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Sample records for 25oh vitamin d2

  1. 25(OH)D2 Half-Life Is Shorter Than 25(OH)D3 Half-Life and Is Influenced by DBP Concentration and Genotype

    PubMed Central

    Assar, S.; Harnpanich, D.; Bouillon, R.; Lambrechts, D.; Prentice, A.; Schoenmakers, I.

    2014-01-01

    Context: There is uncertainty over the equivalence of vitamins D2 and D3 to maintain plasma 25-hydroxyvitamin D (25(OH)D). Objective: The objective of the study was to compare the plasma half-lives of 25(OH)D2 and 25(OH)D3 in two distinct populations with different dietary calcium intake and 25(OH)D status. Participants: Healthy men (aged 24 and 39 y), resident in The Gambia (n = 18) or the United Kingdom (n = 18) participated in the study. Interventions: The intervention included an oral tracer dose of deuterated-25(OH)D2 and deuterated-25(OH)D3 (both 40 nmol). Blood samples were collected over 33 days. Main Outcome Measures: 25(OH)D2 and 25(OH)D3 plasma half-lives, concentrations of 25(OH)D, and vitamin D binding protein (DBP) and DBP genotypes were measured. Results: 25(OH)D2 half-life [mean (SD)] [13.9 (2.6) d] was shorter than 25(OH)D3 half-life [15.1 (3.1) d; P = .001] for countries combined, and in Gambians [12.8 (2.3) d vs 14.7 (3.5) d; P < .001], but not in the United Kingdom [15.1 (2.4) d vs 15.6 (2.5) d; P = .3]. 25(OH)D concentration was 69 (13) and 29 (11) nmol/L (P < .0001), and the DBP concentration was 259 (33) and 269 (23) mg/L (P = .4) in The Gambia and United Kingdom, respectively. Half-lives were positively associated with plasma DBP concentration for countries combined [25(OH)D2 half-life: regression coefficient (SE) 0.03 (0.01) d per 1 mg/L DBP, P = .03; 25(OH)D3 half-life: 0.04 (0.02) d, P = .02] and in Gambians [25(OH)D2 half-life: 0.04 (0.01) d; P = .02; 25(OH)D3 half-life: 0.06 (0.02) d, P = .01] but not in UK participants. The DBP concentration × country interactions were not significant. DBP Gc1f/1f homozygotes had shorter 25(OH)D2 half-lives compared with other combined genotypes (P = .007) after correction for country. Conclusions: 25(OH)D2 half-life was shorter than 25(OH)D3 half-life, and half-lives were affected by DBP concentration and genotype. The stable isotope 25(OH)D half-life measurements provide a novel tool to investigate

  2. Analytical evaluation of the BioPlex® 2200 25-OH vitamin D total assay.

    PubMed

    Abou El Hassan, Mohamed; Lin, Dan C C; Earle, Tammy; Spencer, Megan; Blasutig, Ivan M

    2016-06-01

    Testing for 25-hydroxyvitamin D (25(OH)D) has increased dramatically over the past decade and several automated immunoassays exist to measure serum 25(OH)D. Here we assess the performance of the recently released automated Bio-Rad BioPlex® 2200 25-OH vitamin D immunoassay, claimed to equally detect 25(OH)D2 and 25(OH)D3, and compare its results against a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method and the well-established DiaSorin LIAISON® 25-OH vitamin D total immunoassay. Imprecision was determined using third party controls over 20days. Linearity over the claimed measuring range was assessed using admixtures of a high and a low patient pool. Correlation between the BioPlex and LC-MS/MS (n=137) or the LIAISON (n=56) was assessed using patient samples with varying amounts of 25(OH)D3 and/or 25(OH)D2. The total imprecision was 9.4%, 6.9% and 4.5% at concentrations of 39.4nmol/L, 70.6nmol/L and 242.8nmol/L, respectively. The assay was linear from 33.1-375.0nmol/L with a R(2) of 0.993. Method comparison revealed a strong correlation between the BioPlex assay and LC-MS/MS for samples containing 25(OH)D2 alone (n=5; R(2)=0.999), 25(OH)D3 alone (n=119; R(2)=0.935) and both (n=13; R(2)=0.919). In samples tested by all three methods (n=56), the correlation between the BioPlex and the LIAISON (R(2)=0.853) was poorer than that of the BioPlex and LC-MS/MS (R(2)=0.942). The BioPlex assay is suitable for the measurement of total serum 25(OH)D. The strong correlation between the BioPlex assay and LC-MS/MS in detecting 25(OH)D2 and 25(OH)D3 provides evidence that the BioPlex assay is capable of the equivalent detection of both forms. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  3. Case Report: Three Patients With Substantial Serum Levels of 3-Epi-25(OH)D Including One With 3-Epi-25(OH)D2 While on High-Dose Ergocalciferol

    PubMed Central

    Wiebe, Donald

    2014-01-01

    Context: We report the presence of substantial concentrations of 3-epi-25(OH)D3 in two patients and a third patient with 3-epi-25(OH)D2. Patients: The first patient, a 66-year-old female receiving cholecalciferol 4000 IU daily was originally found to have 53 ng/mL of 25(OH)D3 and almost an equal amount of 3-epi-25(OH)D3. Subsequently, the patient had four additional samples, each of which has similar levels of both 25(OH)D3 and 3-epi-25(OH)D3. The second patient, a 7-year-old male receiving cholecalciferol 1000 IU daily, had a 25(OH)D3 concentration of 37 ng/mL and 3-epi-25(OH)D3 of approximately 10 ng/mL. The third and most intriguing patient, a 55-year-old female was receiving ergocalciferol 50 000 IU twice weekly for approximately 3 months, at which time her serum 25(OH)D2 was 64 ng/mL and her 3-epi-25(OH)D2 was approximately 32 ng/mL. This patient's physician changed her vitamin D therapy to cholecalciferol 1000 IU daily, discontinuing ergocalciferol, and a second specimen was collected 5 months later. Analysis of this last specimen found both 25(OH)D3 and 25(OH)D2 at concentrations of 12 and 24 ng/mL respectively, plus corresponding 3-epimer peaks for both 25(OH)D3 and 25(OH)D2 observed chromatographically. Conclusion: The presence of a substantial concentration of 3-epi-25(OH)D in these three patients documents that one cannot assume 3-epi is a trivial metabolite of 25(OH)D for all patients. In addition, the appearance of 3-epi-25(OH)D3 when the last patient changed her vitamin D supplementation from ergocalciferol to cholecalciferol demonstrates that the 3-epimer is probably an endogenous metabolite of 25(OH)D in humans. PMID:24476080

  4. Multicenter Comparison of Seven 25OH Vitamin D Automated Immunoassays

    PubMed Central

    Lippi, Giuseppe; Salvagno, Gian Luca; Fortunato, Antonio; Dipalo, Mariella; Aloe, Rosalia; Da Rin, Giorgio; Giavarina, Davide

    2015-01-01

    Summary Background The measurement of 25OH vitamin D continues to grow in clinical laboratories. The aim of this multi-center study was to compare the results of seven automated commercial immunoassays with a reference HPLC technique. Methods One hundred and twenty consecutive outpatient serum samples were centrifuged, divided in aliquots, frozen and shipped to the participating laboratories. 25OH Vitamin D was measured with a reference HPLC system and with seven automated commercial immunoassays (Roche Cobas E601, Beckman Coulter Unicel DXI 800, Ortho Vitros ES, DiaSorin Liaison, Siemens Advia Centaur, Abbott Architect i System and IDS iSYS). Results Compared to the reference method, the regression coefficients ranged from 0.923 to 0.961 (all p<0.001). The slope of Deming fit ranged from 0.95 to 1.06, whereas the intercept was comprised between −15.2 and 9.2 nmol/L. The bias from the reference HPLC technique varied from −14.5 to 8.7 nmol/L. The minimum performance goal for bias was slightly exceeded by only one immunoassay. The agreement between HPLC and the different immunoassays at 50 nmol/L 25OH Vitamin D varied between 0.61 and 0.85 (all p<0.001). The percentage of samples below this cut-off was significantly different with only one immunoassay. Conclusions The excellent correlation with the reference HPLC technique attests that all seven automated immunoassays may be reliably used for routine assessment of 25OH-D in clinical laboratories. The significant bias among the different methods seems mostly attributable to the lack of standardization and calls for additional efforts for improving harmonization of 25OH-D immunoassays. PMID:28356846

  5. Effects of vitamin D binding protein phenotypes and vitamin D supplementation on serum total 25(OH)D and directly measured free 25(OH)D.

    PubMed

    Sollid, Stina T; Hutchinson, Moira Y S; Berg, Vivian; Fuskevåg, Ole M; Figenschau, Yngve; Thorsby, Per M; Jorde, Rolf

    2016-04-01

    To determine the relationship between serum total 25-hydroxyvitamin D (25(OH)D), directly measured free 25(OH)D and calculated free 25(OH)D with regard to vitamin D-binding protein (DBP) phenotypes, sex, BMI, age and season, and their interrelationship to vitamin D supplementation. A randomized controlled trial with 20 000 IU of vitamin D3 per week or placebo for 12 months was designed. A total of 472 subjects, 236 in each of the intervention groups, were included in the analyses. Baseline serum concentrations and increases in serum total 25(OH)D, directly measured free 25(OH)D, calculated free 25(OH)D and DBP. Serum total 25(OH)D and DBP concentrations were significantly lower in subjects with the phenotype Gc2/Gc2 compared to phenotypes with the Gc1S allele, and lower in males compared to females. When using directly measured free 25(OH)D, the differences related to DBP phenotypes and sexes were clearly diminished. All calculated free 25(OH)D concentrations were overestimated compared to the directly measured free 25(OH)D. Serum parathyroid hormone showed an inverse correlation with all vitamin D parameters analyzed. The increases after 12 months of vitamin D supplementation were not significantly different for any of the vitamin D parameters regardless of DBP phenotype, sex or age. Supplementation with vitamin D did not affect serum DBP. Direct measurements of free 25(OH)D reduce the differences seen in total 25(OH)D between DBP phenotype groups and sexes, probably caused by differences in DBP concentrations. With conditions affecting serum DBP concentrations, direct measurements of free 25(OH)D should be considered. © 2016 The authors.

  6. Impact of a single oral dose of 100,000 IU vitamin D3 on profiles of serum 25(OH)D3 and its metabolites 24,25(OH)2D3, 3-epi-25(OH)D3, and 1,25(OH)2D3 in adults with vitamin D insufficiency.

    PubMed

    Saleh, Lanja; Tang, Jonathan; Gawinecka, Joanna; Boesch, Lukas; Fraser, William D; von Eckardstein, Arnold; Nowak, Albina

    2017-03-22

    We investigate the effect of a high dose of vitamin D3 on circulating concentrations of 25(OH)D3 and its metabolites 24,25(OH)2D3, 3-epi-25(OH)D3, and 1,25(OH)2D3 in healthy individuals with self-perceived fatigue and vitamin D insufficiency [25(OH)D3<50 nmol/L]. One hundred and seven study participants (age 20-50 years) were randomized to receive a single 100,000 IU dose of vitamin D3 (n=52) or placebo (n=55). Vitamin D metabolite concentrations in serum were measured before, and 4 weeks after, supplementation. Overall, 52% of participants receiving vitamin D3 attained a serum 25(OH)D3 level >75 nmol/L. Among individuals who received vitamin D3, there were significant increases in serum concentrations of 25(OH)D3 and its metabolites 24,25(OH)2D3, 3-epi-25(OH)D3, and 1,25(OH)2D3 at 4 weeks; however, inter-individual variability in these changes was substantial. Positive correlations between serum 25(OH)D3 and 24,25(OH)2D3 and 3-epi-25(OH)D3, and a significant negative correlation between serum 1,25(OH)2D3 and 3-epi-25(OH)D3, were found 4 weeks after supplementation. The 24,25(OH)2D3/25(OH)D3 and 24,25(OH)2D3/1,25(OH)2D3 ratios were significantly increased, compared with baseline, in participants receiving vitamin D3. Baseline 25(OH)D3 concentration was the only factor predictive of the change in 25(OH)D3 after supplementation. Administration of a single high dose of vitamin D3 leads to a significant increase in concentrations of 25(OH)D3, 24,25(OH)2D3, 3-epi-25(OH)D3 and 1,25(OH)2D3; induction of the catabolic pathway predominates over the production of 1,25(OH)2D3. Due to the high inter-individual variation in the 25(OH)D3 response to supplementation, any given dose of vitamin D is unlikely to achieve optimal vitamin D status in all treated individuals.

  7. Effect of phototherapy on plasma 25(OH)-vitamin D in neonates.

    PubMed

    Gillies, D R; Hay, A; Sheltawy, M J; Congdon, P J

    1984-01-01

    The possibility that phototherapy may increase plasma levels of 25(OH)-vitamin D was assessed by measuring levels before and after 48 h continuous phototherapy using a standard phototherapy unit (Vickers, Basingstoke , England). There was no significant increase in plasma 25(OH)-vitamin D after 48 h phototherapy and it is concluded that such treatment does not stimulate photobiosynthesis of vitamin D.

  8. Simultaneous determination of vitamins A, E and 25-OH-vitamin D: application in clinical assessments.

    PubMed

    Granado-Lorencio, F; Olmedilla-Alonso, B; Herrero-Barbudo, C; Blanco-Navarro, I; Blázquez-García, S; Pérez-Sacristán, B

    2006-02-01

    To optimize an HPLC method for the simultaneous determination of vitamins A, E and 25-OH-vitamin D. Modifications include sample volume, internal standard, temperature, detection and injection volume. Validity was supported by performance in interlaboratory exercises. Utility and versatility in clinical practice were assessed in outpatients and hospitalized subjects. The method was shown to be accurate and reliable for the simultaneous determination of vitamins A, E and 25-OH-vitamin D in serum throughout the entire range of clinically relevant concentrations.

  9. Antidepressants differentially related to 1,25-(OH)2 vitamin D3 and 25-(OH) vitamin D3 in late-life depression

    PubMed Central

    Oude Voshaar, R C; Derks, W J; Comijs, H C; Schoevers, R A; de Borst, M H; Marijnissen, R M

    2014-01-01

    A low plasma 25-OH vitamin D3 level is a universal risk factor for a wide range of diseases and has also been implicated in late-life depression. It is currently unknown whether the biologically active form of vitamin D, that is, 1,25-(OH)2 vitamin D3, is also decreased in late-life depression, or whether vitamin D levels correlate with specific depression characteristics. We determined plasma 25-OH vitamin D3, 1,25-(OH)2 vitamin D3 and parathormone levels in 355 depressed older persons and 124 non-depressed comparison subjects (age⩾60 years). Psychopathology was established with the Composite International Diagnostic Interview 2.1, together with potential confounders and depression characteristics (severity, symptom profile, age of onset, recurrence, chronicity and antidepressant drug use). Adjusted for confounders, depressed patients had significantly lower levels of 25-OH vitamin D33 (Cohen's d =0.28 (95% confidence interval: 0.07–0.49), P=0.033) as well as 1,25-(OH)2 vitamin D3 (Cohen's d =0.48 (95% confidence interval: 0.27–0.70), P<0.001) than comparison subjects. Of all depression characteristics tested, only the use of tricyclic antidepressants (TCAs) was significantly correlated with lower 1,25-(OH)2 vitamin D3 levels (Cohen's d =0.86 (95% confidence interval: 0.53–1.19), P<0.001), but not its often measured precursor 25-OH vitamin D3. As vitamin D levels were significantly lower after adjustment for confounders, vitamin D might have an aetiological role in late-life depression. Differences between depressed and non-depressed subjects were largest for the biologically active form of vitamin D. The differential impact of TCAs on 25-OH vitamin D3 and 1,25-(OH)2 vitamin D3 levels suggests modulation of 1-α-hydroxylase and/or 24-hydroxylase, which may in turn have clinical implications for biological ageing mechanisms in late-life depression. PMID:24736799

  10. 25(OH)D and 1,25(OH)D vitamin D fails to predict sepsis and mortality in a prospective cohort study

    PubMed Central

    Ratzinger, Franz; Haslacher, Helmuth; Stadlberger, Markus; Schmidt, Ralf L. J.; Obermüller, Markus; Schmetterer, Klaus G.; Perkmann, Thomas; Makristathis, Athanasios; Marculescu, Rodrig; Burgmann, Heinz

    2017-01-01

    The clinical role of vitamin D in sepsis and mortality prediction is controversially discussed. Therefore, we conducted a prospective cohort study on standard care wards, including 461 patients with suspected sepsis fulfilling two or more SIRS criteria. On the first and third day after onset of SIRS symptoms levels of 25(OH)D, 1,25(OH)D and sepsis biomarkers were analysed for their predictive capacity for identifying infection, bacteraemia and an elevated mortality risk. Additionally, several SNPs associated with vitamin D metabolism were evaluated. Bacteraemic patients (28.5%) presented with significantly lower 1,25(OH)D levels than SIRS patients without bacteraemia on the first and third day, while 25(OH)D did not show a predictive capacity. No significant differences of either 1,25(OH)D or 25(OH)D levels were found between SIRS patients with and without infections or between survivors and non-survivors. Sepsis biomarkers, including procalcitonin and CRP, showed a significantly higher discriminatory capacity for these classification tasks. The vitamin D metabolism-related SNPs analysed did not indicate any association with our outcome measures. In conclusion, 1,25(OH)D but not 25(OH)D showed a minor discriminatory value for the prediction of bacteraemia that was inferior to CRP and PCT but both failed to predict sepsis and mortality in a prospective cohort of SIRS patients. PMID:28079172

  11. 25 (OH) vitamin D level in Crohn's disease: association with sun exposure & disease activity.

    PubMed

    Joseph, A J; George, Biju; Pulimood, A B; Seshadri, M S; Chacko, Ashok

    2009-08-01

    Western studies show that up to 65 per cent of patients with Crohn's disease have low serum 25-hydroxy vitamin D concentrations, and 45 per cent of these patients have metabolic bone disease. No data are available from India or from any country with comparable climatic conditions or ethnicity. We carried out this study to measure the serum 25 (OH) vitamin D levels of Crohn's disease patients and compare with matched controls and to assess the consequences of low 25 (OH) vitamin D levels on bone and mineral metabolism in these patients. Adult patients with Crohn's disease were compared with age and sex matched patients diagnosed to have irritable bowel syndrome. Serum 25 (OH) vitamin D, the effect of disease characteristics, sunlight exposure and milk consumption on 25 (OH) vitamin D level, and the consequences of low 25 (OH) vitamin D level on bone and mineral metabolism were assessed. Thirty four patients with Crohn's disease (M:F, 24:10, age 39.2 +/- 12.9 yr) and 34 controls (M:F, 24:10, age 38.9 +/- 13.4 yr) were studied. 25 (OH) vitamin D levels were significantly lower in patients with Crohn's disease as compared to controls (Crohn's disease vs controls: 16.3 +/- 10.8 vs 22.8 +/- 11.9 ng/ml; P<0.05). The severity of disease activity as assessed by the Harvey Bradshaw score correlated negatively (Correlation coefficient -0.484, significance P<0.004), and the duration of sunlight exposure correlated positively (Correlation coefficient 0.327, significance P=0.007) with the serum 25 (OH) vitamin D level. Serum 25 (OH) vitamin D levels were significantly lower among patients with Crohn's disease as compared to age and sex matched controls. Further, 25 (OH) vitamin D levels in patients with Crohn's disease were lower in those with severe disease activity and less sun exposure. Further studies need to be done to correlate low 25 (OH) vitamin D level with bone density and assess the effect of vitamin D supplementation in these patients.

  12. Vitamin D metabolites in captivity? Should we measure free or total 25(OH)D to assess vitamin D status?

    PubMed

    Bikle, Daniel; Bouillon, Roger; Thadhani, Ravi; Schoenmakers, Inez

    2017-10-01

    There is general consensus that serum 25(OH)D is the best biochemical marker for nutritional vitamin D status. Whether free 25(OH)D would be a better marker than total 25(OH)D is so far unclear. Free 25(OH)D can either be calculated based on the measurement of the serum concentrations of total 25(OH)D, vitamin D-binding protein (DBP), albumin, and the affinity between 25(OH)D and its binding proteins in physiological situations. Free 25(OH)D can also be measured directly by equilibrium dialysis, ultrafitration or immunoassays. During the vitamin D workshop held in Boston in March 2016, a debate was organized about the measurements and clinical value of free 25(OH)D, and this debate is summarized in the present manuscript. Overall there is consensus that most cells apart from the renal tubular cells are exposed to free rather than to total 25(OH)D. Therefore free 25(OH)D may be highly relevant for the local production and action of 1,25(OH)2D. During the debate it became clear that there is a need for standardization of measurements of serum DBP and of direct measurements of free 25(OH)D. There seems to be very limited genetic or racial differences in DBP concentrations or (probably) in the affinity of DBP for its major ligands. Therefore, free 25(OH)D is strongly correlated to total 25(OH)D in most normal populations. Appropriate studies are needed to define the clinical implications of free rather than total 25(OH)D in normal subjects and in disease states. Special attention is needed for such studies in cases of abnormal DBP concentrations or when one could expect changes in its affinity for its ligands. Copyright © 2017. Published by Elsevier Ltd.

  13. Free 25(OH)D and the Vitamin D Paradox in African Americans

    PubMed Central

    Mikhail, Mageda; Dhaliwal, Ruban; Shieh, Albert; Usera, Gianina; Stolberg, Alexandra; Ragolia, Louis; Islam, Shahidul

    2015-01-01

    Context: African Americans have a lower total serum 25-hydroxyvitamin D [25(OH)D] but superior bone health. This has been referred to as a paradox. A recent publication found that free serum 25(OH)D is the same in black and white individuals. However, the study was criticized because an indirect method was used to measure free 25(OH)D. A direct method has recently been developed. Objective: We hypothesized that although total serum 25(OH)D is lower in African Americans, free serum 25(OH)D measured directly would not differ between races. Design: White and black healthy postmenopausal women were matched for age and body mass index. Serum total 25(OH)D, PTH, 1,25-dihydroxyvitamin D, vitamin D binding protein (VDBP), and bone density were measured. Measurement of free 25(OH)D was carried out using an ELISA. Setting: The study was conducted at an ambulatory research unit in a teaching hospital. Outcome: A cross-racial comparison of serum free 25(OH)D was performed. Results: A propensity match resulted in the selection of a total of 164 women. Total 25(OH)D was lower in black women (19.5 ± 4.7 vs 26.9 ± 6.4 ng/mL), but a direct measurement of free 25(OH)D revealed almost identical values (5.25 ± 1.2 vs 5.25 ± 1.3 ng/mL) between races. VDBP was significantly lower in blacks when using a monoclonal-based ELISA but higher with a polyclonal-based ELISA. Serum PTH, 1,25-dihydroxyvitamin D, and bone density were higher in African Americans. Conclusions: Free serum 25(OH)D is the same across races despite the lower total serum 25(OH)D in black women. Results comparing VDBP between races using a monoclonal vs a polyclonal assay were discordant. PMID:26161453

  14. Free 25(OH)D and the Vitamin D Paradox in African Americans.

    PubMed

    Aloia, John; Mikhail, Mageda; Dhaliwal, Ruban; Shieh, Albert; Usera, Gianina; Stolberg, Alexandra; Ragolia, Louis; Islam, Shahidul

    2015-09-01

    African Americans have a lower total serum 25-hydroxyvitamin D [25(OH)D] but superior bone health. This has been referred to as a paradox. A recent publication found that free serum 25(OH)D is the same in black and white individuals. However, the study was criticized because an indirect method was used to measure free 25(OH)D. A direct method has recently been developed. We hypothesized that although total serum 25(OH)D is lower in African Americans, free serum 25(OH)D measured directly would not differ between races. White and black healthy postmenopausal women were matched for age and body mass index. Serum total 25(OH)D, PTH, 1,25-dihydroxyvitamin D, vitamin D binding protein (VDBP), and bone density were measured. Measurement of free 25(OH)D was carried out using an ELISA. The study was conducted at an ambulatory research unit in a teaching hospital. A cross-racial comparison of serum free 25(OH)D was performed. A propensity match resulted in the selection of a total of 164 women. Total 25(OH)D was lower in black women (19.5 ± 4.7 vs 26.9 ± 6.4 ng/mL), but a direct measurement of free 25(OH)D revealed almost identical values (5.25 ± 1.2 vs 5.25 ± 1.3 ng/mL) between races. VDBP was significantly lower in blacks when using a monoclonal-based ELISA but higher with a polyclonal-based ELISA. Serum PTH, 1,25-dihydroxyvitamin D, and bone density were higher in African Americans. Free serum 25(OH)D is the same across races despite the lower total serum 25(OH)D in black women. Results comparing VDBP between races using a monoclonal vs a polyclonal assay were discordant.

  15. Ex vivo culture of primary human colonic tissue for studying transcriptional responses to 1α,25(OH)2 and 25(OH) vitamin D

    PubMed Central

    Mapes, Brandon; Chase, Meredith; Hong, Ellie; Ludvik, Anton; Ceryes, Katy; Huang, Yong

    2014-01-01

    1α,25-Dihydroxyvitamin D3 [1α,25(OH)2D3] is a steroid hormone derived from circulating 25(OH) vitamin D [25(OH)D] with chemopreventive effects in colorectal cancer. 1α,25(OH)2D3 acts through transcriptional mechanisms; however, our understanding of vitamin D transcriptional responses in the colon is derived from studies in transformed cancer cell lines which may not represent responses in normal healthy tissue. Here, we describe the optimization of an ex vivo culture model using primary colonic biopsy samples for studying short-term transcriptional response induced by 1α,25(OH)2D3 and 25(OH)D treatment. Colon biopsy samples from healthy subjects were maintained in primary culture and treated in parallel with 100 nM 1α,25(OH)2D3 or 62.5 nM 25(OH)D and vehicle control (ethanol). Viability was assessed using histology and enzymatic assays. Genome-wide transcriptional responses to 1α,25(OH)2D3 were assessed and expression of 25(OH)D targets CYP27B1 and CYP24A1 were measured by real time PCR. We show that ex vivo culture of colonic tissue remains viable for up to 8 h. The largest number of differentially expressed genes in response to 1α,25(OH)2D3 was noted after 6 h (n = 120). As proof of concept, the top upregulated gene was CYP24A1, a well-established vitamin D-responsive gene. With 25(OH)D treatment, mRNA expression of CYP27B1 was significantly increased after 1 h, while expression of CYP24A1 was greatest at 8 h. Ex vivo culture can be used to assess short-term transcriptional responses to 1α,25(OH)2D3 and 25(OH)D in primary tissue from human colon. Future studies will address interindividual differences in transcriptional responses. PMID:24550213

  16. Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3).

    PubMed

    Nykjaer, A; Fyfe, J C; Kozyraki, R; Leheste, J R; Jacobsen, C; Nielsen, M S; Verroust, P J; Aminoff, M; de la Chapelle, A; Moestrup, S K; Ray, R; Gliemann, J; Willnow, T E; Christensen, E I

    2001-11-20

    Steroid hormones are central regulators of a variety of biological processes. According to the free hormone hypothesis, steroids enter target cells by passive diffusion. However, recently we demonstrated that 25(OH) vitamin D(3) complexed to its plasma carrier, the vitamin D-binding protein, enters renal proximal tubules by receptor-mediated endocytosis. Knockout mice lacking the endocytic receptor megalin lose 25(OH) vitamin D(3) in the urine and develop bone disease. Here, we report that cubilin, a membrane-associated protein colocalizing with megalin, facilitates the endocytic process by sequestering steroid-carrier complexes on the cellular surface before megalin-mediated internalization of the cubilin-bound ligand. Dogs with an inherited disorder affecting cubilin biosynthesis exhibit abnormal vitamin D metabolism. Similarly, human patients with mutations causing cubilin dysfunction exhibit urinary excretion of 25(OH) vitamin D(3). This observation identifies spontaneous mutations in an endocytic receptor pathway affecting cellular uptake and metabolism of a steroid hormone.

  17. Differential extraction of endogenous and exogenous 25-OH-vitamin D from serum makes the accurate quantification in liquid chromatography-tandem mass spectrometry assays challenging.

    PubMed

    Lankes, Ulrich; Elder, Peter A; Lewis, John G; George, Peter

    2015-01-01

    Extraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis is the method of choice when it comes to the accurate quantification of 25-OH-vitamin D in blood samples. It is generally assumed that the addition of exogenous internal standard allows for the determination of the endogenous analyte concentration. In this study we investigated the extraction properties of endogenous and exogenous 25-OH-vitamin D. Eight samples were used for the evaluation of the extraction procedure and 59 patients' samples for a method comparison. The methanol-to-sample ratio (v/v) and the sample-to-hexane ratio (v/v) were varied and the LC-MS/MS signals of endogenous 25-OH-vitamin D3, spiked 25-OH-vitamin D2 and internal standard of the extracts recorded. The optimized 'in-house' LC-MS/MS assay was compared to two automated chemiluminescence immunoassays from DiaSorin and Abbott. Mathematical analysis of the data revealed a differential extraction of endogenous 25-OH-vitamin D3, spiked 25-OH-vitamin D2 and non-equilibrated internal standard. Exogenous 25-OH-vitamin D can be measured accurately if a definite methanol-to-sample ratio is used. Endogenous 25-OH-vitamin D is affected by critical quantification issues due to a differential slope in the extraction profile. The actual 25-OH-vitamin D concentration can be one-third above the measured extractable concentration. Results confirm that the 'in-house' LC-MS/MS assay provides reproducible 25-OH-vitamin D results. Discordant concentrations of 25-OH-vitamin D from LC-MS/MS assays can be caused by selection of suboptimal extraction conditions. Furthermore, a different sample pretreatment or solvent extraction system may result in a different dissociation and extraction yield of endogenous 25-OH-vitamin D and therefore contribute to variations of LC-MS/MS results. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  18. 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.

  19. 25(OH) vitamin D serum values and rheumatoid arthritis disease activity (DA S28 ESR)

    PubMed Central

    Sahebari, Maryam; Mirfeizi, Zahra; Rezaieyazdi, Zahra; Rafatpanah, Houshang; Goshyeshi, Ladan

    2014-01-01

    Background: The role of vitamin D in the pathogenesis of rheumatoid arthritis is under investigation. This study was designed to evaluate the correlation between serum values of 25(OH) vitamin D [25(OH)D] and disease activity in rheumatoid arthritis (RA) patients according to Disease Activity Score 28 joints and ESR (DA S28 ESR). Methods: Ninety-nine patients according to ACR classification criteria for RA and 68 healthy controls were included in this study. The participants with known confounding risk factors affecting serum values of 25(OH)D were excluded. All patients were under treatment with supplementary calcium carbonate (1500mg), 25(OH)D (800U), and Hydroxychloroquine (6mg/kg). The control group was mostly recruited from patients’ relatives who lived with them to minimize the impact of diverse lifestyles on 25(OH)D status. Disease activity was assessed by DA S28 ESR. Serum concentrations of 25(OH)D were measured. Serum values of 25(OH)D less than 50 nmol/L were considered 25(OH)D deficiency. Results: The mean 25(OH)D serum values were 83.74±46.45 nmol/L in patients and 46.53±34.07 nmol/L in controls. After adjustment for age, sex and BMI, multivariate analysis showed no correlation between 25(OH)D serum levels and DAS in RA (P=0.29, rp=0.11). However, 25(OH)D serum values were significantly lower in patients with early diagnosed RA compared with the other patients (p=0.012). In the early diagnosed patients, 25(OH)D and anti-CCP serum values were negatively correlated (P=0.04, rs=-0.5). Conclusion: This study showed that there was no correlation between 25(OH)D serum values and DAS over a short duration of disease course. However, in early RA, 25(OH) D serum values were lower than the established RA. PMID:25202442

  20. [Sociodemographic Factors Related to Plasma Concentrations of 25-OH Vitamin D and PTH in Cord Blood].

    PubMed

    Ortigosa Gómez, Sandra; García-Algar, Oscar; Mur Sierra, Antonio; Ferrer Costa, Roser; Carrascosa Lezcano, Antonio; Yeste Fernández, Diego

    2015-01-01

    Plasma 25(OH)D levels in the newborn are dependent on maternal stores, thus, neonates of vitamin D-deficient mothers present a greater risk of hypocalcaemia, rickets and infections the first year of life. Several studies showing a high prevalence of vitamin D deficiency in pregnant women have been published recently. The aim of the study is to analyze the levels of 25(OH)D in cord blood and determine whether there is a relation with nutritional, socioeconomic and clinical factors of pregnant women and their newborns. Between March and May 2013, 99 pregnant women were recruited in Hospital del Mar (Barcelona), in whom plasma 25(OH)D and PTH levels were measured in cord blood at birth. Clinical history data were collected and a nutritional survey was made on maternal vitamin D and calcium intake and sun exposure. Statistical analysis was performed using SPSS. Comparisons were performed using Kruskal-Wallis and Mann-Whitney U tests, and correction for multiple comparisons using Bonferroni. P value <0.05 and <0.0083 for multiple comparisons were considered statistically significant. Mean 25(OH)D value in cord blood was 10.4 ± 6 .1 ng/ml. 94% of pregnant women had 25(OH)D levels in cord blood <20 ng/ml. Vitamin D and calcium intake was considered adequate in 92% although sun exposure was deficient in 47%. A correlation between serum 25(OH)D and vitamin D (p 0.033) and calcium intake (p 0.005), sun exposure (p<0.001), ethnicity (p<0.001), skin phototype (p<0.001) and use of traditional clothing (p<0.001) was found. There is a high prevalence of low levels of vitamin D after winter months in cord blood. The lowest 25(OH D levels were observed in Indo-Pakistani ethnicity, dark phototype and deficient sun exposure.

  1. [Estimation of plasma 25(OH)D vitamin deficiency in patients with metabolic syndrome].

    PubMed

    Godala, Małgorzata; Materek-Kuśmierkiewicz, Izabela; Moczulski, Dariusz; Szatko, Franciszek; Gaszyńska, Ewelina; Tokarski, Sławomir; Kowalski, Jan

    2016-05-01

    Cardiovascular diseases have been the main cause of mortality in Poland for many years, including premature death and the incidence is systematically growing. These diseases contribute to an increase in the number of disabled people and the cost of medical care. The problem of the so called metabolic syndrome (MS), which includes metabolic risks of atherosclerosis, has been known by doctors for a long time. Results of studies which have been conducted for some years confirm that vitamin D deficiency is a risk factor of MS disorders, including obesity, arterial hypertension, diabetes. The aim of the study was to assess plasma 25(OH)D vitamin deficiency in patients with MS. The study included 268 patients with MS, 136 men and 132 women, aged 30-65 years (mean 59,62±9,21 years). The study group was divided according to the age and season. The plasma level of 25(OH)D above 30 ng/ml was considered normal, between 21 ng/ml and 30 ng/ml - suboptimal (hypovitaminosis) and below 20 ng/ml - insufficient (deficiency). Plasma 25(OH)D vitamin deficiency was observed in 80,97% patients with MS, hipovitaminosis - in 17,16%. The recommended 25(OH)D concentration in the plasma was confirmed only in 1,87%. Plasma 25(OH)D vitamin deficiency was detected more often in men than women (93,38% vs. 68,18%, p<0,05);the lowest percentage of patients with 25(OH)D vitamin deficiency was observed during summer months (47,14%). Plasma 25(OH)D vitamin deficiency was very high in patients with metabolic syndrome, especially in men, people over 55 years and during winter months. © 2016 MEDPRESS.

  2. 25(OH) vitamin D levels in premenopausal women with polycystic ovary syndrome and/or obesity.

    PubMed

    Tsakova, Adelina D; Gateva, Antoaneta T; Kamenov, Zdravko A

    2012-12-01

    Insulin resistance, hyperinsulinemia, and obesity play an important role in development of polycystic ovary syndrome (PCOS). Current evidence suggests that vitamin D (VitD) deficiency may contribute to the disturbance in insulin metabolism and the development of the metabolic syndrome. The aim of this study was to investigate VitD levels, measured as 25(OH)D, in Bulgarian women with PCOS and/or obesity. The study included 103 women, divided into three groups - group 1 Obese (n = 33); group 2 Nonobese PCOS (n = 50), and group 3 Obese PCOS (n = 20). 25(OH)D levels were measured by electrochemiluminescence immunoassay. Almost 2/3 of the women with PCOS and/or obesity appeared to be VitD-deficient. Women with obesity, especially visceral (with or without PCOS), had significantly lower levels of 25(OH)D compared to lean PCOS subjects. Women with and without metabolic syndrome however did not differ significantly in 25(OH)D levels. Women with normal body mass index (BMI) had higher 25(OH)D levels compared to overweight and obese (p = 0.028). There was no correlation between 25(OH)D levels and indices of glucose metabolism - fasting blood glucose and immunoreactive insulin (IRI) and after OGTT and HOMA index.

  3. Serum Concentrations of 1,25-Dihydroxyvitamin D2 and 1,25-Dihydroxyvitamin D3 in Response to Vitamin D2 and Vitamin D3 Supplementation

    PubMed Central

    Biancuzzo, Rachael M.; Clarke, Nigel; Reitz, Richard E.; Travison, Thomas G.

    2013-01-01

    Objective: The purpose of this study was to determine 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and 1,25-dihydroxyvitamin D2 [1,25(OH)2D2] levels in healthy adults consuming 1000 IU vitamin D2 or vitamin D3 per day for 11 weeks. Subjects and Design: Blood from 34 healthy male and female adults, aged 18 to 79 years, from a placebo-controlled, double-blind study who received a placebo, 1000 IU vitamin D3, or 1000 IU vitamin D2 daily for 11 weeks at end of winter was analyzed. Serum levels of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, 1,25(OH)2D2, and 1,25(OH)2D3 were determined by liquid chromatography–tandem mass spectroscopy. Results: Of the adults, 82% were vitamin D insufficient (serum 25-hydroxyvitamin D [25(OH)D <30 ng/mL]) at the start of the study. Administration of vitamin D2 and vitamin D3 induced similar increases in total 25(OH)D as well as in 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3, respectively. Compared with placebo and adjusting for baseline levels, 1000 IU daily of vitamin D2 was associated with a mean increase of 7.4 pg/mL (95% confidence interval, 4.4–10.3) in 1,25(OH)2D2, which was accompanied by a mean decrease of 9.9 pg/mL (−15.8 to −4.0) in 1,25(OH)2D3. No such differences accompanied administration of 1000 IU daily of vitamin D3. Conclusion: Vitamin D2 and vitamin D3 were effective in raising and maintaining total serum concentrations of 25(OH)D. Ingestion of vitamin D2 also resulted in an increase in serum concentrations of 1,25(OH)2D2. This increase was accompanied by a comparable decrease in serum concentrations of 1,25(OH)2D3; therefore, the total 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations did not significantly change after 11 weeks compared with baseline levels. Ingestion of vitamin D3 did not alter serum concentrations of 1,25(OH)2D3 or total 1,25(OH)2D. Therefore, ingestion of 1000 IU vitamin D2 or vitamin D3 for 11 weeks was effective in raising total serum concentrations of 25(OH)D as well as sustaining serum

  4. Serum concentrations of 1,25-dihydroxyvitamin D2 and 1,25-dihydroxyvitamin D3 in response to vitamin D2 and vitamin D3 supplementation.

    PubMed

    Biancuzzo, Rachael M; Clarke, Nigel; Reitz, Richard E; Travison, Thomas G; Holick, Michael F

    2013-03-01

    The purpose of this study was to determine 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and 1,25-dihydroxyvitamin D2 [1,25(OH)2D2] levels in healthy adults consuming 1000 IU vitamin D2 or vitamin D3 per day for 11 weeks. Blood from 34 healthy male and female adults, aged 18 to 79 years, from a placebo-controlled, double-blind study who received a placebo, 1000 IU vitamin D3, or 1000 IU vitamin D2 daily for 11 weeks at end of winter was analyzed. Serum levels of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, 1,25(OH)2D2, and 1,25(OH)2D3 were determined by liquid chromatography-tandem mass spectroscopy. Of the adults, 82% were vitamin D insufficient (serum 25-hydroxyvitamin D [25(OH)D <30 ng/mL]) at the start of the study. Administration of vitamin D2 and vitamin D3 induced similar increases in total 25(OH)D as well as in 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3, respectively. Compared with placebo and adjusting for baseline levels, 1000 IU daily of vitamin D2 was associated with a mean increase of 7.4 pg/mL (95% confidence interval, 4.4-10.3) in 1,25(OH)2D2, which was accompanied by a mean decrease of 9.9 pg/mL (-15.8 to -4.0) in 1,25(OH)2D3. No such differences accompanied administration of 1000 IU daily of vitamin D3. Vitamin D2 and vitamin D3 were effective in raising and maintaining total serum concentrations of 25(OH)D. Ingestion of vitamin D2 also resulted in an increase in serum concentrations of 1,25(OH)2D2. This increase was accompanied by a comparable decrease in serum concentrations of 1,25(OH)2D3; therefore, the total 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations did not significantly change after 11 weeks compared with baseline levels. Ingestion of vitamin D3 did not alter serum concentrations of 1,25(OH)2D3 or total 1,25(OH)2D. Therefore, ingestion of 1000 IU vitamin D2 or vitamin D3 for 11 weeks was effective in raising total serum concentrations of 25(OH)D as well as sustaining serum concentrations of total 1,25(OH)2D.

  5. Elevated Serum 25(OH)-Vitamin D Levels Are Negatively Correlated with Molar-Incisor Hypomineralization

    PubMed Central

    Thiering, E.; Kratzsch, J.; Heinrich-Weltzien, R.; Hickel, R.; Heinrich, J.; Wichmann, HE; Heinrich, J

    2015-01-01

    To date, the precise etiology of molar-incisor hypomineralization (MIH) is uncertain. Vitamin D plays a key role in hard tissue formation. Therefore, this study aimed to analyze the relationship between serum 25-hydroxy-vitamin D (25(OH)D) status and dental health data obtained from 1,048 children in a 10-year follow-up of the Munich GINIplus and LISAplus birth cohorts. The dental examination included the diagnosis of MIH and recording of (non-)cavitated caries lesions in primary and permanent teeth. Serum 25(OH)D concentrations were taken from blood samples of the 10-year investigation and measured with a fully automated, modular system. Different logistic regression and Poisson hurdle models were calculated. MIH was diagnosed in 13.6% of the study population. Approximately 16.4% of the children demonstrated caries-related defects (D3-4MFS > 0). The mean season-adjusted concentration of 25(OH)D was 75.8 nmol/l (standard deviation 22.0 nmol/l). After adjusting for sex, age, body mass index, parental education, equivalent income, and television/personal computer (TV/PC) viewing hours, a 10 nmol/l increase in serum 25(OH)D concentrations was significantly associated with a lower odds ratio of having MIH (OR = 0.89; P = 0.006). Furthermore, higher 25(OH)D values were associated with a lower number of caries-affected permanent teeth. It is concluded that elevated serum 25(OH)D concentrations were associated with better dental health parameters. PMID:25503610

  6. Elevated serum 25(OH)-vitamin D levels are negatively correlated with molar-incisor hypomineralization.

    PubMed

    Kühnisch, J; Thiering, E; Kratzsch, J; Heinrich-Weltzien, R; Hickel, R; Heinrich, J

    2015-02-01

    To date, the precise etiology of molar-incisor hypomineralization (MIH) is uncertain. Vitamin D plays a key role in hard tissue formation. Therefore, this study aimed to analyze the relationship between serum 25-hydroxy-vitamin D (25(OH)D) status and dental health data obtained from 1,048 children in a 10-year follow-up of the Munich GINIplus and LISAplus birth cohorts. The dental examination included the diagnosis of MIH and recording of (non-)cavitated caries lesions in primary and permanent teeth. Serum 25(OH)D concentrations were taken from blood samples of the 10-year investigation and measured with a fully automated, modular system. Different logistic regression and Poisson hurdle models were calculated. MIH was diagnosed in 13.6% of the study population. Approximately 16.4% of the children demonstrated caries-related defects (D3-4MFS > 0). The mean season-adjusted concentration of 25(OH)D was 75.8 nmol/l (standard deviation 22.0 nmol/l). After adjusting for sex, age, body mass index, parental education, equivalent income, and television/personal computer (TV/PC) viewing hours, a 10 nmol/l increase in serum 25(OH)D concentrations was significantly associated with a lower odds ratio of having MIH (OR = 0.89; P = 0.006). Furthermore, higher 25(OH)D values were associated with a lower number of caries-affected permanent teeth. It is concluded that elevated serum 25(OH)D concentrations were associated with better dental health parameters.

  7. 25-OH-vitamin D assay variation and subject management in clinical practice.

    PubMed

    Granado-Lorencio, F; Mosteiro, J Salazar; Herrero-Barbudo, C; Navarro, E Donoso; Blanco-Navarro, I; Pérez-Sacristán, B

    2010-03-01

    To compare two methods for assessing vitamin D status in clinical settings. 25-OH-vitamin D status was measured in 120 patients by HPLC and a commercial immunoassay. Only 53% of the subjects considered as vitamin D sufficient by immunoassay fell within this category according to HPLC although subjects with concentrations above 75 nmol/L, regardless of the method used, presented normal PTH concentrations. Both methods are not exchangeable to classify subjects based on unique cut-offs but they are comparable when interpreted in relation with PTH concentrations. Copyright 2009 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  8. A fast and simple method for simultaneous measurements of 25(OH)D, 24,25(OH)2D and the Vitamin D Metabolite Ratio (VMR) in serum samples by LC-MS/MS.

    PubMed

    Fabregat-Cabello, Neus; Farre-Segura, Jordi; Huyghebaert, Loreen; Peeters, Stéphanie; Le Goff, Caroline; Souberbielle, Jean-Claude; Cavalier, Étienne

    2017-10-01

    Rapid, easy and reliable measurement of the major vitamin D metabolites is required in order to fulfill the needs of a clinical routine laboratory. To overcome these challenges, we have developed and validated a LC-MS/MS method for the quantification of 25-hydroxyvitamin D2 and D3, epi-25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3. Sample preparation was based on precipitation and centrifugation of 100μL of patient serum, followed by injection into the LC-MS/MS system. Samples from Vitamin D Standardization Program (n=80) and patient samples (n=281) have been compared with a reference LC-MS/MS method. For the analytical validation NIST and Labquality quality control materials were used. Mean intra-assay and inter-assay imprecision were <6.0 and 6.4% and mean recoveries were within 95-104%. LOQ's were 0.5μg/L for 24,25(OH)2D3, 1.1μg/L for 25(OH)D3 and epi-25(OH)D3 and 1.7μg/L for 25(OH)D2. A 3% bias obtained between the proposed and the reference method satisfies Vitamin D Standardization Program recommendations. We present a rapid, easy, reliable and cost-effective method completely adequate for routine testing, which permits the measurement of the ratio of 24,25-dihydroxyvitamin D to 25-hydroxyvitamin D, Vitamin D Metabolite Ratio (VMR), in serum samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Vitamin D (25(OH)D) in patients with chronic kidney disease stages 2-5

    PubMed Central

    Aguirre Arango, José Vicente

    2016-01-01

    Objective: To establish the impact the chronic kidney disease stage has in the native vitamin D levels in patients not undergoing dialysis treatment. Methods: A study performed in Manizales, Colombia, a city located 2,200 meters above sea level, without important stational variations. Patients with 18 years of age or more, with chronic kidney disease stages 2 to 5 and not undergoing dialysis treatment were recruited for this study. Demographic and anthropometric variations were evaluated as well as solar exposure, CKD etiology and laboratory variables related to bone and mineral diseases. For each CKD clinical stage, correlations were evaluated for vitamin D levels, laboratory results for bone and mineral diseases, solar exposure and ethnicity. Results: Three hundred thirty-three patients were evaluated with a median age of 71 years, most of them mestizo (71%), 173 were women. The main CKD etiology was hypertensive nephropathy (32.2%). 21.1% of patients had normal vitamin D levels, 70.1% were within insufficient range and 8.8% were in deficit. A negative correlation was found between the levels of vitamin 25 (OH) D and the values for: creatinine, phosphorous, calcium x phosphorous product, PTH, 24 hours urine protein and BMI. A positive relationship was found for calcium and albumin. Positive significant statistical correlation was found for vitamin 25(OH) D levels and solar exposure for stages 3b and 4 of CKD. Conclusions: It is common to find low levels of vitamin 25(OH) D in patients with CKD; these can contribute to the appearance of secondary hyperparathyroidism. PMID:27821896

  10. Vitamin D (25(OH)D) in patients with chronic kidney disease stages 2-5.

    PubMed

    Restrepo Valencia, César Augusto; Aguirre Arango, José Vicente

    2016-09-30

    To establish the impact the chronic kidney disease stage has in the native vitamin D levels in patients not undergoing dialysis treatment. A study performed in Manizales, Colombia, a city located 2,200 meters above sea level, without important stational variations. Patients with 18 years of age or more, with chronic kidney disease stages 2 to 5 and not undergoing dialysis treatment were recruited for this study. Demographic and anthropometric variations were evaluated as well as solar exposure, CKD etiology and laboratory variables related to bone and mineral diseases. For each CKD clinical stage, correlations were evaluated for vitamin D levels, laboratory results for bone and mineral diseases, solar exposure and ethnicity. Three hundred thirty-three patients were evaluated with a median age of 71 years, most of them mestizo (71%), 173 were women. The main CKD etiology was hypertensive nephropathy (32.2%). 21.1% of patients had normal vitamin D levels, 70.1% were within insufficient range and 8.8% were in deficit. A negative correlation was found between the levels of vitamin 25 (OH) D and the values for: creatinine, phosphorous, calcium x phosphorous product, PTH, 24 hours urine protein and BMI. A positive relationship was found for calcium and albumin. Positive significant statistical correlation was found for vitamin 25(OH) D levels and solar exposure for stages 3b and 4 of CKD. It is common to find low levels of vitamin 25(OH) D in patients with CKD; these can contribute to the appearance of secondary hyperparathyroidism.

  11. 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.

  12. 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

  13. 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

    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. 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.

  15. 25(OH) Vitamin D is Associated with Greater Muscle Strength in Healthy Men and Women

    PubMed Central

    Grimaldi, Adam S.; Parker, Beth A.; Capizzi, Jeffrey A.; Clarkson, Priscilla M.; Pescatello, Linda S.; White, C. Michael; Thompson, Paul D.

    2012-01-01

    Purpose The purpose of the study was to examine the relationship between serum 25-hydroxy vitamin D (25(OH)D) levels and muscle strength in 419 healthy men and women over a broad age range (20-76 years of age). Methods Isometric and isokinetic strength of the arms and legs was measured using computerized dynamometry and its relation to vitamin D was tested in multivariate models controlling for age, gender, resting heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), maximal oxygen uptake (VO2max,), physical activity counts, and season of vitamin D measurement. Results Vitamin D was significantly associated with arm and leg muscle strength when controlling for age and gender. When controlling for other covariates listed above, vitamin D remained directly related to both isometric and isokinetic arm strength but only to isometric leg strength. Conclusion These data suggests that there may be a differential effect of vitamin D on upper and lower body strength. The mechanism for this difference remains unclear but could be related to differences in androgenic effects or to differences in vitamin D receptor expression. Our study supports a direct relationship between vitamin D and muscle strength and suggests that vitamin D supplementation be evaluated to determine if it is an effective therapy to preserve muscle strength in adults. PMID:22895376

  16. Vitamin D2 versus vitamin D3 supplementation in hemodialysis patients: a comparative pilot study.

    PubMed

    Daroux, Maïté; Shenouda, Milhad; Bacri, Jean-Louis; Lemaitre, Vincent; Vanhille, Philippe; Bataille, Pierre

    2013-01-01

    In patients with chronic kidney disease, vitamin D insufficiency is highly prevalent. It can be corrected by supplementation with either vitamin D(2) or vitamin D3. Recent studies in patients without impaired kidney function suggest that vitamin D(3) is more efficient than vitamin D(2) in correcting vitamin D insufficiency. However, no direct comparison has been made in hemodialysis (HD) patients. Thirty-nine HD patients with serum 25-hydroxyvitamin D (25(OH)D) levels =20 ng/mL were enrolled in this comparative, prospective pilot study. They were divided into 3 groups and treated over a 3-month period. Each patient received oral doses of 200,000 international units (IU) vitamin D per month according to the following treatment schedule: (i) vitamin D(2) in small fractionated doses at each HD session, 3 times per week (group D2S); (ii) vitamin D(2) once a month (group D2M); or (iii) vitamin D(3) once a month (group D3M). Changes in serum 25(OH)D levels were measured at the end of the study. Posttreatment serum 25(OH)D levels increased significantly in all groups. The mean ± SD serum 25(OH)D value for group D3M patients (40 ± 13 ng/mL) was significantly higher than that for groups D2M (25 ± 9 ng/mL, p<0.01) and D2S patients (25 ± 9 ng/mL, p<0.01). Serum 25(OH)D increased to levels >30 ng/mL in 84% of group D3M patients, but in only 15% and 27% of group D2M and D2S subjects, respectively. Vitamin D(3) is more effective than vitamin D(2) in providing adequate 25(OH)D serum levels in HD patients.

  17. 1,25(OH)2 vitamin D suppresses macrophage migration and reverses atherogenic cholesterol metabolism in type 2 diabetic patients.

    PubMed

    Riek, Amy E; Oh, Jisu; Bernal-Mizrachi, Carlos

    2013-07-01

    Reduced monocyte infiltration into the vessel wall and increased macrophage cholesterol efflux are critical components in atherosclerotic plaque regression. During inflammation, monocyte chemotactic protein 1 (MCP-1) signaling activation and cholesterol deposition in macrophages induce endoplasmic reticulum (ER) stress, which promotes an increased inflammatory response. Increased macrophage ER stress shifts macrophages into an M2 macrophage phenotype with increased cholesterol uptake and deposition. In type 2 diabetes, a population with elevated baseline risk of cardiovascular disease (CVD), vitamin D deficiency doubles that risk. We have found that 1,25-dihydroxy vitamin D [1,25(OH)2D] prevents foam cell formation during macrophage differentiation by suppressing ER stress. However, it is unknown whether suppression of ER stress by 1,25(OH)2D decreases monocyte infiltration and reverses atherogenic cholesterol metabolism in previously differentiated, vitamin D-deplete macrophages. We collected peripheral monocytes from type 2 diabetic patients and differentiated them into macrophages under vitamin D-deplete or 1,25(OH)2D-supplemented conditions. 1,25(OH)2D supplementation suppressed macrophage migration in response to MCP-1 and mRNA expression of chemokine (C-C motif) receptor 2 (CCR2), the MCP-1 receptor, compared to vitamin D-deplete cells. Furthermore, inhibition of ER stress with phenyl butyric acid resulted in similar effects even in vitamin D-deplete cells, while induction of ER stress with Thapsigargin under 1,25(OH)2D-supplemented conditions increased macrophage migration and CCR2 expression, suggesting that the effects of vitamin D on migration are mediated through ER stress suppression. To determine whether the detrimental pattern of macrophage cholesterol metabolism in vitamin D depletion is reversible, we assessed cholesterol uptake in macrophages differentiated under vitamin D-deplete conditions as described above, then supplemented with 1,25(OH)2D or

  18. The effect of body composition and BMI on 25(OH)D response in vitamin D-supplemented athletes.

    PubMed

    Cassity, Evan P; Redzic, Maja; Teager, Cassidy R; Thomas, D Travis

    2016-10-01

    Fat mass is inversely associated with vitamin D status, and athletes with the most adipose tissue may have the greatest risk for insufficient (25(OH)D 20-32 ng mL(-1)) or deficient (25(OH)D < 20 ng ml(-1)) status. The effects of fat and lean mass on 25(OH)D change in response to vitamin D supplementation have yet to be elucidated in athletes. In addition, vitamin D has a known role in bone health yet a link between short-term changes in 25(OH)D and bone turnover in indoor athletes have not yet been described. Thirty-two collegiate swimmers and divers (19 male, 13 female; 19 (1) years) participated in a 6-month randomized controlled trial and consumed either 4000 IU d(-1) of vitamin D3 (n = 19) or placebo (PLA; n = 13). Anthropometry and blood collection of 25(OH)D, bone-specific alkaline phosphatase (B-ALP) and N-terminal telopeptide (NTx) occurred at three time points. Dual-energy X-ray absorptiometry measured body composition analysis at baseline and endpoint. In the vitamin D group, BMI was negatively correlated with 6-month 25(OH)D change (R = -0.496; P = .03) and a stronger predictor of 25(OH)D change (P = .04) than ultraviolet B exposure and fat mass change. Athletes in the high bone turnover group showed significantly greater losses of 25(OH)D over 6-months compared to athletes in the low bone turnover group (P = .03). These results suggest athletes within the normal BMI category experience a diminished response to 4000 IU d(-1) of vitamin D3 supplementation, and periods of high bone turnover may be an additional risk factor for developing compromised vitamin D status in athletes.

  19. The effect of body composition and BMI on 25(OH)D response in vitamin D-supplemented athletes

    PubMed Central

    CASSITY, EVAN P.; REDZIC, MAJA; TEAGER, CASSIDY R.; THOMAS, D. TRAVIS

    2016-01-01

    Fat mass is inversely associated with vitamin D status, and athletes with the most adipose tissue may have the greatest risk for insufficient (25(OH)D 20–32 ng mL−1) or deficient (25(OH)D < 20 ng ml−1) status. The effects of fat and lean mass on 25 (OH)D change in response to vitamin D supplementation have yet to be elucidated in athletes. In addition, vitamin D has a known role in bone health yet a link between short-term changes in 25(OH)D and bone turnover in indoor athletes have not yet been described. Thirty-two collegiate swimmers and divers (19 male, 13 female; 19 (1) years) participated in a 6-month randomized controlled trial and consumed either 4000 IU d−1 of vitamin D3 (n = 19) or placebo (PLA; n = 13). Anthropometry and blood collection of 25(OH)D, bone-specific alkaline phosphatase (B-ALP) and N-terminal telopeptide (NTx) occurred at three time points. Dual-energy X-ray absorptiometry measured body composition analysis at baseline and endpoint. In the vitamin D group, BMI was negatively correlated with 6-month 25(OH)D change (R =−0.496; P = .03) and a stronger predictor of 25(OH)D change (P = .04) than ultraviolet B exposure and fat mass change.Athletes in the high bone turnover group showed significantly greater losses of 25(OH)D over 6-months compared to athletes in the low bone turnover group (P = .03). These results suggest athletes within the normal BMI category experience a diminished response to 4000 IU d−1 of vitamin D3 supplementation, and periods of high bone turnover may be an additional risk factor for developing compromised vitamin D status in athletes. PMID:26698109

  20. Effect of supplementation with vitamin D2-enhanced mushrooms on vitamin D status in healthy adults.

    PubMed

    Stepien, Magdalena; O'Mahony, Louise; O'Sullivan, Aifric; Collier, John; Fraser, William D; Gibney, Michael J; Nugent, Anne P; Brennan, Lorraine

    2013-01-01

    Vitamin D deficiency is emerging worldwide and many studies now suggest its role in the development of several chronic diseases. Due to the low level of vitamin D naturally occurring in food there is a need for supplementation and use of vitamin D-enhanced products. The aim of the present study was to determine if daily consumption of vitamin D2-enhanced mushrooms increased vitamin D status in free-living healthy adults or affected markers of the metabolic syndrome. A total of ninety volunteers (aged 40-65 years) were randomly assigned to one of two 4-week studies: mushroom study (15 µg vitamin D2 or placebo mushroom powder) and capsule study (15 µg vitamin D3 or placebo capsules). Consumption of vitamin D2-enhanced mushrooms increased serum 25-hydroxyvitamin D2 (25(OH)D2) by 128 % from baseline (3·9 (sd 1·9) nmol/l; P < 0·05). Serum 25(OH)D3 increased significantly in the vitamin D3 capsule group (a 55 % increase from a baseline of 44.0 (sd 17·1) nmol/l; P < 0·05). Vitamin D status (25(OH)D) was affected only in the vitamin D3 group. Plasminogen activator inhibitor-1 was lowered by vitamin D2 intake. Vitamin D2 from enhanced mushrooms was bioavailable and increased serum 25(OH)D2 concentration with no significant effect on 25(OH)D3 or total 25(OH)D.

  1. 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

    USDA-ARS?s Scientific Manuscript database

    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...

  2. 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

  3. Performance characteristics of the VIDAS® 25-OH Vitamin D Total assay - comparison with four immunoassays and two liquid chromatography-tandem mass spectrometry methods in a multicentric study.

    PubMed

    Moreau, Emmanuel; Bächer, Silvia; Mery, Sophie; Le Goff, Caroline; Piga, Nadia; Vogeser, Michael; Hausmann, Michael; Cavalier, Etienne

    2016-01-01

    The study was conducted to evaluate the analytical and clinical performance of the VIDAS® 25-OH Vitamin D Total assay. The clinical performance of the assay was compared with four other immunoassays against the results of two different liquid chromatography/mass spectrometry methods (LC-MS/MS) standardized to NIST reference materials. VIDAS® 25-OH Vitamin D Total assay precision, linearity, detection limits and sample matrix comparison were assessed following CLSI guidelines. For method comparison, a total of 150 serum samples ranging from 7 to 92 ng/mL were analyzed by all the methods. Correlation was studied using Passing-Bablok regression and Bland-Altman analysis. The concordance correlation coefficient (CCC) was calculated to evaluate agreement between immunoassays and the reference LC-MS/MS method. In addition, samples containing endogenous 25(OH)D2 were used to assess each immunoassay's ability to detect this analyte. Pregnancy and hemodialysis samples were used to the study the effect of vitamin D binding protein (DBP) concentration over VIDAS® assay performance. The VIDAS® 25-OH Vitamin D Total assay showed excellent correlation to the LC-MS/MS results (y=1.01x+0.22 ng/mL, r=0.93), as obtained from two different sites and distinct LC-MS/MS methods. The limit of quantification was determined at 8.1 ng/mL. Cross-reactivity for 25(OH)D2 was over 80%. At concentrations of 10.5, 26 and 65.1 ng/mL, within-run CVs were 7.9%, 3.6% and 1.7%, while total CVs (between runs, calibrations, lots and instruments) were 16.0%, 4.5% and 2.8%. The VIDAS® performance was not influenced by altered DBP levels, though under-recovery of 25(OH)D as compared to LC-MS/MS was observed for hemodialysis samples. The VIDAS® 25-OH Vitamin D Total assay is therefore considered suitable for assessment of vitamin D status in clinical routine.

  4. 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

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

    PubMed

    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.

  6. Increased vitamin D-binding protein and decreased free 25(OH)D in obese women of reproductive age.

    PubMed

    Karlsson, Therese; Osmancevic, Amra; Jansson, Nina; Hulthén, Lena; Holmäng, Agneta; Larsson, Ingrid

    2014-02-01

    Obese subjects have lower circulating 25-hydroxyvitamin D (25(OH)D) than normal-weight subjects. Knowledge is scarce regarding differences in vitamin D-binding protein (DBP), free 25(OH)D, and intake of vitamin D between normal-weight and obese subjects. The purpose of this study was to examine intake and vitamin D status in obese compared with normal-weight women. Between September 2009 and October 2011, 43 obese and 43 normal-weight women, 22-45 years of age, mean BMI of 39.1 ± 4.6 and 21.6 ± 1.8 kg/m(2), respectively, were recruited in the western Sweden region (latitude 57°N). Blood samples, data regarding diet, and sun exposure were collected. DBP concentrations were 320 ± 121 and 266 ± 104 μg/mL (P = 0.02) in obese and normal-weight women, respectively. Calculated free 25(OH)D was 13.3 ± 5.5 (obese) and 23.7 ± 10.7 (normal-weight) (P < 0.001). The obese women had a 20.1 nmol/L lower mean 25(HO)D concentration compared to normal-weight women (P < 0.001). 56 % of obese women and 12 % of normal-weight women had 25(OH)D concentrations ≤50 nmol/L. There was no statistically significant difference in total vitamin D intake between the groups. 39 % of the women had a total vitamin D intake <7.5 μg/day, the current national recommendation for vitamin D in Sweden. Obese women had higher DBP concentrations compared with normal-weight women and lower free 25(OH)D. The obese women were more likely to have 25(OH)D concentrations that could be considered suboptimal. Vitamin D intake was generally low in normal-weight and obese women of childbearing age.

  7. Influence of Various Factors on Circulating 25(OH) Vitamin D Concentrations in Dogs with Cancer and Healthy Dogs.

    PubMed

    Weidner, N; Woods, J P; Conlon, P; Meckling, K A; Atkinson, J L; Bayle, J; Makowski, A J; Horst, R L; Verbrugghe, A

    2017-09-23

    Low blood 25-hydroxyvitamin D (25(OH)D) concentrations have been associated with cancer in dogs. Little research has examined what other factors may affect 25(OH)D concentrations. (1) To determine whether the presence of cancer (lymphoma, osteosarcoma, or mast cell tumor [MCT]) in dogs is associated with plasma 25(OH)D concentrations and (2) identify other factors related to plasma 25(OH)D concentrations in dogs. Dogs newly diagnosed with osteosarcoma (n = 21), lymphoma (n = 27), and MCT (n = 21) presented to a tertiary referral oncology center, and healthy, client-owned dogs (n = 23). An observational study design was used. Dietary vitamin D intake, sex, age, body condition score (BCS), muscle condition score (MCS), and plasma concentrations of 25(OH)D, 24,25-dihydroxyvitamin D (24,25(OH)2 D) (a marker of CYP24A1 activity), as well as ionized calcium (ICa), parathyroid hormone, and parathyroid hormone-related protein concentrations were measured. An analysis of covariance was used to model plasma 25(OH)D concentrations. Cancer type (P = 0.004), plasma 24,25(OH)2 D concentrations (P < 0.001), and plasma ICa concentrations (P = 0.047) had significant effects on plasma 25(OH)D concentrations. Effects of age, sex, body weight, BCS, MCS, and plasma PTH concentrations were not identified. A significant interaction between ICa and cancer was found (P = 0.005). Plasma 25(OH)D concentrations increased as ICa concentrations increased in dogs with cancer, whereas plasma 25(OH)D concentrations decreased as ICa concentrations increased in healthy dogs. Results support a relationship between cancer and altered vitamin D metabolism in dogs, mediated by plasma ICa concentrations. The CYP24A1 activity and plasma ICa should be measured in studies examining plasma 25(OH)D concentrations in dogs. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  8. Serum 25-OH vitamin D levels in systemic sclerosis: analysis of 140 patients and review of the literature.

    PubMed

    Giuggioli, Dilia; Colaci, M; Cassone, G; Fallahi, P; Lumetti, F; Spinella, A; Campomori, F; Manfredi, A; Manzini, C U; Antonelli, A; Ferri, C

    2017-03-01

    Hypovitaminosis D is increasingly reported in autoimmune diseases. We investigated the 25-OH-vitamin D (25-OH-vitD) levels in systemic sclerosis (SSc) patients, in correlation with disease's features. We measured the 25-OH-vitD serum levels in 140 consecutive patients (F/M 126/15; mean age 61 ± 15.1 years), 91 without (group A) and 49 with (group B) 25-OH-cholecalciferol supplementation. Patients of group A invariably showed low 25-OH-vitD levels (9.8 ± 4.1 ng/ml vs. 26 ± 8.1 ng/ml of group B); in particular, 88/91 (97%) patients showed vitamin D deficiency (<20 ng/ml), with very low vitamin D levels (<10 ng/ml) in 40 (44%) subjects. Only 15/49 (30.6%) patients of group B reached normal levels of 25-OH-vitD (≥30 ng/ml), whereas vitamin D deficiency persisted in 12/49 (24.5%) individuals. Parathormone levels inversely correlated with 25-OH-vitD (r = -0.3, p < 0.0001). Of interest, hypovitaminosis D was statistically associated with autoimmune thyroiditis (p = 0.008), while calcinosis was more frequently observed in patients of group A (p = 0.057). Moreover, we found significantly higher percentage of serum anticentromere antibodies in group B patients with 25-OH-vitD level ≥30 ng/ml (8/15 vs. 6/34; p = 0.017). In literature, hypovitaminosis D is very frequent in SSc patients. An association with disease duration, calcinosis, or severity of pulmonary involvement was occasionally recognized. Hypovitaminosis D is very frequent in SSc and severe in a relevant percentage of patients; furthermore, less than one third of supplemented subjects reached normal levels of 25-OH-vitD. The evaluation of 25-OH-vitD levels should be included in the routine clinical work-up of SSc. The above findings expand previous observations and may stimulate further investigations.

  9. Suboptimal effect of different vitamin D3 supplementations and doses adapted to baseline serum 25(OH)D on achieved 25(OH)D levels in patients with a recent fracture: a prospective observational study.

    PubMed

    Shab-Bidar, Sakineh; Bours, Sandrine P G; Geusens, Piet P M M; van der Velde, Robert Y; Janssen, Marcel J W; van den Bergh, Joop P W

    2013-11-01

    Guidelines on the need for dose adaptation of vitamin D3 supplementation according to baseline serum 25(OH)D are inconclusive. The effects of increasing doses of vitamin D3 at lower baseline serum 25(OH)D values on the serum 25(OH)D after 4.2 and 11 months were determined in an observational study. A prospective observational study. Out of 1481 consecutive women and men with a recent clinical fracture, 707 had a baseline 25(OH)D level <50 nmol/l and were supplemented with increasing doses of vitamin D3 (400, 800, 1700, and ≥3500 IU/day) according to the lower baseline 25(OH)D. Final analysis was restricted to the 221 participants who had full follow-up data available for 11 months. Serum 25(OH)D ≥50 nmol/l was achieved in 57-76% of patients after 4.2 months and in 73-79% after 11 months. These percentages were similar for all doses (P=0.06 and P=0.91 respectively). The mean achieved 25(OH)D was similar for all dose groups (56.1-64.0 nmol/l after 4.2 months and 60.2-76.3 nmol/l after 11 months). With multivariate analysis, the increase in 25(OH)D (17±32.0 after 4.2 months and 24.3±34.0 nmol/l after 11 months) was dependent on the baseline 25(OH)D (P<0.001), not on supplementation dose, season, age, BMI, or gender. The increase in serum 25(OH)D was significantly larger with higher vitamin D3 supplementation doses. However, this dose-effect response was mainly explained by the baseline 25(OH)D, not the supplementation dose, with a greater magnitude of response at lower baseline 25(OH)D concentrations. In 21-27% of patients, serum 25(OH)D3 levels did not reach 50 nmol/l after 11 months, at any dose. Further studies are needed to identify possible causes of suboptimal response such as non-compliance, undiagnosed malabsorption syndromes, or variability in cholecalciferol content of the vitamin D supplements.

  10. Induction of CFTR gene expression by 1,25(OH)2 vitamin D3, 25OH vitamin D3, and vitamin D3 in cultured human airway epithelial cells and in mouse airways.

    PubMed

    DiFranco, Kristina M; Mulligan, Jennifer K; Sumal, Aman S; Diamond, Gill

    2017-01-24

    Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which often leads to protein misfolding and no CFTR surface localization. This then leads to chronic airway infections, inflammation, and tissue damage. Although vitamin D has been explored as a therapy to treat CF due to its antimicrobial-inducing and anti-inflammatory properties, the effect of 1,25-dihydroxyvitamin D3 (1α,25(OH)2D3) on CFTR directly has not been studied. We treated cultured healthy and diseased bronchial epithelial cells (BEC) with 10nM 1α,25(OH)2D3 for 6 and 24h and found that 1α,25(OH)2D3 increases both mRNA and protein CFTR levels using RT-qPCR, flow cytometry and fluorescence immunohistochemistry. Treatment of CF cells with 10nM 1α,25(OH)2D3 led to an increase in both total and surface CFTR expression, suggesting 1α,25(OH)2D3 could be used to increase properly localized CFTR in airway cells. To determine if BEC could convert the more clinically relevant cholecalciferol to 25OHD3, cultured non-CF and CF BECs were treated with a range of cholecalciferol concentrations, and 25OHD3 levels were quantified by ELISA. We found that 25OHD3 levels increased in a concentration-dependent manner. Treatment of BEC with 10μM cholecalciferol led to increases in both CYP24A1 and CFTR mRNA levels, even when added to the apical surface of cells grown in an air-liquid interface, suggesting that topical administration of vitamin D could be used therapeutically. To demonstrate this in vivo, we intranasally delivered 1μM 1α,25(OH)2D3 into mice. After 6h, we observed induction of both Cyp24A1 and CFTR expression in the tracheas of treated mice. The major findings of this study are that vitamin D can be converted to the active form when topically administered to the airway, and this could be used to increase CFTR levels in patients with CF. This could potentially be useful as an adjunctive therapy, together with

  11. Vitamin D, serum 25(OH)D, LL-37 and polymorphisms in a Canadian First Nation population with endemic tuberculosis

    PubMed Central

    Larcombe, Linda; Mookherjee, Neeloffer; Slater, Joyce; Slivinski, Caroline; Dantouze, Joe; Singer, Matthew; Whaley, Chris; Denechezhe, Lizette; Matyas, Sara; Decter, Kate; Turner-Brannen, Emily; Ramsey, Clare; Nickerson, Peter; Orr, Pamela

    2015-01-01

    Background Canadian First Nation populations have experienced endemic and epidemic tuberculosis (TB) for decades. Vitamin D–mediated induction of the host defence peptide LL-37 is known to enhance control of pathogens such as Mycobacterium tuberculosis. Objective Evaluate associations between serum levels of 25-hydroxy vitamin D (25(OH)D) and LL-37, in adult Dene First Nation participants (N = 34) and assess correlations with single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) and vitamin D binding protein (VDBP). Design Venous blood was collected from all participants at baseline (winter and summer) and in conjunction with taking vitamin D supplements (1,000 IU/day) (winter and summer). Samples were analysed using ELISA for concentrations of vitamin D and LL-37, and SNPs in the VDR and VDBP regions were genotyped. Results Circulating levels of 25(OH)D were not altered by vitamin D supplementation, but LL-37 levels were significantly decreased. VDBP and VDR SNPs did not correlate with serum concentrations of 25(OH)D, but LL-37 levels significantly decreased in individuals with VDBP D432E T/G and T/T, and with VDR SNP Bsm1 T/T genotypes. Conclusions Our findings suggest that vitamin D supplementation may not be beneficial as an intervention to boost innate immune resistance to M. tuberculosis in the Dene population. PMID:26294193

  12. Association between 25(OH)-vitamin D and testosterone levels: Evidence from men with chronic spinal cord injury.

    PubMed

    Barbonetti, Arcangelo; Vassallo, Maria Rosaria C; Felzani, Giorgio; Francavilla, Sandro; Francavilla, Felice

    2016-05-01

    As an independent linear association between 25-hydroxyvitamin D (25(OH)D) and testosterone levels is controversial, this study aimed to explore this topic in men with chronic spinal cord injury (SCI), who exhibit a high prevalence of both androgen and vitamin D deficiency. Forty-nine men with chronic SCI consecutively admitted to a rehabilitation program underwent clinical/biochemical evaluations. Deficiency of 25(OH)D (<20 ng/mL) was found in 36 patients (73.5%). They exhibited significantly lower total testosterone and free testosterone levels, higher parathyroid hormone (PTH) and HOMA-IR, a poorer functional independence degree, and were engaged in poorer weekly leisure time physical activity (LTPA). Significant correlates of 25(OH)D levels were: total testosterone, free testosterone, PTH, functional independence degree and weekly LTPA. At the linear regression models, lower 25(OH)D levels were associated with both lower total and free testosterone after adjustment for age, smoking, alcohol consumption, comorbidities and HOMA-IR. However, after full adjustment, also including functional independence degree, BMI and LTPA, only the association of lower 25(OH)D with lower free testosterone was still significant. In men with SCI, 25(OH)D correlates with total and free testosterone and exhibits an independent linear association with free testosterone. Regardless of this independent link, hypovitaminosis D and androgen deficiency are markers of poor health, sharing common risk factors to take into account in the rehabilitative approach to patients with SCI.

  13. Women with recurrent spontaneous abortion have decreased 25(OH) vitamin D and VDR at the fetal-maternal interface.

    PubMed

    Li, N; Wu, H M; Hang, F; Zhang, Y S; Li, M J

    2017-09-12

    Immunological mechanisms have been proposed to underlie the pathogenesis of recurrent spontaneous abortion (RSA). Vitamin D has a potent immunomodulatory effect, which may affect pregnancy outcome. The objective of this study was to investigate 25-hydroxyvitamin D [25(OH) D] concentration and vitamin D receptor (VDR) expression in the decidual tissues of RSA patients. Thirty women with RSA (RSA group) and thirty women undergoing elective abortion (control group) were recruited during 2016 from gynecology outpatient clinics. We measured 25(OH) D, interleukin (IL)-17, IL-23, transforming growth factor β (TGF-β), VDR and 1-α-hydroxylase (CYP27B1) in decidual tissues collected during the abortion procedure. In the RSA group, 25(OH) D and TGF-β were significantly decreased while IL-17 and IL-23 were significantly increased compared with the control group. VDR expression was significantly decreased in the RSA group compared with the control group. Logistic regression analysis showed a significant negative correlation between 25(OH) D in decidual tissues and RSA. These results indicated that vitamin D concentrations in the decidua are associated with inflammatory cytokine production, suggesting that vitamin D and VDR may play a role in the etiology of RSA.

  14. Sequential hydroxylation of vitamin D2 by a genetically engineered CYP105A1.

    PubMed

    Hayashi, Keiko; Yasuda, Kaori; Yogo, Yuya; Takita, Teisuke; Yasukawa, Kiyoshi; Ohta, Miho; Kamakura, Masaki; Ikushiro, Shinichi; Sakaki, Toshiyuki

    2016-05-13

    Our previous studies revealed that the double variants of CYP105A1- R73A/R84A and R73V/R84A-show high levels of activity with respect to conversion of vitamin D3 to its biologically active form, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3). In this study, we found that both the double variants were also capable of converting vitamin D2 to its active form, that is, 1α,25-dihydroxyvitamin D2 (1α,25(OH)2D2), via 25(OH)D2, whereas its 1α-hydroxylation activity toward 25(OH)D2 was much lower than that toward 25(OH)D3. Comparison of the wild type and the double variants revealed that the amino acid substitutions remarkably enhanced both 25- and 26-hydroxylation activity toward vitamin D2. After 25-hydroxylation of vitamin D2, further hydroxylation at C26 may occur frequently without the release of 25(OH)D2 from the substrate-binding pocket. Thus, the double variants of CYP105A1 are quite useful to produce 25,26(OH)2D2 that is one of the metabolites of vitamin D2 detected in human serum. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Seasonal variations of 25-OH vitamin D serum levels are associated with clinical disease activity in multiple sclerosis patients.

    PubMed

    Hartl, Christina; Obermeier, Viola; Gerdes, Lisa Ann; Brügel, Mathias; von Kries, Rüdiger; Kümpfel, Tania

    2017-04-15

    Low 25-hydroxy vitamin D (25-[OH]-D) serum concentrations have been associated with higher disease activity in multiple sclerosis (MS) patients. In a large cross-sectional study we assessed the vitamin D status in MS patients in relation to seasonality and relapse rate. 415 MS-patients (355 relapsing-remitting MS and 60 secondary-progressive, 282 female, mean age 39.1years) of whom 25-(OH)-D serum concentrations were determined at visits between 2010 and 2013 were included in the study. All clinical data including relapse at visit and expanded disability status scale were recorded in a standardized manner by an experienced neurologist. Seasonal variations of 25-(OH)-D serum concentrations were modelled by sinusoidal regression and seasonal variability in the prevalence of relapse by cubic regression. The mean 25-(OH)-D serum concentration was 24.8ng/ml (range 8.3-140ng/ml) with peak levels of 32.2ng/ml in July/August and nadir in January/February (17.2ng/ml). The lowest modelled prevalence of relapse was in September/October (28%) and the highest modelled prevalence in March/April (47%). The nadir of 25-(OH)-D serum concentrations preceded the peak in prevalence of relapses by two months. In summary, seasonal variation of 25-(OH)-D serum levels were inversely associated with clinical disease activity in MS patients. Future studies should investigate whether vitamin D supplementation in MS patients may decrease the seasonal risk for MS relapses.

  16. Automated measurement of 25-OH Vitamin D on the LUMIPULSE(®) G1200: analytical verification and method comparison.

    PubMed

    Parra, Marina; Foj, Laura; Filella, Xavier

    2016-07-01

    Because of its potential value in several pathologies, clinical interest in 25-hydroxy Vitamin D (25OH-D) is increasing. However, the standardisation of assays remains a significant problem. Our aim was to evaluate the performance of the novel Lumipulse G 25-OH Vitamin D assay (Fujirebio), comparing results with the Liaison (Diasorin) method. Analytical verification of the Lumipulse G 25-OH Vitamin D assay was performed. Both methods were compared using sera from 226 patients, including 111 patients with chronic renal failure (39 on haemodialysis) and 115 patients without renal failure. In addition, clinical concordance between assays was assessed. For Lumipulse G 25-OH Vitamin D assay, the limit of detection was 0.3 ng/mL, and the limit of quantification was 2.5 ng/mL with a 9.7% of coefficient of variation. Intra-and inter-assay coefficients of variation were <2.3 and <1.8% (25.4-50.0 ng/mL), respectively. Dilution linearity was in the range of 4.5-144.5 ng/mL. Method comparison resulted in a mean difference of -6.5% (95% CI from -8.8 to -4.1) for all samples between Liaison and Lumipulse G. Clinical concordance assessed by Kappa Index was 0.66. Lumipulse G 25-OH Vitamin D showed a good clinical concordance with the Liaison assay, although overall results measured in Lumipulse were higher by an average of 6.5%.

  17. Seasonal variation of serum alpha- and beta-cryptoxanthin and 25-OH-vitamin D(3) in women with osteoporosis.

    PubMed

    Granado-Lorencio, F; Olmedilla-Alonso, B; Herrero-Barbudo, C; Blanco-Navarro, I; Pérez-Sacristán, B

    2008-05-01

    beta-Cryptoxanthin displays a unique anabolic effect on bone calcification. In women with osteoporosis, serum beta-cryptoxanthin and 25-OH-vitamin D(3) showed a weak but significant correlation and exhibited a complementary seasonal distribution. The potential role of beta-cryptoxanthin as a nutritional approach to improving bone health deserves further evaluation. Dietary intake and serum levels of beta-cryptoxanthin have been inversely related to different bone and joint disorders and in vitro and animal studies have shown that beta-cryptoxanthin displays a unique anabolic effect on bone calcification. Due to the emerging role of beta-cryptoxanthin in bone biology, we aimed to assess the serum distribution and variability of beta-cryptoxanthin and their potential relation to 25-OH-vitamin D(3) in women with osteoporosis. Serum concentrations of alpha- and beta-cryptoxanthin and 25-OH- D(3) in women with osteoporosis (N = 644) were analyzed using a quality-controlled high-performance liquid chromatography (HPLC) method. Overall, significant seasonal variations were found for the three analytes and inter-individual variation was also high (60-73%). beta-cryptoxanthin and 25-OH-vitamin D(3) exhibited a marked complementary seasonal distribution in serum, with vitamin D displaying the highest values in summer and beta-cryptoxanthin in winter. Given the anabolic effect of beta-cryptoxanthin on bone calcification and its complementary seasonal distribution with respect to 25-OH-vitamin D(3), the potential role of beta-cryptoxanthin as a sustainable nutritional approach to improving bone health deserves to be further evaluated.

  18. Vitamin D-binding protein, vitamin D status and serum bioavailable 25(OH)D of young Asian Indian males working in outdoor and indoor environments.

    PubMed

    Goswami, Ravinder; Saha, Soma; Sreenivas, Vishnubhatla; Singh, Namrata; Lakshmy, Ramakrishnan

    2017-03-01

    Urban Asian Indians generally have low serum 25(OH)D. Information on serum bioavailable 25(OH)D and the effect of prolonged sun-exposure in them is not known. We assessed serum 25(OH)D and bioavailable 25(OH)D in males with varying durations of sun-exposure in Delhi during August-September. Serum 25(OH)D, vitamin D-binding protein (DBP), bioavailable 25(OH)D, free 25(OH)D index, iPTH, ionized calcium and sun-index were assessed in outdoor, mixed outdoor-indoor and indoor workers (n = 88, 32 and 74, respectively). The mean sun-index (12.0 ± 6.25, 4.3 ± 2.20 and 0.7 ± 0.62, respectively; P < 0.001) was highest outdoors and lowest indoors. Serum 25(OH)D (29.0 ± 8.61, 19.1 ± 5.73 and 10.9 ± 4.19 ng/ml, respectively; P < 0.001), bioavailable 25(OH)D and free 25(OH)D index were maximum in outdoor workers followed by mixed-exposure and indoor workers. Their mean serum DBP levels (241.2 ± 88.77, 239.3 ± 83.40 and 216.6 ± 63.93 µg/ml, respectively; P = 0.12) were comparable. Mean serum iPTH was significantly lower in outdoor than indoor workers and showed inverse correlations with serum 25(OH)D, bioavailable 25(OH)D and free 25(OH)D index (r = -0.401, -0.269 and -0.236, respectively; P < 0.001 in all). Daily dietary-calorie intake was higher and calcium lower in outdoor than indoor workers. On regression analysis, sun-exposure was the only significant variable, increasing serum 25(OH)D by 2.03 ng/ml per hour of sun-exposure (95 % confidence interval 1.77-2.28; P < 0.001). Outdoor workers with prolonged sun-exposure were vitamin D-sufficient, with higher serum bioavailable 25(OH)D than the indoor workers during summer. Use of serum DBP levels did not affect the interpretation of their vitamin D status.

  19. Colonic transcriptional response to 1α,25(OH)2 vitamin D3 in African- and European-Americans.

    PubMed

    Alleyne, Dereck; Witonsky, David B; Mapes, Brandon; Nakagome, Shigeki; Sommars, Meredith; Hong, Ellie; Muckala, Katy A; Di Rienzo, Anna; Kupfer, Sonia S

    2017-04-01

    Colorectal cancer (CRC) is a significant health burden especially among African Americans (AA). Epidemiological studies have correlated low serum vitamin D with CRC risk, and, while hypovitaminosis D is more common and more severe in AA, the mechanisms by which vitamin D modulates CRC risk and how these differ by race are not well understood. Active vitamin D (1α,25(OH)2D3) has chemoprotective effects primarily through transcriptional regulation of target genes in the colon. We hypothesized that transcriptional response to 1α,25(OH)2D3 differs between AA and European Americans (EA) irrespective of serum vitamin D and that regulatory variants could impact transcriptional response. We treated ex vivo colon cultures from 34 healthy subjects (16 AA and 18 EA) with 0.1μM 1α,25(OH)2D3 or vehicle control for 6h and performed genome-wide transcriptional profiling. We found 8 genes with significant differences in transcriptional response to 1α,25(OH)2D3 between AA and EA with definitive replication of inter-ethnic differences for uridine phosphorylase 1 (UPP1) and zinc finger-SWIM containing 4 (ZSWIM4). We performed expression quantitative trait loci (eQTL) mapping and identified response cis-eQTLs for ZSWIM4 as well as for histone deacetylase 3 (HDAC3), the latter of which showed a trend toward significant inter-ethnic differences in transcriptional response. Allele frequency differences of eQTLs for ZSWIM4 and HDAC3 accounted for observed transcriptional differences between populations. Taken together, our results demonstrate that transcriptional response to 1α,25(OH)2D3 differs between AA and EA independent of serum 25(OH)D levels. We provide evidence in support of a genetic regulatory mechanism underlying transcriptional differences between populations for ZSWIM4 and HDAC3. Further work is needed to elucidate how response eQTLs modify vitamin D response and whether genotype and/or transcriptional response correlate with chemopreventive effects. Relevant biomarkers

  20. The Effect of the Systemic Inflammatory Response on Plasma Vitamin 25 (OH) D Concentrations Adjusted for Albumin

    PubMed Central

    Ghashut, Rawia A.; Talwar, Dinesh; Kinsella, John; Duncan, Andrew; McMillan, Donald C.

    2014-01-01

    Background Plasma 25-hydroxyvitamin D (25(OH) D) deficiencies are associated with several diseases. The magnitude of systemic inflammatory response, as evidenced by C-reactive protein (CRP), is a major factor associated with lower 25(OH)D. Other aspects of the systemic inflammatory response may be important in determining plasma 25 (OH)D concentrations. Aim To examine the relationship between plasma 25(OH)D, CRP and albumin concentrations in two patient cohorts. Methods 5327 patients referred for nutritional assessment and 117 patients with critical illness were examined. Plasma 25 (OH) D concentrations were measured using standard methods. Intra and between assay imprecision was <10%. Result In the large cohort, plasma 25 (OH) D was significantly associated with CRP (rs = −0.113, p<0.001) and albumin (rs = 0.192, p<0.001). 3711 patients had CRP concentrations ≤10 mg/L; with decreasing albumin concentrations ≥35, 25–34 and <25 g/l, median concentrations of 25 (OH) D were significantly lower from 35 to 28 to 14 nmol/l (p<0.001). This decrease was significant when albumin concentrations were reduced between 25–34 g/L (p<0.001) and when albumin <25 g/L (p<0.001). 1271 patients had CRP concentrations between 11–80 mg/L; with decreasing albumin concentrations ≥35, 25–34 and <25 g/l, median concentrations of 25 (OH) D were significantly lower from 31 to 24 to 19 nmol/l (p<0.001). This decrease was significant when albumin concentration were 25–34 g/L (p<0.001) and when albumin <25 g/L (p<0.001). 345 patients had CRP concentrations >80 mg/L; with decreasing albumin concentrations ≥35, 25–34 and <25 g/l, median concentrations of 25 (OH) D were not significantly altered varying from 19 to 23 to 23 nmol/l. Similar relationships were also obtained in the cohort of patients with critical illness. Conclusion Plasma concentrations of 25(OH) D were independently associated with both CRP and albumin and consistent with the systemic inflammatory

  1. Risk in dosing regimens for 25-OH vitamin D supplementation in chronic haemodialysis patients.

    PubMed

    Albalate, M; de la Piedra, C; Ortiz, A; Hernández Pérez, J; Rubert, M; Pérez Garcia, R; Zazo, P; Nieto, L; de Sequera, P; Egido, J

    2012-01-01

    25-OH vitamin D (25-OHvitD) insufficiency or deficiency should be treated in haemodialysis (HD) patients, although the 25-OHvitD target, drug or dosing regimens are unclear. To describe factors associated with 25-OHvitD levels in HD patients and to assess the effect of three dosing regimens to supplement 25-OHvitD (calcifediol) on serum calcium (Ca), phosphate (P), parathyroid hormone (PTH), 25-OHvitD and 1,25-OHvitD. Two hundred and seventeen patients from three HD units were studied. Demographic and biochemical data were collected at baseline. Two different 25-OHvitD assays were used. One hundred and sixty-seven patients were treated with various calcifediol dosing regimens. The same biochemical determinations were repeated after 3 months of treatment. At baseline, 12.9% of patients had 25-OHvitD <10 ng/ml. In multivariate linear regression, the season (lower in winter) and the assay method were determinants of 25-OHvitD concentration. Following calcifediol supplementation, 25-OHvitD, calcium and phosphate increased, while PTH diminished with statistical significance. After treatment, there were positive correlations between 25-OHvitD and Ca (r = 0.28, p < 0.0001) or 1,25-OHvitD (r = 0.75, p < 0.0001) that were not observed in the baseline dataset. High concentrations of post-treatment 25-OHvitD were associated with higher 1,25-OHvitD levels. Calcemia increased more in those treated with concomitant active vitamin D or those having suppressed baseline PTH, while PTH decreased more in those having above-target PTH levels. Standardisation of methods to determine 25-OHvitD blood levels is needed. In HD patients, calcifediol increased 25-OHvitD, calcemia and phosphatemia and lowered PTH. Caution should be exercised with the higher calcifediol dosing regimens, especially in patients with suppressed PTH or on vitamin D receptor activators. Copyright © 2012 S. Karger AG, Basel.

  2. Association between Parathyroid Hormone, 25 (OH) Vitamin D, and Chronic Kidney Disease: A Population-Based Study

    PubMed Central

    Wang, Wei-Hao; Chen, Li-Wei; Sun, Chiao-Yin; Hsu, Heng-Rong; Chien, Rong-Nang

    2017-01-01

    Identification of the accurate risk factor for CKD remains mandatory to combat the high prevalence of diseases. Growing evidence suggests the association of serum vitamin D with diverse health conditions. However, the relationship between vitamin D, intact parathyroid hormone (PTH), and calcium-phosphate metabolism and development of CKD remains controversial. We conduct this cross-sectional observational study to investigate the association between serum 25 (OH) vitamin D, intact PTH, and calcium and phosphate levels with eGFR and albuminuria, as a surrogate marker of CKD, in a community population. A total of 4080 participants were recruited. The mean age was 58.4 ± 13.3 years and 1480 (36.3%) were men. The mean eGFR was 94.1 ± 26.3 mL/min/1.73 m2. The prevalence of CKD was 19.8%. Serum 25 (OH) vitamin D and log intact PTH levels were inversely correlated with eGFR but positively correlated with log albuminuria. Logistic regression analysis identified the log intact PTH as an independent factor associated with eGFR ≤ 60 mL/min/1.73 m2 and proteinuria. This association was consistent when serum intact PTH was analyzed as continuous as well as categorical variables (as hyperparathyroidism). The relationship remains significant using resampling subset analysis with comparable baseline characteristics and adjustment for 25 (OH) vitamin D, calcium, and phosphate levels. This finding warranted further research to clarify the causal relationship of PTH/25 (OH) vitamin D with the risk of CKD in the general population. PMID:28367447

  3. Maternal and cord blood 25(OH)-vitamin D concentrations in relation to child development and behavior

    PubMed Central

    Keim, Sarah A.; Bodnar, Lisa M.; Klebanoff, Mark A.

    2014-01-01

    Background Animal studies have linked in utero vitamin D exposure to various aspects of offspring brain development. Limited research has translated these findings to humans, and none have employed cord blood to measure exposure late in gestation. Methods Our objective was to examine associations between maternal 25(OH)D measured at ≤26 weeks’ gestation or cord blood 25(OH)D and offspring global development, IQ, achievement, and behavior in the U.S. Collaborative Perinatal Project (1959–73). This was a secondary analysis of data from a case-cohort study, with 3896 women and children who participated in at least one outcome assessment. Psychologists assessed global development at eight months, IQ and behavior at four and seven years, and achievement at seven years. Multiple linear and logistic regression was used to examine associations between 25(OH)D and child outcomes, controlling for maternal education, age, parity, race, maternal BMI, marital status, smoking, gestational age and month of blood draw, and study site. Results Positive associations for many outcomes were greatly attenuated upon adjustment for confounders and were generally null. Only IQ at age 7 was associated with both maternal and cord blood 25(OH)D, but the effect estimates were very small (β for 5 nmol/L increment of maternal 25(OH)D=0.10; 95% CI: 0.00, 0.19). Conclusions We observed very little indication that maternal or cord blood 25(OH)D are associated with cognitive development, achievement and behavior between 8 months and 7 years of age. PMID:24938425

  4. Associations between vitamin D-binding protein isotypes, circulating 25(OH)D levels, and vitamin D metabolite uptake in colon cancer cells.

    PubMed

    Hibler, Elizabeth A; Jacobs, Elizabeth T; Stone, Angelika Dampf; Sardo, Christine L; Galligan, Michael A; Jurutka, Peter W

    2014-04-01

    Vitamin D metabolites have been extensively studied as cancer chemopreventive agents. Gc-globulin (GC) isotypes, based on rs7041 and rs4588 diplotypes, have varying affinities for 1α,25-dihydroxyvitamin D (1,25(OH)2D) and 25-hydroxyvitamin D (25(OH)D), which may affect circulating metabolite concentration as well as delivery at the cellular level. We evaluated associations between GC isotype and circulating vitamin D metabolite concentrations in 403 ursodeoxycholic acid (UDCA) clinical trial participants. Metabolite uptake was evaluated in human colon cancer (HCT-116) cells treated with ethanol vehicle, 1,25(OH)2D, or 25(OH)D, and with plasma from individuals with known GC isotype. Mammalian-2-hybrid and vitamin D-responsive element-based luciferase assays were used to measure the vitamin D receptor pathway activation as a marker for metabolite uptake. Regression analysis demonstrated significantly lower serum 25(OH)D concentration for clinical trial participants with 1F_2, 1S_2, or 2_2 isotypes (P < 0.01) compared with 1S_1S. Consistent with these in vivo observations, cellular data revealed that 25(OH)D uptake varied less by GC isotype only at the higher concentration tested (P = 0.05), while 1,25(OH)2D uptake differed markedly by GC isotype across concentration and assay (P < 0.01). The 1F_1S and 1F_2 isotypes produced the greatest reporter gene induction with 1,25(OH)2D treatment and, while activation varied less with 25(OH)D, the 2_2 isotype demonstrated increased induction at the lower concentration. These results suggest that vitamin D metabolite concentration and delivery to colon cells may vary not only by GC isotype, but also that certain isotypes may more effectively deliver 1,25(OH)2D versus 25(OH)D. Overall, these results may help identify populations at risk for cancer and potential recipients of targeted chemoprevention.

  5. Evaluation of 25(OH) Vitamin D3 with Reference to Magnesium Status and Insulin Resistance in T2DM

    PubMed Central

    Gandhe, Mahendra Bhauraoji; Jain, Keerthi; Gandhe, Swapnali Mahendra

    2013-01-01

    Introduction: Calcium is a recognized second messenger implicated in insulin secretion. Vitamin D (1,25-dihydroxycholecalciferol, Calcitriol) plays a role in calcium metabolism. This explains the indirect role of Vitamin D in insulin secretion and insulin sensitivity. Hence, low Vitamin D levels are implicated in decreased insulin secretion and increased insulin resistance. In this study, we tried to find out the probable association of Vitamin D3, calcium and magnesium with reference to insulin resistance in type 2 diabetes mellitus (T2DM) cases. It is well documented that measurement of circulating 25-Hydroxycholecalciferol {25 (OH)Vitamin D3} is a marker of total Vitamin D status. Methodology: We measured 25(OH) Vitamin D3 levels in thirty T2DM subjects with thirty age and sex matched healthy controls. We estimated Vitamin D status, calcium and magnesium levels in the light of insulin resistance. Insulin resistance was measured by homeostasis model assessment of insulin resistance (HOMA-IR). Results: Twenty five (OH) Vitamin-D3 level was significantly low among T2DM cases (12.29+2.32ng/ml) in comparison to healthy controls (19.55+0.50ng/ml) (p<0.01). The levels of calcium and magnesium were also significantly low in T2DM cases as compared to healthy controls (p<0.01). There was significant negative correlation between Vitamin D status and insulin levels, and insulin resistance (p<0.01). Implication: A significant negative correlation between Vitamin D status and insulin levels suggest that the supplementation of Vitamin D has the potential to increase insulin sensitivity and lower the risk of developing type 2 diabetes mellitus. PMID:24392366

  6. PTH level but not 25 (OH) vitamin D level predicts bone loss rates in the elderly.

    PubMed

    Arabi, A; Baddoura, R; El-Rassi, R; El-Hajj Fuleihan, G

    2012-03-01

    We assessed the impact of calciotropic hormones on bone loss in 195 elderly subjects. After a median follow up of 4 years, parathyroid hormone (PTH) correlated negatively with changes in bone mineral density (BMD) at all skeletal sites. After adjustment for potential predictors of bone loss in the elderly, PTH level alone explained 3% of the variance in BMD changes at the hip. This study assessed the impact of calciotropic hormones on bone loss rates in an elderly population-based cohort of 195 ambulatory men and women, aged 65-85 years and followed up for a median of 4 years. Calcium intake, serum calcium, and phosphorus were assessed at baseline. Serum creatinine was measured at follow up visit. The 25 (OH) vitamin D [25-OHD] and PTH were measured at baseline and at follow up. Bone mass at the lumbar spine, hip, forearm and total body, as well as body composition was measured at baseline and at follow up by dual energy X-ray absorptiometry. Mean 25-OHD level was 14.7 ± 6.4 ng/ml and mean PTH level was 47.9 ± 30.4 pg/ml. Age correlated negatively with percent changes in BMD at all skeletal sites (p < 0.05). Changes in body mass index (BMI) and in body composition correlated positively with BMD changes at all sites, except at the forearm. There was no correlation between 25-OHD and changes in BMD except at the trochanter (r = 0.19, p < 0.008). Conversely, PTH negatively correlated with changes in BMD at all skeletal sites (r = -0.14 to -0.27, p < 0.05). This correlation persisted after adjustment for age, changes in BMI, changes in fat mass and lean mass, serum creatinine, calcium intake, and 25-OHD levels. PTH level alone explained 3% of the variance in BMD changes at all hip subregions. Serum PTH, but not 25-OHD, predicted bone loss rates in the elderly. Thus, it is important to normalize PTH level when correcting hypovitaminosis D in the elderly.

  7. 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

  8. Cestrum diurnum leaf as a source of 1,25(OH)2 Vitamin D3 improves egg shell thickness.

    PubMed

    Chennaiah, S; Qadri, S S Y H; Rao, S V Rama; Shyamsunder, G; Raghuramulu, N

    2004-05-01

    A continuing concern of the poultry industry is the high incidence (12%) of egg losses in the laying house due to poor egg shell quality. Calcium (Ca) homeostasis is a key factor in egg shell formation. The economy of Ca utilisation is under the control of Vitamin D(3), particularly its active metabolite 1,25-dihydroxy cholecalciferol [1,25(OH)(2)D(3)]. Supplementation of 1,25(OH)(2)D(3) has been shown to increase specific gravity, shell thickness and shell weight of the egg. However, commercially available synthetic 1,25(OH)(2)D(3) is very expensive. Earlier studies from our Institute [Phytochemistry 37 (1994) 677] have identified a cheap, natural and rich source of 1,25(OH)(2)D(3) in the leaves of Cestrum diurnum (CD), a member of the Solanaceae family. In this study, CD leaves were explored as a source of 1,25(OH)(2)D(3) in the feed of layer birds to improve the egg shell thickness. Fifteen-week-old white leghorn layers were divided into four treatments of 60 birds each and as follows: (I) normal diet with Vitamin D(3), (II) normal diet with Vitamin D(3) + CD, (III) normal diet without Vitamin D(3) and, (IV) normal diet without Vitamin D(3) + CD powder. CD leaf powder was incorporated in to the feed at 0.3% level. The experimental feeding was continued up to 72 weeks of age of the birds. Weekly food intake and daily egg production were noted throughout the experimental period and the specific gravity of the eggs, feed consumed to lay one egg and egg shell thickness were determined. Incorporation of CD leaves in the feed had the maximal effect on all the parameters studied. The feed consumed to lay one egg was 20 g less than the control group. The specific gravity of the egg was higher by 0.005, than the control egg, indicating a 5% decrease in the breakage of eggs in CD fed chicks. Also there was a significant increase (P < 0.001) in egg shell thickness. The data suggest that incorporation of CD leaf powder in the feed of poultry layers increased the egg shell

  9. 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.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  11. Technical and clinical evaluation of the VITROS® Immunodiagnostic Products 25-OH Vitamin D Total Assay--comparison with marketed automated immunoassays and a liquid chromatography-tandem mass spectrometry method.

    PubMed

    Cavalier, Etienne; Rousselle, Olivier; Ferrante, Nunzio; Carlisi, Agnes; Le Goff, Caroline; Souberbielle, Jean-Claude

    2013-10-01

    The study was conducted to evaluate the technical and clinical performance of the VITROS® Immunodiagnostic Products 25-OH Vitamin D Total Assay, and compare it with the performance of five marketed automated assays and a liquid chromatography/mass spectrometry reference method (LC-MS/MS). Three hundred patient serum samples were used to compare the correlation of the VITROS® 25-OH Vitamin D Total Assay with both the other immunoassays and the LC-MS/MS method, using Passing-Bablok regression and Bland-Altman analyses. Concordance of the diagnosis of vitamin D status was calculated to test the agreement between the different assays. In addition, samples containing vitamin D2 were used to test the assay's ability to detect the D2 form of the vitamin. These results from the VITROS® 25-OH Vitamin D Total Assay generally correlated well with those from most of the marketed immunoassays. Cross-reactivity of the D2 form was calculated as being close to 100%. Additionally, we found substantial variability in performance amongst the various assays, which suggests the need for optimisation and recalibration of commercial methods.

  12. Does low serum 25 OH vitamin D interact with very strenuous physical activity, facilitating development of rhabdomyolysis?

    PubMed

    Conrad, Brandon N; Glueck, Charles J

    2013-10-01

    Vitamin D plays an important and increasingly understood role in muscle health and performance. Vitamin D exhibits a nuclear receptor for transcription interaction and a transmembrane receptor, giving it genomic and non-genomic interactions. Vitamin D receptors have been described that affect muscle function. Vitamin D has also been correlated with muscle performance. Beyond its role in normal muscle function, vitamin D deficiency can interact with statins to produce myalgia-myositis, which can be reversed by normalizing serum vitamin D [7,13]. Exertional rhabdomyolysis may occur in diverse settings including marathons, ice skating, bicycling and swimming. Our hypothesis is that subjects with pre-existing low serum 25OHD are selected out for exertional rhabdomyolysis during strenuous activities. We review exercise induced severe rhabdomyolysis in association with heat stroke with subsequent disseminated intravascular coagulation in a thin, athletic, dark skinned, conditioned young man, occurring in the setting of a 5K race, subsequently found to have severe 25 OH vitamin D deficiency (6 ng/ml, laboratory lower normal limit>30 ng/ml). We suggest that when very low vitamin D is documented, it be normalized before major prolonged exertion. We hypothesize that normalization of vitamin D before heavy exertion could perhaps prevent the severe muscle damage events and sequelae as was the case for this patient. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Notch- and vitamin D signaling in 1,25(OH)2D3-resistant glioblastoma multiforme (GBM) cell lines.

    PubMed

    Reichrath, Sandra; Müller, Cornelia S L; Gleissner, Beate; Pfreundschuh, Michael; Vogt, Thomas; Reichrath, Jörg

    2010-07-01

    Recently, an important role of Notch activation for Ras-induced transformation of glial cells and for glioma growth and survival has been demonstrated. It was concluded that activation of Notch-signaling may represent a new target for glioblastoma multiforme (GBM) therapy. We now analyzed five GBM cell lines (Tx3095, Tx3868, U87, U118, U373) for key components of Notch-signaling pathways (Notch-1, Notch-2, Notch-3, Notch-4, Delta-like 1, Delta-like 3, Delta-like 4, Jagged-1, Jagged-2) using conventional RT-PCR. We found that some components (Notch-1, Notch-2, Notch-4, Jagged-1) were consistently expressed in all cell lines analyzed while, in contrast, other key components of Notch-signaling were differentially expressed. Notch-3 was expressed in three out of five cell lines (in U87, U118 and U373), but was missing in Tx3095 and Tx3868 cells. Jagged-2 was expressed in U87, U373 and Tx3868, but not in U118 or Tx3095 cells. Delta-like 1 and Delta-like 3 were not detected in Tx3905 cells, but in all other cell lines. RNA for Delta-like 4 was only found in U373 and Tx3868 GBM cell lines. Treating GBM cell lines with 1,25(OH)2D3 (10(-6), 10(-8), and 10(-10) M), the biologically active form of vitamin D, did not result in significant dose- or time-dependent antiproliferative effects, indicating that GBM cell lines are resistant against the antiproliferative activity of 1,25(OH)2D3. In vitro treatment of GBM cells with 1,25(OH)2D3 did not result in a modulation of the expression of key components of the Notch-signaling pathway. Treatment with HDAC-inhibitor TSA or DNA-methyltransferase inhibitor 5-aza exerted dose- and time-dependent antiproliferative effects on GBM cell lines. We asked the question whether the resistance against 1,25(OH)2D3 could be restored by co-treatment with TSA or 5-aza. However, combination therapy with 1,25(OH)2D3 and TSA or 5-aza did not result in enhanced antiproliferative effects as compared to treatment with TSA or 5-aza alone. In contrast

  14. Analysis of Changes in Parathyroid Hormone and 25 (OH) Vitamin D Levels with Respect to Age, Gender and Season: A Data Mining Study.

    PubMed

    Serdar, Muhittin A; Batu Can, Başar; Kilercik, Meltem; Durer, Zeynep A; Aksungar, Fehime Benli; Serteser, Mustafa; Coskun, Abdurrahman; Ozpinar, Aysel; Unsal, Ibrahim

    2017-01-01

    25 (OH) vitamin D3 (25(OH)D) and parathyroid hormone (PTH) are important regulators of calcium homeostasis. The aim of this study was to retrospectively determine the cut-off for sufficient 25(OH)D in a four-season region and the influence of age, seasons, and gender on serum 25(OH)D and PTH levels. Laboratory results of 9890 female and 2723 male individuals aged 38.8±22.1 years who had simultaneous measurements of 25(OH)D and PTH were retrospectively analyzed by statistical softwares. Serum 25(OH)D and PTH levels were measured by a mass spectrometry method and by an electrochemiluminescence immunoassay, respectively. Mean serum 25(OH)D levels showed a sinusoidal fluctuation throughout the year and were significantly (p<0.01) higher in summer and autumn. On the other hand, PTH levels were significantly higher (p<0.01) in women and showed an opposite response to seasonal effects relative to 25(OH)D. Lowest levels of 25(OH)D were detected in people aged between 20 and 40 years whereas PTH hormone levels were gradually increasing in response to aging. The significant exponential inverse relationship that was found between PTH and 25(OH)D (PTH=exp(4.12-0.064(*)sqrt(25(OH)D)) (r=-0.325, R- squared=0.105, p<0.001)) suggested that the cut-off for sufficient 25(OH)D should be 75 nmol/L. Our retrospective study based on large data set supports the suitability of the currently accepted clinical cut-off of 75 nmol/L for sufficient 25(OH)D. However, the issue of assessing Vitamin D deficiency remains difficult due to seasonal variations in serum 25(OH)D. Therefore, PTH measurements should complement 25(OH)D results for diagnosing Vitamin D deficiency. It is imperative that seasonally different criteria should be considered in future.

  15. Analysis of Changes in Parathyroid Hormone and 25 (OH) Vitamin D Levels with Respect to Age, Gender and Season: A Data Mining Study

    PubMed Central

    Batu Can, Başar; Kilercik, Meltem; Durer, Zeynep A.; Aksungar, Fehime Benli; Serteser, Mustafa; Coskun, Abdurrahman; Ozpinar, Aysel; Unsal, Ibrahim

    2017-01-01

    Summary Background 25 (OH) vitamin D3 (25(OH)D) and parathyroid hormone (PTH) are important regulators of calcium homeostasis. The aim of this study was to retrospectively determine the cut–off for sufficient 25(OH)D in a four-season region and the influence of age, seasons, and gender on serum 25(OH)D and PTH levels. Methods Laboratory results of 9890 female and 2723 male individuals aged 38.8±22.1 years who had simultaneous measurements of 25(OH)D and PTH were retrospectively analyzed by statistical softwares. Serum 25(OH)D and PTH levels were measured by a mass spectrometry method and by an electrochemiluminescence immunoassay, respectively. Results Mean serum 25(OH)D levels showed a sinusoidal fluctuation throughout the year and were significantly (p<0.01) higher in summer and autumn. On the other hand, PTH levels were significantly higher (p<0.01) in women and showed an opposite response to seasonal effects relative to 25(OH)D. Lowest levels of 25(OH)D were detected in people aged between 20 and 40 years whereas PTH hormone levels were gradually increasing in response to aging. The significant exponential inverse relationship that was found between PTH and 25(OH)D (PTH=exp(4.12–0.064*sqrt(25(OH)D)) (r=–0.325, R– squared=0.105, p<0.001)) suggested that the cut–off for sufficient 25(OH)D should be 75 nmol/L. Conclusions Our retrospective study based on large data set supports the suitability of the currently accepted clinical cut–off of 75 nmol/L for sufficient 25(OH)D. However, the issue of assessing Vitamin D deficiency remains difficult due to seasonal variations in serum 25(OH)D. Therefore, PTH measurements should complement 25(OH)D results for diagnosing Vitamin D deficiency. It is imperative that seasonally different criteria should be considered in future. PMID:28680352

  16. Analytical and clinical evaluation of the new Fujirebio Lumipulse®G non-competitive assay for 25(OH)-vitamin D and three immunoassays for 25(OH)D in healthy subjects, osteoporotic patients, third trimester pregnant women, healthy African subjects, hemodialyzed and intensive care patients.

    PubMed

    Cavalier, Etienne; Lukas, Pierre; Bekaert, Anne-Catherine; Peeters, Stéphanie; Le Goff, Caroline; Yayo, Eric; Delanaye, Pierre; Souberbielle, Jean-Claude

    2016-08-01

    In this study, we provide a short analytical evaluation of the new Fujirebio Lumipulse®G non-competitive immunoassay for 25(OH)D. Clinical performance was compared with three commercial competitive automated immunoassays against a Vitamin D Standardization Program (VDSP)-traceable liquid chromatography-tandem mass spectrometry (LC-MS/MS) in six different clinically relevant populations. Lumipulse®G 25(OH)D precision, measurement uncertainty, recovery, limit of quantification were assessed, as well as 25(OH)D2 and C3-epimer recovery. For method comparison, 250 serum samples obtained in healthy Caucasians and Africans, osteoporotic, hemodialyzed and intensive care patients and 3rd trimester pregnant women were analyzed by all methods. Correlation was studied using Passing-Bablok and Bland-Altman analysis. Concordance correlation coefficient (CCC) was calculated to evaluate agreement between immunoassays and the LC-MS/MS. The Lumipulse®G 25(OH)D assay presented interesting analytical features and showed excellent correlation to the LC-MS/MS results (y=1.00×-1.35 ng/mL), as obtained in healthy Caucasian individuals. In the other special populations, Lumipulse®G presented a concordance with LC-MS/MS which was generally higher than competitors, even if all methods significantly under-recovered 25(OH)D in hemodialyzed patients. Intra-assay CV ranged from 12.1% at 9.6 ng/mL to 2.1% at 103.7 ng/mL and inter-assay CV ranged from 16.2 to 3.7% at the same concentrations, respectively. Measurement uncertainty, with a probability of 95%, were respectively 33.1 and 7.6% at these concentrations. LOQ was found to be at 4.6 ng/mL. Mean (95% CI) 25(OH)D2 revovery was 77% (74-81) and no cross-reactivity was observed with C3-epimer. Fujirebio Lumipulse®G 25-OH Vitamin D Total assay is therefore considered suitable for assessment of vitamin D status in clinical routine.

  17. Vitamin D receptor gene polymorphisms/haplotypes and serum 25(OH)D3 levels in Hashimoto's thyroiditis.

    PubMed

    Giovinazzo, Salvatore; Vicchio, Teresa M; Certo, Rosaria; Alibrandi, Angela; Palmieri, Orazio; Campennì, Alfredo; Cannavò, Salvatore; Trimarchi, Francesco; Ruggeri, Rosaria Maddalena

    2017-02-01

    Vitamin D deficiency and/or reduced function, as per certain polymorphisms of the vitamin D receptor (VDR) gene, have been related to several autoimmune disorders. The present study was aimed to investigate the association of Hashimoto's thyroiditis with vitamin D status and functional polymorphisms (SNPs) of the VDR gene. In this case-control study, 200 euthyroid subjects were enrolled: 100 newly diagnosed HT patients (87 F, 13 M; mean age ± SD 42 ± 15 year) and 100 healthy individuals, matched for age, sex, BMI, and month of blood sampling. Serum 25(OH)D3 was measured by HPLC. The VDR SNPs BsmI, ApaI, and TaqI, in strong linkage disequilibrium with each other, were detected by restriction fragment length polymorphism-PCR. The prevalence of vitamin D deficiency in HT patients was significantly higher than that in the control group (70 vs 18.2 %; p < 0.0001), and median serum 25(OH)D3 level was significantly lower in HT patients than controls (median value: 16.2 vs 37.4 ng/ml; p = 0.026). Moreover, there was a significant inverse correlation between serum 25(OH)D3 and TPOAb concentration (r = -0.669; p = 0.034). Contrarily, the genotype distribution of the studied SNPs was not different in the two groups (BsmI p = 0.783; ApaI p = 0.512; TaqI p = 0.471), as was the allelic frequency [f(B) p = 0.776, f(b) p = 0.887; f(A) p = 0.999, f(a) p = 0.999; f(T) p = 0.617; f(t) p = 0.617]. The present study first investigates newly diagnosed untreated HT and suggests that vitamin D deficiency may contribute to HT development and/or progression, acting as an environmental trigger, while the VDR locus does not appear to be involved in conditioning the genetic susceptibility to the disease, at least in Caucasians.

  18. 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

  19. Fortification of orange juice with vitamin D(2) or vitamin D(3) is as effective as an oral supplement in maintaining vitamin D status in adults.

    PubMed

    Biancuzzo, Rachael M; Young, Azzie; Bibuld, Douglass; Cai, Mona H; Winter, Michael R; Klein, Ellen K; Ameri, Allen; Reitz, Richard; Salameh, Wael; Chen, Tai C; Holick, Michael F

    2010-06-01

    Vitamin D has been added to calcium-fortified orange juice. It is unknown whether vitamin D is as bioavailable from orange juice as it is from supplements. The objective was to compare the bioavailability of vitamin D(2) and vitamin D(3) from orange juice with that from vitamin D(2) and vitamin D(3) supplements. A secondary aim was to determine which form of vitamin D is more bioavailable in orange juice. A randomized, placebo-controlled, double-blind study was conducted in healthy adults aged 18-84 y (15-20/group) who received 1000 IU vitamin D(3), 1000 IU vitamin D(2), or placebo in orange juice or capsule for 11 wk at the end of winter. A total of 64% of subjects began the study deficient in vitamin D (ie, 25-hydroxyvitamin D [25(OH)D]) concentrations <20 ng/mL). Analysis of the area under the curve showed no significant difference in serum 25(OH)D between subjects who consumed vitamin D-fortified orange juice and those who consumed vitamin D supplements (P = 0.084). No significant difference in serum 25(OH)D(3) was observed between subjects who consumed vitamin D(3)-fortified orange juice and vitamin D(3) capsules (P > 0.1). Similarly, no significant difference in serum 25(OH)D(2) was observed between subjects who consumed vitamin D(2)-fortified orange juice and vitamin D(2) capsules (P > 0.1). No significant overall difference in parathyroid hormone concentrations was observed between the groups (P = 0.82). Vitamin D(2) and vitamin D(3) are equally bioavailable in orange juice and capsules.

  20. 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

  1. Comparison of metabolism of vitamins D2 and D3 in children with nutritional rickets.

    PubMed

    Thacher, Tom D; Fischer, Philip R; Obadofin, Michael O; Levine, Michael A; Singh, Ravinder J; Pettifor, John M

    2010-09-01

    Children with calcium-deficiency rickets may have increased vitamin D requirements and respond differently to vitamin D(2) and vitamin D(3). Our objective was to compare the metabolism of vitamins D(2) and D(3) in rachitic and control children. We administered an oral single dose of vitamin D(2) or D(3) of 1.25 mg to 49 Nigerian children--28 with active rickets and 21 healthy controls. The primary outcome measure was the incremental change in vitamin D metabolites. Baseline serum 25-hydroxyvitamin D [25(OH)D] concentrations ranged from 7 to 24 and 15 to 34 ng/mL in rachitic and control children, respectively (p < .001), whereas baseline 1,25-dihydroxyvitamin D [1,25(OH)(2)D] values (mean ± SD) were 224 ± 72 and 121 ± 34 pg/mL, respectively (p < .001), and baseline 24,25-dihydroxyvitamin D [24,25(OH)(2)D] values were 1.13 ± 0.59 and 4.03 ± 1.33 ng/mL, respectively (p < .001). The peak increment in 25(OH)D was on day 3 and was similar with vitamins D(2) and D(3) in children with rickets (29 ± 17 and 25 ± 11 ng/mL, respectively) and in control children (33 ± 13 and 31 ± 16 ng/mL, respectively). 1,25(OH)(2)D rose significantly (p < .001) and similarly (p = .18) on day 3 by 166 ± 80 and 209 ± 83 pg/mL after vitamin D(2) and D(3) administration, respectively, in children with rickets. By contrast, control children had no significant increase in 1,25(OH)(2)D (19 ± 28 and 16 ± 38 pg/mL after vitamin D(2) and D(3) administration, respectively). We conclude that in the short term, vitamins D(2) and D(3) similarly increase serum 25(OH)D concentrations in rachitic and healthy children. A marked increase in 1,25(OH)(2)D in response to vitamin D distinguishes children with putative dietary calcium-deficiency rickets from healthy children, consistent with increased vitamin D requirements in children with calcium-deficiency rickets. © 2010 American Society for Bone and Mineral

  2. Pharmacokinetics and effects of demographic factors on blood 25(OH)D3 levels after a single orally administered high dose of vitamin D3

    PubMed Central

    Chen, Pei-zhan; Li, Mian; Duan, Xiao-hua; Jia, Jing-ying; Li, Jing-quan; Chu, Rui-ai; Yu, Chen; Han, Jun-hua; Wang, Hui

    2016-01-01

    Aim: To examine the biological consequences and demographic factors that might affect the pharmacokinetics of vitamin D3 after a single high dose intervention in a young Chinese population with vitamin D insufficiency status. Methods: A total of 28 young subjects (25 to 35 years old) with vitamin D insufficiency status [serum 25(OH)D <30 ng/mL] was recruited in Shanghai, China. The subjects were orally administered a single high dose of vitamin D3 (300 000 IU). Baseline characteristics and blood samples were collected at d 0, 1, 2, 3, 7, 28, 56, 84 and 112 after the intervention. The blood biomarker levels were determined with standardized methods. Results: The intervention markedly increased the blood 25(OH)D3 levels within the first five days (mean Tmax=5.1±2.1 d) and sustained an optimal circulating level of 25(OH)D3 (≥30 ng/mL) for 56 d. After the intervention, body weight and baseline 25(OH)D3 levels were significantly correlated with circulating 25(OH)D3 levels. No adverse events and no consistently significant changes in serum calcium, creatinine, glucose, parathyroid hormone, vitamin D binding protein, or the urinary calcium/reatinine ratio were observed. However, there was a significant increase in phosphorus after the vitamin D3 intervention. Total cholesterol and triglyceride levels were decreased at the end of the trial. Conclusion: The pharmacokinetics of vitamin D after intervention were influenced by baseline 25(OH)D3 levels and the body weight of the subjects. The results suggest that a single high oral vitamin D3 intervention is safe and efficient for improving the vitamin D status of young Chinese people with vitamin D insufficiency. PMID:27569392

  3. Pharmacokinetics and effects of demographic factors on blood 25(OH)D3 levels after a single orally administered high dose of vitamin D3.

    PubMed

    Chen, Pei-Zhan; Li, Mian; Duan, Xiao-Hua; Jia, Jing-Ying; Li, Jing-Quan; Chu, Rui-Ai; Yu, Chen; Han, Jun-Hua; Wang, Hui

    2016-11-01

    To examine the biological consequences and demographic factors that might affect the pharmacokinetics of vitamin D3 after a single high dose intervention in a young Chinese population with vitamin D insufficiency status. A total of 28 young subjects (25 to 35 years old) with vitamin D insufficiency status [serum 25(OH)D <30 ng/mL] was recruited in Shanghai, China. The subjects were orally administered a single high dose of vitamin D3 (300 000 IU). Baseline characteristics and blood samples were collected at d 0, 1, 2, 3, 7, 28, 56, 84 and 112 after the intervention. The blood biomarker levels were determined with standardized methods. The intervention markedly increased the blood 25(OH)D3 levels within the first five days (mean Tmax=5.1±2.1 d) and sustained an optimal circulating level of 25(OH)D3 (≥30 ng/mL) for 56 d. After the intervention, body weight and baseline 25(OH)D3 levels were significantly correlated with circulating 25(OH)D3 levels. No adverse events and no consistently significant changes in serum calcium, creatinine, glucose, parathyroid hormone, vitamin D binding protein, or the urinary calcium/reatinine ratio were observed. However, there was a significant increase in phosphorus after the vitamin D3 intervention. Total cholesterol and triglyceride levels were decreased at the end of the trial. The pharmacokinetics of vitamin D after intervention were influenced by baseline 25(OH)D3 levels and the body weight of the subjects. The results suggest that a single high oral vitamin D3 intervention is safe and efficient for improving the vitamin D status of young Chinese people with vitamin D insufficiency.

  4. Vitamin D(3) is more potent than vitamin D(2) in humans.

    PubMed

    Heaney, Robert P; Recker, Robert R; Grote, James; Horst, Ronald L; Armas, Laura A G

    2011-03-01

    Current unitage for the calciferols suggests that equimolar quantities of vitamins D(2) (D2) and D(3) (D3) are biologically equivalent. Published studies yield mixed results. The aim of the study was to compare the potencies of D2 and D3. The trial used a single-blind, randomized design in 33 healthy adults. Calciferols were dosed at 50,000 IU/wk for 12 wk. Principal outcome variables were area under the curve for incremental total 25-hydroxyvitamin D [25(OH)D] and change in calciferol content of sc fat. Incremental mean (sd) 25(OH)D area under the curve at 12 wk was 1366 ng · d/ml (516) for the D2-treated group and 2136 (606) for the D3 (P < 0.001). Mean (sd) steady-state 25(OH)D increments showed similar differences: 24 ng/ml for D2 (10.3) and 45 ng/ml (16.2) for D3 (P <0.001). Subcutaneous fat content of D2 rose by 50 μg/kg in the D2-treated group, and D3 content rose by 104 μg/kg in the D3-treated group. Total calciferol in fat rose by only 33 ng/kg in the D2-treated, whereas it rose by 104 μg/kg in the D3-treated group. Extrapolating to total body fat D3, storage amounted to just 17% of the administered dose. D3 is approximately 87% more potent in raising and maintaining serum 25(OH)D concentrations and produces 2- to 3-fold greater storage of vitamin D than does equimolar D2. For neither was there evidence of sequestration in fat, as had been postulated for doses in this range. Given its greater potency and lower cost, D3 should be the preferred treatment option when correcting vitamin D deficiency.

  5. Efficacy of high dose Vitamin D supplementation in improving serum 25(OH)D among migrant and non migrant population: a retrospective study.

    PubMed

    Gowda, Usha; Ruwanpathirana, Thilanga; Fong, David P S; Kaur, Ambika; Renzaho, Andre M N

    2016-10-13

    Higher dose of vitamin D supplementation 50000 IU is required for those whose serum 25(OH)D levels are 50 nmol/L and below. The increment in serum 25(OH)D though not significantly affected by race, sex or age it is negatively correlated to the baseline 25(OH)D concentration. This study investigated whether the mean increase in serum 25(OH)D will be higher among participants with lower baseline 25(OH)D levels and whether the duration of supplementation has an influence on the serum 25(OH)D achieved. A clinical audit of patients' medical records from a community health centre in Melbourne for the period 01.01.2010 to 31-12.2012 was undertaken. Paired sample t test was used to determine difference in pre and post dose serum 25(OH)D. Simple and multiple linear regressions were used to examine the association between the difference in pre and post dose serum 25(OH)D and duration of supplementation and baseline serum 25(OH)D, adjusting for socio-demographic factors. A total of 205 patients were included in the study. Mean difference in serum 25(OH)D was highest 52.8 nmol/L (95 % CI: 46.63-58.92) among those whose serum 25(OH)D was below 25 nmol/L at baseline. Baseline 25(OH)D alone accounted for 13.7 % of variance in the effect size (F(2, 202) = 16.0. p < 0.001), with the effect size significantly higher among participants with a baseline 25(OH)D level of 25-49 nmol/L (β = 11.93, 95 % CI: 0.48, 23.40, p < 0.05). Mean serum 25(OH)D difference was highest, 47.53 nmol/L (95 % CI: 40.95-54.11) when measured within 3 months of supplementation. Duration of supplementation explained 2.9 % of the variance in the effect size (F (1, 203) = 6.11, p < 0.05) and there was an inverse relationship between the length of supplementation and mean pre and post supplementation serum 25(OH)D difference (β = -1.45, 95 % CI: -2.62, -0.29, p = 0.014). Following 50000 IU vitamin D3 for 12 months mean serum 25(OH)D increase was highest among those

  6. Long-term vitamin D3 supplementation is more effective than vitamin D2 in maintaining serum 25-hydroxyvitamin D status over the winter months.

    PubMed

    Logan, Victoria F; Gray, Andrew R; Peddie, Meredith C; Harper, Michelle J; Houghton, Lisa A

    2013-03-28

    Public health recommendations do not distinguish between vitamin D2 and vitamin D3, yet disagreement exists on whether these two forms should be considered equivalent. The objective of the present study was to evaluate the effect of a daily physiological dose of vitamin D2 or vitamin D3 on 25-hydroxyvitamin D (25(OH)D) status over the winter months in healthy adults living in Dunedin, New Zealand (latitude 46°S). Participants aged 18-50 years were randomly assigned to 25 μg (1000 IU) vitamin D3 (n 32), 25 μg (1000 IU) vitamin D2 (n 31) or placebo (n 32) daily for 25 weeks beginning at the end of summer. A per-protocol approach, which included ≥ 90 % supplement compliance, was used for all analyses. Serum 25-hydroxyvitamin D3 (25(OH)D3), 25-hydroxyvitamin D2 (25(OH)D2) and parathyroid hormone (PTH) were measured at baseline and at 4, 8, 13 and 25 weeks. Geometric mean total serum 25(OH)D concentrations (sum of 25(OH)D2 and 25(OH)D3) at baseline was 80 nmol/l. After 25 weeks, participants randomised to D2 and placebo had a significant reduction in serum 25(OH)D3 concentrations over the winter months compared with vitamin D3-supplemented participants (both P< 0.001). Supplementation with vitamin D2 increased serum 25(OH)D2 but produced a 9 (95 % CI 1, 17) nmol/l greater decline in the 25(OH)D3 metabolite compared with placebo (P< 0.036). Overall, total serum 25(OH)D concentrations were 21 (95 % CI 14, 30) nmol/l lower in participants receiving vitamin D2 compared with those receiving D3 (P< 0.001), among whom total serum 25(OH)D concentrations remained unchanged. No intervention-related changes in PTH were observed. Daily supplementation of vitamin D3 was more effective than D2; however, the functional consequence of the differing metabolic response warrants further investigation.

  7. 25(OH) vitamin D suppresses macrophage adhesion and migration by downregulation of ER stress and scavenger receptor A1 in type 2 diabetes.

    PubMed

    Riek, Amy E; Oh, Jisu; Darwech, Isra; Moynihan, Clare E; Bruchas, Robin R; Bernal-Mizrachi, Carlos

    2014-10-01

    Cardiovascular disease (CVD) is the leading cause of mortality in patients with type 2 diabetes mellitus (T2DM). Vitamin D deficiency is not only more prevalent in diabetics but also doubles the risk of developing CVD. However, it is unknown whether 25-hydroxy vitamin D [25(OH)D3] replacement slows monocyte adhesion and migration, critical mechanisms involved in atherosclerosis progression. In this study, monocytes from vitamin D-deficient diabetic patients were cultured either in the patient's serum or in vitamin D-deficient media with or without 25(OH)D3 treatment. Adding 25(OH)D3 to monocytes cultured in vitamin D-deficient serum or media decreased monocyte adhesion to fibronectin and migration stimulated by monocyte chemotactic protein 1 (MCP-1). Accordingly, 25(OH)D3 decreased adhesion marker β1- and β2-integrin expression and migration receptor chemokine (C-C motif) receptor 2 (CCR2) expression. 25(OH)D3 treatment downregulated monocyte endoplasmic reticulum (ER) stress and scavenger receptor class A, type 1 (SR-A1) expression. The absence of SR-A1 prevented the increased macrophage adhesion and migration induced by vitamin D deficiency. Moreover, the absence of SR-A1 prevented the induction of adhesion and migration and expression of their associated membrane receptors by Thapsigargin, an ER stress inducer. These results identify cellular activation of monocyte/macrophage vitamin D signaling through 25(OH)D3 as a potential mechanism that could modulate adhesion and migration in diabetic subjects. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Hypercalcemia, hypervitaminosis A and 3-epi-25-OH-D3 levels after consumption of an "over the counter" vitamin D remedy. a case report.

    PubMed

    Granado-Lorencio, F; Rubio, E; Blanco-Navarro, I; Pérez-Sacristán, B; Rodríguez-Pena, R; García López, F J

    2012-06-01

    Intoxication from vitamin D supplements has been rarely reported but, nowadays, it occurs more frequently. 3-epi-25-OH-D(3) is highly prevalent in adults and it is considered of biological relevance. We report a case of vitamin D toxicity with hypercalcemia, acute renal failure and hypervitaminosis A after consuming an over-the-counter vitamin D supplement. Our data suggest that the contribution of 3-epi-25-OH-D(3) is not altered during vitamin D toxicity, although the serum levels of 25-OH-D(3) and 3-epi-25-OH-D(3) may display a different rate of clearance. The patient also displayed hypervitaminosis A unrelated to diet, possibly caused by renal failure related to the hypercalcemia induced by vitamin D toxicity. Because of the increasing use of over-the-counter vitamin D supplements and the potential iatrogenic hypercalcemia related to hypervitaminosis A, the present case highlights the importance of evaluating both the use of (non-) prescribed medication and vitamin A status during vitamin D toxicity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Intestinal Na(+)/Ca(2+) exchanger protein and gene expression are regulated by 1,25(OH)(2)D(3) in vitamin D-deficient chicks.

    PubMed

    Centeno, Viviana; Picotto, Gabriela; Pérez, Adriana; Alisio, Arturo; Tolosa de Talamoni, Nori

    2011-05-15

    The role of 1,25(OH)(2)D(3) on the intestinal NCX activity was studied in vitamin D-deficient chicks (-D) as well as the hormone effect on NCX1 protein and gene expression and the potential molecular mechanisms underlying the responses. Normal, -D and -D chicks treated with cholecalciferol or 1,25(OH)(2)D(3) were employed. In some experiments, -D chicks were injected with cycloheximide or with cycloheximide and 1,25(OH)(2)D(3) simultaneously. NCX activity was decreased by -D diet, returning to normal values after 50 IU daily of cholecalciferol/10 days or a dose of 1μg calcitriol/kg of b.w. for 15 h. Cycloheximide blocked NCX activity enhancement produced by 1,25(OH)(2)D(3). NCX1 protein and gene expression were diminished by -D diet and enhanced by 1,25(OH)(2)D(3). Vitamin D receptor expression was decreased by -D diet, effect that disappeared after 1,25(OH)(2)D(3) treatment. Rapid effects of 1,25(OH)(2)D(3) on intestinal NCX activity were also demonstrated. The abolition of the rapid effects through addition of Rp-cAMPS and staurosporine suggests that non genomic effects of 1,25(OH)(2)D(3) on NCX activity are mediated by activation of PKA and PKC pathways. In conclusion, 1,25(OH)(2)D(3) enhances the intestinal NCX activity in -D chicks through genomic and non genomic mechanisms. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Predictors of serum 25(Oh)D increase following bimonthly supplementation with 100,000IU vitamin D in healthy, men aged 25-65 years.

    PubMed

    Tepper, Sigal; Shahar, Danit R; Geva, Diklah; Ish-Shalom, Sofia

    2014-10-01

    Vitamin D replenishment therapy typically entails standard dosages, but related increases in serum 25(OH)D levels vary between individuals. This study was aimed to identify factors that affect the efficacy of vitamin D supplementation. 79 healthy men aged 25-65 with 25(OH)D<20ng/ml participated in a vitamin D supplementation study. All participants received 100,000IU vitamin D bimonthly, e.g., 1666IU/day. Personal and demographic information, physical activity and sun-exposure questionnaires were completed by the participants. Weight, height, and waist circumference were recorded. Serum calcium, creatinine, 25(OH)D, PTH, lipid profile, and liver-enzyme levels were assessed. All measurements were repeated after 6 and 12 months. The difference between baseline serum 25(OH)D and 12-month measurements was calculated (delta). Linear regression was performed to identify predictors for increases in 25(OH)D levels. Mean serum 25(OH)D level increases according to BMI were 12.6±5.29ng/ml for BMI≤25, 10.12±4.95ng/ml for 2530, which differed significantly from the other BMI categories (p=0.003). In a regression model to predict 25(OH)D increase, BMI was the main predictor (p<0.001), explaining 21.6% of the variance in serum 25(OH)D (inverse association). Age, sun-exposure, serum cholesterol, physical-activity, baseline 25(OH)D levels and seasonality were insignificant. The full model explained 27.9% of the variance in serum 25(OH)D. This study's main findings are that BMI affect vitamin D response in healthy men. Quantitative supplementation adjustments may be warranted in obese men, for whom the dose may need to be doubled. This article is part of a special issue entitled '16th Vitamin D Workshop'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. The vitamin D analogue ED71 but Not 1,25(OH)2D3 targets HIF1α protein in osteoclasts.

    PubMed

    Sato, Yuiko; Miyauchi, Yoshiteru; Yoshida, Shigeyuki; Morita, Mayu; Kobayashi, Tami; Kanagawa, Hiroya; Katsuyama, Eri; Fujie, Atsuhiro; Hao, Wu; Tando, Toshimi; Watanabe, Ryuichi; Miyamoto, Kana; Morioka, Hideo; Matsumoto, Morio; Toyama, Yoshiaki; Miyamoto, Takeshi

    2014-01-01

    Although both an active form of the vitamin D metabolite, 1,25(OH)2D3, and the vitamin D analogue, ED71 have been used to treat osteoporosis, anti-bone resorbing activity is reportedly seen only in ED71- but not in 1,25(OH)2D3 -treated patients. In addition, how ED71 inhibits osteoclast activity in patients has not been fully characterized. Recently, HIF1α expression in osteoclasts was demonstrated to be required for development of post-menopausal osteoporosis. Here we show that ED71 but not 1,25(OH)2D3, suppress HIF1α protein expression in osteoclasts in vitro. We found that 1,25(OH)2D3 or ED71 function in osteoclasts requires the vitamin D receptor (VDR). ED71 was significantly less effective in inhibiting M-CSF and RANKL-stimulated osteoclastogenesis than was 1,25(OH)2D3 in vitro. Downregulation of c-Fos protein and induction of Ifnβ mRNA in osteoclasts, both of which reportedly block osteoclastogenesis induced by 1,25(OH)2D3 in vitro, were both significantly higher following treatment with 1,25(OH)2D3 than with ED71. Thus, suppression of HIF1α protein activity in osteoclasts in vitro, which is more efficiently achieved by ED71 rather than by 1,25(OH)2D3, could be a reliable read-out in either developing or screening reagents targeting osteoporosis.

  12. PKC and PTPα participate in Src activation by 1α,25OH2 vitamin D3 in C2C12 skeletal muscle cells.

    PubMed

    Buitrago, Claudia; Costabel, Marcelo; Boland, Ricardo

    2011-06-06

    We previously demonstrated that 1α,25(OH)(2)-vitamin D(3) [1α,25(OH)(2)D(3)] induces Src activation, which mediates the hormone-dependent ERK1/2 and p38 MAPK phosphorylation in skeletal muscle cells. In the present study, we have investigated upstream steps whereby 1α,25(OH)(2)D(3) may act to transmit its signal to Src. Preincubation with the PKC inhibitor Ro318220 demonstrated the participation of PKC in 1α,25(OH)(2)D(3)-dependent Src activation. Of interest, the hormone promoted the activation of δ the isoform of PKC. We also explored the role of PTPα in PKC-mediated Src stimulation. Silencing of PTPα with a specific siRNA suppressed Src activation induced by 1α,25(OH)(2)D(3). Hormone treatment increased PTPα (Tyr789) phosphorylation and PKC-dependent phosphatase activity. Accordingly, 1α,25(OH)(2)D(3) promoted serine phosphorylation of PTPα in a PKC-dependent manner. Confocal immunocytochemistry and co-immunoprecipitation assays revealed that the hormone induces the co-localization of Src and PTPα with PKC participation. Computational analysis revealed that the electrostatic interaction between Src and PTPα is favored when PTPα is phosphorylated in Tyr789. These data suggest that 1α,25(OH)(2)D(3) acts in skeletal muscle upstream on MAPK cascades sequentially activating PKC, PTPα and Src.

  13. Effect of 1,25(OH)2 vitamin D3 on cytokine production by endometrial cells of women with repeated implantation failure.

    PubMed

    Rajaei, Samira; Mirahmadian, Mahroo; Jeddi-Tehrani, Mahmood; Tavakoli, Maryam; Zonoobi, Mojdeh; Dabbagh, Ali; Zarnani, Amir Hassan

    2012-11-01

    Repeated implantation failure (RIF) is a worldwide health problem that imposes a great deal of cost on patients and health care system. Vitamin D(3) has been proposed to have positive impact on the process of implantation. The present study was performed to compare the effect of 1,25-dihydroxy vitamin D(3) (1,25(OH)(2)D(3)) on cytokine production by endometrial cells of women with RIF and healthy fertile controls. Whole endometrial cells (WECs) and endometrial stromal cells (ESCs) from RIF and normal fertile women were treated with 1,25(OH)(2)D(3). The levels of IL-10, TGF-β, IFNγ, Il-6, IL-8 and IL-17 in culture supernatants were assayed by ELISA. Also, ability of the cells from both groups to produce 1,25(OH)(2)D(3) was evaluated and compared. 1,25(OH)(2)D(3) down-regulated cytokine production in WECs from both groups except for IL-8 which was upraised. Similar trends were also observed in ESCs except up-regulation of TGF-β in RIF group. Endometrial cells of both groups had comparable capacity to produce 1,25(OH)(2)D(3). Based on the minimal differential immunoregulatory effect of vitamin D(3) on endometrial cells from RIF and control women, it may be suggested that circulating levels of maternal vitamin D(3) be the subject of further investigation.

  14. The effects of vitamin D(3) supplementation on serum total 25[OH]D concentration and physical performance: a randomised dose-response study.

    PubMed

    Close, Graeme L; Leckey, Jill; Patterson, Marcelle; Bradley, Warren; Owens, Daniel J; Fraser, William D; Morton, James P

    2013-07-01

    Vitamin D deficiency is common in the general public and athletic populations and may impair skeletal muscle function. We therefore assessed the effects of vitamin D3 supplementation on serum 25[OH]D concentrations and physical performance. 30 club-level athletes were block randomised (using baseline 25[OH]D concentrations) into one of three groups receiving either a placebo (PLB), 20 000 or 40 000 IU/week oral vitamin D3 for 12 weeks. Serum 25[OH]D and muscle function (1-RM bench press and leg press and vertical jump height) were measured presupplementation, 6 and 12 weeks postsupplementation. Vitamin D deficiency was defined in accordance with the US Institute of Medicine guideline (<50 nmol/l). 57% of the subject population were vitamin D deficient at baseline (mean±SD value 51±24 nmol/l). Following 6 and 12 weeks supplementation with 20 000 IU (79±14 and 85±10 nmol/l, respectively) or 40 000 IU vitamin D3 (98±14 and 91±24 nmol/l, respectively), serum vitamin D concentrations increased in all participants, with every individual achieving concentrations greater than 50 nmol/l. In contrast, vitamin D concentration in the PLB group decreased at 6 and 12 weeks (37±18 and 41±22 nmol/l, respectively). Increasing serum 25[OH]D had no significant effect on any physical performance parameter (p>0.05). Both 20 000 and 40 000 IU vitamin D3 supplementation over a 6-week period elevates serum 25[OH]D concentrations above 50 nmol/l, but neither dose given for 12 weeks improved our chosen measures of physical performance.

  15. Polymorphisms affecting vitamin D-binding protein modify the relationship between serum vitamin D (25[OH]D3) and food allergy.

    PubMed

    Koplin, Jennifer J; Suaini, Noor H A; Vuillermin, Peter; Ellis, Justine A; Panjari, Mary; Ponsonby, Anne-Louise; Peters, Rachel L; Matheson, Melanie C; Martino, David; Dang, Thanh; Osborne, Nicholas J; Martin, Pamela; Lowe, Adrian; Gurrin, Lyle C; Tang, Mimi L K; Wake, Melissa; Dwyer, Terry; Hopper, John; Dharmage, Shyamali C; Allen, Katrina J

    2016-02-01

    There is evolving evidence that vitamin D insufficiency may contribute to food allergy, but findings vary between populations. Lower vitamin D-binding protein (DBP) levels increase the biological availability of serum vitamin D. Genetic polymorphisms explain almost 80% of the variation in binding protein levels. We sought to investigate whether polymorphisms that lower the DBP could compensate for adverse effects of low serum vitamin D on food allergy risk. From a population-based cohort study (n = 5276) we investigated the association between serum 25-hydroxyvitamin D3 (25[OH]D3) levels and food allergy at age 1 year (338 challenge-proven food-allergic and 269 control participants) and age 2 years (55 participants with persistent and 50 participants with resolved food allergy). 25(OH)D3 levels were measured using liquid chromatography-tandem mass spectrometry and adjusted for season of blood draw. Analyses were stratified by genotype at rs7041 as a proxy marker of DBP levels (low, the GT/TT genotype; high, the GG genotype). Low serum 25(OH)D3 level (≤50 nM/L) at age 1 years was associated with food allergy, particularly among infants with the GG genotype (odds ratio [OR], 6.0; 95% CI, 0.9-38.9) but not in those with GT/TT genotypes (OR, 0.7; 95% CI, 0.2-2.0; P interaction = .014). Maternal antenatal vitamin D supplementation was associated with less food allergy, particularly in infants with the GT/TT genotype (OR, 0.10; 95% CI, 0.03-0.41). Persistent vitamin D insufficiency increased the likelihood of persistent food allergy (OR, 12.6; 95% CI, 1.5-106.6), particularly in those with the GG genotype. Polymorphisms associated with lower DBP level attenuated the association between low serum 25(OH)D3 level and food allergy, consistent with greater vitamin D bioavailability in those with a lower DBP level. This increases the biological plausibility of a role for vitamin D in the development of food allergy. Copyright © 2015 American Academy of Allergy, Asthma

  16. Genome-wide association study of 25(OH) Vitamin D concentrations in Punjabi Sikhs: Results of the Asian Indian diabetic heart study

    PubMed Central

    Sapkota, Bishwa R.; Hopkins, Ruth; Bjonnes, Andrew; Ralhan, Sarju; Wander, Gurpreet S.; Mehra, Narinder K.; Singh, Jai Rup; Blackett, Piers R.; Saxena, Richa; Sanghera, Dharambir K.

    2016-01-01

    Vitamin D deficiency is implicated in multiple disease conditions and accumulating evidence supports that the variation in serum vitamin D (25(OH)D) levels, including deficiency, is under strong genetic control. However, the underlying genetic mechanism associated with vitamin 25(OH)D concentrations is poorly understood. We earlier reported a very high prevalence of vitamin D deficiency associated with an increased risk for type 2 diabetes and obesity in a Punjabi Sikh diabetic cohort as part of the Asian Indian diabetic heart study (AIDHS). Here we have performed the first genome-wide association study (GWAS) of serum 25(OH)D on 3538 individuals from this Punjabi Sikh population. Our discovery GWAS comprised of 1387 subjects followed by validation of 24 putative SNPs (P <10−4) using an independent replication sample (n = 2151) from the same population by direct genotyping. A novel locus at chromosome 20p11.21 represented by rs2207173 with minor allele frequency (MAF) 0.29, [β = −0.13, p = 4.47 × 10−9] between FOXA2 and SSTR4 was identified to be associated with 25(OH)D levels. Another suggestive association signal at rs11586313 (MAF 0.54) [β = 0.90; p = 1.36 × 10−6] was found within the regulatory region of the IVL gene on chromosome 1q21.3. Additionally, our study replicated 3 of 5 known GWAS genes associated with 25(OH)D concentrations including GC (p = 0.007) and CYP2R1 (p = 0.019) reported in Europeans and the DAB1 (p = 0.003), reported in Hispanics. Identification of novel association signals in biologically plausible regions with 25(OH)D metabolism will provide new molecular insights on genetic drivers of vitamin D status and its implications in health disparities. PMID:26704534

  17. Genome-wide association study of 25(OH) Vitamin D concentrations in Punjabi Sikhs: Results of the Asian Indian diabetic heart study.

    PubMed

    Sapkota, Bishwa R; Hopkins, Ruth; Bjonnes, Andrew; Ralhan, Sarju; Wander, Gurpreet S; Mehra, Narinder K; Singh, Jai Rup; Blackett, Piers R; Saxena, Richa; Sanghera, Dharambir K

    2016-04-01

    Vitamin D deficiency is implicated in multiple disease conditions and accumulating evidence supports that the variation in serum vitamin D (25(OH)D) levels, including deficiency, is under strong genetic control. However, the underlying genetic mechanism associated with vitamin 25(OH)D concentrations is poorly understood. We earlier reported a very high prevalence of vitamin D deficiency associated with an increased risk for type 2 diabetes and obesity in a Punjabi Sikh diabetic cohort as part of the Asian Indian diabetic heart study (AIDHS). Here we have performed the first genome-wide association study (GWAS) of serum 25(OH)D on 3538 individuals from this Punjabi Sikh population. Our discovery GWAS comprised of 1387 subjects followed by validation of 24 putative SNPs (P<10(-4)) using an independent replication sample (n=2151) from the same population by direct genotyping. A novel locus at chromosome 20p11.21 represented by rs2207173 with minor allele frequency (MAF) 0.29, [β=-0.13, p=4.47×10(-9)] between FOXA2 and SSTR4 was identified to be associated with 25(OH)D levels. Another suggestive association signal at rs11586313 (MAF 0.54) [β=0.90; p=1.36×10(-6)] was found within the regulatory region of the IVL gene on chromosome 1q21.3. Additionally, our study replicated 3 of 5 known GWAS genes associated with 25(OH)D concentrations including GC (p=0.007) and CYP2R1 (p=0.019) reported in Europeans and the DAB1 (p=0.003), reported in Hispanics. Identification of novel association signals in biologically plausible regions with 25(OH)D metabolism will provide new molecular insights on genetic drivers of vitamin D status and its implications in health disparities.

  18. 1alpha,25(OH)2-vitamin D3 membrane-initiated calcium signaling modulates exocytosis and cell survival.

    PubMed

    Xiaoyu, Zhang; Payal, Biswas; Melissa, Owraghi; Zanello, Laura P

    2007-03-01

    1alpha,25(OH)(2)-vitamin D(3) (1,25D) is considered a bone anabolic hormone. 1,25D actions leading to bone formation involve gene transactivation, on one hand, and modulation of cytoplasmic signaling, on the other. In both cases, a functional vitamin D receptor (VDR) appears to be required. Here we study 1,25D-stimulated calcium signaling that initiates at the cell membrane and leads to exocytosis of bone materials and increased osteoblast survival. We found that rapid 1,25D-induction of exocytosis couples to cytoplasmic calcium increase in osteoblastic ROS 17/2.8 cells. In addition, we found that elevation of cytoplasmic calcium concentration is involved in 1,25D anti-apoptotic effects via Akt activation in ROS 17/2.8 cells and non-osteoblastic CV-1 cells. In both cases, 1,25D-stimulated elevation of intracellular calcium is due in part to activation of L-type Ca(2+) channels. We conclude that 1,25D bone anabolic effects that involve increased intracellular Ca(2+) concentration in osteoblasts can be explained at two levels. At the single-cell level, 1,25D promotes Ca(2+)-dependent exocytotic activities. At the tissue level, 1,25D protects osteoblasts from apoptosis via a Ca(2+)-dependent Akt pathway. Our studies contribute to the understanding of the molecular basis of bone diseases characterized by decreased bone formation and mineralization.

  19. Serum 25(OH)D3 vitamin status of elderly Finnish women is suboptimal even after summer sunshine but is not associated with bone density or turnover.

    PubMed

    Pekkarinen, Tuula; Turpeinen, Ursula; Hämäläinen, Esa; Löyttyniemi, Eliisa; Alfthan, Henrik; Välimäki, Matti J

    2010-01-01

    Concentrations of 50 and 75 nmol/l are proposed as serum 25-hydroxyvitamin D (25(OH)D) target for older people from the view of bone health. We evaluated vitamin D status of elderly Finnish women in light of these definitions, its relationship to bone mineral density (BMD) and turnover, and improvement by summer sunshine. Population-based study. A total of 1604 ambulatory women aged 62-79 years were studied; 66% used vitamin D supplements. Serum 25(OH)D(3) was measured with HPLC before and after summer, and heel BMD in spring. In subgroups, serum parathyroid hormone (PTH) and type I procollagen aminoterminal propeptide (PINP) were analyzed. In spring, 60.3% of the women had 25(OH)D(3) 25(OH)D(3) did not determine BMD or bone turnover measured by serum PINP. Summer sunshine increased serum 25(OH)D(3) by 17.4% (P<0.0001), but in autumn 84% of the subjects remained under the target of 75 nmol/l. In supplement users, PTH remained stable but decreased in others during summer (P=0.025). Vitamin D status of elderly Finnish women is suboptimal if 25(OH)D(3) levels of 50 or 75 nmol/l are used as a threshold. It is moderately increased by supplement intake and summer sunshine. However, 25(OH)D(3) concentrations did not influence bone density in terms of serum PINP and bone turnover rate.

  20. 1,25(OH)2 vitamin d inhibits foam cell formation and suppresses macrophage cholesterol uptake in patients with type 2 diabetes mellitus.

    PubMed

    Oh, Jisu; Weng, Sherry; Felton, Shaili K; Bhandare, Sweety; Riek, Amy; Butler, Boyd; Proctor, Brandon M; Petty, Marvin; Chen, Zhouji; Schechtman, Kenneth B; Bernal-Mizrachi, Leon; Bernal-Mizrachi, Carlos

    2009-08-25

    Cardiovascular disease is the leading cause of death among those with diabetes mellitus. Vitamin D deficiency is associated with an increased risk of cardiovascular disease in this population. To determine the mechanism by which vitamin D deficiency mediates accelerated cardiovascular disease in patients with diabetes mellitus, we investigated the effects of active vitamin D on macrophage cholesterol deposition. We obtained macrophages from 76 obese, diabetic, hypertensive patients with vitamin D deficiency (25-hydroxyvitamin D <80 nmol/L; group A) and 4 control groups: obese, diabetic, hypertensive patients with normal vitamin D (group B; n=15); obese, nondiabetic, hypertensive patients with vitamin D deficiency (group C; n=25); and nonobese, nondiabetic, nonhypertensive patients with vitamin D deficiency (group D; n=10) or sufficiency (group E; n=10). Macrophages from the same patients in all groups were cultured in vitamin D-deficient or 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] -supplemented media and exposed to modified low-density lipoprotein cholesterol. 1,25(OH)(2)D(3) suppressed foam cell formation by reducing acetylated or oxidized low-density lipoprotein cholesterol uptake in diabetic subjects only. Conversely, deletion of the vitamin D receptor in macrophages from diabetic patients accelerated foam cell formation induced by modified LDL. 1,25(OH)(2)D(3) downregulation of c-Jun N-terminal kinase activation reduced peroxisome proliferated-activated receptor-gamma expression, suppressed CD36 expression, and prevented oxidized low-density lipoprotein-derived cholesterol uptake. In addition, 1,25(OH)(2)D(3) suppression of macrophage endoplasmic reticulum stress improved insulin signaling, downregulated SR-A1 expression, and prevented oxidized and acetylated low-density lipoprotein-derived cholesterol uptake. These results identify reduced vitamin D receptor signaling as a potential mechanism underlying increased foam cell formation and accelerated

  1. Correction of 25-OH-vitamin D deficiency improves control of secondary hyperparathyroidism and reduces the inflammation in stable haemodialysis patients.

    PubMed

    Ojeda López, Raquel; Esquivias de Motta, Elvira; Carmona, Andrés; García Montemayor, Victoria; Berdud, Isabel; Martín Malo, Alejandro; Aljama García, Pedro

    2017-06-30

    Patients on haemodialysis (HD) have a high prevalence of 25-OH-vitamin D (25-OH-D)deficiency. Secondary hyperparathyroidismis a common condition in these patients, which is very important to control. 25-OH-D is involved in regulating calcium homeostasis. As such, appropriate levels of this vitamin could help to control bone mineral metabolism. To evaluate the effect 25-OH-D repletion in HD patients with 25-OH-D deficiency (<20ng/ml) on the control of secondary hyperparathyroidism and microinflammation status. Prospective observational study in which stable patients on HD with 25-OH-D deficiency (<20ng/ml) were treated with oral calcifediol 0.266mcg/every 2 weeks for three months. Dialysis characteristics, biochemical parameters and drug doses administered were analysed before and after the correction of the deficiency. Forty-five stable HD patients with a mean age of 74.08±12.49 years completed treatment. Twenty-seven patients (60%) achieved 25-OH-D levels above 20ng/ml (23 with levels>30ng/ml and 4 between 20-30ng/ml). Parathyroid hormone levels decreased in 32 of the 45 patients, 23 of which (51%) achieved a>30% decrease from baseline. In terms of concomitant treatment, we observed a significant reduction in the selective vitamin D receptor activator dose, but no changes in calcimimetic or phosphate binders administration. In terms of malnutrition-inflammation status, a decrease in C-reactive protein was noted, although other microinflammation parameters, such as activated monocytes (CD14+/CD16+ and CD 14++/CD16+) were unchanged. No changes were observed in the levels of FGF-23. Correcting 25-OH-D deficiency in HD patients is associated with better secondary hyperparathyroidism control with lower doses of vitamin D analogues, as well as an improvement in inflammatory status. Our results support the recommendation to determine 25-OH-D levels and correct its deficiency in these patients. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier

  2. Decreased circulating 25-(OH) Vitamin D concentrations in obese female children and adolescents: positive associations with Retinol Binding Protein-4 and Neutrophil Gelatinase-associated Lipocalin.

    PubMed

    Metheniti, Dimitra; Sakka, Sophia; Dracopoulou, Maria; Margeli, Alexandra; Papassotiriou, Ioannis; Kanaka-Gantenbein, Christina; Chrousos, George P; Pervanidou, Panagiota

    2013-01-01

    Hypovitaminosis D has been associated with adult as well as childhood obesity. Retinol-binding-protein-4 (RBP-4) and Neutrophil Gelatinase-associated Lipocalin (NGAL) are altered in obese individuals. The aim of this study was to examine circulating 25-(OH) Vitamin D (25-(OH) D) concentrations according to BMI and its associations with RBP-4 and NGAL in female children and adolescents. Seventy-nine (79) children, aged 8-16 years, were studied and divided into four groups: 19 control (BMI z-score range -2.15 - 1.24), 20 overweight (1.34 - 2.49), 20 obese (2.50 - 2.87) and 20 ultra-obese (3 - 4.37). Patients were derived from a Pediatric Obesity Clinic. Plasma 25-(OH) D, RBP-4 and NGAL concentrations were measured with specific assays. Plasma 25-(OH) D concentrations were decreased significantly in the ultra-obese (p=0.005) and marginally in the obese group (p=0.05) compared to the control group. In the entire BMI range, Spearman correlations revealed strong positive associations between 25-(OH) D and RBP-4 (r=0.349, p=0.002) and between 25-(OH) D and NGAL (r=0.338, p=0.003). 25-(OH) D is deficient in a clinical population of obese female children and adolescents, whereas in the entire BMI range 25-(OH) D is associated with RBP4 and NGAL concentrations. Longitudinal studies are needed to reveal the role of these associations in metabolic alterations related to childhood and adolescent obesity and associated metabolic morbidities.

  3. Effects of the Administration of 25(OH) Vitamin D3 in an Experimental Model of Chronic Kidney Disease in Animals Null for 1-Alpha-Hydroxylase

    PubMed Central

    Torremadé, Noelia; Bozic, Milica; Goltzman, David; Fernandez, Elvira

    2017-01-01

    The final step in vitamin D activation is catalyzed by 1-alpha-hydroxylase (CYP27B1). Chronic kidney disease (CKD) is characterized by low levels of both 25(OH)D3 and 1,25(OH)2D3 provoking secondary hyperparathyroidism (2HPT). Therefore, treatments with active or native vitamin D compounds are common in CKD to restore 25(OH)D3 levels and also to decrease PTH. This study evaluates the dose of 25(OH)D3 that restores parathyroid hormone (PTH) and calcium levels in a model of CKD in CYP27B1-/- mice. Furthermore, we compare the safety and efficacy of the same dose in CYP27B1+/+ animals. The dose needed to decrease PTH levels in CYP27B1-/- mice with CKD was 50 ng/g. That dose restored blood calcium levels without modifying phosphate levels, and increased the expression of genes responsible for calcium absorption (TRPV5 and calbindinD- 28K in the kidney, TRPV6 and calbindinD-9k in the intestine). The same dose of 25(OH)D3 did not modify PTH in CYP27B1+/+ animals with CKD. Blood calcium remained normal, while phosphate increased significantly. Blood levels of 25(OH)D3 in CYP27B1-/- mice were extremely high compared to those in CYP27B1+/+ animals. CYP27B1+/+ animals with CKD showed increases in TRPV5, TRPV6, calbindinD-28K and calbindinD-9K, which were not further elevated with the treatment. Furthermore, CYP27B1+/+ animals displayed an increase in vascular calcification. We conclude that the dose of 25(OH)D3 effective in decreasing PTH levels in CYP27B1-/- mice with CKD, has a potentially toxic effect in CYP27B1+/+ animals with CKD. PMID:28107527

  4. Effects of the Administration of 25(OH) Vitamin D3 in an Experimental Model of Chronic Kidney Disease in Animals Null for 1-Alpha-Hydroxylase.

    PubMed

    Torremadé, Noelia; Bozic, Milica; Goltzman, David; Fernandez, Elvira; Valdivielso, José M

    2017-01-01

    The final step in vitamin D activation is catalyzed by 1-alpha-hydroxylase (CYP27B1). Chronic kidney disease (CKD) is characterized by low levels of both 25(OH)D3 and 1,25(OH)2D3 provoking secondary hyperparathyroidism (2HPT). Therefore, treatments with active or native vitamin D compounds are common in CKD to restore 25(OH)D3 levels and also to decrease PTH. This study evaluates the dose of 25(OH)D3 that restores parathyroid hormone (PTH) and calcium levels in a model of CKD in CYP27B1-/- mice. Furthermore, we compare the safety and efficacy of the same dose in CYP27B1+/+ animals. The dose needed to decrease PTH levels in CYP27B1-/- mice with CKD was 50 ng/g. That dose restored blood calcium levels without modifying phosphate levels, and increased the expression of genes responsible for calcium absorption (TRPV5 and calbindinD- 28K in the kidney, TRPV6 and calbindinD-9k in the intestine). The same dose of 25(OH)D3 did not modify PTH in CYP27B1+/+ animals with CKD. Blood calcium remained normal, while phosphate increased significantly. Blood levels of 25(OH)D3 in CYP27B1-/- mice were extremely high compared to those in CYP27B1+/+ animals. CYP27B1+/+ animals with CKD showed increases in TRPV5, TRPV6, calbindinD-28K and calbindinD-9K, which were not further elevated with the treatment. Furthermore, CYP27B1+/+ animals displayed an increase in vascular calcification. We conclude that the dose of 25(OH)D3 effective in decreasing PTH levels in CYP27B1-/- mice with CKD, has a potentially toxic effect in CYP27B1+/+ animals with CKD.

  5. 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.

  6. Continuous PTH and PTHrP infusion causes suppression of bone formation and discordant effects on 1,25(OH)2 vitamin D.

    PubMed

    Horwitz, Mara J; Tedesco, Mary Beth; Sereika, Susan M; Syed, Mushtaq A; Garcia-Ocaña, Adolfo; Bisello, Alessandro; Hollis, Bruce W; Rosen, Clifford J; Wysolmerski, John J; Dann, Pamela; Gundberg, Caren; Stewart, Andrew F

    2005-10-01

    Osteoblast activity and plasma 1,25(OH)2 vitamin D are increased in HPT but suppressed in HHM. To model HPT and HHM, we directly compared multiday continuous infusions of PTH versus PTHrP in humans. Continuous infusion of both PTH and PTHrP results in marked and prolonged suppression of bone formation; renal 1,25(OH)2D synthesis was stimulated effectively by PTH but poorly by PTHrP. PTH and PTH-related protein (PTHrP) cause primary hyperparathyroidism (HPT) and humoral hypercalcemia of malignancy (HHM), respectively. Whereas HHM and HPT resemble one another in many respects, osteoblastic bone formation and plasma 1,25(OH)2 vitamin D are increased in HPT but reduced in HHM. We performed 2- to 4-day continuous infusions of escalating doses of PTH and PTHrP in 61 healthy young adults, comparing the effects on serum calcium and phosphorus, renal calcium and phosphorus handling, 1,25(OH)2 vitamin D, endogenous PTH(1-84) concentrations, and plasma IGF-1 and markers of bone turnover. PTH and PTHrP induced comparable effects on renal calcium and phosphorus handling, and both stimulated IGF-1 and bone resorption similarly. Surprisingly, PTH was consistently more calcemic, reflecting a selectively greater increase in renal 1,25(OH)2 vitamin D production by PTH. Equally surprisingly, continuous infusion of both peptides markedly, continuously, and equivalently suppressed bone formation. PTHrP and PTH produce markedly different effects on 1,25(OH)2 vitamin D homeostasis in humans, leading to different calcemic responses. Moreover, both peptides produce profound suppression of bone formation over multiple days, contrasting with events in HPT, but mimicking HHM. These findings underscore the facts that the mechanisms underlying the anabolic skeletal response to PTH and PTHrP in humans is poorly understood, as are the signal transduction mechanisms that link the renal PTH receptor to 1,25(OH)2 vitamin D synthesis. These studies emphasize that much remains to be learned regarding

  7. Betulinic acid and 1,25(OH)₂ vitamin D₃ share intracellular signal transduction in glucose homeostasis in soleus muscle.

    PubMed

    Castro, Allisson Jhonatan Gomes; Frederico, Marisa Jádna Silva; Cazarolli, Luisa Helena; Bretanha, Lizandra Czermainski; Tavares, Luciana de Carvalho; Buss, Ziliani da Silva; Dutra, Márcio Ferreira; de Souza, Ariane Zamoner Pacheco; Pizzolatti, Moacir Geraldo; Silva, Fátima Regina Mena Barreto

    2014-03-01

    The effect of betulinic acid on glycemia and its mechanism of action compared with 1,25(OH)2 vitamin D3 in rat muscle were investigated. Betulinic acid improved glycemia, induced insulin secretion and increased the glycogen content and glucose uptake in muscle tissue. Additionally, the integrity of both PI3K and the cytoskeleton is necessary for the stimulatory action of betulinic acid in glucose uptake. The genomic effect was apparent, since cycloheximide and PD98059 nullified the stimulatory effect of betulinic acid on glucose uptake. Therefore, although this compound did not modify the DNA transcription, the protein translation was significantly improved. Also, betulinic acid increased the GLUT4 immunocontent and its translocation was corroborated by GLUT4 localization at the plasma membrane (after 180 min). On the other hand, the effect of 1,25(OH)2 vitamin D3 on glucose uptake is not mediated by PI3K and microtubule activity. In contrast, the nuclear activity of 1,25(OH)2 vitamin D3 is necessary to trigger glucose uptake. In addition, the increased DNA transcription and GLUT4 immunocontent provide evidence of a mechanism by which 1,25(OH)2 vitamin D3 contributes to glycemia. In conclusion, betulinic acid acts as an insulin secretagogue and insulinomimetic agent via PI3K, MAPK and mRNA translation and partially shares the genomic pathway with 1,25(OH)2 vitamin D3 to upregulate the GLUT4. In summary, betulinic acid regulates glycemia through classical insulin signaling by stimulating GLUT4 synthesis and translocation. In addition, it does not cause hypercalcemia, which is highly significant from the drug discovery perspective. Copyright © 2014. Published by Elsevier Ltd.

  8. Prostaglandin metabolising enzymes and PGE2 are inversely correlated with vitamin D receptor and 25(OH)2D3 in breast cancer.

    PubMed

    Thill, Marc; Fischer, Dorothea; Hoellen, Friederike; Kelling, Katharina; Dittmer, Christine; Landt, Solveig; Salehin, Darius; Diedrich, Klaus; Friedrich, Michael; Becker, Steffi

    2010-05-01

    Breast cancer is associated with inflammatory processes based on an up-regulation of cyclooxygenase-2 (COX-2) expression. The antiproliferative effects of calcitriol (1,25(OH)(2)D(3)) mediated via the vitamin D receptor (VDR) render vitamin D a promising target in breast cancer therapy. First data suggest a correlation between vitamin D and prostaglandin metabolism. We determined the expression of VDR, COX-2, 15-PGDH and the prostaglandin receptors EP(2)/EP(4) in normal and malignant breast tissue by real-time PCR and Western blot analysis, as well as 25(OH)(2)D(3) and PGE(2) plasma levels from healthy and breast cancer patients. Significantly higher COX-2, lower VDR and lower EP(2) and EP(4) receptor protein levels in the malignant tissue and a significantly lower 15-PGDH protein level in normal breast tissue were detected. Breast cancer patients older than 45 years, diagnosed and sampled in the winter time had significantly lower 25(OH)(2)D(3) and higher PGE(2) serum levels. The inverse correlation between VDR and both COX-2 and 15-PGDH, as well as between PGE(2) and 25(OH)(2)D(3) levels, suggests a possible link between VDR-associated target genes and prostaglandin metabolism.

  9. Vitamin D deficiency as a public health issue: using vitamin D2 or vitamin D3 in future fortification strategies.

    PubMed

    Wilson, Louise R; Tripkovic, Laura; Hart, Kathryn H; Lanham-New, Susan A

    2017-03-28

    The role of vitamin D in supporting the growth and maintenance of the skeleton is robust; with recent research also suggesting a beneficial link between vitamin D and other non-skeletal health outcomes, including immune function, cardiovascular health and cancer. Despite this, vitamin D deficiency remains a global public health issue, with a renewed focus in the UK following the publication of Public Health England's new Dietary Vitamin D Requirements. Natural sources of vitamin D (dietary and UVB exposure) are limited, and thus mechanisms are needed to allow individuals to achieve the new dietary recommendations. Mandatory or voluntary vitamin D food fortification may be one of the mechanisms to increase dietary vitamin D intakes and subsequently improve vitamin D status. However, for the food industry and public to make informed decisions, clarity is needed as to whether vitamins D2 and D3 are equally effective at raising total 25-hydroxyvitamin D (25(OH)D) concentrations as the evidence thus far is inconsistent. This review summarises the evidence to date behind the comparative efficacy of vitamins D2 and D3 at raising 25(OH)D concentrations, and the potential role of vitamin D food fortification as a public health policy to support attainment of dietary recommendations in the UK. The comparative efficacy of vitamins D2 and D3 has been investigated in several intervention trials, with most indicating that vitamin D3 is more effective at raising 25(OH)D concentrations. However, flaws in study designs (predominantly under powering) mean there remains a need for a large, robust randomised-controlled trial to provide conclusive evidence, which the future publication of the D2-D3 Study should provide (BBSRC DRINC funded: BB/I006192/1). This review also highlights outstanding questions and gaps in the research that need to be addressed to ensure the most efficacious and safe vitamin D food fortification practices are put in place. This further research, alongside cost

  10. 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. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  11. 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

  12. 25-OH vitamin D level has no impact on the efficacy of antiviral therapy in naïve genotype 1 HCV-infected patients

    PubMed Central

    Belle, Arthur; Gizard, Emmanuel; Conroy, Guillaume; Lopez, Anthony; Bouvier-Alias, Magali; Rouanet, Stéphanie; Peyrin-Biroulet, Laurent; Pawlotsky, Jean-Michel

    2016-01-01

    Background and aim The impact of 25-OH vitamin D on sustained viral response (SVR) to antiviral therapy and on fibrosis progression in hepatitis C is debated. We assessed the impact of 25-OH vitamin D concentration on the efficacy of antiviral therapy in naïve genotype 1 hepatitis C virus (HCV)-infected patients. Methods The study population consisted of treatment-naïve genotype 1 patients enrolled in a randomised controlled trial. A total of 516 patients received peginterferon α-2a 180 µg/week plus ribavirin 800 mg/day for 24 weeks. There were 349 patients with undetectable HCV RNA (<50 IU/ml) at week 24 (W24) who were randomised to continue dual therapy (n = 173) or to continue peginterferon alone (n = 176) until week 48. 25-OH vitamin D concentration was measured at baseline in frozen serum. Results A total of 461 patients could be analysed for virologic response at W24, and 285 (119 non-responders at W24 + 166 responders who continued dual therapy until W48) for the impact of SVR. There were 487 patients who could be analysed for fibrosis progression. Metavir fibrosis scores (centralised analysis) were: F1 30%, F2 34%, F3 27% and F4 9%. Median 25-OH vitamin D concentrations were similar in virologic responders (13.5 ng/ml) and in non-responders at W24 (12.6 ng/ml), as well as in patients with SVR (12.8 ng/ml) and without SVR (12.8 ng/ml, 3.99) at W72. Median 25-OH vitamin D concentrations were: F1: 14.30 ng/ml, F2: 13.50 ng/ml, F3: 13.30 ng/ml and F4: 12.80 ng/ml. Conclusion In this study, 25-OH vitamin D level has no impact on the efficacy of antiviral therapy in naïve genotype 1 HCV-infected patients. PMID:28405324

  13. Effect of Low-Dose Vitamin D Supplementation on Serum 25(OH)D in School Children and White-Collar Workers.

    PubMed

    Zhang, Ronghua; Muyiduli, Xiamusiye; Su, Danting; Zhou, Biao; Fang, Yueqiang; Jiang, Shuying; Wang, Shuojia; Huang, Lichun; Mo, Minjia; Li, Minchao; Shao, Bule; Yu, Yunxian

    2017-05-17

    Our study aimed to investigate the nutritional vitamin D status of school children aged 9-15 years and white-collar workers in Zhejiang province, and evaluate the efficacy of low-dose-oral vitamin D supplementation in both populations. We conducted a prospective controlled trial during March 2014 to November 2015, comparing the efficacy of vitamin D supplements (400 IU/day) with non-intervention for 18 months in school children aged 9-15 years. Meanwhile, a before-after study was conducted among white-collar workers for 1 year. Serum 25(OH)D concentration was measured at baseline and after vitamin D supplementation, respectively. At the baseline, 95% of school children and 84% of adult participants had vitamin D deficiency (<20 ng/mL). In school children, no difference was observed between the intervention and control groups with regard to anthropometric data. Serum 25(OH)D concentrations of the school children intervention group, school children control group and white-collar workers were 12.77 ± 3.01 ng/mL, 14.17 ± 3.59 ng/mL and 16.58 ± 3.66 ng/mL at baseline and increased to 17.34 ± 3.78 ng/mL, 18.04 ± 4.01 ng/mL and 17.75 ± 5.36 ng/mL after vitamin D supplementation, respectively. Although, after adjusting for potential confounders, the 400 IU oral vitamin D supplementation increased serum 25(OH)D concentration in school children (β = 0.81, p = 0.0426) as well as in white-collar workers (p = 0.0839), the prevalence of vitamin D deficiency was still very high among school children (79.23% in intervention group and 72.38% in control group) and white-collar workers (76.00%). High prevalence of vitamin D deficiency was common in these two study populations. Daily doses of 400 IU oral vitamin D supplementation was not able to adequately increase serum 25(OH)D concentrations. A suitable recommendation regarding the level of vitamin D supplementation is required for this Chinese population.

  14. Effect of Low-Dose Vitamin D Supplementation on Serum 25(OH)D in School Children and White-Collar Workers

    PubMed Central

    Zhang, Ronghua; Muyiduli, Xiamusiye; Su, Danting; Zhou, Biao; Fang, Yueqiang; Jiang, Shuying; Wang, Shuojia; Huang, Lichun; Mo, Minjia; Li, Minchao; Shao, Bule; Yu, Yunxian

    2017-01-01

    Objective: Our study aimed to investigate the nutritional vitamin D status of school children aged 9–15 years and white-collar workers in Zhejiang province, and evaluate the efficacy of low-dose-oral vitamin D supplementation in both populations. Methods: We conducted a prospective controlled trial during March 2014 to November 2015, comparing the efficacy of vitamin D supplements (400 IU/day) with non-intervention for 18 months in school children aged 9–15 years. Meanwhile, a before-after study was conducted among white-collar workers for 1 year. Serum 25(OH)D concentration was measured at baseline and after vitamin D supplementation, respectively. Results: At the baseline, 95% of school children and 84% of adult participants had vitamin D deficiency (<20 ng/mL). In school children, no difference was observed between the intervention and control groups with regard to anthropometric data. Serum 25(OH)D concentrations of the school children intervention group, school children control group and white-collar workers were 12.77 ± 3.01 ng/mL, 14.17 ± 3.59 ng/mL and 16.58 ± 3.66 ng/mL at baseline and increased to 17.34 ± 3.78 ng/mL, 18.04 ± 4.01 ng/mL and 17.75 ± 5.36 ng/mL after vitamin D supplementation, respectively. Although, after adjusting for potential confounders, the 400 IU oral vitamin D supplementation increased serum 25(OH)D concentration in school children (β = 0.81, p = 0.0426) as well as in white-collar workers (p = 0.0839), the prevalence of vitamin D deficiency was still very high among school children (79.23% in intervention group and 72.38% in control group) and white-collar workers (76.00%). Conclusions: High prevalence of vitamin D deficiency was common in these two study populations. Daily doses of 400 IU oral vitamin D supplementation was not able to adequately increase serum 25(OH)D concentrations. A suitable recommendation regarding the level of vitamin D supplementation is required for this Chinese population. PMID:28513555

  15. Influence of a single oral dose of vitamin D(2) on serum 25-hydroxyvitamin D concentrations in tuberculosis patients.

    PubMed

    Martineau, A R; Nanzer, A M; Satkunam, K R; Packe, G E; Rainbow, S J; Maunsell, Z J; Timms, P M; Venton, T R; Eldridge, S M; Davidson, R N; Wilkinson, R J; Griffiths, C J

    2009-01-01

    Newham Chest Clinic, London, UK. To determine the safety and efficacy of the administration of bolus-dose vitamin D(2) in elevating serum 25-hydroxyvitamin D (25[OH]D) concentrations in tuberculosis (TB) patients. A multi-ethnic cohort of TB patients was randomised to receive a single oral dose of 2.5 mg vitamin D(2) (n = 11) or placebo (n = 14). Serum 25(OH)D and corrected calcium concentrations were determined at baseline and 1 week and 8 weeks post-dose, and compared to those of a multi-ethnic cohort of 56 healthy adults receiving an identical dose of vitamin D(2). Hypovitaminosis D (serum 25[OH]D < 75 nmol/l) was present in all patients at baseline. A single oral dose of 2.5 mg vitamin D2 corrected hypovitaminosis D in all patients in the intervention arm of the study at 1 week post-dose, and induced a 109.5 nmol/l mean increase in their serum 25(OH)D concentration. Hypovitaminosis D recurred in 10/11 patients at 8 weeks post-dose. No patient receiving vitamin D(2) experienced hypercalcaemia. Patients receiving 2.5 mg vitamin D(2) experienced a greater mean increase in serum 25(OH)D at 1 week post-dose than healthy adults receiving 2.5 mg vitamin D(2). A single oral dose of 2.5 mg vitamin D(2) corrects hypovitaminosis D at 1 week but not at 8 weeks post-dose in TB patients.

  16. 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.

  17. 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.

  18. Effects of diet and exercise on plasma vitamin D (25(OH)D) levels in Vietnamese immigrant elderly in Sydney, Australia.

    PubMed

    Brock, K; Cant, R; Clemson, L; Mason, R S; Fraser, D R

    2007-03-01

    Vitamin D deficiency may be associated with osteoporosis and fractures in the elderly. In Australia where there is a sizeable Vietnamese population, research has not yet clarified the roles of diet, exercise and sun exposure in determining vitamin D status. Plasma samples for 25-hydroxy-vitamin D (25(OH)D); dietary intake of vitamin D and calcium; muscle strength and sun exposure were measured and weekly dairy intake, exercise levels and smoking habits were surveyed in free-living elderly of Vietnamese and Australian/British origin. There was marginal vitamin D deficiency (<37 nmol/L 25(OH)D) in 63% of Vietnamese but only in 37% of Australian/British born. Low dairy intake and no vigorous exercise were best predictors of vitamin D deficiency in Vietnamese, taking into account age, gender, dietary intake and sun exposure. Since these migrant elderly may not get adequate sun exposure due to either clothing customs or cultural norms that encourage fair (untanned) skin, it is important to encourage increased exercise and dairy intake.

  19. Treatment of refractory hyperparathyroidism in patients on hemodialysis by intermittent oral administration of 1,25(OH)2vitamin D3.

    PubMed

    Muramoto, H; Haruki, K; Yoshimura, A; Mimo, N; Oda, K; Tofuku, Y

    1991-01-01

    Intermittent oral administration of high dose 1,25(OH)2vitamin D3 was conducted in 7 patients associated with treatment-resistant secondary hyperparathyroidism (2nd HPT) on hemodialysis (HD) therapy. Each patient had a long history of HD therapy (range: 101-181 months, 145 +/- 29 months). Although serum calcium levels were maintained under the upper limit of the normal range with the appropriate dose of 1 alpha(OH)vitamin D3 every day before the present therapy, 2nd HPT could not have been controlled. The dose of 2-3 micrograms of 1,25(OH)2vitamin D3 3 times a week could successfully suppress serum levels of parathyroid hormone (iPTH) in all 7 patients after 20-32 weeks. The vitamin was given in the evening before each HD session and the dose and frequency of administration were dependent of the serum calcium level in each patient. After 20 weeks the iPTH-C and iPTH-intact levels decreased significantly from 35.0 +/- 15.8 to 18.6 +/- 11.7 ng/ml and from 533.2 +/- 200.0 to 249.5 +/- 136.2 pg/ml, respectively. The frequency of harmful elevations of serum calcium levels was not significantly increased in comparison with that in the previous period of the study, because serum calcium levels were strictly monitored with frequent checks. In conclusion, we could safely obtain an effect similar to the intravenous administration of the vitamin through the intermittent administration of a high oral dose 1,25(OH)2vitamin D3 in the treatment of refractory 2nd HPT in patients on HD therapy.

  20. Vitamin D in corticosteroid-naïve and corticosteroid-treated Duchenne muscular dystrophy: what dose achieves optimal 25(OH) vitamin D levels?

    PubMed

    Alshaikh, Nahla; Brunklaus, Andreas; Davis, Tracey; Robb, Stephanie A; Quinlivan, Ros; Munot, Pinki; Sarkozy, Anna; Muntoni, Francesco; Manzur, Adnan Y

    2016-10-01

    Assessment of the efficacy of vitamin D replenishment and maintenance doses required to attain optimal levels in boys with Duchenne muscular dystrophy (DMD). 25(OH)-vitamin D levels and concurrent vitamin D dosage were collected from retrospective case-note review of boys with DMD at the Dubowitz Neuromuscular Centre. Vitamin D levels were stratified as deficient at <25 nmol/L, insufficient at 25-49 nmol/L, adequate at 50-75 nmol/L and optimal at >75 nmol/L. 617 vitamin D samples were available from 197 boys (range 2-18 years)-69% from individuals on corticosteroids. Vitamin D-naïve boys (154 samples) showed deficiency in 28%, insufficiency in 42%, adequate levels in 24% and optimal levels in 6%. The vitamin D-supplemented group (463 samples) was tested while on different maintenance/replenishment doses. Three-month replenishment of daily 3000 IU (23 samples) or 6000 IU (37 samples) achieved optimal levels in 52% and 84%, respectively. 182 samples taken on 400 IU revealed deficiency in 19 (10%), insufficiency in 84 (47%), adequate levels in 67 (37%) and optimal levels in 11 (6%). 97 samples taken on 800 IU showed deficiency in 2 (2%), insufficiency in 17 (17%), adequate levels in 56 (58%) and optimal levels in 22 (23%). 81 samples were on 1000 IU and 14 samples on 1500 IU, with optimal levels in 35 (43%) and 9 (64%), respectively. No toxic level was seen (highest level 230 nmol/L). The prevalence of vitamin D deficiency and insufficiency in DMD is high. A 2-month replenishment regimen of 6000 IU and maintenance regimen of 1000-1500 IU/day was associated with optimal vitamin D levels. These data have important implications for optimising vitamin D dosing in DMD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  1. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis123

    PubMed Central

    Lambert, Helen; Hart, Kathryn; Smith, Colin P; Bucca, Giselda; Penson, Simon; Chope, Gemma; Hyppönen, Elina; Berry, Jacqueline; Vieth, Reinhold; Lanham-New, Susan

    2012-01-01

    Background: Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D2 and D3 in the raising of serum 25-hydroxyvitamin D [25(OH)D]. Objective: The objective of this article was to report a systematic review and meta-analysis of randomized controlled trials (RCTs) that have directly compared the effects of vitamin D2 and vitamin D3 on serum 25(OH)D concentrations in humans. Design: The ISI Web of Knowledge (January 1966 to July 2011) database was searched electronically for all relevant studies in adults that directly compared vitamin D3 with vitamin D2. The Cochrane Clinical Trials Registry, International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials. Results: A meta-analysis of RCTs indicated that supplementation with vitamin D3 had a significant and positive effect in the raising of serum 25(OH)D concentrations compared with the effect of vitamin D2 (P = 0.001). When the frequency of dosage administration was compared, there was a significant response for vitamin D3 when given as a bolus dose (P = 0.0002) compared with administration of vitamin D2, but the effect was lost with daily supplementation. Conclusions: This meta-analysis indicates that vitamin D3 is more efficacious at raising serum 25(OH)D concentrations than is vitamin D2, and thus vitamin D3 could potentially become the preferred choice for supplementation. However, additional research is required to examine the metabolic pathways involved in oral and intramuscular administration of vitamin D and the effects across age, sex, and ethnicity, which this review was unable to verify. PMID:22552031

  2. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis.

    PubMed

    Tripkovic, Laura; Lambert, Helen; Hart, Kathryn; Smith, Colin P; Bucca, Giselda; Penson, Simon; Chope, Gemma; Hyppönen, Elina; Berry, Jacqueline; Vieth, Reinhold; Lanham-New, Susan

    2012-06-01

    Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D2 and D3 in the raising of serum 25-hydroxyvitamin D [25(OH)D]. The objective of this article was to report a systematic review and meta-analysis of randomized controlled trials (RCTs) that have directly compared the effects of vitamin D2 and vitamin D3 on serum 25(OH)D concentrations in humans. The ISI Web of Knowledge (January 1966 to July 2011) database was searched electronically for all relevant studies in adults that directly compared vitamin D3 with vitamin D2. The Cochrane Clinical Trials Registry, International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials. A meta-analysis of RCTs indicated that supplementation with vitamin D3 had a significant and positive effect in the raising of serum 25(OH)D concentrations compared with the effect of vitamin D2 (P = 0.001). When the frequency of dosage administration was compared, there was a significant response for vitamin D3 when given as a bolus dose (P = 0.0002) compared with administration of vitamin D2, but the effect was lost with daily supplementation. This meta-analysis indicates that vitamin D3 is more efficacious at raising serum 25(OH)D concentrations than is vitamin D2, and thus vitamin D3) could potentially become the preferred choice for supplementation. However, additional research is required to examine the metabolic pathways involved in oral and intramuscular administration of vitamin D and the effects across age, sex, and ethnicity, which this review was unable to verify.

  3. Community Interventional Trial (CITFOMIST) of Vitamin D Fortified Versus Non-fortified Milk on Serum Levels of 25(OH) D in the Students of Tehran.

    PubMed

    Keshtkar, Abbas Ali; Ebrahimi, Mehdi; Khashayar, Patricia; Abdollahi, Zahra; Pouraram, Hamed; Salehi, Forouzan; Mohammadi, Zahra; Khosrokhavar, Roya; Larijani, Bagher

    2015-05-01

    As prevention of osteoporosis becomes more imperative with the global ageing of the population, establishing different measures to fight vitamin D deficiency will also become increasingly important. The aim of this study is to help assess the efficacy of vitamin D-fortified milk on circulating concentrations of 25(OH)D (as the primary outcome), a widely accepted indicator of vitamin D status, in Tehran students. Another objective of the protocol is to help assess the compliance with fortified dairy in students of different socioeconomic classes. The cluster-randomized trial (CITFOMIST) is conducted on 15- to19-year olds guidance and high school students of both genders from different districts of Tehran, in wintertime. The schools enrolled in this study are randomly assigned to receive one of the three groups of milk (whole milk, milk that contained 600 IU Vit D/1000cc, or milk that contained 1000 IU Vit D /1000cc) for a 30-day period. In order to study the effect of vitamin D-fortified milk on the circulating concentrations of 25(OH) D, a serum vitamin D levels are checked in a subgroup before and after the intervention. There are few data on the efficacy of incremental doses of vitamin D from fortified foods among adolescents. This is while developing an optimal model to fight vitamin D deficiency needs further research on bone health outcomes and the safety of vitamin D-fortified products. The modified version of this protocol could be applied in different parts of the country to assess the efficacy of a vitamin-D product.

  4. Selective upregulation of the expression of plasma membrane calcium ATPase isoforms upon differentiation and 1,25(OH)2D3-vitamin treatment of colon cancer cells.

    PubMed

    Ribiczey, Polett; Papp, Béla; Homolya, László; Enyedi, Ágnes; Kovács, Tünde

    2015-08-14

    We have previously presented co-expression of the plasma membrane calcium ATPase isoforms 4b (PMCA4b) and 1b (PMCA1b) in colon carcinoma cells, and selective upregulation of PMCA4b during differentiation initiated by short chain fatty acids or post-confluent growth. Here we show that the induction of PMCA4b expression is a characteristic feature of the post-confluency-induced differentiation of both enterocyte-type and goblet cell-type colon cancer cells. Vitamin D3 (1,25(OH)2D3) is a well-known regulator of intestinal Ca(2+) absorption and of basic cell functions such as growth and differentiation in various cell types. As PMCA proteins are involved both in intestinal Ca(2+) absorption and adenocarcinoma cell differentiation, we investigated the effect of 1,25(OH)2D3 on PMCA expression in enterocyte-like colon carcinoma cells, and monitored its effect on the expression of various differentiation markers. 1,25(OH)2D3 stimulated PMCA1b, but not PMCA4b expression without modulating the expression of the majority of the differentiation markers examined. Caco-2 cells differentiated in post-confluent cultures present normal enterocyte-like intestinal epithelial phenotype. To better understand the role of PMCA proteins in vectorial Ca(2+) transport by enterocytes, we also studied their subcellular localization in mature polarized Caco-2 cells. Both PMCA isoforms were located to the basolateral membrane, and the PMCA-specific immunofluorescent signal was significantly higher in vitamin D3-treated cells, underlining the 1,25(OH)2D3-induced upregulation of PMCA (presumably 1b isoform) expression in differentiated Caco-2 cells. We suggest that while PMCA1b has a housekeeping function in colon cancer cells, PMCA4b participates in the reorganization of the Ca(2+) signalling machinery during cell differentiation. The subcellular localization of PMCA1b and its selective 1,25(OH)2D3-dependent upregulation indicate that this isoform may have a specific role in 1,25(OH)2D3

  5. Elevated serum 1,25(OH)2-vitamin D3 level attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction in kl/kl mice

    PubMed Central

    Sun, Yujing; Zhou, Gengyin; Gui, Ting; Shimokado, Aiko; Nakanishi, Masako; Oikawa, Kosuke; Sato, Fuyuki; Muragaki, Yasuteru

    2014-01-01

    Previous studies have suggested that Klotho provides reno-protection against unilateral ureteral obstruction (UUO)-induced renal tubulointerstitial fibrosis (RTF). Because the existing studies are mainly performed using heterozygous Klotho mutant (HT) mice, we focused on the effect of UUO on homozygous Klotho mutant (kl/kl) mice. UUO kidneys from HT mice showed a significantly higher level of RTF and TGF-β/Smad3 signaling than wild-type (WT) mice, whereas both were greatly suppressed in kl/kl mice. Primary proximal tubular epithelial culture cells isolated from kl/kl mice showed no suppression in TGF-β1-induced epithelial mesenchymal transition (EMT) compared to those from HT mice. In the renal epithelial cell line NRK52E, a large amount of inorganic phosphate (Pi), FGF23, or calcitriol was added to the medium to mimic the in vivo homeostasis of kl/kl mice. Neither Pi nor FGF23 antagonized TGF-β1-induced EMT. In contrast, calcitriol ameliorated TGF-β1-induced EMT in a dose dependent manner. A vitamin D3-deficient diet normalized the serum 1,25 (OH)2 vitamin D3 level in kl/kl mice and enhanced UUO-induced RTF and TGF-β/Smad3 signaling. In conclusion, the alleviation of UUO-induced RTF in kl/kl mice was due to the TGF-β1 signaling suppression caused by an elevated serum 1, 25(OH)2 vitamin D3. PMID:25297969

  6. Evaluation of automated immunoassays for 25(OH)-vitamin D determination in different critical populations before and after standardization of the assays.

    PubMed

    Cavalier, Etienne; Lukas, Pierre; Crine, Yannick; Peeters, Stéphanie; Carlisi, Agnès; Le Goff, Caroline; Gadisseur, Romy; Delanaye, Pierre; Souberbielle, Jean-Claude

    2014-04-20

    Standardization of immunoassays for 25(OH)-vitamin D determination is a major problem in clinical practice. A worldwide standardization program has started to address this and will reduce the bias observed between immunoassays. We aimed to calibrate 5 immunoassays on a LC-MS/MS traceable to the SRM 2972 and the ID-LC-MS/MS 25(OH)D Reference Method Procedure to see if the re-standardization would be efficient in a population of 3rd trimester pregnant women (PW), hemodialysis (HD) and osteoporosis (OP) patient. 184 serum samples (25(OH)D: 8.4-87 ng/ml) were selected to calibrate the immunoassays (Abbott-Architect, Roche-Elecsys, DiaSorin-Liaison, Siemens-Centaur and IDS-iSYS). Chromsystems MassChrom method was used as the referenced. Serum obtained in 34 PW, 25 HD and 34 OP patients were used as comparatives. After adjusting to LC-MS/MS, immunoassays had regression slopes nearly identical to 1.0 with intercepts <0.5 ng/ml. However, in special populations, a systematic bias was still observed, except for iSYS. Re-standardization of 25(OH)D immunoassay will globally improve the differences. However, patients with a different serum matrix will still present significantly different results when they will be run with different methods. For those patients, the LC-MS/MS method seems to be the method of choice, even if some immunoassays are less influenced than others. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Abnormal neurogenesis in the dentate gyrus of adult mice lacking 1,25-dihydroxy vitamin D3 (1,25-(OH)2 D3).

    PubMed

    Zhu, Ying; Zhou, Rong; Yang, Rong; Zhang, Zhuo; Bai, Yinyang; Chang, Fei; Li, Lin; Sokabe, Masahiro; Goltzman, David; Miao, Dengshun; Chen, Ling

    2012-03-01

    In this study, we employed 1α-hydroxylase knockout (1α-(OH)ase(-/-) ) mice to investigate the influence of 1,25-dihydroxy vitamin D(3) (1,25-(OH)(2) D(3) ) deficiency on the adult neurogenesis in the hippocampal dentate gyrus (DG). The numbers of both 24-hr-old BrdU(+) cells and proliferating cell nuclear antigen positive cells in 8-week-old 1α-(OH)ase(-/-) mice increased approximately twofold compared with wild-type littermates. In contrast, the numbers of 7- and 28-day-old BrdU(+) cells in 1α-(OH)ase(-/-) mice decreased by 50% compared with wild-type mice, while the proportion of BrdU(+) /NeuN(+) cells in BrdU(+) population showed no difference between 1α-(OH)ase(-/-) and wild-type mice. Apoptotic cells in the subgranular zone (SGZ) of DG markedly increased in 1α-(OH)ase(-/-) mice. Replenishment of 1,25-(OH)(2) D(3) , but not correction of serum calcium and phosphorus levels, completely prevented changes in the neurogenesis in 1α-(OH)ase(-/-) mice. The absence of 1,25-(OH)(2) D(3) led to an increase in the expression of L-type voltage-gated calcium channel (L-VGCC) and a decrease in the nerve growth factor (NGF) mRNA level. Treatment with the L-VGCC inhibitor nifedipine blocked the increased cell proliferations by 1,25-(OH)(2) D(3) deficiency. Administration of NGF significantly attenuated the loss of newborn neurons in 1α-(OH)ase(-/-) mice. Copyright © 2010 Wiley Periodicals, Inc.

  8. Low 25-OH-vitamin D levels reflect hepatic dysfunction and are associated with mortality in patients with liver cirrhosis.

    PubMed

    Paternostro, Rafael; Wagner, Doris; Reiberger, Thomas; Mandorfer, Mattias; Schwarzer, Remy; Ferlitsch, Monika; Trauner, Michael; Peck-Radosavljevic, Markus; Ferlitsch, Arnulf

    2017-01-01

    Vitamin D deficiency is frequent in patients with cirrhosis. The aims of this study were to evaluate the relation of vitamin D status to portal hypertension, degree of liver dysfunction and survival. Patients with cirrhosis who have been tested for 25-OH-vitamin D levels were retrospectively included. Vitamin D deficiency was defined as 25-OH-vitamin D levels <10 ng/ml. Child-Pugh score, model for end-stage liver disease (MELD) and available hepatic venous pressure gradient (HVPG) were recorded. Mortality was documented during follow-up. A total of 199 patients were included. Prevalence of vitamin D deficiency (<10 ng/ml) was 40% (79/199), with 14% in Child-Pugh stage A, 39% in Child-Pugh stage B and 47% in Child-Pugh stage C (p = 0.001). Vitamin D deficiency was more common in patients with clinically significant portal hypertension (CSPH, HVPG ≥ 10 mm Hg) than in patients without (43.5% vs. 24.4%, p = 0.025). Significantly more deaths were observed in patients with vitamin D deficiency (32.9%, 26/79 vs. 13.3%, 16/120; p = 0.001). COX regression found presence of hepatocellular carcinoma (p < 0.001; HR: 5.763 95%CI:2.183-15.213), presence of CSPH (p = 0.026; HR: 5.487 95%CI: 1.226-24.55) and Child-Pugh stage C (p = 0.003; HR:5.429 95%CI: 1.771-16.638) as independent risk factors for mortality. Furthermore we could show a tendency towards group vitamin D deficiency being an independent risk factor (p = 0.060; HR: 1.86 95%CI:0.974-3.552). Vitamin D levels progressively decrease in more advanced Child stages and in patients with increasing HVPG. Vitamin D deficiency might be a valuable predictor of mortality in cirrhosis.

  9. The Relationship between 25 (OH) D Levels (Vitamin D) and Bone Mineral Density (BMD) in a Saudi Population in a Community-Based Setting

    PubMed Central

    Alkhenizan, Abdullah; Mahmoud, Ahmed; Hussain, Aneela; Gabr, Alia; Alsoghayer, Suad; Eldali, Abdelmoneim

    2017-01-01

    Background Vitamin D deficiency has been linked to an increased risk of osteoporosis. Vitamin D deficiency has reached high levels in the Saudi population, but there is conflicting evidence both in the Saudi population, and worldwide, regarding the existence of a correlation between these low vitamin D levels and reduced BMD (bone mineral density), or osteoporosis. Objective The objective of this study was primarily to determine whether there was a correlation between vitamin D deficiency and osteoporosis in the Saudi population. We aimed to investigate whether the high levels of vitamin D deficiency and insufficiency would translate to higher prevalence of osteoporosis, and whether there is a correlation between vitamin D levels and bone mineral density. Materials and methods This was a community based cross sectional study conducted in the Family Medicine Clinics at King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia. Electronic records of 1723 patients were reviewed. Laboratory and radiology results were collected, including vitamin D levels, calcium levels, and bone mineral density scan results. Results Among the whole population, 61.5% had moderate to severe vitamin D deficiency with levels less than 50nmol/L. 9.1% of the population had osteoporosis, and 38.6% had osteopenia. Among the whole population, there was no significant correlation between spine or total femoral BMD and serum 25(OH) D. Conclusion Vitamin D deficiency is prevalent in the Saudi population. However, no correlation has been found between vitamin D deficiency and reduced bone mineral density in any age group, in males or females, Saudis or Non-Saudis, in our population in Riyadh, Saudi Arabia. PMID:28046015

  10. 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

  11. 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

  12. Vitamin D2 Supplementation Amplifies Eccentric Exercise-Induced Muscle Damage in NASCAR Pit Crew Athletes

    PubMed Central

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

    2013-01-01

    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. PMID:24362707

  13. 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.

  14. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Vitamin D2. 172.379 Section 172.379 Food and Drugs... Dietary and Nutritional Additives § 172.379 Vitamin D2. Vitamin D2 may be used safely in foods as a... prescribed conditions: (a) Vitamin D2, also known as ergocalciferol, is the chemical...

  15. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Vitamin D2. 172.379 Section 172.379 Food and Drugs... Dietary and Nutritional Additives § 172.379 Vitamin D2. Vitamin D2 may be used safely in foods as a... prescribed conditions: (a) Vitamin D2, also known as ergocalciferol, is the chemical...

  16. 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

    2016-06-03

    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.

  17. Dosage de la 25 OH vitamine D: expérience du laboratoire central de biochimie clinique du Centre Hospitalier Ibn Sina

    PubMed Central

    Handor, Najat; Elalami, Sanae; Bouabdellah, Mounya; Srifi, Abdelatif; Esselmani, Hicham; Benchekroun, Laila; Chabraoui, Layachi

    2014-01-01

    La connaissance de la physiologie de la vitamine D a considérablement progressé ces dernières années, la faisant passer de simple vitamine à tropisme purement phosphocalcique et osseux à celui d'hormone jouant un rôle crucial dans de nombreux mécanismes physiologiques et dont le déficit est impliqué dans plusieurs pathologies. Nous présentons, dans ce travail, l'expérience du laboratoire central de biochimie dans le dosage de la 25 OH vitamine D. Enquête descriptive exhaustive portant sur les dosages de la 25 OH vitamine D effectués chez 350 patients du Centre Hospitalier Ibn Sina (CHIS). La méthode adoptée est un dosage immunologique par chimiluminescence sur microparticules réalisés sur l'auto-analyseur ARCHITECT 8200 (ABBOTT®) pendant une période de six mois (du 01 Juin 2011 au 31 Decembre 2011). Quatre vingt et onze pourcent des patients présentent une hypovitaminose. En effet 76,6% des patients souffrent d'une insuffisance en vitamine D, 12,3% de carence vitaminique et 2,6% d'ostéomalacie. L'hypovitaminose est associée dans 92,18% des cas à une normocalcémie, dans 76,87% des cas à une Hyperparathormone, dans 92,81% à des troubles thyroïdiens et dans 97,5% à une insuffisance rénale. Par ailleurs aucune relation statistiquement significative n'est établie entre l'hypovitaminose et le diabète. A la lumière des implications des hypovitaminoses dans plusieurs pathologies ou dans leurs complications et au vu du nombre élevé de patients présentant un déficit en vitamine D, il paraît judicieux d'envisager une étude épidémiologique sur le statut en vitamine D dans la population marocaine comme outil préventif avant d'élargir le dosage de ce marqueur biologique en vue d'une éventuelle supplémentation. PMID:25374649

  18. 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

  19. 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

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

    PubMed

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

    2014-03-05

    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.

  1. 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

  2. 1,25(OH)2-vitamin D3 enhances the stimulating effect of leucine and insulin on protein synthesis rate through Akt/PKB and mTOR mediated pathways in murine C2C12 skeletal myotubes.

    PubMed

    Salles, Jérôme; Chanet, Audrey; Giraudet, Christophe; Patrac, Véronique; Pierre, Philippe; Jourdan, Marion; Luiking, Yvette C; Verlaan, Sjors; Migné, Carole; Boirie, Yves; Walrand, Stéphane

    2013-12-01

    In recent years, there has been a growing body of evidence pointing to an effect of vitamin D on muscle mass and function. Our aim was to investigate the combined effect of 1,25(OH)2-vitamin D3 (1,25(OH)2D3) with anabolic factors insulin and leucine on protein fractional synthesis rate (FSR) and regulation in the mouse C2C12 myotube. After differentiation, myotubes were cultured in 1,25(OH)2D3 solutions at 0, 1, or 10 nM for 72 h. Cells were treated by L-[1-(13) C]valine and puromycin in presence or not of leucine and insulin, and protein FSR was determined by measuring tracer enrichments and puromycin incorporation in proteins, respectively. Protein expression and phosphorylation state of insulin receptor (IR), Akt, GSK3, mTOR, p70 S6 kinase, rpS6, and 4EBP1 were measured by Western blot. Transcript levels of IR and 1,25(OH)2D3 receptor (VDR) were determined by qPCR. 1,25(OH)2D3 (10 nM) with leucine and insulin increased protein FSR in C2C12 myotubes (14-16%). IR and VDR mRNA expression was increased with 1,25(OH)2D3 treatment. The Akt/mTOR-dependent pathway was activated by insulin and leucine and further enhanced by 1,25(OH)2D3. 1,25(OH)2D3 sensitizes the Akt/mTOR-dependant pathway to the stimulating effect of leucine and insulin, resulting in a further activation of protein synthesis in murine C2C12 skeletal myotubes. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. 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 Central

    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. PMID:25435877

  4. 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.

  5. 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 with...

  6. 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...) Vitamin D2 bakers yeast is the substance produced by exposing bakers yeast (Saccharomyces cerevisiae) to...

  7. 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

    USDA-ARS?s Scientific Manuscript database

    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...

  8. 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 generally...

  9. 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...

  10. 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...

  11. 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...

  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. 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

  14. Differential effects of vitamin D2 and D3 supplements on 25-hydroxyvitamin D level are dose, sex, and time dependent: a randomized controlled trial.

    PubMed

    Hammami, Muhammad M; Yusuf, Ahmed

    2017-02-24

    Vitamin D (D) supplements are indispensable for its world-wide deficiency. Controversy continues on ergocalciferol (D2) and cholecalciferol (D3) relative potency as well as on dosing-schedule and sex role in raising 25-hydroxy D (25(OH)D) level, the best indicator of D status. We randomized 279 adults to daily D2, D3, D2/D3, or placebo; 2-weekly D2 or D3; or 4-weekly D2 or D3 (250,000 IU over/140 days). Randomization sequence, stratified by body-mass-index (BMI) and sex, was concealed from study coordinators and participants who were then blinded to capsules' content. D2, D3, 25(OH)D2, and 25(OH)D3 Serum levels were determined blindly on days 0,1,2,3,4,7,14, and 2-weekly thereafter by high performance liquid chromatography assay. The results of 269 participants were available for analysis. Primary endpoint was area-under-the-curve (AUC) of 25(OH)D (25(OH)D2 + 25(OH)D3) adjusted for sex, BMI, and baseline 25(OH)D level. Mean(SD) age was 33.0(8.5) year, 41% were males, and 85% completed follow-up. Baseline 25(OH)D level was 39.8(11.9) and increased by 3.3(11.6) and 28.6(16.3) nmol/L, in the placebo and active-treatment groups, respectively. AUC from day 0 to 140 (AUC140) of 25(OH)D was 40% (D3 daily) to 55% (D3 2-weekly) higher with active-treatment than placebo (p < 0.001). 25(OH)D2 AUC140 was higher in daily than 2-weekly (17%, p = 0.006) and 4-weekly (20%, p = 0.001) D2-treated groups. 25(OH)D3 AUC140 was lower in daily than 2-weekly (11%, p = 0.002) and 4-weekly D3-treated groups (10%, p = 0.008). In D2-treated groups, there was 16.4 nmol/L decrease in 25(OH)D3 level that correlated (p < 0.001) with 25(OH)D2 level increase (r = 0.48) and baseline 25(OH)D level (r = 0.58), in one participant with measurable baseline 25(OH)D2 level, D3 caused a similar decrease in 25(OH)D2 level, while in the D2/D3-treated group, 25(OH)D3 level didn't increase. Incremental AUC from day 0 to 7 (AUC7) of D3 and 25(OH)D3 in D3-treated groups were

  15. Intravenous 1α, 25[OH]2 vitamin D3 (calcitriol) pulse therapy for bone lesions in a murine model of chronic cadmium toxicosis

    PubMed Central

    Kurata, Yoshimasa; Katsuta, Osamu; Hiratsuka, Hideaki; Tsuchitani, Minoru; Umemura, Takashi

    2001-01-01

    The aim of the present study was to clarify the therapeutic effects of 1α, 25[OH]2 vitamin D3 (calcitriol) pulse injection on bone lesions induced in a rat model of chronic cadmium toxicosis. Ovariectomized (OVX) and control-operated (sham-OVX) rats were given repeated intravenous injections of 0.5 mg/kg/day CdCl2 for 70 weeks. The rats were then treated intravenously with 0.02 μg/kg/day calcitriol 3 days per week for 8 weeks. CdCl2 treatment induced increases in osteoid volumes of the femur cortex and trabecula. This change was accompanied by an increase in the volume of iron deposition at the mineralization front of the trabeculae and a reduction in mineral density. Abnormalities of bone metabolic parameters, which were increases in the blood calcium, inorganic phosphorous, bone-specific alkaline phosphatase, parathyroid hormone (PTH) and osteocalcin levels, and in the urine deoxypyridinoline (D-PYR) level, were also induced. Calcitriol treatment increased the blood calcium and inorganic phosphorous levels, and reduced the blood PTH level. Decreases in blood tartrate-resistant acid phosphatase and urine d-PYR levels were also induced indicating that bone resorption was suppressed. The findings indicated that the increased osteoid volume of the cortex and Fe-deposition volume of the trabecula were improved. These effects or improvements were observed in the sham-OVX rats but not in the OVX rats. PMID:11422540

  16. Intravenous 1alpha, 25[OH]2 vitamin D3 (calcitriol) pulse therapy for bone lesions in a murine model of chronic cadmium toxicosis.

    PubMed

    Kurata, Y; Katsuta, O; Hiratsuka, H; Tsuchitani, M; Umemura, T

    2001-02-01

    The aim of the present study was to clarify the therapeutic effects of 1alpha, 25[OH]2 vitamin D3 (calcitriol) pulse injection on bone lesions induced in a rat model of chronic cadmium toxicosis. Ovariectomized (OVX) and control-operated (sham-OVX) rats were given repeated intravenous injections of 0.5 mg/kg/day CdCl2 for 70 weeks. The rats were then treated intravenously with 0.02 microg/kg/day calcitriol 3 days per week for 8 weeks. CdCl2 treatment induced increases in osteoid volumes of the femur cortex and trabecula. This change was accompanied by an increase in the volume of iron deposition at the mineralization front of the trabeculae and a reduction in mineral density. Abnormalities of bone metabolic parameters, which were increases in the blood calcium, inorganic phosphorous, bone-specific alkaline phosphatase, parathyroid hormone (PTH) and osteocalcin levels, and in the urine deoxypyridinoline (D-PYR) level, were also induced. Calcitriol treatment increased the blood calcium and inorganic phosphorous levels, and reduced the blood PTH level. Decreases in blood tartrate-resistant acid phosphatase and urine d-PYR levels were also induced indicating that bone resorption was suppressed. The findings indicated that the increased osteoid volume of the cortex and Fe-deposition volume of the trabecula were improved. These effects or improvements were observed in the sham-OVX rats but not in the OVX rats.

  17. Actions of 1,25(OH)2-vitamin D3 on the cellular cycle depend on VDR and p38 MAPK in skeletal muscle cells.

    PubMed

    Irazoqui, Ana P; Boland, Ricardo L; Buitrago, Claudia G

    2014-12-01

    Previously, we have reported that 1,25(OH)2-vitamin D3 (1,25D) activates p38 MAPK (p38) in a vitamin D receptor (VDR)-dependent manner in proliferative C2C12 myoblast cells. It was also demonstrated that 1,25D promotes muscle cell proliferation and differentiation. However, we did not study these hormone actions in depth. In this study we have investigated whether the VDR and p38 participate in the signaling mechanism triggered by 1,25D. In C2C12 cells, the VDR was knocked down by a shRNA, and p38 was specifically inhibited using SB-203580. Results from cell cycle studies indicated that hormone stimulation prompts a peak of S-phase followed by an arrest in the G0/G1-phase, events which were dependent on VDR and p38. Moreover, 1,25D increases the expression of cyclin D3 and the cyclin-dependent kinase inhibitors, p21(Waf1/Cip1) and p27(Kip1), while cyclin D1 protein levels did not change during G0/G1 arrest. In all these events, p38 and VDR were required. At the same time, a 1,25D-dependent acute increase in myogenin expression was observed, indicating that the G0/G1 arrest of cells is a pro-differentiative event. Immunocytochemical assays revealed co-localization of VDR and cyclin D3, promoted by 1,25D in a p38-dependent manner. When cyclin D3 expression was silenced, VDR and myogenin levels were downregulated, indicating that cyclin D3 was required for 1,25D-induced VDR expression and the concomitant entrance into the differentiation process. In conclusion, the VDR and p38 are involved in control of the cellular cycle by 1,25D in skeletal muscle cells, providing key information on the mechanisms underlying hormone regulation of myogenesis.

  18. 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.

  19. NFκB pathway is down-regulated by 1α,25(OH)(2)-vitamin D(3) in endothelial cells transformed by Kaposi sarcoma-associated herpes virus G protein coupled receptor.

    PubMed

    Gonzalez-Pardo, Verónica; D'Elia, Noelia; Verstuyf, Annemieke; Boland, Ricardo; Russo de Boland, Ana

    2012-09-01

    We have previously demonstrated that 1α,25 dihydroxy-vitamin D(3) (1α,25(OH)(2)D(3)) has antiproliferative effects on the growth of endothelial cells transformed by the viral G protein-coupled receptor associated to Kaposi sarcoma (vGPCR). In this work, we have investigated whether 1α,25(OH)(2)D(3) exerts its growth inhibitory effects by inhibiting the Nuclear Factor κ B (NFκB) pathway which is highly activated by vGPCR. Cell proliferation studies demonstrated that 1α,25(OH)(2)D(3), similarly to bortezomib, a proteosome inhibitor that suppresses the activation of NFκB, reduced the proliferation of endothelial cells transformed by vGPCR (SVEC-vGPCR). The activity of NFκB in these cells decreased by 70% upon 1α,25(OH)(2)D(3) treatment. Furthermore, time and dose response studies showed that the hormone significantly decreased NFκB and increased IκBα mRNA and protein levels in SVEC-vGPCR cells, whereas in SVEC only IκBα increased significantly. Moreover, NFκB translocation to the nucleus was inhibited and occurred by a mechanism independent of NFκB association with vitamin D(3) receptor (VDR). 1α,25(OH)(2)D(3)-induced increase in IκBα required de novo protein synthesis, and was independent of MAPK and PI3K/Akt pathways. Altogether, these results suggest that down-regulation of the NFκB pathway is part of the mechanism involved in the antiproliferative effects of 1α,25(OH)(2)D(3) on endothelial cells transformed by vGPCR. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. 20-Hydroxyvitamin D2 is a noncalcemic analog of vitamin D with potent antiproliferative and prodifferentiation activities in normal and malignant cells

    PubMed Central

    Kim, Tae-Kang; Janjetovic, Zorica; Tuckey, Robert C.; Bieniek, Radoslaw; Yue, Junming; Li, Wei; Chen, Jianjun; Nguyen, Minh N.; Tang, Edith K. Y.; Miller, Duane; Chen, Tai C.; Holick, Michael

    2011-01-01

    20-hydroxyvitamin D2 [20(OH)D2] inhibits DNA synthesis in epidermal keratinocytes, melanocytes, and melanoma cells in a dose- and time-dependent manner. This inhibition is dependent on cell type, with keratinocytes and melanoma cells being more sensitive than normal melanocytes. The antiproliferative activity of 20(OH)D2 is similar to that of 1,25(OH)2D3 and of newly synthesized 1,20(OH)2D2 but significantly higher than that of 25(OH)D3. 20(OH)D2 also displays tumorostatic effects. In keratinocytes 20(OH)D2 inhibits expression of cyclins and stimulates involucrin expression. It also stimulates CYP24 expression, however, to a significantly lower degree than that by 1,25(OH)2D3 or 25(OH)D3. 20(OH)D2 is a poor substrate for CYP27B1 with overall catalytic efficiency being 24- and 41-fold lower than for 25(OH)D3 with the mouse and human enzymes, respectively. No conversion of 20(OH)D2 to 1,20(OH)2D2 was detected in intact HaCaT keratinocytes. 20(OH)D2 also demonstrates anti-leukemic activity but with lower potency than 1,25(OH)2D3. The phenotypic effects of 20(OH)D2 are mediated through interaction with the vitamin D receptor (VDR) as documented by attenuation of cell proliferation after silencing of VDR, by enhancement of the inhibitory effect through stable overexpression of VDR and by the demonstration that 20(OH)D2 induces time-dependent translocation of VDR from the cytoplasm to the nucleus at a comparable rate to that for 1,25(OH)2D3. In vivo tests show that while 1,25(OH)2D3 at doses as low as 0.8 μg/kg induces calcium deposits in the kidney and heart, 20(OH)D2 is devoid of such activity even at doses as high as 4 μg/kg. Silencing of CY27B1 in human keratinocytes showed that 20(OH)D2 does not require its transformation to 1,20(OH)2D2 for its biological activity. Thus 20(OH)D2 shows cell-type dependent antiproliferative and prodifferentiation activities through activation of VDR, while having no detectable toxic calcemic activity, and is a poor substrate for CYP

  1. Determination of vitamins D2, D3, K1 and K3 and some hydroxy metabolites of vitamin D3 in plasma using a continuous clean-up-preconcentration procedure coupled on-line with liquid chromatography-UV detection.

    PubMed

    Ortiz Boyer, F; Fernández Romero, J M; Luque de Castro, M D; Quesada, J M

    1999-03-01

    A semi-automatic procedure for the continuous clean-up and concentration of several fat-soluble vitamins prior to their separation by HPLC and UV detection is reported. The procedure is based on the use of a minicolumn packed with aminopropylsilica as sorbent located prior to the chromatographic detection system. The overall process was developed and applied to the main liposoluble vitamins (A, D2, D3, E, K1, K3) and several hydroxy metabolites of vitamin D3 [25-(OH)-D3,24,25-(OH)2-D3 and 1,25-(OH)2-D3]. All the analytes were monitored at a compromise wavelength of 270 nm. Calibration graphs were constructed between 0.01 and 100 ng ml-1 for vitamin D2 and D3 and their hydroxy metabolites, between 0.1 and 100 ng ml-1 for vitamin A, K1 and K3 and between 1 and 100 ng ml-1 for vitamin E, with excellent regression coefficients (> or = 0.9901) in all cases. The precision was established at two concentration levels with acceptable RSDs in all instances (between 3.6 and 8.7%). The method was appropriate for the determination of vitamin D2, D3, K1 and K3 and the 24,25-dihydroxy and 25-hydroxy metabolites of vitamin D3 in human plasma. The method was applied to plasma samples spiked with the target analytes and the recoveries ranged between 78 and 109%.

  2. 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.

  3. 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.

    PubMed

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

    2002-09-01

    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.

  4. 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.

  5. 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.

  6. Relevance of parathyroid hormone (PTH), vitamin 25(OH)D3, calcitonin (CT), bone metabolic markers, and bone mass density (BMD) in 860 female cases.

    PubMed

    Zhang, M; Li, Y; Ma, Q; Mao, W; Gao, Y; Liu, Y; Liang, B

    2015-01-01

    To study the relevance of PTH, 25(OH)D3, CT, bone resorption markers C-terminal telopeptide of type I (CTX-1), and tartrate-resistant acid phosphatase (TRACP), bone formation markers bone gla protein (BGP), bone alkaline phosphatase (BALP) with the femoral neck BMD in females. PTH, 25(OH)D3, CT, CTX-1, TRACP, BGP, and BALP were detected by an enzyme immunoassay analyzer and femoral neck BMD were measured by a BMD detector. The results of 860 females were divided into several groups according to standard of five-year age intervals. SPSS 13.0 software was used for statistical analysis. The measured values of PTH, 25(OH) D3 and CT had no differences in 35-50 age group. The measured values of 25(OH) D3 began to decline after the age of 50, and 25(OH)D3 had positive relevance with BMD. The values of CT were decreased in the age groups from 65 to 79 years old, and were significant positive correlated with BMD. The CTX-1 and TRACP had negative relevance with BMD in 35-45 age group and BGP and BALP had positive relevance with BMD in 35-45 age group. The BGP, BALP increased significantly in 50-60 age group, and CTX-1, TRACP, BGP, and BALP had negative relevance with BMD in 50-60 age group. BGP and BALP began to decline and had positive relevance with BMD after the age of 65, and CTX-1 and TRACP had negative relevance with BMD after the age of 65. PTH, 25(OH)D3, CT, CTX-1, TRACP, BGP, and BALP were the important technical means for monitoring the level of bone metabolism and the diagnosis and differential diagnosis of osteoporosis.

  7. Prevalence of 25-OH vitamin D deficiency in a population of hemodialysis patients and efficacy of an oral ergocalciferol supplementation regimen.

    PubMed

    Porter, Anna; Gilmartin, Cheryl; Srisakul, Usasiri; Arruda, Jose; Akkina, Sanjeev

    2013-01-01

    Optimal dosing regimens for 25-OH vitamin D (VitD) deficiency are unknown in hemodialysis (HD) patients. Our aim was to evaluate the efficacy of prescribing ergocalciferol supplementation based on KDOQI guidelines for chronic kidney disease (CKD) stages III-IV in HD patients. We conducted a retrospective study of 96 urban, predominately African-American HD patients at a single-center dialysis unit with VitD insufficiency or deficiency treated with ergocalciferol. Patients were classified as either compliant or non-compliant with supplementation as determined by review of pharmacy records. The primary outcome was VitD levels 6 months after initiation of treatment and secondary outcomes were VitD levels at 11 months, bone/mineral and anemia parameters. The population was predominately African-American (69%) and Hispanic (28%). There were 61 individuals in the compliant group and 35 individuals in the non-compliant group. The compliant group was older but otherwise similar in demographics and co-morbid conditions to the non-compliant group. After 6 months of treatment, the compliant group had a significant increase in VitD level (14.7 ± 6.0 to 28.7 ± 10.0 ng/ml, p < 0.0001) compared to the non-compliant group (14.7 ± 5.5 to 14.8 ± 7.1 ng/ml, p = 0.95). There were no differences in the incidence of hypercalcemia between the two groups. Except for a decrease in phosphorus in the compliant group (5.6 ± 1.6 to 4.9 ± 1.7 mg/dl, p = 0.004), there were no significant difference in bone/mineral or anemia parameters including dosing of darbepoetin. An ergocalciferol-prescribing strategy using the KDOQI guidelines for stage III-IV kidney disease in HD patients with VitD deficiency or insufficiency is inadequate to achieve repletion or maintenance of normal VitD levels. Copyright © 2013 S. Karger AG, Basel.

  8. MAP kinases p38 and JNK are activated by the steroid hormone 1alpha,25(OH)2-vitamin D3 in the C2C12 muscle cell line.

    PubMed

    Buitrago, Claudia G; Ronda, Ana C; de Boland, Ana Russo; Boland, Ricardo

    2006-03-01

    In chick skeletal muscle cell primary cultures, we previously demonstrated that 1alpha,25(OH)2-vitamin D3 [1alpha,25(OH)2D3], the hormonally active form of vitamin D, increases the phosphorylation and activity of the extracellular signal-regulated mitogen-activated protein (MAP) kinase isoforms ERK1 and ERK2, their subsequent translocation to the nucleus and involvement in DNA synthesis stimulation. In this study, we show that other members of the MAP kinase superfamily are also activated by the hormone. Using the muscle cell line C2C12 we found that 1alpha,25(OH)2D3 within 1 min phosphorylates and increases the activity of p38 MAPK. The immediately upstream mitogen-activated protein kinase kinases 3/6 (MKK3/MKK6) were also phosphorylated by the hormone suggesting their participation in p38 activation. 1Alpha,25(OH)2D3 was able to dephosphorylate/activate the ubiquitous cytosolic tyrosine kinase c-Src in C2C12 cells and studies with specific inhibitors imply that Src participates in hormone induced-p38 activation. Of relevance, 1alpha,25(OH)2D3 induced in the C2C12 line the stimulation of mitogen-activated protein kinase activating protein kinase 2 (MAPKAP-kinase 2) and subsequent phosphorylation of heat shock protein 27 (HSP27) in a p38 kinase activation-dependent manner. Treatment with the p38 inhibitor, SB203580, blocked p38 phosphorylation caused by the hormone and inhibited the phosphorylation of its downstrean substrates. 1Alpha,25(OH)2D3 also promotes the phosphorylation of c-jun N-terminal protein kinases (JNK 1/2), the response is fast (0.5-1 min) and maximal phosphorylation of the enzyme is observed at physiological doses of 1alpha,25(OH)2D3 (1 nM). The relative contribution of ERK-1/2, p38, and JNK-1/2 and their interrelationships in hormonal regulation of muscle cell proliferation and differentiation remain to be established.

  9. Development of a sensitive LC/MS/MS method for vitamin D metabolites: 1,25 Dihydroxyvitamin D2&3 measurement using a novel derivatization agent.

    PubMed

    Hedman, Curtis J; Wiebe, Donald A; Dey, Subhakar; Plath, Josh; Kemnitz, Joseph W; Ziegler, Toni E

    2014-03-15

    Active vitamin D metabolites 1,25-dihydroxyvitamin D2 [1,25-(OH)2-D2; derived from ergocalciferol] and D3 [1,25-(OH)2-D3; derived from cholecalciferol] are found in low levels in the circulation and require a very sensitive method for measurement. Radioimmunoassay (RIA) has been the method of choice, but it lacks the specificity needed to distinguish between 1,25-(OH)2-D2 and -D3, whereas liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods have the advantage of high specificity and sensitivity. Here, we compare a new derivative for ionizing 1,25-(OH)2-D to enhance the signal and provide the most sensitive assay for measuring vitamin D. We used the Amplifex diene method of derivatizing prior to LC/MS/MS and compared it to the standard RIA method and the 4-phenyl-1,2,4-triazole-3,5-dione (PTAD) method of derivatizing prior to LC/MS/MS. In the evaluation of 20 human serum samples, all methods correlated strongly across the upper levels of the standard 1,25-(OH)2-D2 and -D3 ranges (Amplifex and RIA, pc=0.97; Amplifex and PTAD, pc=0.96) but less strongly on the lower levels of the standard range (Amplifex and RIA, pc=0.81; Amplifex and PTAD, pc=0.65) suggesting differences in the sensitivities between the assays. The Amplifex method was determined to be more sensitive than the PTAD method, as peak areas were significantly higher for the Amplifex method and provided for a 10 fold higher signal-to-noise ratio than PTAD. Therefore, the Amplifex LC/MS/MS method is the most sensitive and specific method available for measuring 1,25-(OH)2-D2 and -D3 while using the smallest sample volume.

  10. Development of a Sensitive LC/MS/MS Method for Vitamin D Metabolites: 1,25 Dihydroxyvitamin D2&3 Measurement Using a Novel Derivatization Agent

    PubMed Central

    Hedman, Curtis J.; Wiebe, Donald A.; Dey, Subhakar; Plath, Josh; Kemnitz, Joseph W.; Ziegler, Toni E.

    2014-01-01

    Active vitamin D metabolites 1,25-dihydroxyvitamin D2 [1,25-(OH)2-D2; derived from ergocalciferol] and D3 [1,25-(OH)2-D3; derived from cholecalciferol] are found in low levels in the circulation and require a very sensitive method for measurement. Radioimmunoassay (RIA) has been the method of choice, but it lacks the specificity needed to distinguish between 1,25-(OH)2-D2 and -D3whereas liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods have the advantage of high specificity and sensitivity. Here, we compare a new derivative for ionizing 1,25-(OH)2-D to enhance the signal and provide the most sensitive assay for measuring vitamin D. We used the Amplifex diene method of derivatizing prior to LC/MS/MS and compared it to the standard RIA method and the 4-phenyl-1,2,4-triazole-3,5-dione (PTAD) method of derivatizing prior to LC/MS/MS. In the evaluation of 20 human serum samples, all methods correlated strongly across the upper levels of the standard 1,25-(OH)2-D2 and - D3 ranges (Amplifex and RIA, pc = 0.97; Amplifex and PTAD, pc = 0.96) but less strongly on the lower levels of the standard range (Amplifex and RIA, pc = 0.81; Amplifex and PTAD, pc = 0.65) suggesting differences in the sensitivities between the assays. The Amplifex method was determined to be more sensitive than the PTAD method, as peak areas were significantly higher for the Amplifex method and provided for a 10 fold higher signal-to-noise ratio than PTAD. Therefore, the Amplifex LC/MS/MS method is the most sensitive and specific method available for measuring 1,25-(OH)2-D2 and -D3 while using the smallest sample volume. PMID:24576767

  11. 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

  12. Exogenous versus endogenous recovery of 25-hydroxyvitamins D2 and D3 in human samples using high-performance liquid chromatography and the DiaSorin LIAISON Total-D Assay.

    PubMed

    Horst, Ronald L

    2010-07-01

    Demand for circulating 25-hydroxyvitamin D [25(OH)D] measurements has exploded due to its relationship with many serious health problems. The present study was designed to investigate the validity of samples "spiked" with 25-hydroxyvitamin D2 [25(OH)D2] or 25-hydroxyvitamin D3 [25(OH)D3] to determine their analytical recovery by the DiaSorin LIAISON 25 OH Vitamin D Total Assay (DiaSorin Assay) and high-performance liquid chromatography (HPLC). 25(OH)D was measured in nine volunteers taking large daily doses of vitamin D2 for 2 weeks. Samples were obtained pre-supplementation and 1 week following vitamin D2. Pre-supplementation samples were used for exogenous recovery studies by adding 25(OH)D2 or 25(OH)D3. Endogenous 25(OH)D [25(OH)D2 plus 25(OH)D3] concentrations reported by the DiaSorin Assay or detected by HPLC were in excellent agreement. However, exogenously added 25(OH)D2 and 25(OH)D3 were under-recovered by the DiaSorin Assay. NIST vitamin D standards containing serum from another species (horse) or exogenous 25(OH)D2 were similarly affected when using the DiaSorin Assay. Exogenous 25(OH)D2, 25(OH)D3 or serum from other species added to human samples is inappropriate in determining the analytical recovery of vitamin D compounds when using the DiaSorin Assay. Only endogenous 25(OH)D2 and/or 25(OH)D3 contained in human blood samples should be utilized for this purpose. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  13. Short-term bisphosphonate treatment reduces serum 25(OH) vitamin D3 and alters values of parathyroid hormone, pentosidine, and bone metabolic markers

    PubMed Central

    Kamimura, Mikio; Uchiyama, Shigeharu; Nakamura, Yukio; Ikegami, Shota; Mukaiyama, Keijiro; Kato, Hiroyuki

    2017-01-01

    This study aimed to clarify the effects of short-term bisphosphonate (BP) administration in Japanese osteoporotic patients retrospectively. Daily minodronate (MIN) at 1 mg/day (MIN group) or weekly risedronate (RIS) at 17.5 mg/week (RIS group) was primarily prescribed for each patient. We analyzed the laboratory data of 35 cases (18 of MIN and 17 of RIS) before the start of treatment and at 4 months afterward. The changes in 25(OH)D3, whole parathyroid hormone (PTH), serum pentosidine, and the bone turnover markers urinary cross-linked N-telopeptide of type I collagen (NTX), serum tartrate-resistant acid phosphatase (TRACP)-5b, bone-specific alkaline phosphatase (BAP), and undercarboxylated osteocalcin were evaluated. Overall, serum 25(OH)D3 was significantly decreased from 21.8 to 18.4 ng/mL at 4 months, with a percent change of −14.7%. Whole PTH increased significantly from 23.4 to 30.0 pg/mL, with a percent change of 32.1%. Serum pentosidine rose from 0.0306 to 0.0337 μg/mL, with a percent change of 15.2%. In group comparisons, 25(OH)D3 and pentosidine showed comparable changes in both groups after 4 months of treatment, whereas whole PTH became significantly more increased in the MIN group. All bone turnover markers were significantly decreased at 4 months in both groups. Compared with the RIS group, the MIN group exhibited significantly larger value changes for urinary NTX, serum TRACP-5b, and BAP at the study end point. This study demonstrated that serum 25(OH)D3 became significantly decreased after only 4 months of BP treatment in Japanese osteoporotic patients and confirmed that MIN more strongly inhibited bone turnover as compared with RIS. PMID:28243105

  14. Activation of vitamin D receptor (VDR)- and peroxisome proliferator-activated receptor (PPAR)-signaling pathways through 1,25(OH)(2)D(3) in melanoma cell lines and other skin-derived cell lines.

    PubMed

    Sertznig, Pit; Seifert, Markus; Tilgen, Wolfgang; Reichrath, Jörg

    2009-07-01

    We have investigated expression of vitamin D receptor (VDR) and peroxisome proliferator-activated receptors (PPAR)alpha, delta, gamma in primary cultured normal melanocytes (NHM), melanoma cell lines (MeWo, SK-Mel-5, SK-Mel-25, SK-Mel-28), a cutaneous squamous cell carcinoma cell line (SCL-1) and an immortalized sebocyte cell line (SZ95). LNCaP prostate cancer cells, MCF-7 breast cancer cells and embryonic kidney cells (HEK-293) were used as controls. VDR and PPAR mRNA were detected, quantitated and compared in these cell lines using real-time quantitative polymerase chain reaction (RTqPCR). The expression patterns of these nuclear receptors (NRs) varied strongly between the different cell lines according to their origin. PPARdelta and PPARgamma were less strongly expressed in the melanoma cell lines and in the other skin-derived cell lines as compared to the control cell lines. PPARalpha and VDR were stronger expressed in the 1,25(OH)(2)D(3)-sensitive melanoma cells (MeWo and in SK-Mel-28) than in the 1,25(OH)(2)D(3)-resistent melanoma cell lines (SK-Mel-5 and SK-Mel-25) or in NHM. Interestingly, VDR expression was increased by the treatment with 1,25(OH)(2)D(3) in 1,25(OH)(2)D(3)-sensitive melanoma cells but not in 1,25(OH)(2)D(3)-resistent melanoma cell lines. 1,25(OH)(2)D(3) increased the expression of PPARalpha in almost all cell lines analyzed. Our results indicate a cross-talk between VDR- and PPAR-signaling pathways in various cell types including melanoma cells. Further investigations are required to investigate the physiological and pathophysiological relevance of this cross-talk. Because VDRand PPAR-signaling pathways regulate a multitude of genes that are of importance for a multitude of cellular functions including cell proliferation, cell differentiation, immune responses and apoptosis, the provided link between VDR and PPAR may open important new perspectives for treatment and prevention of melanoma and other diseases.

  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

    2016-09-22

    (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

  16. Prospective evaluation of bone markers, parathormone and 1,25-(OH)₂ vitamin D in HIV-positive patients after the initiation of tenofovir/emtricitabine with atazanavir/ritonavir or efavirenz.

    PubMed

    Focà, Emanuele; Motta, Davide; Borderi, Marco; Gotti, Daria; Albini, Laura; Calabresi, Alessandra; Izzo, Ilaria; Bellagamba, Rita; Narciso, Pasquale; Sighinolfi, Laura; Clò, Alberto; Gibellini, Davide; Quiros-Roldan, Eugenia; Brianese, Nigritella; Cesana, Bruno Mario; Re, Maria Carla; Torti, Carlo

    2012-02-14

    Increased risk of fractures and osteoporosis have been associated with the use of antiretroviral drugs. There is a paucity of prospective evaluations of bone markers after the initiation of drugs currently recommended to treat HIV infection and results on the evolution of these markers are conflicting. Lastly, the effect of tenofovir on 1,25-(OH)₂ vitamin D is uncertain. We performed a prospective study on the evolution of bone markers, parathormone and 1,25-(OH)₂ vitamin D before and after standard antiretroviral regimens. This was a sub-study of a trial conducted in antiretroviral-naïve patients randomized to tenofovir + emtricitabine in combination with either atazanavir/ritonavir (ATV/r) or efavirenz (EFV). Follow-up lasted 48 weeks. The following bone markers were analyzed: C-terminal cross-laps (CTx), osteocalcin (OC), osteoprotegerin (OPG), and receptor activator of nuclear factor κB ligand (RANKL). Mixed-factorial analysis of variance with random-coefficient general linear model was used to compare their trends over time and linear multivariable regression was performed with a backward selection method to assess predictors of their variations from baseline to week 48. Trends of parathormone and 1,25-(OH)₂ vitamin D were also evaluated. Seventy-five patients were studied: 33 received EFV and 42 ATV/r. Significant increases were found for all markers except for RANKL. There was a significant direct association between CTx and OC increases. Multivariable analysis showed that higher glomerular filtration rate (estimated through cystatin C clearance) predicted greater OPG increase, while older age, higher HIV RNA at baseline and use of ATV/r predicted greater CTx increase. A significant increase of parathormone accompanied the evolution of the study markers. 1,25-(OH)₂ vitamin D remained stable, though a seasonality variation was demonstrated. These data demonstrate CTx increase (bone resorption marker) corresponding to OC increase (bone formation

  17. 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

  18. Time course of 25(OH)D3 vitamin D3 as well as PTH (parathyroid hormone) during fracture healing of patients with normal and low bone mineral density (BMD).

    PubMed

    Wölfl, Christoph; Wöfl, Christoph; Englert, Sarah; Moghaddam, Arash A; Zimmermann, Gerald; Schmidt-Gayk, Heinrich; Schmidt-Gayk, Gerhard; Höner, Bernd; Hogan, Aidan; Lehnhardt, Marcus; Grützner, Paul A; Kolios, Leila

    2013-01-03

    Until now the exact biochemical processes during healing of metaphyseal fractures of healthy and osteoporotic bone remain unclear. Especially the physiological time courses of 25(OH)D(3) (Vitamin D) as well as PTH (Parathyroid Hormone) the most important modulators of calcium and bone homeostasis are not yet examined sufficiently. The purpose of this study was to focus on the time course of these parameters during fracture healing. In the presented study, we analyse the time course of 25(OH)D3 and PTH during fracture healing of low BMD level fractures versus normal BMD level fractures in a matched pair analysis. Between March 2007 and February 2009 30 patients older than 50 years of age who had suffered a metaphyseal fracture of the proximal humerus, the distal radius or the proximal femur were included in our study. Osteoporosis was verified by DEXA measuring. The time courses of 25(OH)D(3) and PTH were examined over an eight week period. Friedmann test, the Wilcoxon signed rank test and the Mann-Withney U test were used as post-hoc tests. A p-value ≤ 0.05 was considered significant. Serum levels of 25(OH)D(3) showed no differences in both groups. In the first phase of fracture healing PTH levels in the low BMD level group remained below those of the normal BMD group in absolute figures. Over all no significant differences between low BMD level bone and normal BMD level bone could be detected in our study. The time course of 25(OH)D(3) and PTH during fracture healing of patients with normal and low bone mineral density were examined for the first time in humans in this setting and allowing molecular biological insights into fracture healing in metaphyseal bones on a molecural level. There were no significant differences between patients with normal and low BMD levels. Hence further studies will be necessary to obtain more detailed insight into fracture healing in order to provide reliable decision criteria for therapy and the monitoring of fracture healing.

  19. [Assay of fat-soluble vitamins--vitamin D].

    PubMed

    Kobayashi, T

    1993-04-01

    Methods for determination of vitamin D, 25-OH-D, 24,25(OH)2D and 1,25(OH)2D in plasma are reviewed. A method for simultaneous determination of the D2 and D3 compounds of vitamin D and the metabolites in plasma is established. The method includes extraction of lipid, followed by three steps of HPLC for clean-up and separation. Vitamin D and 25-OH-D are quantified by HPLC with a UV detector, while 24,25(OH)2D and 1,25(OH)2D are assayed by CPBA and RRA methods, respectively. The assayed values for concentrations of the compounds in plasma of normal subjects and various kinds of patients are shown. A simplified method for assaying 1,25(OH)2D in plasma using calf thymus receptor is also introduced.

  20. Vitamin D2, Ergosterol, and Vitamin B2 Content in Commercially Dried Mushrooms Marketed in China and Increased Vitamin D2 Content Following UV-C Irradiation.

    PubMed

    Huang, Guocheng; Cai, Weixi; Xu, Baojun

    2016-11-21

    Mushrooms are a great source of vitamin D and vitamin B2; however, the content of these vitamins in dried mushrooms has not fully been investigated. Thus, the objectives of this study were to determine the contents of vitamin D2, ergosterol, and vitamin B2 in commercially dried edible mushrooms in China and to investigate the effect of UV-C irradiation on fresh mushrooms. Among the 35 species of dried mushrooms considered for this study, the average ergosterol content was 1.98 mg/g, while the average vitamin D2 content was 16.88 µg/g. The average vitamin B2 content in dried mushrooms was 12.68 µg/g. Fresh shaggy ink caps and oyster mushrooms, when exposed to UV-C at 254 nm at a dose of 0.25 J/cm(2) for 10, 30, and 60 min, showed significantly (p < 0.05) increased vitamin D2 content (229.7 and 67.0 µg/g, respectively) as compared to its fresh counterparts. The conversion of ergosterol to vitamin D2 induced by UV-C irradiation at 0.25 J/cm(2) was significant (p < 0.05). In conclusion, dried commercial mushrooms have higher contents of ergosterol and vitamin D2 than fresh mushrooms. UV-C radiation can be used to increase vitamin D2 content in mushrooms.

  1. Longevity of daily oral vitamin D3 supplementation: differences in 25OHD and 24,25(OH)2D observed 2 years after cessation of a 1-year randomised controlled trial (VICtORy RECALL).

    PubMed

    Macdonald, H M; Gryka, A; Tang, J C Y; Aucott, L S; Fraser, W D; Wood, A D

    2017-09-15

    To determine how long vitamin D lasts after supplementation ceases, the marker of status was measured 2 and 3 years after a 1-year trial. Compared to placebo, the proportion of vitamin D-deficient women was still lower, if they had taken daily vitamin D3, after 2 years, indicating its longevity. The purpose of this study was to determine longevity of vitamin D status following cessation of vitamin D3 supplementation, 2 and 3 years after a 1-year randomised, double-blind placebo controlled trial and to investigate possible predictive factors. Caucasian non-smoking postmenopausal women randomised to ViCtORY (2009-2010), who had not taken vitamin D supplements since the trial ended, were invited to attend follow-up visits. Total 25-hydroxyvitamin D (25OHD) and 24,25-dihydroxyvitamin D (24,25OH2D) were measured by dual tandem mass spectrometry of serum samples following removal of protein and de-lipidation; the original randomised controlled trial (RCT) samples were re-analysed simultaneously. Vitamin D-binding protein (VDBP) was measured by monoclonal immunoassay. In March 2012 and March 2013, 159 women (mean (SD) age 67.6 (2.1) years) re-attended, equally distributed between the original treatment groups: daily vitamin D3 (400 IU, 1000 IU) and placebo. One month after the RCT ended (March 2010), the proportion of women in placebo, 400 IU and 1000 IU vitamin D3 groups, respectively, with 25OHD < 25 nmol/L was 15, 0 and 0 (chi-square p < 0.001, n = 46, 44, 54). After 2 years (March 2012), it was 22, 4 and 4% (p = 0.002, n = 50, 48, 57); after 3 years, it was 23, 13 and 15% (p = 0.429, n = 48, 45, 52). The respective proportions of women with 24,25OH2D < 2.2 nmol/L were 50, 2 and 2% (1 month, p < 0.001, n = 46, 44, 54); 42, 33 and 12% (2 years, p = 0.002, n = 50, 48, 57); and 45, 27 and 29% (3 years, p = 0.138, n = 47, 45, 51). VDBP was a predictor of circulating 25OHD longevity (beta for VDBP in μg/mL 0.736; 95% CI 0.216-1.255, p

  2. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Vitamin D2. 172.379 Section 172.379 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Special...

  3. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Vitamin D2. 172.379 Section 172.379 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Special Dietary and Nutritional Additives § 172...

  4. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Vitamin D2. 172.379 Section 172.379 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Special...

  5. An audit of clinical laboratory data of 25 [OH]D at Aga Khan University as reflecting vitamin D deficiency in Pakistan.

    PubMed

    Hassan, Sidra; Muzammil, Syeda Maria; Jafri, Lena; Khan, Aysha Habib

    2015-11-01

    To estimate the burden of Vitamin D deficiency in people from different geographical areas of Pakistan. The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised specimens of subjects tested for 25-hydroxy D at the clinical laboratory between September 2010 and September 2011. Serum samples received from the phlebotomy centres all over Pakistan and the main laboratory in Karachi were included. SPSS 19 was used for statistical analysis. Of the 60937 specimens in the study, 18721(30.7%) related to men. The overall mean age was 40.5±19.7 years, and median 25-hydroxy D level was 13.5ng/ml (interquartile range: 25.1-7.4 ng/ml).Overall, mean log 25-hydroxy D was 1.14±0.39ng/ml (median: 13.5ng/ml; interquartile range: 25.1-7.4 ng/ml). Out of the total, 40279(66.1%) subjects were vitamin D-deficient. Vitamin D deficiency was common among the subjects.

  6. Comparative 25-OH-vitamin D level in institutionalized women older than 65 years from two cities in Spain and Argentina having a similar solar radiation index.

    PubMed

    Portela, María Luz Pita Martin; Mónico, Amália; Barahona, Antonieta; Dupraz, Hernan; Sol Gonzales-Chaves, Macarena Maria; Zeni, Susana Noemi

    2010-03-01

    The present study evaluated and compared vitamin D nutritional status and calcium-phosphorus metabolism in institutionalized women >65 y from two cities that have a similar sun irradiation index (heliophany). The study was carried out in women living in similar social-status institutions from geographic cities having a similar solar radiation index (Lleida, Spain, n=49, and suburban Buenos Aires, Argentina [BA], n=48) at the end of summer. Fish consumption was higher in the Lleida group, as was red-meat consumption in the BA group. In both groups mean calcium intake was 800 mg/d. The daily intake of vitamin D was higher in the BA group (P<0.001). A total of 90% in Lleida and 86% in BA had 25-hydroxyvitamin D (25OHD) levels <20 ng/mL. A significant inverse correlation between individual 25OHD and parathyroid hormone (PTH) levels was observed in the two groups of women (r=-0.329, P=0.035). PTH levels >100 pg/mL were found in 24% and 20% of women in Lleida and BA, respectively. There was a marked increase in carboxy-terminal telopeptide cross-links of type I collagen levels and a decrease in 25OHD with an increase in PTH levels (P<0.05). Conversely, bone alkaline phosphatase increased significantly only when the PTH concentration duplicated the reference range. Even at the end of summer, vitamin D deficiency/insufficiency was prevalent in the two studied institutionalized elderly women. In the narrow range of the dietary calcium intake (close to 800 mg/d) of both studied groups, secondary hyperparathyroidism was absent when 25OHD levels were >17 ng/dL, indicating changes in the regulation control of serum PTH and consequently the changes in this threshold. As a result, vitamin D deficiency must be reversed to avoid the increment in bone turnover and to ensure the endocrine and paracrine functions of vitamin D for overall health and well-being. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  7. Free 25(OH)D and Calcium Absorption, PTH, and Markers of Bone Turnover

    PubMed Central

    Dhaliwal, Ruban; Mikhail, Mageda; Shieh, Albert; Stolberg, Alexandra; Ragolia, Louis; Fazzari, Melissa; Abrams, Steven A.

    2015-01-01

    Context: It has been proposed that serum free 25-hydroxyvitamin D [25(OH)D] may better reflect vitamin D action than total 25(OH)D. An ELISA for serum free 25(OH)D has recently become available, permitting direct assay. Objective: To determine whether serum free 25(OH)D provides additional information in relation to calcium absorption and other biomarkers of vitamin D action compared to total serum 25(OH)D. Setting: Ambulatory research setting in a teaching hospital. Outcome: Serum free 25(OH)D measured in a previously performed study of varied doses of vitamin D3 (placebo and 800, 2000, and 4000 IU) on calcium absorption, PTH, procollagen type 1 N-terminal propeptide, and C-terminal telopeptides of type I collagen. Free 25(OH)D was measured by ELISA. Calcium absorption was measured at baseline and at 10 weeks using stable dual calcium isotopes. Results: Seventy-one subjects completed this randomized, placebo-controlled trial. Baseline group mean free and total 25(OH)D varied from 4.7 ± 1.8 to 5.4 ± 1.5 pg/mL, and from 23.7 ± 5.9 to 25.9 ± 6.1 ng/mL, respectively. Participants assigned to the 4000-IU dose arm achieved free 25(OH)D levels of 10.4 pg/mL and total 25(OH)D levels of 40.4 ng/mL. Total and free 25(OH)D were highly correlated at baseline and after increasing vitamin D dosing (r = 0.80 and 0.85, respectively). Free 25(OH)D closely reflected changes in total 25(OH)D. PTH was similarly correlated at baseline and follow-up with total and free 25(OH)D. Serum C-terminal telopeptides of type I collagen had a moderate positive correlation with total and free 25(OH)D at follow-up. The serum 1,25-dihydroxyvitamin D change increased significantly with the change in 25(OH)D but not with the change in free 25(OH)D. Conclusion: There was no advantage from measuring free over total 25(OH)D in assessing the response of calcium absorption, PTH, and markers of bone turnover to vitamin D. Free 25(OH)D responded to increasing doses of vitamin D in a similar fashion to

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

    PubMed Central

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

    2016-01-01

    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)2D by 1α‐hydroxylase. Therefore, we investigated in a murine C2C12 myoblast culture whether both 1,25(OH)2D3 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)2D3. We show that myoblasts not only responded to 1,25(OH)2D3, 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)2D3 as well as 25(OH)D3 stimulated VDR mRNA expression and in myotubes 1,25(OH)2D3 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)2D3 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)2D3 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)2D3. J. Cell. Physiol. 231: 2517–2528, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:27018098

  9. 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. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

  10. Insulin and body weight but not hyperandrogenism seem involved in seasonal serum 25-OH-vitamin D3 levels in subjects affected by PCOS.

    PubMed

    Gallea, Mariateresa; Granzotto, Marnie; Azzolini, Sara; Faggian, Diego; Mozzanega, Bruno; Vettor, Roberto; Mioni, Roberto

    2014-10-01

    PCOS patients were frequently characterized by lower plasma vitamin D levels. The mechanisms involved in this dysfunction remains still debated, therefore we evaluated the role of androgen, insulin and body weight on the serum VitD levels in women with or without PCOS. Eighty one patients 18-42 yrs old were studied into "SUMMER" and "WINTER" seasonal period: thirty seven PCOS, seventeen no-ovarian hyperandrogenic (noPCOS), twelve functional hypothalamic amenorrhea (FHA) and finally fifteen healthy (Con). Patients were further divided into: lean (L), obese (O), normo- (nINS) and hyperinsulinemic (hINS). All hormonal and metabolic parameters were measured at 1-7 days of the menstrual cycle. Our results show that VitD levels were lower in PCOS and in noPCOS than in FHA and Con, in particular in (O) and (hINS) PCOSs. Both in summer and in winter, PCOSs had basal VitD levels significantly lower than FHA and Con, whereas they were similar to noPCOS. Yet, LhINS and OPCOS had VitD levels lower than Con and noPCOS. VitD levels were comparable in LnINS PCOS and Con. In conclusion, PCOSs had levels of VitD lower than controls. Weight and hyperinsulinemia had a significant influence on these values. Finally, over 70% of our healthy patients had VitD deficiency.

  11. Treatment of 25-OH vitamin D deficiency in older men with chronic kidney disease stages 3 and 4 is associated with reduction in cardiovascular events.

    PubMed

    Lishmanov, Anton; Dorairajan, Smrita; Pak, Youngju; Chaudhary, Kunal; Chockalingam, Anand

    2013-01-01

    Observational studies in healthy people suggest an inverse relationship between serum 25-hydroxyvitamin D (25OHD) levels and cardiovascular (CV) mortality. Treating vitamin D deficiency in patients with moderate chronic kidney disease (CKD) may reduce CV events in this high-risk population. Study data were abstracted from Harry S. Truman Memorial Veterans Hospital electronic medical record system. The medical records of all veterans who had CKD stages 3 and 4 and had 25OHD levels determined from April 2006 to September 2007 were reviewed. Patients with 25OHD deficiency, serum level <30 ng/mL, were included (N = 126, all men, mean age = 70 years). Successful 25OHD replacement was defined as prescription of ergocalciferol sufficient to increase serum 25OHD level by 25% from baseline within 6 months (treatment group, n = 90). Otherwise patients were considered as untreated controls (n = 36). The date when the 25OHD level was drawn was considered as the date of inclusion. All the patients were followed up from the date of inclusion until July 2009 to capture CV events prospectively. During mean follow-up of 27.2 months, 44% of the controls had CV events, whereas only 21% of the patients in the treatment group had CV events (P = 0.001). In multivariate logistic regression analysis, adjusting for CV disease predictors age, initial parathyroid hormone level, statin use, history of CV disease, and glomerular filtration rate, the estimated odds ratio for 25OHD replacement status was 0.37 (95% confidence interval: 0.14-1.0). Treatment of 25OHD deficiency with ergocalciferol in patients with moderate CKD is associated with significant reduction in CV events.

  12. Plasma 25-hydroxyvitamin D2 and D3 levels and incidence of postoperative atrial fibrillation.

    PubMed

    Skuladottir, G V; Cohen, A; Arnar, D O; Hougaard, D M; Torfason, B; Palsson, R; Indridason, O S

    2016-01-01

    Low circulating levels of total 25-hydroxyvitamin D (25(OH)D) have been associated with an increased risk of adverse effects after cardiac surgery. The metabolites, 25(OH)D2 and 25(OH)D3, provide a good index of vitamin D status. In this study, we examined the association between preoperative plasma levels of total 25(OH)D, 25(OH)D2 and 25(OH)D3 and the risk of postoperative atrial fibrillation (POAF) following open heart surgery. The levels of plasma 25(OH)D2 and 25(OH)D3 in 118 patients, who underwent coronary artery bypass grafting and/or valvular surgery, were measured immediately prior to surgery and on postoperative day 3 by liquid chromatography-tandem mass spectrometry. Patients who developed POAF had higher median plasma levels of 25(OH)D2 than those who remained in sinus rhythm (SR) (P = 0·003), but no significant difference was noted in levels of 25(OH)D3 or total 25(OH)D between the two groups (P > 0·05). By univariate analysis, patients with total 25(OH)D and 25(OH)D2 levels above the median had higher frequency of POAF (P < 0·05) and the incidence of POAF increased significantly with each higher quartile of preoperative plasma levels of 25(OH)D2 (P = 0·001), an association that was independent of confounding factors. In both the SR and POAF groups, the median plasma levels of 25(OH)D2, 25(OH)D3 and total 25(OH)D were lower (P < 0·05) on the third postoperative day compared with preoperatively. Our findings demonstrate that higher plasma levels of 25(OH)D2 are associated with increased risk of POAF, while this is not the case for 25(OH)D3 or total 25(OH)D. The reason for these discrepant results is not clear but warrants further study.

  13. Determination of mono- and dihydroxy-vitamin D metabolites in normal subjects and patients with different calcium metabolic diseases.

    PubMed

    Hummer, L; Riis, B J; Christiansen, C; Rickers, H

    1985-11-01

    Reliable assays to determine the vitamin D metabolites are useful aids in the study of disorders involving vitamin D metabolism, and in the evaluation of the response in patients receiving vitamin D treatment. We report here the establishment in our laboratory of a method capable of measuring 25(OH)D, (including 25(OH)D2 and 25(OH)D3), 1,25(OH)2D and 24,25(OH)2D in a single blood sample. The method involves methanol/dichloromethane extraction and Sephadex LH-20 chromatography. The monhydroxylated fraction was purified on Lipidex 5000 and separated in 25(OH)D2 and 25(OH)D3 on high pressure liquid chromatography (HPLC), followed by ultra violet absorbance (UV) detection. The dihydroxylated fraction was separated by HPLC and quantified by protein-binding assays. The method is precise and accurate. The vitamin D metabolites were measured in different groups of patients and in normal subjects.

  14. Vitamins D2 and D3 in new world primates: influence on calcium absorption.

    PubMed

    Hunt, R D; Garcia, F G; Hegsted, D M; Kaplinsky, N

    1967-08-25

    In Cebus albifrons monkeys it was demonstrated that vitamin D(3) promotes the intestinal absorption of calcium-47 and that vitamin D(2) does not increase absorption above that seen in monkeys deficient in vitamin D. These data support previous observations that vitamin D(2) is not effective in preventing metabolic bone disease in this species.

  15. 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

  16. 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

  17. 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

  18. Vitamin D from different sources is inversely associated with Parkinson disease.

    PubMed

    Wang, Liyong; Evatt, Marian L; Maldonado, Lizmarie G; Perry, William R; Ritchie, James C; Beecham, Gary W; Martin, Eden R; Haines, Jonathan L; Pericak-Vance, Margaret A; Vance, Jeffery M; Scott, William K

    2015-04-01

    An inverse association between Parkinson disease (PD) and total vitamin D levels has been reported, but whether vitamin D from different sources, that is, 25(OH)D2 (from diet and supplements) and 25(OH)D3 (mainly from sunlight exposure), all contribute to the association is unknown. Plasma total 25(OH)D, 25(OH)D2, and 25(OH)D3 levels were measured by liquid chromatography-tandem mass spectrometry in PD patients (n = 478) and controls (n = 431). Total 25(OH)D was categorized by clinical insufficiency or deficiency; 25(OH)D2 and 25(OH)D3 were analyzed in quartiles. Vitamin D deficiency (total 25[OH]D < 20 ng/mL) and vitamin D insufficiency (total 25[OH]D < 30 ng/mL) are associated with PD risk (odds ratio [OR] = 2.6 [deficiency] and 2.1 [insufficiency]; P < 0.0001), adjusting for age, sex, and sampling season. Both 25(OH)D2 and 25(OH)D3 levels are inversely associated with PD (P(trend) < 0.0001). The association between 25(OH)D2 and PD risk is largely confined to individuals with low 25(OH)D3 levels (P(trend) = 0.0008 and 0.12 in individuals with 25[OH]D3 < 20 ng/mL and 25[OH]D3 ≥ 20 ng/mL, respectively). Our data confirm the association between vitamin D deficiency and PD, and for the first time demonstrate an inverse association of 25(OH)D2 with PD. Given that 25(OH)D2 concentration is independent of sunlight exposure, this new finding suggests that the inverse association between vitamin D levels and PD is not simply attributable to lack of sunlight exposure in PD patients with impaired mobility. The current study, however, cannot exclude the possibility that gastrointestinal dysfunction, a non-motor PD symptom, contributes to the lower vitamin D2 levels in PD patients.

  19. 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.

  20. Dietary fructose inhibits lactation-induced adaptations in rat 1,25-(OH)2D3 synthesis and calcium transport

    PubMed Central

    Douard, Veronique; Suzuki, Takuji; Sabbagh, Yves; Lee, Jacklyn; Shapses, Sue; Lin, Sheldon; Ferraris, Ronaldo P.

    2012-01-01

    We recently showed that excessive fructose consumption, already associated with numerous metabolic abnormalities, reduces rates of intestinal Ca2+ transport. Using a rat lactation model with increased Ca2+ requirements, we tested the hypothesis that mechanisms underlying these inhibitory effects of fructose involve reductions in renal synthesis of 1,25-(OH)2D3. Pregnant and virgin (control) rats were fed isocaloric fructose or, as controls, glucose, and starch diets from d 2 of gestation to the end of lactation. Compared to virgins, lactating dams fed glucose or starch had higher rates of intestinal transcellular Ca2+ transport, elevated intestinal and renal expression of Ca2+ channels, Ca2+-binding proteins, and CaATPases, as well as increased levels of 25-(OH)D3 and 1,25-(OH)2D3. Fructose consumption prevented almost all of these lactation-induced increases, and reduced vitamin D receptor binding to promoter regions of Ca2+ channels and binding proteins. Changes in 1,25-(OH)2D3 level were tightly correlated with alterations in expression of 1α-hydroxylase but not with levels of parathyroid hormone and of 24-hydroxylase. Bone mineral density, content, and mechanical strength each decreased with lactation, but then fructose exacerbated these effects. When Ca2+ requirements increase during lactation or similar physiologically challenging conditions, excessive fructose consumption may perturb Ca2+ homeostasis because of fructose-induced reductions in synthesis of 1,25-(OH)2D3.—Douard, V., Suzuki, T., Sabbagh, Y., Lee, J., Shapses, S., Lin, S., Ferraris, R. P. Dietary fructose inhibits lactation-induced adaptations in rat 1,25-(OH)2D3 synthesis and calcium transport. PMID:22038050

  1. Contribution of several metabolites of the vitamin D analog 20-epi-22-oxa-24a,26a,27a-tri-homo-1,25-(OH)(2) vitamin D(3) (KH 1060) to the overall biological activity of KH1060 by a shared mechanism of action.

    PubMed

    van den Bemd, G C; Dilworth, F J; Makin, H L; Prahl, J M; Deluca, H F; Jones, G; Pols, H A; van Leeuwen, J P

    2000-03-15

    The synthetic 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) analog 20-epi-22-oxa-24a,26a,27a-tri-homo-1,25-(OH)(2)vitamin D(3) (KH1060) is considerably more potent than its cognate hormone. The mechanism of action of KH1060 includes interaction with the vitamin D receptor (VDR). We previously showed that KH1060 increases VDR stability in ROS 17/2.8 osteoblastic cells by inducing a specific conformational change in the VDR. KH1060 is metabolized, both in vivo and in vitro, into several stable products. In the present study, we investigated whether these metabolites might contribute to the increased biological activity of KH1060. We found that the potencies of two of these metabolites, 24a-OH-KH1060 and 26-OH-KH1060, were similar to that of 1,25-(OH)(2)D(3) in inducing osteocalcin production by the osteoblast cell line ROS 17/2.8. This report further showed that these metabolites had the same effects as KH1060 on VDR: they increased VDR stability in ROS 17/2.8 cells, while limited proteolytic analysis revealed that they caused a conformational change in the VDR, resulting in an increased resistance against proteolytic cleavage. Furthermore, as shown in gel mobility shift assays, both compounds clearly induced VDR binding to vitamin D response elements. Together, these results show that the potent in vitro activity of KH1060 is not only directed by the effects on the VDR conformation/stabilization of the analog itself, but also by certain of its long-lived metabolites, and emphasizes the importance of detailed knowledge of the metabolism of synthetic hormonal analogs.

  2. 25(OH)D status: Effect of D3 supplement

    PubMed Central

    Luebbers, P. E.

    2017-01-01

    Summary Background Excess adipose tissue may lead to sequestrating of vitamin D, making it less available for use in the body. Objective This study determined if overweight or obese individuals (BMI > 25 kg m−2) had insufficient (<30 ng mL−1) levels of 25‐hydroxyvitamin D [25(OH)D] and, if so, would serum levels respond to exogenous supplementation. Methods Sixty‐three women who were overweight/obese (BMI = 31.07 ± 5.00 kg m−2) were randomly assigned in a double‐blind manner to receive 5,000 IU of vitamin D3 (D3) (n = 31) or a placebo (PL) (n = 32) daily. Serum 25(OH)D concentrations were measured by finger‐stick analyses at baseline and after 8 weeks of supplementation. Data were analyzed by using a 2 × 2 (group × time) repeated measure multivariate analysis of variance to determine group differences for pre‐values and post‐values (p < 0.05). Results On day one of the study, both D3 and PL groups had insufficient levels of vitamin D (mean ± SD) 24.03 ± 9.78 ng mL−1 and 23.62 ± 9.77 ng mL−1, respectively. After 8 weeks of supplementation, the D3 group 25(OH)D level rose to a mean of 43.57 ± 10.87 ng mL−1 (p < 0.001) versus the PL group whose 25(OH)D level remained statistically unchanged 24.31 ± 8.84 ng mL−1. Women who were overweight/obese had insufficient vitamin D levels prior to supplementation. Conclusions Following supplementation with 5,000 IU of vitamin D3, all subjects' 25(OH)D levels rose to a sufficient level (≥30 ng mL−1). The findings of this study concur with the Institute of Medicine and Endocrine Society recommendations in that two to three times the daily requirement of vitamin D is required to improve serum vitamin D levels in individuals who are overweight or obese. PMID:28392936

  3. Daily supplementation with 15 μg vitamin D2 compared with vitamin D3 to increase wintertime 25-hydroxyvitamin D status in healthy South Asian and white European women: a 12-wk randomized, placebo-controlled food-fortification trial.

    PubMed

    Tripkovic, Laura; Wilson, Louise R; Hart, Kathryn; Johnsen, Sig; de Lusignan, Simon; Smith, Colin P; Bucca, Giselda; Penson, Simon; Chope, Gemma; Elliott, Ruan; Hyppönen, Elina; Berry, Jacqueline L; Lanham-New, Susan A

    2017-08-01

    Background: There are conflicting views in the literature as to whether vitamin D2 and vitamin D3 are equally effective in increasing and maintaining serum concentrations of 25-hydroxyvitamin D [25(OH)D], particularly at lower doses of vitamin D.Objective: We aimed to investigate whether vitamin D2 or vitamin D3 fortified in juice or food, at a relatively low dose of 15 μg/d, was effective in increasing serum total 25(OH)D and to compare their respective efficacy in South Asian and white European women over the winter months within the setting of a large randomized controlled trial.Design: A randomized, double-blind, placebo-controlled food-fortification trial was conducted in healthy South Asian and white European women aged 20-64 y (n = 335; Surrey, United Kingdom) who consumed placebo, juice supplemented with 15 μg vitamin D2, biscuit supplemented with 15 μg vitamin D2, juice supplemented with 15 μg vitamin D3, or biscuit supplemented with 15 μg vitamin D3 daily for 12 wk. Serum 25(OH)D was measured by liquid chromatography-tandem mass spectrometry at baseline and at weeks 6 and 12 of the study.Results: Postintervention in the 2 ethnic groups combined, both the vitamin D3 biscuit and the vitamin D3 juice groups showed a significantly greater absolute incremental change (Δ) in total 25(OH)D when compared with the vitamin D2 biscuit group [Δ (95% CI): 15.3 nmol/L (7.4, 23.3 nmol/L) (P < 0.0003) and 16.0 nmol/L (8.0, 23.9 nmol/L) ( P < 0.0001)], the vitamin D2 juice group [Δ (95% CI): 16.3 nmol/L (8.4, 24.2 nmol/L) (P < 0.0001) and 16.9 nmol/L (9.0, 24.8 nmol/L) (P < 0.0001)], and the placebo group [Δ (95% CI): 42.3 nmol/L (34.4, 50.2 nmol/L) (P < 0.0001) and 42.9 nmol/L (35.0, 50.8 nmol/L) (P < 0.0002)].Conclusions: With the use of a daily dose of vitamin D relevant to public health recommendations (15 μg) and in vehicles relevant to food-fortification strategies, vitamin D3 was more effective than vitamin D2 in increasing serum 25(OH)D in the wintertime

  4. Quantification of vitamin D and 25-hydroxyvitamin D in soft tissues by liquid chromatography-tandem mass spectrometry.

    PubMed

    Lipkie, Tristan E; Janasch, Amber; Cooper, Bruce R; Hohman, Emily E; Weaver, Connie M; Ferruzzi, Mario G

    2013-08-01

    Inadequate data on tissue distribution of vitamin D and its metabolites remains a barrier to defining health outcomes of vitamin D intake and 25-hydroxyvitamin D (25(OH)D) status. The purpose of this study was to develop a method for the analysis of vitamin D2 (ergocalciferol), vitamin D3 (cholecalciferol), 25(OH)D2, and 25(OH)D3 in soft tissues, and determine distribution in select tissues from a dose-response study of vitamin D2 and vitamin D3 in rats. Liver, gastrocnemius muscle, and epididymal fat homogenates were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization following liquid-liquid extraction, solid-phase extraction, and derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD). A dose-response was observed in most tissues for vitamin D and 25(OH)D from both vitamers. Vitamin D concentration was greater in epididymal fat than gastrocnemius muscle and liver, but 25(OH)D concentration was not significantly different between tissues. Soft tissues of rats fed crystalline vitamin D3 had higher concentrations of total vitamin D than those of rats fed yeast-derived vitamin D2, while total 25(OH)D concentrations were similar between vitamin D sources. This method is well suited to more complete studies of vitamin D bioavailability and metabolite tissue distribution.

  5. Quantification of vitamin D and 25-hydroxyvitamin D in soft tissues by liquid chromatography—tandem mass spectrometry

    PubMed Central

    Lipkie, Tristan E.; Janasch, Amber; Cooper, Bruce R.; Hohman, Emily E.; Weaver, Connie M.; Ferruzzi, Mario G.

    2013-01-01

    Inadequate data on tissue distribution of vitamin D and its metabolites remains a barrier to defining health outcomes of vitamin D intake and 25-hydroxyvitamin D (25(OH)D) status. The purpose of this study was to develop a method for the analysis of vitamin D2 (ergocalciferol), vitamin D3 (cholecalciferol), 25(OH)D2, and 25(OH)D3 in soft tissues, and determine distribution in select tissues from a dose-response study of vitamin D2 and vitamin D3 in rats. Liver, gastrocnemius muscle, and epididymal fat homogenates were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization following liquid-liquid extraction, solid-phase extraction, and derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD). A dose-response was observed in most tissues for vitamin D and 25(OH)D from both vitamers. Vitamin D concentration was greater in epididymal fat than gastrocnemius muscle and liver, but 25(OH)D concentration was not significantly different between tissues. Soft tissues of rats fed crystalline vitamin D3 had higher concentrations of total vitamin D than those of rats fed yeast-derived vitamin D2, while total 25(OH)D concentrations were similar between vitamin D sources. This method is well suited to more complete studies of vitamin D bioavailability and metabolite tissue distribution. PMID:23811497

  6. 1,25(OH)2 D3 attenuates hepatic steatosis by inducing autophagy in mice.

    PubMed

    Li, Renlong; Guo, Enshuang; Yang, Jiankun; Li, Anyi; Yang, Yan; Liu, Shenpei; Liu, Anding; Jiang, Xiaojing

    2017-03-01

    1,25(OH)2 D3 has been reported to attenuate liver steatosis; however, its exact mechanism of action remains poorly understood. This study aimed to determine whether 1,25(OH)2 D3 can attenuate hepatic steatosis by inducing autophagy. Male C57BL/6 mice fed a high-fat diet (HFD) were injected with 1,25(OH)2 D3 for 4 weeks. These mice were given 3-methyladenine (3-MA) to inhibit autophagy. HepG2 cells were preincubated with a free fatty acid (FFA) and then treated with 1,25(OH)2 D3 . Vitamin D receptor (VDR) shRNA and autophagy-related 16-like 1 (ATG16L1) siRNA were used for VDR knockdown or ATG16L1 silencing, respectively. 1,25(OH)2 D3 diminished HFD-induced liver damage and steatosis, changes accompanied by autophagy and ATG16L1 expression upregulation. Inhibition of 1,25(OH)2 D3 -induced autophagy mediated by 3-MA blocked the protective effects of 1,25(OH)2 D3 on hepatic steatosis. Additionally, 1,25(OH)2 D3 -induced autophagy appeared to play a role in anti-inflammation and lipid metabolism modulation in the liver. In HepG2 cells, 1,25(OH)2 D3 reduced lipid accumulation and increased autophagy and ATG16L1 expression; however, this effect was abrogated after VDR knockdown. The protective effects of 1,25(OH)2 D3 -mediated autophagy against lipid accumulation were abolished by 3-MA. Furthermore, siRNA-mediated ATG16L1 knockdown prevented 1,25(OH)2 D3 -induced autophagy, resulting in increased fat accumulation. The data suggest that 1,25(OH)2 D3 may ameliorate hepatic steatosis by inducing autophagy by upregulating ATG16L1. © 2017 The Obesity Society.

  7. Different effect of vitamin D2 and vitamin D3 on amyloid-β40 aggregation in vitro.

    PubMed

    Suenaga, Midori; Takahashi, Hironobu; Imagawa, Hiroshi; Wagatsuma, Michiru; Ouma, Shinji; Tsuboi, Yoshio; Furuta, Akiko; Matsunaga, Yoichi

    2014-01-01

    The seeding of amyloid-β 40 (Aβ40) oligomers from monomers is the initial step of Aβ aggregation, and many reports have suggested that cholesterol enhances this step. We studied the potential of secosteroid vitamin D derivatives for Aβ40 aggregation in vitro. The quartz-crystal microbalance technique demonstrated that vitamin D3 does not show any effect on Aβ40 aggregation while vitamin D2 promoted it and docking simulation but that vitamin D2 has high potential in this regard. Thus, stacking of the Phe19 benzene ring in Aβ40 and the C22-C23 double bond in vitamin D2 may alter the energy of these molecules. Electron microscopy revealed the potential of vitamin D2 to increase Aβ40 aggregation. Thioflavin-T assays indicated that Vitamin D2 induced increased fluorescence at 490 nm, as typically observed for amyloid fibrils but also for protofibrils; in both cases this reflects of the increase of β-sheet contents. Aβ40 aggregation was further confirmed in ELISA, SDS-PAGE and dot blot analysis which revealed changes in protease K resistance. These results suggest a possible mechanism, of how vitamin D2 could increase Aβ40 aggregation and the docking simulation explains, why the same is not observed with vitamin D3.

  8. Chronic kidney disease and diabetes mellitus predict resistance to vitamin D replacement therapy.

    PubMed

    Alshayeb, Hala M; Wall, Barry M; Showkat, Arif; Mangold, Therese; Quarles, L Darryl

    2013-04-01

    25-Hydroxyvitamin D [25(OH)D] is a marker of nutritional status; however, chronic kidney disease (CKD) results in alterations in vitamin D metabolism, including the loss of vitamin D-binding proteins and alterations in CYP27B1 and CYP24 enzymes that metabolize 25(OH)D. This study was designed to determine the predictors of responsiveness to correction of vitamin D deficiency with oral vitamin D2 (ergocalciferol) in adults. A retrospective study of 183 veterans with 25(OH)D level <30 ng/mL, who were treated with 50,000 IU per week of vitamin D2, was performed. Logistic regression models were developed to determine the factors predicting the response to treatment, defined as either the change in serum 25(OH)D level/1000 IU of vitamin D2 or the number of vitamin D2 doses (50,000 IU per dose) administered. The mean age of the patients was 63 ± 12 years. About 87% were men and 51% diabetic, and 29% had an estimated glomerular filtration rate of <60 mL/min/1.73 m. The average number of vitamin D2 doses was 10.91 ± 5.95; the average increase in 25(OH)D level was 18 ± 10.80 ng/mL. 25(OH)D levels remained <30 ng/mL in 61 patients after treatment. A low estimated glomerular filtration rate and the presence of diabetes mellitus were significant independent predictors for inadequate response to vitamin D2 treatment in logistic regression models. Patients with CKD required greater amounts of vitamin D2 to achieve similar increases in 25(OH)D levels, versus non-CKD patients. The presence of CKD and diabetes mellitus is associated with resistance to correction of 25(OH)D deficiency with vitamin D2 therapy. The underlying mechanism needs to be evaluated in prospective studies.

  9. 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

  10. Analytical and clinical validation of the new Abbot Architect 25(OH)D assay: fit for purpose?

    PubMed

    Cavalier, Etienne; Lukas, Pierre; Bekaert, Anne-Catherine; Carlisi, Agnès; Le Goff, Caroline; Delanaye, Pierre; Souberbielle, Jean-Claude

    2017-03-01

    We provide a clinical and analytical evaluation of the reformulated version of the Abbott Architect 25-hydroxyvitamin D assay. We compared this assay with three commercial automated immunoassays and against a VDSP-traceable liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) in six different populations. We also supplemented 40 healthy volunteers with either 600,000 IU of vitamin D2 or 100,000 of vitamin D3 to evaluate the performance of the immunoassays vs. the LC-MS/MS. Precision and limit of quantification were assessed, 25(OH)D2 and C3-epimer recovery were calculated. Two hundred and forty samples obtained in healthy Caucasians and Africans, osteoporotic, hemodialyzed and intensive care patients and 3rd trimester pregnant women were analyzed by all methods. Correlation was studied using Passing-Bablok and Bland-Altman analysis. Concordance correlation coefficient (CCC) was calculated to evaluate agreement between immunoassays and LC-MS/MS. We verified if patients were homogeneously classified with the immunoassays when they took vitamin D2 or vitamin D3 after 1, 7 and 28 days. We observed excellent analytical features and showed a very good correlation to the LC-MS/MS results in the overall population. Compared to the other immunoassays, concordance of the new Abbott assay with the LC-MS/MS was at least similar, and often better in diseased populations. Althought the cross-reactivity with 25(OH)D2 was not of 100%, there was no significant difference in the classifications of the patients, either supplemented with D2 or D3 or after 7 or 28 days. This modified version of the Abbott Architect assay is clearly improved compared to the previous one and presents a better agreement with the LC-MS/MS.

  11. Plasma profile of hydroxylated vitamin D metabolites: methods and results in normals for spring-winter in Southern Finland.

    PubMed

    Dabek, J T

    1980-02-01

    The spring-winter plasma concentrations of the hydroxylated metabolites of vitamin D have been measured in normal human subjects (20 male, 13 female), using high pressure liquid chromatography with UV-detection for 25-hydroxy vitamin D3/D2 (25(OH)D) and 24,25-dihydroxy vitamin D3/D2 (24,25(OH)2D) and a radioligand receptor assay for 1,25-dihydroxy vitamin D3/D2 (1,25-(OH)2D). The respective levels were 26.6 +/- 16 nmol . l-1, 2.24 +/- 1.3 nmol . l-1 and 114 +/- 35 pmol . l-1. These are in good agreement with levels from other centres for the same season. There was a significant negative correlation between 24,25(OH)2D and 1,25(OH)2 levels. The possible significance of this in the context of the low post-winter body burden of vitamin D is discussed. There was a positive correlation between 25(OH)D and 24,25(OH)2D levels but it did not reach statistical significance. There were no statistically significant differences between the levels of the hydroxylated metabolites in men and women but the 24,25(OH)2D levels were generally lower in the women. The 1,25(OH)2D levels were similar to those measured by isotope dilution mass fragmentography on Norwegian donor blood.

  12. 25(OH)D Status of Elite Athletes with Spinal Cord Injury Relative to Lifestyle Factors.

    PubMed

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

    2016-06-17

    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. 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. 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. 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.

  13. Low bioaccessibility of vitamin D2 from yeast-fortified bread compared to crystalline D2 bread and D3 from fluid milks.

    PubMed

    Lipkie, Tristan E; Ferruzzi, Mario G; Weaver, Connie M

    2016-11-09

    The assessment of the efficacy of dietary and supplemental vitamin D tends to be confounded by differences in the serum 25-hydroxyvitamin D response between vitamin D2 and vitamin D3. Serum response differences from these vitamers may be due to differences in bioavailability. To address this specifically, the bioaccessibility was assessed for vitamin D2 from breads fortified with UV-treated yeast, and a benchmark against staple vitamin D3 fortified foods including bovine milks and infant formula, as well as crystalline vitamin D2 fortified bread. Fortified foods were subjected to a three-stage static in vitro digestion model, and vitamin D was analyzed by HPLC-MS. Vitamin D bioaccessibility was significantly greater from bovine milks and infant formula (71-85%) than from yeast-fortified sandwich breads (6-7%). Bioaccessibility was not different between whole wheat and white wheat bread (p > 0.05), but was ∼4× lower from yeast-fortified bread than from crystalline vitamin D2 fortified bread (p < 0.05). Intact yeast cells were observed in the digesta of yeast fortified bread. These results indicate that the low bioavailability of yeast D2 in comparison to other vitamin D2 sources is likely due to entrapment within a less digestible yeast matrix and not only to metabolic differences between vitamins D2 and D3.

  14. Serum 25(OH)D, PTH and Correlates of Suboptimal 25(OH)D Levels in Persons with Chronic Spinal Cord Injury

    PubMed Central

    Hummel, Kayla; Craven, B. Catharine; Giangregorio, Lora

    2016-01-01

    Study Design Cross-sectional cohort study. Objectives To describe: 1) the prevalence of suboptimal 25-hydroxy vitamin D status (Serum 25(OH)D <75nmol/L) and identify correlates of vitamin D deficiency; and, 2) the prevalence of secondary hyperparathyroidism (Serum intact PTH ≥ 7.0 pmol/L) and identify the relationships between serum parathyroid hormone (PTH) and 25(OH)D in adult men and women with chronic spinal cord injury (SCI). Setting Outpatient services, including an osteoporosis clinic at a tertiary spinal cord rehabilitation hospital in Ontario. Methods Serum levels of 25(OH)D and intact PTH were acquired at enrolment. Clinical correlates of suboptimal vitamin D status were collected via interview and chart abstraction, and identified by univariate logistic regression analysis. Pearson correlations were run to assess the relationships between serum PTH and 25(OH)D. Significance was p<0.05. Results Thirty-nine percent of the cohort, comprised of 62 adult men and women with chronic SCI, had suboptimal serum 25(OH)D levels. Factors associated with suboptimal vitamin D levels included having vitamin D assessed in the winter months (OR=7.38, p=0.001), lack of a calcium supplement (OR=7.19, p=0.003), lack of a vitamin D supplement (OR=7.41, p=0.019), younger age (OR=0.932, p=0.010), paraplegia (OR=4.22, p=0.016), and lack of bisphosphonate (OR=3.85, p=0.015). Significant associations were observed between serum PTH and 25(OH)D (r=−0.304, p=0.032) and between PTH and C-telopeptide of type I collagen (CTX-I) (r=0.308, p=0.025). Conclusions Disruption of the vitamin D-PTH axis may contribute to the bone loss seen in the chronic SCI population. The threshold for optimal serum 25(OH)D levels in the chronic SCI population may be higher than in the non-SCI population. Serum 25(OH)D level are likely important risk factors contributing to declining bone mass and increased fracture risk post-SCI. PMID:22710945

  15. High pressure-assisted encapsulation of vitamin D2 in reassembled casein micelles

    NASA Astrophysics Data System (ADS)

    Menéndez-Aguirre, O.; Stuetz, W.; Grune, T.; Kessler, A.; Weiss, J.; Hinrichs, J.

    2011-03-01

    For the encapsulation of vitamin D2, native casein micelles and vitamin D2 with or without additional Ca2+-Pi were treated at 600 MPa and 37 °C for 60 min. The pressure release rate was set at 20 or 600 MPa/min. Vitamin D2 was quantified by reversed-phase high-performance liquid chromatography, and physical properties of the micelles were analysed by photon correlation spectroscopy. The results demonstrate that simultaneous application of Ca2+-Pi and high pressure treatment with a fast release rate significantly increased loading of vitamin D2 per casein by 6.9-fold. The addition of Ca2+-Pi enhanced micelle aggregation and the vitamin was entrapped within the formed aggregates. However, high pressure treatment without Ca2+-Pi with a slow pressure release rate revealed similar results, increasing vitamin D2 per casein by 6.7-fold. The vitamin D2 loading in reassembled casein micelles is supposed to be due to hydrophobic interactions between the hydrophobic domains of the micelles.

  16. Simultaneous determination of cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2) in foods by selected reaction monitoring.

    PubMed

    Dimartino, Gianluca

    2009-01-01

    Cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2) were determined simultaneously by selected reaction monitoring (SRM) mass spectrometry for different food matrixes. A small amount of starting sample was saponified and extracted before injection into a linear ion trap mass spectrometer equipped with an atmospheric pressure chemical ionization source. Dihydrotachysterol, which is absent from food and has a structure similar to that of vitamins D3 and D2, was used as an internal standard. Calibration curves for the 2 vitamins showed linearity with R2 values of 0.9999 and 0.9989 for vitamins D3 and D2, respectively. Limits of detection for vitamins D3 and D2 were 0.5 ng/g (1.3 pmol/g) and 1.75 ng/g (4.4 pmol/g) and limits of quantitation were 1.25 ng/g (3.24 pmol/g), and 3.75 ng/g (9.45 pmol/g), respectively. Accuracy and precision of the method were tested with the infant formula reference standard of the National Institute of Standards and Technology, which showed a relative standard deviation of 6%. Recoveries ranged from 95 to 105%. Several food products were tested with AOAC Method 982.29, which is currently in use for vitamins D3 and D2, and results were comparable within 6%.

  17. Development and validation of the simultaneous measurement of four vitamin D metabolites in serum by LC-MS/MS for clinical laboratory applications.

    PubMed

    Satoh, Mamoru; Ishige, Takayuki; Ogawa, Shoujiro; Nishimura, Motoi; Matsushita, Kazuyuki; Higashi, Tatsuya; Nomura, Fumio

    2016-11-01

    The quantification of serum 25-hydroxyvitamin D [25(OH)D] as an indicator of vitamin D status is currently primarily conducted by immunoassays, yet LC-MS/MS would allow more accurate determination. Furthermore, LC-MS/MS would allow simultaneous measurement of multiple analytes. The aim of this study was to develop and validate an LC-MS/MS method to simultaneously measure four vitamin D metabolites (25(OH)D3, 3-epi-25(OH)D3, 25(OH)D2, and 24,25(OH)2D3) in serum for clinical laboratory applications. Serum samples were first prepared in a 96-well supported liquid extraction plate and the eluate was derivatized using the Cookson-type reagent 4-(4'-dimethylaminophenyl)-1,2,4-triazoline-3,5-dione (DAPTAD), which rapidly and quantitatively reacts with the s-cis-diene structure of vitamin D metabolites. The derivatized samples were subjected to LC-MS/MS, ionized by electrospray ionization (positive-ion mode), and detected by selected reaction monitoring. The lower limits of quantification for 25(OH)D3, 3-epi-25(OH)D3, 25(OH)D2, and 24,25(OH)2D3 were 0.091, 0.020, 0.013, and 0.024 ng/mL, respectively. The accuracy values and the extraction recoveries for these four metabolites were satisfactory. Serum 25(OH)D levels determined by our LC-MS/MS were compared with those obtained by conventional radioimmunoassay (RIA) that cannot distinguish 25(OH)D3 and 25(OH)D2. The values obtained by the RIA method exhibited a mean bias of about 8.35 ng/mL, most likely as a result of cross reaction of the antibody with low-abundance metabolites, including 24,25(OH)2D3. Various preanalytical factors, such as long sample sitting prior to serum separation, repeated freeze-thaw cycles, and the presence of anticoagulants, had no significant effects on these determinations. This high-throughput LC-MS/MS simultaneous assay of the four vitamin D metabolites 25(OH)D3, 3-epi-25(OH)D3, 25(OH)D2, and 24,25(OH)2D3 required as little as 20 μL serum. This method will aid further understanding of

  18. 25(OH)D levels in trained versus sedentary university students at 64° north.

    PubMed

    Jerome, Scott P; Sticka, Kendra D; Schnurr, Theresia M; Mangum, Sally J; Reynolds, Arleigh J; Dunlap, Kriya L

    2017-01-01

    25-hydroxyvitamin D (25[OH]D) deficiency is associated with compromised bone mineralisation, fatigue, suppressed immune function and unsatisfactory skeletal muscle recovery. We investigated the risk of 25(OH)D insufficiency or deficiency in endurance athletes compared to sedentary non-athletes living at 64° north. University student-athletes (TS) and sedentary students (SS) volunteered to participate in this study. TS engaged in regular exercise while SS exercised no more than 20 minutes/week. Metabolic Equivalent of Task (MET) scores for participants were determined. Vitamin D intake was assessed using the National Cancer Institute's 24-hour food recall (ASA24). Fasting plasma 25(OH)D levels were quantified via enzyme-linked immunosorbent assay. TS reported higher activity levels than SS as assessed with MET-minutes/week and ranking of physical activity levels (p < 0.05). The reported mean daily intake of vitamin D was higher in TS compared to SS (p < 0.05) while 25(OH)D plasma levels were lower in TS than in SS (p < 0.05). In total, 43.8% of the TS were either insufficient (31.3%) or deficient (12.5%) in 25(OH)D, while none of the SS were insufficient and 13.3% were deficient. TS are at increased risk of 25(OH)D insufficiency or deficiency compared to their sedentary counterparts residing at the same latitude, despite higher vitamin D intake.

  19. Serum 25(OH)D, PTH and correlates of suboptimal 25(OH)D levels in persons with chronic spinal cord injury.

    PubMed

    Hummel, K; Craven, B C; Giangregorio, L

    2012-11-01

    Cross-sectional cohort study. To describe: (1) the prevalence of suboptimal 25-hydroxyvitamin D status (serum 25(OH)D <75 nmol l(-1)) and to identify correlates of vitamin D deficiency; (2) the prevalence of secondary hyperparathyroidism (serum intact parathyroid hormone (PTH)>7.0 pmol l(-1)); and (3) the relationships between serum PTH and 25(OH)D in adult men and women with chronic spinal cord injury (SCI). Outpatient services, including an osteoporosis clinic at a tertiary spinal cord rehabilitation hospital in Ontario. Serum levels of 25(OH)D and intact PTH were acquired at enrollment. Clinical correlates of suboptimal vitamin D status were collected via interview and chart abstraction, and identified by univariate logistic regression analysis. Pearson correlations were run to assess the relationships between serum PTH and 25(OH)D. Significance was P<0.05. Thirty-nine percent of the cohort, comprised of 62 adult men and women with chronic SCI, had suboptimal serum 25(OH)D levels. Factors associated with suboptimal vitamin D levels included having vitamin D assessed in the winter months (odds ratio (OR)=7.38, P=0.001), lack of a calcium supplement (OR=7.19, P=0.003), lack of a vitamin D supplement (OR=7.41, P=0.019), younger age (OR=0.932, P=0.010), paraplegia (OR=4.22, P=0.016), and lack of bisphosphonate (OR=3.85, P=0.015). Significant associations were observed between serum PTH and 25(OH)D (r=-0.304, P=0.032) and between PTH and C-telopeptide of type I collagen (CTX-I) (r=0.308, P=0.025). Disruption of the vitamin D-PTH axis may contribute to the bone loss seen in the chronic SCI population. The threshold for optimal serum 25(OH)D levels in the chronic SCI population may be higher than in the non-SCI population. Serum 25(OH)D level are likely important risk factors contributing to declining bone mass and increased fracture risk post-SCI.

  20. The Effect of Vitamin D2 and Vitamin D3 on Intestinal Calcium Absorption in Nigerian Children with Rickets

    PubMed Central

    Thacher, Tom D.; Obadofin, Michael O.; O'Brien, Kimberly O.; Abrams, Steven A.

    2009-01-01

    Context: Children with calcium-deficiency rickets have high 1,25-dihydroxyvitamin D values. Objective: The objective of the study was to determine whether vitamin D increased calcium absorption. Design: This was an experimental study. Setting: The study was conducted at a teaching hospital. Participants: Participants included 17 children with nutritional rickets. Intervention: The participants were randomized to 1.25 mg oral vitamin D3 (n = 8) or vitamin D2 (n = 9). Main Outcome Measure: Fractional calcium absorption 3 da after vitamin D administration was measured. Results: Mean baseline 25-hydroxyvitamin D concentrations were 20 ng/ml (range 5–31 ng/ml). The increase in 25-hydroxyvitamin D was equivalent after vitamin D3 (29 ± 10 ng/ml) or vitamin D2 (29 ± 17 ng/ml). Mean 1,25-dihydroxyvitamin D values increased from 143 ± 76 pg/ml to 243 ± 102 pg/ml (P = 0.001), and the increase in 1,25-dihydroxyvitamin D did not differ between vitamin D2 and vitamin D3 (107 ± 110 and 91 ± 102 ng/ml, respectively). The increment in 1,25-dihydroxyvitamin D was explained almost entirely by the baseline 25-hydroxyvitamin D concentration (r2 = 0.72; P < 0.001). Mean fractional calcium absorption did not differ before (52.6 ± 21.4%) or after (53.2 ± 23.5%) vitamin D, and effects of vitamin D2 and vitamin D3 on calcium absorption were not significantly different. Fractional calcium absorption was not closely related to concentrations of 25-hydroxyvitamin D (r = 0.01, P = 0.93) or 1,25-dihydroxyvitamin D (r = 0.21, P = 0.24). The effect of vitamin D on calcium absorption did not vary with baseline 25-hydroxyvitamin D values or with the absolute increase in 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D values. Conclusions: Despite similar increases in 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D with vitamin D2 or vitamin D3, fractional calcium absorption did not increase, indicating that rickets in Nigerian children is not primarily due to vitamin D-deficient calcium

  1. Traditional foods and 25(OH)D concentrations in a subarctic First Nations community.

    PubMed

    Mansuri, Sudaba; Badawi, Alaa; Kayaniyil, Sheena; Cole, David E; Harris, Stewart B; Mamakeesick, Mary; Wolever, Thomas; Gittelsohn, Joel; Maguire, Jonathon L; Connelly, Philip W; Zinman, Bernard; Hanley, Anthony J

    2016-01-01

    Background Sub-optimal vitamin D status is common worldwide and the condition may be associated with increased risk for various chronic diseases. In particular, low vitamin D status is highly prevalent in indigenous communities in Canada, although limited data are available on the determinants of serum 25-hydroxyvitamin D (25(OH)D) concentrations in this population. The relationship between traditional food consumption and vitamin D status has not been well documented. Objective To investigate the determinants of serum 25(OH)D status in a First Nations community in Ontario, Canada, with a focus on the role of traditional food consumption and activities. Methods A cross-sectional analysis was conducted within the Sandy Lake Health and Diabetes Project (2003-2005). A total of 445 participants (>12 years of age) were assessed for serum 25(OH)D status, anthropometric and lifestyle variables, including traditional and non-traditional dietary practices and activities. Diet patterns were identified using factor analysis, and multivariate linear regression analysis was used to analyse the determinants of 25(OH)D concentrations. Results Mean serum 25(OH)D concentrations were 22.1 nmol/L (16.9, 29.9 nmol/L) in men and 20.5 nmol/L (16.0, 27.3 nmol/L) in women. Multivariate determinants of higher serum 25(OH)D included higher consumption of traditional and healthier market foods, higher wild fish consumption, male gender, spring/summer season of blood collection and more frequent physical activity. Significant negative determinants included hours of TV/day, higher BMI and higher consumption of unhealthy market foods. Conclusions Traditional food consumption contributed independently to higher 25(OH)D concentrations in a First Nations community with a high prevalence of sub-optimal vitamin D status.

  2. Traditional foods and 25(OH)D concentrations in a subarctic First Nations community

    PubMed Central

    Mansuri, Sudaba; Badawi, Alaa; Kayaniyil, Sheena; Cole, David E.; Harris, Stewart B.; Mamakeesick, Mary; Wolever, Thomas; Gittelsohn, Joel; Maguire, Jonathon L.; Connelly, Philip W.; Zinman, Bernard; Hanley, Anthony J.

    2016-01-01

    Background Sub-optimal vitamin D status is common worldwide and the condition may be associated with increased risk for various chronic diseases. In particular, low vitamin D status is highly prevalent in indigenous communities in Canada, although limited data are available on the determinants of serum 25-hydroxyvitamin D (25(OH)D) concentrations in this population. The relationship between traditional food consumption and vitamin D status has not been well documented. Objective To investigate the determinants of serum 25(OH)D status in a First Nations community in Ontario, Canada, with a focus on the role of traditional food consumption and activities. Methods A cross-sectional analysis was conducted within the Sandy Lake Health and Diabetes Project (2003–2005). A total of 445 participants (>12 years of age) were assessed for serum 25(OH)D status, anthropometric and lifestyle variables, including traditional and non-traditional dietary practices and activities. Diet patterns were identified using factor analysis, and multivariate linear regression analysis was used to analyse the determinants of 25(OH)D concentrations. Results Mean serum 25(OH)D concentrations were 22.1 nmol/L (16.9, 29.9 nmol/L) in men and 20.5 nmol/L (16.0, 27.3 nmol/L) in women. Multivariate determinants of higher serum 25(OH)D included higher consumption of traditional and healthier market foods, higher wild fish consumption, male gender, spring/summer season of blood collection and more frequent physical activity. Significant negative determinants included hours of TV/day, higher BMI and higher consumption of unhealthy market foods. Conclusions Traditional food consumption contributed independently to higher 25(OH)D concentrations in a First Nations community with a high prevalence of sub-optimal vitamin D status. PMID:27664115

  3. 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.

  4. Role of the National Institute of Standards and Technology (NIST) in Support of the Vitamin D Initiative of the National Institutes of Health, Office of Dietary Supplements.

    PubMed

    Wise, Stephen A; Tai, Susan S-C; Burdette, Carolyn Q; Camara, Johanna E; Bedner, Mary; Lippa, Katrice A; Nelson, Michael A; Nalin, Federica; Phinney, Karen W; Sander, Lane C; Betz, Joseph M; Sempos, Christopher T; Coates, Paul M

    2017-09-01

    Since 2005, the National Institute of Standards and Technology (NIST) has collaborated with the National Institutes of Health (NIH), Office of Dietary Supplements (ODS) to improve the quality of measurements related to human nutritional markers of vitamin D status. In support of the NIH-ODS Vitamin D Initiative, including the Vitamin D Standardization Program (VDSP), NIST efforts have focused on (1) development of validated analytical methods, including reference measurement procedures (RMPs); (2) development of Standard Reference Materials (SRMs); (3) value assignment of critical study samples using NIST RMPs; and (4) development and coordination of laboratory measurement QA programs. As a result of this collaboration, NIST has developed RMPs for 25-hydroxyvitamin D2 [25(OH)D2], 25(OH)D3, and 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3]; disseminated serum-based SRMs with values assigned for 25(OH)D2, 25(OH)D3, 3-epi-25(OH)D3, and 24R,25(OH)2D3; assigned values for critical samples for VDSP studies, including an extensive interlaboratory comparison and reference material commutability study; provided an accuracy basis for the Vitamin D External Quality Assurance Scheme; coordinated the first accuracy-based measurement QA program for the determination of 25(OH)D2, 25(OH)D3, and 3-epi-25(OH)D3 in human serum/plasma; and developed methods and SRMs for the determination of vitamin D and 25(OH)D in food and supplement matrix SRMs. The details of these activities and their benefit and impact to the NIH-ODS Vitamin D Initiative are described.

  5. An alternative pathway of vitamin D2 metabolism Cytochrome P450scc (CYP11A1)-mediated conversion to 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2

    PubMed Central

    Slominski, Andrzej; Semak, Igor; Wortsman, Jacobo; Zjawiony, Jordan; Li, Wei; Zbytek, Blazej; Tuckey, Robert C.

    2007-01-01

    We report an alternative, hydroxylating pathway for the metabolism of vitamin D2 in a cytochrome P450 side chain cleavage (P450scc; CYP11A1) reconstituted system. NMR analyses identified solely 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2 derivatives. 20-Hydroxyvitamin D2 was produced at a rate of 0.34 mol·min−1·mol−1 P450scc, and 17,20-dihydroxyvitamin D2 was produced at a rate of 0.13 mol·min−1·mol−1. In adrenal mitochondria, vitamin D2 was metabolized to six monohydroxy products. Nevertheless, aminoglutethimide (a P450scc inhibitor) inhibited this adrenal metabolite formation. Initial testing of metabolites for biological activity showed that, similar to vitamin D2, 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2 inhibited DNA synthesis in human epidermal HaCaT keratinocytes, although to a greater degree. 17,20-Dihydroxyvitamin D2 stimulated transcriptional activity of the involucrin promoter, again to a significantly greater extent than vitamin D2, while the effect of 20-hydroxyvitamin D2 was statistically insignificant. Thus, P450scc can metabolize vitamin D2 to generate novel products, with intrinsic biological activity (at least in keratinocytes). PMID:16817851

  6. The differentiation and assay of vitamins D2 and D3 by gas–liquid chromatography

    PubMed Central

    Murray, T. K.; Day, K. C.; Kodicek, E.

    1966-01-01

    1. A method is described for the differentiation and determination of as little as 0·2μg. of vitamins D2 and D3 by gas–liquid chromatography. 2. The vitamins are converted by treatment with antimony trichloride into isovitamins D2 and D3, which show single, separate peaks on gas–liquid chromatography, unlike the unmodified vitamins, which give twin peaks due to the formation of pyro and isopyro derivatives. 3. Since isovitamins D2 and D3 remain together in all steps of the procedure except during gas–liquid chromatography, one may be used as an internal standard for the other. 4. The use of an internal standard reduces the importance of loss during sample preparation and increases precision. 5. The application of the method to biological materials is demonstrated. PMID:4287184

  7. CCQM-K132: low-polarity analytes in a biological matrix: vitamin D metabolites in human serum

    NASA Astrophysics Data System (ADS)

    Wise, Stephen A.; Tai, Susan S.-C.; Duewer, David L.; Bedner, Mary; Camara, Johanna E.; Lippa, Katrice A.; Qinde, Liu; Kang, Dukjin; Kim, Byungjoo; Quan, Can; Shi, Lianhua; Nammoonnoy, Jintana; Vamathevan, Veronica; Ceyhan Gören, Ahmet; Bilsel, Gökhan; Yilmaz, Hasibe

    2017-01-01

    Vitamin D is a fat-soluble vitamin that occurs primarily in two forms, vitamin D2 and vitamin D3. Vitamin D3 is produced naturally when skin is exposed to UV radiation, is naturally-occurring in foods (generally of animal origin), and is fortified in some foods and dietary supplements. Vitamin D2 occurs in food (generally plant sources) and until recently was the form most often used in dietary supplements. Vitamin D is metabolized in the body to produce several closely related, hydroxylated species (metabolites), with 25-hydroxyvitamin D3 [25(OH)D3] and 25-hydroxyvitamin D2 [25(OH)D2] as the most common metabolites measured in human serum. Concentrations of total vitamin D in human serum, calculated as the sum of 25(OH)D2 and 25(OH)D3, are typically in the 16 ng/g to 30 ng/g (40 nmol/L to 75 nmol/L) range, with 25(OH)D3 usually accounting for more than 90 % of the total. An epimer of 25(OH)D3, 3-epi-25(OH)D3, can be present at levels up to 10 % of 25(OH)D3 concentration. Seven National Metrology Institutions participated in the Track C Key Comparison CCQM-K132 low-polarity analytes in a biological matrix: vitamin D metabolites in human serum. Participants were requested to evaluate the mass fractions, expressed in ng/g, of 25(OH)D3, 25(OH)D2, and 3-epi-25(OH)D3 in two human serum materials, termed Serum Pool I and Serum Pool II. Due to the known low levels of 3-epi-25(OH)D3 in both materials and the very low level of 25(OH)D2 in Serum Pool I, the study protocol stated that key comparison reference values (KCRVs) would be assigned only to 25(OH)D3 in both materials and 25(OH)D2 in Serum Pool II. Results for 3-epi-25(OH)D3 were requested to evaluate the separation technologies employed; 3-epi-25(OH)D3 needs to be chromatographically separated from 25(OH)D3 for proper quantification of 25(OH)D3. Results for 25(OH)D2 in Serum Pool I were requested to explore measurement performance at its low level. All participants used isotope dilution liquid chromatography with

  8. 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

  9. Differential Responses to Vitamin D2 and Vitamin D3 Are Associated With Variations in Free 25-Hydroxyvitamin D.

    PubMed

    Chun, Rene F; Hernandez, Ivan; Pereira, Renata; Swinkles, Leon; Huijs, Tonnie; Zhou, Rui; Liu, Nancy Q; Shieh, Albert; Guemes, Miriam; Mallya, Sanjay M; Adams, John S; Hewison, Martin

    2016-09-01

    25-Hydroxyvitamin D (25D) circulates bound primarily to serum vitamin D binding protein (DBP), with DBP showing higher binding affinity for 25D3 than 25D2. We therefore hypothesized that vitamin D2 (D2) promotes higher serum levels of unbound 25D (free 25D), with different functional responses, relative to vitamin D3 (D3). Week 3 C56BL/6 mice were placed on diets containing either D2 or D3 alone (both 1000 IU/kg). At week 8 and week 16, D2 mice had only 25D2 in circulation (26.6 ± 1.9 and 33.3 ± 4.4 ng/mL), and D3 mice had only 25D3 (28.3 ± 2.0 and 31.7 ± 2.1 ng/mL). At week 8 (44.5 ± 6.4 vs 62.4 ± 11.6 pg/mL, P < .05) and week 16 (78.4 ± 12.6 vs 95.5 ± 11.6), D2 mice had lower serum 1,25-dihydroxyvitamin D relative to D3 mice. By contrast, measured free 25D was significantly higher in D2 mice at week 8 (16.8 ± 0.65 vs 8.4 ± 0.63 pg/mL, P < .001) and week 16 (17.4 ± 0.43 vs 8.4 ± 0.44, P < .001). A two-way ANOVA of bone histomorphometry showed that week 8 D2 mice had significantly higher osteoclast surface/bone surface, eroded surface/bone surface, and mineral apposition rate compared with D3 mice. Osteoblast surface/bone surface was higher in week 8 D2 females but not week 8 D2 males. At week 16, D2 mice had significantly higher bone volume/total volume and trabecular number compared with D3 mice. Differences in bone phenotype were observed despite D2 mice reaching similar serum 25D levels and lower 1,25D levels compared with D3 mice. These data indicate that 25D2 binds less well to DBP than 25D3, with resulting higher levels of free 25D promoting differential effects on bone in mice exposed to D2 alone.

  10. Interaction between vitamin D 2 and magnesium in liposomes: Differential scanning calorimetry and FTIR spectroscopy studies

    NASA Astrophysics Data System (ADS)

    Toyran, Neslihan; Severcan, Feride

    2007-08-01

    Magnesium (Mg 2+) ion is of great importance in physiology by its intervention in 300 enzymatic systems, its role in membrane structure, its function in neuromuscular excitability and vitamin D metabolism and/or action. In the present study, the interaction of Mg 2+, at low (1 mole %) and high (7 mole %) concentrations with dipalmitoyl phosphatidylcholine (DPPC) liposomes has been studied in the presence and absence of vitamin D 2 (1 mole %) by using two noninvasive techniques, namely differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. DSC studies reveal that the presence of vitamin D 2 in the pure or Mg 2+ (at both low and high concentrations) containing liposomes diminishes the pretransition. The calorimetric results also reveal that, inclusion of Mg 2+ (more significantly at high concentration) into pure or vitamin D 2 containing DPPC liposomes increases the main phase transition temperature. The investigation of the CH 2 symmetric, the CH 3 asymmetric, the C dbnd O stretching, and the PO2- antisymmetric double bond stretching bands in FTIR spectra with respect to changes occurring in the wavenumber and/or the bandwidth values as a function of temperature reveal that, inclusion of vitamin D 2 or Mg 2+ into pure DPPC liposomes orders and decreases the dynamics of the acyl chains in both gel and liquid-crystalline phases and does not induce hydrogen bond formation in the interfacial region. Furthermore, the dynamics of the head groups of the liposomes decreases in both phases. Our findings reveal that, simultaneous presence of vitamin D 2 and Mg 2+ alters the effect of each other, which is reflected as a decrease in the interactions between these two additives within the model membrane.

  11. Association between Obesity and Serum 25(OH)D Concentrations in Older Mexican Adults.

    PubMed

    Rontoyanni, Victoria G; Avila, Jaqueline C; Kaul, Sapna; Wong, Rebeca; Veeranki, Sreenivas P

    2017-01-31

    Vitamin D is essential for maintaining bone mineralization and calcium homeostasis, and prevents falls and fractures in older adults. Mexico is undergoing an epidemiologic and demographic transition with increasing obesity rates. The study's aim was to determine the association of obesity with serum 25-hydroxyvitamin D [25(OH)D] concentrations in older Mexican adults. Data from 1772 Mexicans, aged ≥50 years, enrolled in a sub-sample of the 3rd wave of the Mexican Health and Aging Study, were included. Serum 25(OH)D concentrations were used to define vitamin D status, and were categorized into tertiles. Body mass index measures were used to categorize older adults into under/normal weight, overweight, and obese groups. Multinomial logistic regression models were used to assess the relationship, adjusting for potential confounders. Approximately 40% and 37% of older Mexican adults were either overweight or obese, respectively. Compared to under/normal weight older Mexicans, obese adults were 1.78 times (95% Confidence Interval (CI) 1.27-2.48) and 1.94 times (95% CI 1.40-2.68) more associated with the first and second tertile concentrations of serum 25(OH)D, respectively. Overweight adults were 1.52 times (95% CI 1.12-2.06) more associated with the second tertile of serum 25(OH)D concentration than under/normal weight adults. Overweight/Obesity was found to be significantly associated with low concentrations of serum 25(OH) in older Mexican adults.

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

    USDA-ARS?s Scientific Manuscript database

    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 c...

  13. 25 (OH) D3 levels, incidence and recurrence of different clinical forms of BPPV.

    PubMed

    Maslovara, Sinisa; Butkovic Soldo, Silva; Sestak, Anamarija; Milinkovic, Katarina; Rogic-Namacinski, Jasna; Soldo, Anamarija

    2017-06-11

    Benign Paroxysmal Positional Vertigo (BPPV) is the most common cause of dizziness in the general population. It is a condition with potential impact of reduced levels of vitamin D on its recurrent attacks. The aim of this study was to measure the serum levels of 25-hydroxyvitamin D3 (25-OH D3) in patients with BPPV and determine whether there is a difference in the serum levels of vitamin D3 between patients with and without recurrence, as well as between the different clinical forms of BPPV. The study included 40 patients who came to the regular medical examination, diagnosed with PC-BPPV based on the positive Dix-Hallpike's test. All patients underwent Epley manoeuvre after the diagnosis. Patients were classified according to current guidelines for levels of vitamin D3 in the serum in three groups: the deficiency, insufficiency and adequate level. The average serum level of 25-OH D3 among respondents was 20.78ng/mL, indicating a lack or insufficiency of the aforementioned 25-OH D3. According to the levels of 25-OH D3, most patients suffer from deficiency (47.5%). 7 (17.5%) respondents had adequate blood level of 25-OH D3, and 14 (35%) respondents suffer from insufficiency. A significant difference was not found in the serum level of 25-OH D3 between patients with and without BPPV recurrence. There was a significant difference in the serum levels of 25-OH D3 in comparison to the clinical form of the disease. Lower 25-OH D3 values were found in patients with canalithiasis compared to those with cupulolithiasis. There were no significant differences in the vitamin D3 serum level in patients with and without recurrence. The study showed a low level of serum vitamin D3 in most patients, indicating the need for supplemental therapy. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  14. Serum levels of 3-epi-25-OH-D3 during hypervitaminosis D in clinical practice.

    PubMed

    Granado-Lorencio, F; Blanco-Navarro, I; Pérez-Sacristán, B; Donoso-Navarro, E; Silvestre-Mardomingo, R

    2012-12-01

    Intoxication from vitamin D supplements has been rarely reported, but nowadays, it occurs more frequently. The presence of the C-3 epimer of 25-hydroxyvitamin D(3) (3-epi-25-OH-D(3)) is highly prevalent in adults, although there is little information regarding its in vivo relevance, if any, especially under pathological conditions. Our aim was to assess the presence of the 3-epi-25-OH-D(3) in serum samples displaying 25-OH-D(3) concentrations indicative of hypervitaminosis D. A total of 58 samples displaying a wide range of concentrations of 25-OH-D(3) (>64-439 ng/ml) by ultrafast liquid chromatography were consecutively recruited and reassessed for the presence of 3-epi-25-OH-D(3) using a second chromatographic system. Data from additional biochemical tests performed as part of the patient evaluation were also recorded. Mean relative contribution of 3-epi-25-OH-D(3) was less than 4%, and concentrations ranged from 2-28.6 ng/ml. Serum levels of the C3 epimer, but not the relative contribution, correlate with serum 25-OH-D(3). Overall, in subjects with 25-OH-D(3) concentrations indicative of hypervitaminosis D, the presence of the C-3 epimer and its levels were apparently unrelated to age, serum markers of renal and liver function, acute-phase reactants, and the presence of hypercalcemia. 3-Epi-25-OH-D(3) did not correlate with PTH, but subjects displaying PTH suppression (<14 pg/ml) showed higher concentrations of 3-epi-25-OH-D(3). The relative contribution of 3-epi-25-D(3) was not significantly altered during hypervitaminosis D, although the absolute levels reached in serum may be biologically relevant. From a clinical viewpoint, although the small size of the group may affect the lack of relationships, the presence of 3-epi-25-OH-D(3) was apparently unrelated to serum markers of renal and liver function, acute-phase reactants, PTH, and the presence of hypercalcemia.

  15. Optimal level of 25-(OH)D in children in Nanjing (32°N Lat) during winter.

    PubMed

    Liang, Guan-Yu; Qin, Rui; Li, Jing; Liang, Guan-Xiang; Guan, Yong-Juan; Gao, Zhan-Hui

    2011-08-01

    The optimal serum level of 25-hydroxyvitamin D (25-(OH)D) for bone health is still unclear, especially in children. Hypovitaminosis D is also re-emerging in developed and developing countries. The purpose of the present study was therefore to determine optimal serum 25-(OH)D level and preliminarily identify the vitamin D nutritional status in Nanjing children. All subjects (76 healthy, 66 suffering from infectious diseases) aged 0-10 years were recruited during the period December 2007-March 2008. Venous blood samples were collected before breakfast and the levels of serum 25-(OH)D, parathyroid hormone (PTH), bone-specific alkaline phosphatase (BAP), calcium (Ca), phosphorus (P) were determined. The optimal level of serum 25-(OH)D was explored using the three response curves of 25-(OH)D versus PTH, 25-(OH)D versus BAP, and 25-(OH)D versus Ca×P product. For 25-(OH)D ≤ 50 nmol/L, PTH and BAP were both inversely correlated with 25-(OH)D (PTH, r=-0.864, P < 0.01; BAP, r=-0.856, P < 0.01). For 25-(OH)D > 50-60 nmol/L, levels of PTH and BAP remained steady. With regard to the Ca×P product, for 25-(OH)D ≤ 50 nmol/L, Ca×P product increased as 25-(OH)D increased (r= 0.037, P > 0.05). For 25-(OH)D > 50-60 nmol/L, Ca×P product remained steady. The mean serum level of 25-(OH)D was 80.5 ± 29.3 nmol/L (mean ± SD) in the healthy children, and 65.7 ± 32.3 nmol/L in the sick children. The optimal 25-(OH)D level may be 50-60 nmol/L for bone health in Nanjing children. The vitamin D nutritional status of Nanjing children is relatively good in winter. © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.

  16. Association between serum 25(OH)D concentrations and bone stress fractures in Finnish young men.

    PubMed

    Ruohola, Juha-Petri; Laaksi, Ilkka; Ylikomi, Timo; Haataja, Riina; Mattila, Ville M; Sahi, Timo; Tuohimaa, Pentti; Pihlajamäki, Harri

    2006-09-01

    Low vitamin D level may predict rickets, osteomalacia, or osteoporosis. We examined serum 25(OH)D concentration as a predisposing factor for bone stress fracture in 756 military recruits. The average serum 25(OH)D concentration was significantly lower in the group with fracture, suggesting a relationship between vitamin D and fatigue bone stress fracture. Low vitamin D level may predict rickets, osteomalacia, or osteoporosis. Fatigue bone stress fracture is one of the most frequently seen types of overuse injuries in athletes and military recruits. An association was recently shown between vitamin D and BMC. A correlation has also been found between low femoral BMD and stress fractures. We measured serum 25(OH)D concentration in a population sample of military recruits to determine if vitamin D is a predisposing factor for fatigue bone stress fracture. We prospectively followed 800 randomly selected, healthy Finnish military recruits with a mean age of 19 years for developing stress fractures in homogenous circumstances. Blood for serum 25(OH)D concentration was drawn at entry into military service, and the weight, height, body mass index (BMI), muscle strength, and 12-minute running were measured for all subjects. Serum 25(OH)D concentrations were measured with enzyme immunoassay. At end of the 90-day follow-up, 756 subjects completed the study. Subjects without fracture constituted controls. Twenty-two recruits with stress fracture were identified (2.9%), the incidence being 11.6 (95% CI: 6.8-16.5) per 100 person-years. In the final multivariate analysis, the significant risk factor for stress fracture in conscripts was a below median serum 25(OH)D level (75.8 nM), OR being 3.6 (95% CI: 1.2-11.1). No significant associations between BMI (p = 0.255), age (p = 0.216), or smoking (p = 0.851) and bone stress fracture were found in this study population. A lower level of serum 25(OH)D concentration may be a generally predisposing element for bone stress fractures

  17. 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

  18. 1,25(OH)2vitamin D3 Enhances Myogenic Differentiation by Modulating the Expression of Key Angiogenic Growth factors and Angiogenic Inhibitors in C2C12 Skeletal Muscle Cells

    PubMed Central

    Garcia, Leah A.; Ferrini, Monica G.; Norris, Keith C.; Artaza, Jorge N.

    2012-01-01

    Vitamin D is mostly recognized for its regulation of calcium homeostasis in relation to the intestine, kidney, and bone. Although clinical studies have linked vitamin D with increased muscle function and strength, little is known of its underlying molecular mechanism. We recently demonstrated that 1,25-D3 exerts a direct pro-myogenic effect on skeletal muscle cells; this has provoked our investigation of 1,25-D’s effect on angiogenesis, a vital process for new capillary development and tissue repair. In this study, we examined the mechanism by which 1,25-D3 modulates key angiogenic growth factors and angiogenic inhibitors. C2C12 myoblasts were incubated with 100 nM 1,25-D3 or placebo for 1, 4 and 10 days. At the end of the respective incubation time, total RNA was isolated for PCR arrays and for qRT-PCR. Total proteins were isolated for western blots and proteome profiler arrays. The addition of 1,25-D3 to C2C12 myoblasts increased VEGFa and FGF-1: two pro-angiogenic growth factors that promote neo-vascularization and tissue regeneration, and decreased FGF-2 and TIMP-3: two myogenic and/or angiogenic inhibitors. Our previous study demonstrated that 1,25-D3 altered IGF-I/II expression, consistent with the observed changes in VEGFa and FGF-2 expression. These results extend our previous findings and demonstrate the modulation of angiogenesis which may be an additional mechanism by which 1,25-D3 promotes myogenesis. This study supports the mechanistic rationale for assessing the administration of vitamin D and/or vitamin D analogues to treat select muscle disorders and may also provide an alternative solution for therapies that directly manipulate VEGF and FGF’s to promote angiogenesis. PMID:22982629

  19. Potential determinants of vitamin D in Finnish adults: a cross-sectional study from the Northern Finland birth cohort 1966

    PubMed Central

    Palaniswamy, Saranya; Hyppönen, Elina; Williams, Dylan M; Jokelainen, Jari; Lowry, Estelle; Keinänen-Kiukaanniemi, Sirkka; Herzig, Karl-Heinz; Järvelin, Marjo-Riitta; Sebert, Sylvain

    2017-01-01

    Objective Evidence from randomised controlled trials suggests that vitamin D may reduce multimorbidity, but very few studies have investigated specific determinants of vitamin D2 and D3 (two isoforms of 25-hydroxyvitamin D). The aim of the study was to investigate the determinants of vitamin D2 and D3 and to identify the risk factors associated with hypovitaminosis D. Design Cross-sectional study. Setting Northern Finland Birth Cohort 1966. Participants 2374 male and 2384 female participants with data on serum 25(OH)D2 and 25(OH)D3 concentrations measured at 31 years of age (1997), together with comprehensive measures of daylight, anthropometric, social, lifestyle and contraceptive cofactors. Methods We assessed a wide range of potential determinants prior to a nationwide fortification programme introduced in Finland. The determinants of 25(OH)D2, 25(OH)D3 and 25(OH)D concentrations were analysed by linear regression and risk factors for being in lower tertile of 25(OH)D concentration by ordinal logistic regression. Results At the time of sampling, 72% of the participants were vitamin D sufficient (≥50 nmol/L). Low sunlight exposure period (vs high) was associated positively with 25(OH)D2 and negatively with 25(OH)D3 concentrations. Use of oral contraceptives (vs non-users) was associated with an increase of 0.17 nmol/L (95% CI 0.08 to 0.27) and 0.48 nmol/L (95% CI 0.41 to 0.56) in 25(OH)D2 and 25(OH)D3 concentrations. Sex, season, latitude, alcohol consumption and physical activity were the factors most strongly associated with 25(OH)D concentration. Risk factors for low vitamin D status were low sunlight exposure defined by time of sampling, residing in northern latitudes, obesity, higher waist circumference, low physical activity and unhealthy diet. Conclusions We demonstrate some differential associations of environmental and lifestyle factors with 25(OH)D2 and 25(OH)D3 raising important questions related to personalised healthcare. Future strategies

  20. Vitamin D2 Stability During the Refrigerated Storage of Ultraviolet B-Treated Cultivated Culinary-Medicinal Mushrooms.

    PubMed

    Slawinska, Aneta; Fornal, Emilia; Radzki, Wojciech; Jablonska-Rys, Ewa; Parfieniuk, Ewa

    2017-01-01

    The effects of ultraviolet B (UVB) irradiation on the synthesis of vitamin D2 and its stability during refrigerated storage was determined in fresh cultivated culinary-medicinal mushrooms (Agaricus bisporus, Pleurotus ostreatus, and Lentinus edodes) after harvest. The irradiated mushrooms were stored at 4°C for up to 10 days. The concentrations of vitamin D2 and ergosterol were determined using ultrahigh-performance liquid chromatography/tandem mass spectrometry. The cultivated mushrooms not treated with UVB were devoid of vitamin D2. After UVB irradiation, we obtained mushrooms with a large amount of ergocalciferol. A. bisporus showed the lowest vitamin D2 content (3.55 ± 0.11 μg D2/g dry weight); P. ostreatus contained 58.96 ± 1.15 μg D2/g dry weight, and L. edodes contained 29.46 ± 2.21 μg/g dry weight. During storage at 4°C, the amount of vitamin D2 was gradually decreased in P. ostreatus and L. edodes, whereas in A. bisporus vitamin D2 gradually increased until the sixth day, then decreased. Mushrooms exposed to UVB radiation contain a significant amount of vitamin D2 and are therefore an excellent food source of vitamin D.

  1. 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.

  2. Maternal serum 25(OH)D levels in the third trimester of pregnancy during the winter season.

    PubMed

    Ustuner, Isik; Keskin, H Levent; Tas, Emre Erdem; Neselioglu, Salim; Sengul, Ozlem; Avsar, Ayse Filiz

    2011-12-01

    To measure serum 25(OH)D levels of pregnant women in the last trimester during the winter season and to determine the factors affecting their serum levels. In all, 79 pregnant women in the third trimester were examined between November 2008 and March 2009. Serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, and 25(OH)D levels were measured. Maternal age, education, socioeconomic status (SES), nutrition, dressing habits, and level of sunlight exposure were determined and their correlation with serum 25(OH)D levels were statistically compared. The mean serum 25(OH)D level of the study group was 11.95 ± 7.20 ng/ml, and the prevalence of severe vitamin D deficiency [25(OH)D < 10 ng/ml] in pregnant women was 45.6%. No association was detected between severe vitamin D deficiency and maternal age, gravidity, skin phototype, benefiting from ultraviolet index, and educational status of the cases. Also in patients who used multivitamin supplements and good SES, 25(OH)D levels were significantly higher (p=0.046, p=0.025, respectively). This study showed a remarkable high rate of vitamin D deficiency in pregnant women during the winter season and we have found high levels of vitamin D in patients supplemented with multivitamins and in ones with good SES.

  3. Plasma appearance and disappearance of an oral dose of 25-hydroxyvitamin D2 in healthy adults

    PubMed Central

    Jones, Kerry S.; Schoenmakers, Inez; Bluck, Les J. C.; Ding, Shujing; Prentice, Ann

    2012-01-01

    25-Hydroxyvitamin D (25(OH)D) half-life is a potential biomarker for investigating vitamin D metabolism and requirements. We performed a pilot study to assess the approach and practical feasibility of measuring 25(OH)D half-life after an oral dose. A total of twelve healthy Gambian men aged 18–23 years were divided into two groups to investigate the rate and timing of (1) absorption and (2) plasma disappearance after an 80 nmol oral dose of 25(OH)D2. Fasting blood samples were collected at baseline and, in the first group, every 2 h post-dose for 12 h, at 24 h, 48 h and on day 15. In the second group, fasting blood samples were collected on days 3, 4, 5, 6, 9, 12, 15, 18 and 21. Urine was collected for 2 h after the first morning void at baseline and on day 15. 25(OH)D2 plasma concentration was measured by ultra-performance liquid chromatography-tandem MS/MS and corrected for baseline. Biomarkers of vitamin D, Ca and P metabolism were measured at baseline and on day 15. The peak plasma concentration of 25(OH)D2 was 9·6 (sd 0·9) nmol/l at 4·4 (sd 1·8) h. The terminal slope of 25(OH)D2 disappearance was identified to commence from day 6. The terminal half-life of plasma 25(OH)D2 was 13·4 (sd 2·7) d. There were no significant differences in plasma 25(OH)D3, total 1,25(OH)2D, parathyroid hormone, P, Ca and ionised Ca and urinary Ca and P between baseline and day 15 and between the two groups. The present study provides data on the plasma response to oral 25(OH)D2 that will underpin and contribute to the further development of studies to investigate 25(OH)D half-life. PMID:21896243

  4. Plasma appearance and disappearance of an oral dose of 25-hydroxyvitamin D2 in healthy adults.

    PubMed

    Jones, Kerry S; Schoenmakers, Inez; Bluck, Les J C; Ding, Shujing; Prentice, Ann

    2012-04-01

    25-Hydroxyvitamin D (25(OH)D) half-life is a potential biomarker for investigating vitamin D metabolism and requirements. We performed a pilot study to assess the approach and practical feasibility of measuring 25(OH)D half-life after an oral dose. A total of twelve healthy Gambian men aged 18-23 years were divided into two groups to investigate the rate and timing of (1) absorption and (2) plasma disappearance after an 80 nmol oral dose of 25(OH)D2. Fasting blood samples were collected at baseline and, in the first group, every 2 h post-dose for 12 h, at 24 h, 48 h and on day 15. In the second group, fasting blood samples were collected on days 3, 4, 5, 6, 9, 12, 15, 18 and 21. Urine was collected for 2 h after the first morning void at baseline and on day 15. 25(OH)D2 plasma concentration was measured by ultra-performance liquid chromatography-tandem MS/MS and corrected for baseline. Biomarkers of vitamin D, Ca and P metabolism were measured at baseline and on day 15. The peak plasma concentration of 25(OH)D2 was 9·6 (sd 0·9) nmol/l at 4·4 (sd 1·8) h. The terminal slope of 25(OH)D2 disappearance was identified to commence from day 6. The terminal half-life of plasma 25(OH)D2 was 13·4 (sd 2·7) d. There were no significant differences in plasma 25(OH)D3, total 1,25(OH)2D, parathyroid hormone, P, Ca and ionised Ca and urinary Ca and P between baseline and day 15 and between the two groups. The present study provides data on the plasma response to oral 25(OH)D2 that will underpin and contribute to the further development of studies to investigate 25(OH)D half-life.

  5. Development of Standard Reference Material (SRM) 2973 Vitamin D Metabolites in Frozen Human Serum (High Level).

    PubMed

    Tai, Susan S-C; Nelson, Michael A; Bedner, Mary; Lang, Brian E; Phinney, Karen W; Sander, Lane C; Yen, James H; Betz, Joseph M; Sempos, Christopher T; Wise, Stephen A

    2017-09-01

    The National Institute of Standards and Technology (NIST), in collaboration with the National Institutes of Health Office of Dietary Supplements and the Vitamin D Standardization Program, has recently issued a new serum-matrix Standard Reference Material (SRM): 2973 Vitamin D Metabolites in Frozen Human Serum (High Level). SRM 2973 was designed to provide a serum material with a total 25-hydroxyvitamin D [25(OH)D] concentration near 100 nmol/L to complement the existing serum-based SRMs with values assigned for total 25(OH)D between 20 and 80 nmol/L. Values were assigned for 25-hydroxyvitamin D2 [25(OH)D2], 25-hydroxyvitamin D3 [25(OH)D3], 3-epi-25(OH)D3, and total 25(OH)D [the sum of 25(OH)D2 + 25(OH)D3] using the NIST isotope dilution LC with tandem MS (MS/MS) reference measurement procedure (RMP) and related methods. SRM 2973 has a certified value of 98.4 ± 2.1 nmol/L for 25(OH)D3 and reference values of 1.59 ± 0.05 nmol/L for 25(OH)D2 and 5.23 ± 0.20 nmol/L for 3-epi-25(OH)D3. In addition, a candidate RMP for 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] based on LC-MS/MS was used to assign values to SRM 2973 and the existing SRM 972a Vitamin D Metabolites in Frozen Human Serum. Reference values for 24R,25(OH)2D3 were assigned to SRM 2973 (7.51 ± 0.26 nmol/L) and the four levels of SRM 972a: Level 1 (6.38 ± 0.23 nmol/L), Level 2 (3.39 ± 0.12 nmol/L), Level 3 (3.88 ± 0.013 nmol/L), and Level 4 (6.32 ± 0.22 nmol/L). The development of SRM 2973 [with a higher concentration of 25(OH)D3] and the addition of values for 24R,25(OH)2D3 assigned to both SRM 972a and SRM 2973 provide laboratories involved in vitamin D measurements with improved QA tools.

  6. High-Dose Intramuscular Vitamin D Provides Long-Lasting Moderate Increases in Serum 25-Hydroxvitamin D Levels and Shorter-Term Changes in Plasma Calcium.

    PubMed

    Gorman, Shelley; Zafirau, Mark Zafir; Lim, Ee Mun; Clarke, Michael W; Dhamrait, Gursimran; Fleury, Naomi; Walsh, John P; Kaufmann, Martin; Jones, Glenville; Lucas, Robyn M

    2017-09-01

    The best management of vitamin D deficiency, defined as a 25-hydroxyvitamin D [(25(OH)D] level <50 nM, is unclear. Intramuscular (IM) injection of a large bolus of vitamin D (≥100 000 IU) is used, but its safety is uncertain. In 10 adults given an IM injection of 600 000IU vitamin D3, we measured at baseline and at 1, 2, 3, and 4 weeks postinjection the serum levels of vitamin D3, 25(OH)D3, 25(OH)D2, total 25(OH)D, 3-epi-25(OH)D3, and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] using a standardized LC with tandem MS (MS/MS) assay; serum levels of 25(OH)D using the Abbott ARCHITECT i2000 immunoassay; and markers of bone metabolism. Bone markers and 25(OH)D (immunoassay) were remeasured at 24 weeks. All participants had baseline total 25(OH)D levels >50 nM. Serum 25(OH)D levels increased at 3, 4, and 24 weeks postinjection, peaking at 4 weeks [mean ± SEM of 126 ± 7.9 nM (immunoassay) and 100 ± 5.5 nM (LC-MS/MS)] but generally remained <125 nM, the upper limit recommended by the U.S. Institute of Medicine. Serum 24,25(OH)2D3 levels increased at 3 and 4 weeks postinjection. Serum ionized calcium levels were higher than baseline at 1, 3, and 4 weeks postinjection but remained within the clinically normal range. Other biochemical parameters, including other vitamin D metabolites, plasma alkaline phosphatase, and parathyroid hormone levels, were unchanged. IM injection of a large bolus of vitamin D effectively increases serum 25(OH)D levels without evidence of metabolic abnormality.

  7. 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

  8. Enhancement of Vitamin D Metabolites in the Eye following Vitamin D3 Supplementation and UV-B Irradiation

    PubMed Central

    Lin, Yanping; Ubels, John L.; Schotanus, Mark P.; Yin, Zhaohong; Pintea, Victorina; Hammock, Bruce D.; Watsky, Mitchell A.

    2013-01-01

    Purpose This study was designed to measure vitamin D metabolites in the aqueous and vitreous humor and in tear fluid, and to determine if dietary vitamin D3 supplementation affects these levels. We also determined if the corneal epithelium can synthesize vitamin D following UV-B exposure. Methods Rabbits were fed a control or vitamin D3 supplemented diet. Pilocarpine-stimulated tear fluid was collected and aqueous and vitreous humor were drawn from enucleated eyes. Plasma vitamin D was also measured. To test for epithelial vitamin D synthesis, a human corneal limbal epithelial cell line was irradiated with two doses of UV-B (10 and 20 mJ/cm2/day for three days) and vitamin D was measured in control or 7-dehydrocholesterol treated culture medium. Measurements were made using mass spectroscopy. Results 25(OH)-vitamin D3 and 24,25(OH)2-vitamin D3 increased significantly following D3 supplementation in all samples except vitreous humor. Tear fluid and aqueous humor had small but detectable 1,25(OH)2-vitamin D3 levels. Vitamin D2 metabolites were observed in all samples. Vitamin D3 levels were below the detection limit for all samples. Minimal vitamin D3 metabolites were observed in control and UV-B-irradiated epithelial culture medium except following 7-dehydrocholesterol treatment, which resulted in a UV-B-dose dependent increase in vitamin D3, 25(OH)-vitamin D3 and 24,25(OH)2-vitamin D3. Conclusions There are measurable concentrations of vitamin D metabolites in tear fluid and aqueous and vitreous humor, and oral vitamin D supplementation affects vitamin D metabolite concentrations in the anterior segment of the eye. In addition, the UV exposure results lead us to conclude that corneal epithelial cells are likely capable of synthesizing vitamin D3 metabolites in the presence of 7-dehydrocholesterol following UV-B exposure. PMID:22632164

  9. Serum 25(OH)D and adipokines levels in people with abdominal obesity.

    PubMed

    Karonova, T; Belyaeva, O; Jude, E B; Tsiberkin, A; Andreeva, A; Grineva, E; Pludowski, P

    2016-09-11

    Abdominal obesity is a risk factor for cardiovascular disease and diabetes mellitus and has been associated with vitamin D deficiency. Some studies have suggested an association between obesity and adipokine levels as well as low serum 25-hydroxyvitamin D (25(OH)D) level but the underlying mechanisms of the interlink between vitamin D status and serum leptin and adiponectin concentrations are still disputed. We included 435 residents (132 males) from St. Petersburg, Russia into this study. All subjects had physical examination and demographics noted. Blood was collected after an overnight fast and plasma glucose, insulin, serum lipids, 25(OH)D and adipokines (adiponectin and leptin) concentrations were determined at baseline in all participants. Abdominal obesity was diagnosed in 310 (71.3%) subjects (251 females and 59 males). Vitamin D insufficiency and deficiency were found in 314 (72.2%) subjects. Mean (95% CI) age, body mass index (BMI) and serum 25(OH)D for the cohort were 47.6±11.3years; 28.7±0.2kg/m(2) and 62.5±24.3nmol/l respectively. Serum 25(OH)D level inversely correlated with body weight, waist circumference (WC) and BMI in females but not in males, was lower in diabetic than non-diabetic subjects, and was not significantly different in subjects with and without MetS. WC was positively correlated with leptin and negatively correlated with adiponectin. We found correlation between leptin and serum 25(OH)D level (r=-0.15, p=0.01) but this finding was a characteristic seen only in women. Our study showed a high prevalence of abdominal obesity, vitamin D deficiency and insufficiency in residents from North-West region of Russia, close association between adipokine (leptin, adiponectin) concentrations as well as vitamin D status and body composition (WC, BMI). However in our study the interlink between leptin level and 25(OH)D was found only in females. Further investigations are required to study the relationship between serum 25(OH)D level, obesity and

  10. 25(OH)D3 and Cardiovascular Risk Factors in Female Nonhuman Primates

    PubMed Central

    Jorgensen, Matthew J.; Rudel, Lawrence L.; Nudy, Matthew; Kaplan, Jay R.; Clarkson, Thomas B.; Pajewski, Nicholas M.

    2012-01-01

    Abstract Objective To determine if interindividual differences in plasma concentrations of 25-hydroxyvitamin D3 (25(OH)D3) have pathophysiologic significance, we evaluated a cohort of female monkeys, seeking to identify associations with clinically relevant cardiovascular risk factors, including age, abdominal obesity (waist circumference), and high-density lipoprotein cholesterol (HDL-C). Methods One hundred fifty-five female vervet monkeys (Chlorocebus aethiops sabaeus) aged 3–25 years consumed a typical western diet for 7–8 weeks that provided a woman's equivalent of approximately 1000 IU/day of vitamin D3. Measurements of vitamin D3 and HDL-C concentrations, as well as waist circumference, were obtained. Results Among young monkeys (aged 3–5 years), compared to older monkeys (aged 16–25 years), the mean plasma 25(OH)D3 concentrations were 82.3±3.2 ng/mL and 58.6±2.9 ng/mL (p<0.0001), respectively. Plasma 25(OH)D3 concentrations had a range of 19.6–142.0 ng/mL (mean±standard error [SE] 66.4±1.7 ng/mL). 25(OH)D3 concentrations were inversely associated with age (p<0.0001) and waist circumference (p=0.016) and were positively correlated with HDL-C (p=0.01). However, when statistically controlling for age, none of these relationships remained significant. Conclusions Higher plasma concentrations of 25(OH)D3 were associated with more favorable cardiovascular risk factors, with inverse associations observed between 25(OH)D3 and abdominal obesity, HDL-C, and age. These associations were no longer significant when controlling for age. PMID:22876774

  11. Hypoparathyroidism: Less Severe Hypocalcemia With Treatment With Vitamin D2 Compared With Calcitriol.

    PubMed

    Streeten, Elizabeth A; Mohtasebi, Yasaman; Konig, Manige; Davidoff, Lisa; Ryan, Kathleen

    2017-05-01

    Options for chronic treatment of hypoparathyroidism include calcitriol, recombinant human parathyroid hormone, and high-dose vitamin D (D2). D2 is used in a minority of patients because of fear of prolonged hypercalcemia and renal toxicity. There is a paucity of recent data about D2 use in hypoparathyroidism. Compare renal function, hypercalcemia, and hypocalcemia in patients with hypoparathyroidism treated chronically with either D2 (D2 group) or calcitriol. A retrospective study of patients with hypoparathyroidism treated at the University of Maryland Hospital. Participants were identified by a billing record search with diagnosis confirmed by chart review. Thirty patients were identified; 16 were treated chronically with D2, 14 with calcitriol. Data were extracted from medical records. Serum creatinine and calcium, hospitalizations, and emergency department (ED) visits for hypercalcemia and hypocalcemia. D2 and calcitriol groups were similar in age (58.9 ± 16.7 vs 50.9 ± 22.6 years, P = 0.28), sex, and treatment duration (17.8 ± 14.2 vs 8.5 ± 4.4 years, P = 0.076). Hospitalization or ED visits for hypocalcemia occurred in none of the D2 group vs four of 14 in the calcitriol group (P = 0.03); three in the calcitriol group had multiple ED visits. There were no differences between D2 and calcitriol groups in hospitalizations or ED visits for hypercalcemia, serum creatinine or calcium, or kidney stones. We found less morbidity from hypocalcemia in hypoparathyroid patients treated chronically with D2 compared with calcitriol and found no difference in renal function or morbidity from hypercalcemia. Treatment with D2 should be considered in patients with hypoparathyroidism, particularly in those who experience recurrent hypocalcemia.

  12. Iatrogenic vitamin D toxicity in an infant--a case report and review of literature.

    PubMed

    Ketha, Hemamalini; Wadams, Heather; Lteif, Aida; Singh, Ravinder J

    2015-04-01

    Public concern over vitamin D deficiency has led to widespread use of over the counter (OTC) vitamin D (-D3 or -D2) supplements, containing up to 10,000 IU/unit dose (400 IU=10μg). Overzealous use of such supplements can cause hypercalcemia due to vitamin D toxicity. Infants are particularly vulnerable to toxicity associated with vitamin D overdose. OTC supplements are not subject to stringent quality control regulations from FDA and high degree of variability in vitamin D content in OTC pills has been demonstrated. Other etiologies of vitamin D induced hypercalcemia include hyperparathyroidism, granulomatous malignancies like sarcoidosis and mutations in the CYP24A1 gene. The differential diagnosis of hypercalcemia should include iatrogenic and genetic etiologies. C24-hydroxylation and C3-epimerization are two important biochemical pathways via which 25-hydroxyvitamin D3 (25(OH)D3) is converted to its metabolites, 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) or its C3 epimer, 3-epi-25-OH-D3 respectively. Mutations in the CYP24A1 gene cause reduced serum 24,25(OH)2D3 to 25(OH)D3 ratio (<0.02), elevated serum 1,25-dihydroxyvitamin D (1,25(OH)2D3), hypercalcemia, hypercalciuria and nephrolithiasis. Studies in infants have shown that 3-epi-25(OH)D3 can contribute 9-61.1% of the total 25(OH)D3. Therefore, measurements of parathyroid hormone (PTH) and vitamin D metabolites 25(OH)D3, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3 are useful to investigate whether the underlying cause of vitamin D toxicity is iatrogenic versus genetic. Here we report a case of vitamin D3 associated toxicity in a 4-month-old female who was exclusively breast-fed and received an oral liquid vitamin D3 supplement at a dose significantly higher than recommended on the label. The vitamin D3 content of the supplement was threefold higher (6000 IU of D/drop) than listed on the label (2000 IU). Due to overdosing and higher vitamin D3 content, the infant received ∼50,000 IU/day for two months

  13. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. 25(OH)D3 Levels Relative to Muscle Strength and Maximum Oxygen Uptake in Athletes

    PubMed Central

    Zagrodna, Aleksandra; Dziubek, Wioletta; Pietraszewski, Bogdan; Ochmann, Bartosz; Słowińska – Lisowska, Małgorzata

    2016-01-01

    Abstract Vitamin D is mainly known for its effects on the bone and calcium metabolism. The discovery of Vitamin D receptors in many extraskeletal cells suggests that it may also play a significant role in other organs and systems. The aim of our study was to assess the relationship between 25(OH)D3 levels, lower limb isokinetic strength and maximum oxygen uptake in well-trained professional football players. We enrolled 43 Polish premier league soccer players. The mean age was 22.7±5.3 years. Our study showed decreased serum 25(OH)D3 levels in 74.4% of the professional players. The results also demonstrated a lack of statistically significant correlation between 25(OH)D3 levels and lower limb muscle strength with the exception of peak torque of the left knee extensors at an angular velocity of 150°/s (r=0.41). No significant correlations were found between hand grip strength and maximum oxygen uptake. Based on our study we concluded that in well-trained professional soccer players, there was no correlation between serum levels of 25(OH)D3 and muscle strength or maximum oxygen uptake. PMID:28149343

  15. Serum 25(OH)D and Type 2 Diabetes Association in a General Population

    PubMed Central

    Husemoen, Lise Lotte N.; Thuesen, Betina H.; Fenger, Mogens; Jørgensen, Torben; Glümer, Charlotte; Svensson, Jannet; Ovesen, Lars; Witte, Daniel R.; Linneberg, Allan

    2012-01-01

    OBJECTIVE This study aimed to examine vitamin D status as a determinant for development of type 2 diabetes and deterioration of glucose homeostasis. RESEARCH DESIGN AND METHODS A random sample of the general population of Copenhagen, Denmark, was taken as part of the Inter99 study. Included were 6,405 men and women aged 30–65 years at baseline (1999–2001), with 4,296 participating in the follow-up examination 5 years later (2004–2006). Vitamin D was determined at baseline as serum 25-hydroxyvitamin D [25(OH)D]. Diabetes was defined based on an oral glucose tolerance test and a glycosylated hemoglobin (HbA1c) test. Secondary outcomes included continuous markers of glucose homeostasis. RESULTS The risk of incident diabetes associated with a 10 nmol/L increase in 25(OH)D was odds ratio (OR) 0.91 (95% CI 0.84–0.97) in crude analyses. The association became statistically nonsignificant after adjustment for confounders, with an OR per 10 nmol/L of 0.94 (0.86–1.03). Low 25(OH)D status was significantly associated with unfavorable longitudinal changes in continuous markers of glucose homeostasis after adjustment for confounders. Fasting and 2-h glucose and insulin as well as the degree of insulin resistance increased significantly more during follow-up among those with low 25(OH)D levels compared with those with higher levels. CONCLUSIONS Low 25(OH)D status was not significantly associated with incident diabetes after adjustment for confounders. However, it was significantly associated with unfavorable longitudinal changes in continuous markers of glucose homeostasis, indicating that low vitamin D status could be related to deterioration of glucose homeostasis. PMID:22688545

  16. Development and Certification of a Standard Reference Material for Vitamin D Metabolites in Human Seruma

    PubMed Central

    Phinney, Karen W.; Bedner, Mary; Tai, Susan S.-C.; Vamathevan, Veronica V.; Sander, Lane C.; Sharpless, Katherine E.; Wise, Stephen A.; Yen, James H.; Schleicher, Rosemary L.; Chaudhary-Webb, Madhulika; Pfeiffer, Christine M.; Betz, Joseph M.; Coates, Paul M.; Picciano, Mary Frances

    2012-01-01

    The National Institute of Standards and Technology (NIST), in collaboration with the National Institutes of Health’s Office of Dietary Supplements (NIH-ODS), has developed a Standard Reference Material (SRM) for the determination of 25-hydroxyvitamin D [25(OH)D] in serum. SRM 972 Vitamin D in Human Serum consists of four serum pools with different levels of vitamin D metabolites and has certified and reference values for 25(OH)D2, 25(OH)D3, and 3-epi-25(OH)D3. Value assignment of this SRM was accomplished using a combination of three isotope-dilution mass spectrometry approaches, with measurements performed at NIST and at the Centers for Disease Control and Prevention (CDC). Chromatographic resolution of the 3-epimer of 25(OH)D3 proved to be essential for accurate determination of the metabolites. PMID:22141317

  17. Development and certification of a standard reference material for vitamin D metabolites in human serum.

    PubMed

    Phinney, Karen W; Bedner, Mary; Tai, Susan S-C; Vamathevan, Veronica V; Sander, Lane C; Sharpless, Katherine E; Wise, Stephen A; Yen, James H; Schleicher, Rosemary L; Chaudhary-Webb, Madhulika; Pfeiffer, Christine M; Betz, Joseph M; Coates, Paul M; Picciano, Mary Frances

    2012-01-17

    The National Institute of Standards and Technology (NIST), in collaboration with the National Institutes of Health's Office of Dietary Supplements (NIH-ODS), has developed a Standard Reference Material (SRM) for the determination of 25-hydroxyvitamin D [25(OH)D] in serum. SRM 972 Vitamin D in Human Serum consists of four serum pools with different levels of vitamin D metabolites and has certified and reference values for 25(OH)D(2), 25(OH)D(3), and 3-epi-25(OH)D(3). Value assignment of this SRM was accomplished using a combination of three isotope-dilution mass spectrometry approaches, with measurements performed at NIST and at the Centers for Disease Control and Prevention (CDC). Chromatographic resolution of the 3-epimer of 25(OH)D(3) proved to be essential for accurate determination of the metabolites.

  18. Serum Vitamin D Levels and Vitamin D Supplement in Adult Patients with Asthma Exacerbation

    PubMed Central

    Chantveerawong, Teerapol; Pradubpongsa, Panitan; Sangasapaviliya, Atik

    2016-01-01

    Introduction. Vitamin D deficiency has been linked to an increased risk of asthma exacerbations. Objective. This study aimed to compare vitamin D status during the period of severe asthma exacerbations and investigate if vitamin D supplementation improves asthma control. Methods. A total of 47 asthmatic patients and 40 healthy subjects participated in this study. Serum 25-hydroxyvitamin D (25(OH)D), asthma control test (ACT) score, and % predicted peak expiratory flow rate were evaluated in the period with and without severe asthma exacerbations. After that, we provided vitamin D2 supplements to the patients with low vitamin D levels for 3 months. Results. At the period of asthma exacerbation, the prevalence of vitamin D deficiency and insufficiency was 38.29% and 34.04%. There was no significant difference in the levels of serum 25(OH)D with and without asthma exacerbations but the levels were significantly higher in the healthy group. Serum 25(OH)D levels significantly correlated with ACT score. Moreover, vitamin D2 supplementation improved asthma control in uncontrolled asthma group. Conclusions. Hypovitaminosis D was common in asthmatic patients but was not the leading cause of asthma exacerbations. Serum 25(OH)D levels correlated with the ability to control asthma. Improving vitamin D status might be a benefit in uncontrolled asthmatic patients. PMID:27974898

  19. Lower Vitamin D Metabolites Levels Were Associated With Increased Coronary Artery Diseases in Type 2 Diabetes Patients in India

    PubMed Central

    Adela, Ramu; Borkar, Roshan M; Bhandi, Murali Mohan; Vishwakarma, Gayatri; Reddy, P. Naveen Chander; Srinivas, R.; Banerjee, Sanjay K

    2016-01-01

    The purpose of the present study was to measure six vitamin D metabolites and to find the association between vitamin D deficiency and coronary artery diseases in diabetes (T2DM_CAD). Four groups [control (n = 50), type 2 diabetes (T2DM, n = 71), coronary artery diseases (CAD, n = 28), T2DM_CAD (n = 38)] of total 187 subjects were included in the study. Six vitamin D metabolites (D2, D3, 25(OH)D2, 25(OH)D3, 1,25(OH)2D2, 1,25(OH)2D3), total 25(OH)D and total 1,25(OH)2D were measured by UPLC/APCI/HRMS method in these subjects. Although all the vitamin D metabolites were significantly decreased in T2DM_CAD as compared to both control and T2DM subjects (p < 0.05), only two metabolites i.e., 25(OH)D3 and total 25(OH)D were significantly (p < 0.05) decreased in the T2DM subjects as compared with the control subjects (p < 0.05). Vitamin D3, 1,25(OH)2D2, 25(OH)D, and 1,25(OH)2D levels were significantly decreased in T2DM_CAD subjects as compared with CAD subjects (p < 0.05). Further, multiple logistic regression analysis revealed that total 25(OH)D and total 1,25(OH)2D can be used to predict T2DM (OR 0.82.95% CI 0.68–0.99; p = 0.0208) and T2DM with CAD (OR 0.460, 95% CI 0.242–0.874; p = 0.0177), respectively. Our data concludes that lower concentration of 1,25(OH)2D is associated with type 2 diabetes coexisting with coronary artery diseases in South Indian subjects. PMID:27883024

  20. Development and validation of an LC-MS/MS based method for quantification of 25 hydroxyvitamin D2 and 25 hydroxyvitamin D3 in human serum and plasma.

    PubMed

    Zhang, Stanley Weihua; Jian, Wenying; Sullivan, Sheryl; Sankaran, Banu; Edom, Richard W; Weng, Naidong; Sharkey, David

    2014-06-15

    Vitamin D deficiency is increasing in the general population and has become a serious public health risk globally. As a reliable clinical indicator of vitamin status, 25 hydroxyvitamin D (25(OH)D) has been measured by various methods. However, the accuracy of these measurements has been the subject of considerable debate. Here, we report the development and validation of a liquid chromatography-triple quadrupole mass spectrometry based method for the quantification of 25(OH)D2 and 25(OH)D3 in human serum and plasma samples. Samples were first processed by protein precipitation to release the analytes from the vitamin D binding protein (DBP), followed by a liquid-liquid extraction procedure. Analysis was performed on an LC-MS/MS system which utilized an AB Sciex API 3000 mass spectrometer. A six point calibration curve ranging from 2.5 to 100ng/mL was established for both 25(OH)D2 and 25(OH)D3. A complete method validation was conducted, including intra- and inter-assay accuracy and precision, LLOQ, dilution QC, specificity, recovery, matrix effect, and a thorough stability profile of stock solutions and QC samples. Matching samples of serum and plasma (containing either heparin or EDTA anticoagulant) generated from the same blood samples were tested, and no significant differences in 25(OH)D2 and 25(OH)D3 concentrations were found in these sample matrices. In method comparison, we analyzed 10 serum samples obtained from the Vitamin D External Quality Assessment Scheme (DEQAS), and the total 25(OH)D concentrations measured by our method were very close to the LC-MS/MS Method Mean values provided by DEQAS (average 0.17% bias, R(2)=0.99). However, comparison with the DiaSorin Liaison 25(OH)D TOTAL Assay demonstrated limited correlation between these two methods (R(2)=0.54). In general, concentrations measured by our LC-MS/MS method were roughly 9% higher than those measured by the DiaSorin Liaison assay. The correlation with DiaSorin Liaison measurement was better for

  1. Low Vitamin D Status: Definition, Prevalence, Consequences and Correction

    PubMed Central

    Binkley, Neil; Ramamurthy, Rekha; Krueger, Diane

    2014-01-01

    Vitamin D is obtained from cutaneous production when 7-dehydrocholesterol is converted to vitamin D3 (cholecalciferol) by ultraviolet B radiation or by oral intake of vitamin D2 (ergocalciferol) and D3. An individual's vitamin D status is best evaluated by measuring the circulating 25-hydroxyvitamin D [25(OH)D] concentration. Though controversy surrounds the definition of low vitamin D status, there is increasing agreement that the optimal circulating 25(OH)D level should be ~30-32 ng/ml or above. Using this definition, it has been is estimated that approximately three quarters of all adults in the United States are low. Classically, low vitamin D status has skeletal consequences such as osteomalacia/rickets. More recently, associations between low vitamin D status and increased risk for various non-skeletal morbidities have been recognized; whether all of these associations are causally related to low vitamin D status remains to be determined. To achieve optimal vitamin D status, daily intakes of at least 1000 IU or more of vitamin D are required. The risk of toxicity with “high” amounts of vitamin D intake is low. Substantial between-individual variability exists in response to the same administered vitamin D dose. When to monitor 25(OH)D levels has received little attention. Supplementation with vitamin D3 may be preferable to vitamin D2. PMID:20511052

  2. Low vitamin D status: definition, prevalence, consequences, and correction.

    PubMed

    Binkley, Neil; Ramamurthy, Rekha; Krueger, Diane

    2010-06-01

    Vitamin D is obtained from cutaneous production when 7-dehydrocholesterol is converted to vitamin D(3) (cholecalciferol) by ultraviolet B radiation or by oral intake of vitamin D(2) (ergocalciferol) and D(3). An individual's vitamin D status is best evaluated by measuring the circulating 25-hydroxyvitamin D (25(OH)D) concentration. Although controversy surrounds the definition of low vitamin D status, there is increasing agreement that the optimal circulating 25(OH)D level should be approximately 30 to 32 ng/mL or above. Using this definition, it has been estimated that approximately three-quarters of all adults in the United States have low levels. Low vitamin D status classically has skeletal consequences such as osteomalacia/rickets. More recently, associations between low vitamin D status and increased risk for various nonskeletal morbidities have been recognized; whether all of these associations are causally related to low vitamin D status remains to be determined. To achieve optimal vitamin D status, daily intakes of at least 1000 IU or more of vitamin D are required. The risk of toxicity with "high" amounts of vitamin D intake is low. Substantial between-individual variability exists in response to the same administered vitamin D dose. When to monitor 25(OH)D levels has received little attention. Supplementation with vitamin D(3) may be preferable to vitamin D(2). Copyright 2010 Elsevier Inc. All rights reserved.

  3. Genetic and environmental predictors of serum 25(OH)D concentrations among middle-aged and elderly Chinese in Singapore

    PubMed Central

    Robien, Kim; Butler, Lesley M.; Wang, Renwei; Beckman, Kenneth B.; Walek, Dinesha; Koh, Woon-Puay; Yuan, Jian-Min

    2012-01-01

    Vitamin D is known for maintaining calcium homeostasis and bone structure, and may also decrease susceptibility to chronic and infectious diseases. However, data on vitamin D status and its predictors among Southeast Asian populations is limited. We evaluated the distribution and determinants (genetic and environmental) of serum 25-hydroxyvitamin D (25(OH)D) concentrations among 504 middle-aged and elderly participants (aged 45–74 years) in the Singapore Chinese Health Study. Data on dietary and other lifestyle factors were collected by trained interviewers. Serum 25(OH)D concentrations and genetic polymorphisms in vitamin D metabolism pathway enzymes [cytochrome P450 (CYP) 2R1, 3A4, 27B1, 24A1; vitamin D binding protein (GC); and vitamin D receptor (VDR)] were measured using stored biospecimens. Mean 25(OH)D concentration was 68.8 nmol/L. Serum 25(OH)D concentrations were positively associated with dietary vitamin D intake, and inversely associated with hours sitting at work. BMI was not associated with 25(OH)D concentrations. CYP2R1 rs10741657, rs12794714, rs1993116; CYP3A4 rs2242480; and GC rs4588, rs7041, rs16847015, rs2298849 were statistically significantly associated with 25(OH)D concentrations. Individuals with the Gc2-2 haplotype (rs4588AA/rs7041TT) had statistically significantly lower 25(OH)D concentrations compared to all other Gc haplotypes (p-trend<0.001). The majority of participants (86%) had 25(OH)D concentrations ≥50 nmol/L, which is consistent with the 2011 Institute of Medicine (United States) recommendation for bone health, and 32% had concentrations of ≥75 nmol/L that are thought to be required for broader health effects. Dietary vitamin D intake, hours spent indoors at work, and genetic variation in CYP2R1, CYP3A4 and GC are significant predictors of 25(OH)D concentrations among Singapore Chinese. PMID:22583563

  4. Antiproliferative action of menadione and 1,25(OH)2D3 on breast cancer cells.

    PubMed

    Marchionatti, Ana M; Picotto, Gabriela; Narvaez, Carmen J; Welsh, Joellen; Tolosa de Talamoni, Nori G

    2009-02-01

    Calcitriol or 1,25(OH)(2)D(3) is a negative growth regulator of MCF-7 breast cancer cells. The growth arrest is due to apoptosis activation, which involves mitochondrial disruption. This effect is blunted in vitamin D resistant cells (MCF-7(DRes) cells). Menadione (MEN), a glutathione (GSH)-depleting compound, may potentiate antitumoral effects of anticancer drugs. The aim of this study was to investigate whether MEN enhances cellular responsiveness of MCF-7 cells to 1,25(OH)(2)D(3). Cells were cultured and treated with different concentrations of 1,25(OH)(2)D(3)+/-MEN or vehicle for 96 h. GSH levels and the activity of antioxidant enzymes were determined by spectrophotometry and ROS production by flow cytometry. Both drugs decreased growth and enhanced ROS in MCF-7 cells, obtaining the maximal effects when 1,25(OH)(2)D(3) was combined with MEN (P<0.01 vs. Control and vs. each compound alone). MCF-7(DRes) cells were not responsive to 1,25(OH)(2)D(3), but the cell proliferation was slightly inhibited by the combined treatment. Calcitriol and MEN separately enhanced antioxidant enzyme activities, but when they were used in combination, the effect was more pronounced (P<0.05 vs. Control and vs. each compound alone). MEN, calcitriol and the combined treatment decreased GSH levels (P<0.05 vs. Control). The data indicate that MEN potentiates the effect of 1,25(OH)(2)D(3) on growth arrest in MCF-7 cells by oxidative stress and increases the activities of antioxidant enzymes, probably as a compensatory mechanism.

  5. Fortification of orange juice with vitamin D: a novel approach for enhancing vitamin D nutritional health.

    PubMed

    Tangpricha, Vin; Koutkia, Polyxeni; Rieke, Suzanne M; Chen, Tai C; Perez, Alberto A; Holick, Michael F

    2003-06-01

    Fortification of milk with vitamin D may not be adequate for satisfying the vitamin D requirement because of variability in vitamin D content after fortification and because many persons have milk allergy or lactose intolerance. Additional foods need to be fortified with vitamin D. We determined whether vitamin D, a fat-soluble vitamin, is bioavailable in orange juice and skim milk, 2 nonfat beverages. On 3 separate occasions, 18 adults ingested 25 000 IU vitamin D(2) in 240 mL whole milk or skim milk or in 0.1 mL corn oil applied to toast. A separate, double-blind, randomized, controlled trial investigated whether the consumption of orange juice fortified with vitamin D(3) would increase serum 25-hydroxyvitamin D [25(OH)D] concentrations: 14 subjects ingested 240 mL orange juice fortified with 1000 IU vitamin D, and 12 subjects ingested a control orange juice daily for 12 wk. Peak serum vitamin D(2) concentrations did not differ significantly after the ingestion of vitamin D(2) in whole milk, skim milk, or corn oil on toast. After subjects consumed orange juice fortified with 1000 IU vitamin D(3) daily for 12 wk, serum 25(OH)D(3) concentrations increased by 150%, and serum parathyroid hormone concentrations decreased by 25% compared with baseline; control subjects had a seasonal increase of 45% in 25(OH)D and no significant change in serum parathyroid hormone. The fat content of milk does not affect vitamin D bioavailability. Vitamin D fortification at 1000 IU/240 mL orange juice for 12 wk safely increased 25(OH)D(3) concentrations in adults.

  6. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Association between Obesity and Serum 25(OH)D Concentrations in Older Mexican Adults

    PubMed Central

    Rontoyanni, Victoria G.; Avila, Jaqueline C.; Kaul, Sapna; Wong, Rebeca; Veeranki, Sreenivas P.

    2017-01-01

    Background: Vitamin D is essential for maintaining bone mineralization and calcium homeostasis, and prevents falls and fractures in older adults. Mexico is undergoing an epidemiologic and demographic transition with increasing obesity rates. The study’s aim was to determine the association of obesity with serum 25-hydroxyvitamin D [25(OH)D] concentrations in older Mexican adults. Methods: Data from 1772 Mexicans, aged ≥50 years, enrolled in a sub-sample of the 3rd wave of the Mexican Health and Aging Study, were included. Serum 25(OH)D concentrations were used to define vitamin D status, and were categorized into tertiles. Body mass index measures were used to categorize older adults into under/normal weight, overweight, and obese groups. Multinomial logistic regression models were used to assess the relationship, adjusting for potential confounders. Results: Approximately 40% and 37% of older Mexican adults were either overweight or obese, respectively. Compared to under/normal weight older Mexicans, obese adults were 1.78 times (95% Confidence Interval (CI) 1.27–2.48) and 1.94 times (95% CI 1.40–2.68) more associated with the first and second tertile concentrations of serum 25(OH)D, respectively. Overweight adults were 1.52 times (95% CI 1.12–2.06) more associated with the second tertile of serum 25(OH)D concentration than under/normal weight adults. Conclusion: Overweight/Obesity was found to be significantly associated with low concentrations of serum 25(OH) in older Mexican adults. PMID:28146127

  8. 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

  9. Effect of vitamin D2- and D3-enriched diets on egg vitamin D content, production, and bird condition during an entire production period.

    PubMed

    Mattila, P; Valaja, J; Rossow, L; Venäläinen, E; Tupasela, T

    2004-03-01

    Vitamin D insufficiency during winter is a common problem for humans in Europe. One way to ease this problem is through the production of vitamin D-fortified eggs. To evaluate such a production process, the effects of vitamin D supplementation during an entire production period were assessed. Transfer of vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol) from the diet to egg yolks was measured using 2 different levels of both vitamins (6,000 and 15,000 IU/kg feed) relative to a control treatment (2,500 IU vitamin D3/kg feed). During the experiment, production parameters, egg quality (egg weight, Haugh unit, specific gravity, eggshell fracture force, and Ca content of eggshell), and the condition of hens were monitored. At the end of the experiment histopathological tests were performed. Supplementing diets with vitamin D3 increased egg yolk vitamin D content more effectively than did supplementation with vitamin D2. For groups of hens receiving 6,000 or 15,000 IU of vitamin D3/kg feed, egg yolk vitamin D3 content ranged from 9.1 to 13.6 and from 25.3 to 33.7 microg/100 g, respectively. Corresponding values for birds fed vitamin D2 were 4.7 to 7.0 and 13.3 to 21.0 microg/100 g. Both supplements enhanced vitamin D3 content of egg yolks relative to the control diet (2.5 to 5.0 microg/100 g of egg yolk). Vitamin D supplements had no effects on production parameters compared with the control diet. However, especially vitamin D3 improved bone strength (P < 0.05). Autopsy at the end of the experiment indicated no detrimental accumulation of calcium in the kidneys, liver, heart, muscles, or lungs.

  10. Development and optimization of an LC-MS/MS-based method for simultaneous quantification of vitamin D2 , vitamin D3 , 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3.

    PubMed

    Adamec, Jiri; Jannasch, Amber; Huang, Jianjie; Hohman, Emily; Fleet, James C; Peacock, Munro; Ferruzzi, Mario G; Martin, Berdine; Weaver, Connie M

    2011-01-01

    Simultaneous and accurate measurement of vitamin D and 25-hydroxyvitamin D in biological samples is a barrier limiting our ability to define "optimal" vitamin D status. Thus, our goal was to optimize conditions and evaluate an LC-MS method for simultaneous detection and quantification of vitamin D(2) , vitamin D(3) , 25-hydroxyvitamin D(2) and 25-hydroxyvitamin D(3) in serum. Extraction and separation of vitamin D forms were achieved using acetone liquid-liquid extraction and by a reversed phase C8 column, respectively. Detection was performed on a triple quadrupole tandem mass spectrometer (QQQ-MS/MS) equipped with atmospheric pressure photo ionization source. The LOQs for all analytes tested were 1 ng/mL for hydroxylated molecules and 2 ng/mL for the parent vitamin Ds. RSD at lower LOQ (2 ng/mL) and in medium (80 ng/mL) and high (200 ng/mL) quality control samples did not exceed 20 and 15% CV, respectively. Accuracy of the method for determination of hydroxylated molecules was also validated using National Institutes of Standards and Technology standard samples and found to be in the range of 90.9-111.2%. In summary, a sensitive and reproducible method is reported for simultaneous quantification of vitamin D(2) , vitamin D(3) , 25-hydroxyvitamin D(2) and 25-hydroxyvitamin D(3) molecules in biological samples.

  11. 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

  12. 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.

  13. 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.

  14. A Candidate Reference Measurement Procedure for Quantifying Serum Concentrations of 25-Hydroxyvitamin D3 and 25-Hydroxyvitamin D2 Using Isotope-Dilution Liquid Chromatography-Tandem Mass Spectrometry

    PubMed Central

    Mineva, Ekaterina M.; Schleicher, Rosemary L.; Chaudhary-Webb, Madhulika; Maw, Khin L.; Botelho, Julianne C.; Vesper, Hubert W.; Pfeiffer, Christine M.

    2016-01-01

    The inaccuracy of routine serum 25-hydroxyvitamin D measurements hampers the interpretation of data in patient care and public health research. We developed and validated a candidate reference measurement procedure (RMP) for highly accurate quantitation of two clinically important 25-hydroxyvitamin D metabolites in serum, 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3]. The two compounds of interest together with spiked deuterium-labeled internal standards [d3-25(OH)D2 and d6-25(OH)D3] were extracted from serum via liquid-liquid extraction. The featured isotope-dilution LC-MS/MS method used reversed-phase chromatography and atmospheric pressure chemical ionization in positive ion mode. A pentafluorophenylpropyl-packed UHPLC column together with isocratic elution allowed for complete baseline resolution of 25(OH)D2 and 25(OH)D3 from their structural C-3 isomers within 12 min. We evaluated method trueness, precision, potential interferences, matrix effects, limits of quantitation, and measurement uncertainty. Calibration materials were, or were traceable to, NIST Standard Reference Materials 2972. Within-day and total imprecision (CV) averaged 1.9% and 2.0% for 25(OH)D3, respectively, and 2.4% and 3.5% for 25(OH)D2, respectively. Mean trueness was 100.4% for 25(OH)D3 and 100.3% for 25(OH)D2. The limits of quantitation/limits of detection were 4.61/1.38 nmol/L for 25(OH)D3 and 1.46/0.13 nmol/L for 25(OH)D2. When we compared our RMP results to an established RMP using 40 serum samples, we found a nonsignificant mean bias of 0.2% for total 25(OH)D. This candidate RMP for 25(OH)D metabolites meets predefined method performance specifications (≤5% total CV and ≤1.7% bias) and provides sufficient sample throughput to meet the needs of the Centers for Disease Control and Prevention Vitamin D Standardization Certification Program. PMID:25967149

  15. 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.

  16. 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.

  17. 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

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

    USDA-ARS?s Scientific Manuscript database

    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...

  19. Standard multivitamin supplementation does not improve vitamin D insufficiency after burns

    PubMed Central

    Herndon, David N.; Chen, Tai C.; Kulp, Gabriela; Holick, Michael F.

    2013-01-01

    Children suffering severe burns develop progressive vitamin D deficiency because of inability of burned skin to produce normal quantities of vitamin D3 and lack of vitamin D supplementation on discharge. Our study was designed to determine whether a daily supplement of a standard multivitamin tablet containing vitamin D2 400 IU (10 μg) for 6 months would raise serum levels of 25-hydroxyvitamin D [25(OH)D] to normal. We recruited eight burned children, ages 5–18, whose families were deemed reliable by the research staff. These children were given a daily multivitamin tablet in the hospital for 3 months in the presence of a member of the research staff and then given the remainder at home. At 6 months, the subjects returned for measurements of serum levels of 25(OH)D,1,25-dihydroxyvitamin D [1,25(OH)2D], intact parathyroid hormone (iPTH), Ca, P, albumin, and total protein as well as bone mass by dual energy X-ray absorptiometry. Serum 25(OH)D levels were compared to a group of seven age-matched burned children studied at an earlier date without the vitamin supplement but with the same method of determination of 25(OH)D at 6 months post-burn. In addition, the chewable vitamins were analyzed for vitamin D2 content by high performance liquid chromatography. Serum concentration of 25(OH)D was 21 ± 11(SD) ng/ml (sufficient range 30–100) with only one of the eight children having a value in the sufficient range. In comparison, the unsupplemented burn patients had mean serum 25(OH)D level of 16 ± 7, P = 0.33 versus supplemented. Serum levels of 1,25(OH)2D, iPTH, Ca, P, albumin, and total protein were all normal in the supplemented group. Vitamin D2 content of the chewable tablets after being saponified and extracted was 460 ± 20 IU. Bone mineral content of the total body and lumbar spine, as well as lumbar spine bone density, failed to increase as expected in the supplemented group. No correlations were found between serum 25(OH)D levels and age, length of stay

  20. 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.

  1. Correction of vitamin D deficiency using sublingually administered vitamin D2 in a Crohn's disease patient with mal-absorption and a new ileostomy.

    PubMed

    McCullough, Patrick; Heaney, Robert

    2016-12-31

    Vitamin D deficiency has been shown to be associated with many adverse health problems. Studies have shown that patients with Crohn's disease who have low vitamin D levels have a poorer quality of life than those with more adequate levels. It has also been shown that patients with mal-absorption problems have a difficult time achieving normal vitamin D levels in spite of aggressive supplementation, and that exposure to UVB radiation may be the most effective treatment option for these patients. We present a case in which 25-hydroxyvitamin D levels were normalized within 2 weeks in a severely vitamin D deficient patient with Crohn's disease with mal-absorption and a new ileostomy, utilizing sublingually administered vitamin D2. A 58 year-old white female was admitted with a new ileostomy following partial bowel resection due to complications from Crohn's disease. She was found to be severely vitamin D deficient at the time of admission, with a level of 6.1ng/ml on hospital day 3. Her treatment with vitamin D was delayed for a few days. She was initially treated with 5000 units of vitamin D3 orally twice a day for 3days (days 7-10). After discussion with the patient and obtaining her consent, vitamin D3 was stopped, and she was then treated with a total of 8 doses of 50,000 units of vitamin D2 administered sublingually. She was given the first 3 doses on alternating days (days 11, 13, 15), and then 5 more doses on consecutive days (days 17-21). The rise in her 25-hydroxyvitamin D level in response to treatment with sublingual vitamin D2 was significant. On day 10, after receiving 3days of orally administered vitamin D3, her level was 9.8ng/ml. One week later, after receiving 3 sublingual doses of vitamin D2, it rose to 20.3ng/ml. It was then measured on alternating days twice over the next 4days, and it rose to 45.5ng/ml, and then to 47.4ng/ml on the day of discharge to home. The major finding of this study is that sublingual administration of vitamin D2 appears to

  2. [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).

  3. 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

  4. An alternative pathway of vitamin D metabolism. Cytochrome P450scc (CYP11A1)-mediated conversion to 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2.

    PubMed

    Slominski, Andrzej; Semak, Igor; Wortsman, Jacobo; Zjawiony, Jordan; Li, Wei; Zbytek, Blazej; Tuckey, Robert C

    2006-07-01

    We report an alternative, hydroxylating pathway for the metabolism of vitamin D2 in a cytochrome P450 side chain cleavage (P450scc; CYP11A1) reconstituted system. NMR analyses identified solely 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2 derivatives. 20-Hydroxyvitamin D2 was produced at a rate of 0.34 mol x min(-1) x mol(-1) P450scc, and 17,20-dihydroxyvitamin D2 was produced at a rate of 0.13 mol x min(-1) x mol(-1). In adrenal mitochondria, vitamin D2 was metabolized to six monohydroxy products. Nevertheless, aminoglutethimide (a P450scc inhibitor) inhibited this adrenal metabolite formation. Initial testing of metabolites for biological activity showed that, similar to vitamin D2, 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2 inhibited DNA synthesis in human epidermal HaCaT keratinocytes, although to a greater degree. 17,20-Dihydroxyvitamin D2 stimulated transcriptional activity of the involucrin promoter, again to a significantly greater extent than vitamin D2, while the effect of 20-hydroxyvitamin D2 was statistically insignificant. Thus, P450scc can metabolize vitamin D2 to generate novel products, with intrinsic biological activity (at least in keratinocytes).

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

    USDA-ARS?s Scientific Manuscript database

    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...

  6. 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'.

  7. Plasma membrane Pdia3 and VDR interact to elicit rapid responses to 1α,25(OH)(2)D(3).

    PubMed

    Chen, Jiaxuan; Doroudi, Maryam; Cheung, Jeffery; Grozier, Ashley L; Schwartz, Zvi; Boyan, Barbara D

    2013-12-01

    1α,25-Dihydroxyvitamin D3 (1α,25(OH)2D3) regulates osteoblasts through genomic and rapid membrane-mediated responses. Here we examined the interaction of protein disulfide isomerase family A, member 3 (Pdia3) and the traditional vitamin D receptor (VDR) in plasma membrane-associated responses to 1α,25(OH)2D3. We found that Pdia3 co-localized with VDR and the caveolae scaffolding protein, caveolin-1 on the surface of MC3T3-E1 osteoblasts. Immunoprecipitation showed that both Pdia3 and VDR interacted with caveolin-1. Pdia3 further interacted with phospholipase A2 activating protein (PLAA), whereas VDR interacted with c-Src. 1α,25(OH)2D3 changed the interactions and transport of the two receptors and rapidly activated phospholipase A2 (PLA2) and c-Src. Silencing either receptor or caveolin-1 inhibited both PLA2 and c-Src, indicating that the two receptors function interdependently. These two receptor dependent rapid responses to 1α,25(OH)2D3 regulated gene expression, proliferation and apoptosis of MC3T3-E1 cells. These data demonstrate the importance of both receptors and caveolin-1 in mediating membrane responses to 1α,25(OH)2D3 and subsequently regulating osteoblast biology. © 2013.

  8. Rationale and Design of the Vitamin D and Type 2 Diabetes (D2d) Study: A Diabetes Prevention Trial

    PubMed Central

    Pittas, Anastassios G.; Dawson-Hughes, Bess; Rosen, Clifford J.; Ware, James H.; Knowler, William C.; Staten, Myrlene A.

    2014-01-01

    OBJECTIVE Observational studies suggest that vitamin D may lower the risk of type 2 diabetes. However, data from long-term trials are lacking. The Vitamin D and Type 2 Diabetes (D2d) study is a randomized clinical trial designed to examine whether a causal relationship exists between vitamin D supplementation and the development of diabetes in people at high risk for type 2 diabetes. RESEARCH DESIGN AND METHODS D2d was designed with support from a U34 planning grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The final protocol was approved by the D2d Research Group, the data and safety monitoring board, and NIDDK. Key eligibility criteria are age ≥30 years, BMI of 24 (22.5 for Asian Americans) to 42 kg/m2, increased risk for diabetes (defined as meeting two of three glycemic criteria for prediabetes established by the American Diabetes Association [fasting glucose 100–125 mg/dL (5.5–6.9 mmol/L), 2-h postload glucose after 75-g glucose load 140–199 mg/dL (7.7–11.0 mmol/L), hemoglobin A1c 5.7–6.4% (39–46 mmol/mol)]), and no hyperparathyroidism, nephrolithiasis, or hypercalcemia. D2d participants are randomized to once-daily vitamin D3 (cholecalciferol 4,000 IU) or placebo and followed for an average of 3 years. The primary end point is time to incident diabetes as assessed by laboratory criteria during the study or by adjudication if diagnosed outside of D2d. Recruitment was initiated at the end of 2013. CONCLUSIONS D2d will test whether vitamin D supplementation is safe and effective at lowering the risk of progression to diabetes in people at high risk for type 2 diabetes. PMID:25205139

  9. 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

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 172 Food Additives Permitted for Direct Addition to Food for Human Consumption; Vitamin D2 Bakers Yeast AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the food additive...

  10. Statistical Optimization of Ultraviolet Irradiate Conditions for Vitamin D2 Synthesis in Oyster Mushrooms (Pleurotus ostreatus) Using Response Surface Methodology

    PubMed Central

    Wu, Wei-Jie; Ahn, Byung-Yong

    2014-01-01

    Response surface methodology (RSM) was used to determine the optimum vitamin D2 synthesis conditions in oyster mushrooms (Pleurotus ostreatus). Ultraviolet B (UV-B) was selected as the most efficient irradiation source for the preliminary experiment, in addition to the levels of three independent variables, which included ambient temperature (25–45°C), exposure time (40–120 min), and irradiation intensity (0.6–1.2 W/m2). The statistical analysis indicated that, for the range which was studied, irradiation intensity was the most critical factor that affected vitamin D2 synthesis in oyster mushrooms. Under optimal conditions (ambient temperature of 28.16°C, UV-B intensity of 1.14 W/m2, and exposure time of 94.28 min), the experimental vitamin D2 content of 239.67 µg/g (dry weight) was in very good agreement with the predicted value of 245.49 µg/g, which verified the practicability of this strategy. Compared to fresh mushrooms, the lyophilized mushroom powder can synthesize remarkably higher level of vitamin D2 (498.10 µg/g) within much shorter UV-B exposure time (10 min), and thus should receive attention from the food processing industry. PMID:24736742

  11. Effect of vitamins D2 and D3 supplement use on serum 25OHD concentration in elderly women in summer and winter.

    PubMed

    Rapuri, P B; Gallagher, J C; Haynatzki, G

    2004-02-01

    Vitamin D2 and D3 are generally considered equipotent in humans. A few studies have reported that serum 25OHD levels are higher in vitamin D3- compared with vitamin D2-supplemented subjects. As both vitamin D2 and D3 supplements are commonly used by elderly in United States, in the present study we determined the effect of self-reported vitamin D2 and vitamin D3 supplement use on serum total 25OHD levels according to season in elderly women aged 65-77 years. Serum total 25OHD levels were determined in winter and summer in unsupplemented women ( N = 307) and in women who reported taking vitamin D2 ( N = 56) and vitamin D3 ( N = 55) supplements by competitive protein binding assay. In vitamin D2-supplemented women, the contribution of vitamin D2 and D3 to the mean serum total 25OHD level was assessed by HPLC. In summer, there were no significant differences in the mean total serum 25OHD levels (ng/ml) among the vitamin D2 (32 +/- 2.1), vitamin D3 (36.7 +/- 1.95), and unsupplemented (32.2 +/- 0.95) groups. In winter, the mean serum total 25OHD levels were higher in women on vitamin D2 (33.6 +/- 2.34, P < 0.05) and vitamin D3 (29.7 +/- 1.76, NS) supplements compared with unsupplemented women (27.3 +/- 0.72). In vitamin D2-supplemented women, about 25% of the mean serum total 25OHD was 25OHD2, in both summer and winter. Twelve percent of unsupplemented women and 3.6% of vitamin D-supplemented women had a mean serum total 25OHD level below 15 ng/ml in winter. In elderly subjects, both vitamin D2 and Vitamin D3 supplements may contribute equally to circulating 25OHD levels, with the role of vitamin D supplement use being more predominant during winter.

  12. Differential gene expression by 1,25(OH)2D3 in an endometriosis stromal cell line.

    PubMed

    Ingles, Sue Ann; Wu, Liang; Liu, Benjamin T; Chen, Yibu; Wang, Chun-Yeh; Templeman, Claire; Brueggmann, Doerthe

    2017-01-28

    Endometriosis is a common female reproductive disease characterized by invasion of endometrial cells into other organs, frequently causing pelvic pain and infertility. Alterations of the vitamin D system have been linked to endometriosis incidence and severity. To shed light on the potential mechanism for these associations, we examined the effects of 1,25(OH)2D3 on gene expression in endometriosis cells. Stromal cell lines derived from endometriosis tissue were treated with 1,25(OH)2D3, and RNA-seq was used to identify genes differentially expressed between treated and untreated cells. Gene ontology and pathway analyses were carried out using Partek Flow and Ingenuity software suites, respectively. We identified 1627 genes that were differentially expressed (886 down-regulated and 741 up-regulated) by 1,25(OH)2D3. Only one gene, CYP24A1, was strongly up-regulated (369-fold). Many genes were strongly down-regulated. 1,25(OH)2D3 treatment down-regulated several genetic pathways related to neuroangiogenesis, cellular motility, and invasion, including pathways for axonal guidance, Rho GDP signaling, and matrix metalloprotease inhibition. These findings support a role for vitamin D in the pathophysiology of endometriosis, and provide new targets for investigation into possible causes and treatments.

  13. Pro-inflammatory cytokines mediate the decrease in serum 25(OH)D concentrations after total knee arthroplasty?

    PubMed

    Henriksen, Vanessa T; Rogers, Victoria E; Rasmussen, G Lynn; Trawick, Roy H; Momberger, Nathan G; Aguirre, Dale; Barker, Tyler

    2014-02-01

    Vitamin D is a fat-soluble micronutrient that regulates inflammation and skeletal muscle size and function. Inflammation and skeletal muscle dysfunction (i.e., atrophy and weakness) are predominant impairments that continue to challenge the rehabilitation from total knee arthroplasty (TKA). Data suggest a decrease in serum 25-hydroxyvitamin D (25(OH)D) concentrations after TKA. Despite the decrease being attributed to a systemic inflammatory response, it is unclear what inflammatory mediator(s) is contributing to the decrease in serum 25(OH)D concentrations after TKA. In immune cells, pro-inflammatory cytokines mediate the enzymatic conversion of 25(OH)D to 1,25-dihydroxyvitamin D, implying that pro-inflammatory cytokines contribute to the decrease in substrate availability (i.e., 25(OH)D). We propose the hypothesis that pro-inflammatory cytokines mediate the decrease in serum 25(OH)D concentrations after TKA. To complement the supporting literature for the proposed hypothesis, we analyzed serum 25(OH)D and pro-inflammatory cytokine concentrations prior to and serially after TKA in a case subject (female; age, 62 year; height, 160 cm; body mass, 63 kg; body mass index, 26.5 kg/m(2)). The subtle decrease (12%) from pre-surgery to 2-d post-surgery and the more pronounced decrease (74%) from 3-week to 8-week post-surgery in serum 25(OH)D concentrations corresponded with the increase in serum pro-inflammatory cytokine (i.e., TNF-α, IFN-γ, IL-1β, GM-CSF, and IL-6) concentrations. This observation lends credence to the proposed hypothesis that pro-inflammatory cytokines could contribute to the decrease in serum 25(OH)D concentrations after TKA. Clearly, future research is needed to confirm the proposed hypothesis and to identify if attenuating the decrease in serum 25(OH)D concentrations improves patient outcomes after TKA. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Total vitamin D assay comparison of the Roche Diagnostics "Vitamin D total" electrochemiluminescence protein binding assay with the Chromsystems HPLC method in a population with both D2 and D3 forms of vitamin D.

    PubMed

    Abdel-Wareth, Laila; Haq, Afrozul; Turner, Andrew; Khan, Shoukat; Salem, Arwa; Mustafa, Faten; Hussein, Nafiz; Pallinalakam, Fasila; Grundy, Louisa; Patras, Gemma; Rajah, Jaishen

    2013-03-22

    This study compared two methods of assaying the 25-hydroxylated metabolites of cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2). A fully automated electrochemiluminescence assay from Roche Diagnostics and an HPLC based method from Chromsystems were used to measure vitamin D levels in surplus sera from 96 individuals, where the majority has the D2 form of the vitamin. Deming regression, concordance rate, correlation and Altman Bland agreement were performed. Seventy two subjects (75%) had a D2 concentration >10 nmol/L while the remaining twenty four subjects had vitamin D2 concentration of less than 10 nmol/L by HPLC. Overall, the Roche Diagnostics method showed a negative bias of -2.59 ± 4.11 nmol/L on the e602 as compared to the HPLC with a concordance rate of 84%. The concordance rate was 91% in samples with D2 of less than 10 nmol/L and 82% in those with D2 concentration >10 nmol/L. The overall correlation had an r value of 0.77. The r value was higher in samples with D2 levels of less than 10 nmol/L, r = 0.96, as compared to those with D2 values of greater than 10 nmol/L, r = 0.74. The observed bias had little impact on clinical decision and therefore is clinically acceptable.

  15. Total Vitamin D Assay Comparison of the Roche Diagnostics “Vitamin D Total” Electrochemiluminescence Protein Binding Assay with the Chromsystems HPLC Method in a Population with both D2 and D3 forms of Vitamin D

    PubMed Central

    Abdel-Wareth, Laila; Haq, Afrozul; Turner, Andrew; Khan, Shoukat; Salem, Arwa; Mustafa, Faten; Hussein, Nafiz; Pallinalakam, Fasila; Grundy, Louisa; Patras, Gemma; Rajah, Jaishen

    2013-01-01

    This study compared two methods of assaying the 25-hydroxylated metabolites of cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2). A fully automated electrochemiluminescence assay from Roche Diagnostics and an HPLC based method from Chromsystems were used to measure vitamin D levels in surplus sera from 96 individuals, where the majority has the D2 form of the vitamin. Deming regression, concordance rate, correlation and Altman Bland agreement were performed. Seventy two subjects (75%) had a D2 concentration >10 nmol/L while the remaining twenty four subjects had vitamin D2 concentration of less than 10 nmol/L by HPLC. Overall, the Roche Diagnostics method showed a negative bias of −2.59 ± 4.11 nmol/L on the e602 as compared to the HPLC with a concordance rate of 84%. The concordance rate was 91% in samples with D2 of less than 10 nmol/L and 82% in those with D2 concentration >10 nmol/L. The overall correlation had an r value of 0.77. The r value was higher in samples with D2 levels of less than 10 nmol/L, r = 0.96, as compared to those with D2 values of greater than 10 nmol/L, r = 0.74. The observed bias had little impact on clinical decision and therefore is clinically acceptable. PMID:23525081

  16. Vitamin D in adipose tissue and serum 25-hydroxyvitamin D after roux-en-Y gastric bypass.

    PubMed

    Pramyothin, Pornpoj; Biancuzzo, Rachael M; Lu, Zhiren; Hess, Donald T; Apovian, Caroline M; Holick, Michael F

    2011-11-01

    Vitamin D is stored in body fat. The purpose of this study was to determine vitamin D concentration in abdominal fat of obese patients who underwent roux-en-Y gastric bypass (RYGB), and to describe changes in serum 25-hydroxyvitamin D (25(OH)D) levels in relation to loss of body fat. Subjects from a single clinic who were scheduled for RYGB were invited into the study. Abdominal subcutaneous, omental, and mesenteric fat were obtained at time of surgery. Adipose vitamin D(2) and vitamin D(3) concentrations were measured by high-performance liquid chromatography (HPLC). Weight and serum 25(OH)D were assessed at baseline and every 3 months up to 1 year. Seventeen subjects were included, and fat samples were available from eleven. Total vitamin D content in subcutaneous abdominal fat was 297.2 ± 727.7 ng/g tissue, and a wide range was observed (4-2,470 ng/g). Both vitamin D(2) and vitamin D(3) were detected in some of the fat samples. At baseline, 25(OH)D was 23.1 ± 12.6 ng/ml. Average weight loss was 54.8 kg at 12 months, of which ~40 kg was fat mass. Despite daily vitamin D intake of ≥2,500 IU throughout the study, no significant increase in serum 25(OH)D was observed, with mean serum concentration of 25(OH)D at 1 year of 26.2 ± 5.36 ng/ml (P = 0.58). We conclude that vitamin D in adipose tissue does not significantly contribute to serum 25(OH)D despite dramatic loss of fat mass after RYGB.

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

    USDA-ARS?s Scientific Manuscript database

    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. Combination of micellar casein with calcium and vitamins D2 and K2 improves bone status of ovariectomized mice.

    PubMed

    Boulier, A; Schwarz, J; Lespesailles, E; Baniel, A; Tomé, D; Blais, A

    2016-10-01

    Nutritional approaches may help to preserve bone quality. The purpose of our study was to demonstrate the efficiency of an innovative bone health product (BHP) including micellar casein rich in calcium, vitamin D2 and vitamin K2, to improve bone mineral density. The aim of postmenopausal osteoporosis treatment is to decrease bone resorption and/or increase bone formation. Because of the slow bone turnover, osteoporosis prevention and therapies are long-lasting, implying great costs and poor compliance. Even if the effects of nutrition on bone are not as marked as that of pharmaceutical agents, it can be of great help. The purpose of our study was to demonstrate the efficiency of an innovative bone health product (BHP) containing micellar casein rich in calcium, vitamin D2 and vitamin K2, for the improvement of bone mineral density (BMD). An ovariectomized mice model was used to study the effect of different concentrations of the ingredient on BMD and microarchitectural parameters. Blood concentrations of C-terminal telopeptide of type I collagen (CTX), N-terminal propeptide of type 1 procollagene (PINP), alkaline phosphatase (ALP), osteocalcin (OC) and RANKL were also measured to evaluate bone remodelling, To evaluate the efficiency of the product to modulate osteoblast and osteoclast growth and differentiation, primary murine bone cells were used. In vivo studies showed that BMD and microarchitectural parameters were dose-dependently improved after ingestion of the supplement for 3 months. We also report increased osteoblast activity as shown by increased OC activity and decreased osteoclastogenesis as shown by reduced CTX activity. In vitro studies support that BHPs stimulate osteoblast differentiation and mineralization and inhibit osteoclast resorption activity. Our results show that, when chronically ingested, BHPs improve BMD of ovariectomized mice. This work supports that providing an ingredient including micellar casein rich in calcium, vitamin D2 and

  19. Vitamin D metabolite concentrations in umbilical cord blood serum and associations with clinical characteristics in a large prospective mother-infant cohort in Ireland.

    PubMed

    Kiely, Mairead; O'Donovan, Sinead M; Kenny, Louise C; Hourihane, Jonathan O'B; Irvine, Alan D; Murray, Deirdre M

    2017-03-01

    Vitamin D deficiency is widespread among mothers and neonates and quality clinical and analytical data are lacking. We used a CDC-accredited LC-MS/MS method to analyze vitamin D metabolites in cord sera from 1050 maternal-infant dyads in the prospective SCOPE Ireland Pregnancy and BASELINE Birth cohort studies, based in Cork, Ireland. The mean±SD total 25(OH)D was 34.9±18.1nmol/L; 35% of cords (50% during winter) had 25(OH)D <25nmol/L, 46% were <30nmol/L and 80% were <50nmol/L. In this predominantly white cohort, the main predictor of cord 25(OH)D [adj. mean difference in nmol/L (95% CI)] was summer delivery [19.2 (17.4, 20.9), P<0.0001]. Maternal smoking during pregnancy (9% prevalence) was negatively associated (P<0.002) with cord 25(OH)D [-4.83 (-7.9, -1.5) nmol/L]. There were no associations between cord 25(OH)D and birth weight or any anthropometric measures at birth. Despite the high prevalence of vitamin D deficiency at birth, there were no documented musculoskeletal complications during infancy, which was likely due to widespread supplementation with vitamin D. The mean±SD concentration of 3-epi-25(OH)D3, detectable in 99.4% of cord samples, was 3.3±1.9nmol/L. The proportion of 25(OH)D as 3-epi-25(OH)D3 was 11.2%. Cord 3-epi-25(OH)D3 concentrations were positively predicted by cord 25(OH)D3 [0.101 (0.099, 0.103) nmol/L, P<0.0001] and negatively by gestational age [-0.104 (-0.131, -0.076) nmol/L, P<0.0001] and maternal age [-0.010 (-0.019, -0.001) nmol/L, P<0.05]. 25(OH)D2 was detected in 98% of cord sera (mean±SD; 2.2±1.9nmol/L) despite low antenatal consumption of vitamin D2 supplements. In conclusion, these first CDC-accredited data of vitamin D metabolites in umbilical cord blood emphasise the high risk of very low vitamin D status in infants born to un-supplemented mothers. Experimental data to define maternal vitamin D requirements for prevention of neonatal deficiency at high latitude are required.

  20. Quantitative determination of vitamin D metabolites in plasma using UHPLC-MS/MS.

    PubMed

    Ding, Shujing; Schoenmakers, Inez; Jones, Kerry; Koulman, Albert; Prentice, Ann; Volmer, Dietrich A

    2010-09-01

    Vitamin D is an important determinant of bone health at all ages. The plasma concentrations of 25-hydroxy vitamin D (25-OH D) and other metabolites are used as biomarkers for vitamin sufficiency and function. To allow for the simultaneous determination of five vitamin D metabolites, 25-OH D(3), 25-OH D(2), 24,25-(OH)(2) D(3), 1,25-(OH)(2) D(3), and 1,25-(OH)(2) D(2), in low volumes of human plasma, an assay using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was established. Plasma samples were spiked with isotope-labeled internal standards and pretreated using protein precipitation, solid-phase extraction (SPE) and a Diels-Alder derivatization step with 4-phenyl-1,2,4-triazoline-3,5-dione. The SPE recovery rates ranged from 55% to 85%, depending on the vitamin D metabolite; the total sample run time was <5 min. Mass spectrometry was conducted using positive ion electrospray ionization in the multiple reaction monitoring mode on a quadrupole-quadrupole-linear ion trap instrument after pre-column addition of methylamine to increase the ionization efficiency. The intra- and inter-day relative standard deviations were 1.6-4.1% and 3.7-6.8%, respectively. The limit of quantitation for these compounds was determined to be between 10 and 20 pg/mL. The 25-OH D results were compared with values obtained for reference materials (DEQAS). In addition, plasma samples were analyzed with two additional Diasorin antibody assays. All comparisons with conventional methods showed excellent correlations (r(2) = 0.9738) for DEQAS samples, demonstrating the high degree of comparability of the new UHPLC-MS/MS technique to existing methods.

  1. Effect of pasteurisation on the concentrations of vitamin D compounds in donor breastmilk.

    PubMed

    Gomes, Fabio P; Shaw, P Nicholas; Whitfield, Karen; Koorts, Pieter; McConachy, Helen; Hewavitharana, Amitha K

    2016-01-01

    Premature infants are the main recipients of pasteurised donor human milk (PDHM), when their mothers are unable to provide their own. In this study, we evaluated the effect of pasteurisation on the concentrations of vitamin D compounds in donor breastmilk. Milk samples were obtained pre- and post-Holder pasteurisation. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyse the samples for vitamins D2 and D3 (D2 and D3) and 25-hydroxyvitamins D2 and D3 (25(OH)D2 and 25(OH)D3). The significance of differences in vitamin D concentrations between the two groups of milk samples was assessed using the Wilcoxon matched-pairs signed rank test, in which p < 0.05 was considered significant. Pasteurisation resulted in a significant reduction (p < 0.05) in the content of D2, D3, 25(OH)D2 and 25(OH)D3. The losses ranged from 10% to 20% following pasteurisation.

  2. Improved Screening Test for Idiopathic Infantile Hypercalcemia Confirms Residual Levels of Serum 24,25-(OH)2 D3 in Affected Patients.

    PubMed

    Kaufmann, Martin; Morse, Nicole; Molloy, Billy Joe; Cooper, Donald P; Schlingmann, Karl Peter; Molin, Arnaud; Kottler, Marie Laure; Gallagher, J Christopher; Armas, Laura; Jones, Glenville

    2017-07-01

    CYP24A1 mutations are now accepted as a cause of idiopathic infantile hypercalcemia (IIH). A rapid liquid-chromatography tandem mass spectrometry (LC-MS/MS)-based blood test enabling measurement of the 25-OH-D3 :24,25-(OH)2 D3 ratio (R) can identify IIH patients on the basis of reduced C24-hydroxylation of 25-OH-D3 by CYP24A1 in vivo. Although values of this ratio are significantly elevated in IIH, somewhat surprisingly, serum 24,25-(OH)2 D3 remains detectable. The current study explores possible explanations for this including: residual CYP24A1 enzyme activity in individuals with certain CYP24A1 genotypes, expression of alternative C24-hydroxylases, and the possibility of isobaric contamination of the 24,25-(OH)2 D3 peak on LC-MS/MS. We employed an extended 20-min run time on LC-MS/MS to study serum vitamin D metabolites in patients with IIH due to mutations of CYP24A1 or SLC34A1; in unaffected heterozygotes and dialysis patients; in patients with vitamin D deficiency; as well as in normal subjects exhibiting a broad range of 25-OH-D levels. We identified 25,26-(OH)2 D3 as a contaminant of the 24,25-(OH)2 D3 peak. In normals, the concentration of 24,25-(OH)2 D3 greatly exceeds 25,26-(OH)2 D3 ; however, 25,26-(OH)2 D3 becomes more significant in IIH with CYP24A1 mutations and in dialysis patients, where 24,25-(OH)2 D3 levels are low when CYP24A1 function is compromised. Mean R in 30 IIH-CYP24A1 patients was 700 (range, 166 to 2168; cutoff = 140) as compared with 31 in 163 controls. Furthermore, patients possessing CYP24A1 L409S alleles exhibited higher 24,25-(OH)2 D3 levels and lower R (mean R = 268; n = 8) than patients with other mutations. We conclude that a chromatographic approach which resolves 24,25-(OH)2 D3 from 25,26-(OH)2 D3 produces a more accurate R that can be used to differentiate pathological states where CYP24A1 activity is altered. The origin of the residual serum 24,25-(OH)2 D3 in IIH patients appears to be multifactorial. © 2017

  3. Vitamin D Metabolism, Mechanism of Action, and Clinical Applications

    PubMed Central

    Bikle, Daniel D.

    2014-01-01

    Vitamin D3 is made in the skin from 7-dehydrocholesterol under the influence of UV light. Vitamin D2 (ergocalciferol) is derived from the plant sterol ergosterol. Vitamin D is metabolized first to 25 hydroxyvitamin D (25OHD), then to the hormonal form 1,25-dihydroxyvitamin D (1,25(OH)2D). CYP2R1 is the most important 25-hydroxylase; CYP27B1 is the key 1-hydroxylase. Both 25OHD and 1,25(OH)2D are catabolized by CYP24A1. 1,25(OH)2D is the ligand for the vitamin D receptor (VDR), a transcription factor, binding to sites in the DNA called vitamin D response elements (VDREs). There are thousands of these binding sites regulating hundreds of genes in a cell-specific fashion. VDR-regulated transcription is dependent on comodulators, the profile of which is also cell specific. Analogs of 1,25(OH)2D are being developed to target specific diseases with minimal side effects. This review will examine these different aspects of vitamin D metabolism, mechanism of action, and clinical application. PMID:24529992

  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. Association of 25(OH)D and PTH with metabolic syndrome and its traditional and nontraditional components.

    PubMed

    Kayaniyil, Sheena; Vieth, Reinhold; Harris, Stewart B; Retnakaran, Ravi; Knight, Julia A; Gerstein, Hertzel C; Perkins, Bruce A; Zinman, Bernard; Hanley, Anthony J

    2011-01-01

    Emerging evidence suggests that 25-hydroxy vitamin D [25(OH)D] and PTH may play a role in the etiology of the metabolic syndrome (MetS). However, evidence to date is limited and inconsistent, and few studies have examined associations with nontraditional MetS components. The objective of the study was to examine the association of vitamin D and PTH with MetS and its traditional and nontraditional components in a large multiethnic sample. In this cross-sectional study, we examined 654 participants from London and Toronto, Ontario, Canada, aged 30 yr and older with risk factors for type 2 diabetes. Presence of MetS and its traditional and nontraditional components was measured. Approximately 43% of the study participants were classified as having MetS. Higher 25(OH)D was significantly associated with a reduced presence of MetS after adjustment for age, sex, season, ethnicity, supplement use, physical activity, and PTH (odds ratio 0.76, 95% confidence interval 0.62-0.93). PTH was not associated with the presence of MetS after multivariate adjustment. Multivariate linear regression analyses indicated significant adjusted inverse associations of 25(OH)D with waist circumference, triglyceride level, fasting insulin, and alanine transaminase (P < 0.041). Elevated PTH was positively associated with waist circumference and high-density lipoprotein cholesterol (P < 0.04). Other associations between PTH and MetS components were attenuated after adjustment for adiposity. Serum 25(OH)D, but not PTH, was significantly associated with MetS as well as a number of MetS components after multivariate adjustment. These results suggest that low 25(OH)D may play a role in the etiology of the MetS.

  6. 25(OH)D deficiency is associated with fatal stroke among whites but not blacks: The NHANES-III linked mortality files

    PubMed Central

    Michos, Erin D.; Reis, Jared P.; Post, Wendy S.; Lutsey, Pamela L.; Gottesman, Rebecca F.; Mosley, Thomas H.; Sharrett, A. Richey; Melamed, Michal L.

    2011-01-01

    Objective Deficient 25-hydroxyvitamin D [25(OH)D] levels are associated with cardiovascular disease (CVD) events and mortality. Both 25(OH)D deficiency and stroke are more prevalent among blacks. We examined whether low 25(OH)D contributes to the excess risk of fatal stroke in blacks compared to whites. Research Methods and Procedures The Third National Health and Nutrition Examination Survey, a probability sample of US civilians, measured 25(OH)D levels and CVD risk factors between 1988–1994. Vital status through December 2006 was obtained via linkage with the National Death Index. Among white and black adults without CVD reported at baseline (n=7981), Cox regression models were fit to estimate hazard ratios (HR) for fatal stroke by 25(OH)D status and race. Results During a median of 14.1 years, there were 116 and 60 fatal strokes among whites and blacks respectively. The risk of fatal stroke was greater in blacks compared to whites in models adjusted for socio-economic status and CVD risk factors, [HR 1.60 (95% CI 1.01–2.53)]. Mean baseline 25(OH)D levels were significantly lower in blacks compared to whites (19.4 vs 30.8 ng/mL, respectively). In multivariable-adjusted models, deficient 25(OH)D levels <15 ng/mL were associated with fatal stroke among whites [HR 2.13 (1.01–4.50)] but not blacks [HR 0.93 (0.49–1.80)]. Conclusions Vitamin D deficiency was associated with increased risk of stroke death in whites but not blacks. Although blacks had a higher rate of fatal stroke compared to whites, the low 25(OH)D levels in blacks were unrelated to stroke incidence and therefore 25(OH)D levels did not explain this excess risk. PMID:22261577

  7. Rationale and design of the Vitamin D and Type 2 Diabetes (D2d) study: a diabetes prevention trial.

    PubMed

    Pittas, Anastassios G; Dawson-Hughes, Bess; Sheehan, Patricia R; Rosen, Clifford J; Ware, James H; Knowler, William C; Staten, Myrlene A

    2014-12-01

    Observational studies suggest that vitamin D may lower the risk of type 2 diabetes. However, data from long-term trials are lacking. The Vitamin D and Type 2 Diabetes (D2d) study is a randomized clinical trial designed to examine whether a causal relationship exists between vitamin D supplementation and the development of diabetes in people at high risk for type 2 diabetes. D2d was designed with support from a U34 planning grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The final protocol was approved by the D2d Research Group, the data and safety monitoring board, and NIDDK. Key eligibility criteria are age ≥30 years, BMI of 24 (22.5 for Asian Americans) to 42 kg/m(2), increased risk for diabetes (defined as meeting two of three glycemic criteria for prediabetes established by the American Diabetes Association [fasting glucose 100-125 mg/dL (5.5-6.9 mmol/L), 2-h postload glucose after 75-g glucose load 140-199 mg/dL (7.7-11.0 mmol/L), hemoglobin A₁c 5.7-6.4% (39-46 mmol/mol)]), and no hyperparathyroidism, nephrolithiasis, or hypercalcemia. D2d participants are randomized to once-daily vitamin D₃ (cholecalciferol 4,000 IU) or placebo and followed for an average of 3 years. The primary end point is time to incident diabetes as assessed by laboratory criteria during the study or by adjudication if diagnosed outside of D2d. Recruitment was initiated at the end of 2013. D2d will test whether vitamin D supplementation is safe and effective at lowering the risk of progression to diabetes in people at high risk for type 2 diabetes. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  8. Accurate and reliable quantification of 25-hydroxy-vitamin D species by liquid chromatography high-resolution tandem mass spectrometry[S

    PubMed Central

    Liebisch, Gerhard; Matysik, Silke

    2015-01-01

    In general, mass spectrometric quantification of small molecules in routine laboratory testing utilizes liquid chromatography coupled to low mass resolution triple-quadrupole mass spectrometers (QQQs). Here we introduce high-resolution tandem mass spectrometry (quadrupole-Orbitrap) for the quantification of 25-hydroxy-vitamin D [25(OH)D], a marker of the vitamin D status, because the specificity of 25(OH)D immunoassays is still questionable and mass spectrometric quantification is becoming increasingly important. Liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-MS/HR-MS) was used to quantify 25-hydroxy-cholecalciferol [25(OH)D3], 25-hydroxy-ergocalciferol [25(OH)D2], and their C3-epimers 3-epi-25(OH)D3 and 3-epi-25(OH)D2. The method has a run time of 5 min and was validated according to the US Food and Drug Administration and the European Medicines Agency guidelines. High mass resolution was advantageously applied to separate a quasi-isobaric interference of the internal standard D6-25(OH)D2 with 3-epi-25(OH)D3. All analytes showed an imprecision of below 10% coefficient of variation (CV), trueness between 90% and 110%, and limits of quantification below 10 nM. Concentrations measured by LC-MS/HR-MS are in good agreement with those of the National Institute of Standards and Technology reference methods using LC-MS/MS (QQQ). In conclusion, quantification of 25(OH)D by LC-MS/HR-MS is applicable for routine testing and also holds promise for highly specific quantification of other small molecules. PMID:25833687

  9. Vitamin D in Health and Disease

    PubMed Central

    Heaney, Robert P.

    2008-01-01

    Vitamin D functions in the body through both an endocrine mechanism (regulation of calcium absorption) and an autocrine mechanism (facilitation of gene expression). The former acts through circulating calcitriol, whereas the latter, which accounts for more than 80% of the metabolic utilization of the vitamin each day, produces, uses, and degrades calcitriol exclusively intracellularly. In patients with end-stage kidney disease, the endocrine mechanism is effectively disabled; however, the autocrine mechanism is able to function normally so long as the patient has adequate serum levels of 25(OH)D, on which its function is absolutely dependent. For this reason, calcitriol and its analogs do not constitute adequate replacement in managing vitamin D needs of such patients. Optimal serum 25(OH)D levels are greater than 32 ng/mL (80 nmol/L). The consequences of low 25(OH)D status include increased risk of various chronic diseases, ranging from hypertension to diabetes to cancer. The safest and most economical way to ensure adequate vitamin D status is to use oral dosing of native vitamin D. (Both daily and intermittent regimens work well.) Serum 25(OH)D can be expected to rise by about 1 ng/mL (2.5 nmol/L) for every 100 IU of additional vitamin D each day. Recent data indicate that cholecalciferol (vitamin D3) is substantially more potent than ergocalciferol (vitamin D2) and that the safe upper intake level for vitamin D3 is 10,000 IU/d. PMID:18525006

  10. 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

  11. 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

  12. 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

  13. The effect of magnesium ions on vitamin D(2)-phospholipid model membrane interactions in the presence of different buffer media.

    PubMed

    Toyran, N; Severcan, F

    2000-10-02

    Vitamin D plays important roles in the bone formation, in calcium and phosphorus homeostasis and in the treatment and prevention of many diseases. Ions, especially divalent cations like Mg(2+), have indispensable roles in many vital biological events. Mg(2+) is involved in many fundamental processes such as stabilization of membranes and macromolecules, synthesis of nucleic acid and proteins and formation and use of high-energy phosphate bonds. Mg(2+) is also required for synthesis of more than 310 different enzymes of the body and is, therefore, involved in many important activities. The roles of vitamin D and major ions in the body are quite well known. While there are still many unresolved points about the exact molecular mechanism behind such diverse functions, in the present study, the interaction of Mg(2+) with dipalmitoyl phosphatidylcholine (DPPC) model membranes has been studied in the presence and absence of vitamin D(2) by using Fourier transform infrared (FTIR) spectroscopy and turbidity technique at 440 nm. The effect of different buffer media on the system has also been investigated. The temperature dependent investigation of the wavelength of the CH(2) antisymmetric stretching bands revealed that, in the presence of N-[2-hydroxyethyl] piperazine-N'-[2-ethanesulfonic acid] (Hepes) and phosphate buffer, addition of Mg(2+) and/or vitamin D(2) into pure DPPC liposomes does not change the shape of the phase transition profile. Turbidity studies support these results. In the presence of Hepes buffer, the inclusion of Mg(2+) and/or vitamin D(2) into pure DPPC liposomes orders the system. In the presence of phosphate buffer, FTIR study showed that, addition of Mg(2+) into pure DPPC liposomes disorders the system in the gel phase. The precipitation of Mg(2+) with phosphates, which is present in phosphate buffer, may be a reason for this difference in the effect. It is seen that, the binary mixture of Mg(2+)-DPPC and the ternary mixture of Mg(2+)-vitamin D(2

  14. Vitamin D-induced ectodomain shedding of TNF receptor 1 as a nongenomic action: D3 vs D2 derivatives.

    PubMed

    Yang, Won Seok; Yu, Hoon; Kim, Jin Ju; Lee, Mee Jeong; Park, Su-Kil

    2016-01-01

    As a nongenomic action, 1,25-dihydroxyvitamin D3 (1,25D3) induces L-type Ca(2+) channel-mediated extracellular Ca(2+) influx in human aortic smooth muscle cells (HASMCs), which activates a disintegrin and metalloprotease 10 (ADAM10) to cleave and shed the ectodomain of tumor necrosis factor receptor 1 (TNFR1). In this study, we examined the potencies of other vitamin D3 and D2 analogs to stimulate the ectodomain shedding of TNFR1 in HASMCs. 25-Hydroxyvitamin D3 (25D3), a precursor of 1,25D3, and elocalcitol, an analog of 1,25D3, caused ectodomain shedding of TNFR1 within 30 min, whereas 1,25-dihydroxyvitamin D2 (1,25D2) and paricalcitol, a derivative of 1,25D2, did not. Both 25D3 and elocalcitol rapidly induced extracellular Ca(2+) influx and markedly increased intracellular Ca(2+), while 1,25D2 and paricalcitol caused only small increases in intracellular Ca(2+). 25D3- and elocalcitol-induced TNFR1 ectodomain sheddings were abolished by verapamil and in Ca(2+)-free media. Both 25D3 and elocalcitol caused the translocation of ADAM10 to the cell surface, which was inhibited by verapamil, while 1,25D2 and paricalcitol did not cause ADAM10 translocation. When ADAM10 was depleted by ADAM10-siRNA, 25D3 and elocalcitol could not induce ectodomain shedding of TNFR1. The plasma membrane receptor, endoplasmic reticulum stress protein 57 (ERp57), but not the classic vitamin D receptor, mediated the nongenomic action of vitamin D to induce ectodomain shedding of TNFR1. In summary, like 1,25D3, 25D3 and elocalcitol caused ADAM10-mediated ectodomain shedding of TNFR1, whereas 1,25D2 and paricalcitol did not. The difference may depend on their affinities to ERp57 through which extracellular Ca(2+) influx is induced.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  16. Model-based meta-analysis for comparing Vitamin D2 and D3 parent-metabolite pharmacokinetics.

    PubMed

    Ocampo-Pelland, Alanna S; Gastonguay, Marc R; Riggs, Matthew M

    2017-08-01

    Association of Vitamin D (D3 & D2) and its 25OHD metabolite (25OHD3 & 25OHD2) exposures with various diseases is an active research area. D3 and D2 dose-equivalency and each form's ability to raise 25OHD concentrations are not well-defined. The current work describes a population pharmacokinetic (PK) model for D2 and 25OHD2 and the use of a previously developed D3-25OHD3 PK model [1] for comparing D3 and D2-related exposures. Public-source D2 and 25OHD2 PK data in healthy or osteoporotic populations, including 17 studies representing 278 individuals (15 individual-level and 18 arm-level units), were selected using search criteria in PUBMED. Data included oral, single and multiple D2 doses (400-100,000 IU/d). Nonlinear mixed effects models were developed simultaneously for D2 and 25OHD2 PK (NONMEM v7.2) by considering 1- and 2-compartment models with linear or nonlinear clearance. Unit-level random effects and residual errors were weighted by arm sample size. Model simulations compared 25OHD exposures, following repeated D2 and D3 oral administration across typical dosing and baseline ranges. D2 parent and metabolite were each described by 2-compartment models with numerous parameter estimates shared with the D3-25OHD3 model [1]. Notably, parent D2 was eliminated (converted to 25OHD) through a first-order clearance whereas the previously published D3 model [1] included a saturable non-linear clearance. Similar to 25OHD3 PK model results [1], 25OHD2 was eliminated by a first-order clearance, which was almost twice as fast as the former. Simulations at lower baselines, following lower equivalent doses, indicated that D3 was more effective than D2 at raising 25OHD concentrations. Due to saturation of D3 clearance, however, at higher doses or baselines, the probability of D2 surpassing D3's ability to raise 25OHD concentrations increased substantially. Since 25OHD concentrations generally surpassed 75 nmol/L at these higher baselines by 3 months, there would be no

  17. Chronic high fructose intake reduces serum 1,25 (OH)2D3 levels in calcium-sufficient rodents.

    PubMed

    Douard, Veronique; Patel, Chirag; Lee, Jacklyn; Tharabenjasin, Phuntila; Williams, Edek; Fritton, J Christopher; Sabbagh, Yves; Ferraris, Ronaldo P

    2014-01-01

    Excessive fructose consumption inhibits adaptive increases in intestinal Ca2+ transport in lactating and weanling rats with increased Ca2+ requirements by preventing the increase in serum levels of 1,25(OH)2D3. Here we tested the hypothesis that chronic fructose intake decreases 1,25(OH)2D3 levels independent of increases in Ca2+ requirements. Adult mice fed for five wk a high glucose-low Ca2+ diet displayed expected compensatory increases in intestinal and renal Ca2+ transporter expression and activity, in renal CYP27B1 (coding for 1α-hydroxylase) expression as well as in serum 1,25(OH)2D3 levels, compared with mice fed isocaloric glucose- or fructose-normal Ca2+ diets. Replacing glucose with fructose prevented these increases in Ca2+ transporter, CYP27B1, and 1,25(OH)2D3 levels induced by a low Ca2+ diet. In adult mice fed for three mo a normal Ca2+ diet, renal expression of CYP27B1 and of CYP24A1 (24-hydroxylase) decreased and increased, respectively, when the carbohydrate source was fructose instead of glucose or starch. Intestinal and renal Ca2+ transporter activity and expression did not vary with dietary carbohydrate. To determine the time course of fructose effects, a high fructose or glucose diet with normal Ca2+ levels was fed to adult rats for three mo. Serum levels of 1,25(OH)2D3 decreased and of FGF23 increased significantly over time. Renal expression of CYP27B1 and serum levels of 1,25(OH)2D3 still decreased in fructose- compared to those in glucose-fed rats after three mo. Serum parathyroid hormone, Ca2+ and phosphate levels were normal and independent of dietary sugar as well as time of feeding. Thus, chronically high fructose intakes can decrease serum levels of 1,25(OH)2D3 in adult rodents experiencing no Ca2+ stress and fed sufficient levels of dietary Ca2+. This finding is highly significant because fructose constitutes a substantial portion of the average diet of Americans already deficient in vitamin D.

  18. Chronic High Fructose Intake Reduces Serum 1,25 (OH)2D3 Levels in Calcium-Sufficient Rodents

    PubMed Central

    Douard, Veronique; Patel, Chirag; Lee, Jacklyn; Tharabenjasin, Phuntila; Williams, Edek; Fritton, J. Christopher; Sabbagh, Yves; Ferraris, Ronaldo P.

    2014-01-01

    Excessive fructose consumption inhibits adaptive increases in intestinal Ca2+ transport in lactating and weanling rats with increased Ca2+ requirements by preventing the increase in serum levels of 1,25(OH)2D3. Here we tested the hypothesis that chronic fructose intake decreases 1,25(OH)2D3 levels independent of increases in Ca2+ requirements. Adult mice fed for five wk a high glucose-low Ca2+ diet displayed expected compensatory increases in intestinal and renal Ca2+ transporter expression and activity, in renal CYP27B1 (coding for 1α-hydroxylase) expression as well as in serum 1,25(OH)2D3 levels, compared with mice fed isocaloric glucose- or fructose-normal Ca2+ diets. Replacing glucose with fructose prevented these increases in Ca2+ transporter, CYP27B1, and 1,25(OH)2D3 levels induced by a low Ca2+ diet. In adult mice fed for three mo a normal Ca2+ diet, renal expression of CYP27B1 and of CYP24A1 (24-hydroxylase) decreased and increased, respectively, when the carbohydrate source was fructose instead of glucose or starch. Intestinal and renal Ca2+ transporter activity and expression did not vary with dietary carbohydrate. To determine the time course of fructose effects, a high fructose or glucose diet with normal Ca2+ levels was fed to adult rats for three mo. Serum levels of 1,25(OH)2D3 decreased and of FGF23 increased significantly over time. Renal expression of CYP27B1 and serum levels of 1,25(OH)2D3 still decreased in fructose- compared to those in glucose-fed rats after three mo. Serum parathyroid hormone, Ca2+ and phosphate levels were normal and independent of dietary sugar as well as time of feeding. Thus, chronically high fructose intakes can decrease serum levels of 1,25(OH)2D3 in adult rodents experiencing no Ca2+ stress and fed sufficient levels of dietary Ca2+. This finding is highly significant because fructose constitutes a substantial portion of the average diet of Americans already deficient in vitamin D. PMID:24718641

  19. Excessive fructose intake causes 1,25-(OH)(2)D(3)-dependent inhibition of intestinal and renal calcium transport in growing rats.

    PubMed

    Douard, Veronique; Sabbagh, Yves; Lee, Jacklyn; Patel, Chirag; Kemp, Francis W; Bogden, John D; Lin, Sheldon; Ferraris, Ronaldo P

    2013-06-15

    We recently discovered that chronic high fructose intake by lactating rats prevented adaptive increases in rates of active intestinal Ca(2+) transport and in levels of 1,25-(OH)2D3, the active form of vitamin D. Since sufficient Ca(2+) absorption is essential for skeletal growth, our discovery may explain findings that excessive consumption of sweeteners compromises bone integrity in children. We tested the hypothesis that 1,25-(OH)2D3 mediates the inhibitory effect of excessive fructose intake on active Ca(2+) transport. First, compared with those fed glucose or starch, growing rats fed fructose for 4 wk had a marked reduction in intestinal Ca(2+) transport rate as well as in expression of intestinal and renal Ca(2+) transporters that was tightly associated with decreases in circulating levels of 1,25-(OH)2D3, bone length, and total bone ash weight but not with serum parathyroid hormone (PTH). Dietary fructose increased the expression of 24-hydroxylase (CYP24A1) and decreased that of 1α-hydroxylase (CYP27B1), suggesting that fructose might enhance the renal catabolism and impair the synthesis, respectively, of 1,25-(OH)2D3. Serum FGF23, which is secreted by osteocytes and inhibits CYP27B1 expression, was upregulated, suggesting a potential role of bone in mediating the fructose effects on 1,25-(OH)2D3 synthesis. Second, 1,25-(OH)2D3 treatment rescued the fructose effect and normalized intestinal and renal Ca(2+) transporter expression. The mechanism underlying the deleterious effect of excessive fructose intake on intestinal and renal Ca(2+) transporters is a reduction in serum levels of 1,25-(OH)2D3. This finding is significant because of the large amounts of fructose now consumed by Americans increasingly vulnerable to Ca(2+) and vitamin D deficiency.

  20. Excessive fructose intake causes 1,25-(OH)2D3-dependent inhibition of intestinal and renal calcium transport in growing rats

    PubMed Central

    Douard, Veronique; Sabbagh, Yves; Lee, Jacklyn; Patel, Chirag; Kemp, Francis W.; Bogden, John D.; Lin, Sheldon

    2013-01-01

    We recently discovered that chronic high fructose intake by lactating rats prevented adaptive increases in rates of active intestinal Ca2+ transport and in levels of 1,25-(OH)2D3, the active form of vitamin D. Since sufficient Ca2+ absorption is essential for skeletal growth, our discovery may explain findings that excessive consumption of sweeteners compromises bone integrity in children. We tested the hypothesis that 1,25-(OH)2D3 mediates the inhibitory effect of excessive fructose intake on active Ca2+ transport. First, compared with those fed glucose or starch, growing rats fed fructose for 4 wk had a marked reduction in intestinal Ca2+ transport rate as well as in expression of intestinal and renal Ca2+ transporters that was tightly associated with decreases in circulating levels of 1,25-(OH)2D3, bone length, and total bone ash weight but not with serum parathyroid hormone (PTH). Dietary fructose increased the expression of 24-hydroxylase (CYP24A1) and decreased that of 1α-hydroxylase (CYP27B1), suggesting that fructose might enhance the renal catabolism and impair the synthesis, respectively, of 1,25-(OH)2D3. Serum FGF23, which is secreted by osteocytes and inhibits CYP27B1 expression, was upregulated, suggesting a potential role of bone in mediating the fructose effects on 1,25-(OH)2D3 synthesis. Second, 1,25-(OH)2D3 treatment rescued the fructose effect and normalized intestinal and renal Ca2+ transporter expression. The mechanism underlying the deleterious effect of excessive fructose intake on intestinal and renal Ca2+ transporters is a reduction in serum levels of 1,25-(OH)2D3. This finding is significant because of the large amounts of fructose now consumed by Americans increasingly vulnerable to Ca2+ and vitamin D deficiency. PMID:23571713

  1. The Correlation Between Serum Vitamin D Deficiency and Preterm Birth

    PubMed Central

    Yang, Lixia; Pan, Shilei; Zhou, Yufeng; Wang, Xiaoyang; Qin, Aikai; Huang, Yuxin; Sun, Suxia

    2016-01-01

    Background Preterm birth is an important cause of death and developmental disorder in neonates. Vitamin D deficiency has been shown to regulate body inflammatory factor levels that stimulate elevation of uterine contraction hormones, such as prostaglandin, thus causing preterm birth. However, current observations regarding the relationship between vitamin D and preterm birth are inconsistent. We performed a nested case-control study to investigate the effect of vitamin D on preterm birth. Material/Methods A prospective cohort study included 200 cases of pregnant women in our hospital from May 2013 to May 2015. Blood samples were collected from early, middle, and late stages of pregnancy. Forty-six patients with preterm delivery were compared with age-matched full-term delivery cases (N=92). High performance liquid chromatography-mass spectrometry (HPLC-MS) was used to detect serum levels of 25(OH)D, 25(OH)D2, and 25(OH)D3. Logistic regression was performed to analyze the correlation between 25(OH)D and risk of preterm birth. Results No significant difference in age, smoking/drinking, education level, BMI and vitamin D levels was found between the preterm birth group and full-term delivery group. No significant difference was found for vitamin D levels across different stages of pregnancy; no difference in concentration of 25(OH)D related to preterm birth risk was found. After adjusting for potentially confounding factors, serum vitamin D level did not increase the risk of preterm birth. Conclusions This study did not found evidence of an increase in preterm birth risk related to vitamin D level during pregnancy. PMID:27851719

  2. Effect of Ultraviolet Light-Exposed Mushrooms on Vitamin D Status: Liquid Chromatography-Tandem Mass Spectrometry Reanalysis of Biobanked Sera from a Randomized Controlled Trial and a Systematic Review plus Meta-Analysis.

    PubMed

    Cashman, Kevin D; Kiely, Mairead; Seamans, Kelly M; Urbain, Paul

    2016-03-01

    Randomized controlled trial (RCT) data on the response of serum total 25-hydroxyvitamin D [25(OH)D] in healthy participants consuming UV light-exposed edible mushrooms are limited and mixed. The objective was to undertake a systematic review and meta-analysis of responses of serum 25(OH)D [and serum 25-hydroxyergocalciferol, 25(OH)D2, and serum 25-hydroxycholecalciferol, 25(OH)D3, if available] to consumption of UV-exposed mushrooms by healthy participants. Biobanked sera from one RCT (originally analyzed by immunoassay) were reanalyzed by LC-MS/MS to generate serum 25(OH)D2 and serum 25(OH)D3 data. Ovid MEDLINE, EMBASE, and Cochrane CENTRAL were searched for RCTs of UV-exposed mushrooms and data on serum 25(OH)D. Studies were screened for eligibility, and relevant data were extracted. Serum 25(OH)D data were re-analyzed by ANOVA and paired t tests. Our structured search yielded 6 RCTs meeting our inclusion criteria. Meta-analysis of all 6 RCTs showed serum 25(OH)D was not significantly increased (P = 0.12) by UV-exposed mushrooms, but there was high heterogeneity (I(2) = 87%). Including only the 3 European-based RCTs [mean baseline 25(OH)D, 38.6 nmol/L], serum 25(OH)D was increased significantly by UV-exposed mushrooms [weighted mean difference (WMD): 15.2 nmol/L; 95% CI: 1.5, 28.8 nmol/L, P = 0.03, I(2) = 88%], whereas there was no significant effect in the 3 US-based RCTs [P = 0.83; mean baseline 25(OH)D: 81.5 nmol/L]. Analysis of serum 25(OH)D2 and serum 25(OH)D3 (n = 5 RCTs) revealed a statistically significant increase (WMD: 20.6 nmol/L; 95% CI: 8.0, 33.3 nmol/L, P = 0.001, I(2 =) 99%) and decrease (WMD: -13.3 nmol/L; 95% CI: -15.8, -10.7 nmol/L, P < 0.00001, I(2) = 0%) after supplementation with UV-exposed mushrooms. Consumption of UV-exposed mushrooms may increase serum 25(OH)D when baseline vitamin D status is low via an increase in 25(OH)D2 (24.2 nmol/L) and despite a concomitant but relatively smaller reduction in 25(OH)D3 (-12.6 nmol/L). When baseline

  3. Increased PTH and 1.25(OH)2D Levels Associated With Increased Markers of Bone Turnover Following Bariatric Surgery

    PubMed Central

    Sinha, Naina; Shieh, Albert; Stein, Emily M.; Strain, Gladys; Schulman, Aaron; Pomp, Alfons; Gagner, Michel; Dakin, Gregory; Christos, Paul; Bockman, Richard S.

    2012-01-01

    The objective of this study was to characterize changes in metabolic bone parameters following bariatric surgery. Seventy-three obese adult patients who underwent either gastric banding (GB), Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion with duodenal switch (BPD/DS) were followed prospectively for 18 months postoperatively. Changes in the calcium–vitamin D axis (25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)2D), calcium, parathyroid hormone (PTH)), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase) and resorption (urinary N-telopeptide (NTx)), as well as bone mineral density (BMD) were assessed at 3-month intervals during this time period. Bariatric surgery resulted in significant and progressive weight loss over 18 months. With supplementation, 25OHD levels increased 65.3% (P < 0.0001) by 3 months, but leveled off and decreased <30 ng/ml by 18 months. PTH initially decreased 21.4% (P = 0.01) at 3 months, but later approached presurgery levels. 1,25(OH)2D increased significantly starting at month 12 (50.3% increase from baseline, P = 0.008), and was positively associated with PTH (r = 0.82, P = 0.0001). When stratified by surgery type, median PTH and 1,25(OH)2D levels were higher following combined restrictive and malabsorptive operations (RYGB and BPD/DS) compared to GB. Bone formation/resorption markers were increased by 3 months (P < 0.05) and remained elevated through 18 months. Radial BMD decreased 3.5% by month 18, but this change was not significant (P = 0.23). Our findings show that after transient improvement, preoperative vitamin D insufficiency and secondary hyperparathyroidism persisted following surgery despite supplementation. Postoperative secondary hyperparathyroidism was associated with increased 1,25(OH)2D levels and increased bone turnover markers. PMID:21617641

  4. Analysis of vitamin D and its metabolites using thermospray liquid chromatography/mass spectrometry.

    PubMed

    Watson, D; Setchell, K D; Ross, R

    1991-07-01

    A new method is described for the analysis of vitamin D and its metabolites utilizing thermospray (TSP) mass spectrometry as an on-line detector for high performance liquid chromatography. Ionization conditions were optimized for use with isocratic reversed phase chromatography. TSP mass spectrometry was employed in series with a UV absorbance detector to facilitate comparisons between the two methods of detection. Positive ion TSP mass spectra were recorded for vitamin D2, vitamin D3, 25-hydroxyvitamin D3 (25(OH)D3), 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3). The spectra contained protonated molecular ions, ammonium adduct ions and fragment ions due to the loss of one or more molecules of water. A comparison of quantitative precision was made by determining UV absorbance and TSP standard curves for vitamin D3 using two different methods: (1) External standard method with post-column (post UV detector) addition of ammonium acetate. (2) As (1) but using the method of internal standards with a closely eluting internal standard (vitamin D2). In each case the quantitative precision (correlation coefficient) for UV absorbance detection was superior owing to intrinsic instability of the TSP ion beam. A stable isotopically labelled internal standard was employed in the development of an assay for 1,25(OH)2D3. The assay was used to quantify in vitro enzymic conversion of 25(OH)D3 to 1,25(OH)2D3 in guinea pig and sheep renal mitochondrial incubations. TSP LC/MS was also applied to analysis of an extract of human blood plasma in which D3 and each of its principal metabolites were identified in a single analysis.

  5. Association between 25(OH)D Level, Ultraviolet Exposure, Geographical Location, and Inflammatory Bowel Disease Activity: A Systematic Review and Meta-Analysis

    PubMed Central

    Lu, Chao; Yang, Jun; Yu, Weilai; Li, Dejian; Xiang, Zun; Lin, Yiming; Yu, Chaohui

    2015-01-01

    Background There is no consensus on the vitamin D levels and inflammatory bowel disease (IBD). Aim To conduct a systematic review and meta-analysis to analyze the relationship between IBD and 25(OH)D, sun exposure, and latitude, and to determine whether vitamin D deficiency affects the severity of IBD. Methods We searched the PubMed, EBSCO, and ClinicalTrials.gov databases to identify all studies that assessed the association between 25(OH)D, sun exposure, latitude, and IBD through November 1, 2014, without language restrictions. Studies that compared 25(OH)D levels between IBD patients and controls were selected for inclusion in the meta-analysis. We calculated pooled standardized mean differences (SMDs) and odds ratios (ORs). Results Thirteen case-control studies investigating CD and 25(OH)D levels were included, and eight studies part of above studies also investigated the relationship between UC and 25(OH)D. Both CD patients (SMD: 0.26 nmol/L, 95% confidence interval [CI]: 0.09–0.42 nmol/L) and UC patients (SMD: 0.5 nmol/L, 95% CI: 0.15–0.85 nmol/L) had lower levels of 25(OH)D than controls. In addition, CD patients and UC patients were 1.95 times (OR, 1.95; 95% CI, 1.48–2.57) and 2.02 times (OR, 2.02; 95% CI, 1.13–3.60) more likely to be 25(OH)D deficient than controls. We also included 10 studies investigating the relationship between CD activity and vitamin D. Results showed that patients with active CD (CD Activity Index≥150) were more likely to have low vitamin D levels. In addition, whether low sun exposure and high latitude were related to a high morbidity of CD need to be provided more evidence. Conclusion Our study shows that IBD patients have lower vitamin D levels. For active CD patients, vitamin D levels were low. These findings suggest that vitamin D may play an important role in the development of IBD, although a direct association could not be determined in our study. PMID:26172950

  6. Effects of a 10-day course of a high dose calciferol versus a single mega dose of ergocalciferol in correcting vitamin D deficiency.

    PubMed

    Melhem, Samar Jamal; Aiedeh, Khaled Mohammad; Hadidi, Kamal Abdelhamid

    2015-01-01

    The correction of vitamin D deficiency is crucial for optimal skeletal and non-skeletal health. Most regimens in current use are based on daily dosing, which may raise concerns of dosage inadequacy and suboptimal patient compliance. Vitamin D is available in 2 forms: D2 (ergocalciferol) and D3 (cholecalciferol). It has been reported that D2 supplements are less effective and may enhance the degradation of 25-hydroxyvitamin D3 (25[OH]D3) metabolite. The aim of this study was to compare the effect of 2 high-dose oral vitamin D regimens--a 10-day course of D3 500,000 IU versus a single mega dose of 600,000 IU D2--on serum 25(OH)D levels. A prospective cohort study was conducted from September 2010 to February 2011 in an urban university tertiary hospital in Amman, Jordan. A total of 109 patients aged 18 to 79 years were enrolled with severe vitamin D deficiency. Fifty-one subjects received 600,000 IU D2 orally and 54 subjects received a total dose of 500,000 IU D3 administered orally, as 50,000 IU D3 daily for 10 consecutive days. Baseline and follow-up total serum 25(OH)D, 25(OH)D2, and 25(OH)D3 levels were compared. The mean total 25(OH)D increment from baseline was 10.33 (5.68) ng/mL over a mean of 43.08 (2.81) days for the D2 group. The mean increment in 25(OH)D for the D3 group was 47.03 (23.67) ng/mL over a mean of 36.9 (2.9) days. The difference between the 2 mean increments was highly significant: P=3.15.10-18. The 600,000 IU D2 single mega-dose decreased 25(OH)D3 levels by an average of 4 ng/mL in 37 subjects. Overall, the 10-day oral D3 regimen rapidly and effectively normalized 25(OH)D levels. The shortened dosing interval over 10 consecutive days might result in higher compliance.

  7. Vitamin D 2 interacts with Human PrP(c) (90-231) and breaks PrP(c) oligomerization in vitro.

    PubMed

    Suenaga, Midori; Hiramoto, Yusuke; Matsunaga, Yoichi

    2013-01-01

    PrP(sc), the pathogenic isoform of PrP(c), can convert PrP(c) into PrP(sc) through direct interactions. PrP(c) oligomerization is a required processing step before PrP(sc) formation, and soluble oligomers appear to be the toxic species in amyloid-related disorders. In the current study, direct interactions between vitamin D 2 and human recombinant PrP(c) (90-231) were observed by Biacore assay, and 3F4 antibody, specific for amino acid fragment 109-112 of PrP(c), inhibited this interaction. An ELISA study using3F4 antibody showed that PrP(c) (101-130), corresponding sequence to human PrP, was affected by vitamin D 2, supporting the results of Biacore studies and suggesting that the PrP(c) sequence around the 3F4 epitope was responsible for the interaction with vitamin D 2. Furthermore, the effects of vitamin D 2 on disruption of PrP(c) (90-231) oligomerization were elucidated by dot blot analysis and differential protease k susceptibilities. While many chemical compounds have been proposed as potential therapeutic agents for the treatment of scrapie, most of these are toxic. However, given the safety and blood brain barrier permeability of vitamin D 2, we propose that vitamin D 2 may be a suitable agent to target PrP(c) in the brain and therefore is a potential therapeutic candidate for prion disease.

  8. 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

  9. Evaluation of Vitamin D3 and D2 Stability in Fortified Flat Bread Samples During Dough Fermentation, Baking and Storage.

    PubMed

    Tabibian, Mehrnaz; Torbati, Mohammadali; Afshar Mogaddam, Mohammad Reza; Mirlohi, Maryam; Sadeghi, Malihe; Mohtadinia, Javad

    2017-06-01

    Purpose: Vitamin D, a fat-soluble secosteroid, has a significant role in bone metabolism and helps calcium absorption in the body. Since vitamin D concentration is altered in fortified foods and dietary supplements, the actual amount of vitamin D may differ from the label value. Methods: In this study, the concentrations of vitamin D2 and D3 of fortified bread sample were analytically determined. For this purpose, dough or homogenized bread sample was saponified using potassium hydroxide solution (30%, w/v) at 80°C, and the saponified analytes were extracted into n-heptane followed by liquid-liquid extraction. Then n-heptane fraction was evaporated to dryness and the sample was reconstituted in methanol. The effect of different parameters was evaluated by one variable at one-time strategy. Results: The analytes concentrations were evaluated in dough fermentation, baking and storage steps. The effect of temperature in dough fermentation and baking was evaluated at the range of 5-30 and 200-250°C, respectively. Also, the fermentation time was studied in the range of 0-120 min. The analytes concentrations were followed for 1 to 5 days after baking. The results indicated that dough fermentation temperature has no significant effect on the concentration of the analytes. On the other hand, when the dough fermentation time and baking temperature are increased, the analytes concentrations are decreased. Also, the storage duration of the spiked bread samples decreased the analytes concentrations after one day. Conclusion: Based on the obtained results, baking the dough at high temperatures lead to decrease in vitamin levels.

  10. Evaluation of Vitamin D3 and D2 Stability in Fortified Flat Bread Samples During Dough Fermentation, Baking and Storage

    PubMed Central

    Tabibian, Mehrnaz; Torbati, Mohammadali; Afshar Mogaddam, Mohammad Reza; Mirlohi, Maryam; Sadeghi, Malihe; Mohtadinia, Javad

    2017-01-01

    Purpose: Vitamin D, a fat-soluble secosteroid, has a significant role in bone metabolism and helps calcium absorption in the body. Since vitamin D concentration is altered in fortified foods and dietary supplements, the actual amount of vitamin D may differ from the label value. Methods: In this study, the concentrations of vitamin D2 and D3 of fortified bread sample were analytically determined. For this purpose, dough or homogenized bread sample was saponified using potassium hydroxide solution (30%, w/v) at 80°C, and the saponified analytes were extracted into n-heptane followed by liquid-liquid extraction. Then n-heptane fraction was evaporated to dryness and the sample was reconstituted in methanol. The effect of different parameters was evaluated by one variable at one-time strategy. Results: The analytes concentrations were evaluated in dough fermentation, baking and storage steps. The effect of temperature in dough fermentation and baking was evaluated at the range of 5-30 and 200-250°C, respectively. Also, the fermentation time was studied in the range of 0-120 min. The analytes concentrations were followed for 1 to 5 days after baking. The results indicated that dough fermentation temperature has no significant effect on the concentration of the analytes. On the other hand, when the dough fermentation time and baking temperature are increased, the analytes concentrations are decreased. Also, the storage duration of the spiked bread samples decreased the analytes concentrations after one day. Conclusion: Based on the obtained results, baking the dough at high temperatures lead to decrease in vitamin levels. PMID:28761835

  11. 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.

  12. 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

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

    PubMed

    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

    2011-09-01

    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). 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)D 2 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. Fifty African Americans and 50 European Americans participated in the study. Compared with SLC24A5 111(Thr) homozygotes, individuals with the SLC24A5 111(Thr/Ala) and 111(Ala/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. The SLC24A5 111(Ala) 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.

  14. Vitamin D status is associated with uteroplacental dysfunction indicated by pre-eclampsia and small-for-gestational-age birth in a large prospective pregnancy cohort in Ireland with low vitamin D status.

    PubMed

    Kiely, Mairead E; Zhang, Joy Y; Kinsella, Michael; Khashan, Ali S; Kenny, Louise C

    2016-08-01

    Associations between vitamin D and pregnancy outcomes have been inconsistent. We described the distribution of 25-hydroxyvitamin D3 [25(OH)D3], 3-epi-25(OH)D3, and 25(OH)D2 in early pregnancy and investigated associations with pre-eclampsia and small-for-gestational-age (SGA) birth, which are indicative of uteroplacental dysfunction. The SCOPE (Screening for Pregnancy Endpoints) Ireland prospective pregnancy cohort study included 1768 well-characterized low-risk, nulliparous women resident at 52°N. Serum 25(OH)D3, 3-epi-25(OH)D3, and 25(OH)D2 were quantified at 15 wk of gestation with the use of a CDC-accredited liquid chromatography-tandem mass spectrometry method. The mean ± SD total 25(OH)D concentration was 56.7 ± 25.9 nmol/L, and 17% and 44% of women had 25(OH)D concentrations <30 and <50 nmol/L, respectively. The prevalence of pre-eclampsia was 3.8%, and 10.7% of infants were SGA. There was a lower risk of pre-eclampsia plus SGA combined (13.6%) at 25(OH)D concentrations >75 nmol/L (adjusted OR: 0.64; 95% CI: 0.43, 0.96). The main predictors of 25(OH)D were the use of vitamin D-containing supplements (adjusted mean difference: 20.1 nmol/L; 95% CI: 18.5, 22.7 nmol/L) and summer sampling (adjusted mean difference: 15.5 nmol/L; 95% CI: 13.4, 17.6 nmol/L). Non-Caucasian ethnicity (adjusted mean difference: -19.3 nmol/L; 95% CI: -25.4, -13.2 nmol/L) and smoking (adjusted mean difference: -7.0 nmol/L; 95% CI: -10.5, -3.6 nmol/L) were negative predictors of 25(OH)D. The mean ± SD concentration of 3-epi-25(OH)D3, which was detectable in 99.9% of samples, was 2.6 ± 1.6 nmol/L. Determinants of 3-epi-25(OH)D3 were 25(OH)D3 (adjusted mean difference: 0.052 nmol/L; 95% CI: 0.050, 0.053 nmol/L) and maternal age (adjusted mean difference: -0.018 nmol/L; 95% CI: -0.026, -0.009 nmol/L). The mean ± SD concentration of 25(OH)D2 was 3.1 ± 2.7 nmol/L, which was present in all samples. No adverse effects of 25(OH)D concentrations >125 nmol/L were observed. In the first

  15. High-performance liquid chromatographic determination of vitamin D3 in fish liver oils and eel body oils.

    PubMed

    Takeuchi, A; Okano, T; Ayame, M; Yoshikawa, H; Teraoka, S; Murakami, Y; Kobayashi, T

    1984-10-01

    Identification and determination of vitamin D3 (or D2) and 25-OH-D3 in fish liver oils and eel body oils were carried out. By co-chromatography on HPLC, UV spectra and/or GC-MS, vitamin D3 was identified in naturally occurring fish liver oils and eel body oils, whereas a drop of fish liver oil contained supplemented vitamin D2. 25-OH-D3 was identified only in skipjack liver oil. The HPLC method proposed in a previous report (Takeuchi, A. et al. (1984): J. Nutr. Sci. Vitaminol., 30, 11-25) was confirmed to also be useful for determination of vitamin D3 (or D2) in fish liver oils and eel body oils. The assayed values of vitamin D3 in skipjack and tuna liver oils were 57,760 and 16,200 IU/g, respectively, which were much higher than those in cod and pollack liver oils. The assayed values of vitamin D3 in eel body oils were very low (16-43 IU/g) and showed no appreciable change despite differences in the farming conditions. Determination of 25-OH-D3 in skipjack oil was performed by using HPLC, and the assayed value was 1.8 micrograms/g. This was about 1/800 lower than that of vitamin D3.

  16. Effect of 1,25(OH)2D3 on transdifferentiation of rat renal tubular epithelial cells induced by high glucose

    PubMed Central

    Hu, Hongtao; Xu, Shen; Hu, Shuang; Gao, Yue; Shui, Hua

    2016-01-01

    Deficiency in vitamin D and its active metabolite is a characteristic of chronic kidney diseases (CKDs). Previous studies have reported that 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active form of vitamin D, can attenuate renal interstitial fibrosis. The present study aimed to explore the effect of 1,25(OH)2D3 on the transdifferentiation of NRK-52E rat renal tubular epithelial cells (RTECs) induced by high glucose, as well as the expression of vitamin D receptor (VDR) and production of angiotensin (Ang) II. Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses were performed to detect the protein and mRNA expression of α-smooth muscle actin (α-SMA), E-cadherin and VDR. Furthermore, the production of Ang II was analyzed by enzyme-linked immunosorbent assay (ELISA). Treatment with high glucose decreased E-cadherin and VDR, while increasing α-SMA and Ang II, and of note, these changes were attenuated by 1,25(OH)2D3 in a dose-dependent manner. In conclusion, the present study revealed that 1,25(OH)2D3 inhibits high glucose-induced transdifferentiation of rat RTECs in a dose-dependent manner, which may be associated with the downregulation of Ang II and upregulation of VDR. PMID:28101343

  17. The influence of lipid droplet size on the oral bioavailability of vitamin D2 encapsulated in emulsions: an in vitro and in vivo study.

    PubMed

    Salvia-Trujillo, L; Fumiaki, B; Park, Y; McClements, D J

    2017-02-22

    Vitamin D deficiency is prevalent in some populations leading to adverse health effects, and therefore there is a need to supplement functional foods and beverages with this important micronutrient. In this study, we examined the influence of the initial lipid droplet size on the in vitro bioaccessibility and in vivo absorption of vitamin D2 encapsulated in oil-in-water emulsions. Changes in particle size, charge, and microstructure were measured as vitamin-loaded lipid droplets were passed through a simulated GIT (mouth, stomach, small intestine). The in vitro studies showed that smaller lipid droplets were digested more rapidly than larger ones, thereby leading to the more rapid formation of mixed micelles in the small intestine capable of solubilizing the lipophilic vitamins. This effect may account for the highest vitamin D2 bioaccessibility being observed for the emulsions containing the smallest droplets. In contrast, the in vivo rat feeding studies suggested that the absorption of vitamin D2 was the highest for the emulsions containing the largest droplets. The poor in vitro-in vivo correlation observed in our study may have occurred for a number of reasons: the simulated GIT did not accurately model the complexity of a real GIT; the in vivo approach used did not monitor changes in vitamin levels in the blood over time. Overall, this study suggests that particle size does influence the gastrointestinal fate of encapsulated oil-soluble vitamins, but that further work is needed to establish strong correlations between in vitro and in vivo methods.

  18. [Chronic kidney insufficiency and respiratory muscle function. Changes induced by treatment with 1,25(OH)2D3].

    PubMed

    Gómez-Fernández, P; Sánchez Agudo, L; Calatrava, J M

    1990-02-17

    A myopathy basically involving proximal respiratory muscles can develop in uremia. To evaluate respiratory muscle force in uremia, maximal inspiratory pressure (MIP) was measured in 27 patients with renal failure. MIP was very limited in patients with a creatinine clearance (Crc) lower than 10/ml/min 1.73 m2 not treated with hemodialysis (HD) and in patients on HD who were not treated with 1.25 (OH)2D3 (45 +/- 9 and 43 +/- 5 cm H2O, respectively), moderately reduced in patients on HD treated with 1.25 (OH)2D3 (58 +/- 5 cmH2O) and normal in patients with Crc higher than 10 ml/min 1.73 m2 (86 +/- 6 cmH2O). The treatment with 1.25 (OH)2D3 during 3 months promoted a significant increase in MIP and serum calcium level and a reduction in parathyroid hormone in patients with Crc lower than 10 ml/min. It was concluded that, in uremia, a respiratory muscle weakness partially reversible with vitamin D therapy may be found.

  19. Vitamin D Metabolites Inhibit Hepatitis C Virus and Modulate Cellular Gene Expression

    PubMed Central

    Gutierrez, Julio A.; Jones, Krysten A.; Flores, Roxana; Singhania, Akul; Woelk, Christopher H.; Schooley, Robert T.; Wyles, David L.

    2015-01-01

    Background and Aims Previous studies suggest that low serum 25-hydroxyvitamin D [25(OH) D] levels are associated with reduced responsiveness to interferon and ribavirin therapy. We investigated the impact of vitamin D metabolites on HCV and cellular gene expression in cultured hepatoma cells. Methods HCV Replicon cell lines stably expressing luciferase reporter constructs (genotype 1b and 2a replicon) or JC1-Luc2a were incubated in the presence of vitamin D2, vitamin D3 or 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Presence of HCV was quantified by a luciferase reporter assay and immunoblot of the Core protein. Synergy of interferon-alpha A/D (IFN-α) and 1,25(OH)2D3 was evaluated using the Chou-Talalay method. Cellular gene expression by microarray analysis using Illumina Bead Chips and real-time quantitative PCR. Results Vitamin D2, D3 and 1,25(OH)2D3 each demonstrated anti-HCV activity at low micro molar concentrations. In vitro conversion from D3 to 25(OH)D3 was shown by LC/MS/MS. Combination indices of 1,25(OH)2D3 and IFN-α demonstrated a synergistic effect (0.23-0.46) and significantly reduced core expression by immunoblot. Differentially expressed genes were identified between Huh7.5.1 cells in the presence and absence of 1,25(OH)2D3 and HCV. Genes involved with classical effects of vitamin D metabolism and excretion were activated, along with genes linked to autophagy such as G-protein coupled receptor 37 (GPR37) and Hypoxia-inducible factor 1-alpha (HIF1a). Additionally, additive effects of 1,25(OH)2D3 and IFN-α were seen on mRNA expression of chemokine motif ligand 20 (CCL20). Conclusions This study shows that vitamin D reduces HCV protein production in cell culture synergistically with IFN-α. Vitamin D also activates gene expression independently and additively with IFN-α and this may explain its ability to aid in the clearance of HCV in vivo. PMID:26594646

  20. 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

  1. Adverse interaction of low-calcium diet and low 25(OH)D levels on lumbar spine mineralization in late-pubertal girls.

    PubMed

    Esterle, Laure; Nguyen, Minh; Walrant-Debray, Odile; Sabatier, Jean-Pierre; Garabedian, Michèle

    2010-11-01

    No consensus has been reached on the serum 25-hydroxyvitamin D [25(OH)D] levels required to ensure optimal bone health around menarche. We searched for a possible interaction of 25(OH)D levels and calcium intake on lumbar spine mineralization and on biologic features of bone metabolism in healthy late-pubertal girls. Lumbar spine parameters (ie, area, mineral content, and density) and calcium intake were evaluated in 211 healthy white adolescent girls at pubertal stages IV-V (11 to 16.9 years), together with biologic markers of calcium and bone metabolism and with International External Quality Assessment Scheme for Vitamin D Metabolite (DEQAS)-validated serum 25(OH)D levels. A high prevalence of 25(OH)D levels ≤ 30 nmol/L (41%), ≤ 40 nmol/L (61%), and ≤ 50 nmol/L (70%) was found during winter-spring. Parathyroid hormone (PTH) levels were inversely associated with 25(OH)D levels (p = .0021). In contrast, lumbar spine mineral content and density were not associated with 25(OH)D, excepted when calcium intake was below 600 mg/day (p = .0081). Girls with such low calcium intake and 25(OH)D levels of 40 nmol/L or less (9% of the cohort) had a 0.4 to 0.7 SD lower mean areal bone mineral density Z-score than girls with higher calcium intake and/or higher 25(OH)D status. The adverse association between lumbar spine mineralization and combined calcium deficiency-low 25(OH)D levels remained significant in the 91 girls who could be followed over 4 years after their initial evaluation. We conclude that low 25(OH)D levels (≤40 nmol/L) are observed frequently during winter-spring in late-pubertal European girls, which may exacerbate the negative impact of calcium deficiency on lumbar spine mineralization. © 2010 American Society for Bone and Mineral Research.

  2. 1alpha,25(OH)2D3 is an autocrine regulator of extracellular matrix turnover and growth factor release via ERp60 activated matrix vesicle metalloproteinases.

    PubMed

    Boyan, Barbara D; Wong, Kevin L; Fang, Mimi; Schwartz, Zvi

    2007-03-01

    Growth plate chondrocytes produce proteoglycan-rich type II collagen extracellular matrix (ECM). During cell maturation and hypertrophy, ECM is reorganized via a process regulated by 1alpha,25(OH)(2)D(3) and involving matrix metalloproteinases (MMPs), including MMP-3 and MMP-2. 1alpha,25(OH)(2)D(3) regulates MMP incorporation into matrix vesicles (MVs), where they are stored until released. Like plasma membranes (PM), MVs contain the 1alpha,25(OH)(2)D(3)-binding protein ERp60, phospholipase A(2) (PLA(2)), and caveolin-1, but appear to lack nuclear Vitamin D receptors (VDRs). Chondrocytes produce 1alpha,25(OH)(2)D(3) (10(-8)M), which binds ERp60, activating PLA(2), and resulting lysophospholipids lead to MV membrane disorganization, releasing active MMPs. MV MMP-3 activates TGF-beta1 stored in the ECM as large latent TGF-beta1 complexes, consisting of latent TGF-beta1 binding protein, latency associated peptide, and latent TGF-beta1. Others have shown that MMP-2 specifically activates TGF-beta2. TGF-beta1 regulates 1alpha,25(OH)(2)D(3)-production, providing a mechanism for local control of growth factor activation. 1alpha,25(OH)(2)D(3) activates PKCalpha in the PM via ERp60-signaling through PLA(2), lysophospholipid production, and PLCbeta. It also regulates distribution of phospholipids and PKC isoforms between MVs and PMs, enriching the MVs in PKCzeta. Direct activation of MMP-3 in MVs requires ERp60. However, when MVs are treated with 1alpha,25(OH)(2)D(3), PKCzeta activity is decreased and PKCalpha is unaffected, suggesting a more complex feedback mechanism, potentially involving MV lipid signaling.

  3. 1α,25(OH)2D3-dependent modulation of Akt in proliferating and differentiating C2C12 skeletal muscle cells.

    PubMed

    Buitrago, Claudia G; Arango, Nadia S; Boland, Ricardo L

    2012-04-01

    We previously reported that 1α,25-dihydroxy-vitamin D(3) [1α,25(OH)(2)D(3)] induces non-transcriptional rapid responses through activation of Src and MAPKs in the skeletal muscle cell line C2C12. In the present study we investigated the modulation of Akt by the secosteroid hormone in C2C12 cells at proliferative stage (myoblasts) and at early differentiation stage. In proliferating cells, 1α,25(OH)(2)D(3) activates Akt by phosphorylation in Ser473 in a time-dependent manner (5-60 min). When these cells were pretreated with methyl-beta-cyclodextrin to disrupt caveolae microdomains, hormone-induced activation of Akt was suppressed. Similar results were obtained by siRNA silencing of caveolin-1 expression, further indicating that hormone effects on cell membrane caveolae are required for downstream signaling. PI3K and p38 MAPK, but not ERK1/2, participate in 1α,25(OH)(2)D(3) activation of Akt in myoblasts. The involvement of p38 MAPK in Akt phosphorylation by the hormone probably occurs through MAPK-activated protein kinase 2 (MK2), which is activated by the steroid. In addition, the participation of Src in Akt phosphorylation by 1α,25(OH)(2)D(3) was demonstrated using the inhibitor PP2 and antisense oligodeoxynucleotides that suppress Src expression. We also observed that PI3K participates in hormone-induced proliferation. During the early phase of C2C12 cell differentiation 1α,25(OH)(2)D(3) also increases Akt phosphorylation and activates Src. Of relevance, Src and PI3K are involved in Akt activation and in MHC and myogenin increased expression by 1α,25(OH)(2)D(3). Altogether, these data suggest that 1α,25(OH)(2)D(3) upregulates Akt through Src, PI(3)K, and p38 MAPK to stimulate myogenesis in C2C12 cells.

  4. 1α,25(OH)2D3 downregulates gene expression levels of muscle ubiquitin ligases MAFbx and MuRF1 in human myotubes.

    PubMed

    Hayakawa, Naohiko; Fukumura, Junko; Yasuno, Hideyuki; Fujimoto-Ouchi, Kaori; Kitamura, Hidemitsu

    2015-01-01

    Clinical trials involving in patients with osteoporosis have reported that activated vitamin D3 (1α,25(OH)2D3, calcitriol) can prevent falling by acting on the skeletal muscles. However, pharmacological mechanisms of 1α,25(OH)2D3 with respect to skeletal muscle hypertrophy or atrophy are still poorly understood. Therefore, we examined changes in the expression of several related genes in human myotubes to test whether 1α,25(OH)2D3 influences hypertrophy and atrophy of skeletal muscle. Myotubes treated with 1α,25(OH)2D3 increased interleukin-6 (IL-6) expression and inhibited expression of tumor necrosis factor alpha (TNF-α), whereas the expression of insulin-like growth factor-1 (IGF-1) that is involved in muscle hypertrophy was not affected. However, 1α,25(OH)2D3 treatment significantly inhibited the expression of muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1), ubiquitin ligases involved in muscle atrophy. The analysis of pathways using microarray data suggested that 1α,25(OH)2D3 upregulates AKT-1 by inhibiting the expression of protein phosphatase 2 (PP2A), a phosphatase acting on AKT-1, in the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, thereby inhibiting the expression of ubiquitin ligases. Thus, this study showed that 1α,25(OH)2D3 might have an inhibitory effect on the expression of MAFbx and MuRF1 in skeletal muscle and a suppressive effect on muscle degradation in patients with osteoporosis.

  5. 1,25(OH)2D3 induces regulatory T cell differentiation by influencing the VDR/PLC-γ1/TGF-β1/pathway.

    PubMed

    Zhou, Qiang; Qin, Shengying; Zhang, Jinyan; Zhon, Lin; Pen, Zhihai; Xing, Tonghai

    2017-09-16

    Vitamin D has been recommended as an immune modulator in recent years, in addition to regulating calcium-phosphorous-bone metabolism. Clinical studies on organ transplantation found that vitamin D sufficiency patients were less likely to develop acute cellular rejection within one year after transplantation compared to those with vitamin D deficiency. Thus, a high percentage of regulatory T cells might play a key role in preventing acute cellular rejection (ACR). In this report, we studied the specific effects of 1,25(OH)2D3 on human T cell diff ;erentiation, and determined the potential molecule mechanism behind. Results showed that 1,25(OH)2D3 induced the differentiation of T-regulatory cells (Treg cells), while inhibiting Th17 cell proliferation. In addition, 1,25(OH)2D3 promoted secretion of the anti-inflammatory cytokine, transforming Growth Factor beta1 (TGF-β1) but suppressed pro-inflammatory cytokines such as interleukin-17 (IL-17). Phospholipase C gamma 1 (PLC-γ1) is an indispensable signaling protein downstream of the classical TCR signaling pathway and was shown to play a crucial role in T cell activation, while Naive T cells expressed less PLC-γ1. Here we showed that Vitamin D could significantly upregulate PLC-γ1 expression, which then induced expression of TGF-β1. In summary, 1,25(OH)2D3 indirectly modulates the differentiation of Treg/Th17 cells by aff ;ecting the VDR/PLC-γ1/TGF-β1pathway. These results indicate that administration 1,25(OH)2D3 supplements may be a beneficial treatment for organ transplantation recipients. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. 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

  7. Assessment of 3-epi-25-OH-D₃ in preterm and full term infant samples and its relationship to demographic, anthropometric and biochemical determinants.

    PubMed

    Granado-Lorencio, F; Garcia-Heras, L Muñoz; Blanco-Navarro, I; Pérez-Sacristán, B

    2014-06-01

    We aim to determine 3-epi-25-OH-D₃ in 155 leftover infant samples (<12 months) and its relationship with demographic, anthropometric and biochemical markers. Samples were randomly collected and assessed for 3-epi-25-OH-D3 by HPLC. Biochemical data were recorded, if available, including C-reactive protein, calcium, liver and renal markers. Season of birth, gestational age (pre-term vs full-term), weight and height were recorded for infants <1 month. 3-Epi-25-OH-D₃ was quantified in 97% of the samples. Serum levels of the epimer increased at the end of the pregnancy and decreased over the first year of life. 3-Epi-25-OH-D₃ was negatively associated with bilirubin and C-reactive protein but unrelated to gestational age, season, age after delivery, height and weight, and calcemia or renal function. Based on the present data, both liver function and acute phase reactants should be considered when measuring 3-epi-25-OH-D₃ and assessing vitamin D status in infants. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  8. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. 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

  11. Use of surface plasmon resonance in the binding study of vitamin D, metabolites and analogues with vitamin D binding protein.

    PubMed

    Canoa, Pilar; Rivadulla, Marcos L; Popplewell, Jonathan; van Oosten, René; Gómez, Generosa; Fall, Yagamare

    2017-04-01

    Vitamin D3 and its metabolites are lipophilic molecules with low aqueous solubility and must be transported bound to plasma carrier proteins, primarily to vitamin D binding protein (DBP). The biological functions of vitamin D3 metabolites are intimately dependent on the protein, hence the importance of determining their affinity for DBP. In this study, we developed a novel procedure for measuring the kinetic and equilibrium constants of human-DBP with vitamin D3 and three metabolites: 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], 25-hydroxyvitamin D3 (25OHD3) and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] by surface plasmon resonance (SPR). At the same time, five different analogues, synthetized in our laboratory, were evaluated in order to compare the affinity values with the metabolites. Real-time SPR measurements showed that 25OHD3 and 24,25(OH)2D3 had higher affinity (0.3 μM) than 1,25(OH)2D3 (5 μM), with the higher affinity of 25OHD3 and 24,25(OH)2D3 due to dissociation constants 1 order of magnitude slower. In the case of the analogues, the affinity values were lower, with 1-hydroxy-25-nitro-vitamin D3 (NO2-446), structurally closer to 1,25(OH)2D3, showing the highest value with a K D of 50 μM. (24R)-1,25-dihydroxyvitamin-24-buthyl-28-norvitamin D2 (Bu-471) and (24R)-1,25-dihydroxyvitamin-24-phenyl-28-norvitamin D2 (Ph-491), structurally similar, had affinities of 180 and 170 μM, respectively. (22R,23E)-1-hydroxy-22-ethenyl-25-methoxy-23-dehydrovitamin D3 (MeO-455) and 1-hydroxy-20(R)-[5(S)-(2,2-dimethyltetrahydropyran-5-yl)]-22,23-dinor vitamin D3 (Oxan-429) had affinities of 310 and 100 μM, respectively. The binding of the metabolites and analogues was reversible allowing the rapid capture of data for replicates. The kinetic and equilibrium data for both the metabolites and the analogues fitted to the Langmuir model describing a 1:1 interaction. Graphical Abstract Label-free, real time binding study between vitamin D binding protein immmobilized on the

  12. 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.

  13. 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

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

    2015-11-01

    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 D₃deficiency 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)₂D₃during avian osteogenesis, chicken bone marrow-derived mesenchymal stem cells (BM-MSCs) were exposed to varying doses of 1,25-(OH)₂D₃during 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)₂D₃with 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)₂D₃than those from broilers. These data suggest that understanding species and strain specific sensitivities to 1,25-(OH)₂D₃is 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.

  14. Inverse associations between cord vitamin D and attention deficit hyperactivity disorder symptoms: A child cohort study.