factors in this population, as there is little access to foods containing vitamin D in Mongolia. No production of previtamin D3 was observed until March and was maximally effective in April and was sustained through July. These data suggest that the prevalence of vitamin D deficiency in spring among reproductive age women in Mongolia is high. Given the lack of naturally vitamin D-rich food in the diet and limited use of vitamin D supplements, food fortification and/or supplementation with vitamin D should be considered

  12. Hepcidin and 1,25(OH)2D3 effectively restore Ca2+ transport in β-thalassemic mice: reciprocal phenomenon of Fe2+ and Ca2+ absorption.

    PubMed

    Kraidith, Kamonshanok; Svasti, Saovaros; Teerapornpuntakit, Jarinthorn; Vadolas, Jim; Chaimana, Rattana; Lapmanee, Sarawut; Suntornsaratoon, Panan; Krishnamra, Nateetip; Fucharoen, Suthat; Charoenphandhu, Narattaphol

    2016-07-01

    Previously, β-thalassemia, an inherited anemic disorder with iron overload caused by loss-of-function mutation of β-globin gene, has been reported to induce osteopenia and impaired whole body calcium metabolism, but the pathogenesis of aberrant calcium homeostasis remains elusive. Herein, we investigated how β-thalassemia impaired intestinal calcium absorption and whether it could be restored by administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or hepcidin, the latter of which was the liver-derived antagonist of intestinal iron absorption. The results showed that, in hemizygous β-globin knockout (BKO) mice, the duodenal calcium transport was lower than that in wild-type littermates, and severity was especially pronounced in female mice. Both active and passive duodenal calcium fluxes in BKO mice were found to be less than those in normal mice. This impaired calcium transport could be restored by 7-day 1,25(OH)2D3 treatment. The 1,25(OH)2D3-induced calcium transport was diminished by inhibitors of calcium transporters, e.g., L-type calcium channel, NCX1, and PMCA1b, as well as vesicular transport inhibitors. Interestingly, the duodenal calcium transport exhibited an inverse correlation with transepithelial iron transport, which was markedly enhanced in thalassemic mice. Thus, 3-day subcutaneous hepcidin injection and acute direct hepcidin exposure in the Ussing chamber were capable of restoring the thalassemia-associated impairment of calcium transport; however, the positive effect of hepcidin on calcium transport was completely blocked by proteasome inhibitors MG132 and bortezomib. In conclusion, both 1,25(OH)2D3 and hepcidin could be used to alleviate the β-thalassemia-associated impairment of calcium absorption. Therefore, our study has shed light on the development of a treatment strategy to rescue calcium dysregulation in β-thalassemia. PMID:27245334

  13. Vitamin D Deficiency in Unselected Patients from Swiss Primary Care: A Cross-Sectional Study in Two Seasons

    PubMed Central

    Merlo, Christoph; Trummler, Michael; Essig, Stefan; Zeller, Andreas

    2015-01-01

    Background As published data on 25-hydroxy-cholecalciferol (25(OH)D) deficiency in primary care settings is scarce, we assessed the prevalence of hypovitaminosis D, potential associations with clinical symptoms, body mass index, age, Vitamin D intake, and skin type in unselected patients from primary care, and the extent of seasonal variations of serum 25(OH)D concentrations. Methodology/Principal Findings 25(OH)D was measured at the end of summer and/or winter in 1682 consecutive patients from primary care using an enzyme-linked immunosorbant assay. Clinical symptoms were assessed by self-report (visual analogue scale 0 to 10), and vitamin D deficiency was defined as 25(OH)D concentrations < 50 nmol/l. 25(OH)D deficiency was present in 995 (59.2%) patients. 25(OH)D deficient patients reported more intense muscle weakness (visual analogue scale 2.7, 95% confidence interval 2.5 to 2.9) and had a higher body mass index (25.9kg/m2, 25.5 to 26.2) than non-deficient patients (2.5, 2.3 to 2.7; and 24.2, 23.9 to 24.5, respectively). 25(OH)D concentrations also weakly correlated with muscle weakness (Spearman’s rho -0.059, 95% confidence interval -0.107 to -0.011) and body mass index (-0.156, -0.202 to -0.108). Self-reported musculoskeletal pain, fatigue, and age were not associated with deficiency, nor with concentrations. Mean 25(OH)D concentrations in patients with vitamin D containing medication were higher (60.6 ± 22.2 nmol/l) than in patients without medication (44.8 ± 19.2 nmol/l, p < 0.0001) but still below the targeted level of 75 nmol/l. Summer and winter 25(OH)D concentrations differed (53.4 ± 19.9 vs. 41.6 ± 19.3nmol/l, p < 0.0001), which was confirmed in a subgroup of 93 patients who were tested in both seasons (p = 0.01). Conclusion/Significance Nearly 60% of unselected patients from primary care met the criteria for 25(OH)D deficiency. Self-reported muscle weakness and high body mass index were associated with lower 25(OH)D levels. As expected 25(OH

  14. Effects of biological type of beef steers on vitamin D, calcium, and phosphorus status.

    PubMed

    Montgomery, J L; Blanton, J R; Horst, R L; Galyean, M L; Morrow, K J; Wester, D B; Miller, M F

    2004-07-01

    Feedlot steers (n = 36) from three biological types (Bos indicus, Bos taurus-Continental, and Bos taurus-English) were used to determine the Ca, P, and vitamin D3 status of feedlot cattle. The USDA yield and quality grade traits were measured at slaughter, and the concentrations of vitamin D3 (VITD) and the metabolites 25-hydroxyvitamin D3 (25-OH D) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D) were determined in LM, liver, kidney, and plasma. Plasma and muscle Ca and P concentrations also were determined. Biological type of cattle affected a number of carcass traits. Carcasses from Bos taurus-English cattle had more marbling, resulting in higher quality grades (P < 0.05). Carcasses from Bos taurus-Continental cattle had lower calculated yield grades (P < 0.05) than did carcasses from cattle in the other biological types. In general, differences in carcass traits resulting from biological type were consistent with other reports. Plasma and LM Ca and P concentrations were not affected (P = 0.06) by biological type of cattle, indicating that Ca and P homeostasis is a conserved trait across the different types of cattle. Plasma VITD and 25-OH D concentrations were not affected (P = 0.41) by biological type, whereas plasma 1,25-(OH)2 D concentration was lower (P < 0.05) in Bos taurus-English cattle than in Bos taurus-Continental and Bos indicus cattle. Liver VITD and 25-OH D were not affected by biological type (P = 0.76), but liver 1,25-(OH)2 D concentration was greater (P < 0.05) in Bos indicus cattle than in Bos taurus-Continental cattle. Kidney vitamin D metabolite concentrations were not affected by biological type of cattle (P = 0.21). Muscle VITD concentration was greater (P < 0.05) in Bos taurus-English cattle than in the other two biological types, and muscle 25-OH D concentrations were greater (P < 0.05) in Bos taurus-English cattle than in Bos indicus cattle. Muscle 1,25-(OH)2 D concentration was less (P < 0.05) in the Bos taurus-Continental cattle than in the

  15. The relationship between vitamin D status and idiopathic lower-extremity deep vein thrombosis

    PubMed Central

    Khademvatani, Kamal; Seyyed-Mohammadzad, Mir Hossein; Akbari, Mohammad; Rezaei, Yousef; Eskandari, Ramin; Rostamzadeh, Alireza

    2014-01-01

    Background Vitamin D has been shown to have an anticoagulant effect. A decrease in 25-hydroxyvitamin D [25(OH)D] concentration has also been associated with an increased risk of venous thromboembolism. Hence, we sought to determine the relationship between 25(OH) D levels and idiopathic lower-extremity deep vein thrombosis (DVT). Methods In a case control study, a total of 82 participants with idiopathic lower-extremity DVT were enrolled along with 85 sex- and age-matched healthy participants as controls. The plasma 25(OH)D levels were measured in all the studied samples. Results The participants’ mean age was 47.1±12.3 years. Baseline characteristics were not significantly different between the groups. The concentration of 25(OH)D was significantly lower in the DVT group compared to that of the control group (17.9±10.3 versus 23.1±12.5 ng/mL, P=0.004). The prevalence of participants with deficient 25(OH)D levels was significantly higher in the both DVT and control groups than those with sufficient 25(OH)D levels (68.3% versus 13.4%, and 49.4% versus 28.2%, respectively, P=0.027). In a multivariate analysis, 25(OH)D levels and sex were found to be the only independent predictors of DVT (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.02–1.08, P=0.001 and OR 0.51, 95% CI 0.26–1.00, P=0.049, respectively). Conclusion Low levels of 25(OH)D are associated with idiopathic lower-extremity DVT. Further investigation is needed to establish determinants and probable causative role of 25(OH)D. PMID:24971035

  16. Immune-modifying properties of topical vitamin D: Focus on dendritic cells and T cells.

    PubMed

    Gorman, Shelley; Judge, Melinda A; Hart, Prue H

    2010-07-01

    Topical creams containing the active form of vitamin D (1,25-dihydroxyvitamin D3; 1,25(OH)2D3) or analogues of this compound are currently used with some success to treat skin conditions including psoriasis and vitiligo. As well as targeting inflammatory processes in the skin, topical application of 1,25(OH)2D3 also affects the function of immune cells in the skin and draining lymph nodes. Topically applied 1,25(OH)2D3 reduces the number of dendritic cells in the skin, resulting in suppressed immunity and in particular reduced contact hypersensitivity (CHS) responses. Topical 1,25(OH)2D3 may also promote the migration of dendritic cells from the skin to the draining lymph nodes. Skin application of 1,25(OH)2D3 prevented the inflammatory effects of UVB irradiation on lymph node hypertrophy, when cell numbers were examined 4 days after skin treatment. In contrast, when 1,25(OH)2D3 was applied to UVB irradiated skin, there was no reversal in the suppression of CHS responses caused by UVB irradiation. Instead, 1,25(OH)2D3 had an additive effect with UVB to suppress CHS responses to a greater degree than UVB alone. In these studies, 1,25(OH)2D3 was applied to the treated skin of BALB/c mice immediately following UVB irradiation. Finally, topical 1,25(OH)2D3 also enhanced the number and suppressive activity of CD4+CD25+ regulatory T cells in the lymphatic tissue draining skin.

  17. Chronic exposure to cadmium did not impair vitamin D metabolism in monkeys

    SciTech Connect

    Kawashima, H.; Nomiyama, H.; Nomiyama, K.

    1988-06-01

    Vitamin D metabolism in primates with chronic exposure to cadmium was studied in relation to Itai-Itai disease. In a series of experiments, crab-eating monkeys were fed cadmium-contaminated rice (1.33 ..mu..g Cd/g) or a diet containing 3 ..mu..g/g cadmium chloride for 6 years. These treatments had no effect on the 1,25-dihydroxyvitamin D (1,25(OH)/sub 2/D), 24,25-dihydroxyvitamin D(24,25(OH)/sub 2/D), and 25-hydroxyvitamin D(25(OH)D) in the serum. No indication of renal dysfunction was observed. In another series of experiments, rhesus monkeys were fed a diet containing 3, 10, 30, or 100 ..mu..g/g cadmium for 9 years. Serum vitamin D metabolites and renal production of 24,25(OH)/sub 2/D also remained unchanged. In contrast, renal 25(OH)D-1-hydroxylase (1-hydroxylase), which is responsible for the production of 1,25(OH)/sub 2/D, seemed to be suppressed in the animals fed 30 or 100 ..mu..g/kg cadmium-contaminated diet (no statistical significance). These animals had indications of mild renal dysfunction, and there was a strong negative correlation between 1-hydroxylase and urinary concentration of either protein or ..beta../sub 2/-microglobulin. These data suggest a slight chance in the total enzyme activity, possibly due to mild renal dysfunction. Since substrate (25(OH)D) concentration is much lower and thus rate-limiting in vivo as compared with that in vitro assay system used in this study, the slight change of enzyme activity would not have been sufficient to affect the serum level of 1,25(OH)/sub 2/D. No skeletal abnormality was observed in any of these animals.

  18. The Role of Vitamin D in the Bone Changes Associated with Simulated Weightlessness

    NASA Technical Reports Server (NTRS)

    Halloran, B. P.; Bikle, D. D.; Holton, E.; Levens, M. J.; Globus, R.

    1985-01-01

    The role of vitamin D in the change in bone metabolism was examined. The serum concentrations in rats sacrificed after 2, 5, 7, 10, 12 and 15 days of suspension was measured. Between days 1 and 5 of suspension and then gradually decreased towards normal between days 5 and 15. The time course of the changes in the circulating concentrations of 1,25(OH)2D and 24,25(OH)2D mirror almost precisely the changes in bone metabolism. The relationship between the changes in vitamin D metabolism and bone metabolism is investigated. Whether the bone changes are due to the change in serum concentration of 1,25(OH)2D or the changes in bone formation causing a reduction in Ca flux out of the serum pool and thereby suppressing 1,25(OH)2D production is examined. It is found that suspension had no effect on hormone concentration in the 1,25(OH)2D infused animals. Nevertheless, both vehicle and 1,25(OH)2D infused suspended rats exhibited the same reduction in bone mineral, and uptake of (45)Ca. It is suggested that the transitory reduction in circulating 1,25(OH)2D during suspension is not likely to cause the abnormalities in bone metabolism but rather that the changes in bone metabolism are primary and cause the fall in serum 1,25(OH)2D concentration. This supports the hypothesis that the metabolic abnormalities in bone associated with simulated weightlessness are due to the direct effect of unweighting on the bone.

  19. Low Vitamin D Status Is Associated with Systemic and Gastrointestinal Inflammation in Dogs with a Chronic Enteropathy

    PubMed Central

    Titmarsh, Helen F.; Gow, Adam G.; Kilpatrick, Scott; Cartwright, Jennifer A.; Milne, Elspeth M.; Philbey, Adrian W.; Berry, Jacqueline; Handel, Ian; Mellanby, Richard J.

    2015-01-01

    Introduction Vitamin D deficiency, as assessed by serum concentrations of 25 hydroxyvitamin D (25(OH)D), has been linked to the development of over-zealous and inappropriate inflammation in humans. However, the relationship between vitamin D status and inflammation in dogs is ill-defined. Chronic enteropathies (CE) are frequently diagnosed in client owned dogs, have a wide range of serum 25(OH)D concentrations, and represent a spontaneous model in which to probe the relationship between vitamin D and inflammation. The hypothesis of this study was that vitamin D status would be negatively associated with systemic and gastrointestinal inflammation in dogs with a CE. The aim of this study was to examine the relationship between serum 25(OH)D concentrations and markers of systemic and gastrointestinal inflammation in a cohort of dogs with CE. Methods and Materials Serum 25(OH)D concentrations, together with neutrophil, monocyte, eosinophil and lymphocyte counts, duodenal histopathology scores, serum IL-2, IL-6, IL-8 and TNFα concentrations and were measured in 39 dogs with histologically confirmed CE. A linear regression model examined the relationship between serum 25(OH)D status and measures of inflammation. Results Serum 25(OH)D concentrations were negatively associated with neutrophil and monocyte counts, duodenal histopathology scores and serum IL-2 and IL-8 concentrations. Dogs with low serum 25(OH)D concentrations typically had an inflammatory signature characterised by high monocyte and neutrophil numbers together with low lymphocyte numbers. There is a need to establish whether low vitamin D status is a cause or consequence of inflammation. PMID:26333093

  20. VITAMIN D DEFICIENCY IN ADULTS: SEARCHING FOR THE PROPER LOADING DOSE.

    PubMed

    Vicenti, G; Pesce, V; Abate, A; Carrozzo, M; Cagnetta, V; Rifino, F; Solarino, G; Moretti, B

    2015-01-01

    Vitamin D is the main hormone regulating calcium phosphate homeostasis and mineral bone metabolism. Vitamin D deficiency is indeed extremely frequent in musculoskeletal diseases. Recent studies have shown that the treatment of osteoporosis needs to have an optimal vitamin D and calcium supplementation for its efficacy. Actually no agreement exists on the estabilished dose of vitamin D to administer in deficency states. We conducted a prospective study to develop a practical cholecalciferol loading dose regimen that would enable rapid correction of vitamin D deficiency. Sixty post-menopausal age woman were enrolled secondary to a fragility fracture (hip, vertebral, wrist) and screened for 25-hydroxyvitamin D (25(OH)D), calcium, and PTH at baseline (T0), after one month (T1), two months (T2), three months (T3) and six months (T4). Secondary to initial blood values of vitamin D patients were divided into 2 groups; the first group (group A, n=30) included patients with 25(OH)D values between 10-30 ng/ml and the second group (group B, n=30) with values under 10 ng/ml. Each group was then divided in 3 subgroups secondary to the randomized administered dose of 25(OH)D. By this, patients can alternatively receive 25000 UI two times monthly, 100000 UI monthly, 10000 UI (25 drops) weekly. The highest values of mean increase of 25(OH)D were observed in patients treated with 100000 UI. Patients treated with 10000 UI weekly did never achieve the target value. Additionally, as vitamin levels increased, pain intensity decreased. Vitamin D supplementation of 100000 UI monthly seems to be adequate to ensure that serum 25(OH)D values reach the threshold level; by this, it will confer the expected effects without risks of toxicity. PMID:26652494

  1. Proceedings of the Rank Forum on Vitamin D

    PubMed Central

    Lanham-New, S. A.; Buttriss, J. L.; Miles, L. M.; Ashwell, M.; Berry, J. L.; Boucher, B. J.; Cashman, K. D.; Cooper, C.; Darling, A. L.; Francis, R. M.; Fraser, W. D.; de Groot, C. P. G. M.; Hyppönen, E.; Kiely, M.; Lamberg-Allardt, C.; Macdonald, H. M.; Martineau, A. R.; Masud, T.; Mavroeidi, A.; Nowson, C.; Prentice, A.; Stone, E. M.; Reddy, S.; Vieth, R.; Williams, C. M.

    2012-01-01

    The Rank Forum on Vitamin D was held on 2nd and 3rd July 2009 at the University of Surrey, Guildford, UK. The workshop consisted of a series of scene-setting presentations to address the current issues and challenges concerning vitamin D and health, and included an open discussion focusing on the identification of the concentrations of serum 25-hydroxyvitamin D (25(OH)D) (a marker of vitamin D status) that may be regarded as optimal, and the implications this process may have in the setting of future dietary reference values for vitamin D in the UK. The Forum was in agreement with the fact that it is desirable for all of the population to have a serum 25(OH)D concentration above 25 nmol/l, but it discussed some uncertainty about the strength of evidence for the need to aim for substantially higher concentrations (25(OH)D concentrations > 75 nmol/l). Any discussion of ‘optimal’ concentration of serum 25(OH)D needs to define ‘optimal’ with care since it is important to consider the normal distribution of requirements and the vitamin D needs for a wide range of outcomes. Current UK reference values concentrate on the requirements of particular subgroups of the population; this differs from the approaches used in other European countries where a wider range of age groups tend to be covered. With the re-emergence of rickets and the public health burden of low vitamin D status being already apparent, there is a need for urgent action from policy makers and risk managers. The Forum highlighted concerns regarding the failure of implementation of existing strategies in the UK for achieving current vitamin D recommendations. PMID:21134331

  2. Vitamin D analogues targeting CYP24 in chronic kidney disease.

    PubMed

    Posner, Gary H; Helvig, Christian; Cuerrier, Dominic; Collop, Drew; Kharebov, Aza; Ryder, Kara; Epps, Tina; Petkovich, Martin

    2010-07-01

    The cytochrome P450 enzyme 24-hydroxylase (CYP24) plays a critical role in regulating levels of vitamin D hormone. Aberrant expression of CYP24 has been implicated in vitamin D insufficiency and resistance to vitamin D therapy. We have demonstrated amplified CYP24 expression in uremic rats, suggesting that CYP24 has an etiological role in vitamin D insufficiency commonly associated with chronic kidney disease (CKD). We have designed two new analogues of 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3), namely CTA091 and CTA018/MT2832, which are potent inhibitors of CYP24. In vitro studies with CTA091 show that it enhances the potency of 1alpha,25(OH)2D3. In vivo studies demonstrate that CTA091 decreases serum intact parathyroid hormone (iPTH) levels and increases circulating 1alpha,25(OH)2D3. CTA091 increases both Cmax and AUC of co-administered 1alpha,25(OH)2D3. These studies indicate that CYP24 inhibition can increase cellular responsiveness to vitamin D hormone and potentiate vitamin D therapy. CTA018/MT2832 differs from CTA091 in that it also has the ability to activate vitamin D receptor-mediated transcription. CTA018/MT2832 effectively suppresses elevated iPTH secretion at doses which do not affect serum calcium or phosphorus levels in a rodent model of CKD. Studies with both new analogues underscore the potential utility of CYP24 inhibition in the treatment of secondary hyperparathyroidism in CKD. PMID:20347976

  3. Serum 25 HydroxyVitamin D Concentrations and the Risk of Hip Fractures: The Women's Health Initiative

    PubMed Central

    Cauley, Jane A.; LaCroix, Andrea Z.; Wu, LieLing; Horwitz, Mara; Danielson, Michelle E.; Bauer, Doug C.; Lee, Jennifer S.; Jackson, Rebecca D.; Robbins, John A.; Wu, Chunyuan; Stanczyk, Frank Z.; LeBoff, Meryl S.; Wactawski-Wende, Jean; Sarto, Gloria; Ockene, Judith; Cummings, Steven R.

    2008-01-01

    Background The association between and vitamin D levels and fractures is uncertain. Objective To test the hypothesis that serum 25-hydroxyVitamin D (25(OH) vitamin D) levels are associated with the risk of hip fracture in community dwelling women. Design Nested case-control study. Setting 40 US clinical centers. Participants We studied 400 cases of incident hip fractures and 400 controls matched on age, race/ethnicity and date of blood draw (average follow-up time, 7.1 years). Subjects were selected from 39,795 postmenopausal women without previous hip fractures, not using estrogens or other bone-active therapies. Measurements Serum 25(OH) vitamin D was measured on baseline serum using radioimmunoassay with DiaSorin reagents and divided into quartiles. Conditional logistic regression was used to estimate the odds ratio with 95% confidence intervals (CI). Multivariable models included age, body mass index, parental and personal history of fractures, smoking, alcohol and calcium intake, geographic location and corticosteroid use. Results The mean (standard deviation, SD) 25(OH) vitamin D (nM) was lower in cases, 56.2(20.3) compared to controls, 59.7(18), p=0.007. A 25 nM (10ng/ml) decrease in 25(OH) vitamin D was associated with a 33% increased risk of hip fracture (odds ratio=1.33; 95%CI,1.06, 1.68) in multivariable models. Compared to women with 25(OH) vitamin D ≥70.7 nM (Quartile 4), the odds ratio of hip fracture was 1.71 (1.05, 2.79), 1.09 (0.70, 1.71) and 0.82 (0.51, 1.31) in women with 25(OH) vitamin D <47.5 nM, 47.5 to 60 nM, 60 to <70 nM, respectively, p trend =0.015. This association was in part mediated by a marker of bone resorption but remained statistically significant. Adjustment for falls, physical function, frailty, renal function, or sex steroid hormones had no effect on this association. Limitations No measure of bone density. Conclusion Low serum 25(OH) vitamin D concentrations are associated with a higher risk of hip fracture. Measurement of 25

  4. Vitamin D status and associated metabolic risk factors among North Korean refugees in South Korea: a cross-sectional study

    PubMed Central

    Kim, Kyeong Jin; Kim, Yoon Jung; Kim, Sun Hwa; An, Jee Hyun; Yoo, Hye Jin; Kim, Hee Young; Seo, Ji A; Kim, Sin Gon; Kim, Nan Hee; Choi, Kyung Mook; Baik, Sei Hyun; Choi, Dong Seop; Kim, Nam Hoon

    2015-01-01

    Objective Vitamin D deficiency is now recognised as a common health problem associated with various chronic diseases; however, it has not been fully elucidated among the minority groups. Here, we aimed to investigate the prevalence of vitamin D deficiency and its associated metabolic risk factors among North Korean refugees living in South Korea. Design Cross-sectional analysis from the longitudinal cohort, the North Korean refugee health in South Korea (NORNS) study. Participants A total of 386 North Korean refugees aged ≥30 years, who measured serum 25-hydroxy vitamin D (25(OH)D) level. Results The prevalence of vitamin D deficiency (25(OH)D <20 ng/mL) was 87% and no participants had an adequate vitamin D level (25(OH)D ≥30 ng/mL). Underweight participants (body mass index (BMI) <18 kg/m2) had significantly lower 25(OH)D levels than individuals with normal BMI (≥18.5 and<23 kg/m2). In the multivariate logistic regression analysis, the lowest 25(OH)D level (<10 ng/mL) was significantly associated with metabolic syndrome (OR, 6.37, 95% CI 1.34 to 30.3), high triglyceride (OR, 6.71, 95% CI 1.75 to 25.7), and low high-density lipoprotein (OR, 5.98, 95% CI 1.54 to 23.2) compared with 25(OH)D levels ≥20 ng/mL after adjusting for age, sex, season, length of residence in South Korea, physical activity and BMI. Conclusions Vitamin D deficiency is very common among North Korean refugees in South Korea. Despite their lower BMI, vitamin D deficiency was associated with metabolic syndrome in this population. PMID:26621518

  5. Reduced serum concentrations of 25-hydroxy vitamin D in Egyptian patients with systemic lupus erythematosus: Relation to disease activity

    PubMed Central

    Hamza, Rasha T.; Awwad, Khaled S.; Ali, Mohamed K.; Hamed, Amira I.

    2011-01-01

    Summary Background Recently, vitamin D deficiency has been implicated as a potential environmental factor triggering some autoimmune disorders, including systemic lupus erythematosus (SLE)). In addition, patients with SLE, especially those with increased disease activity, were suggested to have decreased vitamin D level, suggesting that vitamin D might play a role in regulating autoantibody production. Material/Methods To assess 25 hydroxy vitamin D [25(OH)D] status in Egyptian patients with SLE and its relation to disease activity. Clinical evaluation and assay of serum 25(OH)D, total calcium, phosphorous, alkaline phosphatase (ALP) and parathyroid hormone (PTH) were done on 60 SLE patients in comparison to 60 matched-healthy subjects. Serum 25(OH)D levels <30 and 10 ng/ml were defined as vitamin D insufficiency and deficiency, respectively. Results Serum 25(OH)D was significantly lower in patients than in controls (26.33±12.05 vs. 42.66±9.20 respectively, p<0.0001), with 13.30% and 60% being deficient and insufficient, respectively. Serum 25(OH)D levels were lower with increased disease activity (p=0.03) and frequency of photosensitivity(p=0.02) and photoprotection (p=0.002). Systemic lupus erythematosus disease activity index (SLEDAI) score (OR: 2.72, 95% CI: 1.42–5.18, P=0.002), photosensitivity (OR: 3.6, 95% CI: 1.9–6.8, P<0.01) and photoprotection (OR: 6.7, 95% CI: 2.9–8.8, P<0.001) were significant predictors of 25(OH)D level among SLE cases. Conclusions Low vitamin D status is prevalent in Egyptian SLE patients despite plentiful exposure to sunlight throughout the year, and its level is negatively correlated to disease activity. Future studies looking at a potential role of vitamin D in the pathophysiology and treatment of SLE are warranted. PMID:22129903

  6. Assessment of vitamin D levels in newly diagnosed children with type 1 diabetes mellitus comparing two methods of measurement: a facility’s experience in the Middle Eastern country of Bahrain

    PubMed Central

    Al-Haddad, Fatima Ahmed; Rajab, Mansoor H; Al-Qallaf, S Mahmood; Musaiger, Abdulrahman O; Hart, Kathryn H

    2016-01-01

    Background The number of children being diagnosed with type 1 diabetes mellitus (T1DM) is on the rise and has more than doubled in the past 10 years in Bahrain. Some studies have linked low vitamin D levels with an increased risk of diabetes. There are concerns regarding the variations in circulating 25(OH)D levels measured by different laboratories and by using different analytical techniques. Objective The aim of this study was to evaluate the vitamin D levels of newly diagnosed children with T1DM using the “gold standard method” with high-pressure liquid chromatography–tandem mass spectrometry methods compared to the chemiluminescence micro-particle immunoassay (CMIA) used in a hospital laboratory. Subjects Eighteen children, aged 6–12 years, who received a confirmed diagnosis of T1DM in 2014 were chosen as subjects. Methods Serum vitamin D levels were assessed in a hospital, while an extra aliquot of blood collected during routine blood collection after acquiring informed written consents from the subjects, and sent to Princess Al-Jawhara Center for Molecular Medicine and Inherited Disorders to be analyzed by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Results The mean age of the study group was 9±2 years. The mean total of 25(OH)D levels (D3 and D2) assessed by UPLC-MS/MS was 49.7±18.8, whereas the mean total of 25(OH)D levels obtained from the CMIA assay was 44.60±13.20. The difference in classification between the two methods was found to be statistically significant (P=0.004). A Bland–Altman plot showed a poor level of agreement between the two assay methods. The CMIA overestimated insufficient values and underestimated deficiency, when compared to UPLC-MS/MS. Conclusion There was a statistically significant difference between the two assay methods with CMIA overestimating vitamin D insufficiency. Clinicians should be prudent in their assessment of a single vitamin D reading, when the gold standard method is

  7. The association of vitamin D with inflammatory cytokines in diabetic peripheral neuropathy.

    PubMed

    Bilir, Bulent; Tulubas, Feti; Bilir, Betul Ekiz; Atile, Neslihan Soysal; Kara, Sonat Pinar; Yildirim, Tulay; Gumustas, Seyit Ali; Topcu, Birol; Kaymaz, Ozlem; Aydin, Murat

    2016-07-01

    [Purpose] The effects of vitamin D on the circulating levels of IL-17 and IL-13 were investigated in patients with diabetic peripheral neuropathy, patients with diabetes mellitus type 2 without neuropathy, and healthy controls. [Subjects and Methods] A single-blind controlled clinical study was performed, including70 type 2 diabetic patients with or without diabetic peripheral neuropathy and 33 healthy volunteer controls. The 25(OH)D levels were evaluated using ultra-performance liquid chromatography, and IL-17 and IL-13 levels were assessed using enzyme-linked immunosorbent assays. [Results] The 25(OH) vitamin D concentration was lower in diabetic peripheral neuropathy patients than in diabetes mellitus patients without neuropathy and healthy controls. Similarly, 25(OH)D levels were lower in diabetes mellitus patients than healthy controls. IL-17 and IL-13 levels were higher in diabetes mellitus patients than in controls. Additionally, IL-13 levels were higher in diabetic peripheral neuropathy patients than in diabetes mellitus patients without neuropathy. These differences were statistically significant. There was a significant positive correlation between 25(OH)D and IL-13,and a negative correlation between 25(OH)D andIL-17 in the diabetic and diabetic neuropathy groups. [Conclusion] Vitamin D is a potential modifiable risk factor for diabetic peripheral neuropathy and may regulate inflammatory mediators, e.g., IL-17 and IL-13.

  8. The association of vitamin D with inflammatory cytokines in diabetic peripheral neuropathy

    PubMed Central

    Bilir, Bulent; Tulubas, Feti; Bilir, Betul Ekiz; Atile, Neslihan Soysal; Kara, Sonat Pinar; Yildirim, Tulay; Gumustas, Seyit Ali; Topcu, Birol; Kaymaz, Ozlem; Aydin, Murat

    2016-01-01

    [Purpose] The effects of vitamin D on the circulating levels of IL-17 and IL-13 were investigated in patients with diabetic peripheral neuropathy, patients with diabetes mellitus type 2 without neuropathy, and healthy controls. [Subjects and Methods] A single-blind controlled clinical study was performed, including70 type 2 diabetic patients with or without diabetic peripheral neuropathy and 33 healthy volunteer controls. The 25(OH)D levels were evaluated using ultra-performance liquid chromatography, and IL-17 and IL-13 levels were assessed using enzyme-linked immunosorbent assays. [Results] The 25(OH) vitamin D concentration was lower in diabetic peripheral neuropathy patients than in diabetes mellitus patients without neuropathy and healthy controls. Similarly, 25(OH)D levels were lower in diabetes mellitus patients than healthy controls. IL-17 and IL-13 levels were higher in diabetes mellitus patients than in controls. Additionally, IL-13 levels were higher in diabetic peripheral neuropathy patients than in diabetes mellitus patients without neuropathy. These differences were statistically significant. There was a significant positive correlation between 25(OH)D and IL-13,and a negative correlation between 25(OH)D andIL-17 in the diabetic and diabetic neuropathy groups. [Conclusion] Vitamin D is a potential modifiable risk factor for diabetic peripheral neuropathy and may regulate inflammatory mediators, e.g., IL-17 and IL-13. PMID:27512288

  9. Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects.

    PubMed

    Christakos, Sylvia; Dhawan, Puneet; Verstuyf, Annemieke; Verlinden, Lieve; Carmeliet, Geert

    2016-01-01

    1,25-Dihydroxvitamin D3 [1,25(OH)2D3] is the hormonally active form of vitamin D. The genomic mechanism of 1,25(OH)2D3 action involves the direct binding of the 1,25(OH)2D3 activated vitamin D receptor/retinoic X receptor (VDR/RXR) heterodimeric complex to specific DNA sequences. Numerous VDR co-regulatory proteins have been identified, and genome-wide studies have shown that the actions of 1,25(OH)2D3 involve regulation of gene activity at a range of locations many kilobases from the transcription start site. The structure of the liganded VDR/RXR complex was recently characterized using cryoelectron microscopy, X-ray scattering, and hydrogen deuterium exchange. These recent technological advances will result in a more complete understanding of VDR coactivator interactions, thus facilitating cell and gene specific clinical applications. Although the identification of mechanisms mediating VDR-regulated transcription has been one focus of recent research in the field, other topics of fundamental importance include the identification and functional significance of proteins involved in the metabolism of vitamin D. CYP2R1 has been identified as the most important 25-hydroxylase, and a critical role for CYP24A1 in humans was noted in studies showing that inactivating mutations in CYP24A1 are a probable cause of idiopathic infantile hypercalcemia. In addition, studies using knockout and transgenic mice have provided new insight on the physiological role of vitamin D in classical target tissues as well as evidence of extraskeletal effects of 1,25(OH)2D3 including inhibition of cancer progression, effects on the cardiovascular system, and immunomodulatory effects in certain autoimmune diseases. Some of the mechanistic findings in mouse models have also been observed in humans. The identification of similar pathways in humans could lead to the development of new therapies to prevent and treat disease. PMID:26681795

  10. Circulating 25-Hydroxyvitamin D, Vitamin D Binding Protein, and Risk of Prostate Cancer

    PubMed Central

    Weinstein, Stephanie J.; Mondul, Alison M.; Kopp, William; Rager, Helen; Virtamo, Jarmo; Albanes, Demetrius

    2012-01-01

    We recently reported a significant positive association between 25-hydroxyvitamin D [25(OH)D], the accepted biomarker of vitamin D status, and prostate cancer risk. To further elucidate this association, we examined the influence of vitamin D binding protein (DBP), the primary transporter of vitamin D compounds in the circulation. Prediagnostic serum concentrations of DBP were assayed for 950 cases and 964 matched controls with existing 25(OH)D measurements within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI), and statistical tests were two-sided. Serum DBP modified the association between serum 25(OH)D and prostate cancer, with higher risk for elevated 25(OH)D levels observed primarily among men having DBP concentrations above the median (OR=1.81, 95% CI 1.18–2.79 for highest vs. lowest quintile, p-trend = 0.001) compared to those with DBP below the median (OR=1.22, 95% CI 0.81–1.84, p-trend 0.97; p-interaction = 0.04). Serum DBP was not associated with prostate cancer risk overall (OR=0.96, 95% CI 0.70–1.33 for highest vs. lowest quintile); however, high serum DBP was associated with significantly decreased risk of prostate cancer in men with lower (25(OH)D concentrations (OR=0.59, 95% CI 0.38–0.90 for highest vs. lowest quintile, p-trend = 0.003) and increased risk in men with higher 25(OH)D concentrations (OR = 1.47, 95% CI 0.98–2.20, p-trend 0.10, p-interaction = 0.02). Our data suggest that the primary vitamin D carrier protein, DBP, modulates the impact of vitamin D status on prostate cancer. PMID:23180681

  11. Vitamin D Plasma Levels and In-Hospital and 1-Year Outcomes in Acute Coronary Syndromes

    PubMed Central

    De Metrio, Monica; Milazzo, Valentina; Rubino, Mara; Cabiati, Angelo; Moltrasio, Marco; Marana, Ivana; Campodonico, Jeness; Cosentino, Nicola; Veglia, Fabrizio; Bonomi, Alice; Camera, Marina; Tremoli, Elena; Marenzi, Giancarlo

    2015-01-01

    Abstract Deficiency in 25-hydroxyvitamin D (25[OH]D), the main circulating form of vitamin D in blood, could be involved in the pathogenesis of acute coronary syndromes (ACS). To date, however, the possible prognostic relevance of 25 (OH)D deficiency in ACS patients remains poorly defined. The purpose of this prospective study was to assess the association between 25 (OH)D levels, at hospital admission, with in-hospital and 1-year morbidity and mortality in an unselected cohort of ACS patients. We measured 25 (OH)D in 814 ACS patients at hospital presentation. Vitamin D serum levels >30 ng/mL were considered as normal; levels between 29 and 21 ng/mL were classified as insufficiency, and levels < 20 ng/mL as deficiency. In-hospital and 1-year outcomes were evaluated according to 25 (OH)D level quartiles, using the lowest quartile as a reference. Ninety-three (11%) patients had normal 25 (OH)D levels, whereas 155 (19%) and 566 (70%) had vitamin D insufficiency and deficiency, respectively. The median 25 (OH)D level was similar in ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) patients (14.1 [IQR 9.0–21.9] ng/mL and 14.05 [IQR 9.1–22.05] ng/mL, respectively; P = .88). The lowest quartile of 25 (OH)D was associated with a higher risk for several in-hospital complications, including mortality. At a median follow-up of 366 (IQR 364–379) days, the lowest quartile of 25 (OH)D, after adjustment for the main confounding factors, remained significantly associated to 1-year mortality (P < .01). Similar results were obtained when STEMI and NSTEMI patients were considered separately. In ACS patients, severe vitamin D deficiency is independently associated with poor in-hospital and 1-year outcomes. Whether low vitamin D levels represent a risk marker or a risk factor in ACS remains to be elucidated. PMID:25984675

  12. Acute fluid shifts influence the assessment of serum vitamin D status in critically ill patients

    PubMed Central

    2010-01-01

    Introduction Recent reports have highlighted the prevalence of vitamin D deficiency and suggested an association with excess mortality in critically ill patients. Serum vitamin D concentrations in these studies were measured following resuscitation. It is unclear whether aggressive fluid resuscitation independently influences serum vitamin D. Methods Nineteen patients undergoing cardiopulmonary bypass were studied. Serum 25(OH)D3, 1α,25(OH)2D3, parathyroid hormone, C-reactive protein (CRP), and ionised calcium were measured at five defined timepoints: T1 - baseline, T2 - 5 minutes after onset of cardiopulmonary bypass (CPB) (time of maximal fluid effect), T3 - on return to the intensive care unit, T4 - 24 hrs after surgery and T5 - 5 days after surgery. Linear mixed models were used to compare measures at T2-T5 with baseline measures. Results Acute fluid loading resulted in a 35% reduction in 25(OH)D3 (59 ± 16 to 38 ± 14 nmol/L, P < 0.0001) and a 45% reduction in 1α,25(OH)2D3 (99 ± 40 to 54 ± 22 pmol/L P < 0.0001) and i(Ca) (P < 0.01), with elevation in parathyroid hormone (P < 0.0001). Serum 25(OH)D3 returned to baseline only at T5 while 1α,25(OH)2D3 demonstrated an overshoot above baseline at T5 (P < 0.0001). There was a delayed rise in CRP at T4 and T5; this was not associated with a reduction in vitamin D levels at these time points. Conclusions Hemodilution significantly lowers serum 25(OH)D3 and 1α,25(OH)2D3, which may take up to 24 hours to resolve. Moreover, delayed overshoot of 1α,25(OH)2D3 needs consideration. We urge caution in interpreting serum vitamin D in critically ill patients in the context of major resuscitation, and would advocate repeating the measurement once the effects of the resuscitation have abated. PMID:21110839

  13. Maternal Versus Infant Vitamin D Supplementation During Lactation: A Randomized Controlled Trial

    PubMed Central

    Wagner, Carol L.; Howard, Cynthia R.; Ebeling, Myla; Shary, Judy R.; Smith, Pamela G.; Taylor, Sarah N.; Morella, Kristen; Lawrence, Ruth A.; Hulsey, Thomas C.

    2015-01-01

    OBJECTIVE: Compare effectiveness of maternal vitamin D3 supplementation with 6400 IU per day alone to maternal and infant supplementation with 400 IU per day. METHODS: Exclusively lactating women living in Charleston, SC, or Rochester, NY, at 4 to 6 weeks postpartum were randomized to either 400, 2400, or 6400 IU vitamin D3/day for 6 months. Breastfeeding infants in 400 IU group received oral 400 IU vitamin D3/day; infants in 2400 and 6400 IU groups received 0 IU/day (placebo). Vitamin D deficiency was defined as 25-hydroxy-vitamin D (25(OH)D) <50 nmol/L. 2400 IU group ended in 2009 as greater infant deficiency occurred. Maternal serum vitamin D, 25(OH)D, calcium, and phosphorus concentrations and urinary calcium/creatinine ratios were measured at baseline then monthly, and infant blood parameters were measured at baseline and months 4 and 7. RESULTS: Of the 334 mother-infant pairs in 400 IU and 6400 IU groups at enrollment, 216 (64.7%) were still breastfeeding at visit 1; 148 (44.3%) continued full breastfeeding to 4 months and 95 (28.4%) to 7 months. Vitamin D deficiency in breastfeeding infants was greatly affected by race. Compared with 400 IU vitamin D3 per day, 6400 IU/day safely and significantly increased maternal vitamin D and 25(OH)D from baseline (P < .0001). Compared with breastfeeding infant 25(OH)D in the 400 IU group receiving supplement, infants in the 6400 IU group whose mothers only received supplement did not differ. CONCLUSIONS: Maternal vitamin D supplementation with 6400 IU/day safely supplies breast milk with adequate vitamin D to satisfy her nursing infant’s requirement and offers an alternate strategy to direct infant supplementation. PMID:26416936

  14. Cord blood vitamin D status and neonatal outcomes in a birth cohort in Quebec, Canada

    PubMed Central

    Morgan, Catherine; Dodds, Linda; Langille, Donald B.; Weiler, Hope A.; Armson, B. Anthony; Forest, Jean-Claude; Giguère, Yves

    2016-01-01

    Purpose Some evidence suggests that low maternal vitamin D status adversely affects perinatal health but few studies have examined cord blood vitamin D status. This project aimed to determine the association between the cord blood concentration of 25-hydroxyvitamin D [25(OH)D] and neonatal outcomes. Methods A nested case–control study was conducted in Quebec City, Canada from 2005 to 2010. Included were 83 cases of low birthweight (LBW; <2500 g), 301 cases of small for gestational age (SGA; <10th percentile), 223 cases of preterm birth (PTB; <37 weeks’ gestation), and 1027 controls. Levels of 25(OH)D were determined by chemiluminescence immunoassay. Adjusted odds ratios (OR) and 95 % confidence intervals (CI) were estimated with logistic regression. Results Cord blood [25(OH)D] <50 nmol/L was associated with a lower risk of LBW compared to [25(OH)D] ≥75 nmol/L (OR 0.47 95 % CI 0.23–0.97). For 25(OH)D levels 50–75 nmol/L, a significant association was not demonstrated (OR 0.58, 95 % CI 0.34–1.01). No significant associations were observed between [25(OH)D] and either SGA or PTB after adjustment. Conclusions Although our findings suggest that [25(OH)D] <50 nmol/L is associated with reduced risk of having a LBW infant, prenatal vitamin D recommendations require an examination of the literature that considers the full spectrum of maternal and neonatal outcomes. PMID:26404451

  15. [Metabolic encephalopathy secondary to vitamin D intoxication].

    PubMed

    Herrera Martínez, Aura; Viñals Torràs, Montserrat; Muñoz Jiménez, Ma Concepción; Arenas de Larriva, Antonio Pablo; Molina Puerta, Ma José; Manzano García, Gregorio; Gálvez Moreno, Ma Ángeles; Calañas-Continente, Alfonso

    2014-10-25

    The association between vitamin D deficiency and increased risk of, among others, cardiovascular and autoimmune diseases has lead in the last years to an enhanced interest in the usage of supplements to achieve the normalization of plasmatic values at 25(OH) D. Apparently this search for normalization is resulting in an higher incidence on vitamin D intoxication. We present the case of an 81 years old woman with metabolic encephalopathy and renal failure secondary to iatrogenic vitamin D intoxication. Calcium and vitamin D oral supplements were prescribed after an osteoporotic vertebral fracture. The patient improved clinically as well as analytically after receiving treatment with diuretics and hydration. We emphasize the importance of discarding hypercalcemia as a cause of metabolic encephalopathy; moreover we highly recommend keeping vitamin D intoxication in mind as an uncommon although always possible etiology of reversible hypercalcemia and renal failure.

  16. FGF23 Modifies the Relationship between Vitamin D and Cardiac Remodeling

    PubMed Central

    Ky, Bonnie; Shults, Justine; Keane, Martin G.; St. John Sutton, Martin; Wolf, Myles; Feldman, Harold; Reese, Peter; Anderson, Cheryl; Townsend, Raymond; Deo, Rajat; Lo, Joan; Gadegbeku, Crystal; Carlow, Dean; Sulik, Michael J.; Leonard, Mary B.

    2013-01-01

    Background There is growing evidence to support an important role for vitamin D and related hormones PTH and FGF23 on cardiac remodeling in chronic kidney disease (CKD). Our objective was to determine the relationships between vitamin D and cardiac remodeling in CKD and the effects of PTH and FGF23 on these associations. Methods and Results In 1,431 participants from the Chronic Renal Insufficiency Cohort (CRIC) study, we measured 25(OH)D, 1,25(OH)2D, FGF23, and PTH, and performed quantitative echocardiography. Using linear regression methods, we determined significant negative interactions between 25(OH)D and FGF23 on LV mass (p=0.016); end-diastolic ([EDV], p=0.029); and end-systolic volumes ([ESV], p=0.021). In participants with an FGF23 level >the median of 123.5 RU/ml, each doubling of 25(OH)D was associated with a 2.5% (95%CI −4.8,−0.2) lower LV mass. This association was less pronounced with FGF23 levels 25(OH)D levels <20 ng/ml, each doubling of FGF23 was associated with a 3.4% (95%CI 1.2,5.6) greater LV mass compared to only a 1.6% (95%CI −0.2,3.5) difference in participants with sufficient 25(OH)D. Similar findings were observed with 25(OH)D and volumes (p<0.05), and 1,25(OH)2D and LV mass and volumes (p<0.005). There was no effect modification by PTH. Conclusions We identified significant interactions between 25(OH)D, 1,25(OH)2D, and FGF23 on cardiac remodeling. Increased LV mass and cavity dilatation were observed with low 25(OH)D and high FGF23. Our findings suggest that consideration of both hormones is crucial to understanding the role of either in cardiac remodeling, and may have important therapeutic implications. PMID:23748358

  17. Impact of Increasing Dietary Calcium Levels on Calcium Excretion and Vitamin D Metabolites in the Blood of Healthy Adult Cats

    PubMed Central

    Paßlack, Nadine; Schmiedchen, Bettina; Raila, Jens; Schweigert, Florian J.; Stumpff, Friederike; Kohn, Barbara; Neumann, Konrad; Zentek, Jürgen

    2016-01-01

    Background Dietary calcium (Ca) concentrations might affect regulatory pathways within the Ca and vitamin D metabolism and consequently excretory mechanisms. Considering large variations in Ca concentrations of feline diets, the physiological impact on Ca homeostasis has not been evaluated to date. In the present study, diets with increasing concentrations of dicalcium phosphate were offered to ten healthy adult cats (Ca/phosphorus (P): 6.23/6.02, 7.77/7.56, 15.0/12.7, 19.0/17.3, 22.2/19.9, 24.3/21.6 g/kg dry matter). Each feeding period was divided into a 10-day adaptation and an 8-day sampling period in order to collect urine and faeces. On the last day of each feeding period, blood samples were taken. Results Urinary Ca concentrations remained unaffected, but faecal Ca concentrations increased (P < 0.001) with increasing dietary Ca levels. No effect on whole and intact parathyroid hormone levels, fibroblast growth factor 23 and calcitriol concentrations in the blood of the cats were observed. However, the calcitriol precursors 25(OH)D2 and 25(OH)D3, which are considered the most useful indicators for the vitamin D status, decreased with higher dietary Ca levels (P = 0.013 and P = 0.033). Increasing dietary levels of dicalcium phosphate revealed an acidifying effect on urinary fasting pH (6.02) and postprandial pH (6.01) (P < 0.001), possibly mediated by an increase of urinary phosphorus (P) concentrations (P < 0.001). Conclusions In conclusion, calcitriol precursors were linearly affected by increasing dietary Ca concentrations. The increase in faecal Ca excretion indicates that Ca homeostasis of cats is mainly regulated in the intestine and not by the kidneys. Long-term studies should investigate the physiological relevance of the acidifying effect observed when feeding diets high in Ca and P. PMID:26870965

  18. Vitamin D Status in Women with Gestational Diabetes Mellitus during Pregnancy and Postpartum

    PubMed Central

    Pleskačová, Anna; Bartáková, Vendula; Pácal, Lukáš; Bělobrádková, Jana; Tomandl, Josef; Kaňková, Kateřina

    2015-01-01

    Of many vitamin D extraskeletal functions, its modulatory role in insulin secretion and action is especially relevant for gestational diabetes mellitus (GDM). The aims of the present study were to determine midgestational and early postpartum vitamin D status in pregnant women with and without GDM and to describe the relationship between midgestational and postpartum vitamin D status and parallel changes of glucose tolerance. A total of 76 pregnant women (47 GDM and 29 healthy controls) were included in the study. Plasma levels of 25(OH)D were measured using an enzyme immunoassay. Vitamin D was not significantly decreased in GDM compared to controls during pregnancy; however, both groups of pregnant women exhibited high prevalence of vitamin D deficiency. Prevalence of postpartum 25(OH)D deficiency in post-GDM women remained significantly higher and their postpartum 25(OH)D levels were significantly lower compared to non-GDM counterparts. Finally, based on the oGTT repeated early postpartum persistent glucose abnormality was ascertained in 15% of post-GDM women; however, neither midgestational nor postpartum 25(OH)D levels significantly differed between subjects with GDM history and persistent postpartum glucose intolerance and those with normal glucose tolerance after delivery. PMID:26000285

  19. Low Serum Vitamin D Is Associated with Anti-Thyroid-Globulin Antibody in Female Individuals

    PubMed Central

    Wang, Xinling; Zynat, Jazyra; Guo, Yanying; Osiman, Reziwan; Tuhuti, Aihemaitjan; Zhao, Hongli; Abdunaimu, Munira; Wang, Huili; Jin, Xiaoping; Xing, Shuqing

    2015-01-01

    Objectives. Some evidence has pointed out that vitamin D plays a significant role in reducing the incidence of autoimmune diseases, especially autoimmune thyroid diseases. The authors aimed to examine the relationship between circulating 25-hydroxyvitamin D and thyroid autoantibody in a population-based health survey of Xinjiang Chinese population. Subjects and Methods. A total of 1714 Chinese adults were analyzed. 25(OH)D, anti-thyroid antibodies, and thyroid function were measured. Results. The prevalence of vitamin D insufficiency was 28.3% in Hans and 9.3% in Uyghurs, and the prevalence of vitamin D deficiency was 61.6% in Hans and 87.6% in Uyghurs. Overall prevalence of TgAb positivity was 6.2% (0.9% males; 5.3% females). In female subjects, mean serum 25(OH)D levels were significantly lower in Hans and Uyghurs compared with males, and the difference was statistically significant. Importantly, after adjusting for age and ethnicity, a negative correlation (r = −0.121, P = 0.014) was recognized between 25(OH)D and TgAb levels only in female subjects. Conclusion. Vitamin D insufficiency and deficiency are prevalent among Chinese adults. Low serum 25(OH)D is related to the presence of TgAb in females. The causal effect of low vitamin D level on thyroid autoimmunity should be studied further more. PMID:26681939

  20. Vitamin D and Dental Caries in Children.

    PubMed

    Schroth, R J; Rabbani, R; Loewen, G; Moffatt, M E

    2016-02-01

    The purpose of this study was to assess the relationship between vitamin D status and dental caries in Canadian school-aged children participating in the Canadian Health Measures Survey (CHMS). The CHMS was a national cross-sectional study involving physical assessments, laboratory analysis, and interviews. Analysis was restricted to data for 1,017 children 6 to 11 y of age. Outcome variables included the presence of caries and overall total caries score (dmft/DMFT index). Levels of 25-hydroxyvitamin D (25(OH)D) were measured from serum samples obtained from participants. Bivariate analysis, logistic regression for the presence of caries, and multiple linear regression for total caries scores were used. Significance was set at P ≤ 0.05. Overall, 56.4% of children experienced caries, and the mean dmft/DMFT score was 2.47 (95% CI 2.09 to 2.84). The unadjusted odds of children with 25(OH)D levels ≥75 nmol/L having experienced caries was 0.57 (95% CI 0.39 to 0.82), while the odds for caries at the ≥50 nmol/L level was 0.56 (95% CI 0.39 to 0.89). After controlling for other covariates, backward logistic regression revealed that the presence of caries was significantly associated with 25(OH) levels <75 nmol/L and <50 nmol/L, lower household education, not brushing twice daily, and yearly visits to the dentist. Similarly, multiple linear regression revealed that total dmft/DMFT caries scores were also associated with 25(OH)D concentrations <75 nmol/L, not brushing twice daily, lower household education, and yearly visits to the dentist. Data from a cross-sectional, nationally representative sample of Canadian children suggest that there is an association between caries and lower serum vitamin D. Improving children's vitamin D status may be an additional preventive consideration to lower the risk for caries.

  1. 1,25(OH)2D3 attenuates TGF-β1/β2-induced increased migration and invasion via inhibiting epithelial-mesenchymal transition in colon cancer cells.

    PubMed

    Chen, Shanwen; Zhu, Jing; Zuo, Shuai; Ma, Ju; Zhang, Junling; Chen, Guowei; Wang, Xin; Pan, Yisheng; Liu, Yucun; Wang, Pengyuan

    1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has been reported to inhibit proliferation and migration of multiple types of cancer cells. However, the mechanism underlying its anti-metastasis effect is not fully illustrated. In this study, the effect of 1,25(OH)2D3 on TGF-β1/β2-induced epithelial-mesenchymal transition (EMT) is tested in colon cancer cells. The results suggest that 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased invasion and migration of in SW-480 and HT-29 cells. 1,25(OH)2D3 also inhibited the cadherin switch in SW-480 and HT-29 cells. TGF-β1/β2-induced increased expression of EMT-related transcription factors was also inhibited by 1,25(OH)2D3. 1,25(OH)2D3 also inhibited the secretion of MMP-2 and MMP-9 and increased expression of F-actin induced by TGF-β1/β2 in SW-480 cells. Taken together, this study suggests that the suppression of EMT might be one of the mechanisms underlying the anti-metastasis effect of 1,25(OH)2D3 in colon cancer cells.

  2. Measurement of vitamin D3 metabolites in smelter workers exposed to lead and cadmium

    PubMed Central

    Chalkley, S. R.; Richmond, J.; Barltrop, D.

    1998-01-01

    OBJECTIVES: To investigate the effects of lead and cadmium on the metabolic pathway of vitamin D3. METHODS: Blood and urinary cadmium and urinary total proteins were measured in 59 smelter workers occupationally exposed to lead and cadmium. In 19 of these workers, the plasma vitamin D3 metabolites, (25-hydroxycholecalciferol (25 OHD3), 24R, 25-dihydroxycholecalciferol (24R,25(OH)2D3) and 1 alpha,25- dihydroxycholecalciferol (1 alpha, 25(OH)2D3)) were measured together with blood lead. Vitamin D3 metabolites were measured by radioimmunoassay, (RIA), lead and cadmium by atomic absorption spectrophotometry, and total proteins with a test kit. RESULTS: Ranges for plasma 25(OH)D3, 24R,25(OH)2D3 and 1 alpha,25(OH)2D3 were 1.0-51.9 ng/ml, 0.6-5.8 ng/ml, and 0.1-75.7 pg/ml, respectively. Ranges for blood lead were 1-3.7 mumol/l, (21-76 micrograms/dl), blood cadmium 6- 145 nmol/l, and urinary cadmium 3-161 nmol/l. Total proteins in random urine samples were 2.1-32.6 mg/dl. Concentrations of lead and cadmium in blood showed no correlation (correlation coefficient -0.265) but there was a highly significant correlation between blood and urinary cadmium. Concentrations for 24R,25(OH)2D3 were depressed below the normal range as blood and urinary cadmium increased, irrespective of lead concentrations. High cadmium concentrations were associated with decreased plasma 1 alpha,25(OH)2D3 when lead concentrations were < 1.9 mumol/l and with above normal plasma 1 alpha,25(OH)2D3 when lead concentrations were > 1.9 mumol/l, Kruskal-Wallis analysis of variance (K-W ANOVA) chi 2 = 10.3, p = 0.006. Plasma 25(OH)D3 was negatively correlated with both urinary total proteins and urinary cadmium, but showed no correlation with plasma 24R,25(OH)2D3, 1 alpha,25(OH)2D3, blood lead, or blood cadmium. CONCLUSION: Continuous long term exposure to cadmium may result in a state of equilibrium between blood and urinary cadmium. Cadmium concentrations in blood could be predicted from the cadmium

  3. Vitamin D receptor expression in human bone tissue and dose-dependent activation in resorbing osteoclasts

    PubMed Central

    Zarei, Allahdad; Morovat, Alireza; Javaid, Kassim; Brown, Cameron P

    2016-01-01

    The effects of vitamin D on osteoblast mineralization are well documented. Reports of the effects of vitamin D on osteoclasts, however, are conflicting, showing both inhibition and stimulation. Finding that resorbing osteoclasts in human bone express vitamin D receptor (VDR), we examined their response to different concentrations of 25-hydroxy vitamin D3 [25(OH)D3] (100 or 500 nmol·L−1) and 1,25-dihydroxy vitamin D3 [1,25(OH)2D3] (0.1 or 0.5 nmol·L−1) metabolites in cell cultures. Specifically, CD14+ monocytes were cultured in charcoal-stripped serum in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Tartrate-resistant acid phosphatase (TRAP) histochemical staining assays and dentine resorption analysis were used to identify the size and number of osteoclast cells, number of nuclei per cell and resorption activity. The expression of VDR was detected in human bone tissue (ex vivo) by immunohistochemistry and in vitro cell cultures by western blotting. Quantitative reverse transcription-PCR (qRT-PCR) was used to determine the level of expression of vitamin D-related genes in response to vitamin D metabolites. VDR-related genes during osteoclastogenesis, shown by qRT-PCR, was stimulated in response to 500 nmol·L−1 of 25(OH)D3 and 0.1–0.5 nmol·L−1 of 1,25(OH)2D3, upregulating cytochrome P450 family 27 subfamily B member 1 (CYP27B1) and cytochrome P450 family 24 subfamily A member 1 (CYP24A1). Osteoclast fusion transcripts transmembrane 7 subfamily member 4 (tm7sf4) and nuclear factor of activated T-cell cytoplasmic 1 (nfatc1) where downregulated in response to vitamin D metabolites. Osteoclast number and resorption activity were also increased. Both 25(OH)D3 and 1,25(OH)2D3 reduced osteoclast size and number when co-treated with RANKL and M-CSF. The evidence for VDR expression in resorbing osteoclasts in vivo and low-dose effects of 1,25(OH)2D3 on osteoclasts in vitro

  4. Serum Vitamin D is Llow and Inversely Associated with LDL Cholesterol in the Kazak Ethnic Population: A Cross-Sectional Study

    PubMed Central

    Zhang, Ming Chen; Li, Hai Xia; Liu, Hai Ming; Lei, Hong; Han, Lu; Gao, Ming; Mao, Jiang Feng; Xu, Xin Juan

    2014-01-01

    Background Accumulating evidence suggests that low concentrations of serum 25(OH)D is coupled with increased risks of hypertension, obesity, and cardiovascular disease. However, this relationship has not been established in populations with very low levels of 25(OH)D. Therefore, the aim of our study was to clarify the associations between 25(OH)D and blood pressure, obesity, sex, and lipid profiles in the Kazak ethnic population, who have an extremely low level of 25(OH)D. Material/Methods A multistage-cluster sampling survey was carried out for residents with Kazak ethnicity in Xinjiang, China. Anthropometric measurements of each participant were taken and the concentrations of 25(OH)D, calcium, alkaline phosphatase, and lipid profiles were measured. Individuals were classified into different groups in terms of vitamin D status, degree of adiposity, presence of hypertension, and other comorbidities. Results The madian concentration of 25(OH)D was 16.2 (11.8–20.5) ng/mL and the prevalence of vitamin D deficiency was 72.4% in this Kazak population (n=928, 59.0% women). Females had a lower 25(OH)D concentration than males – 14.6 (10.5–19.4) ng/mL vs. 17.7 (14.8–22.5) ng/mL, P<0.001. The subjects were classified into 3 groups according to their vitamin D status. There were significant differences in BMI (P=0.046), waist circumference (P=0.037), hip circumference (P=0.003), systolic BP (P=0.035), and LDL cholesterol (P=0.008) among the groups after adjustment for sex and age. On the other hand, there was no significant difference in vitamin D levels between groups with or without hypertension (P=0.586), and groups with or without obesity (P=0.639). A multifactor-regression analysis revealed that every increment of 1mg/dL in LDL cholesterol was associated with a 1.0 ng/mL decline in serum 25(OH)D. Conclusions The insufficiency of vitamin D is highly prevalent in Kazaks. Sex, LDL cholesterol, and hip circumference are 3 variables strongly associated with serum 25

  5. High prevalence of vitamin D deficiency in pregnant women: a national cross-sectional survey.

    PubMed

    Vandevijvere, Stefanie; Amsalkhir, Sihame; Van Oyen, Herman; Moreno-Reyes, Rodrigo

    2012-01-01

    An increasing number of studies suggest that vitamin D deficiency during pregnancy is associated with multiple adverse health outcomes in mothers, neonates and children. There are no representative country data available on vitamin D status of pregnant women in Europe. The aim of this study was to estimate the prevalence of vitamin D deficiency among Belgian pregnant women and to assess the determinants of vitamin D status in the first and third trimester of pregnancy. The women were selected via a multi-stage proportionate-to-size sampling design. Blood samples were collected and a questionnaire was completed face-to-face. 55 obstetric clinics were randomly selected and 1311 pregnant women participated in the study. The median serum 25-hydroxyvitamin D [25-(OH)D] concentration was significantly lower in the first trimester (20.4 ng/ml) than in third trimester (22.7 ng/ml). Of all women, 74.1% (95%CI = 71.8-76.5%) were vitamin D insufficient (25-(OH)D <30 ng/ml), 44.6% (95%CI = 41.9-47.3%) were vitamin D deficient (25-(OH)D <20 ng/ml), while 12.1% (95%CI = 10.3-13.8%) were severely vitamin D deficient (25-(OH)D <10 ng/ml). Of all women included, 62.0% reported taking vitamin D-containing multivitamins, of which only 24.2% started taking those before pregnancy. The risk of vitamin D deficiency (25-(OH)D <20 ng/ml) was significantly higher for less educated women and women who reported not going on holidays to sunny climates. The risk of severe vitamin D deficiency (25-(OH)D <10 ng/ml) decreased for women who reported alcohol consumption during pregnancy, decreased with more frequent use of sunscreen lotion and increased for smokers and women who reported preference for shadow. In conclusion, vitamin D deficiency is highly prevalent among pregnant women in Belgium and this raises concerns about the health consequences for the mother and the offspring. A targeted screening strategy to detect and treat women at high risk of severe vitamin D deficiency is needed in

  6. Neonatal vitamin D and childhood brain tumor risk.

    PubMed

    Bhatti, Parveen; Doody, David R; Mckean-Cowdin, Roberta; Mueller, Beth A

    2015-05-15

    Vitamin D deficiency among pregnant women is common. Compelling animal evidence suggests carcinogenic effects of vitamin D deficiency on the brains of offspring; however, the impact of circulating vitamin D [25(OH)D] on childhood brain tumor (CBT) risk has not been previously evaluated. Using linked birth-cancer registry data in Washington State, 247 CBT cases (<15 years at diagnosis; born 1991 or later) were identified. A total of 247 birth year-, sex- and race-matched controls were selected from the remaining birth certificates. Liquid chromatography-tandem mass spectrometry was used to measure circulating levels of vitamin D3 [25(OH)D3] in neonatal dried blood spots. Overall, no significant associations were observed. However, when stratified by median birth weight (3,458 g), there was evidence of increasing risk of CBT with increasing 25(OH)D3 among children in the higher birth weight category. Compared to the lowest quartile (2.8-7.7 ng/mL), odds ratios (ORs) and 95% confidence intervals (CIs) for the second (7.7-<11.0 ng/mL), third (11.0-<14.7 ng/mL) and fourth (14.7-37.0) quartiles of 25(OH)D3 were 1.7 (1.0-3.3), 2.4 (1.2-4.8) and 2.6 (1.2-5.6), respectively. Among children in the lower birth weight category, there was suggestive evidence of a protective effect: ORs and 95% CIs for the second, third and fourth quartiles were 0.9 (0.4-1.9), 0.7 (0.3-1.4) and 0.6 (0.3-1.3), respectively. Any associations of neonatal vitamin D with CBT may be birth weight-specific, suggesting the possible involvement of insulin-like growth factor 1, circulating levels of which have been associated with vitamin D and accelerated fetal growth.

  7. Vitamin D deficiency associates with γ-tocopherol and quadriceps weakness but not inflammatory cytokines in subjects with knee osteoarthritis

    PubMed Central

    Barker, Tyler; Henriksen, Vanessa T.; Rogers, Victoria E.; Aguirre, Dale; Trawick, Roy H.; Lynn Rasmussen, G.; Momberger, Nathan G.

    2014-01-01

    Knee osteoarthritis (OA) is a degenerative joint condition and a leading cause of physical disability in the United States. Quadriceps weakness and inflammatory cytokines contribute to the pathogenesis of knee OA, and both of which, increase with vitamin D deficiency. Other micronutrients, such as vitamins C and E and β-carotene, modulate inflammatory cytokines and decrease during inflammation. The purpose of this study was to test the hypothesis that vitamin D deficiency associates with quadriceps weakness, an increase in serum cytokines, and a decrease in circulating micronutrients in subjects with knee OA. Subjects (age, 48±1 y; serum 25(OH)D, 25.8±1.1 ng/mL) with knee OA were categorized as vitamin D deficient (n=17; serum 25(OH)D≤20 ng/mL), insufficient (n=21; serum 25(OH)D 20–29 ng/mL), or sufficient (n=18; serum 25(OH)D≥30 ng/mL). Single-leg strength (concentric knee extension–flexion contraction cycles at 60 °/s) and blood cytokine, carotene (α and β), ascorbic acid, and tocopherol (α and γ) concentrations were measured. Quadriceps peak torque, average power, total work, and deceleration were significantly (all p<0.05) impaired with vitamin D deficiency. Serum γ-tocopherol concentrations were significantly (p<0.05) increased with vitamin D deficiency. In the vitamin D sufficient group, γ-tocopherol inversely correlated (r=−0.47, p<0.05) with TNF-α, suggesting a pro-inflammatory increase with a γ-tocopherol decrease despite a sufficient serum 25(OH)D concentration. We conclude that vitamin D deficiency is detrimental to quadriceps function, and in subjects with vitamin D sufficiency, γ-tocopherol could have an important anti-inflammatory role in a pathophysiological condition mediated by inflammation. PMID:24624336

  8. Vitamin D deficiency associates with γ-tocopherol and quadriceps weakness but not inflammatory cytokines in subjects with knee osteoarthritis.

    PubMed

    Barker, Tyler; Henriksen, Vanessa T; Rogers, Victoria E; Aguirre, Dale; Trawick, Roy H; Lynn Rasmussen, G; Momberger, Nathan G

    2014-01-01

    Knee osteoarthritis (OA) is a degenerative joint condition and a leading cause of physical disability in the United States. Quadriceps weakness and inflammatory cytokines contribute to the pathogenesis of knee OA, and both of which, increase with vitamin D deficiency. Other micronutrients, such as vitamins C and E and β-carotene, modulate inflammatory cytokines and decrease during inflammation. The purpose of this study was to test the hypothesis that vitamin D deficiency associates with quadriceps weakness, an increase in serum cytokines, and a decrease in circulating micronutrients in subjects with knee OA. Subjects (age, 48±1 y; serum 25(OH)D, 25.8±1.1 ng/mL) with knee OA were categorized as vitamin D deficient (n=17; serum 25(OH)D≤20 ng/mL), insufficient (n=21; serum 25(OH)D 20-29 ng/mL), or sufficient (n=18; serum 25(OH)D≥30 ng/mL). Single-leg strength (concentric knee extension-flexion contraction cycles at 60 °/s) and blood cytokine, carotene (α and β), ascorbic acid, and tocopherol (α and γ) concentrations were measured. Quadriceps peak torque, average power, total work, and deceleration were significantly (all p<0.05) impaired with vitamin D deficiency. Serum γ-tocopherol concentrations were significantly (p<0.05) increased with vitamin D deficiency. In the vitamin D sufficient group, γ-tocopherol inversely correlated (r=-0.47, p<0.05) with TNF-α, suggesting a pro-inflammatory increase with a γ-tocopherol decrease despite a sufficient serum 25(OH)D concentration. We conclude that vitamin D deficiency is detrimental to quadriceps function, and in subjects with vitamin D sufficiency, γ-tocopherol could have an important anti-inflammatory role in a pathophysiological condition mediated by inflammation.

  9. Vitamin D levels in children of asylum seekers in The Netherlands in relation to season and dietary intake.

    PubMed

    Stellinga-Boelen, Annette A M; Wiegersma, P Auke; Storm, Huub; Bijleveld, Charles M A; Verkade, Henkjan J

    2007-03-01

    Low dietary intake and limited sun exposure during Dutch winters, in particular when combined with highly pigmented skin, could compromise the vitamin D status of asylum seekers' children in The Netherlands. We determined the vitamin D status of children living in The Netherlands, but originating from Africa, Central Asia, or Eastern Europe. In a subgroup, we reassessed the vitamin D status after the summer, during which the children had been assigned at random to remain unsupplemented or to receive vitamin D supplementation. In total 112 children (median age 7.1 yr, range 2-12 yr) were assessed for serum concentrations of 25-Hydroxyvitamin D [25(OH)D], intact parathyroid hormone (I-PTH) and plasma alkaline phosphatase (ALP). Vitamin D deficiency (VDD) and hypovitaminosis D were defined as 25(OH)D below 30 or 50 nmol/L, respectively. Dietary intake of vitamin D and calcium was estimated using a 24 h recall interview. In mid-spring, 13% of the children had VDD, and 42% had hypovitaminosis D. I-PTH and ALP levels were significantly higher in children with VDD. The dietary intake of vitamin D was below 80% of the recommended daily allowances (RDA) in 94% of the children, but the dietary calcium intake was not significantly related to the s-25(OH)D levels found. After the summer, median s-25(OH)D increased with +35 nmol/L (+85%) and +19 nmol/L (+42%) in children with or without supplementation, respectively. The effect of supplementation was most prominent among African children. VDD and hypovitaminosis D are highly prevalent in mid-spring among asylum seekers' children in The Netherlands. Although 25(OH)D levels increase in African children during Dutch summer months, this does not completely correct the compromised vitamin D status. Our data indicate that children from African origin would benefit from vitamin D supplementation.

  10. Racial/ethnic considerations in making recommendations for vitamin D for adult and elderly men and women.

    PubMed

    Dawson-Hughes, Bess

    2004-12-01

    Vitamin D is acquired through diet and skin exposure to ultraviolet B light. Skin production is determined by length of exposure, latitude, season, and degree of skin pigmentation. Blacks produce less vitamin D3 than do whites in response to usual levels of sun exposure and have lower 25-hydroxyvitamin D [25(OH)D] concentrations in winter and summer. Blacks in the United States also use dietary supplements less frequently than do whites. However, blacks and whites appear to have similar capacities to absorb vitamin D and to produce vitamin D after repeated high doses of ultraviolet B light. There is a growing consensus that serum 25(OH)D concentrations of at least 75-80 nmol/L are needed for optimal bone health, on the basis of studies of older white subjects living in Europe and the United States. The studies show that increasing serum 25(OH)D concentrations to this level decreases parathyroid hormone (PTH) concentrations, decreases rates of bone loss, and reduces rates of fractures. Among US blacks, low 25(OH)D concentrations are associated with higher concentrations of PTH, which are associated with lower bone mineral density. Vitamin D supplements decrease PTH and bone turnover marker concentrations among blacks. These findings suggest that improving vitamin D status would benefit blacks as well as whites. On the basis of studies conducted in the temperate zone, the intake of vitamin D3 needed to maintain a group average 25(OH)D concentration of 80 nmol/L in winter is approximately 1000 IU/d. Broad-based vitamin D supplementation is needed to remove vitamin D insufficiency as a contributing cause of osteoporosis.

  11. [Vitamin D-dependent type-1 rickets: diagnosis and treatment of a further case].

    PubMed

    Pela, I; Bini, R; Seracini, D

    1996-01-01

    We describe a child with vitamin D dependent rickets type 1, who developed clinical signs of the disease at three months of age. The principal manifestations were hypocalcemia and seizure with EEG abnormalities. The circulating level of 1 alpha, 25 (OH)2D3 was low despite a normal level of 25 (OH)D3 and an adequate vitamin D supplementation. The patient responded to calcium gluconate infusions and pharmacologic doses of 1 alpha, 25 (OH)2D3 and a normalization of calcemia was obtained. After six months the therapy was progressively reduced to physiological dosage with optimal metabolic control. The patient is now 2.5 years old and receive a maintenance dose of calcitriol of 0.125 mcg/day. His clinical, biochemical and radiologic features are normal. PMID:8767587

  12. NIH deltanoids meeting on Vitamin D and cancer. Conclusion and strategic options.

    PubMed

    Bouillon, Roger; Moody, Terry; Sporn, Michael; Barrett, J Carl; Norman, Anthony W

    2005-10-01

    A meeting on "Cancer Chemoprevention and Cancer Treatment; role of vitamin D, 1alpha,25-(OH)(2)D(3) and deltanoids" was held on the NIH Congres, Bethesda in November 2004. The following conclusions were presented at the end of this symposium. Vitamin D deficiency and insufficiency are worldwide problems and are associated with several health problems including higher cancer prevalence. There is convincing evidence that the active vitamin D hormone, 1alpha,25(OH)(2)D(3), can decrease cell proliferation, modify cell apoptosis and control malignant cell growth. Therefore academia, public funding agencies and industry should urgently design appropriate studies to better define the causal relationship between vitamin D nutrition and cancer, define the optimal vitamin D nutrition based on accurate 25(OH)D measurement and inform the public and medical profession accordingly. Selective vitamin D receptor modulators are a potentially interesting new class of chemopreventive and chemotherapeutic agents as demonstrated by several first generation analogs have provided a convincing proof of concept. In the mean time, the public should be informed about the risks of vitamin D deficiency and insufficiency and appropriate steps should be taken to improve the vitamin D nutritional status of large parts of the world population. PMID:16043351

  13. The Association of Adiposity Indices and Plasma Vitamin D in Young Females in Saudi Arabia.

    PubMed

    Al Asoom, Lubna Ibrahim

    2016-01-01

    Background. Vitamin D deficiency is a global health problem. Some evidences indicate its association with metabolic syndrome, type II diabetes, and cardiovascular diseases. In the current study we aim to study the association of vitamin D level and indicators of adiposity in young Saudi females. Subjects and Methods. 87 young healthy Saudi females were recruited from University of Dammam, Dammam, Saudi Arabia. Each subject filled vitamin D questionnaire and had exercise stress test to determine VO2 peak. Body weight, BMI, waist and hip circumference, and ratios were determined. Blood was analyzed for 25-OH vitamin D, glucose, triglycerides, total cholesterol, and differential cholesterol. Results. 25-OH vitamin D/body weight was negatively associated with waist circumference and waist/stature ratio. No significant difference was found between the groups of BMI with regard to the data of questionnaire or 25-OH vitamin D/body weight. Obese and overweight subjects had lower VO2 peak. Conclusion. In young Saudi females we found that the relative value of vitamin D to body weight is a better indicator of vitamin D status particularly in obese subjects and it is negatively associated with adiposity measures of waist circumference and waist/stature ratio. PMID:27525007

  14. The Association of Adiposity Indices and Plasma Vitamin D in Young Females in Saudi Arabia

    PubMed Central

    2016-01-01

    Background. Vitamin D deficiency is a global health problem. Some evidences indicate its association with metabolic syndrome, type II diabetes, and cardiovascular diseases. In the current study we aim to study the association of vitamin D level and indicators of adiposity in young Saudi females. Subjects and Methods. 87 young healthy Saudi females were recruited from University of Dammam, Dammam, Saudi Arabia. Each subject filled vitamin D questionnaire and had exercise stress test to determine VO2 peak. Body weight, BMI, waist and hip circumference, and ratios were determined. Blood was analyzed for 25-OH vitamin D, glucose, triglycerides, total cholesterol, and differential cholesterol. Results. 25-OH vitamin D/body weight was negatively associated with waist circumference and waist/stature ratio. No significant difference was found between the groups of BMI with regard to the data of questionnaire or 25-OH vitamin D/body weight. Obese and overweight subjects had lower VO2 peak. Conclusion. In young Saudi females we found that the relative value of vitamin D to body weight is a better indicator of vitamin D status particularly in obese subjects and it is negatively associated with adiposity measures of waist circumference and waist/stature ratio. PMID:27525007

  15. Structural evidence for enhancement of sequential vitamin D3 hydroxylation activities by directed evolution of cytochrome P450 vitamin D3 hydroxylase.

    PubMed

    Yasutake, Yoshiaki; Fujii, Yoshikazu; Nishioka, Taiki; Cheon, Woo-Kwang; Arisawa, Akira; Tamura, Tomohiro

    2010-10-01

    Vitamin D(3) hydroxylase (Vdh) isolated from actinomycete Pseudonocardia autotrophica is a cytochrome P450 (CYP) responsible for the biocatalytic conversion of vitamin D(3) (VD(3)) to 1α,25-dihydroxyvitamin D(3) (1α,25(OH)(2)VD(3)) by P. autotrophica. Although its biological function is unclear, Vdh is capable of catalyzing the two-step hydroxylation of VD(3), i.e. the conversion of VD(3) to 25-hydroxyvitamin D(3) (25(OH)VD(3)) and then of 25(OH)VD(3) to 1α,25(OH)(2)VD(3), a hormonal form of VD(3). Here we describe the crystal structures of wild-type Vdh (Vdh-WT) in the substrate-free form and of the highly active quadruple mutant (Vdh-K1) generated by directed evolution in the substrate-free, VD(3)-bound, and 25(OH)VD(3)-bound forms. Vdh-WT exhibits an open conformation with the distal heme pocket exposed to the solvent both in the presence and absence of a substrate, whereas Vdh-K1 exhibits a closed conformation in both the substrate-free and substrate-bound forms. The results suggest that the conformational equilibrium was largely shifted toward the closed conformation by four amino acid substitutions scattered throughout the molecule. The substrate-bound structure of Vdh-K1 accommodates both VD(3) and 25(OH)VD(3) but in an anti-parallel orientation. The occurrence of the two secosteroid binding modes accounts for the regioselective sequential VD(3) hydroxylation activities. Moreover, these structures determined before and after directed evolution, together with biochemical and spectroscopic data, provide insights into how directed evolution has worked for significant enhancement of both the VD(3) 25-hydroxylase and 25(OH)VD(3) 1α-hydroxylase activities.

  16. Evidence of associations between feto-maternal vitamin D status, cord parathyroid hormone and bone-specifi