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Sample records for 25-hydroxyvitamin d3 25ohd

  1. Proficiency testing of 25-hydroxyvitamin D (25-OHD) assays.

    PubMed

    Carter, G D; Berry, J L; Gunter, E; Jones, G; Jones, J C; Makin, H L J; Sufi, S; Wheeler, M J

    2010-07-01

    The Vitamin D External Quality Assessment Scheme (DEQAS) has been monitoring 25-OHD assay performance since 1989. The scheme has expanded rapidly in recent years and has 670 participants in 35 countries (July 2009). Five samples of human serum are distributed quarterly and the results analyzed to give an All-Laboratory Trimmed Mean (ALTM) and SD. Each participant has internet access to a preliminary report after submission of results and, following the results deadline, a final report is e-mailed to designated staff in each laboratory. The last 15 years has seen an improvement in mean inter-laboratory imprecision (CV), from 32.0% (1994) to 15.3% (2009) and most major methods are now giving results within plus or minus 7.4% of the ALTM (2009). DEQAS has regularly conducted and reported on a number of investigations into the performance of 25-OHD methods. A gas chromatography-mass spectrometry (GC-MS) reference method for 25-OHD is under development and will be used to assess whether the ALTM remains the most appropriate target for DEQAS samples. PMID:20302938

  2. Data in support for the measurement of serum 25-hydroxyvitamin D (25OHD) by tandem mass spectrometry.

    PubMed

    Jensen, M E; Ducharme, F M; Théorêt, Y; Bélanger, A-S; Delvin, E

    2016-09-01

    This article provides data and a method related to a research paper entitled "Assessing vitamin D nutritional status: is capillary blood adequate?" (Jensen et al., 2016) [1]. Circulating 25OHD, the accepted biomarker of the vitamin D nutritional status, is routinely measured by automated immunoassays, that although may be performed in hospital central laboratories, often suffer from a lack of specificity with regards to the different vitamin D metabolites, "Measurement of circulating 25-hydroxyvitamin D: a historical review" (Le Goff et al., 2015) [2]. Mass spectrometry offers this specificity. This article describes the performance of an in-house tandem mass spectrometry method for the individual measurement of 25OHD3, 25OHD2 and 3-épi-25OHD3. PMID:27508244

  3. Automated immunoassays for 25-hydroxyvitamin D (25-OHD): do plasticisers interfere?

    PubMed

    Carter, G D; Jones, J; Ketheeswaran, M; Shannon, J; Singh, B; Kearney, E; Berry, J L

    2015-04-01

    The international quality assessment scheme for vitamin D metabolites (DEQAS) was established in 1989. The scheme involves the quarterly distribution of 5 serum samples prepared from blood collected in plain plastic bags. Following transfer of the donors to a clinic using different bags, sera were found to contain a contaminant that interfered in both the local LC-MS/MS assay and the NIST reference measurement procedure for 25-OHD. It seemed likely that the contaminant was a substance, possibly a plasticiser, leached from the plastic bag. It was subsequently suggested that the unidentified contaminant might also cause interference in certain automated non-extraction assays for 25-OHD. This was investigated in 3 automated immunoassays by comparing serum 25-OHD results from blood collected simultaneously into plain glass tubes and plastic bags. There was no significant difference in results, indicating that the leached substance had no effect on any of the 3 immunoassays examined. PMID:25448742

  4. High-performance liquid chromatography and coulometric electrode array detector in serum 25-hydroxyvitamin D(3) and 25-hydroxyvitamin D(2) analyses.

    PubMed

    Nurmi, Tarja; Tuomainen, Tomi-Pekka; Virtanen, Jyrki; Mursu, Jaakko; Voutilainen, Sari

    2013-04-01

    The diode array detector in our high-performance liquid chromatography (HPLC) method for 25-hydroxyvitamin D(3) (25OHD(3)) and 25-hydroxyvitamin D(2) (25OHD(2)) did not perform satisfactorily for measuring human serum concentrations below 30nM. Because of a need for a reliable self-managed method in ongoing and starting vitamin D studies of the laboratory, we decided to develop a chromatographic method applying coulometric electrode array detector (CEAD) and evaluate reliability of the method by participating in the Vitamin D External Quality Assessment Scheme (DEQAS). The limit of quantification for 25OHD(3) and 25OHD(2) of the new method was 0.36pmol on column (3.6nM), and linearity ranged from 5 to 2400nM. Accuracy of the method was 90% for 25OHD(3) and 69% for 25OHD(2). The HPLC-CEAD results from five DEQAS rounds were in line with those of the other participating laboratories using HPLC methods. The HPLC-CEAD results for 25OHD(3) also corresponded to the results obtained with the Chromsystems HPLC method in a certified laboratory. The long-term coefficients of variation for 25OHD(3) were 6.2%, 7.8%, 5.2%, 6.7%, and 7.3% in concentrations of 27.5, 38.7, 48.4, 78.4, and 88.0nM, respectively. The developed HPLC-CEAD method was shown to be applicable for determining 25OHD(3) and 25OHD(2) in human serum samples. PMID:23274364

  5. Type of dietary fat is associated with the 25-hydroxyvitamin D3 increment in response to vitamin D supplementation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mono- and polyunsaturated fats may have opposing effects on vitamin D absorption. The purpose of this study was to determine whether intakes of different dietary fats are associated with the increase in serum 25-hydroxyvitamin D (25OHD) following supplementation with vitamin D3. This analysis was co...

  6. Is the metabolism of 25-hydroxyvitamin D3 age-dependent in dairy cows?

    PubMed

    Wilkens, Mirja R; Cohrs, Imke; Lifschitz, Adrian L; Fraser, David R; Olszewski, Katharina; Schröder, Bernd; Breves, Gerhard

    2013-07-01

    It has recently been demonstrated that prepartum administered 25-hydroxyvitamin D3 (25-OHD3) is a promising candidate to assist the maintenance of peripartal calcium homeostasis in dairy cows. Since the incidence of peripartal hypocalcemia and the reported beneficial effects of the treatment are both associated with the lactation number, we investigated pharmacokinetic aspects of 25-OHD3 related to the age of dairy cows. The daily oral administration of 3mg 25-OHD3 in rapeseed oil as well as a treatment with 4 and 6mg included in the feed during the last eight to ten days of gestation resulted in linear dosage- and age-dependent increases in plasma 25-OHD3. After parturition the administration was stopped and blood samples were taken to calculate the plasma half-life. Irrespective of the supplemented dosage, cows starting the 2nd lactation showed a significantly longer plasma half-life of 25-OHD3 than cows starting the 3rd or higher lactation. Age-dependent differences in the increase of plasma 25-OHD3 could already be found before parturition when calcium homeostasis was not yet significantly challenged. Additionally, no correlations between plasma half-life of 25-OHD3 and 1,25-dihydroxyvitamin D3, PTH or the bone resorption marker CrossLaps were observed after parturition. Thus we conclude that the influence of the lactation number on the pharmacokinetics of 25-OHD3 is related directly to the age of the cows. This article is part of a Special Issue entitled 'Vitamin D Workshop'. PMID:23220546

  7. Biliary excretion of radioactivity after intravenous administration of (3H)25-hydroxyvitamin D3 in man

    SciTech Connect

    Ledger, J.E.; Watson, G.J.; Compston, J.E.

    1986-04-01

    The biliary excretion of radioactivity after intravenous (3H)25-hydroxyvitamin D3 was studied in nine patients with T-tube bile drainage. The mean +/- SD 24-hr radioactivity excretion in T-tube bile expressed as a percentage of the administered dose was 6.7 +/- 2.9%; after correction for incomplete bile collection, the value obtained was 16.0 +/- 11.1%. Chloroform solubility of biliary radioactivity increased from 27.4 +/- 8.9% to 72.9 +/- 10.1% following incubation with beta-glucuronidase. High-performance liquid chromatographic analysis of chloroform extracts of bile revealed that most of the eluted radioactivity was more polar than (3H)25-hydroxyvitamin D3. No free (3H)25-hydroxyvitamin D3 was demonstrated. Thus in man, most of the biliary radioactivity excreted following (3H)25-hydroxyvitamin D3 is in the form of water-soluble compounds, mainly glucuronides. However, our results suggest that glucuronides of metabolites other than 25-OHD3 are predominantly formed.

  8. 21 CFR 584.725 - 25-Hydroxyvitamin D3.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false 25-Hydroxyvitamin D3. 584.725 Section 584.725 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE IN FEED...

  9. 21 CFR 584.725 - 25-Hydroxyvitamin D3.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false 25-Hydroxyvitamin D3. 584.725 Section 584.725 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE IN FEED...

  10. 21 CFR 584.725 - 25-Hydroxyvitamin D3.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false 25-Hydroxyvitamin D3. 584.725 Section 584.725 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE IN FEED...

  11. 21 CFR 584.725 - 25-Hydroxyvitamin D3.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false 25-Hydroxyvitamin D3. 584.725 Section 584.725 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE IN FEED...

  12. 21 CFR 584.725 - 25-Hydroxyvitamin D3.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false 25-Hydroxyvitamin D3. 584.725 Section 584.725 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE IN FEED...

  13. In vitro formation of 25-hydroxyvitamin D3 metabolites in endometrium: dependence on the hormonal status of the rat.

    PubMed

    Acker, G M; Garabedian, M; Guillozo, H; Pecquinot, M A; Balsan, S

    1982-12-01

    Rat myometrial tissue and endometrial cells were incubated with labeled 25-hydroxyvitamin D3 ([3H-26,27] 25OHD3) for 70 min at 37 C, and the resulting metabolites were isolated by sequential Sephadex LH-20 chromatography and high performance liquid chromatography. Two peaks more polar than 25OHD3 were present on the Sephadex LH-20 chromatograms. One of these metabolites had an identical chromatographic behavior on three different HPLC systems and an identical sensitivity to periodate cleavage as biosynthetic [3H-26,27] 24,25-dihydroxyvitamin D3 ([3H-26,27]24,25-(OH)2D3]. The in vitro production of this putative 24,25-(OH)2D3 was significantly higher in castrated animals than in normal adult rats. Treatment of rats with 17 beta-estradiol and/or medroxyprogesterone acetate reversed the effect of ovariectomy on 25OHD3 conversion. The in vitro production of the putative 24,25-(OH)2D3 was low during the estrous cycle and the initial stage of pregnancy. A dramatic increase in its production was observed on days 12 and 14 of pregnancy. 25OHD3 conversion was higher in endometrium than in myometrium under every experimental condition tested. These results demonstrate the ability of rat uterine tissue to convert 25OHD3 into more polar derivatives in vitro, and show the influence of the hormonal status of the rat on this in vitro capacity. PMID:6982812

  14. The relations between vitamin D2 and D3 in the diet and plasma 25OHD2 and 25OHD3 in elderly women in Great Britain.

    PubMed

    Newton, H M; Sheltawy, M; Hay, A W; Morgan, B

    1985-04-01

    Vitamin D2 and D3 intake and plasma 25OHD2 and 25OHD3 were measured in 70 elderly women; 13 living at home and 57 long-stay patients with no access to sunlight. Vitamin D2 intake and plasma 25OHD2 were correlated in the whole group (p less than .005) and vitamin D3 intake and plasma 25OHD3 and total D intake and total 25OHD were significantly correlated (p less than .005) in the patients. In the whole group the plasma 25OHD2 increased by 4.5 nmol/l for every 1 microgram increase in vitamin D2 intake. This was also the increase observed in a longitudinal study of vitamin D2 supplements in 11 patients. Vitamin D intake is a significant determinant of plasma 25OHD and the relation between them suggests that stores of vitamin D can be maintained at 20 nmol/l in the elderly by a daily intake of 4 micrograms of vitamin D, even in the absence of sunlight. PMID:2984915

  15. Enzyme immunoassay for measuring 25-hydroxyvitamin D3 in serum.

    PubMed

    Lind, C; Chen, J; Byrjalsen, I

    1997-06-01

    We developed a rapid, competitive enzyme immunoassay (EIA) for measuring 25-hydroxyvitamin D3 [25(OH)D3] in serum. The EIA was based upon 25(OH)D3-3-hemisuccinate covalently coupled to secondary amino groups grafted onto the polystyrene surface of microtiter wells. Optimal coupling conditions were established, and we found that inclusion of 40 mumol/L chloramine T, an agent not previously described for use in coupling to these plates, resulted in both more reproducible coupling as well as more than a twofold increase in the coupling efficiency. Before EIA, 25(OH)D3 was extracted from the serum samples by acetonitrile, and the redissolved extract was incubated with polyclonal rabbit antibody raised against 1,25-dihydroxyvitamin D3-3-hemisuccinate conjugated to bovine serum albumin. Peroxidase-labeled antibody raised in goat against rabbit immunoglobulins was used for detection. The detection limit of the EIA was 4.4 micrograms/L; recovery 102%; on-plate CV 11%; within-run CV including extraction 12%, and between-run CV 15%. There was no clinically important cross-reactivity with other vitamin D metabolites, and results obtained by the EIA were compared with results obtained by a previously described RIA. PMID:9191544

  16. Treatment of an intramammary bacterial infection with 25-hydroxyvitamin D(3).

    PubMed

    Lippolis, John D; Reinhardt, Timothy A; Sacco, Randy A; Nonnecke, Brian J; Nelson, Corwin D

    2011-01-01

    Deficiency of serum levels of 25-hydroxyvitamin D(3) has been correlated with increased risk of infectious diseases such as tuberculosis and influenza. A plausible reason for this association is that expression of genes encoding important antimicrobial proteins depends on concentrations of 1,25-dihydroxyvitamin D(3) produced by activated immune cells at sites of infection, and that synthesis of 1,25-dihydroxyvitamin D(3) is dependent on the availability of 25-hydroxyvitamin D(3). Thus, increasing the availability of 25(OH)D(3) for immune cell synthesis of 1,25-dihydroxyvitamin D(3) at sites of infection has been hypothesized to aid in clearance of the infection. This report details the treatment of an acute intramammary infection with infusion of 25-hydroxyvitamin D(3) to the site of infection. Ten lactating cows were infected with in one quarter of their mammary glands. Half of the animals were treated intramammary with 25-hydroxyvitamin D(3). The 25-hydroxyvitamin D(3) treated animal showed significantly lower bacterial counts in milk and showed reduced symptomatic affects of the mastitis. It is significant that treatment with 25-hydroxyvitamin D(3) reduced the severity of an acute bacterial infection. This finding suggested a significant non-antibiotic complimentary role for 25-hydroxyvitamin D(3) in the treatment of infections in compartments naturally low in 25-hydroxyvitamin D(3) such as the mammary gland and by extension, possibly upper respiratory tract infections. PMID:21991312

  17. Feeding 25-hydroxyvitamin D3 to improve beef tenderness.

    PubMed

    Wertz, A E; Knight, T J; Trenkle, A; Sonon, R; Horst, R L; Huff-Lonergan, E J; Beitz, D C

    2004-05-01

    The objective of this trial was to determine if a single oral bolus of 25-hydroxyvitamin D3 (25-OH D3) given at various times before slaughter would enhance the tenderness of beef loin steaks. One hundred eight crossbred steers were allotted to 18 pens so that the mean weight of the cattle in each pen was similar. Treatments (25-OH D3 dose [62.5 or 125 mg]) and time of administration of the single oral bolus (4, 7, 21, or 35 d before slaughter) were assigned randomly to each pen of steers. Serial plasma samples were collected at each bolus administration time for control animals. For steers assigned to a treatment group, a baseline blood sample was collected before bolus administration and at each subsequent administration when other treatment groups received their bolus. Plasma samples were assayed for 25-OH D3 and calcium concentrations. Troponin-T degradation and Warner-Bratzler shear force were measured as indicators of tenderness for loin steaks collected at slaughter and aged for 6 or 14 d postmortem. Muscle samples, collected concurrently, were assayed for 25-OH D3 and calcium concentrations. A single oral bolus of 25-OH D3 was sufficient to increase plasma 25-OH D3 concentrations (P < 0.001) through slaughter, regardless of dose or time of bolus administration. The single oral bolus of 25-OH D3, however, did not increase plasma calcium concentrations (P > 0.05). As a result, neither troponin-T degradation nor Warner-Bratzler shear force was improved (P > 0.05) by treatment. Muscle 25-OH D3 concentrations were increased (P > 0.001) by treatment with 25-OH D3. Although sustained plasma 25-OH D3 concentrations did not increase plasma or muscle calcium at slaughter nor influence tenderness, the use of 25-OH D3 as a nutritional means of improving beef tenderness is in its infancy, and more research to delineate an effective dose and the potential interaction of seasonal exposure to ultraviolet light is warranted. PMID:15144081

  18. The Vitamin D Receptor (VDR) Is Expressed in Skeletal Muscle of Male Mice and Modulates 25-Hydroxyvitamin D (25OHD) Uptake in Myofibers

    PubMed Central

    Mokbel, Nancy; Cha, Kuan Minn; Houweling, Peter J.; Abboud, Myriam; Fraser, David R.; Mason, Rebecca S.; Clifton-Bligh, Roderick J.

    2014-01-01

    Vitamin D deficiency is associated with a range of muscle disorders, including myalgia, muscle weakness, and falls. In humans, polymorphisms of the vitamin D receptor (VDR) gene are associated with variations in muscle strength, and in mice, genetic ablation of VDR results in muscle fiber atrophy and motor deficits. However, mechanisms by which VDR regulates muscle function and morphology remain unclear. A crucial question is whether VDR is expressed in skeletal muscle and directly alters muscle physiology. Using PCR, Western blotting, and immunohistochemistry (VDR-D6 antibody), we detected VDR in murine quadriceps muscle. Detection by Western blotting was dependent on the use of hyperosmolar lysis buffer. Levels of VDR in muscle were low compared with duodenum and dropped progressively with age. Two in vitro models, C2C12 and primary myotubes, displayed dose- and time-dependent increases in expression of both VDR and its target gene CYP24A1 after 1,25(OH)2D (1,25 dihydroxyvitamin D) treatment. Primary myotubes also expressed functional CYP27B1 as demonstrated by luciferase reporter studies, supporting an autoregulatory vitamin D-endocrine system in muscle. Myofibers isolated from mice retained tritiated 25-hydroxyvitamin D3, and this increased after 3 hours of pretreatment with 1,25(OH)2D (0.1nM). No such response was seen in myofibers from VDR knockout mice. In summary, VDR is expressed in skeletal muscle, and vitamin D regulates gene expression and modulates ligand-dependent uptake of 25-hydroxyvitamin D3 in primary myofibers. PMID:24949660

  19. Local Sustained Delivery of 25-Hydroxyvitamin D3 for Production of Antimicrobial Peptides

    PubMed Central

    Jiang, Jiang; Chen, Guojun; Shuler, Franklin D.; Wang, Chi-Hwa; Xie, Jingwei

    2015-01-01

    Purpose This study seeks to develop fiber membranes for local sustained delivery of 25-hydroxyvitamin D3 to induce the expression and secretion of LL-37 at or near the surgical site, which provides a novel therapeutic approach to minimize the risk of infections. Methods 25-hydroxyvitamin D3 loaded poly(L-lactide) (PLA) and poly(ε-caprolactone) (PCL) fibers were produced by electrospinning. The morphology of obtained fibers was characterized using atomic force microscope (AFM) and scanning electron microscope (SEM). 25-hydroxyvitamin D3 releasing kinetics were quantified by enzyme-linked immunosorbent assay (ELISA) kit. The expression of cathelicidin (hCAP 18) and LL-37 was analyzed by immunofluorescence staining and ELISA kit. The antibacterial activity test was conducted by incubating pseudomonas aeruginosa in a monocytes’ lysis solution. Results AFM images suggest that the surface of PCL fibers is smooth, however, the surface of PLA fibers is relatively rough, in particular, after encapsulation of 25-hydroxyvitamin D3. The duration of 25-hydroxyvitamin D3 release can last more than 4 weeks for all the tested samples. Plasma treatment can promote the release rate of 25-hydroxyvitamin D3. Human keratinocytes and monocytes express significantly higher levels of hCAP18/LL-37 after incubation with plasma treated and 25-hydroxyvitamin D3 loaded PCL fibers than the cells incubated with around 10 times amount of free drug. After incubation with this fiber formulation for 5 days LL-37 in the lysis solutions of U937 cells can effectively kill the bacteria. Conclusions plasma treated and 25-hydroxyvitamin D3 loaded PCL fibers induce significantly higher levels of antimicrobial peptide production in human keratinocytes and monocytes without producing cytotoxicity. PMID:25773720

  20. Photoaffinity labeling of serum vitamin D binding protein by 3-deoxy-3-azido-25-hydroxyvitamin D3

    SciTech Connect

    Link, R.P.; Kutner, A.; Schnoes, H.K.; DeLuca, H.F.

    1987-06-30

    3-Deoxy-3-azido-25-hydroxyvitamin D3 was covalently incorporated in the 25-hydroxyvitamin D3 binding site of purified human plasma vitamin D binding protein. Competition experiments showed that 3-deoxy-3-azido-25-hydroxyvitamin D3 and 25-hydroxyvitamin D3 bind at the same site on the protein. Tritiated 3-deoxy-3-azido-25-hydroxyvitamin D3 was synthesized from tritiated 25-hydroxyvitamin D3, retaining the high specific activity of the parent compound. The tritiated azido label bound reversibly to human vitamin D binding protein in the dark and covalently to human vitamin D binding protein after exposure to ultraviolet light. Reversible binding of tritiated 3-deoxy-3-azido-25-hydroxyvitamin D3 was compared to tritiated 25-hydroxyvitamin D3 binding to human vitamin D binding protein. Scatchard analysis of the data indicated equivalent maximum density binding sites with a KD,app of 0.21 nM for 25-hydroxyvitamin D3 and a KD,app of 1.3 nM for the azido derivative. Covalent binding was observed only after exposure to ultraviolet irradiation, with an average of 3% of the reversibly bound label becoming covalently bound to vitamin D binding protein. The covalent binding was reduced 70-80% when 25-hydroxyvitamin D3 was present, indicating strong covalent binding at the vitamin D binding site of the protein. When tritiated 3-deoxy-3-azido-25-hydroxyvitamin D3 was incubated with human plasma in the absence and presence of 25-hydroxyvitamin D3, 12% of the azido derivative was reversibly bound to vitamin D binding protein. After ultraviolet irradiation, four plasma proteins covalently bound the azido label, but vitamin D binding protein was the only protein of the four that was unlabeled in the presence of 25-hydroxyvitamin D3.

  1. Serum 25-Hydroxyvitamin D Response to Vitamin D3 Supplementation 50,000 IU Monthly in Youth with HIV-1 Infection

    PubMed Central

    Mulligan, Kathleen; Hazra, Rohan; Flynn, Patricia; Rutledge, Brandy; Van Loan, Marta D.; Lujan-Zilbermann, Jorge; Kapogiannis, Bill G.; Wilson, Craig M.; Stephensen, Charles B.

    2012-01-01

    Context: Vitamin D deficiency and insufficiency occur frequently in youth with HIV infection, particularly among those receiving the antiretroviral drug efavirenz. Optimal vitamin D dosing for treatment is unclear. Objective: Our objective was to evaluate safety and measure change in 25-hydroxyvitamin D (25-OHD) concentration from baseline to study wk 4 and 12 during treatment with vitamin D3, 50,000 IU monthly. Design, Setting, and Participants: We conducted a randomized double-blind, placebo-controlled multicenter trial of HIV-infected youth ages 18–24 yr, with viral load below 5000 copies/ml, on stable antiretroviral therapy. Intervention: Intervention included vitamin D3, 50,000 IU (n = 102), or matching placebo (n = 101) administered in three directly observed oral doses at monthly intervals. Results: At baseline, mean (sd) age was 20.9 (2.0) yr; 37% were female and 52% African-American, and 54% were vitamin D deficient/insufficient (25-OHD < 20 ng/ml), with no randomized group differences. Of evaluable participants vitamin D deficient/insufficient at baseline who were administered vitamin D, 43 of 46 (93%) had sufficient 25-OHD by wk 12. Vitamin D supplementation increased 25-OHD serum concentration from a baseline of 21.9 (13.3) to 35.9 (19.1) ng/ml at wk 12 (P < 0.001) with no change for placebo. Although use of the antiretroviral efavirenz was associated with lower baseline 25-OHD concentration, efavirenz did not diminish the response to vitamin D supplementation. There was no treatment-related toxicity. Conclusions: Supplementation with vitamin D3 50,000 IU monthly for three doses was safe. Increases in 25-OHD occurred in treated participants regardless of antiretroviral regimen. PMID:22933542

  2. Regulation of Mycobacterium-specific mononuclear cell responses by 25-hydroxyvitamin D3

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), has been shown to be an important regulator of innate and adaptive immune function. In addition, synthesis of 1,25(OH)2D3 from 25-hydroxyvitamin D3 (25[OH]D3) by the enzyme 1alpha-hydroxylase in monocytes upon activation by TLR...

  3. Kinetics of intravenously administered 25-hydroxyvitamin D3 in sheep and the effect of exposure to ultraviolet radiation

    SciTech Connect

    Hidiroglou, M.

    1987-09-01

    This report describes studies of 25-hydroxyvitamin D3 (25OHD3) kinetics in 10 yearling crossbred wethers (40 to 52 kg body weight) administered (/sup 3/H) 25-hydroxyvitamin D3 (( /sup 3/H) 250HD3). The wethers were divided into two groups of five before dosing with the labeled compound: Group 1 wethers were exposed 2 h daily for 8 to 10 wk to ultraviolet radiation from fluorescent sunlamps. Plasma 250HD3 increased from 13 to 31 ng/ml by d 25 and then remained at a steady-state concentration until d 70. In the non-ultraviolet-exposed wethers (Group 2), plasma 250HD3 averaged 13.2 ng/ml and did not change over the course of the experiment. Six weeks after the start of the experiment three wethers from each group were injected intravenously with 50 microCi of (/sup 3/H)250HD3, and the other two wethers from each group were similarly dosed 2 wk later. Blood was drawn at suitable time intervals for up to 240 h post-dosing. The kinetic data were satisfied by curve-fitting the data to a two-compartment, pharmacokinetic mathematical model. Individual and mean values for these kinetic analyses are presented with their statistical analyses. Physiological half-life of the tritiated 2500 HD3 in wethers exposed to ultraviolet irradiation was 388 +/- 26.4 h (means +/- SE); in the control it was 393 +/- 29.6 h (P greater than .05). In the wethers exposed to ultraviolet the elimination and clearance rates of 250HD3 were significantly greater than in the control wethers. A two-compartment model provided an acceptable description of 250HD3 disposition kinetics in wethers. Turnover rate constants did not seem to change, but changes were due to increased pool size in the irradiated wethers.

  4. Treatment of an intramammary bacterial infection with 25-hydroxyvitamin D3

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Deficiency of serum levels of 25-hydroxyvitamin D3 has been correlated with increased risk of infectious diseases, such as tuberculosis and influenza. A plausible reason for this association is that expression of genes encoding important antimicrobial proteins depends on concentrations of 1,25-dihyd...

  5. Influence of the combination of 25-hydroxyvitamin D3 and a diet negative in cation-anion difference on peripartal calcium homeostasis of dairy cows.

    PubMed

    Wilkens, M R; Oberheide, I; Schröder, B; Azem, E; Steinberg, W; Breves, G

    2012-01-01

    Around parturition, many dairy cows experience varying degrees of hypocalcemia, which increases the incidence of several diseases in early lactation. In the current study, an established concept of feeding a diet negative in cation-anion difference (DCAD) was combined with oral supplementation of 25-hydroxyvitamin D(3) (25-OHD(3)) from d 270 of gestation until parturition. Fifty-six dairy cows were divided into 2 feeding groups (low DCAD and control). Fourteen animals of each group received a daily dosage of 3mg of 25-OHD(3). From the beginning of the treatment to d 10 after parturition, plasma samples for analysis of 25-OHD(3), 1,25-dihydroxyvitamin D(3), parathyroid hormone (PTH), Ca(2+), phosphate, the bone resorption marker CrossLaps, and osteocalcin were collected every other day, at calving, and at 6, 12, and 24h after calving. Urine samples for determination of macrominerals and measures of acid-base status were collected on d 6 of treatment and on d 6 after calving. The induction of a compensated metabolic acidosis by the animals on the DCAD diet could be demonstrated by decreased urinary pH. A linear correlation between treatment duration and the plasma concentration of 25-OHD(3) indicated effective absorption of 25-OHD(3) in supplemented animals. The mean plasma concentrations of Ca(2+) from d -4 prepartum to d 4 postpartum were significantly higher in animals treated with the combination of the low DCAD diet and 25-OHD(3) supplementation (1.24±0.02 mmol/mL) compared with the 3 other groups (low DCAD: 1.17±0.02 mmol/mL; control diet plus 25-OHD(3): 1.16±0.02 mmol/mL; control diet: 1.18±0.02 mmol/mL). We postulate that the increased tissue responsiveness to parathyroid hormone induced by the low DCAD is crucial for the observed positive effects of the 25-OHD(3) treatment. PMID:22192194

  6. Species differences in the binding kinetics of 25-hydroxyvitamin D3 to vitamin D binding protein.

    PubMed

    Vieth, R; Kessler, M J; Pritzker, K P

    1990-10-01

    The specific binding of 25-hydroxyvitamin D3 to its binding protein was studied in serum of the human, rhesus monkey, cow, horse, and rat. The free fraction of 25-hydroxyvitamin D3 in the rat was 0.34 +/- 0.15 pmol free/nmol total (+/- SD) and this was lower than in any of the other species (p less than 0.01). In the human, the free fraction was 1.5 +/- 0.32 pmol free/nmol total, which was higher than in any of the other species (p less than 0.001). The differences in the free fraction were mainly due to differences in dissociation constant. The relative levels of free 25-hydroxyvitamin D should be taken into account when extrapolating findings about vitamin D metabolism in animals to the human. A technical outcome of this study is that of the species tested, vitamin D binding protein from rat serum is the most suitable as a reagent component for methods used to measure total 25-hydroxyvitamin D by competitive protein binding assay. PMID:2078829

  7. Serum 25-hydroxyvitamin D3 levels are elevated in South Indian patients with ischemic heart disease.

    PubMed

    Rajasree, S; Rajpal, K; Kartha, C C; Sarma, P S; Kutty, V R; Iyer, C S; Girija, G

    2001-01-01

    Several lines of evidence point to a possible relationship between vitamin D and cardiovascular disease. Animal experiments and observational studies in humans suggest vitamin D to be arteriotoxic and an association of high intake of vitamin D with increased incidence of ischemic heart disease (IHD). The major source of vitamin D in adults is vitamin D synthesized in the skin through exposure to the sun. In tropical environment there is a possibility of high level of solar exposure and enhanced serum levels of vitamin D in the population. We explored the relation between serum level of 25-hydroxyvitamin D3 and IHD in a case-control study involving 143 patients with either angiographic evidence of coronary artery disease or patients with acute myocardial infarction and 70 controls, all men in the age group of 45-65 years. Fasting blood samples were collected, serum separated and serum levels of 25-hydroxyvitamin D3 was measured by protein binding radioligand assay. Serum levels of cholesterol, triglyceride, calcium, magnesium and inorganic phosphate were also determined. Prevalences of diabetes, hypertension and smoking history were noted. Statistical comparisons of variables between cases and controls were done using chi2-tests. Multivariate logistic regression analysis was done to examine the association of IHD with serum levels of 25-hydroxyvitamin D3 controlling for selected variables. Serum levels of 25-hydroxyvitamin D3, calcium, inorganic phosphate, total cholesterol, low density lipoprotein and triglycerides were elevated in a higher proportion of patients, compared to controls. Serum levels of 25-OH-D3 above 222.5 nmol/l (89 ng/ml) was observed in 59.4% of cases compared to 22.1% in controls (p < 0.001; unadjusted odds ratio (OR): 5.17; 95% confidence interval (CI): 2.62-10.21). When controlled for age and selected variables using the multivariate logistic regression, the adjusted OR relating elevated serum 25-hydroxyvitamin D3 levels (> or = 222.5 nmol

  8. Anti-proliferative activity of 25-hydroxyvitamin D3 in human prostate cells.

    PubMed

    Munetsuna, Eiji; Kawanami, Rie; Nishikawa, Miyu; Ikeda, Shinnosuke; Nakabayashi, Sachie; Yasuda, Kaori; Ohta, Miho; Kamakura, Masaki; Ikushiro, Shinichi; Sakaki, Toshiyuki

    2014-02-15

    1α-Hydroxylation of 25-hydroxyvitamin D3 is believed to be essential for its biological effects. In this study, we evaluated the biological activity of 25(OH)D3 itself comparing with the effect of cell-derived 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3). First, we measured the cell-derived 1α,25(OH)2D3 level in immortalized human prostate cell (PZ-HPV-7) using [(3)H]-25(OH)D3. The effects of the cell-derived 1α,25(OH)2D3 on vitamin D3 24-hydroxylase (CYP24A1) mRNA level and the cell growth inhibition were significantly lower than the effects of 25(OH)D3 itself added to cell culture. 25-Hydroxyvitamin D3 1α-hydroxylase (CYP27B1) gene knockdown had no significant effects on the 25(OH)D3-dependent effects, whereas vitamin D receptor (VDR) gene knockdown resulted in a significant decrease in the 25(OH)D3-dependent effects. These results strongly suggest that 25(OH)D3 can directly bind to VDR and exerts its biological functions. DNA microarray and real-time RT-PCR analyses suggest that semaphorin 3B, cystatin E/M, and cystatin D may be involved in the antiproliferative effect of 25(OH)D3. PMID:24291609

  9. 25-Hydroxyvitamin D3-Deficiency Enhances Oxidative Stress and Corticosteroid Resistance in Severe Asthma Exacerbation

    PubMed Central

    Yang, Xiaoqiong; Cheng, Yuanyuan; zhang, Yun; Wang, Xiaoyun; Wang, Xing; Xie, Tao; Li, Guoping; Liu, Zhigang; Zhong, Nanshan

    2014-01-01

    Oxidative stress plays a significant role in exacerbation of asthma. The role of vitamin D in oxidative stress and asthma exacerbation remains unclear. We aimed to determine the relationship between vitamin D status and oxidative stress in asthma exacerbation. Severe asthma exacerbation patients with 25-hydroxyvitamin D3-deficiency (V-D deficiency) or 25-hydroxyvitamin D-sufficiency (V-D sufficiency) were enrolled. Severe asthma exacerbation with V-D-deficiency showed lower forced expiratory volume in one second (FEV1) compared to that with V-D-sufficiency. V-D-deficiency intensified ROS release and DNA damage and increased TNF-α, OGG1 and NFκB expression and NFκB phosphorylation in severe asthma exacerbation. Supplemental vitamin D3 significantly increased the rates of FEV1 change and decreased ROS and DNA damage in V-D-deficiency. Vitamin D3 inhibited LPS-induced ROS and DNA damage and were associated with a decline in TNF-α and NFκB in epithelial cells. H2O2 reduces nuclear translocation of glucocorticoid receptors in airway epithelial cell lines. V-D pretreatment enhanced the dexamethasone-induced nuclear translocation of glucocorticoid receptors in airway epithelial cell lines and monocytes from 25-hydroxyvitamin D3-deficiency asthma patients. These findings indicate that V-D deficiency aggravates oxidative stress and DNA damage, suggesting a possible mechanism for corticosteroid resistance in severe asthma exacerbation. PMID:25380286

  10. 25-Hydroxyvitamin D(3) suppresses PTH synthesis and secretion by bovine parathyroid cells.

    PubMed

    Ritter, C S; Armbrecht, H J; Slatopolsky, E; Brown, A J

    2006-08-01

    Active vitamin D compounds repress parathyroid hormone (PTH) gene transcription and block chief cell hyperplasia, making them integral tools in the treatment of secondary hyperparathyroidism in patients with chronic kidney disease. Recently, human parathyroid glands have been shown to express 25-hydroxyvitamin D 1alpha-hydroxylase (1alphaOHase), but documentation of the 1alphaOHase activity in parathyroid cells and its potential role in activating 25-hydroxyvitamin D(3) (25(OH)D(3)) to 1,25-dihydroxyvitamin D(3) (1,25(OH)2D3) have not been reported. The relative potencies of 25(OH)D(3) and 1,25(OH)(2)D(3) in reducing PTH secretion and mRNA were determined in primary cultures of bovine parathyroid cells (bPTC). The effects of blocking 1alphaOHase activity on suppression of PTH mRNA and induction of 24-hydroxylase mRNA were examined. Vitamin D receptor (VDR) affinities were estimated by intact cell competitive binding assay. Metabolism of 25(OH)D(3) by bPTC was assessed using a radioimmunoassay that measures all 1-hydroxylated metabolites of vitamin D. 25(OH)D(3) suppressed PTH secretion and mRNA (ED(50)=2 nM), but was several hundred times less potent than 1,25(OH)(2)D(3). The lower potency of 25(OH)D(3) correlated with its lower VDR affinity. bPTCs converted 25(OH)D(3) to 1-hydroxylated metabolites, but the rate of conversion was low. Inhibition of 1alphaOHase with the cytochrome P450 inhibitor clotrimazole did not block 25(OH)D(3)-mediated suppression of PTH. Clotrimazole enhanced 24-hydroxylase mRNA induction, presumably by inhibiting catabolism of 25(OH)D(3). In conclusion, 25(OH)D(3) suppresses PTH synthesis by parathyroid cells, possibly by direct activation of the VDR. PMID:16807549

  11. The Association of 25-Hydroxyvitamin D3 and D2 with Behavioural Problems in Childhood

    PubMed Central

    Tolppanen, Anna-Maija; Sayers, Adrian; Fraser, William D.; Lewis, Glyn; Zammit, Stanley; Lawlor, Debbie A.

    2012-01-01

    Background Higher serum concentrations of 25-hydroxyvitamin D (25(OH)D), an indicator of vitamin D synthesis and intake, have been associated with better mental health and cognitive function. Concentrations of 1,25-dihydroxyvitamin D3 (the active vitamin D3 metabolite) have been associated with openness and extrovert behaviour, but 25(OH)D concentrations have not been associated with behavioural problems in humans. Methods We investigated the prospective association between the different forms of 25(OH)D - 25(OH)D3 and 25(OH)D2– and childhood behavioural problems in Avon Longitudinal Study of Parents and Children (ALSPAC). Serum 25(OH)D3 and 25(OH)D2 concentrations were assessed at mean age 9.9 years. Incident behavioural problems were assessed with Strengths and Difficulties Questionnaire (SDQ; emotional symptoms, conduct problems, hyperactivity-inattention problems, peer relationship problems and pro-social behaviour subscales and total difficulties score) at mean age 11.7. Sample sizes varied between 2413-2666 depending on the outcome. Results Higher 25(OH)D3 concentrations were weakly associated with lower risk of prosocial problems (fully adjusted odds ratio: OR (95% confidence interval: CI) 0.85 (0.74, 0.98)). Serum 25(OH)D3 or 25(OH)D2 concentrations were not associated with other subscales of SDQ or total difficulties score after adjusting for concfounders and other measured analytes related to vitamin D. Conclusions Our findings do not support the hypothesis that 25-hydroxyvitamin D status in childhood has important influences on behavioural traits in humans. PMID:22808099

  12. Serum 25-Hydroxyvitamin D3 and Mammography Density among Mexican Women.

    PubMed

    Amadou, Amina; Biessy, Carine; Rinaldi, Sabina; Fedirko, Veronika; Assi, Nada; Lajous, Martin; Ortiz-Panozo, Eduardo; Yunes, Elsa; Lopez-Ridaura, Ruy; Torres-Mejia, Gabriela; Romieu, Isabelle

    2016-01-01

    Low circulating levels of vitamin D and high mammographic density (MD) have been associated with higher risk of breast cancer. Although some evidence suggested an inverse association between circulating vitamin D and MD, no studies have investigated this association among Mexican women. We examined whether serum 25-hydroxyvitamin D3 [25(OH)D3] levels were associated with MD in a cross-sectional study nested within the large Mexican Teacher's Cohort. This study included 491 premenopausal women with a mean age of 42.9 years. Serum 25(OH)D3 levels were measured by liquid chromatography/tandem mass spectrometry. Linear regression and non-linear adjusted models were used to estimate the association of MD with serum 25(OH)D3. Median serum 25(OH)D3 level was 27.3 (23.3-32.8) (ng/ml). Forty one (8%) women had 25(OH)D3 levels in the deficient range (< 20 ng/ml). Body mass index (BMI) and total physical activity were significantly correlated with 25(OH)D3 (r = -0.109, P = 0.019 and r = 0.095, P = 0.003, respectively). In the multivariable linear regression, no significant association was observed between 25(OH)D3 levels and MD overall. However, in stratified analyses, higher serum 25(OH)D3 levels (≥27.3 ng/ml) were significantly inversely associated with percent MD among women with BMI below the median (β = -0.52, P = 0.047). Although no significant association was observed between serum 25(OH)D3 and percent MD in the overall population, specific subgroups of women may benefit from higher serum 25(OH)D3 levels. PMID:27564705

  13. Role of 25-hydroxyvitamin D3 dose in determining rat 1,25-dihydroxyvitamin D3 production

    SciTech Connect

    Vieth, R.; McCarten, K.; Norwich, K.H. )

    1990-05-01

    To understand the relationships among (1) the dose of 25-hydroxyvitamin D (25(OH)D) in vivo, (2) the activity of 1-hydroxylase in renal mitochondria, and (3) the production of 1,25-dihydroxyvitamin D (1,25(OH)2D) in vivo, we gave rats different chronic or acute doses of 25-hydroxyvitamin D3 (25(OH)D3). We followed the metabolism of intracardially administered (25-hydroxy-26,27-methyl-3H)cholecalciferol (25(OH)(3H)D3) for 24 h before killing by measuring extracts of serum by chromatography. Specific activity of 1-hydroxylase in kidney was measured at death. In rats given 0-2,000 pmol 25(OH)D3 chronically by mouth, there was a dose-dependent decline in the percent of serum radioactivity made up of 1,25-dihydroxy-(26,27-methyl-3H)cholecalciferol (1,25(OH)2(3H)D3) as well as a decline in mitochondrial 1-hydroxylase, and these correlated significantly (r = 0.83, P less than 0.001). Serum %1,25(OH)2(3H)D3 in this experiment ranged from 0.8 to 42%. A small part of this range could be accounted for by a faster metabolic clearance rate (MCR) of 1,25(OH)2D3 from rats supplemented with 25(OH)D3 (MCR, 2.12 +/- 0.10 ml/min) compared with rats restricted in vitamin D (MCR, 0.94 +/- 0.06 ml/min, P less than 0.001). The activity of 1-hydroxylase was by far the major factor determining serum %1,25(OH)2(3H)D3. When different acute doses of 25(OH)D3 were given to rats with identical specific activities of 1-hydroxylase, the resulting 1,25(OH)2D3 concentrations in serum correlated with the 25(OH)D3 dose (r = 0.99, P less than 0.001). We conclude that the behavior of 1-hydroxylase in vivo is analogous to the classic behavior in vitro of an enzyme functioning below its Michaelis constant (Km). The amount of 1-hydroxylase present in renal mitochondria determines the fraction (not simply the quantity) of 25(OH)D metabolized to 1,25(OH)2D3 in vivo.

  14. 25-Hydroxyvitamin D3 Deficiency Independently Predicts Cognitive Impairment in Patients with Systemic Lupus Erythematosus

    PubMed Central

    Tay, Sen Hee; Ho, Chung Shun; Ho, Roger Chun-Man; Mak, Anselm

    2015-01-01

    Objectives Cognitive dysfunction has been reported in 20–80% of SLE patients. Converging evidence has indicated the importance of vitamin D as a neuroimmunomodulator for cognitive function. In this study, we evaluated the relationship between vitamin D and cognitive dysfunction. Methods Consecutive age- and gender-matched SLE patients and healthy controls (HCs) were administered Automated Neuropsychological Assessment Metrics in this cross-sectional study. The primary outcome was the total throughput score (TTS). Anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS). Levels of 25-hydroxyvitamin D [25(OH)D3 and total 25(OH)D] were measured using Liquid Chromatography-Tandem Mass Spectrometry. Results In total, 61 SLE patients and 61 HCs were studied. SLE patients scored significantly lower than HCs in the TTS (p = 0.004). There were no statistically significant differences in 25(OH)D3 levels, total 25(OH)D levels and total 25(OH)D deficiency between SLE patients and HCs. However, more SLE patients had 25(OH)D3 deficiency compared to HCs [12 (19.7%) versus 2 (3.3%), p = 0.003]. Deficiency of 25(OH)D3 (β = -63.667, SE = 27.456, p = 0.025), but not other vitamin D variables, independently predicted worse TTS after adjusting for age, education, gender, ethnicity, HADS-Total, duration of SLE, SELENA-SLEDAI, SLICC/ACR Damage Index and cumulative steroid dose in SLE patients. Age (β = -4.261, SE = 0.866, p < 0.001) was the only predictor of TTS after adjusting for education, gender, ethnicity, HADS-Total, vitamin D levels or status in HCs. Conclusions Deficiency of 25(OH)D3, a potentially modifiable risk factor, independently predicted cognitive impairment in SLE patients. PMID:26636681

  15. Regulation of Mycobacterium-specific mononuclear cell responses by 25-hydroxyvitamin D3.

    PubMed

    Nelson, Corwin D; Nonnecke, Brian J; Reinhardt, Timothy A; Waters, W Ray; Beitz, Donald C; Lippolis, John D

    2011-01-01

    The active vitamin D metabolite, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), has been shown to be an important regulator of innate and adaptive immune function. In addition, synthesis of 1,25(OH)(2)D(3) from 25-hydroxyvitamin D(3) (25(OH)D(3)) by the enzyme 1α-hydroxylase in monocytes upon activation by TLR signaling has been found to regulate innate immune responses of monocytes in an intracrine fashion. In this study we wanted to determine what cells expressed 1α-hydroxylase in stimulated peripheral blood mononuclear cell (PBMC) cultures and if conversion of 25(OH)D(3) to 1,25(OH)(2)D(3) in PBMC cultures regulated antigen-specific immune responses. Initially, we found that stimulation of PBMCs from animals vaccinated with Mycobacterium bovis (M. bovis) BCG with purified protein derivative of M. bovis (M. bovis PPD) induced 1α-hydroxylase gene expression and that treatment with a physiological concentration of 25(OH)D(3) down-regulated IFN-γ and IL-17F gene expression. Next, we stimulated PBMCs from M. bovis BCG-vaccinated and non-vaccinated cattle with M. bovis PPD and sorted them by FACS according to surface markers for monocytes/macrophages (CD14), B cells (IgM), and T cells (CD3). Sorting the PBMCs revealed that 1α-hydroxylase expression was induced in the monocytes and B cells, but not in the T cells. Furthermore, treatment of stimulated PBMCs with 25(OH)D(3) down-regulated antigen-specific IFN-γ and IL-17F responses in the T cells, even though 1α-hydroxylase expression was not induced in the T cells. Based on evidence of no T cell 1α-hydroxylase we hypothesize that activated monocytes and B cells synthesize 1,25(OH)(2)D(3) and that 1,25(OH)(2)D(3) down-regulates antigen-specific expression of IFN-γ and IL-17F in T cells in a paracrine fashion. PMID:21738762

  16. Tolerance evaluation of overdosed dietary levels of 25-hydroxyvitamin D3 in growing piglets.

    PubMed

    von Rosenberg, S J; Weber, G M; Erhardt, A; Höller, U; Wehr, U A; Rambeck, W A

    2016-04-01

    Forty-eight, cross-bred (GL × LW × P) piglets were used in a 42-day tolerance trial to assess the effects of feeding diets supplemented with vitamin D or increasing levels of 25-hydroxyvitamin D3 (25-OH-D3 ). Six-week-old piglets (24 castrate males, 24 females) were used. Two replicate groups of 6 piglets were randomized by weight and allocated to four dietary treatments. The control group (T1) was supplemented with 50 μg vitamin D3 /kg feed. The experimental groups received 25-OH-D3 at the recommended dose (T2: 50 μg/kg = 1x), at 250 μg/kg (T3: 5x) or at 500 μg/kg (T4: 10x) respectively. Feed intake and daily weight gain were measured weekly, and the animals were examined by a veterinarian daily. After 42 days, body mass, blood, urine, bone and tissue samples were analysed and a pathology examination conducted. Dietary treatments had no significant effect on final body mass or daily weight gain. The 25-OH-D3 plasma concentration in T1 was 17 ± 3 ng/ml (mean ± SD) while the respective values of the experimental groups were significantly increased in T2, T3 and T4. Tissue concentrations of 25-OH-D3 were higher in liver and muscle for T3 and T4 and in skin for T4 than in T1. However, neither gross pathology nor histology, nor blood and urine characteristics, nor bone parameters were affected by dietary treatments. Weight of organs as well as dry matter, ash and calcium content of kidneys remained unaffected by dietary 25-OH-D3 intake. Furthermore, no changes were observed for general indicators of health. The results of this study demonstrated that feeding piglets with 25-OH-D3 at 5 or 10 times the recommended level had no adverse effects on any of the biological parameters measured. It was concluded that 25-OH-D3 can be regarded as a supplement with a very high safety margin when used at the recommended level. PMID:26248819

  17. Tissue distribution of 7-dehydrocholesterol, vitamin D3 and 25-hydroxyvitamin D3 in several species of fishes.

    PubMed

    Takeuchi, A; Okano, T; Sayamoto, M; Sawamura, S; Kobayashi, T; Motosugi, M; Yamakawa, T

    1986-02-01

    A high-performance liquid chromatographic (HPLC) method for simultaneous determination of 7-dehydrocholesterol (7-DHC), vitamin D3 and 25-hydroxyvitamin D3 (25-OH-D3) in tissues of fishes was established, and using this method the tissue distribution of the sterols in lamprey (Entosphenus japonicus), great blue shark (Prionace glauca), skipjack (Katsuwonus pelamis) and albacore (Thunnus alalunga) was investigated. The results are summarized in the following: Although the alimentary canal, gall bladder and roe of lamprey and the alimentary canal of great blue shark contained comparatively high levels of 7-DHC (higher than 2,000 ng/wet tissue g), the other tissues of lamprey and great blue shark and all tissues of skipjack and albacore contained only low levels of 7-DHC (lower than 1,000 ng/g). There was no significant correlation between the levels of 7-DHC and vitamin D3. The contents of 7-DHC in the skin of skipjack and albacore were only 1/1,000 of those in the skin of rats. Although the contents of vitamin D3 in the liver of skipjack and albacore were extremely high (41,240 and 21,000 ng/g, respectively), those in the skin were very low (454 and 257 ng/g, respectively). 25-OH-D3 was detected in the viscera of skipjack, but the levels were not very high (lower than 150 ng/g). These levels were not significantly correlated with those of vitamin D3. The results suggest that large quantities of vitamin D3 in the liver of skipjack and albacore are supplied by other biosynthetic routes or by intake of vitamin D3 rather than by photochemical biosynthesis. PMID:3012050

  18. 1 alpha-hydroxyvitamin D3 plus 25-hydroxyvitamin D3 reduces parturient paresis in dairy cows fed high dietary calcium.

    PubMed

    Hodnett, D W; Jorgensen, N A; Deluca, H F

    1992-02-01

    The effectiveness of a combination of 1 alpha-hydroxyvitamin D3 and 25-hydroxyvitamin D3 for reducing incidence of parturient paresis in aged Holstein cows was tested. Intramuscular injection of .5 mg of 1 alpha-hydroxyvitamin D3 plus 4 mg of 25-hydroxyvitamin D3 increased plasma 1,25-dihydroxyvitamin D concentrations through parturition. Treatment with 1 alpha-hydroxyvitamin D3 plus 25-hydroxyvitamin D3 raised prepartum serum Ca approximately 2 mg/dl and prepartum serum P approximately 4 to 5 mg/dl higher than untreated controls. Both treated and control cows had approximately a 2-mg/dl decrease in serum Ca following parturition. The prepartum diet of alfalfa silage and hay was supplemented with a grain mixture supplying 100 g of Ca/d from ground limestone. Under these dietary conditions, incidence of parturient paresis was reduced from 33 to 8%. In a separate experiment, treatment with 1 alpha-hydroxyvitamin D3 plus 25-hydroxyvitamin D3 did not reduce incidence of parturient paresis when cows consumed mixed diets of different feed-stuff composition. Further experiments are required to determine specifically the factor or factors responsible for the difference in response to active vitamin D compound administration between the two experiments. Prepartum dietary Ca intake may be one such factor. PMID:1560144

  19. 25-Hydroxyvitamin D3-23-hydroxylase, a renal enzyme in several animal species.

    PubMed

    Engstrom, G W; Reinhardt, T A; Horst, R L

    1986-10-01

    The presence of 23,25-dihydroxyvitamin D3 has been demonstrated in vivo and in vitro by a number of laboratories. In order to evaluate the significance of 23-hydroxylation, renal 23-hydroxylase activity was compared to renal 24-hydroxylase activity in several species before and after treatment with 1,25-dihydroxyvitamin D3. The maximum activity of 23-hydroxylase varied widely among species. Treatment of animals with 1,25-dihydroxyvitamin D3 24 h and again 2 h prior to assay of renal tissue resulted in a 1.7- to 5.2-fold increase in 23-hydroxylase activity and a 3.8- to 20.6-fold increase in 24-hydroxylase activity compared to untreated controls. Maximum activity for both 23- and 24-hydroxylase required the enzyme substrate, 25-hydroxyvitamin D3, and an optimum concentration (30 mM) of an oxidizable substrate such as L-malate to supply the reducing equivalents of NADPH needed. Addition of 10 mumol of magnesium chloride resulted in 19 and 24% increases in activity for 23- and 24-hydroxylase, respectively. L-Malate supported the hydroxylation reactions better than succinate, alpha-ketoglutarate, or pyruvate. The apparent Km of calf renal 23-hydroxylase was 5.7 +/- 1.0 microM and of 24-hydroxylase, 2.0 +/- 0.2 microM. Apparent Km's for 23-hydroxylase varied from a low of 2.7 +/- 0.3 microM in the sheep to a high of 19.1 +/- 0.5 microM in the chick, and for 24-hydroxylase from 0.5 +/- 0.1 microM for the chick to 2.0 +/- 0.2 microM for the calf. Maximum velocity values (Vmax) ranged from 40 +/- 9 pmol/min/g for 23-hydroxylase in the chick to 396 +/- 92 in the calf, and for 24-hydroxylase from 108 +/- 89 pmol/min/g in the chick to 851 +/- 88 in the pig. These results help explain the in vivo metabolite concentrations and the predominance of the C(24)- over C(23)-oxidation pathways. Renal 23-hydroxylase was similar to 24-hydroxylase in that it was inhibited by carbon monoxide (63%), cyanide (51%), and antimycin (67%), required molecular oxygen, and functioned best at

  20. Serum 25-Hydroxyvitamin D3 Levels Are Associated With Breslow Thickness at Presentation and Survival From Melanoma

    PubMed Central

    Newton-Bishop, Julia A.; Beswick, Samantha; Randerson-Moor, Juliette; Chang, Yu-Mei; Affleck, Paul; Elliott, Faye; Chan, May; Leake, Susan; Karpavicius, Birute; Haynes, Sue; Kukalizch, Kairen; Whitaker, Linda; Jackson, Sharon; Gerry, Edwina; Nolan, Clarissa; Bertram, Chandra; Marsden, Jerry; Elder, David E.; Barrett, Jennifer H.; Bishop, D. Timothy

    2009-01-01

    Purpose A cohort study was carried out to test the hypothesis that higher vitamin D levels reduce the risk of relapse from melanoma. Methods A pilot retrospective study of 271 patients with melanoma suggested that vitamin D may protect against recurrence of melanoma. We tested these findings in a survival analysis in a cohort of 872 patients recruited to the Leeds Melanoma Cohort (median follow-up, 4.7 years). Results In the retrospective study, self-reports of taking vitamin D supplements were nonsignificantly correlated with a reduced risk of melanoma relapse (odds ratio = 0.6; 95% CI, 0.4 to 1.1; P = .09). Nonrelapsers had higher mean 25-hydroxyvitamin D3 levels than relapsers (49 v 46 nmol/L; P = .3; not statistically significant). In the cohort (prospective) study, higher 25-hydroxyvitamin D3 levels were associated with lower Breslow thickness at diagnosis (P = .002) and were independently protective of relapse and death: the hazard ratio for relapse-free survival (RFS) was 0.79 (95% CI, 0.64 to 0.96; P = .01) for a 20 nmol/L increase in serum level. There was evidence of interaction between the vitamin D receptor (VDR) BsmI genotype and serum 25-hydroxyvitamin D3 levels on RFS. Conclusion Results from the retrospective study were consistent with a role for vitamin D in melanoma outcome. The cohort study tests this hypothesis, providing evidence that higher 25-hydroxyvitamin D3 levels, at diagnosis, are associated with both thinner tumors and better survival from melanoma, independent of Breslow thickness. Patients with melanoma, and those at high risk of melanoma, should seek to ensure vitamin D sufficiency. Additional studies are needed to establish optimal serum levels for patients with melanoma. PMID:19770375

  1. Photoactivable analogs for labeling 25-hydroxyvitamin D3 serum binding protein and for 1,25-dihydroxyvitamin D3 intestinal receptor protein

    NASA Technical Reports Server (NTRS)

    Kutner, A.; Link, R. P.; Schnoes, H. K.; DeLuca, H. F.

    1986-01-01

    3-Azidobenzoates and 3-azidonitrobenzoates of 25-hydroxyvitamin D3 as well as 3-deoxy-3-azido-25-hydroxyvitamin D3 and 3-deoxy-3-azido-1,25-dihydroxyvitamin D3 were prepared as photoaffinity labels for vitamin D serum binding protein and 1,25-dihydroxyvitamin D3 intestinal receptor protein. The compounds prepared were easily activated by short- or long-wavelength uv light, as monitored by uv and ir spectrometry. The efficacy of the compounds to compete with 25-hydroxyvitamin D3 or 1,25-dihydroxyvitamin D3 for the binding site of serum binding protein and receptor, respectively, was studied to evaluate the vitamin D label with the highest affinity for the protein. The presence of an azidobenzoate or azidonitrobenzoate substituent at the C-3 position of 25-OH-D3 significantly decreased (10(4)- to 10(6)-fold) the binding activity. However, the labels containing the azido substituent attached directly to the vitamin D skeleton at the C-3 position showed a high affinity, only 20- to 150-fold lower than that of the parent compounds with their respective proteins. Therefore, 3-deoxy-3-azidovitamins present potential ligands for photolabeling of vitamin D proteins and for studying the structures of the protein active sites.

  2. 25-Hydroxyvitamin D3 Levels, BsmI Polymorphism and Insulin Resistance in Brazilian Amazonian Children

    PubMed Central

    Cobayashi, Fernanda; Hatzlhoffer Lourenço, Bárbara; Augusto Cardoso, Marly

    2015-01-01

    Vitamin D is associated with a wide range of other functions beyond bone development. We evaluated the factors associated with 25-hydroxyvitamin D levels in 974 children aged ≤10 years and the impact of BsmI polymorphism of the vitamin D receptor (VDR) gene (rs1544410) on metabolic parameters in a subsample (n: 430) with a follow-up 2 years later from the initial population-based cross-sectional study. Multiple linear regression models were used in the analyses. The prevalence (95% CI) of vitamin D deficiency, insufficiency and sufficiency of children was 11.1% (9.2–13.2), 21.8% (19.2–24.5) and 67.2% (64.1–70.1), respectively. Overall, 23% of the variation in serum 25-hydroxyvitamin D concentrations was accounted for by BsmI polymorphism β = −0.053 (95% CI) (−0.100, −0.006), maternal schooling (≥9 years) β = 0.100 (0.039, 0.161), serum vitamin E β = 0.478 (0.381, 0.574), total cholesterol concentration β = 0.232 (0.072, 0.393) and serum folate β = 0.064 (0.013, 0.115). BsmI polymorphism was positively associated with HOMA-IR β = 0.122 (0.002, 0.243) and fasting glucose concentration β = 1.696 (0.259, 3.133). In conclusion, variables related to socioeconomic level, the presence of the allele risk for BsmI and other nutrient concentrations were associated with serum 25-hydroxyvitamin D concentrations. Our results suggest that BsmI polymorphism is correlated with metabolic outcomes. PMID:26047339

  3. Isolation and identification of vitamin D3, 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and 1,24,25-trihydroxyvitamin D3 in Solanum malacoxylon incubated with ruminal fluid.

    PubMed

    Skliar, M I; Boland, R L; Mourino, A; Tojo, G

    1992-12-01

    It has been shown that Solanum malacoxylon contains 1 alpha,25-dihydroxyvitamin D3-glycoside. The presence of vitamin D3 and 25-hydroxyvitamin D3 has also been suggested. In the present study vitamin D3 and three of its metabolites, including 1 alpha,25-dihydroxyvitamin D3, were detected in plant leaf extracts preincubated with ruminal fluid (SMRF). Extraction of SMRF with non-polar organic solvents and purification of the lipid extract by TLC followed by HPLC yielded nine ultraviolet-absorbing (264 nm) peaks. Four of them comigrated on a Zorbax-Sil HPLC column with synthetic standards of vitamin D3, 25-hydroxyvitamin D3, 1 alpha,25-dihydroxyvitamin D3 and 1,24R,25-trihydroxyvitamin D3, respectively. These compounds were unequivocally identified by means of mass spectrometry. The results confirm that Solanum malacoxylon contains, in addition to 1 alpha,25-dihydroxyvitamin D3, vitamin D3, 25-hydroxyvitamin D3 and possibly other as yet unidentified derivatives. As 1,24,25-trihydroxyvitamin D3 is absent in plant extracts not incubated with ruminal fluid, the data also indicate that rumen microbes may convert 1 alpha,25-dihydroxyvitamin D3 into 1,24,25-trihydroxyvitamin D3. PMID:1335278

  4. Primary Human Osteoblasts in Response to 25-Hydroxyvitamin D3, 1,25-Dihydroxyvitamin D3 and 24R,25-Dihydroxyvitamin D3

    PubMed Central

    van der Meijden, Karen; Lips, Paul; van Driel, Marjolein; Heijboer, Annemieke C.; Schulten, Engelbert A. J. M.; den Heijer, Martin; Bravenboer, Nathalie

    2014-01-01

    The most biologically active metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has well known direct effects on osteoblast growth and differentiation in vitro. The precursor 25-hydroxyvitamin D3 (25(OH)D3) can affect osteoblast function via conversion to 1,25(OH)2D3, however, it is largely unknown whether 25(OH)D3 can affect primary osteoblast function on its own. Furthermore, 25(OH)D3 is not only converted to 1,25(OH)2D3, but also to 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) which may have bioactivity as well. Therefore we used a primary human osteoblast model to examine whether 25(OH)D3 itself can affect osteoblast function using CYP27B1 silencing and to investigate whether 24R,25(OH)2D3 can affect osteoblast function. We showed that primary human osteoblasts responded to both 25(OH)D3 and 1,25(OH)2D3 by reducing their proliferation and enhancing their differentiation by the increase of alkaline phosphatase, osteocalcin and osteopontin expression. Osteoblasts expressed CYP27B1 and CYP24 and synthesized 1,25(OH)2D3 and 24R,25(OH)2D3 dose-dependently. Silencing of CYP27B1 resulted in a decline of 1,25(OH)2D3 synthesis, but we observed no significant differences in mRNA levels of differentiation markers in CYP27B1-silenced cells compared to control cells after treatment with 25(OH)D3. We demonstrated that 24R,25(OH)2D3 increased mRNA levels of alkaline phosphatase, osteocalcin and osteopontin. In addition, 24R,25(OH)2D3 strongly increased CYP24 mRNA. In conclusion, the vitamin D metabolites 25(OH)D3, 1,25(OH)2D3 and 24R,25(OH)2D3 can affect osteoblast differentiation directly or indirectly. We showed that primary human osteoblasts not only respond to 1,25(OH)2D3, but also to 24R,25(OH)2D3 by enhancing osteoblast differentiation. This suggests that 25(OH)D3 can affect osteoblast differentiation via conversion to the active metabolite 1,25(OH)2D3, but also via conversion to 24R,25(OH)2D3. Whether 25(OH)D3 has direct actions on osteoblast function needs further

  5. Conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 in renal slices from the rat

    SciTech Connect

    Armbrecht, H.J.; Zenser, T.V.; Davis, B.B.

    1981-07-01

    Isolated renal cortical slices were used to study the conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25)(OH2)D3) by the rat kidney. Production of 1,25-(OH)2D3 and 24,25-(OH)2D3 was linear with time (30-90 min) and tissue weight (40-250 mg). Production of 1,25-(OH)2D3 was greatest (134 +/- 17 pg/mg tissue.h) in animals fed a low calcium, vitamin D-deficient diet. The greatest 24,25-(OH)2D3 production (106 +/- 17 pg/mg tissue.h) was seen in animals fed a high calcium, vitamin D-replete diet, 1,25-(OH)2D3 production was reduced to 23% of maximum by the addition of 1.2% calcium or 0.8% strontium to the vitamin D-deficient, low calcium diet. Production of 1,25-(OH)2D3 and 24,25-(OH)2D3 was greatly reduced in renal cortical slices that had been heated before incubation. Slices of renal medulla produced only small amounts of 1,25-(OH)2D3 compared to slices of renal cortex. These studies provide direct evidence for the production of 1,25-(OH)2D3 and 24,25-(OH)2D3 by the mammalian renal cortex. They also demonstrate that this production may be modulated by dietary calcium, strontium, and vitamin D.

  6. Effects of vitamin D3, 25-hydroxyvitamin D3, and 24,25-dihydroxyvitamin D3 on parathyroid hormone secretion.

    PubMed

    Cantley, L K; Russell, J B; Lettieri, D S; Sherwood, L M

    1987-07-01

    The active vitamin D metabolite 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] causes marked suppression of both pre-proparathyroid hormone messenger RNA (pre-proPTH mRNA) and parathyroid hormone (PTH) secretion. These effects are dose dependent and reversible when tested in an in vitro primary tissue culture cell system using normal bovine parathyroid cells. In the current studies, the precursors of 1,25(OH)2D3 and the related metabolite 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], were used in the same culture system to test for possible regulatory effects. The results were compared with identically prepared cells exposed to 1,25(OH)2D3. In short-term studies (30-120 minutes), none of the vitamin D-related compounds produced any effect on PTH secretion. In long-term studies (24-48 hours, using primary tissue culture in the presence of test agents), neither vitamin D3 nor 25(OH)D3 affected PTH secretion or pre-proPTH mRNA over the concentration range 10(-11)-10(-7) M. On the other hand, 24,25(OH)2D3 produced significant suppression of both pre-proPTH mRNA (77% of control, P less than .01) and PTH secretion (75% of control, P less than .005) at 10(-7) M. By comparison, 10(-11) M 1,25(OH)2D3 produced levels of suppression (25-30%) of both pre-proPTH mRNA and PTH secretion comparable to 10(-7) M 24,25(OH)2D3, while even greater suppression (40-50%) occurred at 10(-9)-10(-7) M 1,25(OH)2D3. From these studies, we conclude that vitamin D3 and 25(OH)D3 do not have significant effects on PTH synthesis and secretion over the range of doses tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3040201

  7. Variations in cord 25-hydroxyvitamin D levels in Hispanic and Caucasian infants are not related to neonatal bone mineral status

    Technology Transfer Automated Retrieval System (TEKTRAN)

    At birth, an infant’s vitamin D status, as assessed by 25-hydroxyvitamin D level (25-OHD), is dependent on the 25-OHD status of the mother. There are few data regarding 25-OHD in Hispanic infants and the relationship between 25-OHD and bone mineral outcomes. To evaluate the range of 25-OHD in Hispan...

  8. Effects of different doses of testosterone on gonadotropins, 25-hydroxyvitamin D3, and blood lipids in healthy men

    PubMed Central

    Gårevik, Nina; Rane, Anders; Björkhem-Bergman, Linda; Ekström, Lena

    2014-01-01

    Aims To study the effect and time profile of different doses of testosterone enanthate on the blood lipid profile and gonadotropins. Experimental design Twenty-five healthy male volunteers aged 27–43 years were given 500 mg, 250 mg, and 125 mg of testosterone enanthate as single intramuscular doses of Testoviron® Depot. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), blood lipid profile (total cholesterol, plasma [p-] low-density lipoprotein, p-high-density lipoprotein [HDL], p-apolipoprotein A1 [ApoA1], p-apolipoprotein B, p-triglycerides, p-lipoprotein(a), serum [s-] testosterone, and 25-hydroxyvitamin D3) were analyzed prior to, and 4 and 14 days after dosing. Testosterone and epitestosterone in urine (testosterone/epitestosterone ratio) were analyzed prior to each dose after a washout period of 6–8 weeks. Results and discussion All doses investigated suppressed the LH and FSH concentrations in serum. LH remained suppressed 6 weeks after the 500 mg dose. These results indicate that testosterone has a more profound endocrine effect on the hypothalamic–pituitary–gonadal axis than was previously thought. There was no alteration in 25-hydroxyvitamin D3 levels after testosterone administration compared to baseline levels. The 250 and 500 mg doses induced decreased concentrations of ApoA1 and HDL, whereas the lowest dose (125 mg) did not have any effect on the lipid profile. Conclusion The single doses of testosterone produced a dose-dependent increase in serum testosterone concentrations together with suppression of s-LH and s-FSH. Alterations in ApoA1 and HDL were observed after the two highest single doses. It is possible that long-time abuse of anabolic androgenic steroids will lead to alteration in vitamin D status. Knowledge and understanding of the side effects of anabolic androgenic steroids are important to the treatment and care of abusers of testosterone. PMID:25525405

  9. Blood mineral, hormone, and osteocalcin responses of multiparous Jersey cows to an oral dose of 25-hydroxyvitamin D3 or vitamin D3 before parturition.

    PubMed

    Taylor, M S; Knowlton, K F; McGilliard, M L; Seymour, W M; Herbein, J H

    2008-06-01

    Twenty-seven multiparous Jersey cows were randomly assigned to receive an oral bolus containing corn starch (control, CON), corn starch plus 15 mg of 25-hydroxyvitamin D(3) (25-OH), or 15 mg of cholecalciferol (D(3)) at 6 d before expected parturition. Cows were maintained in individual box stalls from 20 d before expected parturition and fed a common diet. Jugular blood samples were collected at -14, -13, -5, -4, -3, -2, -1 d before expected calving, at calving, and at 1, 3, 5, 7, 9, 11, 13, 28, 56, and 84 d postcalving. After calving, cows were housed in 1 pen in a free-stall barn and consumed a common diet. Colorimetric assays were used to analyze Ca, P, and Mg concentrations in serum. Serum concentrations of osteocalcin (OC), an indicator of bone formation, serum 25-hydroxyvitamin D(3), and parathyroid hormone (PTH) were determined in samples obtained from d -5 through d 13. The 9 control multiparous cows and 5 untreated primiparous cows were used to evaluate the effect of parity on the variables that were measured. There was no effect of parity on Ca, PTH, or 25-OH concentration. Compared with second-lactation cows and older cows (>2 lactations), first-lactation cows had greater serum OC (22.3, 32.0, and 48.3 ng/mL, respectively), indicating that younger animals were forming more bone. Blood Ca, P, and Mg decreased near the time of calving and then increased over time. Serum 25-hydroxyvitamin D(3) was greater for cows dosed with 25-OH (119.0 ng/mL) compared with those dosed with D(3) (77.5 ng/mL) or CON (69.3 ng/mL). Cows dosed with 25-OH tended to have lower serum PTH concentration, but treatments did not affect serum Ca, P, or Mg. Serum OC was greater in second-lactation cows compared with cows entering their third or fourth lactation but OC was unaffected by treatment. Although results indicated a 60% increase in serum 25-hydroxyvitamin D(3) due to a single oral dose of 25-OH before calving, the amount administered in this study apparently was not

  10. Model-based meta-analysis for development of a population-pharmacokinetic (PPK) model for Vitamin D3 and its 25OHD3 metabolite using both individual and arm-level data.

    PubMed

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

    2016-04-01

    Clinical studies investigating relationships between D3 and 25OHD3 vary in dosing regimen, assays, demographics, and control of exogenous D3. This leads to uncertain and conflicting exposure-related associations with D3 and 25OHD3. To elucidate this parent-metabolite system, a PPK model was developed to predict mean D3 and 25OHD3 exposure from varied doses and administration routes. Sources of exposure variability related to metabolite baseline, weight, and assay type were explored. Specific search criteria were used in PUBMED to identify public source PK data pertaining to D3 and 25OHD3 in healthy or osteoporotic populations. Overall 57 studies representing 5395 individuals were selected, including 25 individual-level profiles and treatment-arm data. IV, oral, single and multiple dose data were used, with D3 and 25OHD3 dosing. A nonlinear mixed effects model was developed to simultaneously model PK dispositions of D3 and 25OHD3 (NONMEM v7.2), which were described by 2-compartment models with nonlinear and linear clearances, respectively. Proportional and additive assay variances were included on the 25OHD3 prediction. Unit-level random effects were weighted by treatment-arm size. D3 model estimates, relative to bioavailability were: maximum rate of metabolism ([Formula: see text], 1.62 nmol/h), Michaelis-Menten constant ([Formula: see text], 6.39 nmol/L), central volume of distribution ([Formula: see text], 15.5 L), intercompartmental clearance ([Formula: see text], 0.185 L/h), peripheral volume of distribution ([Formula: see text], 2333 L/h), and baseline concentration ([Formula: see text], 3.75 nmol/L). For 25OHD3 ([Formula: see text] = metabolite): [Formula: see text] = 0.0153 L/h, [Formula: see text] = 4.35 L, [Formula: see text] = 6.87 L, [Formula: see text] = 0.0507 L/h. Simulations of 25OHD3 concentration indicated an inverse relationship between 25OHD3 baseline and response, as well as a less than proportional 25OHD3 response. Estimation of assay bias

  11. Simultaneous Quantification of 25-Hydroxyvitamin D3 and 24,25-Dihydroxyvitamin D3 in Rats Shows Strong Correlations between Serum and Brain Tissue Levels.

    PubMed

    Xue, Ying; He, Xin; Li, Huan-De; Deng, Yang; Yan, Miao; Cai, Hua-Lin; Tang, Mi-Mi; Dang, Rui-Li; Jiang, Pei

    2015-01-01

    While vitamin D3 is recognized as a neuroactive steroid affecting both brain development and function, efficient analytical method in determining vitamin D3 metabolites in the brain tissue is still lacking, and the relationship of vitamin D3 status between serum and brain remains elusive. Therefore, we developed a novel analysis method by using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to simultaneously quantify the concentrations of 25-hydroxyvitamin D3 (25(OH)D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) in the serum and brain of rats fed with different dose of vitamin D3. We further investigated whether variations of serum vitamin D3 metabolites could affect vitamin D3 metabolite levels in the brain. Serum and brain tissue were analyzed by HPLC-MS/MS with electrospray ionization following derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD). The method is highly sensitive, specific, and accurate to quantify 25(OH)D3 and 24,25(OH)2D3 in animal brain tissue. Vitamin D3 metabolites in brain tissue were significantly lower in rats fed with a vitamin D deficiency diet than in rats fed with high vitamin D3 diet. There was also a strong correlation of vitamin D3 metabolites in serum and brain. These results indicate that vitamin D3 status in serum affects bioavailability of vitamin D3 metabolites in the brain. PMID:26713090

  12. Simultaneous Quantification of 25-Hydroxyvitamin D3 and 24,25-Dihydroxyvitamin D3 in Rats Shows Strong Correlations between Serum and Brain Tissue Levels

    PubMed Central

    Xue, Ying; He, Xin; Li, Huan-De; Deng, Yang; Yan, Miao; Cai, Hua-Lin; Tang, Mi-Mi; Dang, Rui-Li; Jiang, Pei

    2015-01-01

    While vitamin D3 is recognized as a neuroactive steroid affecting both brain development and function, efficient analytical method in determining vitamin D3 metabolites in the brain tissue is still lacking, and the relationship of vitamin D3 status between serum and brain remains elusive. Therefore, we developed a novel analysis method by using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to simultaneously quantify the concentrations of 25-hydroxyvitamin D3 (25(OH)D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) in the serum and brain of rats fed with different dose of vitamin D3. We further investigated whether variations of serum vitamin D3 metabolites could affect vitamin D3 metabolite levels in the brain. Serum and brain tissue were analyzed by HPLC-MS/MS with electrospray ionization following derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD). The method is highly sensitive, specific, and accurate to quantify 25(OH)D3 and 24,25(OH)2D3 in animal brain tissue. Vitamin D3 metabolites in brain tissue were significantly lower in rats fed with a vitamin D deficiency diet than in rats fed with high vitamin D3 diet. There was also a strong correlation of vitamin D3 metabolites in serum and brain. These results indicate that vitamin D3 status in serum affects bioavailability of vitamin D3 metabolites in the brain. PMID:26713090

  13. Summer/winter differences in the serum 25-hydroxyvitamin D3 and parathyroid hormone levels of Japanese women

    NASA Astrophysics Data System (ADS)

    Nakamura, K.; Nashimoto, Mitsue; Yamamoto, Masaharu

    Serum 25-hydroxyvitamin D3 [25(OH)D3] is produced in the skin in response to exposure to ultraviolet radiation, and is a good indicator of vitamin D nutritional status. The aim of this study was to determine summer/winter differences in serum 25(OH)D3 and parathyroid hormone (PTH) in Japanese women and how the summer and winter values are related. The subjects were 122 healthy Japanese women aged 45-81 years (average age: 65.7 years). They were medically examined twice, in September 1997 and February 1999. Serum 25(OH)D3 and intact PTH were determined by high-performance liquid chromatography and a two-site immunoradiometric assay respectively. Lifestyle information was obtained through an interview. The seasonal differences (winter minus summer) in 25(OH)D325(OH)D3] and intact PTH concentrations were -18.8 nmol/l (SD 19.2, P<0.0001) and 0.98pmol/l (SD 1.02, P<0.0001) respectively. The correlation coefficient between summer (x) and winter (y) 25(OH)D3 levels was 0.462 (P<0.0001), with a linearly fitted line of y=0.42x+26.4. This relationship was interpreted as subjects with higher summer 25(OH)D3 values having greater reductions in winter 25(OH)D3 concentrations. There were inter-individual differences in Δ25(OH)D3, although the summer and winter 25(OH)D3 concentrations were well-correlated. Since Δ25(OH)D3 was not associated with any of the lifestyle factors, seasonal differences in the 25(OH)D3 concentrations of an individual appeared to reflect her ability to produce 25(OH)D3 photochemically in the skin. Sun bathing would be a less effective means of attaining adequate vitamin D nutritional status in a person with a small seasonal difference in 25(OH)D3, i.e., one with a low 25(OH)D3 level.

  14. Differential expression of cytokines in response to respiratory syncytial virus infection of calves with high or low circulating 25-hydroxyvitamin D3

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Deficiency of serum levels of 25-hydroxyvitamin D3 has been related to increased risk of lower respiratory tract infections (LRTI) in children. Respiratory syncytial virus (RSV) is the leading cause of LRTI in infants and young children. The neonatal calf model of RSV infection shares many features ...

  15. Use of 25-hydroxyvitamin D3 and vitamin E to improve tenderness of beef from the longissimus dorsi of heifers.

    PubMed

    Carnagey, K M; Huff-Lonergan, E J; Trenkle, A; Wertz-Lutz, A E; Horst, R L; Beitz, D C

    2008-07-01

    The objective of this trial was to determine whether a single bolus of 25-hydroxyvitamin D(3) (25-OH D(3)), vitamin E, or a combination of the 2 would improve the tenderness of steaks from the LM of beef heifers. Forty-eight Angus crossbred heifers were allotted randomly to 8 pens. Six heifers were in each pen, and there were 2 pens per treatment. The 4 treatments included control (no 25-OH D(3) or vitamin E); 25-OH D(3) (500 mg of 25-OH D(3) administered as a one-time oral bolus 7 d before slaughter); vitamin E (1,000 IU of vitamin E administered daily as a top-dress for 104 d before slaughter); or combination (500 mg of 25-OH D(3) administered as a one-time oral bolus 7 d before slaughter and 1,000 IU of vitamin E administered daily as a top-dress for 104 d before slaughter). Blood samples were obtained on the day that heifers were allotted to treatments, on the day 25-OH D(3) was administered, and on the day before slaughter. Plasma calcium concentration was increased when 25-OH D(3) was administered with or without vitamin E (P < 0.007). In LM, calcium concentration tended to increase (P = 0.10) when 25-OH D(3) was administered alone but not when 25-OH D(3) was administered with vitamin E. Concentrations of 25-OH D(3) and 1,25-dihydroxyvitamin D(3) in plasma were increased when 25-OH D(3) was administered with or without vitamin E (P < 0.001). Steaks from heifers treated with 25-OH D(3) or vitamin E, but not both, tended to have lower Warner-Bratzler shear force than steaks in the control group at 14 d postmortem (P = 0.08). Postmortem protein degradation as measured by Western blot of the 30-kDa degradation product of troponin-T was increased with all treatments after 3 d postmortem (P D(3) fed as an oral bolus 7 d before slaughter or 1,000 IU of vitamin E administered daily for 104 d before slaughter alone, but not in combination, effectively decreased Warner-Bratzler shear

  16. Use of 25-hydroxyvitamin D3 and dietary calcium to improve tenderness of beef from the round of beef cows.

    PubMed

    Carnagey, K M; Huff-Lonergan, E J; Lonergan, S M; Trenkle, A; Horst, R L; Beitz, D C

    2008-07-01

    The objective of this trial was to determine how 25-hydroxyvitamin D(3) (25-OH D(3)) supplementation, altering supplemental dietary calcium, or their combination influence postmortem biochemical and tenderness changes in muscles from the round of mature cows. Twenty-seven Angus cows (3 to 7 yr old) were allotted randomly to 9 pens with 3 cows per pen. Treatments were arranged in a 3 x 3 factorial design with 3 dosages of 25-OH D(3) (0, 250, or 500 mg of 25-OH D(3) administered as a 1-time oral bolus 7 d before slaughter) and 3 percentages of supplemental limestone (0.5, 0.75, and 1.0%) replenished in the diet for 3 d before slaughter and after a 2-wk limestone withdrawal. Plasma samples were obtained during the feeding period. Upon slaughter, adductor, gracilus, pectineus, sartorius, semimembranosus, vastus intermedius, and vastus lateralis muscles were obtained and aged for 1, 3, or 7 d. Calcium concentrations were increased in plasma when 250 or 500 mg of 25-OH D(3) were administered (P D(3) were administered. Concentrations of 25-OH D(3) in meat and in plasma and 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2) D(3)] in plasma were increased when 25-OH D(3) was administered (P D(3) or 1,25-(OH)(2) D(3) in meat or in plasma. Calpastatin activity was affected by treatments only in the gracilus and vastus intermedius muscles (P D(3) has some influence on muscle characteristics known to improve tenderness, but improved tenderness was not observed. PMID:18344286

  17. Exploratory Metabolomics Profiling in the Kainic Acid Rat Model Reveals Depletion of 25-Hydroxyvitamin D3 during Epileptogenesis

    PubMed Central

    Heischmann, Svenja; Quinn, Kevin; Cruickshank-Quinn, Charmion; Liang, Li-Ping; Reisdorph, Rick; Reisdorph, Nichole; Patel, Manisha

    2016-01-01

    Currently, no reliable markers are available to evaluate the epileptogenic potential of a brain injury. The electroencephalogram is the standard method of diagnosis of epilepsy; however, it is not used to predict the risk of developing epilepsy. Biomarkers that indicate an individual’s risk to develop epilepsy, especially those measurable in the periphery are urgently needed. Temporal lobe epilepsy (TLE), the most common form of acquired epilepsy, is characterized by spontaneous recurrent seizures following brain injury and a seizure-free “latent” period. Elucidation of mechanisms at play during epilepsy development (epileptogenesis) in animal models of TLE could enable the identification of predictive biomarkers. Our pilot study using liquid chromatography-mass spectrometry metabolomics analysis revealed changes (p-value ≤ 0.05, ≥1.5-fold change) in lipid, purine, and sterol metabolism in rat plasma and hippocampus during epileptogenesis and chronic epilepsy in the kainic acid model of TLE. Notably, disease development was associated with dysregulation of vitamin D3 metabolism at all stages and plasma 25-hydroxyvitamin D3 depletion in the acute and latent phase of injury-induced epileptogenesis. These data suggest that plasma VD3 metabolites reflect the severity of an epileptogenic insult and that a panel of plasma VD3 metabolites may be able to serve as a marker of epileptogenesis. PMID:27526857

  18. Significance of serum 25-hydroxyvitamin D3 and interleukin-6 levels in immunoglobulin treatment of Kawasaki disease in children

    PubMed Central

    An, Xinjiang; Fu, Mingyu; Tian, Jing; Xue, Ying; Xu, Hui

    2016-01-01

    The aim of the study was to investigate the significance of the level of serum 25-hydroxyvitamin D3 [25-(OH)D3] and interleukin (IL)-6 in serum prior to and after immunoglobulin treatment in children suffering from Kawasaki disease in order to provide a reference for the successful treatment of Kawasaki disease in children. From February, 2013 to February, 2015, 45 patients with Kawasaki disease were enrolled in the observation group. The normal control group comprised 43 healthy volunteers and the feverish control group 46 patients with respiratory infection and fever. Venous blood was collected from each case before and after immunoglobulin treatment and the level of 25-(OH)D3 and IL-6 in the serum were measured using fluorescent quantitative PCR, enzyme-linked immunosorbent assay and western blotting. Before treatment, the level of 25-(OH)D3 in the feverish control group was significantly lower than that of the normal control group, while the level of 25-(OH)D3 in the observation group was significantly higher than that of the normal control group. The level of 25-(OH)D3 in the feverish control group was lower than the IL-6 level in the normal children, but the difference was not statistically significant (P>0.05). The level 25-(OH)D3 in the observation group was significantly higher than the IL-6 level in the normal control group. The serum content of 25-(OH)D3 was significantly higher after the treatment compared to before treatment levels and after treatment IL-6 level was only slightly lower. It was observed that the 25-(OH)D3 level in the observation group was significantly increased after immunoglobulin treatment and this was positively correlated with the effects of the treatment. The IL-6 level had no significant changes after treatment and had little correlation with the treatment effect. The results suggested that 25-(OH)D3 may be involved in the occurrence of Kawasaki disease in children and in the aggravation of the disease to some extent. PMID

  19. A Randomised, Cross-Over Study to Estimate the Influence of Food on the 25-Hydroxyvitamin D3 Serum Level after Vitamin D3 Supplementation

    PubMed Central

    Cavalier, Etienne; Jandrain, Bernard; Coffiner, Monte; Da Silva, Stéphanie; De Niet, Sophie; Vanderbist, Francis; Souberbielle, Jean-Claude

    2016-01-01

    Vitamin D3 is known to be liposoluble and its release could be a factor limiting the rate of absorption. It was presumed that the presence of fat could favor absorption of vitamin D3. However, as bioavailability is related not only to the active molecules but also to the formulations and excipients used, the optimization of the pharmaceutical form of vitamin D3 is also important. The objective of this study was to evaluate if there is a food effect on absorption when a high dose of vitamin D3 is completely solubilized in an oily solution. In the present cross-over study, 88 subjects were randomized and received a single dose of 50,000 IU of vitamin D3 in fasting state or with a standardized high-fat breakfast. Assessment of serum concentrations of 25 hydroxyvitamin D3 (25(OH)D3) was performed three, five, seven, 14, 30 and 60 days after supplementation. In fed and fast conditions, the 25(OH)D3 serum concentrations were significantly higher than the baseline value three days after administration and remained significantly higher during the first month. No significant difference between fasting vs. fed conditions was observed. It is therefore concluded that the vitamin D3 absorption from an oily solution was not influenced by the presence or absence of a meal. PMID:27213447

  20. Calcium absorption is not consistently enhanced by maintaining serum 25-hydroxyvitamin D levels > 50 or 80 nmol/L

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing serum 25-hydroxyvitamin D (25-OHD) in adults may enhance calcium absorption (Ca-abs). Targeting of 25-OHD values for the entire population has been widely advocated recently with goals of 25-OHD of at least 50 or 80 nmol/L advocated. There are few pediatric data that relate 25-OHD to Ca-a...

  1. Distribution of hydroxylated vitamin D metabolites [25OHD3 and 1,25(OH)2D3] in domestic pigs: evidence that 1,25(OH)2D3 is stored outside the blood circulation?

    PubMed

    Rungby, J; Mortensen, L; Jakobsen, K; Brock, A; Mosekilde, L

    1993-03-01

    1. The distribution of 25-hydroxycholecalciferol (25OHD3) and 1,25-dihydroxycholecalciferol [1,25(OH)2D3] in various organs from domestic pigs was examined by HPLC. 2. Plasma levels of both metabolites corresponded to those found in healthy human subjects. 3. Tissue concentrations of 25OHD3 in fat, kidney, liver, and intestinal mucosa were low (< 1/3 of plasma levels), whereas tissue concentrations of 1,25(OH)2D3 exceeded plasma levels by factors 3-7, adipose tissue concentrations being the highest. 4. Substantial amounts of activated vitamin D are stored outside the blood-streams and may actively participate in vitamin D and calcium homeostasis. PMID:8097149

  2. Differences in metabolic parameters and gene expression related to osteochondrosis/osteoarthrosis in pigs fed 25-hydroxyvitamin D3.

    PubMed

    Jefferies, David; Farquharson, Colin; Thomson, Jill; Smith, William; Seawright, Elaine; McCormack, Heather; Whitehead, Colin

    2002-01-01

    Osteochondrosis/osteoarthrosis (OC/OA) are common terms for various joint pathologies that occur in pigs. Pathologies that may contribute to these disorders have been described, but the primary cause(s) remain unknown. We hypothesised that as OC has some similarities to dyschondroplasia, which involves a failure of growth plate chondrocytes to fully differentiate and hypertrophy, treatment with 25-hydroxyvitamin D3 (25-D) might reduce the incidence and/or severity of lesions in pigs, as it does in chickens with dyschondroplasia. Control pigs were fed a commercial diet ad libitum. In the treated group this diet was supplemented with 25-D at 0.1 mg/kg. Ten pigs from each of the control and treated groups were sampled at 7, 12, 16 and 21 weeks. Treatment with 25-D had no effect on the incidence or severity of OC/OA lesions. Cartilage dry weight, total collagen content and proteoglycan content, and plasma levels oftotal calcium, inorganic phosphorous, vitamin C, insuline-like growth factor-I, parathyroid hormone and tumour necrosis factor alpha were unaffected by treatment. In addition, none of these parameters were correlated with the incidence or severity of OC/OA lesions. The mRNA expression levels of 21 out of 23 genes assayed by RT-PCR were unaltered in articular cartilage from OA lesion samples as compared to normal articular cartilage. However, collagen type II was reduced and collagen type X increased in OA lesion and near lesion samples. These results suggest that OA in pigs may share some features of osteoarthritis in other mammalian species. PMID:12199365

  3. Plasma levels of 25-hydroxyvitamin D3 and in vivo markers of cytochrome P450 3A activity in Swedes and Koreans: effects of a genetic polymorphism and oral contraceptives.

    PubMed

    Nylén, Hanna; Björkhem-Bergman, Linda; Ekström, Lena; Roh, Hyung-Keun; Bertilsson, Leif; Eliasson, Erik; Lindh, Jonatan D; Diczfalusy, Ulf

    2014-10-01

    In vitro studies have shown that vitamin D may induce several cytochrome P450 (CYP) enzymes in general and CYP3A4 in particular. The primary aim of this study was to investigate the relationship between plasma levels of 25-hydroxyvitamin D3 and suggested in vivo markers of CYP3A activity in healthy volunteers from Sweden and Korea. Plasma concentrations of 25-hydroxyvitamin D3 were analysed in samples from three previously performed studies, and the correlation between these levels and suggested in vivo markers of CYP3A activity was investigated by means of nonparametric correlation. In addition, we studied the modulating effects of three vitamin D receptor promoter polymorphisms on the association between 25-hydroxyvitamin D3 and CYP3A enzyme activity in Swedish subjects. The plasma levels of 25-hydroxyvitamin D3 were not significantly associated with CYP3A phenotypes in any of the three studies, but after accounting for the vitamin D receptor polymorphism rs4516035, there was a significant positive association between 25-hydroxyvitamin D3 and CYP3A activity (p = 0.004). Swedes (n = 65) had significantly higher 25-hydroxyvitamin D3 levels than Koreans (n = 67), 75 nM compared with 31 nM (p < 0.001). Swedish women taking oral contraceptives (OC) (n = 19) had somewhat higher plasma levels of 25-hydroxyvitamin D3 compared with Swedish women not taking oral contraceptives (n = 21), 89 and 72 nM, respectively (p = 0.02). In conclusion, our results suggest that the overall influence on the CYP3A activity by 25-hydroxyvitamin D3 is of marginal importance. PMID:24655660

  4. Comparative evaluation of new Cookson-type reagents for LC/ESI-MS/MS assay of 25-hydroxyvitamin D3 in neonatal blood samples.

    PubMed

    Ogawa, Shoujiro; Kittaka, Hiroki; Shinoda, Kenta; Ooki, Satoshi; Nakata, Akiho; Higashi, Tatsuya

    2016-06-01

    The screening of vitamin D deficiency in neonatal infants, which is based on the blood 25-hydroxyvitamin D3 [25(OH)D3 ] quantification, is important for the early detection, diagnosis and health risk assessment of several diseases. In this study, two new Cookson-type reagents, 4-(4-diethylaminophenyl)-1,2,4-triazoline-3,5-dione (DEAPTAD) and 4-(6-quinolyl)-1,2,4-triazoline-3,5-dione, were designed and synthesized, then compared with the previous reagents, 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) and 4-(4-dimethylaminophenyl)-1,2,4-triazoline-3,5-dione (DAPTAD), in terms of sensitivity and specificity in the assay of 25(OH)D3 in neonatal blood samples by liquid chromatography/electrospray ionization-tandem mass spectrometry. Among the reagents, DEAPTAD was found to be the most promising. The limit of detection (0.38 fmol on the column) of the DEAPTAD-derivatized 25(OH)D3 was 60 and 2 times lower than those of the intact 25(OH)D3 and the PTAD derivative, respectively. 25(OH)D3 was more clearly detected in the plasma sample as the DEAPTAD derivative than the DAPTAD derivative owing to the lower background noise. DEAPTAD derivatization was also useful for the separation of 25(OH)D3 from a potent interfering metabolite, 3-epi-25-hydroxyvitamin D3 . By using DEAPTAD, a trace amount of 25(OH)D3 in dried blood spots was reproducibly determined without interference from coexisting compounds. Thus, DEAPTAD was proved useful in the measurement of 25(OH)D3 in neonatal blood samples. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26451531

  5. Differential expression of cytokines in response to respiratory syncytial virus infection of calves with high or low circulating 25-hydroxyvitamin D3.

    PubMed

    Sacco, Randy E; Nonnecke, Brian J; Palmer, Mitchell V; Waters, W Ray; Lippolis, John D; Reinhardt, Timothy A

    2012-01-01

    Deficiency of serum levels of 25-hydroxyvitamin D(3) has been related to increased risk of lower respiratory tract infections in children. Respiratory syncytial virus (RSV) is a leading cause of low respiratory tract infections in infants and young children. The neonatal calf model of RSV infection shares many features in common with RSV infection in infants and children. In the present study, we hypothesized that calves with low circulating levels of 25-hydroxyvitamin D(3) (25(OH)D(3)) would be more susceptible to RSV infection than calves with high circulating levels of 25(OH)D(3). Calves were fed milk replacer diets with different levels of vitamin D for a 10 wk period to establish two treatment groups, one with high (177 ng/ml) and one with low (32.5 ng/ml) circulating 25(OH)D(3). Animals were experimentally infected via aerosol challenge with RSV. Data on circulating 25(OH)D(3) levels showed that high and low concentrations of 25(OH)D(3) were maintained during infection. At necropsy, lung lesions due to RSV were similar in the two vitamin D treatment groups. We show for the first time that RSV infection activates the vitamin D intracrine pathway in the inflamed lung. Importantly, however, we observed that cytokines frequently inhibited by this pathway in vitro are, in fact, either significantly upregulated (IL-12p40) or unaffected (IFN-γ) in the lungs of RSV-infected calves with high circulating levels of 25(OH)D(3). Our data indicate that while vitamin D does have an immunomodulatory role during RSV infection, there was no significant impact on pathogenesis during the early phases of RSV infection. Further examination of the potential effects of vitamin D status on RSV disease resolution will require longer-term studies with immunologically sufficient and deficient vitamin D levels. PMID:22412984

  6. Higher serum 25-hydroxyvitamin D levels in school-age children are inconsistently associated with increased calcium absorption

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing serum 25-hydroxyvitamin D (25-OHD) in adults may enhance calcium absorption (Ca-abs). There are few similar pediatric data leading to uncertainty about the optimal target for 25-OHD to maximize Ca-abs.Our objective was to evaluate the relationship between 25-OHD and Ca-abs in a large coho...

  7. Total 25-Hydroxyvitamin D Determination by an Entry Level Triple Quadrupole Instrument: Comparison between Two Commercial Kits

    PubMed Central

    Cocci, Andrea; Zuppi, Cecilia; Persichilli, Silvia

    2013-01-01

    Objective. 25-hydroxyvitamin D2/D3 (25-OHD2/D3) determination is a reliable biomarker for vitamin D status. Liquid chromatography-tandem mass spectrometry was recently proposed as a reference method for vitamin D status evaluation. The aim of this work is to compare two commercial kits (Chromsystems and PerkinElmer) for 25-OHD2/D3 determination by our entry level LC-MS/MS. Design and Methods. Chromsystems kit adds an online trap column to an HPLC column and provides atmospheric pressure chemical ionization, isotopically labeled internal standard, and 4 calibrator points. PerkinElmer kit uses a solvent extraction and protein precipitation method. This kit can be used with or without derivatization with, respectively, electrospray and atmospheric pressure chemical ionization. For each analyte, there are isotopically labeled internal standards and 7 deuterated calibrator points. Results. Performance characteristics are acceptable for both methods. Mean bias between methods calculated on 70 samples was 1.9 ng/mL. Linear regression analysis gave an R2 of 0.94. 25-OHD2 is detectable only with PerkinElmer kit in derivatized assay option. Conclusion. Both methods are suitable for routine. Chromsystems kit minimizes manual sample preparation, requiring only protein precipitation, but, with our system, 25-OHD2 is not detectable. PerkinElmer kit without derivatization does not guarantee acceptable performance with our LC-MS/MS system, as sample is not purified online. Derivatization provides sufficient sensitivity for 25-OHD2 detection. PMID:23555079

  8. Short communication: serum and tissue concentrations of vitamin D metabolites in beef heifers after buccal dosing of 25-hydroxyvitamin D3.

    PubMed

    Rivera, J D; Bachman, S E; Hubbert, M E; Branine, M E; Horst, R L; Williams, S N; Galyean, M L

    2005-04-01

    Sixteen crossbred (British x Continental; average un-shrunk body weight = 507.9 kg; SD = 45.6 kg) beef heifers fed a steam-flaked corn-based finishing diet with melengestrol acetate (0.4 mg/heifer daily) included to suppress estrus were used in a completely random design to evaluate the efficacy of buccal administration of 0, 10, 100, or 1000 mg of 25-hydroxyvitamin D3, (25-OH D3). Serum Ca, P, Mg, 25-OH D3, 1,25-dihydroxyvitamin D [1,25-(OH)2 D3], albumin, and protein were measured 24 h before dosing (-24 h), at dosing (0 h), and 6 and 24 h after dosing, after which the cattle were slaughtered at a commercial facility. Samples of kidneys, liver, longissimus lumborum, and triceps brachii were collected and evaluated for concentrations of 1,25-(OH)2 D3. With -24 and 0 h as baseline covariates, a significant time x treatment interaction was observed for serum 25-OH D3 and Ca concentrations, but not for serum 1,25-(OH)2 D3. Supplemental 25-OH D3 doses of 100 and 1000 mg significantly increased serum 25-OH D3 at 24 h after dosing, 1,25-(OH)2 D3 at 6 and 24 h after dosing, and serum Ca at 24 h after dosing. Similarly, buccal dosing of 1000 mg of supplemental 25-OH D3 significantly increased (approximately 2- to 3-fold) concentrations of 1,25-(OH)2 D3 in the kidney, liver, and longissimus lumborum relative to the other 3 treatments but not in triceps brachii. Serum albumin, protein, P, and Mg were not affected by treatment. Based on these results, buccal administration of 100 and 1000 mg 25-OH D3 increased vitamin D3 metabolites in serum and tissues, and it should be an effective method of delivering the vitamin. PMID:15778304

  9. Effects of 25-hydroxyvitamin D3 and manipulated dietary cation-anion difference on the tenderness of beef from cull native Korean cows.

    PubMed

    Cho, Y M; Choi, H; Hwang, I H; Kim, Y K; Myung, K H

    2006-06-01

    In this study, we characterized the effects of 25-hydroxyvitamin D3 (25-OH D3) and manipulated dietary cation-anion difference (DCAD) on the performance, urine pH, serum constituents, carcass traits, tissue residual vitamin D and its metabolites, beef tenderness, and mRNA and protein concentrations of Ca-dependent proteinases in LM using 24 cull native Korean cows. The cows were divided into 3 groups of 8: control, 25-OH D3 supplemented (25-OH D3), and manipulated DCAD plus 25-OH D3 supplemented (DCAD+25-OH D3). Cows receiving 25-OH D3 or DCAD+25-OH D3 were dosed with 125 mg of 25-OH D3 6 d before slaughter. The manipulated DCAD (-10 mEq/100 g of DM) diet was fed from 20 to 6 d (14 d) before slaughter. The DCAD+25-OH D3 treatment decreased urine pH and increased serum Ca concentrations. Although the vitamin D concentrations in LM, liver, and kidney were not affected by 25-OH D3 or DCAD+25-OH D3, muscle tissue 25-OH D3 concentrations were increased by both regimens. Serum 25-OH D3 concentrations were increased by 25-OH D3 supplementation, and the increase was even greater for DCAD+25-OH D3. The same pattern was observed for serum 1,25- (OH)2 D3. However, the LM concentration of 1,25-(OH)2 D3 was less for DCAD+25-OH D3 than for control. Although Ca concentrations of LM increased numerically in response to 25-OH D3 supplementation, no statistical differences in Warner-Bratzler shear force or sensory traits of LM were detected. The LM of cows receiving 25-OH D3 with or without manipulated DCAD had greater concentrations of mu-calpain and m-calpain mRNA, whereas the reverse was observed for calpastatin mRNA. Expression of mu-calpain protein was increased relative to control by DCAD+25-OH D3. The amount of 25-OH D3 and manipulated DCAD administered to cull native Korean cows was insufficient to improve tenderness of beef by increasing muscle Ca concentration. However, DCAD+25-OH D3 induced greater expressions of mu-calpain protein as well as mRNA. PMID:16699104

  10. Response to Teriparatide in Patients with Baseline 25-Hydroxyvitamin D Insufficiency or Sufficiency

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Serum 25-hydroxyvitamin D (25OHD) concentrations >30 ng/ml have been recommended for lowering fracture risk. The objective of this study was to determine if 25OHD sufficiency is a prerequisite for effective response to teriparatide (TPTD). Study data came from 1620 osteoporotic postmenopausal wome...

  11. Abnormal regulation of 25-hydroxyvitamin D3-1 alpha-hydroxylase activity by calcium and calcitonin in renal cortex from hypophosphatemic (Hyp) mice.

    PubMed

    Fukase, M; Avioli, L V; Birge, S J; Chase, L R

    1984-04-01

    25-Hydroxyvitamin D3-1 alpha-hydroxylase activity was assayed in primary serum-free monolayer tissue culture of renal cortical cells from hypophosphatemic (Hyp) mice and normal litter mates. Morphological and growth characteristics of cells from the two genotypes were indistinguishable. Basal enzyme activity was not significantly different in either type of cell over a wide range of substrate concentration. The enzyme from both genotypes was stimulated by PTH and suppressed by increased phosphate concentration in the culture medium. Whereas 1 alpha-hydroxylase activity in cells from normal mice was increased in low calcium medium and suppressed in high calcium medium, the enzyme in cells from Hyp mice was not altered by similar changes in the medium calcium concentration. Salmon calcitonin caused a significant increase in 1 alpha-hydroxylase in cells from normal mice, but did not stimulate enzyme activity in cells from Hyp mice. These studies indicate that control of 1 alpha-hydroxylase activity is abnormal in renal cortical cells from Hyp mice. Impaired control of this enzyme could result in the inappropriately low circulating concentrations of 1,25-dihydroxyvitamin D3 that have been observed in humans with hypophosphatemic rickets and in the relatively low activity of 1 alpha-hydroxylase in renal cortical homogenates of Hyp mice compared to that in normal mice on a low phosphate diet. PMID:6705736

  12. The Ontogeny of 25-Hydroxyvitamin D3 1α-Hydroxylase Expression in Human Placenta and Decidua

    PubMed Central

    Zehnder, Daniel; Evans, Katie N.; Kilby, Mark D.; Bulmer, Judith N.; Innes, Barbara A.; Stewart, Paul M.; Hewison, Martin

    2002-01-01

    In addition to its classical calciotropic effects, the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is a potent anti-proliferative/immunomodulatory secosteroid. The enzyme that catalyzes the synthesis of 1,25(OH)2D3, 1α-hydroxylase (1α-OHase), is expressed in many human tissues, highlighting its possible role as an autocrine/paracrine activator of vitamin D. Immunohistochemical and RNA analyses were used to characterize the ontogeny of 1α-OHase expression in human placenta and decidua. Protein for 1α-OHase was detectable in trophoblast and decidua; the latter being stronger in decidualized stromal cells than macrophages, with no staining of lymphocytes. Quantitative reverse transcriptase-polymerase chain reaction was used to assess changes in mRNA expression for 1α-OHase at different gestations: first (mean, 9.1 ± 1.5 weeks); second (mean, 14 ± 1.8 weeks), and third trimester (mean, 39.3 ± 2.5 weeks). 1α-OHase expression in decidua was ∼1000-fold higher in first (95% confidence limits, 611 to 1376) and second (95% confidence limits, 633 to 1623) trimester biopsies when compared with the third trimester (95% confidence limits, 0.36 to 2.81) (both P < 0.001). In placenta, 1α-OHase expression was 80-fold higher in the first (range, 42 to 137) and second (range, 30 to 199) trimester when compared with third trimester biopsies (0.6 to 1.6) (both P < 0.001). Similar results were obtained by semiquantitative IHC. Parallel analysis of the receptor for 1,25(OH)2D3 (vitamin D receptor) indicated that, as with 1α-OHase, highest levels of expression occurred in first trimester decidua. However, changes in vitamin D receptor mRNA expression across gestation were less pronounced than 1α-OHase. These spatiotemporal data emphasize the potential importance of 1α-OHase during early fetoplacental life and, in particular, suggest an autocrine/paracrine immunomodulatory function for the enzyme. PMID:12107095

  13. The association of serum 25-hydroxyvitamin D3 and D2 with depressive symptoms in childhood – a prospective cohort study

    PubMed Central

    Tolppanen, Anna-Maija; Sayers, Adrian; Fraser, William D; Lewis, Glyn; Zammit, Stanley; Lawlor, Debbie A

    2012-01-01

    Background Depression in adolescence is common and early onset predicts worse outcome in adulthood. Studies in adults have suggested a link between higher total 25-hydroxyvitamin D [25(OH)D] concentrations and lower risk of depression. Objectives To investigate (a) the association between serum 25(OH)D2 and 25(OH)D3 concentrations and depressive symptoms in children, and (b) whether the associations of 25(OH)D2 and 25(OH)D3 are different from, and independent of, each other. Methods Prospective cohort study with serum 25(OH)D2 and 25(OH)D3 concentrations measured at mean age of 9.8 years and depressive symptoms assessed with the Mood and Feelings Questionnaire by a trained interviewer at the mean ages of 10.6 years (n = 2,759) and 13.8 years (n = 2,752). Results Higher concentrations of 25(OH)D3 assessed at mean age 9.8 years were associated with lower levels of depressive symptoms at age 13.8 years [adjusted risk ratio (RR; 95% confidence interval (CI)): 0.90 (0.86–0.95)], but not at age 10.6 years [adjusted RR (95% CI): 0.98 (0.93–1.03)] and with increased odds of decreasing symptoms between age 10.6 and 13.8 years [adjusted RR (95% CI): 1.08 (1.01–1.16)]. Serum 25(OH)D2 concentrations were not associated with depressive symptoms. Conclusions This is the first study in children to suggest that the association between 25(OH)D3 concentrations and depression emerges in childhood. The association is independent of a wide range of potential confounding factors, and appears to be stronger with greater time separation between assessment of 25(OH)D3 and assessment of depressive symptoms. Confirmation of our findings in large prospective studies and trials would be valuable. PMID:22211693

  14. Independent associations of polymorphisms in vitamin D binding protein (GC) and vitamin D receptor (VDR) genes with obesity and plasma 25OHD3 levels demonstrate sex dimorphism.

    PubMed

    Almesri, Norah; Das, Nagalla S; Ali, Muhallab E; Gumaa, Khalid; Giha, Hayder Ahmed

    2016-04-01

    We investigated a possible association between polymorphisms in vitamin D binding protein (GC) and vitamin D receptor (VDR) genes and obesity in Bahraini adults. For this purpose, 406 subjects with varying body mass indexes (BMIs) were selected. Plasma levels of 25-hydroxyvitamin D3 (25OHD3) were measured by chemiluminescence immunoassay. Six single nucleotide polymorphisms, 2 in the VDR gene (rs731236 TC and rs12721377 AG) and 4 in the GC gene (rs2282679 AC, rs4588 CA, rs7041 GT, and rs2298849 TC), were genotyped by real-time polymerase chain reaction. We found that the rs7041 minor allele (G) and rare genotype (GG) were associated with higher BMI (p = 0.007 and p = 0.012, respectively), but they did not influence 25OHD3 levels. However, the minor alleles of rs2282679 (A) and rs4588 (C) were associated with low 25OHD3 plasma levels (p = 0.039 and p = 0.021, respectively), but not with BMI. Having categorized the subjects based on their sex, we found that (i) rs7041 GG associated with high BMI in females (p = 0.003), (ii) rs4588 CC associated with high BMI in females (p = 0.034) and low 25OHD3 levels in males (p = 0.009), and (iii) rs12721377 AA associated with low 25OHD3 levels in females (p = 0.039). Notably, none of the common haplotypes (6 in the GC gene and 3 in the VDR gene) were associated with BMI. Therefore, polymorphisms in the GC (rs2282679, rs4588, rs7041) and VDR (rs12721377) genes were independently associated with obesity and 25OHD3 levels with a clear sex dimorphism. PMID:26881316

  15. The Association of Serum 25-Hydroxyvitamin D3 and D2 with Depressive Symptoms in Childhood--A Prospective Cohort Study

    ERIC Educational Resources Information Center

    Tolppanen, Anna-Maija; Sayers, Adrian; Fraser, William D.; Lewis, Glyn; Zammit, Stanley; Lawlor, Debbie A.

    2012-01-01

    Background: Depression in adolescence is common and early onset predicts worse outcome in adulthood. Studies in adults have suggested a link between higher total 25-hydroxyvitamin D [25(OH)D] concentrations and lower risk of depression. Objectives: To investigate (a) the association between serum 25(OH)D[subscript 2] and 25(OH)D[subscript 3]…

  16. Serum 25-hydroxyvitamin D response to vitamin D3 supplementation 50,000 IU monthly in youth with HIV-1 infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Context: Vitamin D deficiency and insufficiency occur frequently in youth with HIV infection, particularly among those receiving the antiretroviral drug efavirenz. Optimal vitamin D dosing for treatment is unclear. Objective: Measure change in 25-hydroxy vitamin D (25-OHD) concentration from basel...

  17. Free 25-Hydroxyvitamin D: Impact of Vitamin D Binding Protein Assays on Racial-Genotypic Associations

    PubMed Central

    Nielson, Carrie M.; Jones, Kerry S.; Chun, Rene F.; Jacobs, Jon M.; Wang, Ying; Hewison, Martin; Adams, John S.; Swanson, Christine M.; Lee, Christine G.; Vanderschueren, Dirk; Pauwels, Steven; Prentice, Ann; Smith, Richard D.; Shi, Tujin; Gao, Yuqian; Schepmoes, Athena A.; Zmuda, Joseph M.; Lapidus, Jodi; Cauley, Jane A.; Schoenmakers, Inez; Orwoll, Eric S.

    2016-01-01

    Context: Total 25-hydroxyvitamin D (25OHD) is a marker of vitamin D status and is lower in African Americans than in whites. Whether this difference holds for free 25OHOD (f25OHD) is unclear, considering reported genetic-racial differences in vitamin D binding protein (DBP) used to calculate f25OHD. Objectives: Our objective was to assess racial-geographic differences in f25OHD and to understand inconsistencies in racial associations with DBP and calculated f25OHD. Design: This study used a cross-sectional design. Setting: The general community in the United States, United Kingdom, and The Gambia were included in this study. Participants: Men in Osteoporotic Fractures in Men and Medical Research Council studies (N = 1057) were included. Exposures: Total 25OHD concentration, race, and DBP (GC) genotype exposures were included. Outcome Measures: Directly measured f25OHD, DBP assessed by proteomics, monoclonal and polyclonal immunoassays, and calculated f25OHD were the outcome measures. Results: Total 25OHD correlated strongly with directly measured f25OHD (Spearman r = 0.84). Measured by monoclonal assay, mean DBP in African-ancestry subjects was approximately 50% lower than in whites, whereas DBP measured by polyclonal DBP antibodies or proteomic methods was not lower in African-ancestry. Calculated f25OHD (using polyclonal DBP assays) correlated strongly with directly measured f25OHD (r = 0.80–0.83). Free 25OHD, measured or calculated from polyclonal DBP assays, reflected total 25OHD concentration irrespective of race and was lower in African Americans than in US whites. Conclusions: Previously reported racial differences in DBP concentration are likely from monoclonal assay bias, as there was no racial difference in DBP concentration by other methods. This confirms the poor vitamin D status of many African-Americans and the utility of total 25OHD in assessing vitamin D in the general population. PMID:27007693

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

    PubMed

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

    2016-04-14

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

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

    SciTech Connect

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

    1986-08-26

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

  20. Plasma 25-hydroxyvitamin D concentration and risk of type 2 diabetes in women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamin D may modify risk of type 2 diabetes; however, the association between vitamin D and type 2 diabetes is uncertain. To determine prospectively the association between 25-hydroxyvitamin D (25-OHD) concentration and risk of incident type 2 diabetes, independent of obesity and other known diabet...

  1. Determinants of the 25-hydroxyvitamin D response to vitamin D supplements

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Supplemental vitamin D is now widely recommended but little guidance is provided on how or when to take vitamin D supplements. The process of vitamin D replacement is complicated by the fact that the increment in 25-hydroxyvitamin D (25OHD) in response to a given dose varies greatly from person to p...

  2. Accuracy of 25-hydroxyvitamin D assays: confronting the issues.

    PubMed

    Carter, Graham D

    2011-01-01

    Measurement of 25-hydroxyvitamin D (25-OHD) is widely used for assessing vitamin D status. There has been a dramatic increase in 25-OHD requests over recent years prompting many laboratories to consider the use of automated immunoassays. To achieve higher throughput, these methods have abandoned the traditional solvent extraction of samples and are therefore more prone to non-specific interference. The Vitamin D External Quality Assessment Scheme (DEQAS) has revealed method-related differences in 25-OHD results, raising concerns about the comparability and accuracy of different assays. This paper highlights some of the pre-analytical, analytical and post-analytical issues which may influence the accuracy of 25-OHD assays and interpretation of results. Recent attention has focused on reconciling the relatively high results given by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to those of the DiaSorin radioimmunoassay (RIA) on which clinical decision points have previously been based. Data is presented on 20 DEQAS samples which were analysed by an LC-MS/MS assay developed as a candidate reference measurement procedure by the US National Institute of Standards and Technology (NIST). The NIST results were on average 11.2% lower than those given by routine LC-MS/MS methods. If confirmed, these results suggest that most routine LC-MS/MS assays are perhaps overestimating 25-OHD by failing to resolve a molecule having the same mass as 25-OHD(3) and a similar fragmentation pattern. All 25-OHD assays should be monitored by a proficiency testing scheme and the results made available to clinicians and editors of scientific journals. PMID:20795940

  3. Effects of 1,25(OH)2D3, 25OHD3, and EB1089 on cell growth and Vitamin D receptor mRNA and 1alpha-hydroxylase mRNA expression in primary cultures of the canine prostate.

    PubMed

    Kunakornsawat, S; Rosol, T J; Capen, C C; Omdahl, J L; Leroy, B E; Inpanbutr, N

    2004-05-01

    The aim of this study was to investigate effects of 1,25(OH)(2)D(3) (calcitriol), 25OHD(3), and EB1089 on cell growth and on Vitamin D receptor (VDR) mRNA and 1alpha-hydroxylase (1alpha-OHase) mRNA expression in normal canine prostatic primary cultures. Canine prostatic epithelial cells were isolated, cultured, and treated with vehicle (ethanol), calcitriol, 25OHD(3), and EB1089 at 10(-9) and 10(-7)M. The VDR was present in epithelial and stromal cells of the canine prostate gland. 1,25(OH)(2)D(3), 25OHD(3), and EB1089 inhibited epithelial cell growth at 10(-7)M compared to vehicle-treated controls [calcitriol (P < 0.01), EB1089 (P < 0.01), and 25OHD(3) (P < 0.05)]. Epithelial cells treated with calcitriol and EB1089 at 10(-7)M had slightly increased VDR mRNA expression (0.2-0.3-fold) at 6 and 12h compared to controls. There was no difference in 1alpha-OHase mRNA expression in epithelial cells treated with these three compounds. 1,25(OH)(2)D(3) and its analogs may be effective antiproliferative agents of epithelial cells in certain types of prostate cancer. PMID:15225811

  4. Regulation of calf renal 25-hydroxyvitamin D-hydroxylase activities by calcium-regulating hormones.

    PubMed

    Engstrom, G W; Goff, J P; Horst, R L; Reinhardt, T A

    1987-11-01

    Parathyroid hormone and 1,25-dihydroxyvitamin D3 had opposite effects on calf renal 25-hydroxyvitamin D3 24-, 23-, and 1 alpha-hydroxylase activities. Parathyroid hormone administration increased renal 25-hydroxyvitamin D3-1 alpha-hydroxylase activity 7-fold while 25-hydroxyvitamin D3-23- and 24-hydroxylase activities were essentially the same as controls. Administration of 1,25-dihydroxyvitamin D3 increased 25-hydroxyvitamin D3-23-hydroxylase and 24-hydroxylase activities 4-fold and decreased 25-hydroxyvitamin D3-1 alpha-hydroxylase activity to undetectable concentrations. Vitamin D deficiency increased 25-hydroxyvitamin D3-1 alpha -hydroxylase activity 13-fold, and 25-hydroxyvitamin D3-23-hydroxylase and 24-hydroxylase activities were undetectable. These results confirm previous reports with regard to control of renal 25-hydroxyvitamin D3-24-hydroxylase and 1 alpha -hydroxylase in other species and represent new findings relative to the control of 25-hydroxyvitamin D3-23-hydroxylase. Plasma P was lower and 1,25-dihydroxyvitamin D3 higher in calves treated with parathyroid hormone, and Ca and 1,25-dihydroxyvitamin D3 were lower in the vitamin D-deficient calves. 1,25-Dihydroxyvitamin D3-treated calves had higher plasma P and lower Mg than controls. Further studies using this calf model should lead to better understanding of Ca-regulating hormones control of vitamin D metabolism. PMID:3693631

  5. Diet-derived 25-hydroxyvitamin D3 activates vitamin D receptor target gene expression and suppresses EGFR mutant non-small cell lung cancer growth in vitro and in vivo

    PubMed Central

    Verone-Boyle, Alissa R.; Shoemaker, Suzanne; Attwood, Kristopher; Morrison, Carl D.; Makowski, Andrew J.; Battaglia, Sebastiano; Hershberger, Pamela A.

    2016-01-01

    Epidemiologic studies implicate vitamin D status as a factor that influences growth of EGFR mutant lung cancers. However, laboratory based evidence of the biological effect of vitamin D in this disease is lacking. To fill this knowledge gap, we determined vitamin D receptor (VDR) expression in human lung tumors using a tissue microarray constructed of lung cancer cases from never-smokers (where EGFR gene mutations are prevalent). Nuclear VDR was detected in 19/19 EGFR mutant tumors. Expression tended to be higher in tumors with EGFR exon 19 deletions than those with EGFR L858R mutations. To study anti-proliferative activity and signaling, EGFR mutant lung cancer cells were treated with the circulating metabolite of vitamin D, 25-hydroxyvitamin D3 (25D3). 25D3 inhibited clonogenic growth in a dose-dependent manner. CYP27B1 encodes the 1α-hydroxylase (1αOHase) that converts 25D3 to the active metabolite, 1,25-dihydroxyvitamin D3 (1,25D3). Studies employing VDR siRNA, CYP27B1 zinc finger nucleases, and pharmacologic inhibitors of the vitamin D pathway indicate that 25D3 regulates gene expression in a VDR-dependent manner but does not strictly require 1αOHase-mediated conversion of 25D3 to 1,25D3. To determine the effects of modulating serum 25D3 levels on growth of EGFR mutant lung tumor xenografts, mice were fed diets containing 100 or 10,000 IU vitamin D3/kg. High dietary vitamin D3 intake resulted in elevated serum 25D3 and significant inhibition of tumor growth. No toxic effects of supplementation were observed. These results identify EGFR mutant lung cancer as a vitamin D-responsive disease and diet-derived 25D3 as a direct VDR agonist and therapeutic agent. PMID:26654942

  6. Association between body weight and composition and plasma 25 hydroxyvitamin D level in the diabetes prevention program

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: We examined associations between body weight and plasma 25-hydroxyvitamin D concentration (25OHD) in prediabetes and sought to estimate the impact of adiposity on these associations. Methods: The study was conducted in the placebo (n = 1082) and intensive lifestyle (n = 1079) groups of ...

  7. Effect of feeding 25-hydroxyvitamin D3 with a negative cation-anion difference diet on calcium and vitamin D status of periparturient cows and their calves.

    PubMed

    Weiss, W P; Azem, E; Steinberg, W; Reinhardt, T A

    2015-08-01

    Holstein cows (>1 gestation) were fed 1 of 3 diets during the last 13 d of gestation (ranged from 22 to 7 d). The control diet (16 cows) was formulated to provide 18,000 IU/d of vitamin D3 and had a dietary cation-anion difference (DCAD) of 165mEq/kg (DCAD=Na + K - Cl - S). The second diet (DCAD + D) provided the same amount of vitamin D3 but had a DCAD of -139mEq/kg (17 cows). The third diet (DCAD + 25D) had no supplemental vitamin D3 but provided 6mg/d of 25-(OH) vitamin D3 [25-(OH)D3] with a DCAD of -138mEq/kg (20 cows). Diets were fed until parturition and then all cows were fed a common lactation diet that contained vitamin D3. Negative DCAD diets reduced urine pH, with the greatest decrease occurring with the DCAD + D treatment. Urinary Ca excretion was greatest for cows fed DCAD + 25D followed by cows fed DCAD + D. Urinary pH was negatively correlated with urinary excretion of Ca for cows fed DCAD + D. No such correlation was observed with the DCAD + 25D treatment because substantial excretion of urinary Ca occurred at moderate urinary pH values for that treatment. Cows fed DCAD + 25D had greater serum concentrations of 25-(OH)D3 than other treatments from 5 d after supplementation started through 7 d in milk. Concentrations of 1,25-(OH)2D3 in serum were greatest in DCAD + 25D cows starting at 2 d before calving and continued through 7 d in milk. Serum Ca concentrations 5 d before calving were greatest for cows fed DCAD + 25D, but at other time points before and after parturition treatment did not affect serum Ca. Incidence of clinical hypocalcemia was not statistically different between treatments, but cows fed DCAD + 25 had the highest incidence rate (12.5, 0, and 20% for control, DCAD + D, and DCAD + 25D). Calves born from cows fed DCAD + 25D had greater concentrations of 25-(OH)D3 in serum at birth than calves from other treatments (before colostrum consumption), but concentrations were similar by 3 d of age. Concentrations of 25-(OH)D3 in colostrum and

  8. Effect of feeding 25-hydroxyvitamin D3 with a negative cation-anion difference diet on calcium and vitamin D status of periparturient cows and their calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Holstein cows (>1 gestation) were fed 1 of 3 diets during the last 13 d of gestation (ranged from 22 to 7 d). The Control diet was formulated to provide 18,000 IU/d of vitamin D3 and had a dietary cation-anion difference (DCAD) of 165 mEq/kg (DCAD = Na + K – Cl – S). The second diet (DCAD+D) provi...

  9. Targeted 25-hydroxyvitamin D3 1α-hydroxylase adoptive gene therapy ameliorates dss-induced colitis without causing hypercalcemia in mice.

    PubMed

    Li, Bo; Baylink, David J; Walter, Michael H; Lau, Kin-Hing William; Meng, Xianmei; Wang, Jun; Cherkas, Andriy; Tang, Xiaolei; Qin, Xuezhong

    2015-02-01

    Systemic 1,25(OH)2D3 treatment ameliorating murine inflammatory bowel diseases (IBD) could not be applied to patients because of hypercalcemia. We tested the hypothesis that increasing 1,25(OH)2D3 synthesis locally by targeting delivery of the 1α-hydroxylase gene (CYP27B1) to the inflamed bowel would ameliorate IBD without causing hypercalcemia. Our targeting strategy is the use of CD11b(+)/Gr1(+) monocytes as the cell vehicle and a macrophage-specific promoter (Mac1) to control CYP27B1 expression. The CD11b(+)/Gr1(+) monocytes migrated initially to inflamed colon and some healthy tissues in dextran sulfate sodium (DSS) colitis mice; however, only the migration of monocytes to the inflamed colon was sustained. Adoptive transfer of Gr1(+) monocytes did not cause hepatic injury. Infusion of Mac1-CYP27B1-modified monocytes increased body weight gain, survival, and colon length, and expedited mucosal regeneration. Expression of pathogenic Th17 and Th1 cytokines (interleukin (IL)-17a and interferon (IFN)-α) was decreased, while expression of protective Th2 cytokines (IL-5 and IL-13) was increased, by the treatment. This therapy also enhanced tight junction gene expression in the colon. No hypercalcemia occurred following this therapy. In conclusion, we have for the first time obtained proof-of-principle evidence for a novel monocyte-based adoptive CYP27B1 gene therapy using a mouse IBD model. This strategy could be developed into a novel therapy for IBD and other autoimmune diseases. PMID:25327179

  10. Prevalence and correlates of 25-hydroxyvitamin D deficiency in the Chronic Kidney Disease in Children (CKiD) cohort

    PubMed Central

    McDermott, Kelly; Abraham, Alison G.; Friedman, Lisa Aronson; Johnson, Valerie L.; Kaskel, Frederick J.; Furth, Susan L.; Warady, Bradley A.; Portale, Anthony A.; Melamed, Michal L.

    2016-01-01

    Background Vitamin D plays an important role in the mineral and bone disorder seen in chronic kidney disease (CKD). Deficiency of 25-hydroxyvitamin D (25OHD) is highly prevalent in the adult CKD population. Methods The prevalence and determinants of 25OHD deficiency (defined as a level <20 ng/ml) were examined longitudinally in 506 children in the CKiD cohort. Predictors of secondary hyperparathyroidism and the determinants of 1,25-dihydroxyvitamin D (1,25(OH)2D) levels were also evaluated. Results Deficiency of 25OHD was observed in 28 % of the cohort at enrollment. Significant predictors of 25OHD deficiency were older age, non-white race, higher body mass index, assessment during winter, less often than daily milk intake, non-use of nutritional vitamin D supplement and proteinuria. Lower values of glomerular filtration rate (GFR), serum 25OHD, calcium and higher levels of FGF23 were significant determinants of secondary hyperparathyroidism. Lower GFR, low serum 25OHD, nephrotic-range proteinuria, and high FGF23 levels were significant determinants of serum 1, 25(OH)2 D levels. Conclusions Deficiency of 25OHD is prevalent in children with CKD and is associated with potentially modifiable risk factors such as milk intake, nutritional vitamin D supplement use, and proteinuria. 25OHD deficiency is a risk factor for secondary hyperparathyroidism and decreased serum 1, 25(OH)2D in children with CKD. PMID:26307635

  11. Serum 25-hydroxyvitamin d concentration, life factors and obesity in Mexican children.

    PubMed

    Elizondo-Montemayor, Leticia; Ugalde-Casas, Patricia A; Serrano-González, Mónica; Cuello-García, Carlos A; Borbolla-Escoboza, José R

    2010-09-01

    Although current evidence emphasizes a high prevalence of vitamin D deficiency and an inverse association between serum 25-hydroxyvitamin D (25-OHD) concentration and obesity, no studies have been conducted in Mexican children. The objective was to determine the prevalence of vitamin D deficiency and its association with obesity and lifestyle factors in a sample of school-aged Mexican children. A cross-sectional study of 99 obese and 99 nonobese 6-12 year-old children, skin phototypes III-V, from six public schools was conducted during summer at latitude 25 degrees 40', in northeastern Mexico. Anthropometric measurements were determined. Serum 25-OHD was measured by immunoluminometric direct assay. Consumption of foods rich in vitamin D, sunscreen use and vitamin consumption were assessed through applied questionnaires. 62.1% of the subjects had insufficiency of 25-OHD (21-29 ng/ml) and 20.2% had deficiency (<20 ng/ml). Obese subjects (BMI >or=95th percentile for age and gender) had significantly lower concentration of 25-OHD than nonobese. Predictors of 25-OHD concentration were, in order of significance: percentage of body fat, BMI, triceps skin fold, and waist circumference (WC). A significantly higher rate of 25-OHD deficiency was observed in children with inadequate milk/yoghurt consumption, but no difference was found for other foods, physical activity (PA) or screen-time. In a multivariate model, being obese was significantly associated with the risk of 25-OHD deficiency, after adjustment for PA, screen-time, skin phototype, ingestion of milk/yoghurt, fish, cheese, and carbonated beverages. A high prevalence of vitamin D deficiency and an inverse association between serum 25-OHD concentration and obesity was found. PMID:20010726

  12. 25-Hydroxyvitamin D isomerizes to pre-25-hydroxyvitamin D in solution: considerations for calibration in clinical measurements.

    PubMed

    Bedner, Mary; Lippa, Katrice A

    2015-10-01

    Reference standards for the vitamin D metabolites 25-hydroxyvitamin D3, 25-hydroxyvitamin D2, and 3-epi-25-hydroxyvitamin D3 were evaluated using liquid chromatography (LC) with ultraviolet (UV) absorbance and mass spectrometric (MS) detection to assess purity. The chromatograms for solutions of all three 25(OH)D compounds, obtained using a pentafluorophenyl (PFP) stationary phase, revealed peaks that increased in area over time and had MS spectra that were nearly identical to the parent compound, indicating isomers had formed in solution that were unrelated to the reference standard purity. However, when the purity evaluations were completed with a cyanopropyl stationary phase, the isomeric products coeluted with the parent compounds and were not observable. The rates of formation of the isomeric products were found to increase when heated and were confirmed to be pre-25-hydroxyvitamin D compounds using spectral information from both MS detection and nuclear magnetic resonance (NMR) spectroscopy. The rates of conversion of 25(OH)D3 to pre-25(OH)D3 was studied in solutions of ethanol and bovine serum albumin (BSA) in phosphate-buffered saline (PBS). The solutions prepared with BSA/PBS were found to form twice as much pre-25(OH)D3 as the solutions in ethanol. The isomerization of 25(OH)D in solution has implications for calibration of 25(OH)D in clinical measurements, which are discussed. PMID:26359234

  13. Vitamin D supplementation is associated with higher serum 25OHD in Asian and White infants living in Vancouver, Canada.

    PubMed

    Green, Tim J; Li, Wangyang; Barr, Susan I; Jahani, Mitra; Chapman, Gwen E

    2015-04-01

    To prevent rickets, the Health Canada and the American Academy of Pediatrics recommend that breastfed infants receive a daily vitamin D supplement of 10 μg d(-1) . Compliance with this recommendation is variable and its effect on infant vitamin D status is unclear. We measured serum 25-hydroxyvitamin D (25OHD) in Asian immigrant (n=28) and White (n=37) mothers and their infants aged 2-4 months living in Vancouver (49°N). Mothers completed health and demographic questionnaires. All subjects were term infants who were primarily breastfed. Analysis of variance, χ(2) , multiple regression and logistic regression analysis were performed as appropriate. Mean 25OHD of the infants was 31 (95% confidence interval 28-34) ng mL(-1) . Only two infants had a 25OHD concentration indicative of deficiency, <10 ng mL(-1) . Of the infants, 14% (n=9) and 49% (n=32) were vitamin D insufficient based on two commonly used cut-offs of 20 and 30 ng mL(-1) , respectively. Fifty-eight (89%) infants had been given a vitamin D supplement. Mean 25OHD was 9.4 ng mL(-1) higher in infants consuming ≥10 μg d(-1) of vitamin D from supplements vs. those consuming less (P=0.003). Mother's 25OHD, season, skin colour or ethnicity (Asian vs. White) did not influence infant 25OHD. The infants in our study, most of whom received vitamin D supplements, were generally protected against low 25OHD. The study was limited by sample size and the nature of the cross-sectional study design. PMID:23061469

  14. Association of serum 25-hydroxyvitamin D with race/ethnicity and constitutive skin color in urban schoolchildren

    PubMed Central

    Au, Lauren E.; Harris, Susan S.; Dwyer, Johanna T.; Jacques, Paul F.; Sacheck, Jennifer M.

    2015-01-01

    The objective of this study was to determine the extent to which constitutive skin color explains racial/ethnic differences in serum 25-hydroxyvitamin D (25OHD) concentrations in urban schoolchildren. Analysis of covariance (ANCOVA) was used to determine associations of 25OHD with parent-reported race/ethnicity and constitutive skin color as measured by reflectance colorimeter [individual typology angle (ITA°; higher value corresponds to lighter skin)] in 307 Greater Boston schoolchildren aged 9–15 during October–December 2011. Nearly 60% of all children were inadequate in 25OHD (<20 ng/mL). Prevalence of inadequate 25OHD differed by race/ethnicity (p<0.001): white (46.6%), black (74.5%), Hispanic (64.7%), Asian (88.9%), and multi-racial/other (52.7%). Serum 25OHD increased 0.6 ng/mL per 10° increase in ITA° value (p<0.001). The prediction of 25OHD by race/ethnicity was slightly stronger than the prediction by skin color in separate models (R2=0.19, R2=0.16, respectively). Most of the variability in 25OHD in race/ethnicity was due to constitutive skin color in this group of racially diverse US children. PMID:24945426

  15. Motor imagery of gait in non-demented older community-dwellers: performance depends on serum 25-hydroxyvitamin D concentrations.

    PubMed

    Beauchet, Olivier; Launay, Cyrille P; Fantino, Bruno; Annweiler, Cédric; Allali, Gilles

    2015-01-01

    Hypovitaminosis D has been associated with poorer physical and cognitive performances in older adults. The objectives of this study were (1) to measure and compare the time to perform (pTUG) and to imagine (iTUG) the Timed "Up & Go" test (TUG) test, and the time difference between these two performances (i.e., TUG delta time) in non-demented community-dwelling older adults with and without lower serum 25-hydroxyvitamin D (25OHD) concentrations and (2) to examine the association between the TUG delta time and serum 25OHD concentrations. Durations of pTUG, iTUG and TUG delta time, and serum 25OHD concentrations (severe insufficiency <10 ng/mL; moderate insufficiency: 10-30 ng/mL; normal status >30 ng/mL) were measured in 359 non-demented participants (mean age 70.4 ± 4.8 years; 40.7 % women). Participants with severe 25OHD insufficiency (15.6 %) had higher TUG delta time compared to those with moderate insufficiency (P = 0.010) and normal status (P = 0.048). TUG delta time was negatively associated with serum 25OHD concentrations (P < 0.010). Accurate motor imagery of gait was explained in part by serum 25OHD concentrations, increased discrepancy between pTUG and iTUG being associated with lower serum 25OHD concentrations. PMID:25701394

  16. Baculovirus-expressed vitamin D-binding protein-macrophage activating factor (DBP-maf) activates osteoclasts and binding of 25-hydroxyvitamin D(3) does not influence this activity.

    PubMed

    Swamy, N; Ghosh, S; Schneider, G B; Ray, R

    2001-01-01

    Vitamin D-binding protein (DBP) is a multi-functional serum protein that is converted to vitamin D-binding protein-macrophage activating factor (DBP-maf) by post-translational modification. DBP-maf is a new cytokine that mediates bone resorption by activating osteoclasts, which are responsible for resorption of bone. Defective osteoclast activation leads to disorders like osteopetrosis, characterized by excessive accumulation of bone mass. Previous studies demonstrated that two nonallelic mutations in the rat with osteopetrosis have independent defects in the cascade involved in the conversion of DBP to DBP-maf. The skeletal defects associated with osteopetrosis are corrected in these mutants with in vivo DBP-maf treatment. This study evaluates the effects of various forms of DBP-maf (native, recombinant, and 25-hydroxyvitamin D(3) bound) on osteoclast function in vitro in order to determine some of the structural requirements of this protein that relate to bone resorbing activities. Osteoclast activity was determined by evaluating pit formation using osteoclasts, isolated from the long bones of newborn rats, incubated on calcium phosphate coated, thin film, Ostologic MultiTest Slides. Incubation of osteoclasts with ex vivo generated native DBP-maf resulted in a dose dependent, statistically significant, activation of the osteoclasts. The activation was similar whether or not the vitamin D binding site of the DBP-maf was occupied. The level of activity in response to DBP-maf was greater than that elicited by optimal doses of other known stimulators (PTH and 1,25(OH(2)D(3)) of osteoclast function. Furthermore, another potent macrophage activating factor, interferon--gamma, had no effect on osteoclast activity. The activated form of a full length recombinant DBP, expressed in E. coli showed no activity in the in vitro assay. Contrary to this finding, baculovirus-expressed recombinant DBP-maf demonstrated significant osteoclast activating activity. The normal

  17. Serum concentrations of 25-hydroxyvitamin D and its association with bone mineral density and serum parathyroid hormone levels during winter in urban males from Guiyang, Southwest China.

    PubMed

    Zhang, Qiao; Shi, Lixin; Peng, Nianchun; Xu, Shujing; Zhang, Miao; Zhang, Song; Li, Hong; Zhuang, Huijun; Gong, Mingxian; Wu, Danrong; Wang, Rui

    2016-03-28

    Serum vitamin D (25-hydroxyvitamin D (25OHD)) may influence serum parathyroid hormone (PTH) levels and bone mineral density (BMD). In the present study, we assessed serum 25OHD concentration and its association with PTH and BMD in urban males from Guiyang (N26.57°), the capital city of Guizhou province, Southwest China. We recruited 634 males aged >20 years from the Guiyang Health Measures Survey, and stratified them into three groups according to age: young (20-39 years), middle aged (40-59 years) and older (60-79 years). We measured serum concentrations of 25OHD, PTH levels and BMD of the lumbar spine (L1-L4), femoral neck and total hip. In addition, we also explored the relationship between 25OHD and lifestyle, socio-economic characteristics and medical history by applying covariance analysis and locally weighted regression plots. The results showed that serum 25OHD was 75 nmol/l in 12·6 % of the subjects. Higher level of serum PTH was detected in relation to lower concentrations of serum 25OHD up to 50 nmol/l. A negative correlation between serum 25OHD and PTH concentrations was observed (r -0·207, P=0·003). Mean concentration of serum PTH increased gradually and plateaued while concentrations of serum 25OHD decreased to 50 nmol/l. Gradual increase in serum PTH was observed as 25OHD concentration was <25 nmol/l (P=0·004). BMD values at all sites were greater in the higher serum 25OHD concentration group. This study shows that low concentrations of serum 25OHD were common in males, and bone health was likely to be improved when serum 25OHD values were between 30 and 50 nmol/l. PMID:26843386

  18. Plasma 25-hydroxyvitamin D and risk of premenstrual syndrome in a prospective cohort study

    PubMed Central

    2014-01-01

    Background Moderate to severe premenstrual syndrome (PMS) affects 8–20 percent of premenopausal women. Previous studies suggest that high dietary vitamin D intake may reduce risk. However, vitamin D status is influenced by both dietary vitamin D intake and sunlight exposure and the association of vitamin D status with PMS remains unclear. Methods We assessed the relation of plasma 25-hydroxyvitamin D (25OHD), total calcium and parathyroid hormone levels with risk of PMS and specific menstrual symptoms in a case–control study nested within the prospective Nurses’ Health Study II. Cases were 401 women free from PMS at baseline who developed PMS during follow-up (1991–2005). Controls were women not experiencing PMS (1991–2005), matched 1:1 with cases on age and other factors. Timed luteal phase blood samples were collected between 1996 and 1999 from cases and controls. We used conditional logistic regression to model the relation of 25OHD levels with risk of PMS and individual menstrual symptoms. Results In analyses of all cases and controls, 25OHD levels were not associated with risk of PMS. However, results differed when the timing of blood collection vs. PMS diagnosis was considered. Among cases who had already been diagnosed with PMS at the time of blood collection (n = 279), 25OHD levels were positively associated with PMS, with each 10 nmol/L change in 25OHD associated with a 13% higher risk. Among cases who developed PMS after blood collection (n = 123), 25OHD levels were unrelated to risk of PMS overall, but inversely related to risk of specific menstrual symptoms. For example, each 10 nmol/L increase was associated with a significant 21% lower risk of breast tenderness (P = 0.02). Total calcium or parathyroid hormone levels were unrelated to PMS. Conclusions 25OHD levels were not associated with overall risk of PMS. The positive association observed among women already experiencing PMS at the time of 25OHD measurement is likely due to

  19. Serum 25-Hydroxyvitamin D Levels: Variability, Knowledge Gaps, and the Concept of a Desirable Range.

    PubMed

    Fuleihan, Ghada El-Hajj; Bouillon, Roger; Clarke, Bart; Chakhtoura, Marlene; Cooper, Cyrus; McClung, Michael; Singh, Ravinder J

    2015-07-01

    Hypovitaminosis D is prevalent worldwide but proportions vary widely between regions, depending on genetic and lifestyle factors, the threshold to define deficiency, and accuracy of 25-hydroxyvitamin D (25OHD) assays used. Latitude, pollution, concealing clothing, sun exposure, gender, dietary habits, and lack of government regulation account for up to 50% in variations in serum 25OHD levels, whereas genetic polymorphisms in the vitamin D pathway account for less than 5%. Organizations/societies have developed guidelines for recommended desirable 25OHD levels and vitamin D doses to reach them, but their applicability across age groups and populations are still debated. This article and the accompanying online Supporting Information highlight sources of variations in circulating 25OHD levels, uncertainties and knowledge gaps, and analytical problems facing 25OHD assays, while keeping efficacy and safety data as the dominant factors when defining a desirable range for 25OHD levels. We propose a desirable range of 20 to 40 ng/mL (50 to 100 nmol/L), provided precise and accurate assays are used. Although slightly lower levels, 15 to 20 ng/mL, may be sufficient for some infants and adults, higher levels, 40 to 60 ng/mL, may still be safe. This desirable range allows physicians to tailor treatment while taking season, lifestyle, vitamin D intake, and other sources of variation into account. We reserve 25OHD measurements for at-risk patients, defined by disease or lifestyle, and the use of 25OHD assays calibrated against the recommended international standards. Most target groups reach desirable target levels by a daily intake of 400 to 600 IU for children and 800 IU for adults. A total daily allowance of vitamin D of up to 1000 IU in the pediatric age groups, and up to 2000 IU in adults, tailored to an individual patient risk profile, is probably safe over long durations. Additional data are needed to validate the proposed range and vitamin D doses

  20. Supplementing dairy steers and organically managed dairy cows with synthetic vitamin D3 is unnecessary at pasture during exposure to summer sunlight.

    PubMed

    Hymøller, Lone; Jensen, Søren K; Lindqvist, Hanna; Johansson, Birgitta; Nielsen, Mette O; Nadeau, Elisabet

    2009-08-01

    Use of synthetic feed additives, including synthetic vitamin D3 (D3) in the feed for cows and other ruminants, is not consistent with the international principles of organic farming. If dairy farmers wish to produce in accordance with the organic principles, production animals would be left with only their endogenous production of D3 from summer sunlight as a source of D3. To examine the impact of supplemental synthetic D3 from the feed on the D3 status of dairy cattle in organic production in Nordic countries, 20 high-yielding dairy cows and 30 dairy steers were divided into two groups: one supplemented with synthetic D3 in the feed and one not supplemented with synthetic D3. Vitamin D3 status of the animals was assessed by measuring the concentration of the liver-derived 25-hydroxyvitamin D3 (25OHD3) in plasma. Results showed that 25OHD3 concentration in plasma from dairy cattle as well as from steers decreased during winter for both supplemented and unsupplemented groups. Unsupplemented cows and steers had approximately 2 ng 25OHD3 per ml plasma during winter, whereas supplemented animals had between 10 (cows) and 30 (steers) ng/ml. During summer and autumn there was no additive effect of supplementing with synthetic D3 since unsupplemented and supplemented animals had the same D3 status at this time of year. In all cows summer concentrations of 25OHD3 were 20-25 ng/ml and in all steers 40-50 ng/ml plasma. The decrease in vitamin D3 status during winter indicates that cows and steers are able to store D3 only to a limited extent. The results also show that cows or steers fed supplemental D3 according to Swedish recommendation throughout the year are not able to maintain their summer value of 25OHD3 during winter. PMID:19450368

  1. Performance evaluation of two immunoassays for 25-hydroxyvitamin D

    PubMed Central

    Li, Lusha; Zeng, Qin; Yuan, Jingjing; Xie, Zhongjian

    2016-01-01

    Although immunoassays in measuring 25-hydroxyvitamin D [25(OH)D] have been improved recently, relatively large differences are still seen between results of 25(OH)D measured by immunoassays and by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In the present studies, we compared two immunoassays with LC-MS/MS for measuring 25(OH)D concentrations. Concentrations of 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] in serum samples from 59 healthy subjects were measured by two immunoassays including Siemens ADVIA Centaur Vitamin D Total (Centaur) and Roche Elecsys Vitamin D Total (Elecsys) and LC-MS/MS. To determine the cross reactivity of Elecsys and Centaur toward 25(OH)D2, a dosage of 200,000 IU vitamin D2 was given after first sampling. Serum samples were obtained 30 days later and concentrations of 25(OH)D2 and 25(OH)D3 were measured again. The results showed poor agreement between the immunoassays and LC-MS/MS in 25(OH)D2 and 25(OH)D3 measurements. The percentage of 25(OH)D2 cross-reactivity was 45.3% for Centaur and 41.2% for Elecsys and there was no significant difference between Centaur and Elecsys. In conclusion, Centaur and Elecsys perform unsatisfactorily in measuring 25(OH)D levels, especially for 25(OH)D2 cross-reactivity. Therefore, clinicians need to be aware of the underestimation of vitamin D status when using these immunoassays for measuring individuals supplemented with vitamin D2. PMID:27257343

  2. Low serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in institutionalized old people: influence of solar exposure and vitamin D supplementation.

    PubMed

    Egsmose, C; Lund, B; McNair, P; Lund, B; Storm, T; Sørensen, O H

    1987-01-01

    The vitamin D status was investigated in 94 geriatric patients in a Danish long-stay ward. The influence of mobility and thus possibility of outdoor activity was studied as well as the influence of regular vitamin D intake. Serum levels of 25-hydroxyvitamin D (25-OHD) were significantly reduced in all groups compared with age-matched controls. In 50% of the patients hypocalcaemia and elevated levels of alkaline phosphatase and immunoreactive parathyroid hormone (iPTH) were found in combination with severely reduced serum 25-OHD values (less than 5 ng/ml) indicating the presence of osteomalacia. Supplementation with 400 IU vitamin D daily in the winter months resulted in significantly higher 25-OHD levels and normocalcaemia while slightly elevated levels of alkaline phosphatase and iPTH persisted. The serum concentrations of 25-OHD were highest in the subjects who were not confined to bed. In these patients the biochemical parameters reflecting osteomalacia were normal. Low serum 1,25-dihydroxyvitamin D levels were found in the patients with low 25-OHD while 24,25-dihydroxyvitamin D levels were within the normal range in all groups and correlated with 25-OHD. Daily vitamin D supplementation appears to be indicated for geriatric patients, especially when bedridden, even in countries where the nutritional vitamin D intake is high. PMID:3565167

  3. Associations of vitamin D intake with 25-hydroxyvitamin D in overweight and racially/ethnically diverse US children.

    PubMed

    Au, Lauren E; Rogers, Gail T; Harris, Susan S; Dwyer, Johanna T; Jacques, Paul F; Sacheck, Jennifer M

    2013-11-01

    Overweight children and minorities are at risk of vitamin D deficiency. Little information exists on whether overweight children and minorities who do not meet dietary vitamin D recommendations are at risk for low 25-hydroxyvitamin D (25OHD) status. Vitamin D intake from foods and dietary supplements was estimated in 3,310 children/adolescents who were examined as part of the 2005-2006 National Health and Nutrition Examination Survey. Weight status was dichotomized into healthy weight or overweight/obese. Parent-reported race/ethnicity was categorized as non-Hispanic white, non-Hispanic black, Mexican American, or other. Adjusted logistic regression was used to determine whether children who did not achieve the Estimated Average Requirement (EAR) were at increased risk for inadequate 25OHD. Nearly 75% of children failed to meet the EAR. Overall, not meeting the EAR was associated with inadequate 25OHD (odds ratio=2.5; 95% CI 1.4 to 4.5). However, this association differed by weight status (P=0.02) and race/ethnicity (P=0.02). Overweight/obese children who failed to meet the EAR were five times more likely to be at risk for inadequate 25OHD than overweight/obese children who met it (95% CI 2.0 to 12.7; P<0.001). Non-Hispanic blacks with intakes below the EAR were nearly four times more likely to be at risk for inadequate 25OHD than those who met the EAR (95% CI 1.5 to 9.7; P<0.01). The majority of US children failed to meet current vitamin D recommendations. Overweight/obese and non-Hispanic black children were especially likely to be at risk for inadequate 25OHD when not consuming the EAR. PMID:23916971

  4. Human keratinocyte line HaCaT metabolizes 1alpha-hydroxyvitamin D3 and vitamin D3 to 1alpha,25-dihydroxyvitamin D3 (calcitriol).

    PubMed

    Lehmann, B; Pietzsch, J; Kämpf, A; Meurer, M

    1998-11-01

    Cultured human keratinocytes have the property to hydroxylate exogenous 25-hydroxyvitamin D3 (25OHD3) at the C-1alpha position thus producing 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3). In this study we investigated whether keratinocytes can also hydroxylate vitamin D3 and one of its metabolites at the C-25 position. We could demonstrate that HaCaT keratinocytes can metabolize 1alpha-hydroxyvitamin D3 (1alpha-OHD3) and vitamin D3 to 1alpha,25(OH)2D3. Identification of the generated product as 1alpha,25(OH)2D3 was based on its elution pattern in two different high performance liquid chromatography systems, on its specific binding in a calf thymus receptor assay and on its gas chromatography-mass spectrometry characteristics. The hydroxylation of vitamin D3 to 1alpha,25(OH)2D3 was dose- and time-dependent. Bovine serum albumin added up to 1.5% (w/v) to the culture medium greatly increased the hydroxylation rates. These results show that HaCaT cells have the capacity to hydroxylate vitamin D3 at the C-1/25 positions. The generation of endogenous 1alpha,25(OH)2D3 from vitamin D3 within the skin may indicate a novel pathway which is of importance for the regulation of epidermal cell growth and differentiation. PMID:9833978

  5. Vitamin D metabolism in pregnant rabbits: differences between the maternal and fetal response to administration of large amounts of vitamin D3.

    PubMed

    Kubota, M; Ohno, J; Shiina, Y; Suda, T

    1982-06-01

    Maternal and fetal metabolism of vitamin D was examined in term pregnant rabbits fed a normal diet and in those supplemented with a large amount of vitamin D3. Term pregnant rabbits (27--30 days of gestation) fed the normal diet showed lower levels of plasma calcium, 25-hydroxyvitamin D3 (250HD3), and 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] and higher plasma 1 alpha, 25-dihydroxyvitamin D3 [1 alpha, 25-(OH)2D3] levels than age-matched nonpregnant female rabbits. Kidney homogenates from pregnant rabbits produced mainly 1 alpha 25-(OH)2D3, while those from nonpregnant animals produced 24,25-(OH)2D3 primarily. Plasma concentrations of calcium and phosphorus were significantly higher in fetuses than in mothers. Plasma levels of 250HD3 and 24,25-(OH)2D3 in fetuses were almost identical to those in mothers, whereas 1 alpha,25-(OH)2D3 levels in plasma were significantly higher in mothers than in their fetuses. A daily administration of 650 nmol vitamin D3 for 3 days to term pregnant rabbits caused a significant increase in calcium, phosphorus, 25OHD3, and 24,25-(OH)2D3 in maternal plasma, and in 25OHD3 and 24,25-(OH)2D3, but not calcium and phosphorus in fetal plasma. Treatment with large amounts of vitamin D3 also induced a marked suppression of 1 alpha-hydroxylase activity and a concomitant increase of 24-hydroxylase activity in the maternal but not in the fetal kidney. Plasma concentrations of 1 alpha,25-(OH)2D3 were not affected by treatment with large amounts of vitamin D3 in either the fetuses or the mothers. These results clearly indicate that the renal 25OHD3 metabolism in the fetus is regulated independently of that in the mother. PMID:6280980

  6. 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

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

    2015-07-01

    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 [d 3-25(OH)D2 and d 6-25(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 100.3% for 25(OH)D3 and 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. Graphical abstract Bias assessment using NIST standard reference materials. Legend CDC mean mass fractions (ng/g) ± U 95 (6

  7. Vitamin D3 represses IgE-dependent mast cell activation via mast cell-CYP27B1 and -vitamin D receptor activity

    PubMed Central

    Yip, Kwok-Ho; Kolesnikoff, Natasha; Yu, Chunping; Hauschild, Nicholas; Taing, Houng; Biggs, Lisa; Goltzman, David; Gregory, Philip A.; Anderson, Paul H.; Samuel, Michael S.; Galli, Stephen J.; Lopez, Angel F.; Grimbaldeston, Michele A.

    2014-01-01

    Background Mast cells have gained notoriety based on their detrimental contributions to IgE-mediated allergic disorders. Although mast cells express the vitamin D receptor (VDR), it is not clear to what extent 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), or its predominant inactive precursor metabolite in circulation, 25-hydroxyvitamin D3 (25OHD3), can influence IgE-mediated mast cell activation and passive cutaneous anaphylaxis (PCA) in vivo. Objective We sought to assess whether the vitamin D3 metabolites, 25OHD3 and 1α,25(OH)2D3, can repress IgE-dependent mast cell activation via mast cell-CYP27B1 and -vitamin D receptor activity. Methods We measured the extent of vitamin D3 suppression of IgE-mediated mast cell degranulation and mediator production in vitro, as well as the vitamin D3-induced curtailment of PCA responses in WBB6F1-KitW/W-v or C57BL/6J-KitW-sh/W-sh mice engrafted with mast cells that did or did not express VDR or CYP27B1. Results Here we show that mouse and human mast cells can convert 25OHD3 to 1α,25(OH)2D3 via 25-hydroxyvitamin D-1α–hydroxylase (CYP27B1) activity, and that both of these vitamin D3 metabolites suppressed IgE-induced mast cell-derived pro-inflammatory and vasodilatory mediator production in a VDR-dependent manner in vitro. Furthermore, epicutaneously applied vitamin D3 metabolites significantly reduced the magnitude of skin swelling associated IgE-mediated PCA reactions in vivo; a response that required functional mast cell-VDRs and mast cell-CYP27B1. Conclusion Taken together, our findings provide a mechanistic explanation for the anti-inflammatory effects of vitamin D3 on mast cell function by demonstrating that mast cells can actively metabolize 25OHD3 to dampen IgE-mediated mast cell activation in vitro and in vivo. PMID:24461581

  8. 25OHD analogues and vacuum blood collection tubes dramatically affect the accuracy of automated immunoassays.

    PubMed

    Yu, Songlin; Cheng, Xinqi; Fang, Huiling; Zhang, Ruiping; Han, Jianhua; Qin, Xuzhen; Cheng, Qian; Su, Wei; Hou, Li'an; Xia, Liangyu; Qiu, Ling

    2015-01-01

    Variations in vitamin D quantification methods are large, and influences of vitamin D analogues and blood collection methods have not been systematically examined. We evaluated the effects of vitamin D analogues 25OHD2 and 3-epi 25OHD3 and blood collection methods on vitamin D measurement, using five immunoassay systems and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Serum samples (332) were selected from routine vitamin D assay requests, including samples with or without 25OHD2 or 3-epi 25OHD3, and analysed using various immunoassay systems. In samples with no 25OHD2 or 3-epi 25OHD3, all immunoassays correlated well with LC-MS/MS. However, the Siemens system produced a large positive mean bias of 12.5 ng/mL and a poor Kappa value when using tubes with clot activator and gel separator. When 25OHD2 or 3-epi 25OHD3 was present, correlations and clinical agreement decreased for all immunoassays. Serum 25OHD in VACUETTE tubes with gel and clot activator, as measured by the Siemens system, produced significantly higher values than did samples collected in VACUETTE tubes with no additives. Bias decreased and clinical agreement improved significantly when using tubes with no additives. In conclusion, most automated immunoassays showed acceptable correlation and agreement with LC-MS/MS; however, 25OHD analogues and blood collection tubes dramatically affected accuracy. PMID:26420221

  9. 25OHD analogues and vacuum blood collection tubes dramatically affect the accuracy of automated immunoassays

    PubMed Central

    Yu, Songlin; Cheng, Xinqi; Fang, Huiling; Zhang, Ruiping; Han, Jianhua; Qin, Xuzhen; Cheng, Qian; Su, Wei; Hou, Li’an; Xia, Liangyu; Qiu, Ling

    2015-01-01

    Variations in vitamin D quantification methods are large, and influences of vitamin D analogues and blood collection methods have not been systematically examined. We evaluated the effects of vitamin D analogues 25OHD2 and 3-epi 25OHD3 and blood collection methods on vitamin D measurement, using five immunoassay systems and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Serum samples (332) were selected from routine vitamin D assay requests, including samples with or without 25OHD2 or 3-epi 25OHD3, and analysed using various immunoassay systems. In samples with no 25OHD2 or 3-epi 25OHD3, all immunoassays correlated well with LC-MS/MS. However, the Siemens system produced a large positive mean bias of 12.5 ng/mL and a poor Kappa value when using tubes with clot activator and gel separator. When 25OHD2 or 3-epi 25OHD3 was present, correlations and clinical agreement decreased for all immunoassays. Serum 25OHD in VACUETTE tubes with gel and clot activator, as measured by the Siemens system, produced significantly higher values than did samples collected in VACUETTE tubes with no additives. Bias decreased and clinical agreement improved significantly when using tubes with no additives. In conclusion, most automated immunoassays showed acceptable correlation and agreement with LC-MS/MS; however, 25OHD analogues and blood collection tubes dramatically affected accuracy. PMID:26420221

  10. Severe vitamin D deficiency in a case of primary hyperparathyroidism caused by parathyroid lipoadenoma, effect of 25OHD3 treatment.

    PubMed

    Coen, G; Bondatti, F; de Matteis, A; Ballanti, P; Mazzaferro, S; Sardella, D; Smacchi, A

    1989-01-01

    This report describes the case of a 60-year-old woman with severe metabolic bone disease and fractures due to vitamin D deficiency and hyperparathyroidism. 25OHDH3 and 1,25(OH)2D3 serum levels were undetectable and increased immediately following 25OHD3 oral administration. Serum 1,25(OH)2D3 following vitamin D repletion reached values above the normal range, and remained elevated with strict dependence on the serum 25OHD3 levels. Parathyroid hormone and alkaline phosphatase decreased during treatment, without reaching normality during 1 year of observation. Bone biopsies before and after 8-month 25OHD3 treatment showed disappearance of the osteomalacic and hyperparathyroid lesions. During treatment an increase in serum and urine calcium and formation of renal stones were observed. The patient underwent neck exploration with the finding and removal of a lipoadenoma, a rare parathyroid tumor, followed by complete and permanent remission of the disease. In conclusion, this case is suggestive of the key role played by the long-term vitamin D status in the clinical expression of primary hyperparathyroidism. PMID:2615720

  11. The Association between Maternal 25-Hydroxyvitamin D Concentration during Gestation and Early Childhood Cardio-metabolic Outcomes: Is There Interaction with Pre-Pregnancy BMI?

    PubMed Central

    Hrudey, E. Jessica; Reynolds, Rebecca M.; Oostvogels, Adriëtte J. J. M.; Brouwer, Ingeborg A.; Vrijkotte, Tanja G. M.

    2015-01-01

    Both maternal 25-hydroxyvitamin D(25OHD) status and pre-pregnancy BMI(pBMI) may influence offspring cardio-metabolic outcomes. Lower 25OHD concentrations have been observed in women with both low and high pBMIs, but the combined influence of pBMI and 25OHD on offspring cardio-metabolic outcomes is unknown. Therefore, this study investigated the role of pBMI in the association between maternal 25OHD concentration and cardio-metabolic outcomes in 5-6 year old children. Data were obtained from the ABCD cohort study and 1882 mother-child pairs were included. The offspring outcomes investigated were systolic and diastolic blood pressure, heart rate, BMI, body fat percentage(%BF), waist-to-height ratio, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, glucose, C-peptide, and insulin resistance(HOMA2-IR). 62% of the C-peptide samples were below the detection limit and were thus imputed using survival analysis. Models were corrected for maternal and offspring covariates and tested for interaction with pBMI. Interaction with pBMI was observed in the associations with insulin resistance markers: in offspring of overweight mothers(≥25.0kg/m2), a 10 nmol/L increase in maternal 25OHD was associated with a 0.007(99%CI:-0.01,-0.001) nmol/L decrease in C-peptide and a 0.02(99%CI:-0.03,-0.004) decrease in HOMA2-IR. When only non-imputed data were analyzed, there was a trend for interaction in the relationship but the results lost significance. Interaction with pBMI was not observed for the other outcomes. A 10 nmol/L increase in maternal 25OHD was significantly associated with a 0.13%(99%CI:-0.3,-0.003) decrease in %BF after correction for maternal and child covariates. Thus, intrauterine exposure to both low 25OHD and maternal overweight may be associated with increased insulin resistance in offspring, while exposure to low 25OHD in utero may be associated with increased offspring %BF with no interactive effects from pBMI. Due to the limitations of this study

  12. The beneficial effects of vitamin D3 on reducing antibody titers against Epstein-Barr virus in multiple sclerosis patients.

    PubMed

    Najafipoor, Adeleh; Roghanian, Rasoul; Zarkesh-Esfahani, Sayyed Hamid; Bouzari, Majid; Etemadifar, Masoud

    2015-03-01

    Recently, the relationship between immunoreactivity to Epstein-Barr virus (EBV) and hypo-vitamin D in multiple sclerosis (MS) patients has been described. The aim of this study was to investigate whether vitamin D3 supplementation in MS patients could influence the immune response against latent EBV infection. Forty MS patients were recruited in this study. Twenty-seven patients were supplemented with 50,000 IU/week of vitamin D3 for 6 months and thirteen enrolled as controls. 25-Hydroxyvitamin D (25OHD) levels and IgG titers against EBNA1 and VCA were determined pre- and post-supplementation. All the patients were seropositive for EBV prior to vitamin D supplementation. In this cohort, 22.5% and 47.5% of the MS patients had deficient and insufficient levels of 25OHD, respectively. Our findings confirm that antibody titers against EBV in MS patients rise after the onset of the disease and indicate that vitamin D3 supplementation could limit augmentation of these titers in MS patients. PMID:25666504

  13. Pretreatment Serum Concentrations of 25-Hydroxyvitamin D and Breast Cancer Prognostic Characteristics: A Case-Control and a Case-Series Study

    PubMed Central

    Yao, Song; Sucheston, Lara E.; Millen, Amy E.; Johnson, Candace S.; Trump, Donald L.; Nesline, Mary K.; Davis, Warren; Hong, Chi-Chen; McCann, Susan E.; Hwang, Helena; Kulkarni, Swati; Edge, Stephen B.; O'Connor, Tracey L.; Ambrosone, Christine B.

    2011-01-01

    Background Results from epidemiologic studies on the relationship between vitamin D and breast cancer risk are inconclusive. It is possible that vitamin D may be effective in reducing risk only of specific subtypes due to disease heterogeneity. Methods and Findings In case-control and case-series analyses, we examined serum concentrations of 25-hydroxyvitamin D (25OHD) in relation to breast cancer prognostic characteristics, including histologic grade, estrogen receptor (ER), and molecular subtypes defined by ER, progesterone receptor (PR) and HER2, among 579 women with incident breast cancer and 574 controls matched on age and time of blood draw enrolled in the Roswell Park Cancer Institute from 2003 to 2008. We found that breast cancer cases had significantly lower 25OHD concentrations than controls (adjusted mean, 22.8 versus 26.2 ng/mL, p<0.001). Among premenopausal women, 25OHD concentrations were lower in those with high- versus low-grade tumors, and ER negative versus ER positive tumors (p≤0.03). Levels were lowest among women with triple-negative cancer (17.5 ng/mL), significantly different from those with luminal A cancer (24.5 ng/mL, p = 0.002). In case-control analyses, premenopausal women with 25OHD concentrations above the median had significantly lower odds of having triple-negative cancer (OR = 0.21, 95% CI = 0.08–0.53) than those with levels below the median; and every 10 ng/mL increase in serum 25OHD concentrations was associated with a 64% lower odds of having triple-negative cancer (OR = 0.36, 95% CI = 0.22–0.56). The differential associations by tumor subtypes among premenopausal women were confirmed in case-series analyses. Conclusion In our analyses, higher serum levels of 25OHD were associated with reduced risk of breast cancer, with associations strongest for high grade, ER negative or triple negative cancers in premenopausal women. With further confirmation in large prospective studies, these findings could warrant

  14. Cross-talk among structural domains of human DBP upon binding 25-hydroxyvitamin D

    PubMed Central

    Ray, Arjun; Swamy, Narasimha; Ray, Rahul

    2007-01-01

    Serum vitamin D-binding protein (DBP) is structurally very similar to serum albumin (ALB); both have three distinct structural domains and high cysteine-content. Yet, functionally they are very different. DBP possesses high affinity for vitamin D metabolites and G-actin, but ALB does not. It has been suggested that there may be cross-talk among the domains so that binding of one ligand may influence the binding of others. In this study we have employed 2-p-toluidinyl-6-sulphonate (TNS), a reporter molecule that fluoresces upon binding to hydrophobic pockets of DBP. We observed that recombinant domain III possesses strong binding for TNS, which is not influenced by 25-hydroxyvitamin D3 (25-OH-D3), yet TNS-fluorescence of the whole protein is quenched by 25-OH-D3. These results provide a direct evidence of cross-talk among the structural domains of DBP. PMID:18035050

  15. Serum 25-Hydroxyvitamin D Concentration and Cognitive Impairment

    PubMed Central

    Llewellyn, David J.; Langa, Kenneth M.; Lang, Iain A.

    2009-01-01

    Vitamin D may be of interest in the prevention of cognitive impairment, though previous findings are inconclusive. Participants were 1766 adults aged 65 years and older from the Health Survey for England 2000, a nationally representative population-based study. Cognitive impairment was assessed using the Abbreviated Mental Test Score. The cross-sectional relation of serum 25-hydroxyvitamin D quartiles to cognitive impairment was modeled using logistic regression. In all, 212 participants (12%) were cognitively impaired. Odds ratios (95% confidence intervals) for cognitive impairment in the first (8–30 nmol/L), second (31–44 nmol/L), and third (45–65 nmol/L) quartiles of serum 25-hydroxyvitamin D compared with the fourth (66–170 nmol/L) were 2.3 (1.4–3.8), 1.4 (0.8–2.4), and 1.1 (0.6–1.9), after adjustment for age, sex, education, ethnicity, season of testing, and additional risk factors for cognitive impairment (P for linear trend = .001). Our data suggest low serum 25-hydroxyvitamin D is associated with increased odds of cognitive impairment. PMID:19073839

  16. NHANES Monitoring of Serum 25-Hydroxyvitamin D: A Roundtable Summary123

    PubMed Central

    Yetley, Elizabeth A.; Pfeiffer, Christine M.; Schleicher, Rosemary L.; Phinney, Karen W.; Lacher, David A.; Christakos, Sylvia; Eckfeldt, John H.; Fleet, James C.; Howard, George; Hoofnagle, Andrew N.; Hui, Siu L.; Lensmeyer, Gary L.; Massaro, Joseph; Peacock, Munro; Rosner, Bernard; Wiebe, Donald; Bailey, Regan L.; Coates, Paul M.; Looker, Anne C.; Sempos, Christopher; Johnson, Clifford L.; Picciano, Mary Frances

    2010-01-01

    A roundtable to discuss monitoring of serum 25-hydroxyvitamin D [25(OH)D] in the NHANES was held in late July 2009. Topics included the following: 1) options for dealing with assay fluctuations in serum 25(OH)D in the NHANES conducted between 1988 and 2006; 2) approaches for transitioning between the RIA used in the NHANES between 1988 and 2006 to the liquid chromatography tandem MS (LC-MS/MS) measurement procedure to be used in NHANES 2007 and later; 3) approaches for integrating the recently available standard reference material for vitamin D in human serum (SRM 972) from the National Institute of Standards and Technology (NIST) into the NHANES; 4) questions regarding whether the C-3 epimer of 25-hydroxyvitamin D3 [3-epi-25(OH)D3] should be measured in NHANES 2007 and later; and 5) identification of research and educational needs. The roundtable experts agreed that the NHANES data needed to be adjusted to control for assay fluctuations and offered several options for addressing this issue. The experts suggested that the LC-MS/MS measurement procedure developed by NIST could serve as a higher order reference measurement procedure. They noted the need for a commutability study for the recently released NIST SRM 972 across a range of measurement procedures. They suggested that federal agencies and professional organizations work with manufacturers to improve the quality and comparability of measurement procedures across all laboratories. The experts noted the preliminary nature of the evidence of the 3-epi-25(OH)D3 but felt that it should be measured in 2007 NHANES and later. PMID:20881084

  17. End product inhibition of hepatic 25-hydroxyvitamin D production in the rat: specificity and kinetics

    SciTech Connect

    Milne, M.L.; Baran, D.T.

    1985-11-01

    The role of vitamin D metabolites in the regulation of hepatic 25-hydroxyvitamin D production was investigated by examining the effects of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin D on the synthesis of (25-/sup 3/H)hydroxyvitamin D by rachitic rat liver homogenates. Production of (25-/sup 3/H)hydroxyvitamin D was inhibited by 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, but not by 24,25-dihydroxyvitamin D. 25-Hydroxyvitamin D increased the Km of the vitamin D-25-hydroxylase enzyme(s), while 1,25-dihydroxyvitamin D decreased the Vmax with a Ki of 88.7 ng/ml. Inhibition of hepatic 25-hydroxyvitamin D production by 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D may be another control mechanism to regulate circulating vitamin D levels.

  18. 25-Hydroxyvitamin D: functional outcomes in infants and young children.

    PubMed

    Greer, Frank R

    2008-08-01

    Vitamin D deficiency occurs in the United States in exclusively breastfed infants who have high levels of skin pigmentation, inadequate vitamin D supplementation, and insufficient sunlight exposure. I review serum 25-hydroxyvitamin D [25(OH)D] concentrations and functional outcomes of vitamin deficiency in young children and breastfed and nonbreastfed infants. These outcomes include the presence or absence of vitamin D deficiency rickets, bone mineral content, and serum parathyroid hormone concentration. Daily vitamin D supplements of 400 IU/L keep serum 25(OH)D concentrations higher than 50 nmol/L and prevent rickets in infants and young children. The available evidence is not sufficient to support the use of bone mineral content or parathyroid hormone concentrations in infants and young children as functional outcomes to define deficient or sufficient levels of 25(OH)D. I therefore propose a research agenda to establish the functional definitions of vitamin D sufficiency or deficiency in infants and young children. PMID:18689395

  19. A rapid assay for 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D 24-hydroxylase

    SciTech Connect

    Burgos-Trinidad, M.; Brown, A.J.; DeLuca, H.F. )

    1990-10-01

    A rapid method for the measurement of the 24-hydroxylated metabolites of 25-hydroxy(26,27-3H)vitamin D3 and 1,25-dihydroxy(26,27-3H)vitamin D3 has been developed. This measurement has, in turn, made possible a rapid assay for the 24-hydroxylases of the vitamin D system. The assay involves the use of 26,27-3H-labeled 1,25-dihydroxyvitamin D3 or 25-hydroxyvitamin D3 as the substrate and treatment of the enzyme reaction mixture with sodium periodate, which specifically cleaves the 24-hydroxylated products between carbons 24 and 25, releasing tritiated acetone. The acetone is measured after its separation from the labeled substrate by using a reversed-phase cartridge. The results obtained with this assay were validated by comparison with the results obtained with a well-established high-performance liquid chromatography assay. The activity of the enzyme determined by both methods was equal. This assay has been successfully used for the rapid screening of column fractions during purification of the enzyme and in the screening for monoclonal antibodies to the 24-hydroxylase.

  20. The Association between Plasma 25OHD3 Concentrations, C-Reactive Protein Levels, and Coronary Artery Atherosclerosis in Postmenopausal Monkeys

    PubMed Central

    Schnatz, Peter F.; Vila-Wright, Sharon; Jiang, Xuezhi; Register, Thomas C.; Kaplan, Jay R.; Clarkson, Thomas B.; Appt, Susan E.

    2012-01-01

    Objective To identify potential relationships between plasma 25OHD, C-reactive protein (CRP), coronary artery atherosclerosis (CAA), and coronary artery remodeling in monkeys consuming atherogenic diets. Methods Female cynomolgus monkeys (n=74) were fed a casein-lactalbumin (C/L) based, moderately atherogenic diet for 12 months. They then consumed either a soy (n=35) or C/L (n=39) based diet for 32 months. CRP concentrations were then determined and monkeys underwent surgical menopause. Each diet group was then re-randomized to receive soy (n=36) or C/L (n=38). After 32 post-menopausal months, 25OHD, CRP, CAA, and coronary artery remodeling were determined. All monkeys received a women’s equivalent of 1,000 IU/day of 25OHD3 and 1,200 mg/day of calcium, throughout the study. Results The pre and post-menopausal dietary protein sources had no effect on post-menopausal 25OHD3 concentrations (p=0.6). Across treatment groups, there was a statistically significant inverse relationship between 25OHD3 concentrations and CRP at necropsy (r=-0.35, p=0.003). A significant inverse correlation between 25OHD3 concentration and the change in CRP, from pre-menopause to post-menopause, was observed (r=-0.32, p=0.007). The significant associations identified between plasma 25OHD3 and CRP remained after controlling for postmenopausal diet. Those monkeys with a greater increase in CRP also had significantly more CAA and less ability to maintain normal lumens by remodeling. Conclusions Higher plasma concentrations of 25OHD3 were associated with lower CRP. Lower CRP was associated with less coronary atherosclerosis and improved coronary artery remodeling. These findings suggest that 25OHD3 concentrations are associated with an anti-inflammatory state and may support an association between oral 25OHD3 and cardioprotection. PMID:22713861

  1. Association between Prediagnostic Serum 25-Hydroxyvitamin D Concentration and Glioma

    PubMed Central

    Zigmont, Victoria; Garrett, Amy; Peng, Jin; Seweryn, Michal; Rempala, Grzegorz A.; Harris, Randall; Holloman, Christopher; Gundersen, Thomas E.; Ahlbom, Anders; Feychting, Maria; Johannesen, Tom Borge; Grimsrud, Tom Kristian; Schwartzbaum, Judith

    2016-01-01

    There are no previous studies of the association between prediagnostic serum vitamin D concentration and glioma. Vitamin D has immunosuppressive properties; as does glioma. It was, therefore, our hypothesis that elevated vitamin D concentration would increase glioma risk. We conducted a nested case–control study using specimens from the Janus Serum Bank cohort in Norway. Blood donors who were subsequently diagnosed with glioma (n = 592), between 1974 and 2007, were matched to donors without glioma (n = 1112) on date and age at blood collection and sex. We measured 25-hydroxyvitamin D (25(OH)D), an indicator of vitamin D availability, using liquid chromatography coupled with mass spectrometry. Seasonally adjusted odds ratios (ORs) and 95% confidence intervals (95%CIs) were estimated for each control quintile of 25(OH)D using conditional logistic regression. Among men diagnosed with high grade glioma >56, we found a negative trend (P=.04). Men diagnosed ≤ 56 showed a borderline positive trend (P=.08). High levels (>66 nmol/L) of 25(OH)D in men > 56 were inversely related to high grade glioma from ≥ 2 years before diagnosis (OR=0.59; 95%CI=0.38,0.91) to ≥ 15 years before diagnosis (OR=0.61; 95%CI=0.38,0.96). Our findings are consistent long before glioma diagnosis and are therefore unlikely to reflect preclinical disease. PMID:26317248

  2. Serum 25-Hydroxyvitamin D Levels in Pediatric Burn Patients

    PubMed Central

    Sobouti, Behnam; Riahi, Aina; Fallah, Shahrzad; Ebrahimi, Masoumeh; Shafiee Sabet, Azin; Ghavami, Yaser

    2016-01-01

    Background Previous studies have implicated the important and active role of vitamin D in the immune system. Objectives The aim of this study was to evaluate serum levels of 25-hydroxyvitamin D in children with burn injuries. Materials and Methods In this cross-sectional study, 118 patients with various degrees of burn injuries were enrolled. A checklist consisting of demographic data, total body surface area (TBSA) affected by burn, degree of burn, serum level of 25(OH)D, total protein, albumin, electrolytes, and parathyroid hormone was recorded for each patient. Results Sixty-eight (57.6%) males and 50 (42.4%) females with a mean age of 4.04 years (SD = 3.04) were evaluated. The mean level of 25(OH)D was 14.58 ng/mL (SD = 6.94). Levels of 25(OH)D in four (3.39%) cases were higher than 30 ng/mL, while 95 (81.35%) cases had levels lower than 20 ng/mL, and 19 (16.10%) cases had levels of 21 - 30 ng/mL. The level of 25(OH)D was below recommended levels in 96.61% of cases, while 81.34% had vitamin D deficiency and 16.1% had insufficiency. We found a significant correlation between vitamin 25(OH)D and total protein, albumin, and total and ionized calcium (P < 0.001). There was also a significant negative correlation between 25(OH)D and TBSA affected by burn (P = 0.001). Conclusions The levels of 25(OH)D in children suffering from severe burns were low. Supplementation might be useful in patients with very low levels of serum vitamin D. PMID:27218060

  3. Determinants of serum 25-hydroxyvitamin D in Hong Kong.

    PubMed

    Xu, Cuiling; Perera, Ranawaka A P M; Chan, Yap-Hang; Fang, Vicky J; Ng, Sophia; Ip, Dennis K M; Kam, Andrea May-Sin; Leung, Gabriel M; Peiris, J S Malik; Cowling, Benjamin J

    2015-07-14

    Vitamin D plays an important role in skeletal health throughout life. Some studies have hypothesised that vitamin D may reduce the risk of other diseases. Our study aimed to estimate age-specific and sex-specific serum 25-hydroxyvitamin D (25(OH)D) status and to identify the determinants of serum 25(OH)D status in Hong Kong, a subtropical city in southern China. In 2009-2010, households in Hong Kong were followed up to identify acute respiratory illnesses, and sera from 2694 subjects were collected in three to four different study phases to permit measurement of 25(OH)D levels at different times of the year. A questionnaire survey on diet and lifestyle was conducted among children, with simultaneous serum collection in April and May 2010. The mean of serum 25(OH)D levels in age groups ranged from 39 to 63 nmol/l throughout the year with the mean values in all age groups in spring below 50 nmol/l. Children aged 6-17 years, and girls and women had significantly lower serum 25(OH)D levels than adults, and boys and men, respectively (all P< 0.001). We estimated that serum 25(OH)D levels in Hong Kong followed a lagged pattern relative to climatic season by 5 weeks with lowest observed levels in early spring (March). For children aged 6-17 years, reporting a suntan, having at least 1 servings of fish/week and having at least 1 serving of eggs/week were independently associated with higher serum 25(OH)D levels. Adequate sunlight exposure and increased intake of dietary vitamin D could improve vitamin D status, especially for children and females in the winter and spring. PMID:26051634

  4. Effect of 25-Hydroxyvitamin D Status on Serological Response to Influenza Vaccine in Prostate Cancer Patients

    PubMed Central

    Chadha, Manpreet K.; Fakih, Marwan; Muindi, Josephia; Tian, Lili; Mashtare, Terry; Johnson, Candace S.; Trump, Donald

    2015-01-01

    BACKGROUND Epidemiologic data suggest that there is an association between vitamin D deficiency and influenza infection. We conducted a prospective influenza vaccination study to determine the influence of vitamin D status on serological response to influenza vaccine in prostate cancer (CaP) patients. METHODS During the 2006–2007 influenza season, CaP patients treated at Roswell Park Cancer Institute were offered vaccination with the trivalent influenza vaccine (Fluzone®, 2006–2007) and sera collected for hemagglutination inhibition (HI) assay titers before and 3 months after vaccination. Response to vaccination was defined as ≥1:40 titer ratio or a fourfold increase in titer at 3 months, against any of the three strains. Serum 25-hydroxyvitamin D (25-D3) levels were measured using DiaSorin 125I radioimmunoassay kits. RESULTS Thirty-five patients with CaP participated in the study. Median baseline 25-D3 level was 44.88 ng/ml (range: 9.16–71.98 ng/ml) Serological response against any of the three strains was noted in 80%. There was a significant effect of baseline 25-D3 level when tested as a continuous variable in relation to serological response (P = 0.0446). All patients in the upper quartile of 25-D3 level responded by mounting a serological response (P = 0.0344). None of the other baseline variables (age, race, chemotherapy status, or white cell count) had an effect on serological response. CONCLUSIONS In this study in CaP patients, a replete vitamin D status was associated with more frequent serological response to influenza vaccine. PMID:20812224

  5. Triple Quadrupole Versus High Resolution Quadrupole-Time-of-Flight Mass Spectrometry for Quantitative LC-MS/MS Analysis of 25-Hydroxyvitamin D in Human Serum

    NASA Astrophysics Data System (ADS)

    Geib, Timon; Sleno, Lekha; Hall, Rabea A.; Stokes, Caroline S.; Volmer, Dietrich A.

    2016-08-01

    We describe a systematic comparison of high and low resolution LC-MS/MS assays for quantification of 25-hydroxyvitamin D3 in human serum. Identical sample preparation, chromatography separations, electrospray ionization sources, precursor ion selection, and ion activation were used; the two assays differed only in the implemented final mass analyzer stage; viz. high resolution quadrupole-quadrupole-time-of-flight (QqTOF) versus low resolution triple quadrupole instruments. The results were assessed against measured concentration levels from a routine clinical chemiluminescence immunoassay. Isobaric interferences prevented the simple use of TOF-MS spectra for extraction of accurate masses and necessitated the application of collision-induced dissociation on the QqTOF platform. The two mass spectrometry assays provided very similar analytical figures of merit, reflecting the lack of relevant isobaric interferences in the MS/MS domain, and were successfully applied to determine the levels of 25-hydroxyvitamin D for patients with chronic liver disease.

  6. Triple Quadrupole Versus High Resolution Quadrupole-Time-of-Flight Mass Spectrometry for Quantitative LC-MS/MS Analysis of 25-Hydroxyvitamin D in Human Serum

    NASA Astrophysics Data System (ADS)

    Geib, Timon; Sleno, Lekha; Hall, Rabea A.; Stokes, Caroline S.; Volmer, Dietrich A.

    2016-05-01

    We describe a systematic comparison of high and low resolution LC-MS/MS assays for quantification of 25-hydroxyvitamin D3 in human serum. Identical sample preparation, chromatography separations, electrospray ionization sources, precursor ion selection, and ion activation were used; the two assays differed only in the implemented final mass analyzer stage; viz. high resolution quadrupole-quadrupole-time-of-flight (QqTOF) versus low resolution triple quadrupole instruments. The results were assessed against measured concentration levels from a routine clinical chemiluminescence immunoassay. Isobaric interferences prevented the simple use of TOF-MS spectra for extraction of accurate masses and necessitated the application of collision-induced dissociation on the QqTOF platform. The two mass spectrometry assays provided very similar analytical figures of merit, reflecting the lack of relevant isobaric interferences in the MS/MS domain, and were successfully applied to determine the levels of 25-hydroxyvitamin D for patients with chronic liver disease.

  7. 25-hydroxyvitamin D levels are associated with multiple sclerosis in Iran: A cross-sectional study.

    PubMed

    Karampoor, Sajad; Zahednasab, Hamid; Ramagopalan, Sreeram; Mehrpour, Masoud; Safarnejad Tameshkel, Fahimeh; Keyvani, Hossein

    2016-01-15

    Vitamin D is being increasingly studied in multiple sclerosis (MS). A number of studies have shown that MS patients have lower levels of 25-hydroxyvitamin D as compared to comparator populations, but previous studies in Iran have been conflicting, perhaps due to their small sample size. We performed the largest study to date investigating 25-hydroxyvitamin D levels in Iranian MS patients (n=700) and controls (n=1000). 25-hydroxyvitamin D was measured using a quantitative chemiluminescent immunometric assay. 25-hydroxyvitamin D levels were lower in patients with MS. Over 24% of controls were vitamin D sufficient as compared to 3.4% of patients. Logistic regression showed that for every 1 ng/mL increase in 25-hydroxyvitamin D, the odds for MS decreased (odds ratio=0.87; 95% confidence interval (CI) 0.85-0.88; p<0.001), after adjusting for age and sex. There was no association between 25-hydroxyvitamin D levels and disability scores in MS patients. Iranian Patients with MS have low levels of vitamin D and, where deemed necessary, appropriate supplementation should be given. PMID:26711568

  8. Positive Association between Blood 25-Hydroxyvitamin D Levels and Pterygium after Control for Sunlight Exposure

    PubMed Central

    Jee, Donghyun; Kim, Eun Chul; Cho, Eunyoung; Arroyo, Jorge G.

    2016-01-01

    Purpose To investigate the association between blood 25-hydroxyvitamin D levels and pterygium. Methods Korean National Health and Nutrition Examination Survey 2008–2011 were used for the present epidemiologic study. A total of 19,178 participants aged ≥ 30 years were evaluated for blood 25-hydroxyvitamin D levels and performed ophthalmic slit lamp examinations. Pterygium was considered as a growth of fibrovascular tissue over the cornea. Results The average blood 25-hydroxyvitamin D levels were 18.6 ng/mL, and prevalence of pterygium was 6.5%. The odds of pterygium significantly increased across blood 25-hydroxyvitamin D quintiles after controlling sun exposure time as well as other confounders such as sex, age, smoking, diabetes, hypertension (P < 0.001). The odds ratios (OR) for pterygium was 1.51 (95% Confidence Interval[95%CI]; 1.19–1.92) in the highest blood vitamin D quintile. Stratified analysis by sex showed a positive association between blood 25-hydroxyvitamin D levels and pterygium in both men (quintile 5 versus 1, OR; 1.68, 95%CI; 1.19–2.37) and women (quintile 5 versus 1, OR; 1.37, 95% CI; 1.00–1.88). Conclusions Even after controlling sun light exposure time, we found a positive association between blood 25-hydroxyvitamin D levels and pterygium in a representative Korean population. The mechanism underlying this association is unknown. PMID:27286036

  9. A Randomized Study on the Effect of Vitamin D3 Supplementation on Skeletal Muscle Morphology and Vitamin D Receptor Concentration in Older Women

    PubMed Central

    Niramitmahapanya, Sathit; da Silva Morais, Mauricio; Rivas, Donato A.; Harris, Susan S.; Bischoff-Ferrari, Heike; Fielding, Roger A.; Dawson-Hughes, Bess

    2013-01-01

    Context: Studies examining whether vitamin D supplementation increases muscle mass or muscle-specific vitamin D receptor (VDR) concentration are lacking. Objective: Our objective was to determine whether vitamin D3 4000 IU/d alters muscle fiber cross-sectional area (FCSA) and intramyonuclear VDR concentration over 4 months. Design and Setting: This was a randomized, double-blind, placebo-controlled study in a single center. Participants: Participants were 21 mobility-limited women (aged ≥65 years) with serum 25-hydroxyvitamin D (25OHD) levels of 22.5 to 60 nmol/L. Main Outcome Measures: Baseline and 4-month FCSA and intramyonuclear VDR were measured from vastus lateralis muscle cross-sections probed for muscle fiber type (I/IIa/IIx) and VDR using immunofluorescence. Results: At baseline, mean (±SD) age was 78 ± 5 years; body mass index was 27 ± 5 kg/m2, 25OHD was 46.3 ± 9.5 nmol/L, and a short physical performance battery score was 7.95 ± 1.57 out of 12. At 4 months, 25OHD level was 52.5 ± 17.1 (placebo) vs 80.0 ± 11.5 nmol/L (vitamin D [VD]; P < .01), and change in 25OHD level was strongly associated with percent change in intramyonuclear VDR concentration-independent of group (r = 0.87, P < .001). By treatment group, percent change in intramyonuclear VDR concentration was 7.8% ± 18.2% (placebo) vs 29.7% ± 11.7% (VD; P = .03) with a more pronounced group difference in type II vs I fibers. Percent change in total (type I/II) FCSA was −7.4% ± 18.9% (placebo) vs 10.6% ± 20.0% (VD; P = .048). Conclusion: Vitamin D3 supplementation increased intramyonuclear VDR concentration by 30% and increased muscle fiber size by 10% in older, mobility-limited, vitamin D-insufficient women. Further work is needed to determine whether the observed effect of vitamin D on fiber size is mediated by the VDR and to identify which signaling pathways are involved. PMID:24108316

  10. Unique form of rickets with low serum 25-hydroxyvitamin D in two normally nourished children.

    PubMed

    Asami, T; Kawasaki, T; Uchiyama, M

    1995-04-01

    We present an unusual type of rickets involving two children: a 2 year old boy and a 15 month old boy, who presented with marked bowing of the lower extremities and bulging of costochondral junctions. Both children had normal growth, with their height and body weight greater than the 50th and 97th percentile for age. Roentgenograms of their extremities showed the typical changes of vitamin D refractory rickets. Serum alkaline phosphatase levels were elevated and serum levels of calcium and phosphate were both within the normal range. No primary cause for the rickets, including nutritional deficiencies, was found in the two patients. Characteristic findings were persistently low serum 25-hydroxyvitamin D (25-OH-D) and normal 1,25-dihydroxyvitamin D (1,25-(OH)2-D). Improvements in clinical and X-ray findings were observed after either oral administration of 1 alpha-(OH)-D3 (9-15 micrograms per day) or massive vitamin D2 therapy (600,000 IU single injection). The low serum levels of 25-OH-D did not increase unless massive vitamin D2 therapy was also given. These two cases represent a unique form of rickets that does not meet the criteria for any type of previously known rickets. PMID:7793252

  11. Circulating 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Concentrations and Postoperative Infections in Cardiac Surgical Patients: The CALCITOP-Study

    PubMed Central

    Zittermann, Armin; Kuhn, Joachim; Ernst, Jana B.; Becker, Tobias; Larisch, Julia; Dreier, Jens; Knabbe, Cornelius; Börgermann, Jochen; Gummert, Jan F.

    2016-01-01

    Background Vitamin D has immunomodulatory properties and seems to reduce the risk of infections. Whether low vitamin D concentrations are independent risk factors for nosocomial postoperative infections in surgical patients remains to be studied in detail. Methods In 3,340 consecutive cardiac surgical patients, we investigated the association of circulating 25-hydroxyvitamin D (25OHD; indicator of nutritional vitamin D status) and 1,25-dihydroxyvitamin D (1,25[OH]2D; active vitamin D hormone) with nosocomicial infections. The primary endpoint was a composite of thoracic wound infection, sepsis, and broncho-pulmonary infection. Vitamin D status was measured on the last preoperative day. Infections were assessed until discharge. Logistic regression analysis was used to examine the association between vitamin D metabolite concentrations and the composite endpoint. Results The primary endpoint was reached by 5.6% (n = 186). In patients who reached and did not reach the endpoint, in-hospital mortality was 13.4% and 1.5%, respectively (P<0.001). Median (IQR) 25OHD and 1,25(OH)2D concentrations were 43. 2 (29.7–61.9) nmol/l and 58.0 (38.5–77.5) pmol/l, respectively. Compared with the highest 1,25(OH)2D quintile (>81.0 pmol/l), the multivariable–adjusted odds ratio of infection was 2.57 (95%CI:1.47–4.49) for the lowest 1,25(OH)2D quintile (<31.5 pmol/l) and 1.85 (95%CI:1.05–3.25) for the second lowest quintile (31.5–49.0 pmol/l). There was no significant association between 25OHD concentrations and the primary endpoint. Conclusions Our data indicate an independent association of low 1,25(OH)2D levels with the risk of postoperative infections in cardiac surgical patients. Future studies should pay more attention on the clinical relevance of circulating 1,25(OH)2D and its regulation. PMID:27355377

  12. Determinants of 25-Hydroxyvitamin D Concentrations in Infants and Toddlers

    PubMed Central

    Michel, Hilary; Olabopo, Flora; Wang, Li; Nucci, Anita; Greenspan, Susan L; Rajakumar, Kumaravel

    2015-01-01

    Background Resurgence of rickets and recognition of excessive prevalence of hypovitaminosis D among all age groups in the western hemisphere have refocused attention on vitamin D nutrition. Objective To examine the prevalence of hypovitaminosis D [25-hydroxyvitamin D [25(OH)D] <30ng/mL] and characterize the determinants of 25(OH)D concentrations in 8- to 24-month-old healthy infants and toddlers living in Pittsburgh, Pennsylvania. Methods Serum 25(OH)D concentrations were measured and dietary intake of vitamin D, mode of feeding, summertime sun exposure characteristics, and skin color (sun-reactive skin type and melanin index) were assessed. Results A total of 111 healthy 8- to 24-month-old children (mean age [±SD] 14.4 [±3.5] months; male, 51%; black, 67%) were studied. Serum 25(OH)D concentration was <30 ng/mL in 16% (n=18) of the children. Median (interquartile) 25(OH)D concentration was lower in children who were ≥ 13 months vs. <13 months of age [35 (31, 40.5) vs. 40 (35.8, 44.3) ng/mL, p=0.013]; with sun-reactive skin type IV and V vs. I, II, and III [36 (31, 41) vs. 44 (36.5, 48.5) ng/mL, p=0.001]; and examined during fall/winter vs. spring/summer [35.5 (32.5, 38.5) vs. 39 (32.5, 44) ng/mL, p=0.05]. Age and skin type were significant independent predictors of 25(OH)D. Conclusions Concentrations of 25(OH)D tend to be lower in infants and toddlers during fall/winter, and in children who are older (≥13 months vs. <13 months of age) and have darker skin tone. Benefits of enhancement of 25(OH)D concentrations during fall/winter and in children with higher sun-reactive skin type need further exploration. PMID:26417213

  13. Serum 25-Hydroxyvitamin D Levels are not Associated with Adverse Outcomes in Clostridium Difficile Infection

    PubMed Central

    Micic, Dejan; Rao, Krishna; Trindade, Bruno Caetano; Walk, Seth T.; Chenoweth, Elizabeth; Jain, Ruchika; Trivedi, Itishree; Santhosh, Kavitha; Young, Vincent B.; Aronoff, David M.

    2015-01-01

    Clostridium difficile infection (CDI) is a significant source of healthcare-associated morbidity and mortality. This study investigated whether serum 25-hydroxyvitamin D is associated with adverse outcomes from CDI. Patients with CDI were prospectively enrolled. Charts were reviewed and serum 25-hydroxyvitamin D was measured. The primary outcome was a composite definition of severe disease: fever (temperature >38°C), acute organ dysfunction, or serum white blood cell count >15,000 cells/µL within 24-48 hours of diagnosis; lack of response to therapy by day 5; and intensive care unit admission; colectomy; or death within 30 days. Sixty-seven patients were included in the final analysis. Mean (±SD) serum 25-hydroxyvitamin D was 26.1 (±18.54) ng/mL. Severe disease, which occurred in 26 (39%) participants, was not associated with serum 25-hydroxyvitamin D [odds ratio (OR) 1.00; 95% confidence interval (CI) 0.96-1.04]. In the adjusted model for severe disease only serum albumin (OR 0.12; 95%CI 0.02-0.64) and diagnosis by detection of stool toxin (OR 5.87; 95%CI 1.09-31.7) remained independent predictors. We conclude that serum 25-hydroxyvitamin D is not associated with the development of severe disease in patients with CDI. PMID:26500740

  14. Association of Serum 25-Hydroxyvitamin D with Life Style and Dietary Factors in Egyptian Prepubescent Children

    PubMed Central

    Shady, Mones M. Abu; Youssef, Mai M.; Shehata, Manal A.; El-Din, Ebtissam M. Salah; ElMalt, Heba A.

    2015-01-01

    BACKGROUND: There had been a growing evidence of high prevalence of vitamin D deficiency especially among children which may increase the risk of many chronic diseases in adulthood. AIM: Assessment of different lifestyles and dietary behaviour influencing the level of serum 25-OHD in a group of Egyptian prepubescent children. SUBJECTS AND METHODS: Two hundred boys and girls aged from 9 to 11 years were recruited from two primary public schools situated in Giza governorate in Egypt. A questionnaire was developed to obtain relevant information related to age, dietary habits, and physical activity. Thorough clinical examination and measurement of weight and height were performed. Body mass index was calculated. Serum samples were assayed for 25-hydroxy vitamin D (25-OHD). RESULTS: Low serum 25-OHD (< 20 ng/ml) was found in 11.5% of the whole sample. Mean serum 25-OHD was significantly lower in obese subjects and in those with low physical activity (p < 0.05). Multiple stepwise linear regression analysis showed that BMI and physical activity were the main predictors of serum 25-OHD (P < 0.05). CONCLUSIONS: Lifestyle factors in terms of physical activity and BMI may contribute significantly to the optimal vitamin D status of apparently healthy children. PMID:27275201

  15. Plasma 25-hydroxyvitamin D and colorectal cancer risk according to tumour immunity status

    PubMed Central

    Qian, Zhi Rong; Inamura, Kentaro; Zhang, Xuehong; Ng, Kimmie; Kim, Sun A; Mima, Kosuke; Sukawa, Yasutaka; Nosho, Katsuhiko

    2014-01-01

    Objective Evidence suggests protective effects of vitamin D and anti-tumour immunity on colorectal cancer risk. Immune cells in tumour microenvironment can convert 25-hydroxyvitamin D [25(OH)D] to bioactive 1α,25-dihydroxyvitamin D3, which influences neoplastic and immune cells as an autocrine and paracrine factor. Thus, we hypothesised that the inverse association between vitamin D and colorectal cancer risk might be stronger for cancers with high-level immune response than those with low-level immune response. Design We designed a nested case-control study (318 rectal and colon carcinoma cases and 624 matched controls) within the Nurses’ Health Study and Health Professionals Follow-up Study, using molecular pathological epidemiology database. Multivariable conditional logistic regression was used to assess the association of plasma 25(OH)D with tumour subtypes according to the degree of lymphocytic reaction, tumour-infiltrating T-cells (CD3+, CD8+, CD45RO+ and FOXP3+ cells), microsatellite instability, or CpG island methylator phenotype. Results The association of plasma 25(OH)D with colorectal carcinoma differed by the degree of intratumoural periglandular reaction (Pheterogeneity=0.001); high 25(OH)D was associated with lower risk of tumour with high-level reaction [comparing the highest vs. lowest tertile: odds ratio, 0.10; 95% confidence interval, 0.03 to 0.35; Ptrend<0.001], but not risk of tumour with lower-level reaction (Ptrend>0.50). A statistically non-significant difference was observed for the associations of 25(OH)D with tumour subtypes according to CD3+ T-cell density (Pheterogeneity=0.03; adjusted statistical significance level of α=0.006). Conclusion High plasma 25(OH)D level is associated with lower risk of colorectal cancer with intense immune reaction, supporting a role of vitamin D in cancer immunoprevention through tumour-host interaction. PMID:25591978

  16. Association between subcutaneous white adipose tissue and serum 25-hydroxyvitamin D in overweight and obese adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Cholecalciferol is known to be deposited in human adipose tissue, but the distribution of 25-hydroxyvitamin D (25(OH)D) in adipose tissue is not known. Objectives: To determine whether 25(OH)D is detectable in subcutaneous white adipose tissue (SWAT) in overweight and obese persons an...

  17. 25-hydroxyvitamin D levels and juvenile idiopathic arthritis: is there an association with disease activity?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To examine the association between serum levels of 25-hydroxyvitamin D [25(OH)D] and disease activity in juvenile idiopathic arthritis (JIA), to determine the prevalence of vitamin D (VD) deficiency [25(OH)D=19 ng/ml] and insufficiency [25(OH)D 20-29 ng/ml], and to determine factors associated with ...

  18. Low 25-hydroxyvitamin D levels and cognitive impairment in hemodialysis patients

    Technology Transfer Automated Retrieval System (TEKTRAN)

    25-hydroxyvitamin D (25[OH]D) deficiency and cognitive impairment are both prevalent in hemodialysis patients in the United States. This study tested the hypothesis that 25(OH)D deficiency may be associated with cognitive impairment because of its vasculoprotective, neuroprotective, and immune-modul...

  19. Serum 25-hydroxyvitamin D is related to indicators of overall physical fitness in healthy postmenopausal women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Inadequate vitamin D status is related to increased adiposity, risk of falls, and muscle weakness, particularly in the elderly. We hypothesized that serum 25-hydroxyvitamin D (25(OH) vitamin D) is related to physical fitness indices (androidal fat, whole body lean mass, balance, strength) in healthy...

  20. Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes.

    PubMed

    Bischoff-Ferrari, Heike A

    2014-01-01

    Recent evidence suggests that vitamin D deficiency has harmful effects on health and that recent vitamin D intake recommendations may be associated with better health outcomes. In this chapter, evidence is summarized from different studies that evaluate threshold levels for serum 25(OH)D levels in relation to bone mineral density (BMD), lower extremity function, dental health, risk of falls, fractures, cancer prevention, incident hypertension and mortality. For all endpoints, levels in the deficient range (< 50 nmol/l; < 20 ng/ml) are associated with no benefit or adverse effects, while the most advantageous serum levels for 25(OH)D appeared to be close to 75 nmol/l (30 ng/ml). An intake of 800 IU (20 microg) of vitamin D3 (cholecalciferol) per day for all adults may bring 97% of the population to level of at least 50 nmol/l and about 50% up to 75 nmol/l. Thus, higher doses of vitamin D than currently recommended are needed to bring most individuals to75 nmol/l. While estimates suggest that 1600 to 2000 IU vitamin D3 per day may successfully and safely achieve this goal, the implications of higher doses for the total adult population need to be addressed in future studies. PMID:25207384

  1. 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

  2. Serum 25-hydroxyvitamin D concentrations and cardiometabolic risk factors in adolescents and young adults.

    PubMed

    Black, Lucinda J; Burrows, Sally; Lucas, Robyn M; Marshall, Carina E; Huang, Rae-Chi; Chan She Ping-Delfos, Wendy; Beilin, Lawrence J; Holt, Patrick G; Hart, Prue H; Oddy, Wendy H; Mori, Trevor A

    2016-06-01

    Evidence associating serum 25-hydroxyvitamin D (25(OH)D) concentrations and cardiometabolic risk factors is inconsistent and studies have largely been conducted in adult populations. We examined the prospective associations between serum 25(OH)D concentrations and cardiometabolic risk factors from adolescence to young adulthood in the West Australian Pregnancy Cohort (Raine) Study. Serum 25(OH)D concentrations, BMI, homoeostasis model assessment for insulin resistance (HOMA-IR), TAG, HDL-cholesterol and systolic blood pressure (SBP) were measured at the 17-year (n 1015) and 20-year (n 1117) follow-ups. Hierarchical linear mixed models with maximum likelihood estimation were used to investigate associations between serum 25(OH)D concentrations and cardiometabolic risk factors, accounting for potential confounders. In males and females, respectively, mean serum 25(OH)D concentrations were 73·6 (sd 28·2) and 75·4 (sd 25·9) nmol/l at 17 years and 70·0 (sd 24·2) and 74·3 (sd 26·2) nmol/l at 20 years. Deseasonalised serum 25(OH)D3 concentrations were inversely associated with BMI (coefficient -0·01; 95 % CI -0·03, -0·003; P=0·014). No change over time was detected in the association for males; for females, the inverse association was stronger at 20 years compared with 17 years. Serum 25(OH)D concentrations were inversely associated with log-HOMA-IR (coefficient -0·002; 95 % CI -0·003, -0·001; P<0·001) and positively associated with log-TAG in females (coefficient 0·002; 95 % CI 0·0008, 0·004; P=0·003). These associations did not vary over time. There were no significant associations between serum 25(OH)D concentrations and HDL-cholesterol or SBP. Clinical trials in those with insufficient vitamin D status may be warranted to determine any beneficial effect of vitamin D supplementation on insulin resistance, while monitoring for any deleterious effect on TAG. PMID:27153206

  3. Oral vitamin D supplementation at five times the recommended allowance marginally affects serum 25-hydroxyvitamin D concentrations in dogs.

    PubMed

    Young, Lauren R; Backus, Robert C

    2016-01-01

    Little is known regarding optimal vitamin D status in adult dogs. To date no studies on vitamin D supplementation for improving vitamin D status have been reported for adult dogs. The aims of this study were to identify dogs with low vitamin D status and evaluate an oral dosage of cholecalciferol (D3) for effectiveness in increasing vitamin D status. For this, forty-six privately owned dogs were evaluated. Of the dogs, thirty-three (or 71·7 %) had serum 25-hydroxyvitamin D (25(OH)D) concentrations less than 100 ng/ml, a minimum previously suggested for vitamin D sufficiency in dogs. Subsequently, thirteen dogs were enrolled in a supplementation trial. Dogs were given either a D3 supplement (n 7; 2·3 µg/kg(0·75)) or olive oil placebo (n 6) daily with food. Serum concentrations of 25(OH)D were determined at weeks 1, 3 and 6, and at the trial end. Only at the trial end (weeks 9-10) was 25(OH)D significantly greater (P = 0·05) in supplemented v. placebo dogs. Serum concentrations of 24R,25-dihydroxycholecalciferol determined at the trial end were about 40 % of that of 25(OH)D3 and not significantly different between the groups. Concentrations of parathyroid hormone, ionised Ca, P and creatinine measured in initial and final serum samples indicated supplementation caused no toxicity. We conclude that vitamin D3 supplementation at a dosage near the National Research Council recommended safe-upper limit was not effective for rapidly raising serum 25(OH)D concentrations in healthy, adult dogs. Further work is needed in evaluating the metabolism of orally administered D3 in dogs before dosing recommendations can be made. PMID:27547394

  4. 25-Hydroxyvitamin D status, arterial stiffness and the renin-angiotensin system in healthy humans.

    PubMed

    Abdi-Ali, Ahmed; Nicholl, David D M; Hemmelgarn, Brenda R; MacRae, Jennifer M; Sola, Darlene Y; Ahmed, Sofia B

    2014-01-01

    Vitamin D deficiency is associated with increased arterial stiffness. We sought to clarify the influence of vitamin D in modulating angiotensin II-dependent arterial stiffness. Thirty-six healthy subjects (33 ± 2 years, 67% female, mean 25-hydroxyvitamin D 69 ± 4 nmol/L) were studied in high salt balance. Arterial stiffness, expressed as brachial pulse wave velocity (bPWV) and aortic augmentation index (AIx), was measured by tonometry at baseline and in response to angiotensin II infusion (3 ng/kg/min × 30 min then 6 ng/kg/min × 30 min). The primary outcome was change in bPWV after an angiotensin II challenge. Results were analyzed according to plasma 25-hydroxyvitamin D status: deficient (<50 nmol/L) and sufficient (≥ 50 nmol/L). There were no differences in baseline arterial stiffness between vitamin D deficient (25-hydroxyvitamin D 40 ± 2 nmol/L) and sufficient (25-hydroxyvitamin D 80 ± 4 nmol/L) groups. Compared with sufficient vitamin D status, vitamin D deficiency was associated with a decreased arterial response to angiotensin II challenge (Δbrachial pulse wave velocity: 0.48 ± 0.44 m/s versus 1.95 ± 0.22 m/s, p=0.004; Δaortic augmentation index: 9.4 ± 3.4% versus 14.2 ± 2.7%, p=0.3), which persisted for brachial pulse wave velocity response after adjustment for covariates (p=0.03). Vitamin D deficiency is associated with increased arterial stiffness in healthy humans, possibly through an angiotensin II-dependent mechanism. PMID:24164282

  5. Seasonal variation of serum 25-hydroxyvitamin D in patients with chronic renal failure treated by regular haemodialysis.

    PubMed

    Cook, D B; Pierides, A M; Shannan, G

    1977-04-15

    Serum 25-hydroxyvitamin D was measured by a competitive protein-binding assay in 44 normal subjects, 60 uraemic patients on regular haemodialysis at different times of the year and in 13 non-dialyzed uraemic patients. The results obtained indicate that uraemic patients on regular haemodialysis have a mean serum 25-hydroxyvitamin D concentration comparable to controls and that they also exhibit a seasonal variation with a significant reduction during the winter months. However, serum 25-hydroxyvitamin D concentration remained essentially within the normal range and did not reflect the increased incidence of osteomalacia in these patients. In the 13 non-dialyzed uraemic patients, serum 25-hydroxyvitamin D concentrations were lower than in the dialyzed patients, but the explanation is not yet clear. This reduction in serum 25-hydroxyvitamin D was not accompanied by any osteomalacia. The results indicate that deficiency of 25-hydroxyvitamin D in our patients on regular haemodialysis is uncommon and clearly not the explanation of dialysis osteomalacia. PMID:862199

  6. Triple Quadrupole Versus High Resolution Quadrupole-Time-of-Flight Mass Spectrometry for Quantitative LC-MS/MS Analysis of 25-Hydroxyvitamin D in Human Serum.

    PubMed

    Geib, Timon; Sleno, Lekha; Hall, Rabea A; Stokes, Caroline S; Volmer, Dietrich A

    2016-08-01

    We describe a systematic comparison of high and low resolution LC-MS/MS assays for quantification of 25-hydroxyvitamin D3 in human serum. Identical sample preparation, chromatography separations, electrospray ionization sources, precursor ion selection, and ion activation were used; the two assays differed only in the implemented final mass analyzer stage; viz. high resolution quadrupole-quadrupole-time-of-flight (QqTOF) versus low resolution triple quadrupole instruments. The results were assessed against measured concentration levels from a routine clinical chemiluminescence immunoassay. Isobaric interferences prevented the simple use of TOF-MS spectra for extraction of accurate masses and necessitated the application of collision-induced dissociation on the QqTOF platform. The two mass spectrometry assays provided very similar analytical figures of merit, reflecting the lack of relevant isobaric interferences in the MS/MS domain, and were successfully applied to determine the levels of 25-hydroxyvitamin D for patients with chronic liver disease. Graphical Abstract ᅟ. PMID:27154021

  7. Impact of oral vitamin D supplementation on serum 25-hydroxyvitamin D levels in oncology

    PubMed Central

    2010-01-01

    Background Serum 25-hydroxyvitamin D [25(OH)D] is the major circulating form of vitamin D and a standard indicator of vitamin D status. Emerging evidence in the literature suggests a high prevalence of suboptimal vitamin D (as defined by serum 25(OH)D levels of <32 ng/ml) as well as an association between lower serum levels and higher mortality in cancer. We investigated the effect of oral vitamin D supplementation as a means for restoring suboptimal levels to optimal levels in cancer. Methods This is a retrospective observational study of 2198 cancer patients who had a baseline test prior to initiation of cancer therapy at our hospital to evaluate serum 25(OH)D levels between Jan 08 and Dec 09 as part of their initial nutritional evaluation. Patients with baseline levels of < = 32 ng/ml (n = 1651) were considered to have suboptimal serum 25(OH)D levels and were supplemented with 8000 IU of Vitamin D3 (four 2000 IU D3 capsules) daily as part of their nutritional care plan. The patients were retested at their first follow-up visit. Of 1651 patients, 799 were available for follow up assessment. The mean serum 25(OH)D levels were compared in these 799 patients across the 2 time points (baseline and first follow-up) using paired sample t-test. We also investigated the factors associated with response to vitamin D supplementation. Results Of 2198 patients, 814 were males and 1384 females. 1051 were newly diagnosed and treated at our hospital while 1147 were diagnosed and treated elsewhere. The mean age at presentation was 55.4 years. The most common cancer types were breast (500, 22.7%), lung (328, 14.9%), pancreas (214, 9.7%), colorectal (204, 9.3%) and prostate (185, 8.4%). The mean time duration between baseline and first follow-up assessment was 14.7 weeks (median 10.9 weeks and range 4 weeks to 97.1 weeks). The mean serum 25(OH)D levels were 19.1 ng/ml (SD = 7.5) and 36.2 ng/ml (SD = 17.1) at baseline and first follow-up respectively; p < 0.001. Patients with

  8. Serum 25-Hydroxyvitamin D Concentrations and Season-Specific Correlates in Japanese Adults

    PubMed Central

    Nanri, Akiko; Foo, Leng Huat; Nakamura, Kazutoshi; Hori, Ai; Poudel-Tandukar, Kalpana; Matsushita, Yumi; Mizoue, Tetsuya

    2011-01-01

    Background Several lines of evidence indicate an important role for vitamin D in the prevention of a range of diseases. Blood vitamin D levels show clear seasonal variation; however, data on the determinants of vitamin D status for each season are limited. We investigated the association between lifestyle and serum vitamin D concentration by season in Japanese workers. Methods Subjects were 312 men and 217 women aged 21 to 67 years who worked in municipal offices in Northern Kyushu, Japan and participated in a periodic checkup in July or November. Multiple linear regression analysis was used to examine the association between serum 25-hydroxivitamin D concentrations and lifestyle factors for each season. Results Mean serum 25-hydroxyvitamin D concentration was 27.4 ng/ml (68.4 nmol/L) and 21.4 ng/ml (53.4 nmol/L) for workers surveyed in July and November, respectively (P < 0.001); the prevalence of vitamin D deficiency (<20 ng/ml) was 9.3% and 46.7%, respectively (P < 0.001). In November, dietary vitamin D intake (in both sexes) and nonsmoking and physical activity (in men) were significantly associated with higher concentrations of serum 25-hydroxyvitamin D. In summer, fish/shellfish intake was associated with higher serum 25-hydroxyvitamin D concentrations in women. Conclusions Vitamin D deficiency is common in Japanese workers during seasons with limited sunlight. The lifestyle correlates of favorable vitamin D status in November were physical activity, dietary vitamin D intake, and nonsmoking. PMID:21747209

  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. Evaluation of Maternal Serum 25-Hydroxyvitamin D, Paraoxonase 1 Levels, and Neutrophil-to-Lymphocyte Ratio in Spontaneous Preterm Birth

    PubMed Central

    Akkar, Ozlem Bozoklu; Sancakdar, Enver; Karakus, Savas; Yildiz, Caglar; Akkar, Ismail; Arslan, Murat; Sahin, Irfan Oguz; Yenicesu, Ayse Gonca Imir; Cetin, Ali

    2016-01-01

    Background The aim of this study was to evaluate the association of maternal serum 25-hydroxyvitamin D, paraoxonase 1, and neutrophil-to-lymphocyte ratio in women having early spontaneous preterm birth without clinical chorioamnionitis. Material/Methods This study was prospectively administered in women referred to our obstetrics service with preterm labor that resulted in preterm birth (n=35) and term labor that ended in term birth (n=44). The maternal serum levels of 25-hydroxyvitamin D and paraoxonase 1 were measured and neutrophil-to-lymphocyte ratio was calculated. Results The 25-hydroxyvitamin D and paraoxonase 1 levels of the preterm group were significantly lower than those of the term group (p<0.05). The neutrophil-to-lymphocyte ratio value of the preterm group was significantly higher than that of the term group (p<0.05). There was a significant but small positive correlation between the serum levels of 25-hydroxyvitamin D and paraoxonase 1 in the preterm group (r=0.35; p=0.021). Conclusions Decreased maternal serum 25-hydroxyvitamin D and paraoxonase 1 levels and increased neutrophil-to-lymphocyte ratio may have a role in the etiology of spontaneous preterm birth. PMID:27072780

  11. Predictors of Serum 25-Hydroxyvitamin D Concentrations among a Sample of Egyptian Schoolchildren

    PubMed Central

    2016-01-01

    Objective. To assess the level of 25-hydroxyvitamin D status among a sample of Egyptian schoolchildren and to evaluate predictors of deficiency and insufficiency. Subjects and Methods. A cross-sectional study comprising 200 prepubescent schoolchildren aged from 9 to 11 years was performed. A questionnaire including frequency of midday sun exposure, milk intake, physical activity, and level of maternal education was taken. Body mass index (BMI) was calculated; serum 25-hydroxyvitamin D [25(OH)D], serum calcium, phosphorus, and parathyroid hormone were measured. Results. Vitamin D deficiency [serum 25(OH)D < 20 ng/mL] was detected in 11.5% of subjects while its insufficiency (serum 25(OH)D is between 20 and 29.9 ng/mL) was detected in 15%. Results revealed that obesity, low physical activity, low sun exposure, and low maternal education level are significant predictors of insufficiency, though female gender, low maternal education level, and low milk intake are significant predictors of deficiency. Lower serum phosphorus and higher serum parathyroid hormone were significantly associated with both deficiency and insufficiency (p < 0.05). Conclusion. Vitamin D deficiency and insufficiency are common among schoolchildren in Egypt. Food fortification, vitamin D supplementation, and increasing maternal awareness about the importance of physical activity and exposure of their children to ultraviolet light may help to overcome this problem. PMID:26942211

  12. Serum 25-hydroxyvitamin D levels in children with recurrent tonsillitis living in Milan.

    PubMed

    Torretta, S; Marchisio, P; Iofrida, E; Capaccio, P; Pignataro, L

    2015-01-01

    Involvement of 25-hydroxyvitamin D in the etiopathogenesis of tonsillar disease in children is still debated; this study assesses possible differences in serum 25-hydroxyvitamin D levels between 309 Caucasian children (58.1% males; mean age 55.7 ± 31.0 months) living in Milan with a history of recurrent tonsillitis (RT) and healthy controls. Mean serum 25(OH)D levels were significantly reduced in the children with a history of RT (22.0 ± 8.7 ng/mL vs 24.6 ± 7.8 ng/mL; p=0.03), and the proportion of children with insufficient or deficient serum 25(OH)D levels was higher in the RT group (81.5% and 6.5% respectively) than in the control group (75.1% and 3.5%) (not significant). The multivariable model created to test the independent association between serum 25(OH)D levels and a history of RT after adjusting for age and season showed that the association was not significant. Our study failed to find any significant reduction in serum 25(OH)D levels after adjustment for age and season in a case series of children with RT in comparison with healthy controls, which suggests that vitamin D does not play a relevant role in the etiology of pediatric tonsillar infections. PMID:26753657

  13. 25-Hydroxyvitamin D in the Range of 20 to 100 ng/mL and Incidence of Kidney Stones

    PubMed Central

    Nguyen, Stacie; Baggerly, Leo; French, Christine; Heaney, Robert P.; Gorham, Edward D.

    2014-01-01

    Objectives. Increasing 25-hydroxyvitamin D serum levels can prevent a wide range of diseases. There is a concern about increasing kidney stone risk with vitamin D supplementation. We used GrassrootsHealth data to examine the relationship between vitamin D status and kidney stone incidence. Methods. The study included 2012 participants followed prospectively for a median of 19 months. Thirteen individuals self-reported kidney stones during the study period. Multivariate logistic regression was applied to assess the association between vitamin D status and kidney stones. Results. We found no statistically significant association between serum 25-hydroxyvitamin D and kidney stones (P = .42). Body mass index was significantly associated with kidney stone risk (odds ratio = 3.5; 95% confidence interval = 1.1, 11.3). Conclusions. We concluded that a serum 25-hydroxyvitamin D level of 20 to 100 nanograms per milliliter has no significant association with kidney stone incidence. PMID:24134366

  14. Supplemental vitamin D3 and zilpaterol hydrochloride. I. Effect on performance, carcass traits, tenderness, and vitamin D metabolites of feedlot steers.

    PubMed

    Korn, K T; Lemenager, R P; Claeys, M C; Engstrom, M; Schoonmaker, J P

    2013-07-01

    Angus × Simmental steers (n = 210; initial BW 314 ± 11 kg) were separated into heavy and light BW blocks and allotted evenly by BW to 6 treatments (3 heavy and 2 light pens per treatment) to determine the effect of supplemental vitamin D3: 0 IU (no D), 250,000 IU for 165 d (long-term D), or 5 × 10(6) IU for 10 d (short-term D) on performance, carcass traits, vitamin D metabolites, and meat tenderness in steers fed either 0 (NZ) or 8.38 mg/kg zilpaterol hydrochloride (ZH) daily for 21 d. Placebo or ZH was added to the diet 24 d, and short-term D was added 13 d before slaughter. Vitamin D3, ZH, and placebo were all removed from the diet 3 d before slaughter. Steers fed ZH tended to have improved overall G:F compared with steers not fed ZH (P < 0.09). Overall performance was not affected by long-term D, with or without ZH (P = 0.11) compared with no D, with or without ZH. Short-term D decreased final BW, ADG, and G:F (P = 0.04) compared with no D, when ZH was not fed. Zilpaterol hydrochloride increased HCW, dressing percentage, and LM area (P < 0.01); and decreased fat thickness, yield grade, and marbling (P < 0.03). Carcass traits were not impacted by long-term D without ZH (P > 0.13), but long-term D with ZH decreased percentage KPH (P < 0.02). Compared with no D, short-term D tended to decrease HCW (P < 0.07), decreased fat thickness (P < 0.01), and tended to increase dressing percentage (P < 0.10) when ZH was not fed, yet did not impact carcass traits when ZH was fed (P < 0.13). Feeding ZH tended to decrease (P < 0.09) LM 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The long-term D treatment increased LM vitamin D3 and 25-hydroxyvitamin D3 (25OHD3) 18- and 5-fold, respectively, when ZH was not fed (P < 0.04) and increased LM 25OHD3 by 4-fold when ZH was fed (P < 0.01). Short-term D increased LM vitamin D3 and 25OHD3 by 52- and 9-fold, respectively, when ZH was not fed (P < 0.01), and by 24- and 9-fold, respectively, when ZH was fed (P < 0.01). Also, short-term D

  15. Interlaboratory Trial for Measurement of Vitamin D and 25-Hydroxyvitamin D [25(OH)D] in Foods and a Dietary Supplement Using Liquid Chromatography-Mass Spectrometry.

    PubMed

    Roseland, Janet Maxwell; Patterson, Kristine Y; Andrews, Karen W; Phillips, Katherine M; Phillips, Melissa M; Pehrsson, Pamela R; Dufresne, Guy L; Jakobsen, Jette; Gusev, Pavel A; Savarala, Sushma; Nguyen, Quynhanh V; Makowski, Andrew J; Scheuerell, Chad R; Larouche, Guillaume P; Wise, Stephen A; Harnly, James M; Williams, Juhi R; Betz, Joseph M; Taylor, Christine L

    2016-04-27

    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 performance has been needed. The primary goal of this study was to evaluate whether vitamin D3 and 25(OH)D3 concentrations in food and DS materials could be measured with acceptable reproducibility. Five experienced laboratories from the United States and other countries participated, all using liquid chromatography tandem-mass spectrometry but no common analytical protocol; however, various methods were used for determining vitamin D3 in the DS. Five animal-based materials (including three commercially available RMs) and one DS were analyzed. Reproducibility results for the materials were acceptable. Thus, it is possible to obtain consistent results among experienced laboratories for vitamin D3 and 25(OH)D3 in foods and a DS. PMID:27045951

  16. Effects of Vitamin D Supplementation on Serum 25-Hydroxyvitamin D Concentrations in Cirrhotic Patients: A Randomized Controlled Trial

    PubMed Central

    Pilz, Stefan; Putz-Bankuti, Csilla; Gaksch, Martin; Spindelboeck, Walter; Haselberger, Marius; Rainer, Florian; Posch, Andreas; Kreuzer, Philipp; Stojakovic, Tatjana; Stadlbauer, Vanessa; Obermayer-Pietsch, Barbara; Stauber, Rudolf E.

    2016-01-01

    Background: The liver is crucial for 25-hydroxyvitamin D (25(OH)D) metabolism, and vitamin D deficiency is highly prevalent in patients with cirrhosis and predicts adverse outcomes. We aimed to evaluate whether vitamin D supplementation in patients with cirrhosis is effective in increasing 25(OH)D serum concentrations. Secondary outcome measures included liver function tests (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), and alkaline phosphatase (AP)), albumin, International Normalized Ratio (INR), bilirubin, the liver fibrosis marker hyaluronic acid, and parameters of mineral metabolism including parathyroid hormone (PTH). Methods: This is a double-center, double-blind, placebo-controlled study conducted from December 2013 to May 2014 at the Medical University of Graz, and the hospital Hoergas-Enzenbach, Austria. We enrolled 36 consecutive patients with cirrhosis and 25(OH)D concentrations below 30 ng/mL. Study participants were randomly allocated to receive either 2800 International Units of vitamin D3 per day as oily drops (n = 18) or placebo (n = 18) for 8 weeks. Results: Thirty-three study participants (mean (SD) age: 60 (9) years; 21% females; 25(OH)D: 15.6 (7.4) ng/mL) completed the trial. The mean treatment effect (95% CI) for 25(OH)D was 15.2 (8.0 to 22.4) ng/mL (p < 0.001). There was no significant effect on any secondary outcome. Conclusions: In this randomized controlled trial, vitamin D supplementation increases 25(OH)D serum concentrations, even in cirrhotic patients. PMID:27171112

  17. Cow-level association between serum 25-hydroxyvitamin D concentration and Mycobacterium avium subspecies paratuberculosis antibody seropositivity: a pilot study.

    PubMed

    Sorge, U S; Molitor, T; Linn, J; Gallaher, D; Wells, S W

    2013-02-01

    Vitamin D deficiency has been associated with various human diseases. Therefore, the objective of this study was to evaluate the cow-level association between serum 25-hydroxyvitamin D [25(OH)D] concentration and Mycobacterium avium ssp. paratuberculosis (MAP) seropositivity of dairy cows, adjusting for diet, breed, hair coat color, stage of lactation, reproductive status, and cow age. The sera of 80 MAP antibody ELISA-positive and 80 test-negative herd mates from 5 Minnesota dairy herds were analyzed for 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. The cows' age, production records, and hair coat color were recorded. Additionally, feed samples were obtained and analyzed for vitamin D(2) and vitamin D(3) content. A linear mixed model was used to identify potential predictors for serum 25(OH)D concentration, accounting for herd of origin. The majority of rations analyzed had over 22,000 IU of vitamin D/day (maximum: 52,000 I U/d) and the study cows' average serum 25(OH)D concentration was 62.5 ± 13.8 ng/mL. Serum ELISA-positive cows had, on average, 5.3 ng/mL lower 25(OH)D serum levels than test-negative herd mates. The reproductive status of cows was also associated with the 25(OH)D levels, with fresh cows having the lowest serum concentration. In this cross-sectional study, a temporal or causal association between MAP antibody ELISA status and serum 25(OH)D concentration could not be evaluated. In addition, the high levels of vitamin D in the rations of participating farms and the average 25(OH)D serum concentration suggest that additional supplementation with vitamin D in the ration is likely to be ineffective. PMID:23261386

  18. 25-Hydroxyvitamin D levels and cognitive performance and decline in elderly men

    PubMed Central

    Slinin, Y; Paudel, M L.; Taylor, B C.; Fink, H A.; Ishani, A; Canales, M T.; Yaffe, K; Barrett-Connor, E; Orwoll, E S.; Shikany, J M.; LeBlanc, E S.; Cauley, J A.; Ensrud, K E.

    2010-01-01

    Objective: To test the hypothesis that lower 25-hydroxyvitamin D [25(OH)D] levels are associated with a greater likelihood of cognitive impairment and risk of cognitive decline. Methods: We measured 25(OH)D and assessed cognitive function using the Modified Mini-Mental State Examination (3MS) and Trail Making Test Part B (Trails B) in a cohort of 1,604 men enrolled in the Osteoporotic Fractures in Men Study and followed them for an average of 4.6 years for changes in cognitive function. Results: In a model adjusted for age, season, and site, men with lower 25(OH)D levels seemed to have a higher odds of cognitive impairment, but the test for trend did not reach significance (impairment by 3MS: odds ratio [OR] 1.84, 95% confidence interval [CI] 0.81–4.19 for quartile [Q] 1; 1.41, 0.61–3.28 for Q2; and 1.18, 0.50–2.81 for Q3, compared with Q4 [referent group; p trend = 0.12]; and impairment by Trails B: OR 1.66, 95% CI 0.98–2.82 for Q1; 0.96, 0.54–1.69 for Q2; and 1.30, 0.76–2.22 for Q3, compared with Q4 [p trend = 0.12]). Adjustment for age and education further attenuated the relationships. There was a trend for an independent association between lower 25(OH)D levels and odds of cognitive decline by 3MS performance (multivariable OR 1.41, 95% CI 0.89–2.23 for Q1; 1.28, 0.84–1.95 for Q2; and 1.06, 0.70–1.62 for Q3, compared with Q4 [p = 0.10]), but no association with cognitive decline by Trails B. Conclusion: We found little evidence of independent associations between lower 25-hydroxyvitamin D level and baseline global and executive cognitive function or incident cognitive decline. GLOSSARY 3MS = Modified Mini-Mental State Examination; 25(OH)D = 25-hydroxyvitamin D; BMI = body mass index; CI = confidence interval; IADL = instrumental activities of daily living; MrOS = Osteoporotic Fractures in Men; OR = odds ratio; PASE = Physical Activity Scale for the Elderly; Q = quartile; Trails B = Trail Making Test Part B. PMID:19940271

  19. Metabolism of 25-hydroxyvitamin D in copper-laden rat: A model of Wilson's disease

    SciTech Connect

    Carpenter, T.O.; Pendrak, M.L.; Anast, C.S. Yale Univ. School of Medicine, New Haven, CT )

    1988-02-01

    Wilson's disease results in excess tissue accumulation of copper and is often complicated by skeletal and mineral abnormalities. The authors investigated vitamin D metabolism in rats fed a copper-laden diet rendering hepatic copper content comparable with that found in Wilson's disease. Injection of 25-hydroxyvitamin D{sub 3} (25(OH)D{sub 3}) resulted in reduced 1,25--dihydroxyvitamin D (1,25(OH){sub 2}D) levels in copper-intoxicated rats. In vitro 25(OH)D-1{alpha}-hydroxylase activity was impaired in renal mitochondria from copper-intoxicated animals. Activity was also inhibited in mitochondrial from controls when copper was added to incubation media. Impaired conversion of 25(OH)D to 1,25(OH){sub 2}D occurs in copper intoxication and suggests that altered vitamin D metabolism is a potential factor in the development of bone and mineral abnormalities in Wilson's disease.

  20. Reduced Sun Exposure Does Not Explain the Inverse Association of 25-Hydroxyvitamin D with Percent Body Fat in Older Adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Greater adiposity is associated with lower blood levels of 25-hydroxyvitamin D [25(OH)D]. The extent to which this may result from reduced sun exposure among heavier individuals is unknown. This analysis was conducted to determine whether sun exposure habits differ according to percent body fat (%...

  1. 25-hydroxyvitamin D in obese youth across the spectrum of glucose tolerance from normal to prediabetes to type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to 1) determine if plasma 25-hydroxyvitamin D (25[OH]D) concentrations differ among obese youth with normal glucose tolerance (NGT) versus prediabetes versus type 2 diabetes and 2) assess the relationships between 25(OH)D and in vivo insulin sensitivity and Beta-cell ...

  2. Plasma 25-Hydroxyvitamin D is Associated with Markers of the Insulin Resistance Phenotype in Non-diabetic Adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We examined the cross-sectional association between plasma 25-hydroxyvitamin D [25(OH)D] and markers of the insulin resistance phenotype. Plasma 25(OH)D concentrations were measured in 808 non-diabetic participants of the Framingham Offspring Study. Outcome measures included fasting and 2-hour pos...

  3. Dietary calcium and serum 25-hydroxyvitamin D status in relation to bone mineral density among US adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A higher calcium intake is still the primary recommendation for the prevention of osteoporosis, while vitamin D deficiency is often not addressed. To study the relative importance of dietary calcium intake and serum 25-hydroxyvitamin D (25(OH)D) status in regard to hip bone mineral density (BMD) in ...

  4. Studies on the analysis of 25-hydroxyvitamin D{sub 3} by isotope-dilution liquid chromatography–tandem mass spectrometry using enzyme-assisted derivatisation

    SciTech Connect

    Abdel-Khalik, Jonas; Crick, Peter J.; Carter, Graham D.; Makin, Hugh L.; Wang, Yuqin; Griffiths, William J.

    2014-04-11

    Highlights: • New method for the analysis of 25-hydroxyvitamin D{sub 3} exploiting Girard P derivatisation. • Method also applicable to vitamin D{sub 3}, 1α,25- and 24,25-dihydroxyvitamin D{sub 3}. • By modification of the method 3-epi-25-hydroxyvitamin D{sub 3} can also be analysed. - Abstract: The total serum concentration of 25-hydroxyvitamins D (25-hydroxyvitamin D{sub 3} and 25-hydroxyvitamin D{sub 2}) is currently used as an indicator of vitamins D status. Vitamins D insufficiency is claimed to be associated with multiple diseases, thus accurate and precise reference methods for the quantification of 25-hydroxyvitamins D are needed. Here we present a novel enzyme-assisted derivatisation method for the analysis of vitamins D metabolites in adult serum utilising 25-[26,26,26,27,27,27-{sup 2}H{sub 6}]hydroxyvitamin D{sub 3} as the internal standard. Extraction of 25-hydroxyvitamins D from serum is performed with acetonitrile, which is shown to be more efficient than ethanol. Cholesterol oxidase is used to oxidize the 3β-hydroxy group in the vitamins D metabolites followed by derivatisation of the newly formed 3-oxo group with Girard P reagent. 17β-Hydroxysteroid dehydrogenase type 10 is shown to oxidize selectively the 3α-hydroxy group in the 3α-hydroxy epimer of 25-hydroxyvitamin D{sub 3}. Quantification is achieved by isotope-dilution liquid chromatography–tandem mass spectrometry. Recovery experiments for 25-hydroxyvitamin D{sub 3} performed on adult human serum give recovery of 102–106%. Furthermore in addition to 25-hydroxyvitamin D{sub 3}, 24,25-dihydroxyvitamin D{sub 3} and other uncharacterised dihydroxy metabolites, were detected in adult human serum.

  5. Serum 25-Hydroxyvitamin D Levels and Dry Eye Syndrome: Differential Effects of Vitamin D on Ocular Diseases

    PubMed Central

    Jee, Donghyun; Kang, Seungbum; Yuan, Changzheng; Cho, Eunyoung; Arroyo, Jorge G.

    2016-01-01

    Purpose To investigate associations between serum 25-hydroxyvitamin D levels and dry eye syndrome (DES), and to evaluate the differential effect of vitamin D on ocular diseases including age-related macular disease (AMD), diabetic retinopathy (DR), cataract, and DES. Methods A total of 16,396 participants aged >19 years were randomly selected from the Korean National Health and Nutrition Examination Survey. All participants participated in standardized interviews, blood 25-hydroxyvitamin D level evaluations, and comprehensive ophthalmic examinations. DES was defined by a history of clinical diagnosis of dry eyes by a physician. The association between vitamin D and DES was compared to the associations between vitamin D and AMD, DR, cataract, and DES from our previous studies. Results The odds of DES non-significantly decreased as the quintiles of serum 25-hydroxyvitamin D levels increased (quintile 5 versus 1, OR = 0.85, 95%CI: 0.55–1.30, P for trend = 0.076) after adjusting for potential confounders including age, sex, hypertension, diabetes, smoking status, and sunlight exposure times. The relative odds of DES (OR = 0.70, 95% CI: 0.30–1.64) and cataract (OR = 0.76, 95% CI: 0.59–0.99) were relatively high, while those of DR (OR = 0.37, 95% CI: 0.18–0.76) and late AMD (OR = 0.32, 95% CI: 0.12–0.81) were lower in men. Conclusions The present study does not support an association between serum 25-hydroxyvitamin D levels and DES. The preventive effect of serum 25-hydroxyvitamin D may be more effective for DR and late AMD than it is for cataract and DES. PMID:26894581

  6. Meal conditions affect the absorption of supplemental vitamin D3 but not the plasma 25-hydroxyvitamin D response to supplementation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is sometimes assumed that dietary fat is required for vitamin D absorption, although the impact of different amounts of dietary fat on vitamin D absorption is not established. This study was conducted to determine whether the presence of a meal and the fat content of the meal influences vitamin D...

  7. Low levels of serum 25-hydroxyvitamin D and risk of metabolic syndrome in China

    PubMed Central

    Lu, Yanhui; Liu, Minyan; Pei, Yu; Li, Jian; Tian, Hui; Cheng, Xiaoling; Fang, Fusheng; Sun, Banruo; Xiao, Haiying; Li, Nan; Miao, Xinyu; Li, Chunlin

    2015-01-01

    Recent evidence indicates the potential role of vitamin D in the prevention of Metabolic syndrome (MetSyn). This is an analytical cross sectional study. A total of 3275 subjects were investigated. 25-hydroxyvitamin D(25[OH]D) was detected by electrochemiluminescence immunoassay (ECLIA) technology. Metabolic syndrome was defined according to the definition of International Diabetes Federation (IDF). Among the participants, the prevalence of the MetSyn was 6.0%. The prevalence of vitamin D deficiency and insufficiency was 50.1% and 25.0% respectively. Subjects with MetSyn presented with significantly lower 25(OH)Vit D serum levels compared with non-MetSyn group. The results shows that vitamin D deficiency is common in Chinese adults, and subjects with lower serum 25(OH)D have a higher risk of the MetSyn. The cut-off value of serum 25(OH)D that reflected MetSyn in Chinese adluts was 15.655 ng/mL. PMID:26550327

  8. A prospective study of plasma 25-hydroxyvitamin D concentration and prostate cancer risk.

    PubMed

    Deschasaux, Mélanie; Souberbielle, Jean-Claude; Latino-Martel, Paule; Sutton, Angela; Charnaux, Nathalie; Druesne-Pecollo, Nathalie; Galan, Pilar; Hercberg, Serge; Le Clerc, Sigrid; Kesse-Guyot, Emmanuelle; Ezzedine, Khaled; Touvier, Mathilde

    2016-01-28

    Mechanistic hypotheses suggest that vitamin D and the closely related parathyroid hormone (PTH) may be involved in prostate carcinogenesis. However, epidemiological evidence is lacking for PTH and inconsistent for vitamin D. Our objectives were to prospectively investigate the association between vitamin D status, vitamin D-related gene polymorphisms, PTH and prostate cancer risk. A total of 129 cases diagnosed within the Supplémentation en Vitamines et Minéraux Antioxydants cohort were included in a nested case-control study and matched to 167 controls (13 years of follow-up). 25-Hydroxyvitamin D (25(OH)D) and PTH concentrations were assessed from baseline plasma samples. Conditional logistic regression models were computed. Higher 25(OH)D concentration was associated with decreased risk of prostate cancer (ORQ4 v. Q1 0·30; 95 % CI 0·12, 0·77; P trend=0·007). PTH concentration was not associated with prostate cancer risk (P trend=0·4) neither did the studied vitamin D-related gene polymorphisms. In this prospective study, prostate cancer risk was inversely associated with 25(OH)D concentration but not with PTH concentration. These results bring a new contribution to the understanding of the relationship between vitamin D and prostate cancer, which deserves further investigation. PMID:26568368

  9. Serum 25-hydroxyvitamin D concentrations in dogs - correlation with health and cancer risk.

    PubMed

    Selting, K A; Sharp, C R; Ringold, R; Thamm, D H; Backus, R

    2016-09-01

    25-hydroxyvitamin D (25(OH)D) is important in bone health as well as many diseases including cancer. Supplementation may increase responsiveness of cancer cells to chemotherapy. Serum 25(OH)D, intact parathyroid hormone (iPTH) and canine C-reactive protein (c-CRP) were measured in healthy dogs and dogs with haemoabdomen. Regression analysis determined optimal 25(OH)D concentrations. In healthy dogs (n = 282), mean iPTH concentrations correlated inversely (r(2) = 0.88, P < 0.001) to 25(OH)D concentrations. Variation in both iPTH and c-CRP plateaued at 25(OH)D concentrations of 100-120 ng mL(-1) . Haemoabdomen dogs (n = 63, 43 malignant and 20 benign) had 25(OH)D concentrations ranging from 19.4 to >150 ng mL(-1) . Relative risk of cancer increased with decreasing 25(OH)D concentrations [RR = 3.9 for 25(OH)D below 40 ng mL(-1) (P = 0.0001)]. Serum 25(OH)D concentrations in dogs vary widely, and are influenced by dietary VitD content. Serum vitD measurement can identify dogs for which supplementation may improve health and response to cancer therapy. PMID:25041357

  10. Widespread 25-Hydroxyvitamin D Deficiency in Affluent and Nonaffluent Pregnant Indian Women

    PubMed Central

    Jani, Rati; Palekar, Suhaila; Munipally, Tanya; Ghugre, Padmini; Udipi, Shobha

    2014-01-01

    Objectives. This cross-sectional study primarily aimed to assess vitamin D adequacy in the third trimester of pregnancy using 25-hydroxyvitamin D (25(OH)D) and explore lifestyle characteristics (sun exposure index, diet, and economic indicators) associated with serum 25(OH)D. The secondary aim was to examine the relationship of serum 25(OH)D with birth weight and gestational age. Methods. Serum 25(OH)D was measured by chemiluminescent immunoassay in 150 pregnant women from Mumbai. Sun exposure index was computed. Dietary calcium, phytate : calcium ratio, and dietary phosphorus was calculated using the 24-hour diet recall method. Results. All women had 25(OH)D levels < 30.00 ng/ml. Multivariable linear regression showed that nonaffluent women had poorer 25(OH)D status than their affluent counterparts (β = −0.20; P = 0.03). Higher sun exposure index was associated with higher 25(OH)D concentrations (β = 0.31; P < 0.001), which remained significant after controlling for covariates. At the bivariate level, mothers of infants weighing <2500 g had lower serum 25(OH)D concentrations compared to mothers whose infants weighed ≥2500 g (P = 0.02). This association became non-significant after controlling for covariates. Conclusions. Vitamin D deficiency was universally prevalent in the cohort studied. There is a need to develop culturally sensitive strategies for improving the 25(OH)D status. PMID:25045711

  11. Cord Blood 25-hydroxyvitamin D and Fetal Growth in the China-Anhui Birth Cohort Study.

    PubMed

    Zhu, Peng; Tong, Shi-lu; Hu, Wen-biao; Hao, Jia-hu; Tao, Rui-xue; Huang, Kun; Mou, Zhe; Zhou, Qi-fan; Jiang, Xiao-min; Tao, Fang-biao

    2015-01-01

    We determined the association of cord blood 25-hydroxyvitamin D [25(OH)D] with birth weight and the risk of small for gestational age (SGA). As part of the China-Anhui Birth Cohort (C-ABC) study, we measured cord blood levels of 25(OH)D in 1491 neonates in Hefei, China. The data on maternal sociodemographic characteristics, health status, lifestyle, birth outcomes were prospectively collected. Multiple regression models were used to estimate the association of 25(OH)D levels with birth weight and the risk of SGA. Compared with neonates in the lowest decile of cord blood 25(OH)D levels, neonates in four deciles (the fourth, fifth, sixth and seventh deciles) had significantly increased birth weight and decreased risk of SGA. Multiple linear regression models showed that per 10 nmol/L increase in cord blood 25(OH)D, birth weight increased by 61.0 g (95% CI: 31.9, 89.9) at concentrations less than 40 nmol/L, and then decreased by 68.5 g (95% CI: -110.5, -26.6) at concentrations from 40 to 70 nmol/L. This study provides the first epidemiological evidence that there was an inverted U shaped relationship between neonatal vitamin D status and fetal growth, and the risk of SGA reduced at moderate concentration. PMID:26450157

  12. Correlates of circulating 25-hydroxyvitamin D: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

    PubMed

    McCullough, Marjorie L; Weinstein, Stephanie J; Freedman, D Michal; Helzlsouer, Kathy; Flanders, W Dana; Koenig, Karen; Kolonel, Laurence; Laden, Francine; Le Marchand, Loic; Purdue, Mark; Snyder, Kirk; Stevens, Victoria L; Stolzenberg-Solomon, Rachael; Virtamo, Jarmo; Yang, Gong; Yu, Kai; Zheng, Wei; Albanes, Demetrius; Ashby, Jason; Bertrand, Kimberly; Cai, Hui; Chen, Yu; Gallicchio, Lisa; Giovannucci, Edward; Jacobs, Eric J; Hankinson, Susan E; Hartge, Patricia; Hartmuller, Virginia; Harvey, Chinonye; Hayes, Richard B; Horst, Ronald L; Shu, Xiao-Ou

    2010-07-01

    Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geographic area. Demographic and lifestyle characteristics were examined in relation to 25(OH)D using stepwise linear regression and polytomous logistic regression. The prevalence of 25(OH)D concentrations less than 25 nmol/L ranged from 3% to 36% across cohorts, and the prevalence of 25(OH)D concentrations less than 50 nmol/L ranged from 29% to 82%. Seasonal differences in circulating 25(OH)D were most marked among whites from northern latitudes. Statistically significant positive correlates of 25(OH)D included male sex, summer blood draw, vigorous physical activity, vitamin D intake, fish intake, multivitamin use, and calcium supplement use. Significant inverse correlates were body mass index, winter and spring blood draw, history of diabetes, sedentary behavior, smoking, and black race/ethnicity. Correlates varied somewhat within season, race/ethnicity, and sex. These findings help identify persons at risk for low vitamin D status for both clinical and research purposes. PMID:20562191

  13. Meta-analysis of All-Cause Mortality According to Serum 25-Hydroxyvitamin D

    PubMed Central

    Kim, June Jiwon; Mohr, Sharif Burgette; Gorham, Edward Doerr; Grant, William B.; Giovannucci, Edward L.; Baggerly, Leo; Hofflich, Heather; Ramsdell, Joe Wesley; Zeng, Kenneth; Heaney, Robert P.

    2014-01-01

    We examined the relationship between serum 25-hydroxyvitamin D (25[OH]D) and all-cause mortality. We searched biomedical databases for articles that assessed 2 or more categories of 25(OH)D from January 1, 1966, to January 15, 2013. We identified 32 studies and pooled the data. The hazard ratio for all-cause mortality comparing the lowest (0–9 nanograms per milliliter [ng/mL]) to the highest (> 30 ng/mL) category of 25(OH)D was 1.9 (95% confidence interval = 1.6, 2.2; P < .001). Serum 25(OH)D concentrations less than or equal to 30 ng/mL were associated with higher all-cause mortality than concentrations greater than 30 ng/mL (P < .01). Our findings agree with a National Academy of Sciences report, except the cutoff point for all-cause mortality reduction in this analysis was greater than 30 ng/mL rather than greater than 20 ng/mL. PMID:24922127

  14. Plasma concentrations of 25-hydroxyvitamin D among Jordanians: Effect of biological and habitual factors on vitamin D status

    PubMed Central

    2011-01-01

    Background Vitamin D is cutaneously synthesized following sun exposure (vitamin D3) as well as it is derived from dietary intake (vitamin D3 and D2). Vitamin D2 and D3 are metabolized in the liver to 25-hydroxyvitamin D (25(OH)D). This metabolite is considered the functional indicator of vitamin D stores in humans. Since Jordan latitude is 31°N, cutaneous synthesis of vitamin D3 should be sufficient all year round. However, many indications reveal that it is not the case. Thus, this study was conducted to determine the 25(OH)D status among Jordanians. Methods Three hundred healthy volunteers were enrolled in a cross sectional study; 201 females and 99 males. 25(OH)D and calcium concentrations were measured by enzyme linked immunosorbent assay and spectroscopy techniques, respectively. All participants filled a study questionnaire that covered age, sex, height, weight, diet, and dress style for females. Females were divided according to their dress style: Western style, Hijab (all body parts are covered except the face and hands), and Niqab (all body parts are covered including face and hands). Results The average plasma 25(OH)D levels in males and females were 44.5 ± 10.0 nmol/l and 31.1 ± 12.0 nmol/l, respectively. However, when female 25(OH)D levels were categorized according to dress styles, the averages became 40.3, 31.3 and 28.5 nmol/l for the Western style, Hijab and Niqab groups, respectively. These 25(OH)D levels were significantly less than those of males (p < 0.05, 0.001, 0.001, respectively). In addition, the plasma 25(OH)D levels of the Western style group was significantly higher than those of Hijab and Niqab groups (p < 0.001). Furthermore, dairy consumption in males was a positive significant factor in vitamin D status. Even though calcium concentrations were within the reference range, the Hijab and Niqab-dressed females have significantly less plasma calcium levels than males (p < 0.01). Conclusions Very low plasma 25(OH)D levels in females

  15. 25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services

    PubMed Central

    Buell, J S.; Dawson-Hughes, B; Scott, T M.; Weiner, D E.; Dallal, G E.; Qui, W Q.; Bergethon, P; Rosenberg, I H.; Folstein, M F.; Patz, S; Bhadelia, R A.; Tucker, K L.

    2010-01-01

    Background: Vitamin D deficiency has potential adverse effects on neurocognitive health and subcortical function. However, no studies have examined the association between vitamin D status, dementia, and cranial MRI indicators of cerebrovascular disease (CVD). Methods: Cross-sectional investigation of 25-hydroxyvitamin D [25(OH)D], dementia, and MRI measures of CVD in elders receiving home care (aged 65–99 years) from 2003 to 2007. Results: Among 318 participants, the mean age was 73.5 ± 8.1 years, 231 (72.6%) were women, and 109 (34.3%) were black. 25(OH)D concentrations were deficient (<10 ng/mL) in 14.5% and insufficient (10–20 ng/mL) in 44.3% of participants. There were 76 participants (23.9%) with dementia, 41 of which were classified as probable AD. Mean 25(OH)D concentrations were lower in subjects with dementia (16.8 vs 20.0 ng/mL, p < 0.01). There was a higher prevalence of dementia among participants with 25(OH)D insufficiency (≤20 ng/mL) (30.5% vs 14.5%, p < 0.01). 25(OH)D deficiency was associated with increased white matter hyperintensity volume (4.9 vs 2.9 mL, p < 0.01), grade (3.0 vs 2.2, p = 0.04), and prevalence of large vessel infarcts (10.1% vs 6.9%, p < 0.01). After adjustment for age, race, sex, body mass index, and education, 25(OH)D insufficiency (≤20 ng/mL) was associated with more than twice the odds of all-cause dementia (odds ratio [OR] = 2.3, 95% confidence interval [CI] 1.2–4.2), Alzheimer disease (OR = 2.5, 95% CI 1.1–6.1), and stroke (with and without dementia symptoms) (OR = 2.0, 95% CI 1.0–4.0). Conclusions: Vitamin D insufficiency and deficiency was associated with all-cause dementia, Alzheimer disease, stroke (with and without dementia symptoms), and MRI indicators of cerebrovascular disease. These findings suggest a potential vasculoprotective role of vitamin D. GLOSSARY 25(OH)D = 25-hydroxyvitamin D; AIREN = Association Internationale pour la Recherché et l'Enseignement en Neurosciences; BMI = body mass index; CI

  16. Association between Plasma 25-Hydroxyvitamin D, Ancestry and Aggressive Prostate Cancer among African Americans and European Americans in PCaP

    PubMed Central

    Steck, Susan E.; Arab, Lenore; Zhang, Hongmei; Bensen, Jeannette T.; Fontham, Elizabeth T. H.; Johnson, Candace S.; Mohler, James L.; Smith, Gary J.; Su, Joseph L.; Trump, Donald L.; Woloszynska-Read, Anna

    2015-01-01

    Background African Americans (AAs) have lower circulating 25-hydroxyvitamin D3 [25(OH)D3] concentrations and higher prostate cancer (CaP) aggressiveness than other racial/ethnic groups. The purpose of the current study was to examine the relationship between plasma 25(OH)D3, African ancestry and CaP aggressiveness among AAs and European Americans (EAs). Methods Plasma 25(OH)D3 was measured using LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry) in 537 AA and 663 EA newly-diagnosed CaP patients from the North Carolina-Louisiana Prostate Cancer Project (PCaP) classified as having either ‘high’ or ‘low’ aggressive disease based on clinical stage, Gleason grade and prostate specific antigen at diagnosis. Mean plasma 25(OH)D3 concentrations were compared by proportion of African ancestry. Logistic regression was used to calculate multivariable adjusted odds ratios (OR) and 95% confidence intervals (95%CI) for high aggressive CaP by tertile of plasma 25(OH)D3. Results AAs with highest percent African ancestry (>95%) had the lowest mean plasma 25(OH)D3 concentrations. Overall, plasma 25(OH)D3 was associated positively with aggressiveness among AA men, an association that was modified by calcium intake (ORT3vs.T1: 2.23, 95%CI: 1.26–3.95 among men with low calcium intake, and ORT3vs.T1: 0.19, 95%CI: 0.05–0.70 among men with high calcium intake). Among EAs, the point estimates of the ORs were <1.0 for the upper tertiles with CIs that included the null. Conclusions Among AAs, plasma 25(OH)D3 was associated positively with CaP aggressiveness among men with low calcium intake and inversely among men with high calcium intake. The clinical significance of circulating concentrations of 25(OH)D3 and interactions with calcium intake in the AA population warrants further study. PMID:25919866

  17. Lifestyle and Dietary Factors Associated with Serum 25-Hydroxyvitamin D Levels in Korean Young Adults.

    PubMed

    Joh, Hee-Kyung; Lim, Chun Soo; Cho, BeLong

    2015-08-01

    Inadequate vitamin D status is highly prevalent in the Korean population, especially among young adults. Nonetheless, correlates of suboptimal vitamin D levels in young adults are not well defined. This study aimed to investigate potentially modifiable determinants of vitamin D levels in young adults in Korea. This cross-sectional study was based on health check-up data from 3,450 healthy male and female university students aged 18-29 yr in Seoul between April and May 2013. Serum 25-hydroxyvitamin D [25(OH)D] levels were determined using chemiluminescent immunoassay. Anthropometric data were measured, and lifestyle, dietary, and sociodemographic factors were obtained through self-administered questionnaires. General linear regression was used to assess correlates of serum 25(OH)D levels. The mean serum 25(OH)D level was 11.1 ng/mL, and the prevalence of 25(OH)D levels less than 10 ng/mL was 44.7% (39.5% in men, 50.2% in women). In a final multivariable model, significant positive correlates of serum 25(OH)D were older age, male sex, increased physical activity, sunlight exposure ≥ 30 min/day, eating breakfast regularly, consumption of dairy and fatty fish, and use of vitamin D-containing supplements. In contrast, significant inverse correlates were obesity (body mass index, BMI ≥ 25 kg/m(2)) or underweight (BMI < 18.5 kg/m(2)), abdominal obesity, increased sedentary time, and frequent consumption of instant noodles and sugar-sweetened beverages. In conclusion, many modifiable lifestyle and dietary factors were associated with low serum 25(OH)D levels in Korean young adults. Further studies on potential mechanisms of the correlates and optimal strategies to improve vitamin D status in this vulnerable subpopulation are warranted. PMID:26240489

  18. Serum 25-hydroxyvitamin D is not related to cardiac natriuretic peptide in nulliparous and lactating women

    PubMed Central

    Saadi, Hussein F; Nicholls, M Gary; Frampton, Christopher M; Benedict, Sheela; Yasin, Javed

    2009-01-01

    Background Vitamin D deficiency is associated with heightened risk of cardiovascular disease. Potential mechanisms include involvement of vitamin D in regulation of renin-angiotensin system and manufacture and secretion of cardiac natriuretic peptides. Our aim was to document relationships between 25 hydroxyvitamin [25(OH)D] and N-terminal pro B-type natriuretic peptide (NT-proBNP) and plasma renin activity (PRA) levels and to document the effect of vitamin D administration on NT-proBNP and PRA levels in vitamin D deficient subjects. Methods Serum 25(OH)D, parathyroid hormone (PTH), plasma or serum NT-proBNP and PRA levels were measured at baseline in nulliparous and lactating women and after 2 months of oral vitamin D2 (2,000 IU/day or 60,000 IU/month) supplementation to lactating women. Results Baseline levels of 25(OH)D were low (<50 nmol/L) in most women whereas PRA and NT-proBNP levels were within the normal range. There were no significant correlations between baseline 25(OH)D or PTH with NT-proBNP and PRA. Vitamin D administration over a 2-month period in lactating women was associated with a decline in NT-proBNP (by 9.1 ± 2.0 pmol/L; p < 0.001) and PRA (by 0.32 ± 0.17 nmol/L/hr; p = 0.064). However, there were no significant correlations between the changes from baseline in 25(OH)D and either NT-proBNP (r = -0.04, p = 0.8) or PRA (r = -0.04, p = 0.8). Conclusion We found no significant correlations between 25(OH)D or PTH with NT-proBNP and PRA in vitamin D deficient women. Further information is required to clarify the effects of vitamin D administration on cardiac structure and function. PMID:19178708

  19. 25-Hydroxyvitamin D Status and Change in Physical Performance and Strength in Older Adults

    PubMed Central

    Houston, Denise K.; Tooze, Janet A.; Neiberg, Rebecca H.; Hausman, Dorothy B.; Johnson, Mary Ann; Cauley, Jane A.; Bauer, Doug C.; Cawthon, Peggy M.; Shea, M. Kyla; Schwartz, Gary G.; Williamson, Jeff D.; Tylavsky, Frances A.; Visser, Marjolein; Simonsick, Eleanor M.; Harris, Tamara B.; Kritchevsky, Stephen B.

    2012-01-01

    Low 25-hydroxyvitamin D (25(OH)D) concentrations are common among older adults and are associated with poorer physical performance and strength, but results from longitudinal studies have been inconsistent. The 25(OH)D threshold for physical performance and strength was determined, and both cross-sectional and longitudinal associations between 25(OH)D and physical performance and strength were examined, in men and women aged 71–80 years from the Health, Aging, and Body Composition Study (n = 2,641). Baseline serum 25(OH)D was measured in 1998–1999, and physical performance and strength were measured at baseline and at 2- and 4-year follow-up. Piecewise regression models were used to determine 25(OH)D thresholds. Linear regression and mixed models were used to examine cross-sectional and longitudinal associations. The 25(OH)D thresholds were 70–80 nmol/L for physical performance and 55–70 nmol/L for strength. Participants with 25(OH)D <50 nmol/L had poorer physical performance at baseline and at 2- and 4-year follow-up than participants with 25(OH)D ≥75 nmol/L (P < 0.01). Although physical performance and strength declined over 4 years of follow-up (P < 0.0001), in general, the rate of decline was not associated with baseline 25(OH)D. Older adults with low 25(OH)D concentrations had poorer physical performance over 4 years of follow-up, but low 25(OH)D concentrations were not associated with a faster rate of decline in physical performance or strength. PMID:23118104

  20. Circulating 25-Hydroxyvitamin D, Vitamin D Binding Protein, and Risk of Prostate Cancer

    PubMed Central

    Weinstein, Stephanie J.; Mondul, Alison M.; Kopp, William; Rager, Helen; Virtamo, Jarmo; Albanes, Demetrius

    2012-01-01

    We recently reported a significant positive association between 25-hydroxyvitamin D [25(OH)D], the accepted biomarker of vitamin D status, and prostate cancer risk. To further elucidate this association, we examined the influence of vitamin D binding protein (DBP), the primary transporter of vitamin D compounds in the circulation. Prediagnostic serum concentrations of DBP were assayed for 950 cases and 964 matched controls with existing 25(OH)D measurements within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI), and statistical tests were two-sided. Serum DBP modified the association between serum 25(OH)D and prostate cancer, with higher risk for elevated 25(OH)D levels observed primarily among men having DBP concentrations above the median (OR=1.81, 95% CI 1.18–2.79 for highest vs. lowest quintile, p-trend = 0.001) compared to those with DBP below the median (OR=1.22, 95% CI 0.81–1.84, p-trend 0.97; p-interaction = 0.04). Serum DBP was not associated with prostate cancer risk overall (OR=0.96, 95% CI 0.70–1.33 for highest vs. lowest quintile); however, high serum DBP was associated with significantly decreased risk of prostate cancer in men with lower (25(OH)D concentrations (OR=0.59, 95% CI 0.38–0.90 for highest vs. lowest quintile, p-trend = 0.003) and increased risk in men with higher 25(OH)D concentrations (OR = 1.47, 95% CI 0.98–2.20, p-trend 0.10, p-interaction = 0.02). Our data suggest that the primary vitamin D carrier protein, DBP, modulates the impact of vitamin D status on prostate cancer. PMID:23180681

  1. Locally harvested foods support serum 25-hydroxyvitamin D sufficiency in an indigenous population of Western Alaska

    PubMed Central

    Luick, Bret; Bersamin, Andrea; Stern, Judith S.

    2014-01-01

    Background Low serum vitamin D is associated with higher latitude, age, body fat percentage and low intake of fatty fish. Little documentation of vitamin D concentrations is available for Alaska Native populations. Objective This study was undertaken to investigate serum 25-hydroxyvitamin D (25(OH)D) concentrations of the Yup'ik people of southwestern Alaska in relation to demographic and lifestyle variables, particularly with the use of locally harvested (local) foods. Design Cross-sectional study. Methods We estimated 25(OH)D, dietary vitamin D and calcium, percent of energy from local foods and demographic variables in 497 Yup'ik people (43% males) aged 14–92 residing in southwestern Alaska. Sampling was approximately equally divided between synthesizing and non-synthesizing seasons, although the preponderance of samples were drawn during months of increasing daylight. Results Mean vitamin D intake was 15.1±20.2 µg/d, while local foods accounted for 22.9±17.1% of energy intake. The leading sources of vitamin D were local fish (90.1%) followed by market foods. Mean 25(OH)D concentration was 95.6±40.7 nmol/L. Participants in the upper 50th percentile of 25(OH)D concentration tended to be older, male, of lower body mass index, sampled during the synthesizing season, and among the upper 50th percentile of local food use. Conclusions A shift away from locally harvested foods will likely increase the risk for serum 25(OH)D insufficiency in this population. PMID:24665435

  2. Vitamin D receptor polymorphisms and 25-hydroxyvitamin D in a group of Sicilian multiple sclerosis patients.

    PubMed

    Agnello, Luisa; Scazzone, C; Ragonese, P; Salemi, G; Lo Sasso, B; Schillaci, R; Musso, G; Bellia, C; Ciaccio, M

    2016-02-01

    Multiple sclerosis (MS) is an auto-immune disease whose etiology remains controversial. Both genetic and environmental factors are thought to be involved in the risk of developing the disease. The purpose of our study was to assess the association of Vitamin D receptor (VDR) polymorphisms with MS and to investigate the interaction of these polymorphisms with vitamin D levels. A total of 179 Sicilian subjects, including 104 MS patients and 75 healthy controls, were studied. The most common VDR polymorphisms (Fok-I, Bsm-I, Taq-I and Apa-I) were genotyped by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analyses in both groups and serum 25-hydroxyvitamin D [25(OH)D] levels were determined in MS patients by high-performance liquid chromatography (HPLC). The distribution of genotype and allele frequencies of the four VDR polymorphisms did not differ significantly between MS patients and healthy controls, and were unrelated to the forms and the course of MS. Low serum levels of 25(OH)D were observed in MS patients but no association was observed between VDR and 25(OH)D levels except for Fok-I. Moreover, MS patients with FF and Ff genotype had a significantly lower serum levels of 25(OH)D compared with ff carriers (P < 0.05 FF vs Ff and Ff vs ff). Our findings showed no association between VDR polymorphisms and risk of MS. Interestingly, F allele could confer a genetic predisposition to lower 25(OH)D levels. PMID:26506927

  3. Serum 25-Hydroxyvitamin D Concentrations in Children Progressing to Autoimmunity and Clinical Type 1 Diabetes

    PubMed Central

    Mykkänen, Juha; Koskinen, Maarit; Simell, Ville; Veijola, Riitta; Hyöty, Heikki; Ilonen, Jorma; Knip, Mikael; Simell, Olli; Toppari, Jorma

    2016-01-01

    Context: The role of vitamin D in the development of type 1 diabetes (T1D) remains controversial. Objective: The objective of the investigation was to study whether there are detectable differences in serum 25-hydroxyvitamin D (25[OH]D) concentrations between children who later progressed to T1D (cases) and matched children who remained nondiabetic and negative for islet autoantibodies (controls) when followed up from birth until disease onset. Design: A total of 3702 prospective serum samples from 252 children were measured for 25(OH)D from the age of 3 months onward using an enzyme immunoassay. Differences between the groups were compared by the mixed-model analysis of variance. Setting: T1D prediction and prevention study clinics in Turku, Oulu, and Tampere University Hospitals, Finland, participated in the study. Participants: By the end of 2012, all 126 case children were diagnosed with T1D. The control children (n = 126) were matched for age, sex, study site, and human leukocyte antigen-HLA-DQ-conferred risk for T1D. Main Outcome Measure: Median circulating 25(OH)D concentration (nanomoles per liter) was measured. Results: The patterns of variation in circulating 25(OH)D concentrations were similar between cases and controls and did not correlate with the age at seroconversion to autoantibody positivity (P = .79) or disease onset (P = .13). The median concentration of all collected samples did not differ between case and control children (66.6 nmol/L [range 14.0–262.8] vs 67.4 nmol/L [range 19.9–213.0]) P = .56). Conclusions: This study shows that serum 25(OH)D concentrations are not associated with the development of T1D in Finland. PMID:26695863

  4. Serum 25-hydroxyvitamin D levels are inversely associated with systemic inflammation in severe obese subjects.

    PubMed

    Bellia, Alfonso; Garcovich, Caterina; D'Adamo, Monica; Lombardo, Mauro; Tesauro, Manfredi; Donadel, Giulia; Gentileschi, Paolo; Lauro, Davide; Federici, Massimo; Lauro, Renato; Sbraccia, Paolo

    2013-02-01

    Obesity is frequently characterized by a reduced vitamin D bioavailability, as well as insulin-resistance and a chronic inflammatory response. We tested the hypothesis of an independent relationship between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and several circulating inflammatory markers in a cohort of severely obese individuals. Cross-sectional study was carried out among obese patients undergoing a clinical evaluation before bariatric surgery in our University Hospital. Serum 25(OH)D, fasting and post load glucose and insulin, high-sensitive C-reactive protein (hs CRP), fibrinogen, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leptin, adiponectin and lipid profile were collected. Insulin-resistance was assessed by insulin sensitivity index (ISI). Total body fat (FAT kg), total percent body fat (FAT%) and truncal fat mass (TrFAT) were assessed with dual-energy X-ray absorptiometry. A total of 147 obese subjects (89 women, 37.8 ± 7.1 years) with mean body mass index (BMI) of 43.6 ± 4.3 kg/m(2) were enrolled. Patients in the lowest tertile of 25(OH)D were significantly more obese with a higher amount of TrFAT, more insulin-resistant, and had higher levels of fasting and post-challenge glucose (p < 0.05 for all). In a multivariate regression analysis, serum 25(OH)D was inversely related to significant levels of hs CRP, IL-6 and TNF-α after accounting for age, gender, season of recruitment, BMI, FAT kg and TrFAT (p < 0.01 for all). In extremely obese subjects, 25(OH)D serum concentrations are inversely associated with several biomarkers of systemic inflammation, regardless of the total quantity of fat mass. PMID:21437585

  5. Partial purification of cytosolic 25 hydroxyvitamin D binding protein from rate enterocytes

    SciTech Connect

    Teegarden, D.; Meredith, S.; Sitrin, M.

    1986-01-01

    The authors have characterized and partially purified an enterocyte cytosolic 25 hydroxyvitamin D (250HD) binding protein which may participate in transcellular vitamin D metabolite transport. Triglyceride-rich emulsion particles (1%/wt/vol) containing /sup 3/H-250HD were incubated with rat intestinal cytosol or buffer for 0.5 hr. The reaction mixture was rapidly cooled and the mixture was centrifuged at 65,000g for 1 hr. Aliquots of buffer or cytosol infranatant were taken for scintillation counting. Only 4% of /sup 3/H-250HD transferred from the emulsion particles to buffer whereas 29% transferred to cytosol. Fractionation of cytosol by ammonium sulfate precipitation showed that the 60-80% saturation cut contained the 250HD binding activity. When this ammonium sulfate fraction was labeled with /sup 3/H-250HD and then subjected to gel permeation HPLC using a Toyo Soda G3000SW column, the /sup 3/H-250HD eluted in association with a peak of protein of MW/sup app/=68,000. The protein bound /sup 3/H-250HD eluted as a single peak on DEAE Sephacel anion exchange chromatography. The cytosolic 250HD binding activity was totally inactivated by heating to 60/sup 0/C for 1 hr. Serum vitamin D binding protein (sDBP) is stable under these heating conditions and has a MW/sup app/=58,000. They conclude that rat intestinal cytosol contains a 250HD binding protein whose MW and heat stability characteristics indicate that the cytosolic protein is distinct from sDBP.

  6. Association of plasma 25-hydroxyvitamin D concentrations and pathogenic oral bacteria in postmenopausal women

    PubMed Central

    Sahli, Michelle W; Wactawski-Wende, Jean; Ram, Pavani K; LaMonte, Michael J.; Hovey, Kathleen M.; Genco, Robert J.; Andrews, Christopher A.; Millen, Amy E.

    2014-01-01

    Background Previous findings of an association between 25-hydroxyvitamin D (25(OH)D) concentrations and periodontal disease, may be partially explained by vitamin D’s antimicrobial properties. To our knowledge, no study has investigated the association between 25(OH)D and pathogenic oral bacteria, a putative cause of periodontal disease. Methods We examined the association between plasma 25(OH)D concentrations and pathogenic oral bacteria among postmenopausal women in the Buffalo Osteoporosis and Periodontal Disease Study (1997–2000), an ancillary study of the Women’s Health Initiative Observational Study. Subgingival plaque samples were assessed using immunofluorescence for the presence of Porphyromonas gingivalis, Tannerella forsythensis, Fusobacterium nucleatum, Prevotella intermedia and Campylobacter rectus. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for prevalent bacteria by quintile (Q) of 25(OH)D concentrations adjusting for age and body mass index. Results Of the 855 participants, 288 (34%) had deficient/inadequate (<50 nmol/L) 25(OH)D concentrations and 497 (58%) had at least one species of pathogenic bacteria. No significant association was found between 25(OH)D and presence of any of these bacteria (adjusted OR for high (Q5) compared to low (Q1) 25(OH)D=0.96; 95% CI: 0.61–1.50, p for trend=0.50). Inverse, although not statistically significant, associations were found between 25(OH)D and more than one species of pathogenic bacteria (adjusted OR for adequate compared to deficient/inadequate 25(OH)D=0.85; 95% CI: 0.60–1.19). Conclusions No association was observed between pathogenic oral bacteria and 25(OH)D concentrations in postmenopausal women. This may be due to the species of bacteria assessed, small effect size or a true absence of an association. PMID:24261910

  7. Plasma 25-hydroxyvitamin D concentrations and periodontal disease in postmenopausal women

    PubMed Central

    Millen, Amy E.; Hovey, Kathleen M.; LaMonte, Michael J.; Swanson, Mya; Andrews, Christopher A.; Kluczynski, Melissa A.; Genco, Robert J.; Wactawski-Wende, Jean

    2013-01-01

    Background Vitamin D has anti-inflammatory and anti-microbial properties that, together with its influence on bone health, may confer periodontal benefit. Methods We investigated cross-sectional associations (1997–2000) between plasma 25-hydroxyvitamin D concentrations [25(OH)D] and periodontal measure among 920 postmenopausal women. Chronic measures of disease were defined based on: 1) alveolar crestal height (ACH) measures from intraoral radiographs and tooth loss, and the 2) Center for Disease Control and Prevention (CDC)/American Academy of Periodontology (AAP) criteria using measures of clinical attachment level (CAL) and probing pocket depth (PD). Acute oral inflammation was assessed by the % of gingival sites that bled upon assessment with a probe. Logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CIs) for periodontal disease among participants with adequate ([25(OH)D]≥50 nmol/L) compared to deficient/inadequate ([25(OH)D]<50 nmol/L) vitamin D status adjusted for age, dental visit frequency, and body mass index. Results No association was observed between vitamin D status and periodontal disease defined by ACH and tooth loss (adjusted OR=0.96, 95% CI: 0.68–1.35). In contrast, women with adequate compared to deficient/inadequate vitamin D status had a 33% lower odds (95% CI: 5%–53%) of periodontal disease defined using the CDC/AAP definition and a 42% lower odds (95% CI: 21%-58%) of having ≥50% of gingival sites that bled. Conclusion Vitamin D status was inversely associated with gingival bleeding, an acute measure of oral health and inflammation and inversely associated with clinical categories of chronic periodontal disease that incorporated PD, an indicator of oral inflammation. However, vitamin D was not associated with chronic periodontal disease based on measures of ACH in combination with tooth loss. PMID:23259413

  8. Intraindividual variation in plasma 25-hydroxyvitamin D measures 5 years apart among postmenopausal women

    PubMed Central

    Meng, Jennifer E.; Hovey, Kathleen M.; Wactawski-Wende, Jean; Andrews, Christopher A; LaMonte, Michael J.; Horst, Ronald L.; Genco, Robert J.; Millen, Amy E.

    2012-01-01

    Background Current literature examining associations between vitamin D and chronic disease generally use a single assessment of 25-hydroxyvitamin D (25(OH)D), assuming an individual’s 25(OH)D concentration is consistent over time. Methods We investigated the intraindividual variability between two measures of plasma 25(OH)D concentrations collected ~5 years apart (1997-2000 to 2002-2005) in 672 postmenopausal women participating in the Women’s Health Initiative. Plasma 25(OH)D was assessed using the DiaSorin LIAISON® chemiluminescence immunoassay. The within-pair coefficient of variation (CV) was 4.9% using blinded quality control samples. Mean and standard deviations (SD) of 25(OH)D at the two time points were compared using a paired t-test. An intraindividual CV and intra-class correlation coefficient (ICC) were used to assess intraindividual variability. A Spearman correlation coefficient (r) assessed the strength of the association between the two measures and concordance in vitamin D status at two time points Results Mean 25(OH)D concentrations (nmol/L) significantly increased over time from 60.0 (SD=22.2) to 67.8 (SD=22.2) (p<0.05). The CV was 24.6%, the ICC (95% Confidence Interval (CI)) was 0.59 (0.54-0.64), and the Spearman r was 0.61 (95% CI=0.56-0.66). Greater concordance over 5 years was observed in participants with sufficient compared to deficient or inadequate baseline 25(OH)D concentrations (weighted kappa=0.39). Reliability measures were moderately influenced by season of blood draw and vitamin D supplement use. Conclusion There is moderate intraindividual variation in 25(OH)D concentrations over approximately 5 years. Impact These data support the use of a one-time measure of blood 25(OH)D in prospective studies with ≤ 5 years of follow-up. PMID:22523182

  9. Premenopausal plasma 25-hydroxyvitamin D, mammographic density, and risk of breast cancer.

    PubMed

    Bertrand, Kimberly A; Rosner, Bernard; Eliassen, A Heather; Hankinson, Susan E; Rexrode, Kathryn M; Willett, Walter; Tamimi, Rulla M

    2015-01-01

    Epidemiologic evidence for an association between plasma 25-hydroxyvitamin D [25(OH)D] and breast cancer is inconsistent. Data are especially limited for premenopausal women and for associations with mammographic density. To test the hypothesis that plasma concentration of 25(OH)D is associated with mammographic density, we conducted a cross-sectional study among 835 premenopausal women in the Nurses' Health Studies. We measured 25(OH)D in blood samples and used multivariable linear regression to quantify the association of average percent density by quartile of plasma 25(OH)D. In a nested case-control analysis including 493 breast cancer cases, we evaluated risk of breast cancer associated with vitamin D status within tertiles of mammographic density. Women in the top quartile of plasma 25(OH)D levels had an average percent breast density 5.2 percentage points higher than women in the bottom quartile (95 % confidence interval: 1.8, 8.7; P trend <0.01), after adjusting for predictors of 25(OH)D and established breast cancer risk factors. Plasma 25(OH)D concentration was significantly inversely associated with breast cancer risk among women with high mammographic density (P trend < 0.01) but not among women in lower tertiles of mammographic density (P-interaction < 0.01). These results do not support the hypothesis that vitamin D is inversely associated with percent mammographic density in premenopausal women. There was evidence that the association between premenopausal 25(OH)D and breast cancer risk varies by mammographic density, with an inverse association apparent only among women with high mammographic density. PMID:25543181

  10. Premenopausal plasma 25-hydroxyvitamin D, mammographic density, and risk of breast cancer

    PubMed Central

    Bertrand, Kimberly A.; Rosner, Bernard; Eliassen, A. Heather; Hankinson, Susan E.; Rexrode, Kathryn M.; Willett, Walter; Tamimi, Rulla M.

    2015-01-01

    Purpose Epidemiologic evidence for an association between plasma 25-hydroxyvitamin D [25(OH)D] and breast cancer is inconsistent. Data are especially limited for premenopausal women and for associations with mammographic density. Methods To test the hypothesis that plasma concentration of 25(OH)D is associated with mammographic density, we conducted a cross-sectional study among 835 premenopausal women in the Nurses’ Health Studies. We measured 25(OH)D in blood samples and used multivariable linear regression to quantify the association of average percent density by quartile of plasma 25(OH)D. In a nested case-control analysis including 493 breast cancer cases, we evaluated risk of breast cancer associated with vitamin D status within tertiles of mammographic density. Results Women in the top quartile of plasma 25(OH)D levels had an average percent breast density 5.2 percentage points higher than women in the bottom quartile (95% confidence interval: 1.8, 8.7; P-trend <0.01), after adjusting for predictors of 25(OH)D and established breast cancer risk factors. Plasma 25(OH)D concentration was significantly inversely associated with breast cancer risk among women with high mammographic density (odds ratio comparing top to bottom tertile of 25(OH)D = 0.50; 95% confidence interval= 0.30, 0.83; P-trend <0.01) but not among women in lower tertiles of mammographic density (P-interaction <0.01). Conclusions These results do not support the hypothesis that vitamin D is inversely associated with percent mammographic density in premenopausal women. There was evidence that the association between premenopausal 25(OH)D and breast cancer risk varies by mammographic density, with an inverse association apparent only among women with high mammographic density. PMID:25543181

  11. Raised serum 25-hydroxyvitamin D levels in patients with active diabetic foot ulcers.

    PubMed

    Afarideh, Mohsen; Ghanbari, Parvaneh; Noshad, Sina; Ghajar, Alireza; Nakhjavani, Manouchehr; Esteghamati, Alireza

    2016-06-01

    Studies have emerged to demonstrate bidirectional changes in circulating cytokines of inflammation in active diabetic foot ulcers (DFU). To further expand the understanding of inflammatory status present in chronic active DFU, we comparatively assessed the associations of selected pro-inflammatory cytokines and 25-hydroxyvitamin D (25(OH)D) with the presence of DFU. In a cross-sectional setting, thirty patients with type 2 diabetes and active DFU matched with thirty control non-ulcerative patients with type 2 diabetes and twenty-eight healthy subjects underwent anthropometric and biochemical assessment of study parameters. Recruited patients with DFU were selected from the grade II active chronic DFU at the time of hospitalisation according to the University of Texas wound classification system. Patients with DFU and controls had comparable age, sexual distribution, diastolic blood pressure and TAG, LDL-cholesterol and glycated Hb. The trend changes from healthy controls towards DFU showed a significant increase for serum monocyte chemoattractant protein-1, IL-6, 25(OH)D and highly sensitive C-reactive protein and a decrease for IL-8. In the multivariate adjusted logistic regression model, 25(OH)D emerged as the only independent correlate of DFU (OR 2·194; 95 % CI 1·003, 4·415). Unprecedented increase of serum 25(OH)D in chronic active DFU is possibly related to a selective alteration in the inflammatory status. In particular, 25(OH)D and IL-8 seem to share a common pathway in the pathogenesis of diabetic foot. PMID:27153203

  12. Circulating 25-Hydroxyvitamin-D and Risk of Colorectal Adenomas and Hyperplastic Polyps

    PubMed Central

    Adams, Scott V.; Newcomb, Polly A.; Burnett-Hartman, Andrea N.; White, Emily; Mandelson, Margaret T.; Potter, John D.

    2011-01-01

    Colorectal adenomas are clear precursors of cancer; hyperplastic polyps may also have malignant potential. An inverse association between circulating vitamin D metabolites and adenoma risk has been reported, but less is known about vitamin D and hyperplastic polyps. We conducted a case-control study of adenomas and hyperplastic polyps among 459 members of an integrated health plan evaluated via colonoscopy. Questionnaires provided information on colorectal polyp risk factors, and plasma samples were assayed for 25-hydroxyvitamin-D (25(OH)D). Polytomous regression was used to estimate odds ratios for adenomas (N=149) and hyperplastic polyps (N=85) compared to polyp-free controls (N=225) by tertile of 25(OH)D. An inverse association between 25(OH)D and adenomas was suggested after adjustment for potential confounding factors (comparing upper to lower tertiles, OR[95%CI]: 0.71 [0.38–1.30]). After restriction of the analyses to study participants with no history of polyps, this OR estimate was reduced further (adjusted OR [95%CI]: 0.52 [0.23–1.20]). In comparison, no inverse association between hyperplastic polyps and 25(OH)D was observed among the full study participants (adjusted OR [95%CI]: 1.17 [0.55–2.51]) or among those without prior polyps (adjusted OR [95%CI]: 1.42 [0.55–3.65]). Our study suggests that the established inverse association between circulating 25(OH)D and adenoma may not apply to hyperplastic polyps. PMID:21432725

  13. Association between serum 25-hydroxyvitamin D and ovarian reserve in pre-menopausal women

    PubMed Central

    Jukic, Anne Marie Z.; Steiner, Anne Z.; Baird, Donna D.

    2014-01-01

    Objective Vitamin D has been linked to anti-Müllerian hormone levels, suggesting a possible association with greater ovarian reserve, but large population-based studies are lacking. Our objective was to explore the association between vitamin D and FSH in premenopausal women. Methods The Uterine Fibroid Study (1996 – 1999) enrolled randomly-selected 30 – 49 year-old members of a Washington D. C. health plan (N=1430). Women provided a blood and urine sample in addition to questionnaire data. The vitamin D metabolite 25-hydroxyvitamin D (25(OH)D) was measured in stored plasma samples. Urinary FSH (mIU/mg creatinine) was measured with an immunofluorometric assay. To obtain baseline measures, this investigation was limited to urine samples collected in the first 5 days of the menstrual cycle or 5 days prior to menses onset. Additionally, post-menopausal women and women using oral contraceptives were excluded, leaving 527 women in our analysis. FSH was creatinine-adjusted, normalized by log-transformation, and then modeled with multivariable linear regression. Results The median 25(OH)D level was 12 ng/mL, with approximately 75% of participants below the recommended level of 20 ng/mL. FSH and 25(OH)D were inversely related. For an increase of 10 ng/mL in 25(OH)D, urinary FSH decreased 14% (95% Confidence Interval: −23%, −5%), p=0.003. Conclusions Vitamin D is inversely related to FSH. This is consistent with literature relating low vitamin D with lower anti-Müllerian hormone. Prospective studies should investigate whether low levels of vitamin D contribute to decreased ovarian reserve. PMID:25093721

  14. Anionic salts and dietary 25-hydroxyvitamin D stimulate calcium availability in steers.

    PubMed

    McGrath, J J; Savage, D B; Nolan, J V; Rodgers, N J; Elliott, R

    2013-03-01

    The influence of feeds containing varying dietary cation-anion differences (DCADs) with and without supplements of 25-hydroxyvitamin D (25(OH)D) on urine pH and excretion of macro minerals was determined in fistulated crossbred steers (mean live weight 315 ± 45 kg). A basal forage diet comprising lucerne hay and wheat chaff was used, to which varying quantities of MgCl(2) or K(2)CO(3) were added to achieve four levels of DCAD: -300, 50, 150 or 250 mEq/kg dry matter (DM). Steers were allocated to one of six treatments, one treatment for each diet and a further treatment for both the 50 and 150 mEq/kg DCAD diets, which were supplemented with 25(OH)D at a rate of 3 mg/steer per day. Urine pH from steers offered the diets comprising DCADs of 50, 150 and 250 mEq/kg ranging from 8.3 to 8.8. In treatments not containing 25(OH)D with DCADs of 50 to 250 mEq/kg, there were no significant differences in urine pH or Ca excretion. However, steers offered the diet with a DCAD of -300 mEq/kg DM produced urine with a significantly lower pH (6.5 to 7.5). Daily output of Ca in urine was also significantly higher from steers given this diet. Supplementation with 25(OH)D significantly increased urinary Ca excretion from steers offered diets of DCADs 50 and 150 mEq/kg DM. Estimates of daily urinary Ca excretion, calculated using the ratio of creatinine to Ca in 'spot' urine samples, were less variable than those based on total collection (residual mean square of 0.54 and 0.63, respectively). PMID:23084000

  15. Vitamin D status and predictors of serum 25-hydroxyvitamin D concentrations in Western Australian adolescents.

    PubMed

    Black, Lucinda J; Burrows, Sally A; Jacoby, Peter; Oddy, Wendy H; Beilin, Lawrence J; Chan She Ping-Delfos, Wendy; Marshall, Carina E; Holt, Patrick G; Hart, Prue H; Mori, Trevor A

    2014-10-14

    Despite the importance of skeletal growth during adolescence, there is limited research reporting vitamin D status and its predictors in adolescents. Using prospective data from the Western Australian Pregnancy Cohort (Raine) Study, we investigated vitamin D status and predictors of serum 25-hydroxyvitamin D (25(OH)D) concentrations in adolescents. Serum 25(OH)D concentrations were measured in the same participants at 14 and 17 years (n 1045 at both time points). The percentage of adolescents with serum 25(OH)D concentrations < 50, 50-74·9 and ≥ 75 nmol/l was reported year-round and by month of blood collection. We examined the predictors of serum 25(OH)D concentrations, including sex, race, month of blood collection, physical activity, BMI, family income, and Ca and vitamin D intakes (n 919 at 14 years; n 570 at 17 years), using a general linear mixed model. At 14 years, 31 % of adolescents had serum 25(OH)D concentrations between 50 and 74·9 nmol/l and a further 4 % had concentrations < 50 nmol/l. At 17 years, 40 % of adolescents had serum 25(OH)D concentrations between 50 and 74·9 nmol/l and 12 % had concentrations < 50 nmol/l. Caucasian ethnicity, being sampled at the end of summer, exercising more, having a lower BMI, a higher Ca intake and a higher family income were significantly associated with higher serum 25(OH)D concentrations. The proportion of adolescents with serum 25(OH)D concentrations < 50 nmol/l was low in this Western Australian cohort. There is a need for international consensus on defining adequate vitamin D status in order to determine whether strategies to increase vitamin D status in adolescents are warranted. PMID:25137493

  16. 1,25-Dihydroxyvitamin D3 Enhances Innate Immune Responses of Bovine Mammary Epithelial Cells that are Triggered by Toll-like Receptor Signaling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recently, 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) has been found to play an important role in the bovine innate immune response. 1,25(OH)2D3 is the active vitamin D metabolite and is produced from the major circulating metabolite, 25-hydroxyvitamin D3, by the enzyme 1alpha-hydroxylase (1alpha-OHase)...

  17. Seasonal variations of 25 hydroxyvitamin D and parathyroid hormone in Ushuaia (Argentina), the southernmost city of the world.

    PubMed

    Oliveri, M B; Ladizesky, M; Mautalen, C A; Alonso, A; Martinez, L

    1993-01-01

    Serum levels of calcium, phosphorus, alkaline phosphatase, 250HD, 1.25(OH)2D and PTH were studied in a group of 42 children aged 8.5 +/- 1.8 years (X +/- SD) from the city of Ushuaia (latitude 55 degrees S), at both the end of the winter and the end of summer. Calcium, phosphorus, alkaline phosphatase and 1.25(OH)2D serum levels were not different in summer and winter. The levels of serum 25OHD were significantly higher in summer (18.4 +/- 7.3 ng/ml) than in winter (9.8 +/- 3.8 ng/ml P < 0.001). The levels of 25OHD in children with fair or dark skin were similar in winter but were significantly higher in children with fair skin in summer (20.0 +/- 7.2 ng/l vs 15.3 +/- 5.1 ng/ml (P < 0.05). Serum levels of PTH were higher in winter (58.2 +/- 30.5 pg/ml) than in summer (47.9 +/- 28.3 pg/ml) (P < 0.03). The results demonstrate the existence of a population with low serum levels of 25OHD in winter. The higher levels of PTH in winter when serum 25OHD levels are lower could be the cause of the lack of seasonal variation in serum calcium and 1.25(OH)2D levels. Further studies are needed to establish whether these changes besides increasing the incidence of rickets, could also affect the mineral density of the skeleton in the population of this vitamin-D-deficient area. PMID:8453326

  18. Low Serum 25-Hydroxyvitamin D Levels Are Associated with Dry Eye Syndrome

    PubMed Central

    Yoon, Sam Young; Bae, Seok Hyun; Shin, Young Joo; Park, Shin Goo; Hwang, Sang-Hee; Hyon, Joon Young; Wee, Won Ryang

    2016-01-01

    Background Dry eye syndrome (DES) is a common tear film and ocular surface disease that results in discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. Systemic diseases associated with DES include diabetes mellitus, rheumatoid arthritis, depression, anxiety, thyroid disease, allergic diseases, irritable bowel syndrome, chronic pain syndrome, and hyperlipidemia. Interestingly, it has been found that most of these are associated with low levels of serum 25-hydroxyvitamin D (25(OH)D) or inadequate sunlight exposure. Methods In this cross-sectional data analysis, noninstitutionalized adults aged ≥19 years (N = 17,542) who participated in Korean National Health and Nutrition Examination Survey 2010–2012 were included. Information regarding duration of sunlight exposure was collected from the survey participants. Serum 25(OH)D and zinc levels were measured. The confounding variables were age, gender, sunlight exposure time, region of residence, obesity, serum 25(OH)D level, diabetes mellitus, rheumatoid arthritis, depression, thyroid disorder, atopic dermatitis, history of ocular surgery, regular exercise, and walking exercise. Results Mean serum 25(OH)D levels of subjects with and without DES were 16.90 ± 6.0 and 17.52 ± 6.07 (p<0.001). Inadequate sunlight exposure time (odds ratio [OR], 1.554; 95% confidence interval [CI], 1.307–1.848), urban residence (OR, 1.669; 95% CI, 1.456–1.913), indoor occupation (OR, 1.578; 95% CI, 1.389–1.814), and low serum 25(OH)D level (OR, 1.158; 95% CI, 1.026–1.308) were the risk factors for DES. After adjusting for age, sex, obesity, diabetes mellitus, rheumatoid arthritis, depression, thyroid disorder, atopic dermatitis, history of ocular surgery, regular exercise, and occupation, low serum 25(OH)D level (OR, 1.178; 95% CI, 1.010–1.372) and deficient sunlight exposure time (OR, 1.383; 95% CI, 1.094–1.749) were the risk factors for diagnosed DES. Conclusion Low serum 25

  19. New, tritium-release assay for 25-hydroxyvitamin D-1. cap alpha. -hydroxylase

    SciTech Connect

    Brown, A.J.; Perlman, K.; DeLuca, H.F.

    1986-05-01

    A new, rapid assay for 25-hydroxyvitamin D (25-OH-D)-1..cap alpha..-hydroxylase has been developed using 25-OH-(1..cap alpha..-/sup 3/H)D/sub 3/ as substrate. This compound was prepared by reduction of 1-oxo-25-hydroxycyclovitamin D/sub 3/ with (/sup 3/H)NaBH/sub 4/, separation of the 1..cap alpha..- and 1..beta..-hydroxy products by HPLC, subsequent treatments with methylsulfonylchloride and lithium aluminum hydride, cycloreversion, and saponification. The 1..cap alpha..- and 1..beta..-tritiated substrates were tested in the solubilized and reconstituted chick 1..cap alpha..-hydroxylase system. After incubation, the reaction mixture was passed through a reversed phase silica cartridge to separate (/sup 3/H)H/sub 2/O from the labeled substrate. The cartridges were then washed with methanol to elute all vitamin D metabolites, and the amount of 1,25-(OH)/sub 2/(/sup 3/H)D/sub 3/ was measured by HPLC. In addition, identical reaction mixtures using 25-OH-(26,27-/sup 3/H)D/sub 3/ as substrate were extracted and analyzed by HPLC for 1,25-(OH)/sub 2/(/sup 3/H)D/sub 3/. Reactions with 25-OH-(1..cap alpha..-/sup 3/H)D/sub 3/ produced (/sup 3/H)H/sub 2/O comparable to the amount of 1,25-(OH)/sub 2/(26,27-/sup 3/H)D/sub 3/ and negligible (/sup 3/H) in 1,25-(OH)/sub 2/D/sub 3/. Conversely, reactions with 25-OH-(1..beta..-/sup 3/H)D/sub 3/ produced negligible (/sup 3/H)H/sub 2/O but produced 1,25-(OH)/sub 2/(/sup 3/H)D/sub 3/ comparable to that from reactions with 25-OH-(26,27-/sup 3/H)D/sub 3/. The results indicate that 1..cap alpha..-hydroxylation specifically displaces the 1..cap alpha..-hydrogen of 25-OH-D/sub 3/ and that the release of the 1..cap alpha..-/sup 3/H provides an accurate measure of vitamin D 1..cap alpha..-hydroxylation.

  20. Comparison of 25-hydroxyvitamin D and Calcium Levels between Polycystic Ovarian Syndrome and Normal Women

    PubMed Central

    Moini, Ashraf; Shirzad, Nooshin; Ahmadzadeh, Marzieh; Hosseini, Reihaneh; Hosseini, Ladan; Sadatmahalleh, Shahideh Jahanian

    2015-01-01

    Background Given the relationship of vitamin D deficiency with insulin resistance syndrome as the component of polycystic ovary syndrome (PCOS), the main aim of this study was to compare serum level of 25hydroxyvitamin D [25(OH)D] between PCOS patients and normal individuals. Materials and Methods A cross sectional study was conducted to compare 25(OH)D level between117 normal and 125 untreated PCOS cases at our clinic in Arash Hospital, Tehran, Iran, during 2011-2012. The obtained levels of 25(OH)D were classified as follows: lower than 25 nmol/ml as severe deficiency, between 25-49.9 nmol/ml as deficiency, 50-74.9 nmol/ml as insufficiency, and above 75 nmol/ml asnormal. In addition, endocrine and metabolic variables were evaluated. Results Among PCOS patients, our findings shows 3(2.4%) normal, 7(5.6%) with insufficiency, 33(26.4%) with deficiency and 82(65.6%) with severe deficiency, whereas in normal participants, 5(4.3%) normal, 4(3.4%) with insufficiency, 28(23.9%) with deficiency and 80(68.4%) with severe deficiency. Comparison of 25(OH)D level between two main groups showed no significant differences (p= 0.65). Also, the calcium and 25(OH)D levels had no significant differences in patients with overweight (p=0.22) and insulin resistance (p=0.64). But we also found a relationship between 25(OH)D level and metabolic syndrome (p=0.01). Furthermore, there was a correlation between 25(OH)D and body mass index (BMI) in control group (p=0.01), while the C-reactive protein (CRP) level was predominantly higher in PCOS group (p<0.001). Conclusion Although the difference of 25(OH)D level between PCOS and healthy women is not significant, the high prevalence of 25(OH)D deficiency is a real alarm for public health care system and may influence our results. PMID:25918586

  1. Serum 25 Hydroxyvitamin D, Bone Mineral Density and Fracture Risk Across the Menopause

    PubMed Central

    Greendale, Gail A.; Ruppert, Kristine; Lian, Yinjuan; Randolph, John F.; Lo, Joan C.; Burnett-Bowie, Sherri-Ann; Finkelstein, Joel S.

    2015-01-01

    Context: Low levels of serum 25 Hydroxyvitamin D [25(OH)D] have been linked to greater fracture risk in older women. Objective: This study aimed to determine whether higher 25(OH)D is associated with slower loss of bone mineral density (BMD) and lower fracture risk during the menopausal transition. Design, Setting, and Participants: This was a prospective cohort study at five clinical centers in the United States. Mean age was 48.5 ± 2.7 years. The fracture analysis included 124 women with an incident traumatic fracture, 88 with incident nontraumatic fracture, and 1532 women without incident fractures; average followup was 9.5 years. BMD analysis included 922 women with a documented final menstrual period. Main Outcome Measures: Serum 25(OH)D was measured by liquid chromatography tandem mass spectrometry at the third annual clinic visit. BMD was measured and incident fractures ascertained at each annual visit. Results: The mean 25(OH)D was 21.8 ng/mL; seven-hundred two (43%) of the women had 25(OH)D values <20 ng/mL. There was no significant association between 25(OH)D and traumatic fractures. In multivariate adjusted hazards models, the hazard ratio (HR) for nontraumatic fractures (95% confidence interval [CI]) was 0.72 (0.54–0.96) for each 10-ng/mL increase in 25(OH)D. Comparing women whose 25(OH)D was ≥20 vs <20 ng/mL, the HR (95% CI) for fracture was 0.54 (0.32–0.89). Changes in lumbar spine and femoral neck bone mineral density across menopause were not significantly associated with serum 25(OH)D level. Conclusion: Serum 25(OH)D levels are inversely associated with nontraumatic fracture in mid-life women. Vitamin D supplementation is warranted in midlife women with 25(OH)D levels <20 ng/mL. PMID:25719933

  2. Plasma 25-Hydroxyvitamin D Concentration and Metabolic Syndrome Among Middle-Aged and Elderly Chinese Individuals

    PubMed Central

    Lu, Ling; Yu, Zhijie; Pan, An; Hu, Frank B.; Franco, Oscar H.; Li, Huaixing; Li, Xiaoying; Yang, Xilin; Chen, Yan; Lin, Xu

    2009-01-01

    OBJECTIVE To evaluate the association between 25-hydroxyvitamin D [25(OH)D] and metabolic syndrome in the Chinese population. RESEARCH DESIGN AND METHODS Plasma 25(OH)D was measured in a cross-sectional sample of 1,443 men and 1,819 women aged 50–70 years from Beijing and Shanghai. Metabolic syndrome was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian Americans. Fasting plasma glucose, insulin, lipid profile, A1C, and inflammatory markers were measured. RESULTS The geometric mean of plasma 25(OH)D was 40.4 nmol/l, and percentages of vitamin D deficiency [25(OH)D <50 nmol/l] and insufficiency [50 ≤ 25(OH)D <75 nmol/l] were 69.2 and 24.4%, respectively. Compared with the highest 25(OH)D quintile (≥57.7 nmol/l), the odds ratio for metabolic syndrome in the lowest quintile (≤28.7 nmol/l) was 1.52 (95% CI 1.17–1.98, Ptrend = 0.0002) after multiple adjustment. Significant inverse associations also existed between 25(OH)D and individual metabolic syndrome components plus A1C. Moreover, we observed significant inverse associations of 25(OH)D with fasting insulin and the insulin resistance index (homeostasis model assessment of insulin resistance [HOMA-IR]) in overweight and obese individuals (BMI ≥24 kg/m2) but not in their normal-weight counterparts (test for interaction: P = 0.0363 and 0.0187 for insulin and HOMA-IR, respectively). CONCLUSIONS Vitamin D deficiency is common in the middle-aged and elderly Chinese population, and a low 25(OH)D level is significantly associated with an increased risk of having metabolic syndrome and insulin resistance. Prospective studies and randomized clinical trials are warranted to determine the role of 25(OH)D in the development of metabolic syndrome and related metabolic diseases. PMID:19366976

  3. Temporal trends and determinants of longitudinal change in 25-hydroxyvitamin D and parathyroid hormone levels.

    PubMed

    Berger, Claudie; Greene-Finestone, Linda S; Langsetmo, Lisa; Kreiger, Nancy; Joseph, Lawrence; Kovacs, Christopher S; Richards, J Brent; Hidiroglou, Nick; Sarafin, Kurtis; Davison, K Shawn; Adachi, Jonathan D; Brown, Jacques; Hanley, David A; Prior, Jerilynn C; Goltzman, David

    2012-06-01

    Vitamin D is essential for facilitating calcium absorption and preventing increases in parathyroid hormone (PTH), which can augment bone resorption. Our objectives were to examine serum levels of 25-hydroxyvitamin D [25(OH)D] and PTH, and factors related to longitudinal change in a population-based cohort. This is the first longitudinal population-based study looking at PTH and 25(OH)D levels. We analyzed 3896 blood samples from 1896 women and 829 men in the Canadian Multicentre Osteoporosis Study over a 10-year period starting in 1995 to 1997. We fit hierarchical models with all available data and adjusted for season. Over 10 years, vitamin D supplement intake increased by 317 (95% confidence interval [CI] 277 to 359) IU/day in women and by 193 (135 to 252) IU/day in men. Serum 25(OH)D (without adjustment) increased by 9.3 (7.3 to 11.4) nmol/L in women and by 3.5 (0.6 to 6.4) nmol/L in men but increased by 4.7 (2.4 to 7.0) nmol/L in women and by 2.7 (-0.6 to 6.2) nmol/L in men after adjustment for vitamin D supplements. The percentage of participants with 25(OH)D levels <50 nmol/L was 29.7% (26.2 to 33.2) at baseline and 19.8% (18.0 to 21.6) at year 10 follow-up. PTH decreased over 10 years by 7.9 (5.4 to 11.3) pg/mL in women and by 4.6 (0.2 to 9.0) pg/mL in men. Higher 25(OH)D levels were associated with summer, younger age, lower body mass index (BMI), regular physical activity, sun exposure, and higher total calcium intake. Lower PTH levels were associated with younger age and higher 25(OH)D levels in both women and men and with lower BMI and participation in regular physical activity in women only. We have observed concurrent increasing 25(OH)D levels and decreasing PTH levels over 10 years. Secular increases in supplemental vitamin D intake influenced both changes in serum 25(OH)D and PTH levels. PMID:22407786

  4. Relationships between 25-Hydroxyvitamin D and Nocturnal Enuresis in Five- to Seven-Year-Old Children

    PubMed Central

    Li, Luanluan; Zhou, Huafei; Yang, Xin; Zhao, Li; Yu, Xiaodan

    2014-01-01

    Background Vitamin D has been recognized to contribute to various physiological processes. However, no study has investigated serum 25-hydroxyvitamin D [25(OH)D] concentrations in children with nocturnal enuresis (NE) in the English literature. Objective In the present study, serum 25(OH)D concentrations were measured in five- to seven-year-old children with NE and compared with those in non-enuretic children to investigate whether there was any relationship between 25(OH)D and NE as the first time in the literature. Design Two hundred forty-seven five- to seven-year-old children were recruited from Taizhou, Zhejiang Province, China. Serum 25(OH)D concentrations were measured, and the structured questionnaire was administered to the parents of all children. Low 25(OH)D was defined as serum 25(OH)D concentrations below 20 ng/ml. Results The prevalence of NE was 7.3% in the group of children with 25(OH)D concentrations that exceeded 20 ng/ml; this prevalence was much lower than the 17.5% observed in the group of children with 25(OH)D concentrations below 20 ng/ml (p<0.05). After adjusting for potential confounders, serum 25(OH)D (≥20 ng/ml) was significantly associated with NE and represented a protective factor against NE (OR = 0.31, 95%CI = 0.092, 1.0, P<0.05). A nonlinear relationship between 25(OH)D and NE was observed. The prevalence of NE decreased with increasing 25(OH)D concentrations above 19 ng/ml. Additionally, children exhibiting higher frequencies of bedwetting had lower 25(OH)D concentrations [5–7 times/week: 18.3±4.8; 2–4 times/week: 20.9±4.1; 0–1 times/week: 23.6±6.4 (ng/ml), P<0.05)]. Conclusions Low 25(OH)D was associated with an increased risk of NE in children aged five to seven years. PMID:24911026

  5. 25-Hydroxyvitamin D and Parathyroid Hormone Levels Are Independently Associated with the Hemoglobin A1c Level of Korean Type 2 Diabetic Patients: The Dong-Gu Study

    PubMed Central

    Choi, Jin-Su; Rhee, Jung-Ae; Nam, Hae-Sung; Jeong, Seul-Ki; Park, Kyeong-Soo; Kim, Hee Nam; Shin, Min-Ho

    2016-01-01

    In type 2 diabetic patients, the relationships between 25-hydroxyvitamin D and parathyroid hormone levels, and glycemic control, remain unclear. We evaluated associations between 25-hydroxyvitamin D, parathyroid hormone, and hemoglobin A1c levels after adjusting for other covariates, including log transformed 25-hydroxyvitamin D levels and log transformed parathyroid hormone levels, in Korean patients with type 2 diabetes. In total, 1,175 patients with type 2 diabetes were selected from 8,857 individuals who completed the baseline survey of the Dong-gu study, conducted in Korea from 2007 to 2010. After adjusting for other covariates, we found that the mean hemoglobin A1c level was inversely associated with the 25-hydroxyvitamin D level (Q1: 7.47% [7.30–7.63], Q2: 7.25% [7.09–7.40], Q3: 7.17% [7.02–7.32], Q4: 7.19% [7.02–7.35]; p for trend = 0.021, p for between groups = 0.050) and the parathyroid hormone level (Q1: 7.35% [7.19–7.51], Q2: 7.34% [7.19–7.50], Q3: 7.28% [7.13–7.43], Q4: 7.09% [6.94–7.24]; p for trend = 0.022, p for between groups = 0.048). However, the mean fasting glucose level was not associated with either the 25-hydroxyvitamin D or parathyroid hormone level. In conclusion, inverse associations were evident between hemoglobin A1c, 25-hydroxyvitamin D and parathyroid hormone levels in Korean patients with type 2 diabetes. The associations remained significant after adjusting for other covariates, including the log transformed 25-hydroxyvitamin D levels and log transformed parathyroid hormone levels. PMID:27362844

  6. Fate of tritium-labeled vitamin D/sub 3/ and 25-hydroxyvitamin D/sub 3/ in rabbit does and thier pups

    SciTech Connect

    Hidiroglou, H.

    1984-01-01

    Mammary transfer of label from intraperitoneally injected 50 ..mu..Ci (1..cap alpha.., 2..cap alpha..(n)-hydrogen-3) cholecalciferol, and 50 ..mu..Ci (26,27-methyl-hydrogen-3)cholecalciferol was studied in nursing rabbits. Does were injected at 3 days postpartum with one of the two labeled compounds. Pups were killed at either 1, 2, 3, 4, or 5 days after dosing of the does, and does were killed after 5 days. Concentrations of radioactivity were greater in tissues of does dosed with tritiated vitamin D/sub 3/ than in tissues of those dosed with tritiated 25-hydroxyvitamin D/sub 3/. Concentrations of radioactivity were greater in maternal tissues than in tissues of pups. On the 5th day following administration of tritiated vitamin D/sub 3/ or 25-hydroxyvitamin D/sub 3/, the major portion of the radioactivity in does' plasma and liver was associated with tritiated 25-hydroxyvitamin D/sub 3/. In pups from the tritiated vitamin D/sub 3/ group, the concentration of plasma radioactivity associated with 25-hydroxyvitamin D/sub 3/ (isolated by high pressure liquid chromatography) increased significantly with time, reaching 85% of the total vitamin D and metabolite radioactivity in the pups at the 5th day. Over 90% of the total recovered plasma radioactivity of pups of the tritiated 25-hydroxyvitamin D/sub 3/ group was associated with the 25-hydroxyvitamin D/sub 3/. Much more radioactivity was secreted in the milk of tritiated 25-hydroxyvitamin D/sub 3/ dosed does than in milk of does dosed with tritiated vitamin D/sub 3/. 16 references, 3 tables.

  7. 25-Hydroxyvitamin D and Parathyroid Hormone Levels Are Independently Associated with the Hemoglobin A1c Level of Korean Type 2 Diabetic Patients: The Dong-Gu Study.

    PubMed

    Choi, Seong-Woo; Kweon, Sun-Seog; Lee, Young-Hoon; Ryu, So-Yeon; Choi, Jin-Su; Rhee, Jung-Ae; Nam, Hae-Sung; Jeong, Seul-Ki; Park, Kyeong-Soo; Kim, Hee Nam; Shin, Min-Ho

    2016-01-01

    In type 2 diabetic patients, the relationships between 25-hydroxyvitamin D and parathyroid hormone levels, and glycemic control, remain unclear. We evaluated associations between 25-hydroxyvitamin D, parathyroid hormone, and hemoglobin A1c levels after adjusting for other covariates, including log transformed 25-hydroxyvitamin D levels and log transformed parathyroid hormone levels, in Korean patients with type 2 diabetes. In total, 1,175 patients with type 2 diabetes were selected from 8,857 individuals who completed the baseline survey of the Dong-gu study, conducted in Korea from 2007 to 2010. After adjusting for other covariates, we found that the mean hemoglobin A1c level was inversely associated with the 25-hydroxyvitamin D level (Q1: 7.47% [7.30-7.63], Q2: 7.25% [7.09-7.40], Q3: 7.17% [7.02-7.32], Q4: 7.19% [7.02-7.35]; p for trend = 0.021, p for between groups = 0.050) and the parathyroid hormone level (Q1: 7.35% [7.19-7.51], Q2: 7.34% [7.19-7.50], Q3: 7.28% [7.13-7.43], Q4: 7.09% [6.94-7.24]; p for trend = 0.022, p for between groups = 0.048). However, the mean fasting glucose level was not associated with either the 25-hydroxyvitamin D or parathyroid hormone level. In conclusion, inverse associations were evident between hemoglobin A1c, 25-hydroxyvitamin D and parathyroid hormone levels in Korean patients with type 2 diabetes. The associations remained significant after adjusting for other covariates, including the log transformed 25-hydroxyvitamin D levels and log transformed parathyroid hormone levels. PMID:27362844

  8. Association between circulating 25-hydroxyvitamin D and incident type 2 diabetes: a mendelian randomisation study

    PubMed Central

    Ye, Zheng; Sharp, Stephen J; Burgess, Stephen; Scott, Robert A; Imamura, Fumiaki; Langenberg, Claudia; Wareham, Nicholas J; Forouhi, Nita G

    2015-01-01

    Summary Background Low circulating concentrations of 25-hydroxyvitamin D (25[OH]D), a marker of vitamin D status, are associated with an increased risk of type 2 diabetes, but whether this association is causal remains unclear. We aimed to estimate the unconfounded, causal association between 25(OH)D concentration and risk of type 2 diabetes using a mendelian randomisation approach. Methods Using several data sources from populations of European descent, including type 2 diabetes cases and non-cases, we did a mendelian randomisation analysis using single nucleotide polymorphisms (SNPs) within or near four genes related to 25(OH)D synthesis and metabolism: DHCR7 (related to vitamin D synthesis), CYP2R1 (hepatic 25-hydroxylation), DBP (also known as GC; transport), and CYP24A1 (catabolism). We assessed each SNP for an association with circulating 25(OH)D concentration (5449 non-cases; two studies), risk of type 2 diabetes (28 144 cases, 76 344 non-cases; five studies), and glycaemic traits (concentrations of fasting glucose, 2-h glucose, fasting insulin, and HbA1c; 46 368 non-cases; study consortium). We combined these associations in a likelihood-based mendelian randomisation analysis to estimate the causal association of 25(OH)D concentration with type 2 diabetes and the glycaemic traits, and compared them with that from a meta-analysis of data from observational studies (8492 cases, 89 698 non-cases; 22 studies) that assessed the association between 25(OH)D concentration and type 2 diabetes. Findings All four SNPs were associated with 25(OH)D concentrations (p<10−6). The mendelian randomisation-derived unconfounded odds ratio for type 2 diabetes was 1·01 (95% CI 0·75–1·36; p=0·94) per 25·0 nmol/L (1 SD) lower 25(OH)D concentration. The corresponding (potentially confounded) relative risk from the meta-analysis of data from observational studies was 1·21 (1·16–1·27; p=7·3 × 10−19). The mendelian randomisation-derived estimates for

  9. Phosphorylation of ferredoxin and regulation of renal mitochondrial 25-hydroxyvitamin D-1 alpha-hydroxylase activity in vitro.

    PubMed

    Nemani, R; Ghazarian, J G; Moorthy, B; Wongsurawat, N; Strong, R; Armbrecht, H J

    1989-09-15

    The kidney is the principal physiologic site of production of biologically active 1,25-dihydroxyvitamin D. The 25-hydroxyvitamin D-1 alpha-hydroxylase (1-OHase) activity found in renal mitochondria is under tight hormonal control. Parathyroid hormone stimulates the renal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D in young animals, which is accompanied by dephosphorylation of ferredoxin (Fx), a component of the mitochondrial 1-OHase enzyme complex (Siegel, N., Wongsurawat, N., and Armbrecht, H. J. (1986) J. Biol. Chem. 261, 16998-17003). The present study investigates the capacity of Fx to be phosphorylated in vitro and to modulate the 1-OHase activity of a reconstituted system. Fx was phosphorylated by renal mitochondrial type II protein kinase. Phosphorylation did not alter Fx mobility on sodium dodecyl sulfate gels but did decrease the pI as measured by isoelectric focusing. Amino acid analysis demonstrated that 1 mol of serine and 1 mol of threonine were phosphorylated per mol of Fx. Peptide mapping of phosphorylated Fx was consistent with phosphorylation of serine 88 and threonine 85 or 97. Fx was selectively dephosphorylated by rabbit skeletal muscle protein phosphatase C2 but not C1. Phosphorylation of Fx significantly inhibited the 1-OHase activity of a reconstituted system consisting of Fx reductase, Fx, and renal mitochondrial cytochrome P-450. These findings suggest that phosphorylation/dephosphorylation of Fx may play a role in modulating renal 1,25-dihydroxyvitamin D production. PMID:2768268

  10. Modulation of the Bovine Innate Immune Response by Production of 1alpha,25-Dihydroxyvitamin D3 in Bovine Monocytes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In cattle, the kidney has been the only known site for production of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) from 25-hydroxyvitamin D3 25(OH)D3 by 1alpha-hydroxylase (1alpha-OHase). However, recent studies have shown that human monocytes express 1alpha-OHase and produce 1,25(OH)2D3 in response to to...

  11. Transformation of 25- and 1 alpha-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3 by using Streptomyces sp. strains.

    PubMed Central

    Sasaki, J; Mikami, A; Mizoue, K; Omura, S

    1991-01-01

    To enzymatically synthesize vitamin D derivatives, we screened about 300 Streptomyces sp. strains. Streptomyces sclerotialus FERM BP-1370 and Streptomyces roseoporus FERM BP-1574 were found to have the ability to convert 25-hydroxyvitamin D3 and 1 alpha-hydroxyvitamin D3, respectively, to 1 alpha, 25-dihydroxyvitamin D3. The average rates of 1 alpha hydroxylation of 25-hydroxyvitamin D3 were 6.9 micrograms liter-1 min-1 with FERM BP-1370 and 7.0 micrograms liter-1 min-1 with FERM BP-1574. The specific cytochrome P-450 inhibitors carbon monoxide, SKF-525-A, and metyrapone inhibited the hydroxylation of 1 alpha- and 25-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3 by FERM BP-1370 and FERM BP-1574. The cytochromes P-450 of these strains were detected by reduced CO difference spectra in the whole-cell suspensions. The appearance of cytochrome P-450 suggests that the cytochromes P-450 of FERM BP-1370 and FERM BP-1574 carry out the hydroxylation of 25- and 1 alpha-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3. PMID:1746944

  12. Abnormal parathyroid hormone stimulation of 25-hydroxyvitamin D-1 alpha-hydroxylase activity in the hypophosphatemic mouse. Evidence for a generalized defect of vitamin D metabolism.

    PubMed Central

    Nesbitt, T; Drezner, M K; Lobaugh, B

    1986-01-01

    Abnormal regulation of vitamin D metabolism is a feature of X-linked hypophosphatemic rickets in man and of the murine homologue of the disease in the hypophosphatemic (Hyp)-mouse. We previously reported that mutant mice have abnormally low renal 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-hydroxylase) activity for the prevailing degree of hypophosphatemia. To further characterize this defect, we examined whether Hyp-mouse renal 1 alpha-hydroxylase activity responds normally to other stimulatory and inhibitory controls of enzyme function. We studied stimulation by parathyroid hormone (PTH) using: (a) a calcium-deficient (0.02% Ca) diet to raise endogenous PTH; or (b) 24-h continuous infusion of 0.25 IU/h bovine PTH via osmotic minipump. In both cases enzyme activity of identically treated normal mice increased to greater levels than those attained by Hyp-mice. The relative inability of PTH to stimulate 1 alpha-hydroxylase activity is not a function of the hypophosphatemia in the Hyp-mouse since PTH-infused, phosphate-depleted normal mice sustained a level of enzyme activity greater than that of normal and Hyp-mice. In further studies we investigated inhibition of enzyme activity by using: (a) a calcium-loaded (1.2% Ca) diet to suppress endogenous PTH; or (b) 24-h continuous infusion of 0.2 ng/h 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). The 1 alpha-hydroxylase activity of normal and Hyp-mice was significantly reduced to similar absolute levels following maintenance on the calcium-loaded diet. Further, infusion of 1,25(OH)2D3 caused a comparable reduction of 1 alpha-hydroxylase activity in normal, Hyp-, and phosphate-depleted normal mice. These observations indicate that the inhibitory control of 1 alpha-hydroxylase by reduced levels of PTH or increased 1,25(OH)2D3 concentrations is intact in the mutants. However, the inability of PTH and hypophosphatemia to stimulate enzyme activity in a manner analogous to that in normal and phosphate-depleted mice indicates

  13. Influence of Vitamin D Binding Protein on Accuracy of 25-Hydroxyvitamin D Measurement Using the ADVIA Centaur Vitamin D Total Assay

    PubMed Central

    Freeman, James; Wilson, Kimberly; Spears, Ryan; Shalhoub, Victoria; Sibley, Paul

    2014-01-01

    Vitamin D status in different populations relies on accurate measurement of total serum 25-hydroxyvitamin D [25(OH)D] concentrations [i.e., 25(OH)D3 and 25(OH)D2]. This study evaluated agreement between the ADVIA Centaur Vitamin D Total assay for 25(OH)D testing (traceable to the NIST-Ghent reference method procedure) and a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for various populations with different levels of vitamin D binding protein (DBP). Total serum 25(OH)D concentrations were measured for 36 pregnant women, 40 hemodialysis patients, and 30 samples (DBP-spiked or not) from healthy subjects. ELISA measured DBP levels. The mean serum DBP concentrations were higher for pregnancy (415 μg/mL) and lower for hemodialysis subjects (198 μg/mL) than for healthy subjects and were highest for spiked serum (545 μg/mL). The average bias between the ADVIA Centaur assay and the LC-MS/MS method was −1.4% (healthy), −6.1% (pregnancy), and 4.4% (hemodialysis). The slightly greater bias for samples from some pregnancy and hemodialysis subjects with serum DBP levels outside of the normal healthy range fell within a clinically acceptable range—reflected by analysis of their low-range (≤136 μg/mL), medium-range (137–559 μg/mL), and high-range (≥560 μg/mL) DBP groups. Thus, the ADVIA Centaur Vitamin D Total assay demonstrates acceptable performance compared with an LC-MS/MS method for populations containing different amounts of DBP. PMID:25045351

  14. CYP2R1 Mutations Impair Generation of 25-hydroxyvitamin D and Cause an Atypical Form of Vitamin D Deficiency

    PubMed Central

    Fischer, Philip R.; Singh, Ravinder J.; Roizen, Jeffrey; Levine, Michael A.

    2015-01-01

    Context: Production of the active vitamin D hormone 1,25-dihydroxyvitamin D requires hepatic 25-hydroxylation of vitamin D. The CYP2R1 gene encodes the principal vitamin D 25-hydroxylase in humans. Objective: This study aimed to determine the prevalence of CYP2R1 mutations in Nigerian children with familial rickets and vitamin D deficiency and assess the functional effect on 25-hydroxylase activity. Design and Participants: We sequenced the CYP2R1 gene in subjects with sporadic rickets and affected subjects from families in which more than one member had rickets. Main Outcome Measures: Function of mutant CYP2R1 genes as assessed in vivo by serum 25-hydroxyvitamin D values after administration of vitamin D and in vitro by analysis of mutant forms of the CYP2R1. Results: CYP2R1 sequences were normal in 27 children with sporadic rickets, but missense mutations were identified in affected members of 2 of 12 families, a previously identified L99P, and a novel K242N. In silico analyses predicted that both substitutions would have deleterious effects on the variant proteins, and in vitro studies showed that K242N and L99P had markedly reduced or complete loss of 25-hydroxylase activity, respectively. Heterozygous subjects were less affected than homozygous subjects, and oral administration of vitamin D led to significantly lower increases in serum 25-hydroxyvitamin D in heterozygous than in control subjects, whereas homozygous subjects showed negligible increases. Conclusion: These studies confirm that CYP2R1 is the principal 25-hydroxylase in humans and demonstrate that CYP2R1 alleles have dosage-dependent effects on vitamin D homeostasis. CYP2R1 mutations cause a novel form of genetic vitamin D deficiency with semidominant inheritance. PMID:25942481

  15. Circulating 25-hydroxyvitamin D, IRS1 variant rs2943641 and insulin resistance: replication of a gene-nutrient interaction in four populations of different ancestries

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Associations of either insulin receptor substrate 1 (IRS1) variants or circulating 25-hydroxyvitamin D (25(OH)D) with type 2 diabetes and insulin resistance are inconsistent. This study sought to determine whether circulating 25(OH)D modulates the association of a potentially functional variant at I...

  16. The reverse J shaped association between serum total 25- hydroxyvitamin D and all-cause mortality: The impact of assay standardization

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The impact of standardizing the originally measured serum total 25-hydroxyvitamin D [25(OH)D] values from Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) on the association between 25(OH)D and rate of all-cause mortality was evaluated. Values were standardized to gold ...

  17. UV-dependent production of 25-hydroxyvitamin D{sub 2} in the recombinant yeast cells expressing human CYP2R1

    SciTech Connect

    Yasuda, Kaori; Endo, Mariko; Ikushiro, Shinichi; Kamakura, Masaki; Ohta, Miho; Sakaki, Toshiyuki

    2013-05-03

    Highlights: •We produce 25-hydroxyvitamin D in the recombinant yeast expressing human CYP2R1. •Vitamin D2 is produced in yeast from endogenous ergosterol with UV irradiation. •We produce 25-hydroxyvitamin D2 in the recombinant yeast without added substrate. -- Abstract: CYP2R1 is known to be a physiologically important vitamin D 25-hydroxylase. We have successfully expressed human CYP2R1 in Saccharomyces cerevisiae to reveal its enzymatic properties. In this study, we examined production of 25-hydroxylated vitamin D using whole recombinant yeast cells that expressed CYP2R1. When vitamin D{sub 3} or vitamin D{sub 2} was added to the cell suspension of CYP2R1-expressing yeast cells in a buffer containing glucose and β-cyclodextrin, the vitamins were converted into their 25-hydroxylated products. Next, we irradiated the cell suspension with UVB and incubated at 37 °C. Surprisingly, the 25-hydroxy vitamin D{sub 2} was produced without additional vitamin D{sub 2}. Endogenous ergosterol was likely converted into vitamin D{sub 2} by UV irradiation and thermal isomerization, and then the resulting vitamin D{sub 2} was converted to 25-hydroxyvitamin D{sub 2} by CYP2R1. This novel method for producing 25-hydroxyvitamin D{sub 2} without a substrate could be useful for practical purposes.

  18. Plasma 25-hydroxyvitamin D and progression to diabetes in patients at risk for diabetes: an ancillary analysis in the diabetes prevention program

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We investigated the association between vitamin D status, assessed by plasma 25-hydroxyvitamin D, and risk of incident diabetes. The research design and methods were a prospective observational study with a mean follow-up of 2.7 years in the Diabetes Prevention Program (DPP), a multi-center trial co...

  19. Is there a reverse J-shaped association between 25-Hydroxyvitamin D and all-cause mortality? Results from the US Nationally Representative NHANES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The concentration or threshold of 25-Hydroxyvitamin D [25(OH)D] needed to maximally suppress intact serum parathyroid hormone (iPTH) has been suggested as a measure of optimal vitamin D status. Depending upon the definition of maximal suppression of iPTH and the two-phase regression approach used, ...

  20. An inflection point of serum 25-hydroxyvitamin D for maximal suppression of parathyroid hormone is not evident from multi-site pooled data in children and adolescents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In adults, maximal suppression of serum parathyroid hormone (PTH) has commonly been used to determine the sufficiency of serum 25-hydroxyvitamin D [25(OH) D]. In children and adolescents, the relationship between serum 25(OH) D and PTH is less clear, and most studies reporting a relationship are der...

  1. Three-Phase Model Harmonizes Estimates of the Maximal Suppression of Parathyroid Hormone by 25-Hydroxyvitamin D in Persons 65 Years of Age and Older 1–3

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The concentration or threshold of 25-hydroxyvitamin D [25(OH)D] needed to maximally suppress intact serum parathyroid hormone (iPTH) has been suggested as a measure of optimal vitamin D status. Depending upon the definition of maximal suppression of iPTH and the 2-phase regression approach used, 2 d...

  2. Three-phase model harmonizes estimates of the maximal suppression of parathyroid hormone by 25-hydroxyvitamin D in persons 65 y of age and older

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The concentration or threshold of 25-Hydroxyvitamin D [25(OH)D] needed to maximally suppress intact serum parathyroid hormone (iPTH) has been suggested as a measure of optimal vitamin D status. Depending upon the definition of maximal suppression of iPTH and the two-phase regression approach used, ...

  3. Serum 25-hydroxyvitamin D, mortality, and incident cardiovascular disease, respiratory disease, cancers, and fractures: a 13-y prospective population study1234

    PubMed Central

    Khaw, Kay-Tee; Luben, Robert; Wareham, Nicholas

    2014-01-01

    Background: Vitamin D is associated with many health conditions, but optimal blood concentrations are still uncertain. Objectives: We examined the prospective relation between serum 25-hydroxyvitamin D [25(OH)D] concentrations [which comprised 25(OH)D3 and 25(OH)D2] and subsequent mortality by the cause and incident diseases in a prospective population study. Design: Serum vitamin D concentrations were measured in 14,641 men and women aged 42–82 y in 1997–2000 who were living in Norfolk, United Kingdom, and were followed up to 2012. Participants were categorized into 5 groups according to baseline serum concentrations of total 25(OH)D <30, 30 to <50, 50 to <70, 70 to <90, and ≥90 nmol/L. Results: The mean serum total 25(OH)D was 56.6 nmol/L, which consisted predominantly of 25(OH)D3 (mean: 56.2 nmol/L; 99% of total). The age-, sex-, and month-adjusted HRs (95% CIs) for all-cause mortality (2776 deaths) for men and women by increasing vitamin D category were 1, 0.84 (0.74, 0.94), 0.72 (0.63, 0.81), 0.71 (0.62, 0.82), and 0.66 (0.55, 0.79) (P-trend < 0.0001). When analyzed as a continuous variable and with additional adjustment for body mass index, smoking, social class, education, physical activity, alcohol intake, plasma vitamin C, history of cardiovascular disease, diabetes, or cancer, HRs for a 20-nmol/L increase in 25(OH)D were 0.92 (0.88, 0.96) (P < 0.001) for total mortality, 0.96 (0.93, 0.99) (P = 0.014) (4469 events) for cardiovascular disease, 0.89 (0.85, 0.93) (P < 0.0001) (2132 events) for respiratory disease, 0.89 (0.81, 0.98) (P = 0.012) (563 events) for fractures, and 1.02 (0.99, 1.06) (P = 0.21) (3121 events) for incident total cancers. Conclusions: Plasma 25(OH)D concentrations predict subsequent lower 13-y total mortality and incident cardiovascular disease, respiratory disease, and fractures but not total incident cancers. For mortality, lowest risks were in subjects with concentrations >90 nmol/L, and there was no evidence of increased

  4. Pharmacokinetics of a single oral dose of vitamin D3 (70,000 IU) in pregnant and non-pregnant women

    PubMed Central

    2012-01-01

    Background Improvements in antenatal vitamin D status may have maternal-infant health benefits. To inform the design of prenatal vitamin D3 trials, we conducted a pharmacokinetic study of single-dose vitamin D3 supplementation in women of reproductive age. Methods A single oral vitamin D3 dose (70,000 IU) was administered to 34 non-pregnant and 27 pregnant women (27 to 30 weeks gestation) enrolled in Dhaka, Bangladesh (23°N). The primary pharmacokinetic outcome measure was the change in serum 25-hydroxyvitamin D concentration over time, estimated using model-independent pharmacokinetic parameters. Results Baseline mean serum 25-hydroxyvitamin D concentration was 54 nmol/L (95% CI 47, 62) in non-pregnant participants and 39 nmol/L (95% CI 34, 45) in pregnant women. Mean peak rise in serum 25-hydroxyvitamin D concentration above baseline was similar in non-pregnant and pregnant women (28 nmol/L and 32 nmol/L, respectively). However, the rate of rise was slightly slower in pregnant women (i.e., lower 25-hydroxyvitamin D on day 2 and higher 25-hydroxyvitamin D on day 21 versus non-pregnant participants). Overall, average 25-hydroxyvitamin D concentration was 19 nmol/L above baseline during the first month. Supplementation did not induce hypercalcemia, and there were no supplement-related adverse events. Conclusions The response to a single 70,000 IU dose of vitamin D3 was similar in pregnant and non-pregnant women in Dhaka and consistent with previous studies in non-pregnant adults. These preliminary data support the further investigation of antenatal vitamin D3 regimens involving doses of ≤70,000 IU in regions where maternal-infant vitamin D deficiency is common. Trial registration ClinicalTrials.gov (NCT00938600) PMID:23268736

  5. Combined Effects of Circulating Levels of 25-Hydroxyvitamin D and Th1 and Th2 Cytokines on Breast Cancer Estrogen Receptor Status

    PubMed Central

    Yao, Song; Hong, Chi-Chen; McCann, Susan E.; Zirpoli, Gary; Quan, Lei; Gong, Zhihong; Johnson, Candace S.; Trump, Donald L.; Ambrosone, Christine B.

    2014-01-01

    Vitamin D has been recognized for its immune-modulating properties. We have previously found that levels of 25OHD, and cytokines including IL5, IFNα2, and TNFα, are also associated with estrogen receptor (ER) negative breast cancer in younger women. Thus, we hypothesized that there may be interactions between vitamin D and the immune system in influencing breast cancer ER status, which was tested in 490 women with incident breast cancer. There was no correlation of the levels of 25OHD with any cytokine, and their associations with tumor ER negative status were independent of each other. However, premenopausal women with low 25OHD and high TNFα levels had the highest likelihood of having ER negative cancer (odds ratio [OR] = 7.32, 95% confidence interval [CI] = 2.44−21.98), with evidence of synergy between the two (relative excess risk due to interaction [RERI] = 5.46, p for additive interaction = 0.14, and p for multiplicative interaction = 0.09). There were similar synergistic associations between 25OHD and IL5, and several IFNα2 to Th2 cytokine ratios. This is the first study to provide evidence of interactions between vitamin D and the immune system in relation to breast cancer ER status, which may inform combinational use of vitamin D and anti-inflammatory drugs for cancer prevention and therapy. PMID:24473087

  6. Combined effects of circulating levels of 25-hydroxyvitamin d and Th1 and th2 cytokines on breast cancer estrogen receptor status.

    PubMed

    Yao, Song; Hong, Chi-Chen; McCann, Susan E; Zirpoli, Gary; Quan, Lei; Gong, Zhihong; Johnson, Candace S; Trump, Donald L; Ambrosone, Christine B

    2014-01-01

    Vitamin D has been recognized for its immune-modulating properties. We have previously found that levels of 25OHD, and cytokines including IL5, IFNα2, and TNFα, are also associated with estrogen receptor (ER) negative breast cancer in younger women. Thus, we hypothesized that there may be interactions between vitamin D and the immune system in influencing breast cancer ER status, which was tested in 490 women with incident breast cancer. There was no correlation of the levels of 25OHD with any cytokine, and their associations with tumor ER negative status were independent of each other. However, premenopausal women with low 25OHD and high TNFα levels had the highest likelihood of having ER negative cancer (odds ratio [OR] = 7.32, 95% confidence interval [CI] = 2.44-21.98), with evidence of synergy between the two (relative excess risk due to interaction [RERI] = 5.46, p for additive interaction = 0.14, and p for multiplicative interaction = 0.09). There were similar synergistic associations between 25OHD and IL5, and several IFNα2 to Th2 cytokine ratios. This is the first study to provide evidence of interactions between vitamin D and the immune system in relation to breast cancer ER status, which may inform combinational use of vitamin D and anti-inflammatory drugs for cancer prevention and therapy. PMID:24473087

  7. Photoaffinity labeling of serum vitamin D binding protein by 3-deoxy-3-azido-25-hydroxyvitamin D/sub 3/

    SciTech Connect

    Link, R.P.; Kutner, A.; Schnoes, H.K.; DeLuca, H.F.

    1986-05-01

    3-Deoxy-3-azido-25-hydroxyvitamin D/sub 3/ (3-Az-25-OH-D/sub 3/) was covalently incorporated into the 25-hydroxyvitamin D/sub 3/ (25-OH-D/sub 3/) binding site of purified human serum vitamin D binding protein (hDBP). Competition experiments showed that 3-Az-25-OH-D/sub 3/ and 25-OH-D/sub 3/ bound at the same site. A K/sub I/ of 80 nM was determined from 3-Az-25-OH-D/sub 33/ inhibition of 25-OH-D/sub 3/ binding to hDBP. 3-Az-25-OH-(26,27-/sup 3/H)D/sub 3/, prepared from 25-OH-(26,27-/sup 3/H)D/sub 3/, bound reversibly to hDBP in the dark. Scatchard analysis of the data indicated a single class of sites with a K/sub D. app/ of 0.71 nM and a B/sub max/ of 0.11 nM for 3-Az-25-OH-(26,27-/sup 3/H)D/sub 3/ as compared to a K/sub D. app/ of 0.37 nM and a B/sub max/ of 0.43 nM for 25-OH-(26,27-/sup 3/H)D/sub 3/. The stability of 25-OH-D/sub 3/ binding to hDBP was tested under the UV irradiation conditions required for photoactivation of 3-Az-25-OH-D/sub 3/. After 3 minutes of medium intensity, short wavelength (254 nm) UV irradiation, 40-50% of the previously bound 25-OH-(26,27-/sup 3/H)D/sub 3/ was retained by hDBP and 60% of the unliganded protein was capable of subsequently binding 25-OH-(26,27-/sup 3/H)D/sub 3/. Maximum specific covalent incorporation of 3-Az-25-OH-(26,27-/sup 3/H)D/sub 3/ by hDBP was after 3 to 5 minutes of irradiation. As much as 7.5% of the initially reversibly bound 3-Az-25-OH-(26,27-/sup 3/H)D/sub 3/ could be covalently bound to the 25-OH-D/sub 3/ binding site of hDBP.

  8. Identification and immune regulation of 25-hydroxyvitamin D-1-α-hydroxylase in murine macrophages

    PubMed Central

    Overbergh, L; Decallonne, B; Valckx, D; Verstuyf, A; Depovere, J; Laureys, J; Rutgeerts, O; Saint-Arnaud, R; Bouillon, R; Mathieu, C

    2000-01-01

    Receptors for 1,25(OH)2vitaminD3 are found in most immune cells and important immunological effects have been described in vitro, reflected by its capacity to prevent autoimmunity and to prolong graft survival. The aim of this study was to examine the presence and nature of the enzyme responsible for final activation of the molecule, 1-α-hydroxylase, in murine macrophages and to analyse its regulation and possible role in the immune system. Peritoneal macrophages from C57Bl/6 mice were incubated with lipopolysaccharide (LPS; 100 μg/ml), interferon-gamma (IFN-γ; 500 U/ml) or a combination of both. By quantitative reverse transcriptase-polymerase chain reaction, using primers based on the murine renal cDNA sequence, low levels of 1-α-hydroxylase mRNA were detected in freshly isolated cells (18 ± 7 × 10−6 copies/β-actin copies). Analysis of the cDNA sequence of the gene revealed identical coding sequences for the macrophage and renal enzymes. mRNA levels rose three-fold with LPS (NS), but a six-fold increase was seen after IFN-γ stimulation (P < 0·05). Combining LPS and IFN-γ did not result in a major additional increase, but addition of cyclosporin A further increased levels 2·5-fold both in IFN-γ- and combination-stimulated cells (P < 0·05). Time course analysis revealed that up-regulation of 1-α-hydroxylase was a late phenomenon, preceded by the up-regulation of activating macrophage products such as IL-1 and tumour necrosis factor-alpha. Finally, a defect in 1-α-hydroxylase up-regulation by immune stimuli was found in autoimmune non-obese diabetic mice. In conclusion, we propose that the up-regulation of 1-α-hydroxylase in activated macrophages, resulting in the synthesis of 1,25(OH)2D3, might be a negative feedback loop in inflammation. A defect in this system might be an additional element in tipping the balance towards autoimmunity. PMID:10759775

  9. Circulating 25-hydroxyvitamin D and risk of pancreatic cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

    PubMed

    Stolzenberg-Solomon, Rachael Z; Jacobs, Eric J; Arslan, Alan A; Qi, Dai; Patel, Alpa V; Helzlsouer, Kathy J; Weinstein, Stephanie J; McCullough, Marjorie L; Purdue, Mark P; Shu, Xiao-Ou; Snyder, Kirk; Virtamo, Jarmo; Wilkins, Lynn R; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Albanes, Demetrius; Cai, Qiuyin; Harvey, Chinonye; Hayes, Richard; Clipp, Sandra; Horst, Ronald L; Irish, Lonn; Koenig, Karen; Le Marchand, Loic; Kolonel, Laurence N

    2010-07-01

    Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D (25(OH)D) concentrations (the best indicator of vitamin D derived from diet and sun) have been inconsistent. Therefore, the authors conducted a pooled nested case-control study of participants from 8 cohorts within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) (1974-2006) to evaluate whether prediagnostic circulating 25(OH)D concentrations were associated with the development of pancreatic cancer. In total, 952 incident pancreatic adenocarcinoma cases occurred among participants (median follow-up, 6.5 years). Controls (n = 1,333) were matched to each case by cohort, age, sex, race/ethnicity, date of blood draw, and follow-up time. Conditional logistic regression analysis was used to calculate smoking-, body mass index-, and diabetes-adjusted odds ratios and 95% confidence intervals for pancreatic cancer. Clinically relevant 25(OH)D cutpoints were compared with a referent category of 50-<75 nmol/L. No significant associations were observed for participants with lower 25(OH)D status. However, a high 25(OH)D concentration (> or =100 nmol/L) was associated with a statistically significant 2-fold increase in pancreatic cancer risk overall (odds ratio = 2.12, 95% confidence interval: 1.23, 3.64). Given this result, recommendations to increase vitamin D concentrations in healthy persons for the prevention of cancer should be carefully considered. PMID:20562185

  10. Circulating vitamin D binding protein, total, free and bioavailable 25-hydroxyvitamin D and risk of colorectal cancer

    PubMed Central

    Ying, Hou-Qun; Sun, Hui-Ling; He, Bang-Shun; Pan, Yu-Qin; Wang, Feng; Deng, Qi-Wen; Chen, Jie; Liu, Xian; Wang, Shu-Kui

    2015-01-01

    Epidemiological investigation have suggested that there is a significantly inverse association between circulating 25-hydroxyvitamin D (25(OH)D) and the risk for developing colorectal cancer (CRC) in humans. However, little is known about the role of vitamin D binding protein (VDBP) in colorectal carcinogenesis. Blood samples were collected from 212 CRC patients and 212 controls matched with age, gender and blood collection time. We used logistic regression to calculate the odds ratios and 95% confidence intervals for further estimation of the association of the quartiles of VDBP, total, free and bioavailable 25(OH)D with CRC risk. The results revealed that there was no significant association between circulating VDBP concentrations and CRC in the present study, and that a negative association existed between total 25(OH)D and the risk of CRC, which was unchanged after adjustment for VDBP. Higher levels of free and bioavailable 25(OH)D were significantly associated with decreased risk of CRC. After stratifying by VDBP, high levels of total, free and bioavailable 25(OH)D were associated significantly with decreased CRC risk among participants with circulating VDBP below the median. These findings indicate that VDBP is not directly associated with the risk of CRC, but it modulates circulating free and bioavailable 25(OH)D concentration. PMID:25609140

  11. 25-Hydroxyvitamin D Concentration and Leukocyte Telomere Length in Young Adults: Findings From the Northern Finland Birth Cohort 1966.

    PubMed

    Williams, Dylan M; Palaniswamy, Saranya; Sebert, Sylvain; Buxton, Jessica L; Blakemore, Alexandra I F; Hyppönen, Elina; Jarvelin, Marjo-Riitta

    2016-02-01

    Higher vitamin D status, lower adiposity, and longer telomere length are each reportedly associated with lower risk of several chronic diseases and all-cause mortality. However, direct relationships between vitamin D status (measured by circulating 25-hydroxyvitamin D (25(OH)D) concentration), adiposity, and telomere length are not well established. We conducted a cross-sectional analysis of associations of 25(OH)D and body mass index (BMI; weight (kg)/height (m)(2)) with mean relative leukocyte telomere length (LTL) using data gathered on 5,096 participants from Northern Finland Birth Cohort 1966 at age 31 years (1997). 25(OH)D was not associated with LTL in either basic or confounder/mediator-adjusted models. BMI was inversely associated with LTL after adjustment for potential confounding by age, sex, socioeconomic position, physical activity, diet, smoking, alcohol intake, and use of oral contraceptives (per 1-unit increase in BMI, mean difference in LTL = -0.4%, 95% confidence interval: -0.6, -0.2). The BMI-LTL association was also independent of 25(OH)D and was attenuated slightly, but remained, after adjustment for C-reactive protein, a marker of low-grade inflammation (mean difference in LTL = -0.3%, 95% confidence interval -0.6, -0.1). These findings suggest that vitamin D status is unlikely to be an important determinant of LTL, at least by young adulthood. Inflammation may partly mediate associations of adiposity with LTL. PMID:26797572

  12. Do studies reporting 'U'-shaped serum 25-hydroxyvitamin D-health outcome relationships reflect adverse effects?

    PubMed

    Grant, William B; Karras, Spyridon N; Bischoff-Ferrari, Heike A; Annweiler, Cedric; Boucher, Barbara J; Juzeniene, Asta; Garland, Cedric F; Holick, Michael F

    2016-01-01

    Several reports describe U-shaped 25-hydroxyvitamin D [25(OH)D] concentration-health outcomes, including musculo-skeletal disorders such as falls and fractures, several cancers, cardiovascular disease (CVD), cognitive function, all-cause mortality rates, birth outcomes, allergic reactions, frailty, and some other disorders. This paper reviews reports of U-shaped outcome associations with vitamin D status for evidence of underlying pathophysiological processes, or of confounding, finding that some U-shaped associations appear to be biologically meaningful, but that many could well reflect confounding by factors such as lifestyle, or hypovitaminosis D-related disease onset being masked by self-supplementation that was begun too late to correct developing health problems but before baseline vitamin D status assessment. However, the various U-shaped associations for allergic reactions may be due to vitamin D modulation of the phenotype of the immune response, shifting the Th1-Th2 balance toward Th2 formation. For prostate cancer, there seems to be little effect of 25(OH)D concentration on incidence; however, there is an inverse correlation between 25(OH)D concentration and mortality rates. Future observational studies, and randomized controlled trial data analyses, should include adjustment for data collected on prior long-term vitamin D supplementation and solar UVB exposure, as well as other potential confounders. PMID:27489574

  13. Sunlight and Other Determinants of Circulating 25-Hydroxyvitamin D Levels in Black and White Participants in a Nationwide US Study

    PubMed Central

    Freedman, D. Michal; Cahoon, Elizabeth K.; Rajaraman, Preetha; Major, Jacqueline M.; Doody, Michele M.; Alexander, Bruce H.; Hoffbeck, Richard W.; Kimlin, Michael G.; Graubard, Barry I.; Linet, Martha S.

    2013-01-01

    Circulating 25-hydroxyvitamin D (25(OH)D), a marker for vitamin D status, is associated with bone health and possibly cancers and other diseases; yet, the determinants of 25(OH)D status, particularly ultraviolet radiation (UVR) exposure, are poorly understood. Determinants of 25(OH)D were analyzed in a subcohort of 1,500 participants of the US Radiologic Technologists (USRT) Study that included whites (n = 842), blacks (n = 646), and people of other races/ethnicities (n = 12). Participants were recruited monthly (2008–2009) across age, sex, race, and ambient UVR level groups. Questionnaires addressing UVR and other exposures were generally completed within 9 days of blood collection. The relation between potential determinants and 25(OH)D levels was examined through regression analysis in a random two-thirds sample and validated in the remaining one third. In the regression model for the full study population, age, race, body mass index, some seasons, hours outdoors being physically active, and vitamin D supplement use were associated with 25(OH)D levels. In whites, generally, the same factors were explanatory. In blacks, only age and vitamin D supplement use predicted 25(OH)D concentrations. In the full population, determinants accounted for 25% of circulating 25(OH)D variability, with similar correlations for subgroups. Despite detailed data on UVR and other factors near the time of blood collection, the ability to explain 25(OH)D was modest. PMID:23292956

  14. Altitude, pasture type, and sheep breed affect bone metabolism and serum 25-hydroxyvitamin D in grazing lambs.

    PubMed

    Willems, Helen; Leiber, Florian; Kohler, Martina; Kreuzer, Michael; Liesegang, Annette

    2013-05-15

    This study aimed to investigate the bone development of two mountain sheep breeds during natural summer grazing either in the lowlands or on different characteristic alpine pastures. Pasture types differed in topographic slope, plant species composition, general nutritional feeding value, Ca and P content, and Ca:P ratio of herbage. Twenty-seven Engadine sheep (ES) lambs and 27 Valaisian Black Nose sheep (VS) lambs were divided into four groups of 6 to 7 animals per breed and allocated to three contrasting alpine pasture types and one lowland pasture type. The lambs were slaughtered after 9 wk of experimental grazing. The steep alpine pastures in combination with a high (4.8) to very high (13.6) Ca:P ratio in the forage decreased total bone mineral content as measured in the middle of the left metatarsus of the lambs from both breeds, and cortical bone mineral content and cortical bone mineral density of ES lambs. Breed × pasture type interactions occurred in the development of total and cortical bone mineral content, and in cortical thickness, indicating that bone metabolism of different genotypes obviously profited differently from the varying conditions. An altitude effect occurred for 25-hydroxyvitamin D with notably higher serum concentrations on the three alpine sites, and a breed effect led to higher concentrations for ES than VS. Despite a high variance, there were pasture-type effects on serum markers of bone formation and resorption. PMID:23471950

  15. The Association Between Serum 25-Hydroxyvitamin D Concentration and Consumption Frequencies of Vitamin D Food Sources in Korean Adolescents

    PubMed Central

    Yu, Areum; Kim, Jihye; Kwon, Oran; Oh, Se-Young; Kim, Junghyun

    2013-01-01

    The objectives of this study were to investigate the status of vitamin D in Korean adolescents and to determine the association between serum 25-hydroxyvitamin D (25(OH)D) concentration and consumption frequencies of vitamin D food sources by season (June to November and December to May). The subjects were 1,579 adolescents aged 12-18 years participating in the 2008-2009 Korean National Health and Nutrition Examination Survey (KNHANES). Consumption frequencies of vitamin D food sources were estimated by using a qualitative food frequency questionnaire (FFQ). Thirteen food items were selected as vitamin D food sources including beef, egg, mackerel, tuna, yellow corvine, pollack, anchovy, mushroom, milk, yoghurt, ice cream, all fish and dairy products from the FFQ based on previous research. The data was analyzed using proc survey procedures. The deficiency (5.25-12 ng/mL), inadequacy (12-20 ng/mL) and sufficiency (> 20 ng/mL) proportions of serum 25(OH)D from June to November and December to May were 9.9%, 51.4%, 38.7%, and 39.4%, 51.4%, 9.2%, respectively. Mean serum 25(OH)D concentration was positively related to the consumption frequencies of mackerel, anchovy, all fish and milk. These results suggest high proportion (> 61%) of Korean adolescents were vitamin D deficiency or inadequacy, and serum 25(OH)D was associated with the consumption of vitamin D food sources including fish and milk. PMID:23908977

  16. Janus kinase 3 regulates renal 25-hydroxyvitamin D 1α-hydroxylase expression, calcitriol formation, and phosphate metabolism.

    PubMed

    Umbach, Anja T; Zhang, Bingbing; Daniel, Christoph; Fajol, Abul; Velic, Ana; Hosseinzadeh, Zohreh; Bhavsar, Shefalee K; Bock, C-Thomas; Kandolf, Reinhard; Pichler, Bernd J; Amann, Kerstin U; Föller, Michael; Lang, Florian

    2015-04-01

    Calcitriol, a powerful regulator of phosphate metabolism and immune response, is generated by 25-hydroxyvitamin D 1α-hydroxylase in the kidney and macrophages. Renal 1α-hydroxylase expression is suppressed by Klotho and FGF23, the expression of which is stimulated by calcitriol. Interferon γ (INFγ) regulates 1α-hydroxylase expression in macrophages through transcription factor interferon regulatory factor-1. INFγ-signaling includes Janus kinase 3 (JAK3) but a role of JAK3 in the regulation of 1α-hydroxylase expression and mineral metabolism has not been shown. Thus, the impact of JAK3 deficiency on calcitriol formation and phosphate metabolism was measured. Renal interferon regulatory factor-1 and 1α-hydroxylase transcript levels, serum calcitriol and FGF23 levels, intestinal phosphate absorption as well as absolute and fractional renal phosphate excretion were significantly higher in jak3 knockout than in wild-type mice. Coexpression of JAK3 increased the phosphate-induced current in renal sodium-phosphate cotransporter-expressing Xenopus oocytes. Thus, JAK3 is a powerful regulator of 1α-hydroxylase expression and phosphate transport. Its deficiency leads to marked derangement of phosphate metabolism. PMID:25493954

  17. The existence of 25-hydroxyvitamin D sub 3 -1. alpha. -hydroxylase in the liver of carp and bastard halibut

    SciTech Connect

    Takeuchi, Atsuko; Okano, Toshio; Kobayashi, Tadashi )

    1991-01-01

    We have found that carp and bastard halibut contain 25-hydroxyvitamin D{sub 3}(25-D{sub 3})-1{alpha}-hydroxylase in the liver besides in the kidney by the following in vivo and in vitro experiments. When ({sup 3}H)-25-D{sub 3} was intraperitoneally injected to vitamin D(D)-deficient carp and normal bastard halibut, the profiles of high-performance liquid chromatography (HPLC) of the plasma lipid extract showed the formation of a peak corresponding to ({sup 3}H)-1{alpha},25-dihydroxyvitamin D{sub 3}(1,25-D{sub 3}). When ({sup 3}H)25-D{sub 3} was incubated with liver homogenates of the fish, a peak corresponding to ({sup 3}H)-1,25-D{sub 3} was also observed in the profile of HPLC. The formation of the metabolite was confirmed by the thermal isomerization into the pre-isomer and mass fragmentography. Although the 1{alpha}-hydroxylase was also observed in the kidney, the activity of the enzyme was lower than that in the liver. The results suggest that 25-D{sub 3}-1{alpha}-hydroxylase exists in the liver of carp and bastard halibut and the 25-D{sub 3} formed from D{sub 3} in the liver is immediately metabolized into 1,25-D{sub 3} in the same tissue.

  18. Assay and properties of rat yolk sac 25-hydroxyvitamin D/sub 3/ 1. cap alpha. -hydroxylase

    SciTech Connect

    Paulson, S.K.; Phelps, M.; DeLuca, H.F.

    1986-11-04

    An in vitro assay has been developed for the rat yolk sac 25-hydroxyvitamin D/sub 3/ 1..cap alpha..-hydroxylase (1..cap alpha..-hydroxylase). The subcellular location and some properties of the enzyme are described. 1,25-Dihydroxyvitamin D/sub 3/ produced from incubations of yolk sac homogenates was extracted, purified by Sephadex LH-20 chromatography and straight- and reverse-phase high-performance liquid chromatography (HPLC), and measured by a competitive binding assay using chick intestinal receptor. The reaction is linear with time for up to 45 min at a substrate concentration of 80 ..mu..M and 4-6 mg/mL microsomal protein. The enzyme, located in the microsomes, requires molecular oxygen and NADPH. Metyrapone (1 x 10/sup -3/ M) was found to inhibit 1-hydroxylation, but a 90% carbon monoxide-10% oxygen atmosphere did not, leaving open the question of involvement of cytochrome P-450. Diphenyl-p-phenylenediamine, a lipid peroxidase inhibitor, inhibited 1..cap alpha..-hydroxylation.

  19. Relationship between 25-Hydroxyvitamin D Levels and Liver Fibrosis as Assessed by Transient Elastography in Patients with Chronic Liver Disease

    PubMed Central

    Ko, Bong Jin; Kim, Young Seok; Kim, Sang Gyune; Park, Jung Hwan; Lee, Sae Hwan; Jeong, Soung Won; Jang, Jae Young; Kim, Hong Soo; Kim, Boo Sung; Kim, Sun Mi; Kim, Young Don; Cheon, Gab Jin; Lee, Bo Ra

    2016-01-01

    Background/Aims Deficiencies of 25-hydroxyvitamin D (25(OH)D) are prevalent in patients with chronic liver disease (CLD). Liver fibrosis is the main determinant of CLD prognosis. The present study was performed to evaluate the correlation between 25(OH)D levels and liver fibrosis as assessed by transient elastography (TE) in patients with compensated CLD. Methods Serum 25(OH)D levels and liver stiffness were determined in a total of 207 patients who were subjected to the following exclusion criteria: patients with decompensated CLD; patients who had malignancies; patients who were taking medications; and patients who were pregnant. Results The most common etiology was chronic hepatitis B (53.1%). Advanced liver fibrosis (defined by TE [≥9.5 kPa]) was present in 75 patients (36.2%). There was a significant correlation between 25(OH)D deficiency and liver stiffness. Based on the multivariate analysis, the following factors were independently associated with advanced liver fibrosis: 25(OH)D deficiency (odds ratio [OR], 3.46; p=0.004), diabetes mellitus (OR, 3.04; p=0.041), and fibrosis-4 index (OR, 2.01; p<0.001). Conclusions Patients with compensated CLD exhibit a close correlation between vitamin D level and liver stiffness as assessed by TE. Vitamin D deficiency was independently associated with advanced liver fibrosis. PMID:27114415

  20. Do studies reporting ‘U’-shaped serum 25-hydroxyvitamin D–health outcome relationships reflect adverse effects?

    PubMed Central

    Grant, William B.; Karras, Spyridon N.; Bischoff-Ferrari, Heike A.; Annweiler, Cedric; Boucher, Barbara J.; Juzeniene, Asta; Garland, Cedric F.; Holick, Michael F.

    2016-01-01

    ABSTRACT Several reports describe U-shaped 25-hydroxyvitamin D [25(OH)D] concentration–health outcomes, including musculo-skeletal disorders such as falls and fractures, several cancers, cardiovascular disease (CVD), cognitive function, all-cause mortality rates, birth outcomes, allergic reactions, frailty, and some other disorders. This paper reviews reports of U-shaped outcome associations with vitamin D status for evidence of underlying pathophysiological processes, or of confounding, finding that some U-shaped associations appear to be biologically meaningful, but that many could well reflect confounding by factors such as lifestyle, or hypovitaminosis D-related disease onset being masked by self-supplementation that was begun too late to correct developing health problems but before baseline vitamin D status assessment. However, the various U-shaped associations for allergic reactions may be due to vitamin D modulation of the phenotype of the immune response, shifting the Th1-Th2 balance toward Th2 formation. For prostate cancer, there seems to be little effect of 25(OH)D concentration on incidence; however, there is an inverse correlation between 25(OH)D concentration and mortality rates. Future observational studies, and randomized controlled trial data analyses, should include adjustment for data collected on prior long-term vitamin D supplementation and solar UVB exposure, as well as other potential confounders. PMID:27489574

  1. Seasonal Changes in Vitamin D-Effective UVB Availability in Europe and Associations with Population Serum 25-Hydroxyvitamin D.

    PubMed

    O'Neill, Colette M; Kazantzidis, Andreas; Ryan, Mary J; Barber, Niamh; Sempos, Christopher T; Durazo-Arvizu, Ramon A; Jorde, Rolf; Grimnes, Guri; Eiriksdottir, Gudny; Gudnason, Vilmundur; Cotch, Mary Frances; Kiely, Mairead; Webb, Ann R; Cashman, Kevin D

    2016-01-01

    Low vitamin D status is common in Europe. The major source of vitamin D in humans is ultraviolet B (UVB)-induced dermal synthesis of cholecalciferol, whereas food sources are believed to play a lesser role. Our objectives were to assess UVB availability (Jm(-2)) across several European locations ranging from 35° N to 69° N, and compare these UVB data with representative population serum 25-hydroxyvitamin D (25(OH)D) data from Ireland (51-54° N), Iceland (64° N) and Norway (69° N), as exemplars. Vitamin D-effective UVB availability was modelled for nine European countries/regions using a validated UV irradiance model. Standardized serum 25(OH)D data was accessed from the EC-funded ODIN project. The results showed that UVB availability decreased with increasing latitude (from 35° N to 69° N), while all locations exhibited significant seasonal variation in UVB. The UVB data suggested that the duration of vitamin D winters ranged from none (at 35° N) to eight months (at 69° N). The large seasonal fluctuations in serum 25(OH)D in Irish adults was much dampened in Norwegian and Icelandic adults, despite considerably lower UVB availability at these northern latitudes but with much higher vitamin D intakes. In conclusion, increasing the vitamin D intake can ameliorate the impact of low UVB availability on serum 25(OH)D status in Europe. PMID:27589793

  2. 25-hydroxyvitamin D, APOE ɛ4 genotype and cognitive function: findings from the 1958 British birth cohort.

    PubMed

    Maddock, J; Cavadino, A; Power, C; Hyppönen, E

    2015-04-01

    Both high and low vitamin D statuses have been associated with lower memory function. Apolipoprotein E (APOE) ɛ4 alleles have been associated with reduced memory function, and separately with higher vitamin D concentrations. This report aims to examine if the presence of APOE ɛ4 alleles contributes to the relationship between vitamin D and memory function. A total of 4848 (46% female) participants from the 1958 British birth cohort had information on APOE genotypes and completed memory tests at 50 years, where 4644 also had 25-hydroxyvitamin D (25(OH)D) concentrations measured at 45 years. Both low and high 25(OH)D concentrations were associated with lower memory function after adjustment for number of APOE ɛ4 alleles (P curvature=0.02). There was evidence of interaction between APOE ɛ4 and 25(OH)D, suggesting the association between 25(OH)D concentrations and memory function is different for those with two APOE ɛ4 alleles compared with those with zero or one APOE ɛ4 alleles (recessive model P interaction=0.01). Among participants with two APOE ɛ4 alleles, higher 25(OH)D concentrations were associated with higher memory function, whereas in others, memory scores were slightly lower for individuals with higher versus lower concentrations. Further studies are required to replicate these findings. PMID:25293430

  3. The association between serum 25-hydroxyvitamin d concentration and consumption frequencies of vitamin d food sources in korean adolescents.

    PubMed

    Yu, Areum; Kim, Jihye; Kwon, Oran; Oh, Se-Young; Kim, Junghyun; Yang, Yoon Jung

    2013-07-01

    The objectives of this study were to investigate the status of vitamin D in Korean adolescents and to determine the association between serum 25-hydroxyvitamin D (25(OH)D) concentration and consumption frequencies of vitamin D food sources by season (June to November and December to May). The subjects were 1,579 adolescents aged 12-18 years participating in the 2008-2009 Korean National Health and Nutrition Examination Survey (KNHANES). Consumption frequencies of vitamin D food sources were estimated by using a qualitative food frequency questionnaire (FFQ). Thirteen food items were selected as vitamin D food sources including beef, egg, mackerel, tuna, yellow corvine, pollack, anchovy, mushroom, milk, yoghurt, ice cream, all fish and dairy products from the FFQ based on previous research. The data was analyzed using proc survey procedures. The deficiency (5.25-12 ng/mL), inadequacy (12-20 ng/mL) and sufficiency (> 20 ng/mL) proportions of serum 25(OH)D from June to November and December to May were 9.9%, 51.4%, 38.7%, and 39.4%, 51.4%, 9.2%, respectively. Mean serum 25(OH)D concentration was positively related to the consumption frequencies of mackerel, anchovy, all fish and milk. These results suggest high proportion (> 61%) of Korean adolescents were vitamin D deficiency or inadequacy, and serum 25(OH)D was associated with the consumption of vitamin D food sources including fish and milk. PMID:23908977

  4. Vitamin D3 and D3 metabolites in young goats fed varying amounts of calcium and vitamin D3.

    PubMed

    Hines, T G; Horst, R L; Littledike, E T; Beitz, D C; Jacobson, N L

    1986-02-01

    Twenty-four male goats, 2 to 4 wk of age, were allotted to four dietary treatments in a 2 X 2 factorial design and, for 20 wk, were fed a milk diet at 12.5% body weight. Treatments varied in amounts of supplemental calcium and vitamin D3. Daily allowances per kilogram body weight were: 9.4 IU vitamin D3 (basal), 9.4 IU vitamin D3 plus 406 mg calcium carbonate (basal plus Ca), 940 IU vitamin D3 (basal plus D3), and 940 IU vitamin D3 plus 406 mg calcium carbonate (basal plus Ca plus D3). At the end of wk 7, a corn supplement was added to all diets at 1% body weight daily. Addition of vitamin D3 to the diet resulted in a dramatic increase in plasma concentrations of vitamin D3. Goats in the basal plus D3 and basal plus Ca plus D3 groups had nearly 100 X greater concentrations of vitamin D3 than goats in the basal and basal plus Ca groups. When greater amounts of vitamin D3 were fed, dietary calcium interacted to decrease plasma vitamin D3 concentrations. Plasma concentrations of 25-hydroxyvitamin D3 were unaffected by additional dietary calcium but were increased by dietary vitamin D3, increasing sixfold to seven-fold in the basal plus D3 and basal plus Ca plus D3 groups. Supplemental calcium resulted in decreased plasma 1,25-dihydroxyvitamin D3. No signs of vitamin D toxicity were noted. The physiological responses reported implicate the goat as a potential animal model for vitamin D research in dairy cattle. PMID:3009577

  5. 25-Hydroxyvitamin D in pregnancy and genome wide cord blood DNA methylation in two pregnancy cohorts (MoBa and ALSPAC)

    PubMed Central

    Suderman, M.; Stene, L.C.; Bohlin, J.; Page, C.M.; Holvik, K.; Parr, C.L.; Magnus, M.C.; Håberg, S.E.; Joubert, B.R.; Wu, M.C.; London, S.J.; Relton, C.; Nystad, W.

    2016-01-01

    The aim of the study was to investigate whether maternal mid-pregnancy 25-hydroxyvitamin D concentrations are associated with cord blood DNA methylation. DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip, and maternal plasma 25-hydroxyvitamin D was measured in 819 mothers/newborn pairs participating in the Norwegian Mother and Child Cohort (MoBa) and 597 mothers/newborn pairs participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Across 473,731CpG DNA methylation sites in cord blood DNA, none were strongly associated with maternal 25-hydroxyvitamin D after adjusting for multiple tests (false discovery rate (FDR) > 0.5; 473,731 tests). A meta-analysis of the results from both cohorts, using the Fisher method for combining p-values, also did not strengthen findings (FDR > 0.2). Further exploration of a set of CpG sites in the proximity of four a priori defined candidate genes (CYP24A1, CYP27B1, CYP27A1 and CYP2R1) did not result in any associations with FDR < 0.05 (56 tests). In this large genome wide assessment of the potential influence of maternal vitamin D status on DNA methylation, we did not find any convincing associations in 1416 newborns. If true associations do exist, their identification might require much larger consortium studies, expanded genomic coverage, investigation of alternative cell types or measurements of 25-hydroxyvitamin D at different gestational time points. PMID:26953979

  6. 25-Hydroxyvitamin D in pregnancy and genome wide cord blood DNA methylation in two pregnancy cohorts (MoBa and ALSPAC).

    PubMed

    Suderman, M; Stene, L C; Bohlin, J; Page, C M; Holvik, K; Parr, C L; Magnus, M C; Håberg, S E; Joubert, B R; Wu, M C; London, S J; Relton, C; Nystad, W

    2016-05-01

    The aim of the study was to investigate whether maternal mid-pregnancy 25-hydroxyvitamin D concentrations are associated with cord blood DNA methylation. DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip, and maternal plasma 25-hydroxyvitamin D was measured in 819 mothers/newborn pairs participating in the Norwegian Mother and Child Cohort (MoBa) and 597 mothers/newborn pairs participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Across 473,731CpG DNA methylation sites in cord blood DNA, none were strongly associated with maternal 25-hydroxyvitamin D after adjusting for multiple tests (false discovery rate (FDR)>0.5; 473,731 tests). A meta-analysis of the results from both cohorts, using the Fisher method for combining p-values, also did not strengthen findings (FDR>0.2). Further exploration of a set of CpG sites in the proximity of four a priori defined candidate genes (CYP24A1, CYP27B1, CYP27A1 and CYP2R1) did not result in any associations with FDR<0.05 (56 tests). In this large genome wide assessment of the potential influence of maternal vitamin D status on DNA methylation, we did not find any convincing associations in 1416 newborns. If true associations do exist, their identification might require much larger consortium studies, expanded genomic coverage, investigation of alternative cell types or measurements of 25-hydroxyvitamin D at different gestational time points. PMID:26953979

  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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  8. The Effect of Serum 25-Hydroxyvitamin D on Elevated Homocysteine Concentrations in Participants of a Preventive Health Program

    PubMed Central

    Pham, Truong-Minh; Ekwaru, John Paul; Mastroeni, Silmara S.; Mastroeni, Marco F.; Loehr, Sarah A.; Veugelers, Paul J.

    2016-01-01

    Both lower serum 25-hydroxyvitamin D [25(OH)D] and elevated homocysteine concentrations are potential risk factors for cardiovascular disease (CVD). A recent analysis of the National Health and Nutrition Examination Survey reported an inverse association of serum 25(OH)D with homocysteine, however, the longitudinal relationship has yet to be investigated. We hypothesized and examined whether a temporal increase in 25(OH)D concentrations is paralleled by a reduction in the risk for elevated homocysteine. We analyzed data of 4475 participants with repeated assessments of serum 25(OH)D and homocysteine concentrations who enrolled in a preventive health program that encourages vitamin D supplementation and monitors serum 25(OH)D and homocysteine concentrations. We defined elevated homocysteine as concentrations greater than 13 micromoles per liter. Logistic regression was applied to assess the association of temporal changes in serum 25(OH)D with the risk of elevated homocysteine. We observed an inverse gradient whereby greater increases in 25(OH)D concentrations were associated with a lower prevalence of elevated homocysteine. Relative to those without temporal increases in 25(OH)D, participants who showed improvements in their serum 25(OH)D concentrations of “<25”, “25–50”, “50–75”, and “≥75” nanomoles per liter at follow up were 0.92 (95% confidence interval: 0.62–1.37), 0.52 (0.33–0.80), 0.34 (0.20–0.58), and 0.32 (0.19–0.54) times as likely to have elevated homocysteine, respectively. These observations suggest that temporal improvements in vitamin D status reduce serum homocysteine concentrations, and therefore may potentially contribute to the primary prevention of CVD. PMID:27548258

  9. Association between Intake of Sugar-Sweetened Beverages and Circulating 25-Hydroxyvitamin D Concentration among Premenopausal Women

    PubMed Central

    Duchaine, Caroline S.; Diorio, Caroline

    2014-01-01

    Intake of sugar-sweetened beverages has increased in North America and seems to have several adverse health effects possibly through decreased circulating 25-hydroxyvitamin D (25(OH)D) concentrations. The aim of this cross-sectional study was to evaluate the association between sugar-sweetened beverages intake and 25(OH)D concentrations among premenopausal women. Intake of sugar-sweetened beverages including colas, other carbonated beverages and sweet fruit drinks was assessed using a validated food frequency questionnaire among 741 premenopausal women. Plasma concentrations of 25(OH)D were quantified by radioimmunoassay. The association between sugar-sweetened beverages intake and 25(OH)D concentrations was evaluated using multivariate generalized linear models and Spearman correlations. A higher intake of colas was associated with lower mean 25(OH)D levels (67.0, 63.7, 64.7 and 58.5 nmol/L for never, <1, 1–3 and >3 servings/week, respectively; r = −0.11 (p = 0.004)). A correlation was observed between intake of other carbonated beverages and 25(OH)D concentrations but was not statistically significant (r = −0.06 (p = 0.10)). No association was observed between intake of sweet fruit drinks and 25(OH)D concentrations. This study suggests that high intake of colas may decrease 25(OH)D levels in premenopausal women. Considering the high consumption of these drinks in the general population and the possible consequences of vitamin D deficiency on health, this finding needs further investigation. PMID:25072269

  10. Dietary products consumption in relation to serum 25-hydroxyvitamin D and selenium level in Saudi children and adults.

    PubMed

    Al-Daghri, Nasser M; Al-Attas, Omar; Yakout, Sobhy; Aljohani, Naji; Al-Fawaz, Hanan; Alokail, Majed S

    2015-01-01

    Vitamin D deficiency is a global health threat that has been associated with several chronic diseases. Selenium is an essential trace element because of role in major metabolic processes, immune function, thyroid hormone metabolism, male infertility, neoplasms and cardiovascular disease. We aimed to investigate for the first time in the Saudi population the association between vitamin D and selenium status with various dietary products consumption. A total of 259 children and 95 adults were included in this cross-sectional study. We estimated the consumption frequencies of various dietary food products using a qualitative food frequency questionnaire (FFQ) and also measured serum levels of 25-hydroxyvitamin D and selenium. Associations between variables of interest were assessed. Vitamin D deficiency and insufficiency were observed in 80% of the boys, 90% of the girls, 64% of men and 50% of women. Modest associations were found between mean serum 25 (OH) D concentration and consumption frequencies of fresh milk in children (r=0.11; P<0.05), more specifically in girls (r=0.12; P<0.05), and to the overall consumption of dairy products in women (r=0.12; P<0.05). Vitamin D status was also inversely associated with selenium in adults (r=-0.43; P<0.05). There was a significant correlation between delta changes of serum selenium, triglycerides and HDL levels (P-values <0.05). Vitamin D and selenium levels are modestly associated with dietary products consumption. Changes in selenium levels were associated with increased serum triglyceride levels, indicating a potential biomarker for cardiovascular risk and dyslipidemia. The widespread vitamin D deficiency observed in the present study highlight the need for adequate fortification of dairy products. PMID:25785131

  11. 25-Hydroxyvitamin D level does not reflect intestinal calcium absorption: an assay using strontium as a surrogate marker.

    PubMed

    Camargo, Marília Brasilio Rodrigues; Vilaça, Tatiane; Hayashi, Lilian Fukusima; Rocha, Olguita G Ferreira; Lazaretti-Castro, Marise

    2015-05-01

    There is conflicting evidence as to the optimal serum 25-hydroxyvitamin D [25(OH)D] concentration for intestinal calcium absorption (Abs-Ca). Our purpose was to assess the relationship between vitamin D status and Abs-Ca in postmenopausal women. Fifty volunteers with low bone mass were grouped according to their serum 25(OH)D concentration as follows: mild deficient, <50 nmol/L (DEF) and sufficient, ≥75 nmol/L (SUF). The subjects were submitted to an oral strontium overload test to assess their Abs-Ca. Fasting blood samples were obtained to perform the relevant hormonal and biochemical tests. After the subjects received the test solution, blood samples were drawn at 30, 60, 120, and 240 min to determine the strontium concentrations. Abs-Ca was indirectly expressed as the area under the serum strontium concentration curve (AUC). A repeated measures ANOVA was performed to determine the differences among the groups. Pearson's correlation and multiple linear regression analysis were used to study the associations between the variables. The mean 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations differed between the groups (SUF vs. DEF) as follows: 98.7 ± 18.2 vs. 38.4 ± 8.5 nmol/L (p < 0.001) and 36.2 ± 10.2 vs. 24.9 ± 4.6 pg/mL (p < 0.001), respectively. There was no statistically significant difference between the groups for parathyroid hormone and AUC. Only 1,25(OH)2D influenced the strontium absorption in the last 2 h of the test. In the studied population, no correlation between levels of 25(OH)D and Abs-Ca was found. Only 1,25(OH)2D influenced Abs-Ca as measured by a strontium absorption test. PMID:24858975

  12. Dietary products consumption in relation to serum 25-hydroxyvitamin D and selenium level in Saudi children and adults

    PubMed Central

    Al-Daghri, Nasser M; Al-Attas, Omar; Yakout, Sobhy; Aljohani, Naji; Al-Fawaz, Hanan; Alokail, Majed S

    2015-01-01

    Vitamin D deficiency is a global health threat that has been associated with several chronic diseases. Selenium is an essential trace element because of role in major metabolic processes, immune function, thyroid hormone metabolism, male infertility, neoplasms and cardiovascular disease. We aimed to investigate for the first time in the Saudi population the association between vitamin D and selenium status with various dietary products consumption. A total of 259 children and 95 adults were included in this cross-sectional study. We estimated the consumption frequencies of various dietary food products using a qualitative food frequency questionnaire (FFQ) and also measured serum levels of 25-hydroxyvitamin D and selenium. Associations between variables of interest were assessed. Vitamin D deficiency and insufficiency were observed in 80% of the boys, 90% of the girls, 64% of men and 50% of women. Modest associations were found between mean serum 25 (OH) D concentration and consumption frequencies of fresh milk in children (r=0.11; P<0.05), more specifically in girls (r=0.12; P<0.05), and to the overall consumption of dairy products in women (r=0.12; P<0.05). Vitamin D status was also inversely associated with selenium in adults (r=-0.43; P<0.05). There was a significant correlation between delta changes of serum selenium, triglycerides and HDL levels (P-values <0.05). Vitamin D and selenium levels are modestly associated with dietary products consumption. Changes in selenium levels were associated with increased serum triglyceride levels, indicating a potential biomarker for cardiovascular risk and dyslipidemia. The widespread vitamin D deficiency observed in the present study highlight the need for adequate fortification of dairy products. PMID:25785131

  13. The Effect of Serum 25-Hydroxyvitamin D on Elevated Homocysteine Concentrations in Participants of a Preventive Health Program.

    PubMed

    Pham, Truong-Minh; Ekwaru, John Paul; Mastroeni, Silmara S; Mastroeni, Marco F; Loehr, Sarah A; Veugelers, Paul J

    2016-01-01

    Both lower serum 25-hydroxyvitamin D [25(OH)D] and elevated homocysteine concentrations are potential risk factors for cardiovascular disease (CVD). A recent analysis of the National Health and Nutrition Examination Survey reported an inverse association of serum 25(OH)D with homocysteine, however, the longitudinal relationship has yet to be investigated. We hypothesized and examined whether a temporal increase in 25(OH)D concentrations is paralleled by a reduction in the risk for elevated homocysteine. We analyzed data of 4475 participants with repeated assessments of serum 25(OH)D and homocysteine concentrations who enrolled in a preventive health program that encourages vitamin D supplementation and monitors serum 25(OH)D and homocysteine concentrations. We defined elevated homocysteine as concentrations greater than 13 micromoles per liter. Logistic regression was applied to assess the association of temporal changes in serum 25(OH)D with the risk of elevated homocysteine. We observed an inverse gradient whereby greater increases in 25(OH)D concentrations were associated with a lower prevalence of elevated homocysteine. Relative to those without temporal increases in 25(OH)D, participants who showed improvements in their serum 25(OH)D concentrations of "<25", "25-50", "50-75", and "≥75" nanomoles per liter at follow up were 0.92 (95% confidence interval: 0.62-1.37), 0.52 (0.33-0.80), 0.34 (0.20-0.58), and 0.32 (0.19-0.54) times as likely to have elevated homocysteine, respectively. These observations suggest that temporal improvements in vitamin D status reduce serum homocysteine concentrations, and therefore may potentially contribute to the primary prevention of CVD. PMID:27548258

  14. Serum 25-hydroxyvitamin D levels and testosterone deficiency in middle-aged Korean men: a cross-sectional study.

    PubMed

    Tak, Young Jin; Lee, Jeong Gyu; Kim, Yun Jin; Park, Nam Cheol; Kim, Sang Soo; Lee, Sangyeoup; Cho, Byung Mann; Kong, Eun Hee; Jung, Dong Wook; Yi, Yu Hyeon

    2015-01-01

    Previous studies have demonstrated that male hypogonadism is associated with a low level of vitamin D. However, no reports have investigated the effects of vitamin D on testosterone levels in Korean men. Our aim was to investigate whether testosterone levels are associated with serum vitamin D levels and whether seasonal variation exists. This cross-sectional study analyzed serum 25-hydroxyvitamin D [25(OH)D], total testosterone (TT), and free testosterone (FT) in 652 Korean men over 40 years of age who had undergone a comprehensive medical examination. The average age of the subjects was 56.7 ± 7.9 years, and the mean serum 25(OH)D, TT and FT levels were 21.23 ± 7.9 ng ml-1 , 4.70 ± 1.6 ng ml-1 , and 8.12 ± 3.3 pg ml-1 , respectively. In the multiple linear regression model, 25(OH)D showed positive association with TT (β =0.137, P< 0.001) and FT (β =0.103, P= 0.008). 25(OH)D and FT showed similar seasonal or monthly variation after adjustment for age. A vitamin D deficiency [25(OH)D < 20 ng ml-1 ] was associated with an increased risk of deficiencies of TT (<2.30 ng ml-1 ) (odds ratio [OR]: 2.65; 95% confidence interval [CI]: 1.21-5.78, P= 0.014) and FT (<6.50 pg ml-1 ) (OR: 1.44; 95% CI: 1.01-2.06 P= 0.048) after adjusting for age, season, body mass index, body composition, chronic disease, smoking, and alcohol use. In conclusion, we demonstrated a positive correlation between 25(OH)D and testosterone, which showed similar seasonal variation in Korean men. PMID:25532570

  15. Serum 25-hydroxyvitamin D levels and testosterone deficiency in middle-aged Korean men: a cross-sectional study

    PubMed Central

    Tak, Young Jin; Lee, Jeong Gyu; Kim, Yun Jin; Park, Nam Cheol; Kim, Sang Soo; Lee, Sangyeoup; Cho, Byung Mann; Kong, Eun Hee; Jung, Dong Wook; Yi, Yu Hyeon

    2015-01-01

    Previous studies have demonstrated that male hypogonadism is associated with a low level of vitamin D. However, no reports have investigated the effects of vitamin D on testosterone levels in Korean men. Our aim was to investigate whether testosterone levels are associated with serum vitamin D levels and whether seasonal variation exists. This cross-sectional study analyzed serum 25-hydroxyvitamin D [25(OH)D], total testosterone (TT), and free testosterone (FT) in 652 Korean men over 40 years of age who had undergone a comprehensive medical examination. The average age of the subjects was 56.7 ± 7.9 years, and the mean serum 25(OH)D, TT and FT levels were 21.23 ± 7.9 ng ml−1, 4.70 ± 1.6 ng ml−1, and 8.12 ± 3.3 pg ml−1, respectively. In the multiple linear regression model, 25(OH)D showed positive association with TT (β =0.137, P < 0.001) and FT (β =0.103, P = 0.008). 25(OH)D and FT showed similar seasonal or monthly variation after adjustment for age. A vitamin D deficiency [25(OH)D < 20 ng ml−1] was associated with an increased risk of deficiencies of TT (<2.30 ng ml−1) (odds ratio [OR]: 2.65; 95% confidence interval [CI]: 1.21–5.78, P = 0.014) and FT (<6.50 pg ml−1) (OR: 1.44; 95% CI: 1.01–2.06 P = 0.048) after adjusting for age, season, body mass index, body composition, chronic disease, smoking, and alcohol use. In conclusion, we demonstrated a positive correlation between 25(OH)D and testosterone, which showed similar seasonal variation in Korean men. PMID:25532570

  16. Relation of serum 25-hydroxyvitamin D status with skeletal muscle mass by sex and age group among Korean adults.

    PubMed

    Ko, Min Jung; Yun, Sungha; Oh, Kyungwon; Kim, Kirang

    2015-12-14

    The objective of this study was to examine whether high serum 25-hydroxyvitamin D (25(OH)D) concentration was associated with high skeletal muscle mass, taking into account the effects of sex and age among the participants of the Korea National Health and Nutrition Examination Survey (KNHANES) aged 40 years or older. This was a cross-sectional study using data from the 2009 to 2010 KNHANES; a total of 8406 subjects (3671 men and 4735 women) were included. The appendicular skeletal muscle mass index (ASMMI, kg/m2) was estimated to measure the skeletal muscle mass. Hypovitaminosis was classified when the level of serum 25(OH)D was <20 ng/ml. The general linear model adjusted for confounding factors was used to determine differences in means of ASMMI by 25(OH)D status. The mean values of ASMMI were higher for men when compared with women. Women had a greater proportion of hypovitaminosis (71·1%) compared with men (53·2%). After adjusting for multiple factors, men were seen to have significant differences in ASMMI based on 25(OH)D status regardless of age, showing a lower mean value of ASSMI in those with hypovitaminosis. However, there was no difference in ASMMI by 25(OH)D status among women in both younger and older age groups. In conclusion, we found that there might be a positive relationship between 25(OH)D and skeletal muscle mass in men, indicating that interventions to improve 25(OH)D levels that are aimed at increasing muscle mass could be beneficial for men with more rapid decreased rate of skeletal muscle mass. PMID:26420417

  17. 25-Hydroxyvitamin D Concentration and Leukocyte Telomere Length in Young Adults: Findings From the Northern Finland Birth Cohort 1966

    PubMed Central

    Williams, Dylan M.; Palaniswamy, Saranya; Sebert, Sylvain; Buxton, Jessica L.; Blakemore, Alexandra I. F.; Hyppönen, Elina; Jarvelin, Marjo-Riitta

    2016-01-01

    Higher vitamin D status, lower adiposity, and longer telomere length are each reportedly associated with lower risk of several chronic diseases and all-cause mortality. However, direct relationships between vitamin D status (measured by circulating 25-hydroxyvitamin D (25(OH)D) concentration), adiposity, and telomere length are not well established. We conducted a cross-sectional analysis of associations of 25(OH)D and body mass index (BMI; weight (kg)/height (m)2) with mean relative leukocyte telomere length (LTL) using data gathered on 5,096 participants from Northern Finland Birth Cohort 1966 at age 31 years (1997). 25(OH)D was not associated with LTL in either basic or confounder/mediator-adjusted models. BMI was inversely associated with LTL after adjustment for potential confounding by age, sex, socioeconomic position, physical activity, diet, smoking, alcohol intake, and use of oral contraceptives (per 1-unit increase in BMI, mean difference in LTL = −0.4%, 95% confidence interval: −0.6, −0.2). The BMI-LTL association was also independent of 25(OH)D and was attenuated slightly, but remained, after adjustment for C-reactive protein, a marker of low-grade inflammation (mean difference in LTL = −0.3%, 95% confidence interval −0.6, −0.1). These findings suggest that vitamin D status is unlikely to be an important determinant of LTL, at least by young adulthood. Inflammation may partly mediate associations of adiposity with LTL. PMID:26797572

  18. A comparison between two different automated total 25-hydroxyvitamin D immunoassay methods using liquid chromatography-tandem mass spectrometry

    PubMed Central

    Kocak, Fatma Emel; Ozturk, Bahadir; Isiklar, Ozben Ozden; Genc, Ozlem; Unlu, Ali; Altuntas, Irfan

    2015-01-01

    Introduction Total 25-hydroxyvitamin D [25(OH)D] is the most reliable indicator of vitamin D status. In this study, we compared two automated immunoassay methods, the Abbott Architect 25-OH Vitamin D assay and the Roche Cobas Vitamin D total assay, with the liquid chromatography-tandem mass spectrometry (LC-MS/MS). Materials and methods One hundred venous blood samples were randomly selected from routine vitamin D tests. Two of the serum aliquots were analyzed at the Abbott Architect i2000 and the Roche Cobas 6000’s module e601 in our laboratory within the same day. The other serum aliquots were analyzed at the LC-MS/MS in different laboratory. Passing-Bablok regression analysis and Bland-Altman plot were used to compare methods. Inter-rater agreement was analyzed using kappa (κ) analysis. Results The Roche assay showed acceptable agreement with the LC-MS/MS based on Passing-Bablok analysis (intercept: -5.23 nmol/L, 95% CI: -8.73 to 0.19; slope: 0.97, 95% CI: 0.77 to 1.15). The Abbott assay showed proportional (slope: 0.77, 95% CI: 0.67 to 0.85) and constant differences (intercept: 17.08 nmol/L; 95% CI: 12.98 to 21.39). A mean bias of 15.1% was observed for the Abbott and a mean bias of -14.1% was observed for the Roche based on the Bland-Altman plots. We found strong to nearly perfect agreement in vitamin D status between the immunoassays and LC-MS/MS. (κ: 0.83 for Abbott, κ: 0.93 for Roche) using kappa analysis. Conclusion Both immunoassays demonstrated acceptable performance, but the Roche Cobas assay demonstrated better performance than the Abbott Architect in the studied samples. PMID:26526462

  19. Higher Serum 25-Hydroxyvitamin D Concentrations Associate with a Faster Recovery of Skeletal Muscle Strength after Muscular Injury

    PubMed Central

    Barker, Tyler; Henriksen, Vanessa T.; Martins, Thomas B.; Hill, Harry R.; Kjeldsberg, Carl R.; Schneider, Erik D.; Dixon, Brian M.; Weaver, Lindell K.

    2013-01-01

    The primary purpose of this study was to identify if serum 25-hydroxyvitamin D (25(OH)D) concentrations predict muscular weakness after intense exercise. We hypothesized that pre-exercise serum 25(OH)D concentrations inversely predict exercise-induced muscular weakness. Fourteen recreationally active adults participated in this study. Each subject had one leg randomly assigned as a control. The other leg performed an intense exercise protocol. Single-leg peak isometric force and blood 25(OH)D, aspartate and alanine aminotransferases, albumin, interferon (IFN)-γ, and interleukin-4 were measured prior to and following intense exercise. Following exercise, serum 25(OH)D concentrations increased (p < 0.05) immediately, but within minutes, subsequently decreased (p < 0.05). Circulating albumin increases predicted (p < 0.005) serum 25(OH)D increases, while IFN-γ increases predicted (p < 0.001) serum 25(OH)D decreases. Muscular weakness persisted within the exercise leg (p < 0.05) and compared to the control leg (p < 0.05) after the exercise protocol. Serum 25(OH)D concentrations inversely predicted (p < 0.05) muscular weakness (i.e., control leg vs. exercise leg peak isometric force) immediately and days (i.e., 48-h and 72-h) after exercise, suggesting the attenuation of exercise-induced muscular weakness with increasing serum 25(OH)D prior to exercise. Based on these data, we conclude that pre-exercise serum 25(OH)D concentrations could influence the recovery of skeletal muscle strength after an acute bout of intense exercise. PMID:23595134

  20. Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/l.

    PubMed

    Luxwolda, Martine F; Kuipers, Remko S; Kema, Ido P; Dijck-Brouwer, D A Janneke; Muskiet, Frits A J

    2012-11-14

    Cutaneous synthesis of vitamin D by exposure to UVB is the principal source of vitamin D in the human body. Our current clothing habits and reduced time spent outdoors put us at risk of many insufficiency-related diseases that are associated with calcaemic and non-calcaemic functions of vitamin D. Populations with traditional lifestyles having lifelong, year-round exposure to tropical sunlight might provide us with information on optimal vitamin D status from an evolutionary perspective. We measured the sum of serum 25-hydroxyvitamin D₂ and D₃ (25(OH)D) concentrations of thirty-five pastoral Maasai (34 (SD 10) years, 43 % male) and twenty-five Hadzabe hunter-gatherers (35 (SD 12) years, 84 % male) living in Tanzania. They have skin type VI, have a moderate degree of clothing, spend the major part of the day outdoors, but avoid direct exposure to sunlight when possible. Their 25(OH)D concentrations were measured by liquid chromatography-MS/MS. The mean serum 25(OH)D concentrations of Maasai and Hadzabe were 119 (range 58-167) and 109 (range 71-171) nmol/l, respectively. These concentrations were not related to age, sex or BMI. People with traditional lifestyles, living in the cradle of mankind, have a mean circulating 25(OH)D concentration of 115 nmol/l. Whether this concentration is optimal under the conditions of the current Western lifestyle is uncertain, and should as a possible target be investigated with concomitant appreciation of other important factors in Ca homeostasis that we have changed since the agricultural revolution. PMID:22264449

  1. Low 25-hydroxyvitamin D levels and low bone density assessed by quantitative ultrasonometry in a cohort of postmenopausal Italian nuns.

    PubMed

    Nuzzo, Vincenzo; Zuccoli, Antonio; de Terlizzi, Francesca; Colao, Annamaria; Tauchmanova, Libuse

    2013-01-01

    This study was aimed at evaluating the effect of clothing style on bone mass and fractures in 70 postmenopausal nuns residing in a monastery in Naples. Sixty healthy women matched for age, body mass index, and menopausal status were enrolled as controls. Each participant underwent measurement by quantitative ultrasonometry (QUS) using a DBM Sonic Bone Profiler (IGEA S.p.A., Carpi, Modena, Italy) at proximal phalanges, responded to questionnaires regarding lifestyle, calcium intake, medical history, including clinical fragility fractures, and was submitted to routine biochemical assessment. A significant reduction in ultrasonometric parameters of bone mass was found in nuns compared with controls (p from 0.007 to <0.0001). 25-hydroxyvitamin D (25-OH vit D) levels were reduced by more than 50% in nuns (9.8 ± 4.2 vs 23.5 ± 5.7 nmol/L; p < 0.0001), whereas their estimated daily calcium intake was higher (1.004 ± 0.23 vs 0.721 ± 0.25 g of controls; p = 0.0007). Age at menopause was significantly lower in nuns' group (p = 0.016). Incidence of fractures was higher in nuns (39% vs 10%; p = 0.0029), and the best predictors of fractures were age at menopause (odds ratio [OR]: 1.12; 95% confidence interval [CI]: 1.01-1.30), amplitude-dependent speed of sound T-score (OR: 1.15; 95% CI: 1.03-1.63), and bone transmission time T-score (OR: 1.30; 95% CI: 1.15-1.81). This study documented low 25-OH vit D levels, increased frequency of clinical fractures, and low bone mass detected by QUS in Southern Italian nuns. PMID:22832035

  2. Expression of Inducible Nitric Oxide Synthase is Up-Regulated by Production of 1,25-Dihydroxyvitamin D3 in Bovine Monocytes in Response to Toll-Like Receptor Signaling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the endocrine pathway of vitamin D signaling 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] is produced from 25-hydroxyvitamin D3 [25(OH)D3] by the enzyme CYP27B1 in the kidney. Production of 1,25(OH)2D3 in the kidney functions to regulate gene expression systemically. However, recent studies have show...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  4. Normal 25-Hydroxyvitamin D Levels Are Associated with Less Proteinuria and Attenuate Renal Failure Progression in Children with CKD.

    PubMed

    Shroff, Rukshana; Aitkenhead, Helen; Costa, Nikola; Trivelli, Antonella; Litwin, Mieczyslaw; Picca, Stefano; Anarat, Ali; Sallay, Peter; Ozaltin, Fatih; Zurowska, Aleksandra; Jankauskiene, Augustina; Montini, Giovanni; Charbit, Marina; Schaefer, Franz; Wühl, Elke

    2016-01-01

    Angiotensin-converting enzyme inhibitors (ACEi) for renin-angiotensin-aldosterone system (RAAS) blockade are routinely used to slow CKD progression. However, vitamin D may also promote renoprotection by suppressing renin transcription through cross-talk between RAAS and vitamin D-fibroblast growth factor-23 (FGF-23)-Klotho pathways. To determine whether vitamin D levels influence proteinuria and CKD progression in children, we performed a post hoc analysis of the Effect of Strict Blood Pressure Control and ACE Inhibition on Progression of CKD in Pediatric Patients (ESCAPE) cohort. In 167 children (median eGFR 51 ml/min per 1.73 m(2)), serum 25-hydroxyvitamin D (25(OH)D), FGF-23, and Klotho levels were measured at baseline and after a median 8 months on ACEi. Children with lower 25(OH)D levels had higher urinary protein/creatinine ratios at baseline (P=0.03) and at follow-up (P=0.006). Levels of 25(OH)D and serum vitamin D-binding protein were not associated, but 25(OH)D ≤50 nmol/L associated with higher diastolic BP (P=0.004). ACEi therapy also associated with increased Klotho levels (P<0.001). The annualized loss of eGFR was inversely associated with baseline 25(OH)D level (P<0.001, r=0.32). Five-year renal survival was 75% in patients with baseline 25(OH)D ≥50 nmol/L and 50% in those with lower 25(OH)D levels (P<0.001). This renoprotective effect remained significant but attenuated with ACEi therapy (P=0.05). Renal survival increased 8.2% per 10 nmol/L increase in 25(OH)D (P=0.03), independent of eGFR; proteinuria, BP, and FGF-23 levels; and underlying renal diagnosis. In children with CKD, 25(OH)D ≥50 nmol/L was associated with greater preservation of renal function. This effect was present but attenuated with concomitant ACEi therapy. PMID:26069294

  5. Serum 25-hydroxyvitamin D and parathyroid hormone in relation to plasma B-type natriuretic peptide: the Hoorn Study

    PubMed Central

    van Ballegooijen, Adriana J; Visser, Marjolein; Snijder, Marieke B; Dekker, Jacqueline M; Nijpels, Giel; Stehouwer, Coen D A; Diamant, Michaela; Brouwer, Ingeborg A

    2012-01-01

    Objective A disturbed vitamin D–parathyroid hormone (PTH)–calcium axis may play a role in the pathogenesis of heart failure. Therefore, we investigated whether lower 25-hydroxyvitamin D (25(OH)D) and higher PTH are cross sectionally and after 8 years of follow-up associated with higher B-type natriuretic peptide (BNP) levels in older men and women. Design and methods We measured baseline 25(OH)D, PTH, and BNP in 502 subjects in 2000–2001 in the Hoorn Study, a population-based cohort. Follow-up BNP was available in 2007–2009 in 278 subjects. Subjects were categorized according to season- and sex-specific quartiles of 25(OH)D and PTH at baseline. We studied the association of 25(OH)D and PTH quartiles with BNP using linear regression analyses adjusting for confounders. Analyses were stratified by kidney function estimated glomerular filtration rate (eGFR; ≤60 ml/min per 1.73 m2) because of significant interaction. Results At baseline, subjects had a mean age of 69.9±6.6 years, mean 25(OH)D level was 52.2±19.5 nmol/l and mean PTH 6.1±2.4 pmol/l. Cross sectionally, 25(OH)D was associated with BNP in subjects with impaired kidney function (eGFR ≤60 ml/min) only. The association attenuated after adjustment for PTH. PTH was cross sectionally associated with BNP, also in subjects with impaired kidney function only: regression coefficient of highest quartile 9.9 pmol/l (95% confidence interval 2.5, 17.4) with a significant trend across quartiles. Neither 25(OH)D nor PTH was associated with BNP in longitudinal analyses. Conclusion This study showed overall no strong association between 25(OH)D and BNP. However, PTH was associated with BNP in subjects with impaired kidney function and may point to a potential role in myocardial function. PMID:23781303

  6. 25-Hydroxyvitamin D in African-origin populations at varying latitudes challenges the construct of a physiologic norm123

    PubMed Central

    Durazo-Arvizu, Ramon A; Camacho, Pauline; Bovet, Pascal; Forrester, Terrence; Lambert, Estelle V; Plange-Rhule, Jacob; Hoofnagle, Andrew N; Aloia, John; Tayo, Bamidele; Dugas, Lara R; Cooper, Richard S; Luke, Amy

    2014-01-01

    Background: The vitamin D–endocrine system is thought to play a role in physiologic processes that range from mineral metabolism to immune function. Serum 25-hydroxyvitamin D [25(OH)D] is the accepted biomarker for vitamin D status. Skin color is a key determinant of circulating 25(OH)D concentrations, and genes responsible for melanin content have been shown to be under strong evolutionary selection in populations living in temperate zones. Little is known about the effect of latitude on mean concentrations of 25(OH)D in dark-skinned populations. Objective: The objective was to describe the distribution of 25(OH)D and its subcomponents in 5 population samples of African origin from the United States, Jamaica, Ghana, South Africa, and the Seychelles. Design: Participants were drawn from the Modeling of the Epidemiologic Transition Study, a cross-sectional observational study in 2500 adults, ages 25–45 y, enrolled between January 2010 and December 2011. Five hundred participants, ∼50% of whom were female, were enrolled in each of 5 study sites: Chicago, IL (latitude: 41°N); Kingston, Jamaica (17°N); Kumasi, Ghana (6°N); Victoria, Seychelles (4°S); and Cape Town, South Africa (34°S). All participants had an ancestry primarily of African origin; participants from the Seychelles trace their history to East Africa. Results: A negative correlation between 25(OH)D and distance from the equator was observed across population samples. The frequency distribution of 25(OH)D in Ghana was almost perfectly normal (Gaussian), with progressively lower means and increasing skewness observed at higher latitudes. Conclusions: It is widely assumed that lighter skin color in populations outside the tropics resulted from positive selection, driven in part by the relation between sun exposure, skin melanin content, and 25(OH)D production. Our findings show that robust compensatory mechanisms exist that create tolerance for wide variation in circulating concentrations of 25(OH)D

  7. Determinants of serum 25-hydroxyvitamin D concentration in Finnish children: the Physical Activity and Nutrition in Children (PANIC) study.

    PubMed

    Soininen, Sonja; Eloranta, Aino-Maija; Lindi, Virpi; Venäläinen, Taisa; Zaproudina, Nina; Mahonen, Anitta; Lakka, Timo A

    2016-03-28

    We studied vitamin D intake, serum 25-hydroxyvitamin D (S-25(OH)D) concentration, determinants of S-25(OH)D and risk factors for S-25(OH)D <50 nmol/l in a population sample of Finnish children. We studied 184 girls and 190 boys aged 6-8 years, analysed S-25(OH)D by chemiluminescence immunoassay and assessed diet quality using 4-d food records and other lifestyle factors by questionnaires. We analysed the determinants of S-25(OH)D using linear regression and risk factors for S-25(OH)D <50 nmol/l using logistic regression. Mean dietary intake of vitamin D was 5·9 (sd 2·1) µg/d. Altogether, 40·8 % of children used no vitamin D supplements. Of all children, 82·4 % did not meet the recommended total vitamin D intake of 10 µg/d. Milk fortified with vitamin D was the main dietary source of vitamin D, providing 48·7 % of daily intake. S-25(OH)D was <50 nmol/l in 19·5 % of children. Consumption of milk products was the main determinant of S-25(OH)D in all children (standardised regression coefficient β=0·262; P<0·001), girls (β=0·214; P=0·009) and boys (β=0·257; P=0·003) in multivariable models. Vitamin D intake from supplements (β=0·171; P=0·035) and age (β=-0·198; P=0·015) were associated with S-25(OH)D in girls. Children who drank ≥450 g/d of milk, spent ≥2·2 h/d in physical activity, had ≥13·1 h/d of daylight time or were examined in autumn had reduced risk for S-25(OH)D <50 nmol/l. Insufficient vitamin D intake was common among Finnish children, one-fifth of whom had S-25(OH)D <50 nmol/l. More attention should be paid to the sufficient intake of vitamin D from food and supplements, especially among children who do not use fortified milk products. PMID:26836317

  8. Clinical and microbiological outcome in septic patients with extremely low 25-hydroxyvitamin D levels at initiation of critical care.

    PubMed

    De Pascale, G; Vallecoccia, M S; Schiattarella, A; Di Gravio, V; Cutuli, S L; Bello, G; Montini, L; Pennisi, M A; Spanu, T; Zuppi, C; Quraishi, S A; Antonelli, M

    2016-05-01

    A relationship between vitamin D status and mortality in patients in intensive care units (ICU) has been documented. The present study aims to describe the clinical profile and sepsis-related outcome of critically ill septic patients with extremely low (<7 ng/mL) vitamin D levels at ICU admission. We conducted an observational study in the ICU of a teaching hospital including all patients admitted with severe sepsis/septic shock and undergoing 25-hydroxyvitamin D (25(OH)D) testing within the first 24 hours from admission. We studied 107 patients over 12 months. At ICU admission vitamin D deficiency (≤20 ng/mL) was observed in 93.5% of the patients: 57 (53.3%) showed levels <7 ng/mL. As primary outcome, sepsis-related mortality rate was higher in patients with vitamin D levels <7 ng/mL (50.9% versus 26%). Multivariate regression analysis showed that vitamin D concentration <7 ng/mL on ICU admission (p 0.01) and higher mean SAPS II (p <0.01) score were independent predictors of sepsis-related mortality. Patients with very low vitamin D levels suffered higher rate of microbiologically confirmed infections but a lower percentage of microbiological eradication with respect to patients whose values were >7 ng/mL (80.7% versus 58%, p 0.02; 35.3% versus 68%; p 0.03, respectively). Post hoc analysis showed that, in the extremely low vitamin D group, the 52 patients with pneumonia showed a longer duration of mechanical ventilation (9 days (3.75-12.5 days) versus 4 days (2-9 days), p 0.04) and the 66 with septic shock needed vasopressor support for a longer period of time (7 days (4-10 days) versus 4 days (2-7.25 days), p 0.02). Our results suggest that in critical septic patients extremely low vitamin D levels on admission may be a major determinant of clinical outcome. Benefits of vitamin D replacement therapy in this population should be elucidated. PMID:26721785

  9. Serum 25-Hydroxyvitamin D Status and Longitudinal Changes in Weight and Waist Circumference: Influence of Genetic Predisposition to Adiposity.

    PubMed

    Larsen, Sofus C; Ängquist, Lars; Moldovan, Max; Huikari, Ville; Sebert, Sylvain; Cavadino, Alana; Ahluwalia, Tarunveer Singh; Skaaby, Tea; Linneberg, Allan; Husemoen, Lise Lotte N; Toft, Ulla; Pedersen, Oluf; Hansen, Torben; Herzig, Karl-Heinz; Jarvelin, Marjo-Riitta; Power, Chris; Hyppönen, Elina; Heitmann, Berit L; Sørensen, Thorkild I A

    2016-01-01

    Studies of the relationship between serum 25-hydroxyvitamin D (25(OH)D) and changes in measures of adiposity have shown inconsistent results, and interaction with genetic predisposition to obesity has rarely been examined. We examined whether 25(OH)D was associated with subsequent annual changes in body weight (ΔBW) or waist circumference (ΔWC), and whether the associations were modified by genetic predisposition to a high BMI, WC or waist-hip ratio adjusted for BMI (WHRBMI). The study was based on 10,898 individuals from the Danish Inter99, the 1958 British Birth Cohort and the Northern Finland Birth Cohort 1966. We combined 42 adiposity-associated Single Nucleotide Polymorphisms (SNPs) into four scores indicating genetic predisposition to BMI, WC and WHRBMI, or all three traits combined. Linear regression was used to examine the association between serum 25(OH)D and ΔBW or ΔWC, SNP-score × 25(OH)D interactions were examined, and results from the individual cohorts were meta-analyzed. In the meta-analyses, we found no evidence of an association between 25(OH)D and ΔBW (-9.4 gram/y per 10 nmol/L higher 25(OH)D [95% CI: -23.0, +4.3; P = 0.18]) or ΔWC (-0.06 mm/y per 10 nmol/L higher 25(OH)D [95% CI: -0.17, +0.06; P = 0.33]). Furthermore, we found no statistically significant interactions between the four SNP-scores and 25(OH)D in relation to ΔBW or ΔWC. Thus, in view of the narrow CIs, our results suggest that an association between 25(OH)D and changes in measures of adiposity is absent or marginal. Similarly, the study provided evidence that there is either no or very limited dependence on genetic predisposition to adiposity. PMID:27077659

  10. 25-Hydroxyvitamin D levels in acute monosymptomatic optic neuritis: relation to clinical severity, paraclinical findings and risk of multiple sclerosis.

    PubMed

    Pihl-Jensen, Gorm; Frederiksen, Jette Lautrup

    2015-07-01

    Optic neuritis (ON) is a common first symptom of MS and only few studies have thus far investigated vitamin D at this early stage of MS. The objectives of the study were to examine total 25-hydroxyvitamin D levels (25HVITDL) in patients in acute (A) ON and to determine whether 25HVITD levels in AON (1) predict risk of RRMS and (2) are associated with visual tests of ON severity. A cross-sectional study was conducted of mean 25HVITDL differences between ON (n = 164) and MS (n = 948) patients and of prevalence of 25HVITDL deficiency (<50 nmol/L) in ON and MS (two-sample t test, χ (2) test). Associations between 25HVITDL and (1) clinical ON severity, (2) paraclinical findings suggestive of MS [logistic regression (LRA), Spearman correlation] and (3) hazard of MS development [Cox (C) RA] in ON patients were assessed. 25HVITDL were deseasonalized before analysis. The mean levels were 47.6 (ON) and 63.9 (MS) nmol/L (p < 0.0001), and a significantly higher prevalence of 25HVITD deficiency in ON (56 %; 35 %) (p < 0.0001), most pronounced in females, was shown. Associations were found between 25HVITDL and both CSF leukocyte count (ρ = -0.177, p = 0.028) and IgG index elevation (OR 0.980, p = 0.031). Forty-one ON patients developed MS during the study. Multivariate CRA showed no effect on hazard of MS (HR: 0.991, p 0.284). No association was found between 25HVITDL and visual tests (acuity, contrast vision) or OCT RNFL or GCL thickness. The study indicates a high prevalence of 25HVITD deficiency in AON. 25HVITDL was significantly associated with CSF leukocyte count, but not ON severity. The study indicates a possible role of vitamin D in the early stages of MS, but does not support the use of 25HVITDL as a predictor of MS development in acute ON. PMID:25929657

  11. Plasma 25-Hydroxyvitamin D, Vitamin D Binding Protein, and Risk of Colorectal Cancer in the Nurses' Health Study.

    PubMed

    Song, Mingyang; Konijeti, Gauree Gupta; Yuan, Chen; Ananthakrishnan, Ashwin N; Ogino, Shuji; Fuchs, Charles S; Giovannucci, Edward L; Ng, Kimmie; Chan, Andrew T

    2016-08-01

    Total circulating 25-hydroxyvitamin D [25(OH)D)] has been associated with lower risk of colorectal cancer. The physiologic mechanism, however, may be more directly related to the free or bioavailable fraction of 25(OH)D, which is influenced by levels of vitamin D binding protein (VDBP). We assessed the association of prediagnosis total, free, and bioavailable 25(OH)D and VDBP with colorectal cancer risk among predominantly white women in the Nurses' Health Study (NHS) who provided a blood specimen in 1989-1990. We documented 378 cases of colorectal cancer through 2011 and matched them to 689 controls according to age and time of blood draw. We genotyped two common polymorphisms in the gene coding VDBP and calculated free and bioavailable 25(OH)D levels based on total 25(OH)D, VDBP, albumin, and their estimated genotype-specific binding affinities. Total 25(OH)D was associated with lower colorectal cancer risk (P for trend = 0.01). Compared with women in the lowest quintile of total 25(OH)D, those in the highest quintile had a multivariable-adjusted odds ratio (OR) for colorectal cancer of 0.54 [95% confidence interval (CI), 0.33-0.87]. Comparing extreme quintiles, we did not find any significant association with risk of colorectal cancer for VDBP (OR, 0.98; 95% CI, 0.65-1.47), free 25(OH)D (OR, 0.71; 95% CI, 0.46-1.10), or bioavailable 25(OH)D (OR, 0.92; 95% CI, 0.60-1.42). In conclusion, prediagnosis levels of total, but not free or bioavailable 25(OH)D, were associated with lower colorectal cancer risk. Although our findings support an inverse association of vitamin D with colorectal cancer, this association does not appear to be due to the unbound or bioavailable fraction of circulating vitamin D. Cancer Prev Res; 9(8); 664-72. ©2016 AACR. PMID:27246684

  12. 25-Hydroxyvitamin D insufficiency discriminates cardiovascular risk factors accumulation in peri-pubertal boys undergoing overweight screening.

    PubMed

    Di Nisio, Andrea; De Toni, Luca; D'Addato, Elvio; Pizzo, Maria R; Sabatino, Pasquale; Foresta, Carlo

    2016-08-01

    The aim of this study was to evaluate the possible association between cardiometabolic risk factors accumulation and vitamin D status in a cohort of Italian normal weight and overweight male children. 108 boys enrolled in an andrological health prevention project underwent physical examination, anthropometric measurements, and fasting blood sampling. Serum blood glucose, HDL-cholesterol, triglycerides, parathyroid hormone, and 25-hydroxyvitamin D (25(OH)D) were measured. Cardiovascular risk factors were defined according to the National Cholesterol Education Program Adult Treatment Panel III modified for age. Lean and overweight subjects differed in terms of waist circumference (P < 0.001), HDL-cholesterol (P = 0.001), triglycerides (P = 0.001), systolic blood pressure (P < 0.001) and diastolic blood pressure (P = 0.002). Both groups had similar mean 25(OH)D levels (P = 0.160) and were below the sufficiency threshold: indeed only 24 % of normal weight had 25(OH)D ≥30 ng/ml, and even less in the overweight/obese group (8 %, P = 0.03 vs. normal weight). A significant accumulation of risk factors in course of 25(OH)D insufficiency was detected in both the whole cohort and in the normal weight group (P = 0.003 and P = 0.04, respectively) with odd ratios of 1.31 (1.16-1.49 95%CI) and 1.41 (1.18-1.69 95%CI), respectively. In course of vitamin D deficiency, the odd ratios were 2.24 (1.34-3.77 95%CI, P = 0.003) in the whole cohort and 2.40 (1.27-4.82 95%CI, P = 0.03) in lean subjects. We reported a considerable occurrence of cardiovascular risk factors in course of hypovitaminosis D in overweight/obese boys and even in lean subjects, which normally would not have been further evaluated by considering the sole BMI-related parameters. In this regard, 25(OH)D levels appear as a potential discriminating parameter able to identify male children at higher health risk. PMID:26323345

  13. Serum concentrations of 25-hydroxyvitamin D and immunoglobulins in an older Swiss cohort: results of the Senior Labor Study

    PubMed Central

    2013-01-01

    Background Vitamin D and the components of humoral immunity play important roles in human health. Older people have lower 25-hydroxyvitamin D (25(OH)D) serum levels than younger adults. We aimed to determine the levels of 25(OH)D serum concentrations in healthy senior citizens and to study their relationship to the levels of components of humoral immunity. Methods A total of 1,470 healthy Swiss men and women, 60 years or older, were recruited for this study. A total of 179 subjects dropped out of the study because of elevated serum concentrations of C-reactive protein. Fasting blood sera were analyzed for 25(OH)D with the high-performance liquid chromatography (HPLC) and for parathyroid hormone (PTH), immunoglobulins and complement C4 and C3 concentrations with immunoassays. The percentage of participants in each of the four 25(OH)D deficiency groups - severely deficient (<10 ng/ml), deficient (10 to 20), insufficient (21 to 29 ng/ml) and normal (>=30 ng/ml) - were statistically compared. The relationship of the major components of the humoral system and age with 25(OH)D levels was also assessed. Results About 66% of the subjects had insufficient levels of 25(OH)D. Normal levels of 25(OH)D were found in 26.1% of the subjects of which 21% were males and 30.5% were females (total study population). Severely deficient levels of 25(OH)D were found in 7.98% of the total study population. Low levels of 25(OH)D were positively associated with IgG2 (P = 0.01) and with C4 (P = 0.02), yet were inversely related to levels of IgG1 and IgA (P < 0.05) and C3 (P = 0.01). Serum levels of total IgA, IgG, IgG2 and IgG4 peaked together with 25(OH)D during late summer. Conclusions Approximately two-thirds of the healthy, older Swiss population presented with Vitamin D insufficiency. The incremental shift in IgA and C3 levels might not necessarily reflect a deranged humoral immune defense; however, given the high prevalence of vitamin D deficiency, the importance of

  14. Serum 25-hydroxyvitamin-D responses to multiple UV exposures from solaria: inferences for exposure to sunlight.

    PubMed

    McKenzie, Richard; Scragg, Robert; Liley, Ben; Johnston, Paul; Wishart, John; Stewart, Alistair; Prematunga, Roshani

    2012-07-01

    We investigate the relationship between blood serum 25-hydroxyvitamin D (25(OH)D) and UV exposure from two artificial sources. We then use the results to test the validity of the action spectrum for vitamin D production, and to infer the production from summer and winter sunlight. The results are based on a two-arm randomised clinical trial of biweekly UV exposure for 12 weeks using two different types of dermatological booths: one emitting primarily UV-A radiation, and the other emitting primarily UV-B radiation (booth A and booth B respectively). In terms of the vitamin D production per unit erythema, one of the booths mimics summer noon sunlight, while the other mimics winter noon sunlight. Blood samples were taken before and after the exposures. For all participants, the phototherapy booth treatments arrested the usual wintertime decline in 25(OH)D, and for most the treatments from either booth resulted in significant increases. The increases were highly non-linear and there was a high degree of variability in 25(OH)D and its response to UV from person to person. By the end of the 12 week period, the mean increase was >30 nmol l(-1) from a cumulative exposure of 17 SED from the UV-A booth, and twice that for the UV-B booth for which the cumulative exposure was 268 SED. Assuming a logarithmic relationship between UV and vitamin D, the results for the two booths show no obvious inconsistency in the action spectrum for pre-vitamin D production. However, further measurements with similar exposures from each booth are required to confirm its validity. A model was developed to describe the increases in serum 25(OH)D resulting from the UV exposures, which differed markedly between the two booths. The deduced initial rate of increase of 25(OH)D was approximately 5 nmol l(-1) per SED. From the large increases in 25(OH)D from each booth, along with knowledge of the spectral distribution of sunlight and assuming the currently-accepted action spectrum for photo

  15. Serum 25-Hydroxyvitamin D Status and Longitudinal Changes in Weight and Waist Circumference: Influence of Genetic Predisposition to Adiposity

    PubMed Central

    Larsen, Sofus C.; Ängquist, Lars; Moldovan, Max; Huikari, Ville; Sebert, Sylvain; Cavadino, Alana; Singh Ahluwalia, Tarunveer; Skaaby, Tea; Linneberg, Allan; Husemoen, Lise Lotte N.; Toft, Ulla; Pedersen, Oluf; Hansen, Torben; Herzig, Karl-Heinz; Jarvelin, Marjo-Riitta; Power, Chris; Hyppönen, Elina; Heitmann, Berit L.; Sørensen, Thorkild I. A.

    2016-01-01

    Studies of the relationship between serum 25-hydroxyvitamin D (25(OH)D) and changes in measures of adiposity have shown inconsistent results, and interaction with genetic predisposition to obesity has rarely been examined. We examined whether 25(OH)D was associated with subsequent annual changes in body weight (ΔBW) or waist circumference (ΔWC), and whether the associations were modified by genetic predisposition to a high BMI, WC or waist-hip ratio adjusted for BMI (WHRBMI). The study was based on 10,898 individuals from the Danish Inter99, the 1958 British Birth Cohort and the Northern Finland Birth Cohort 1966. We combined 42 adiposity-associated Single Nucleotide Polymorphisms (SNPs) into four scores indicating genetic predisposition to BMI, WC and WHRBMI, or all three traits combined. Linear regression was used to examine the association between serum 25(OH)D and ΔBW or ΔWC, SNP-score × 25(OH)D interactions were examined, and results from the individual cohorts were meta-analyzed. In the meta-analyses, we found no evidence of an association between 25(OH)D and ΔBW (-9.4 gram/y per 10 nmol/L higher 25(OH)D [95% CI: -23.0, +4.3; P = 0.18]) or ΔWC (-0.06 mm/y per 10 nmol/L higher 25(OH)D [95% CI: -0.17, +0.06; P = 0.33]). Furthermore, we found no statistically significant interactions between the four SNP-scores and 25(OH)D in relation to ΔBW or ΔWC. Thus, in view of the narrow CIs, our results suggest that an association between 25(OH)D and changes in measures of adiposity is absent or marginal. Similarly, the study provided evidence that there is either no or very limited dependence on genetic predisposition to adiposity. PMID:27077659

  16. Synthesis of 25-hydroxyvitamin D sub 3 3. beta. -3 prime -(N-(4-azido-2-nitrophenyl)amino)propyl ether, a second-generation photoaffinity analogue of 25-hydroxyvitamin D sub 3 : Photoaffinity labeling of rat serum vitamin D binding protein

    SciTech Connect

    Ray, R.; Holick, M.F. ); Bouillon, R.; Van Baelen, H. )

    1991-05-14

    Vulnerability of 25-hydroxy-(26,27-{sup 3}H)vitamin D{sub 3} 3{beta}-N-(4-azido-2-nitrophenyl)glycinate, a photoaffinity analogue of 25-hydroxyvitamin D{sub 3} (25-OH-D{sub 3}) toward standard conditions of carboxymethylationin promoted the authors to synthesize 25-hydroxyvitamin D{sub 3} 3{beta}-3{prime}-(N-(4-azido-2-nitrophenyl)amino)propyl ether (25-ANE), a hydrolytically stable photoaffinity analogue of 25-OH-D{sub 3}, and 25-hydroxyvitamin D{sub 3} 3{beta}-3{prime}-(N-(4-azido-2-nitro-(3,5-{sup 3}H)phenyl)amino)propyl ether ({sup 3}H-25-ANE), the radiolabeled counterpart of 25-ANE competes for the 25-OH-D{sub 3} binding site in rat serum vitamin D binding protein (rDBP). On the other hand, UV exposure of a sample of purified rat DBP (rDBP), preincubated in the dark with {sup 3}H-25-ANE, covalently labeled the protein. However, very little covalent labeling was observed in the absence of UV light or in the presence of a large excess of 25-OH-D{sub 3}. These results provide strong evidence for the covalent labeling of the 25-OH-D{sub 3} binding site in rDPB by {sup 3}H-25-ANE.

  17. Clinical and laboratory determinants of low serum level of 25-hydroxyvitamin D during escalation of pharmacotherapy in heart failure patients

    PubMed Central

    Rozentryt, Piotr; Niedziela, Jacek T.; Ociessa, Aneta; Kasperova, Maria; Hudzik, Bartosz; Nowak, Jolanta U.; Gąsior, Mariusz

    2015-01-01

    Introduction The activation of the renin-angiotensin-aldosterone (RAA) system is a main element of the pathophysiology of chronic heart failure (CHF), determining its symptoms and prognosis. Vitamin D is an RAA inhibitor, and its deficiency frequently accompanies CHF. The factors determining the concentration of 25-hydroxyvitamin D [25(OH)D] in CHF are not well understood, although an association has been suggested between the deficiency and the advancement of CHF. Also unknown is the influence of therapeutic escalation using recommended agents on the serum level of 25(OH)D. The aim of this study was to examine the incidence of abnormal 25(OH)D concentrations in CHF patients and to establish the clinical and laboratory determinants of low activity of this metabolite. Material and methods The retrospective analysis included the data of 412 CHF patients not receiving optimal pharmacological treatment who were initially in NYHA (New York Heart Association) class III or IV. Over the period of 3 months the therapy was escalated until reaching maximum tolerated doses or those recommended by the current guidelines. After optimizing the therapy, the incidence of 25(OH)D deficiency (< 30 ng/ml) and insufficiency (< 20 ng/ml) was established, and clinical and laboratory determinants for these abnormal concentrations were analyzed. Results Normal serum level, insufficiency, and deficiency of 25(OH)D were observed in, respectively, 41.5%, 26.0% and 32.5% of patients. The NYHA class improved by at least 1 class in 63.6% of patients, remained unchanged in 32.8% of patients, and deteriorated in 3.6% of patients. In multivariables analysis, low availability of natural ultraviolet B (UVB) radiation, loss of body mass during the CHF, higher concentrations of phosphates and albumins, and the presence of diabetes increased the risk of 25(OH)D deficiency, while higher concentrations of uric acid reduced this risk. In patients with a positive response to therapy, the concentration of 25

  18. High frequency of deficient consumption and low blood levels of 25-hydroxyvitamin D in HIV-1-infected adults from São Paulo city, Brazil

    PubMed Central

    Sales, Stephanie Hael; Matta, Sandra da; Silva, Daniela Cardeal da; Assone, Tatiane Assone; Fonseca, Luiz Augusto M.; Duarte, Alberto J. S.; Casseb, Jorge

    2015-01-01

    Micronutrient deficiency is common in patients with HIV/AIDS, usually caused by mal-absorption and/or drug interactions. 25-hydroxyvitamin D is of fundamental importance for the homeostasis of musculoskeletal health. The current study aimed to evaluate the nutritional status of HIV-infected subjects in order to make their nutritional diagnoses, including their vitamin D blood levels, and to estimate their consumption of vitamin D. The study included 98 HIV-1-infected subjects, followed at University of São Paulo Medical School - HC-FMUSP. We performed a nutritional evaluation, along with the determination of patients’ serum 25-hydroxyvitamin D and calcium concentration, biochemical analyses, and an anthropometric assessment. In the medical interview a 24-hour food recall was used (R24) to estimate daily calorie intake, macronutrients, calcium, and vitamin D. A high level of vitamin D deficiency was observed in our patients: 83.4% of them had levels below 30 ng/ml; they also presented an increased risk of cardiovascular disease, along with a high consumption of dietary fat. Factors related to the virus itself and to the use of antiretroviral drugs may have contributed for the low vitamin D levels seen in our HIV-1-infected patients. PMID:26257370

  19. High throughput LC-MS/MS method for the simultaneous analysis of multiple vitamin D analytes in serum.

    PubMed

    Jenkinson, Carl; Taylor, Angela E; Hassan-Smith, Zaki K; Adams, John S; Stewart, Paul M; Hewison, Martin; Keevil, Brian G

    2016-03-01

    Recent studies suggest that vitamin D-deficiency is linked to increased risk of common human health problems. To define vitamin D 'status' most routine analytical methods quantify one particular vitamin D metabolite, 25-hydroxyvitamin D3 (25OHD3). However, vitamin D is characterized by complex metabolic pathways, and simultaneous measurement of multiple vitamin D metabolites may provide a more accurate interpretation of vitamin D status. To address this we developed a high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to analyse multiple vitamin D analytes, with particular emphasis on the separation of epimer metabolites. A supportive liquid-liquid extraction (SLE) and LC-MS/MS method was developed to quantify 10 vitamin D metabolites as well as separation of an interfering 7α-hydroxy-4-cholesten-3-one (7αC4) isobar (precursor of bile acid), and validated by analysis of human serum samples. In a cohort of 116 healthy subjects, circulating concentrations of 25-hydroxyvitamin D3 (25OHD3), 3-epi-25-hydroxyvitamin D3 (3-epi-25OHD3), 24,25-dihydroxyvitamin D3 (24R,25(OH)2D3), 1,25-dihydroxyvitamin D3 (1α,25(OH)2D3), and 25-hydroxyvitamin D2 (25OHD2) were quantifiable using 220μL of serum, with 25OHD3 and 24R,25(OH)2D3 showing significant seasonal variations. This high-throughput LC-MS/MS method provides a novel strategy for assessing the impact of vitamin D on human health and disease. PMID:26874878

  20. Lack of evidence for existence of vitamin D and 25-hydroxyvitamin D sulfates in human breast and cow's milk.

    PubMed

    Okano, T; Kuroda, E; Nakao, H; Kodama, S; Matsuo, T; Nakamichi, Y; Nakajima, K; Hirao, N; Kobayashi, T

    1986-10-01

    The presence of water-soluble vitamin D and 25-OH-D sulfates in human breast and cow's milk was studied. We first confirmed that synthetic vitamin D2 and D3 sulfates could not be hydrolyzed by alkali but by acid. Breast or cow's milk was separated into milk whey containing water-soluble components and milk curd containing crude proteins and lipophilic components. The separated milk whey and curd were hydrolyzed by acid or alkali and each lipid extract was subjected to HPLC analysis. Neither peak due to vitamin D and 25-OH-D was observed in the chromatograms of acid- and alkali-hydrolyzed milk whey, whereas the peaks due to vitamin D3 and 25-OH-D3 were found in the chromatograms of both acid- and alkali-hydrolyzed milk curd and there was no significant difference between the respective peak heights. The eluates corresponding to the respective peaks observed on the latter's chromatograms were collected and subjected to UV, HPLC, GC-MS and GLC to identify the existence of vitamin D3 and 25-OH-D3, respectively. We concluded from these results that neither breast nor cow's milk contained water-soluble vitamin D and 25-OH-D sulfates, whereas they contained fat-soluble vitamin D3 and 25-OH-D3. The concentrations of vitamin D3 and 25-OH-D3 in breast milk were about 125 and 350 ng/liter, while those in cow's milk were about 420 and 270 ng/liter, respectively. The experiments on the transfer of 3H-D3 and 3H-25-OH-D3 perorally dosed to lactating rats into suckling pups through their milk also supported the above conclusion. PMID:3494111

  1. Effect of vitamin D supplementation, directly or via breast milk for term infants, on serum 25 hydroxyvitamin D and related biochemistry, and propensity to infection: a randomised placebo-controlled trial.

    PubMed

    Chandy, David D; Kare, Jahnavi; Singh, Shakal N; Agarwal, Anjoo; Das, Vinita; Singh, Urmila; Ramesh, V; Bhatia, Vijayalakshmi

    2016-07-01

    We assessed the effect of vitamin D supplementation on related biochemistry, infection and dentition of the infant. In a double-blind, placebo-controlled trial conducted in Lucknow, India (latitude 26°N), 230 mother -newborn pairs were randomised to receive, for 9 months, 3000µg/month oral vitamin D3 by the mother (group A) or 10µg/d by the infant (group B) or double placebo (group C). All babies received 15 min of sun exposure (unclothed) during massage. Infants' median 25-hydroxyvitamin D (25(OH)D) was lower in group C (median 45·3; interquartile range (IQR) 22-59·5 nmol/l) than in groups A (median 60·8; IQR 41·3-80·5 nmol/l (P7.5µkat/l) was significantly more frequent in group C babies (16 %) than in group A (4 %) or group B (0 %) babies. The number of days with respiratory or diarrhoeal infection by 9 months of age was higher in group C (median 46·5; IQR 14·8-73·3 d) than in group A (median 18·5; IQR 8·8-31·0 d (P<0·01)) or group B (median 13·0; IQR 7·0-28·5 (P<0·05)). We conclude that monthly maternal or daily infant supplementation with vitamin D along with sun exposure is superior to sun exposure alone in maintaining normal infant 25(OH)D at 3·5 months, and provide protection from elevated alkaline phosphatase and infectious morbidity. PMID:27184759

  2. 1,25-hydroxyvitamin D relieves colitis in rats via down-regulation of toll-like receptor 9 expression

    PubMed Central

    Dai, Zhang-han; Tan, Bei; Yang, Hong; Wang, Ou; Qian, Jia-ming; Lv, Hong

    2015-01-01

    Aim To investigate the therapeutic and immunoregulatory effects of 1,25-dihydroxyvitamin D (1,25(OH)D3) on 2,4,6-trinitrobenzenesulfonic acid (TNBS) -induced colitis in rats. Methods Experimental colitis induced by enema administration of TNBS plus ethanol was treated with 5-aminosalicylic acid (5-ASA) and/or 1,25(OH)D3. Disease activity was measured using the disease activation index (DAI), colon macroscopic damage index (CMDI), histological colonic damage score, and myeloperoxidase (MPO) activity. The expression of toll-like receptor 9 (TLR9) in the colon was determined by reverse transcription-polymerase chain reaction and immunohistochemistry. Results Rats with TNBS-induced colitis had significantly elevated DAI, CMDI, histological colonic damage score, and MPO activity (all P < 0.001) compared to rats without colitis. Treatment with 5-ASA or 1,25(OH)D3 ameliorated colitis by lowering CMDI (P = 0.049, P = 0.040, respectively), histological colonic damage score (P = 0.010, P = 0.005, respectively), and MPO activity (P = 0.0003, P = 0.0013, respectively) compared with the TNBS group. Combined treatment with 5-ASA and 1,25(OH)D3 significantly decreased MPO activity (P = 0.003). 1,25(OH)D3 attenuated colitis without causing hypercalcemia or renal insufficiency. TNBS significantly increased the number of TLR9 positive cells compared to control (P < 0.010), while 5-ASA, 1,25(OH)D3, and combined treatment with 5-ASA and 1,25(OH)D3 significantly decreased it compared to TNBS group (all P < 0.010). In TNBS group a moderate correlation was observed between MPO activity and the number of TLR9-positive cells (r = 0.654, P < 0.001). Conclusion TLR9 expression correlates with the extent of inflammation in TNBS-induced colitis. 1,25(OH)D3 relieves this inflammation possibly by decreasing TLR9 expression. PMID:26718757

  3. Two-dimensional liquid chromatography coupled to tandem mass spectrometry for vitamin D metabolite profiling including the C3-epimer-25-monohydroxyvitamin D3.

    PubMed

    Mena-Bravo, A; Priego-Capote, F; Luque de Castro, M D

    2016-06-17

    A method based on automated on-line solid phase extraction coupled to two-dimensional liquid chromatography with tandem mass spectrometry detection (SPE-2DLC-MS/MS) is here reported for vitamin D metabolite profiling in human serum with absolute quantitation. Two-dimensional LC was configured with two complementary analytical columns, pentafluorophenyl (PFP) and C18 phases, for determination of 25 hydroxyvitamin D3 epimers and the resting bioactive metabolites of vitamin D (D3 and D2)-25-hydroxyvitamin D2, 1,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D2 and 24,25-dihydroxyvitamin D3. Quantitative determination was supported on the use of a stable isotopic labelled internal standard for each analyte and the resulting method was validated by analysis of a standard reference material certified by the National Institute of Standards & Technology (NIST-972a) and 5 samples provided by the vitamin D External Quality Assurance Scheme (DEQAS). The limits of detection were between 9 and 90pg/mL for the eight analytes, and precision, expressed as relative standard deviation, was lower than 11.6%. Two-dimensional LC has shown to be the key to discriminate between 25 hydroxyvitamin D3 epimers in a quantitative analysis also involving dihydroxyvitamin D metabolites. PMID:27180887

  4. A systematic review of the influence of skin pigmentation on changes in the concentrations of vitamin D and 25-hydroxyvitamin D in plasma/serum following experimental UV irradiation.

    PubMed

    Xiang, Fan; Lucas, Robyn; de Gruijl, Frank; Norval, Mary

    2015-12-01

    Defining whether skin pigmentation influences vitamin D photosynthesis is important for delivering accurate public health messages. Current evidence is contradictory. We undertook a systematic review of the published literature to examine the association between skin pigmentation and change in blood concentrations of vitamin D and 25-hydroxyvitamin D following experimental UV irradiation. Twelve studies fulfilled the inclusion criteria: human study in vivo with non-diseased participants; controlled artificial UV radiation; vitamin D or 25-hydroxyvitamin D measured in serum or plasma; full text in English. In seven studies, vitamin D photosynthesis was reduced in dark-skinned compared with fairer-skinned individuals. In the remaining five studies, only one of which was published after 1990, there was no difference in vitamin D photosynthesis according to skin type. The disparities in these results may be due to small sample sizes and variations in study methodology, including the source, dose and frequency of UV irradiation, phototype classification, and analysis of vitamin D and 25-hydroxyvitamin D. Of these, the spectrum emitted by the UV lamps may be significant. No study considered potential modifying factors, such as relevant genetic polymorphisms. On balance, we conclude that pigmented skin has less effective photoproduction of vitamin D and 25-hydroxyvitamin D. The quantity of sun exposure needed for dark-skinned, compared with light-skinned, people to achieve vitamin D sufficiency remains uncertain. PMID:26548800

  5. Antenatal endotoxin disrupts lung vitamin D receptor and 25-hydroxyvitamin D 1α-hydroxylase expression in the developing rat.

    PubMed

    Mandell, Erica; Seedorf, Gregory J; Ryan, Sharon; Gien, Jason; Cramer, Scott D; Abman, Steven H

    2015-11-01

    Vitamin D [vit D; 1,25-(OH)2D] treatment improves survival and lung alveolar and vascular growth in an experimental model of bronchopulmonary dysplasia (BPD) after antenatal exposure to endotoxin (ETX). However, little is known about lung-specific 1,25-(OH)2D3 regulation during development, especially regarding maturational changes in lung-specific expression of the vitamin D receptor (VDR), 1α-hydroxylase (1α-OHase), and CYP24A1 during late gestation and the effects of antenatal ETX exposure on 1,25-(OH)2D3 metabolism in the lung. We hypothesized that vit D regulatory proteins undergo maturation regulation in the late fetal and early neonatal lung and that prenatal exposure to ETX impairs lung growth partly through abnormal endogenous vit D metabolism. Normal fetal rat lungs were harvested between embryonic day 15 and postnatal day 14. Lung homogenates were assayed for VDR, 1α-OHase, and CYP24A1 protein contents by Western blot analysis. Fetal rats were injected on embryonic day 20 with intra-amniotic ETX, ETX + 1,25-(OH)2D3, or saline and delivered 2 days later. Pulmonary artery endothelial cells (PAECs) from fetal sheep were assessed for VDR, 1α-OHase, and CYP24A1 expression after treatment with 25-(OH)D3, 1,25-(OH)2D3, ETX, ETX + 25-(OH)D3, or ETX + 1,25-(OH)2D3. We found that lung VDR, 1α-OHase, and CYP2741 protein expression dramatically increase immediately before birth (P < 0.01 vs. early fetal values). Antenatal ETX increases CYP24A1 expression (P < 0.05) and decreases VDR and 1α-OHase expression at birth (P < 0.001), but these changes are prevented with concurrent vit D treatment (P < 0.001). ETX-induced reduction of fetal PAEC growth and tube formation and lung 1α-OHase expression are prevented by vit D treatment (P < 0.001). We conclude that lung VDR, 1α-OHase, and CYP24A1 protein content markedly increase before birth and that antenatal ETX disrupts lung vit D metabolism through downregulation of VDR and increased vit D catabolic enzyme

  6. Effects of dietary vitamin D3 on concentrations of vitamin D and its metabolites in blood plasma and milk of dairy cows.

    PubMed

    McDermott, C M; Beitz, D C; Littledike, E T; Horst, R L

    1985-08-01

    To determine the effect of supplemental dietary vitamin D3 on concentration of vitamin D and its metabolites in milk, 20 Holstein cows were assigned to four groups and fed either 0, 10,000, 50,000, or 250,000 IU of vitamin D3/d beginning approximately 2 wk prepartum and continuing through wk 12 of lactation. Samples of blood plasma and milk were assayed for concentrations of vitamin D, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D. Only the daily dosage of 250,000 IU caused significant increases of concentrations of vitamin D or 25-hydroxyvitamin D in plasma. Concentrations of vitamin D and 25-hydroxyvitamin D in milk were approximately equal and averaged .2 ng/ml. Little 1,25-dihydroxyvitamin D and no 24,25-dihydroxyvitamin D could be detected in milk from any of the four treatment groups. Cows fed 250,000 IU of vitamin D3/d produced milk containing 54 IU of vitamin D activity per liter, whereas unsupplemented cows produced milk containing 17 IU/L. Oral supplementation with up to 250,000 IU of vitamin D3/d does not increase effectively vitamin D activity of milk. PMID:2995465

  7. Effects of Vitamin D Supplementation on C-peptide and 25-hydroxyvitamin D Concentrations at 3 and 6 Months

    PubMed Central

    Chandler, Paulette D.; Giovannucci, Edward L.; Scott, Jamil B.; Bennett, Gary G.; Ng, Kimmie; Chan, Andrew T.; Hollis, Bruce W.; Rifai, Nader; Emmons, Karen M.; Fuchs, Charles S.; Drake, Bettina F.

    2015-01-01

    The link between African-Americans’ disproportionate rates of diabetes, obesity and vitamin D deficiency may be marked by C-peptide as an indicator of insulin secretion. We hypothesize that vitamin D supplementation will increase C-peptide, a marker of insulin secretion. During 3 winters from 2007-2010, 328 healthy African-Americans (median age, 51 years) living in Boston, MA were randomized into a 4-arm, double-blind trial for 3 months of placebo, 1000, 2000, or 4000 IU of vitamin D3. The differences in non-fasting C-peptide between baseline and 3 months were −0.44 ng/mL for those receiving placebo, −0.10 ng/mL for those receiving 1000 IU/d, 0 ng/mL for those receiving 2000 IU/d, 1.24 ng/mL for those receiving 4000 IU/d (C-peptide increased 0.42 ng/mL for each additional 1000 IU/d of vitamin D3, p < 0.001). Vitamin D supplementation increased C-peptide in overweight African-Americans and may be compatible with other recommendations for diabetes prevention and management including weight loss and increased physical activity. PMID:26095242

  8. The AusD Study: a population-based study of the determinants of serum 25-hydroxyvitamin D concentration across a broad latitude range.

    PubMed

    Brodie, A M; Lucas, R M; Harrison, S L; van der Mei, I A F; Armstrong, B; Kricker, A; Mason, R S; McMichael, A J; Nowak, M; Whiteman, D C; Kimlin, M G

    2013-05-01

    Observational studies suggest that people with a high serum 25-hydroxyvitamin D (25(OH)D) concentration may have reduced risk of chronic diseases such as osteoporosis, multiple sclerosis, type 1 diabetes, cardiovascular disease, and some cancers. The AusD Study (A Quantitative Assessment of Solar UV Exposure for Vitamin D Synthesis in Australian Adults) was conducted to clarify the relationships between ultraviolet (UV) radiation exposure, dietary intake of vitamin D, and serum 25(OH)D concentration among Australian adults residing in Townsville (19.3°S), Brisbane (27.5°S), Canberra (35.3°S), and Hobart (42.8°S). Participants aged 18-75 years were recruited from the Australian Electoral Roll between 2009 and 2010. Measurements were made of height, weight, waist:hip ratio, skin, hair, and eye color, blood pressure, and grip strength. Participants completed a questionnaire on sun exposure and vitamin D intake, together with 10 days of personal UV dosimetry and an associated sun-exposure and physical-activity diary that was temporally linked to a blood test for measurement of 25(OH)D concentration. Ambient solar UV radiation was also monitored at all study sites. We collected comprehensive, high-quality data from 1,002 participants (459 males, 543 females) assessed simultaneously across a range of latitudes and through all seasons. Here we describe the scientific and methodological issues considered in designing the AusD Study. PMID:23524036

  9. A Randomised, Cross-Over Study to Estimate the Influence of Food on the 25-Hydroxyvitamin D₃ Serum Level after Vitamin D₃ Supplementation.

    PubMed

    Cavalier, Etienne; Jandrain, Bernard; Coffiner, Monte; Da Silva, Stéphanie; De Niet, Sophie; Vanderbist, Francis; Souberbielle, Jean-Claude

    2016-01-01

    Vitamin D₃ is known to be liposoluble and its release could be a factor limiting the rate of absorption. It was presumed that the presence of fat could favor absorption of vitamin D₃. However, as bioavailability is related not only to the active molecules but also to the formulations and excipients used, the optimization of the pharmaceutical form of vitamin D₃ is also important. The objective of this study was to evaluate if there is a food effect on absorption when a high dose of vitamin D₃ is completely solubilized in an oily solution. In the present cross-over study, 88 subjects were randomized and received a single dose of 50,000 IU of vitamin D₃ in fasting state or with a standardized high-fat breakfast. Assessment of serum concentrations of 25 hydroxyvitamin D₃ (25(OH)D₃) was performed three, five, seven, 14, 30 and 60 days after supplementation. In fed and fast conditions, the 25(OH)D₃ serum concentrations were significantly higher than the baseline value three days after administration and remained significantly higher during the first month. No significant difference between fasting vs. fed conditions was observed. It is therefore concluded that the vitamin D₃ absorption from an oily solution was not influenced by the presence or absence of a meal. PMID:27213447

  10. Predictors of Vitamin D-Containing Supplement Use in the Australian Population and Associations between Dose and Serum 25-Hydroxyvitamin D Concentrations.

    PubMed

    Black, Lucinda J; Jacoby, Peter; Nowson, Caryl A; Daly, Robin M; Lucas, Robyn M

    2016-01-01

    Despite concerns about vitamin D deficiency in the Australian population, little is known about the prevalence and predictors of vitamin D-containing supplement use. We described the use of vitamin D-containing supplements, and investigated associations between supplemental vitamin D intake and serum 25-hydroxyvitamin D (25(OH)D) concentrations, using a single 24-h dietary recall from the 2011-2013 Australian Health Survey (n = 12,153; ages ≥ 2 years). Multiple regression models were used to investigate predictors of vitamin D-containing supplement use in adults, and associations between dose and serum 25(OH)D concentrations/vitamin D sufficiency (≥50 nmol/L), adjusting for potential confounders. The prevalence of vitamin D-containing supplement use was 10%, 6% and 19% in children, adolescents and adults, respectively. Predictors of vitamin D-containing supplement use in adults included being female, advancing age, higher educational attainment, higher socio-economic status, not smoking, and greater physical activity. After adjusting for potential confounders, a 40 IU (1 µg) increase in vitamin D intake from supplements was associated with an increase of 0.41 nmol/L in serum 25(OH)D concentrations (95% CI 0.35, 0.47; p < 0.001). However, the prevalence of vitamin D-containing supplement use was generally low in the Australian population, particularly for single vitamin D supplements, with most supplement users obtaining only low levels of vitamin D from other supplement types. PMID:27338462

  11. Associations of Sun Exposure with 25-Hydroxyvitamin D and Parathyroid Hormone Levels in a Cohort of Hypertensive Patients: The Graz Endocrine Causes of Hypertension (GECOH) Study

    PubMed Central

    Pilz, Stefan; Kienreich, Katharina; Stückler, Daniel; Meinitzer, Andreas; Tomaschitz, Andreas

    2012-01-01

    Sunlight-induced vitamin D, synthesis in the skin is the major source of vitamin D, but data on the relationship of sun-related behaviour with vitamin D and parathyroid hormone (PTH) levels are relatively sparse. We evaluated whether habitual sun exposure is associated with 25-hydroxyvitamin D (25[OH]D) and PTH levels and whether there exist seasonal variations. We examined 111 hypertensive patients in Austria (latitude 47° N). Frequent sunbathing at home and outdoor sports were associated with higher 25(OH)D levels (P < 0.05 for both). Red or blond scalp hair as a child, memory of sunburns, preferring sunbathing, frequent stays on the beach or in open-air pools, and solarium use were associated with lower PTH levels (P < 0.05 for all). Multiple linear regression analyses including age, sex, and body mass index showed that sun exposure score was significantly associated with 25(OH)D (beta coefficient = 0.27; P = 0.004) and by trend with PTH (beta coefficient = −0.16; P = 0.09). These associations were more prominent in summer in which 25(OH)D levels were significantly higher compared to winter. Translation of these findings into recommendations for the prevention and treatment of vitamin D deficiency remains a challenge for the future. PMID:22518130

  12. Serum 25-hydroxyvitamin D and CD4+CD25(+high) FoxP3+ Regulatory T cell as Predictors of Severity of Bronchial Asthma in Children.

    PubMed

    Ismail, Ahlam M; Aly, Sanaa S; Fayed, Hanan M; Ahmed, Samar S

    2015-01-01

    Bronchial asthma (BA) is one of the common chronic diseases of childhood. Vitamin D deficiency has been associated with BA. Suppressor regulatory T cells (Treg) are important for the induction, maintenance of immunological tolerance to allergens. This study assessed serum 25-hydroxyvitamin D (vitamin D) and the percentages of CD4+CD25+(high) Foxp3+ Treg, in peripheral blood, as predictors of asthma severity and level of clinical control. The study enrolled 72 children divided equally between asthmatic children (AC) and age and sex matched controls. Diagnostic criteria and level of asthma severity followed the Global Initiative for Asthma guidelines. Serum vitamin D was determined by an immunoassay and the percentages of CD4+CD25+ig Foxp3+ Treg by flow cytometry. Serum vitamin D level and percentage of CD4+CD25+(high) Treg were lower in AC compared to controls (P < 0.001) whereas Fox p3 expression was higher in AC compared to controls, P < 0.001. Serum vitamin D levels were lower in severe asthma compared to mild and moderate forms (P = 0.008) and in uncontrolled attacks compared to partially or completely controlled children. No difference in percentage of Treg in relation to asthma severity and clinical control was observed. Since AC has decreased serum vitamin D with inverse relationship between its levels and asthma severity, we conclude that it can be used to predict severity of asthma. PMID:26415368

  13. Predictors of Vitamin D-Containing Supplement Use in the Australian Population and Associations between Dose and Serum 25-Hydroxyvitamin D Concentrations

    PubMed Central

    Black, Lucinda J.; Jacoby, Peter; Nowson, Caryl A.; Daly, Robin M.; Lucas, Robyn M.

    2016-01-01

    Despite concerns about vitamin D deficiency in the Australian population, little is known about the prevalence and predictors of vitamin D-containing supplement use. We described the use of vitamin D-containing supplements, and investigated associations between supplemental vitamin D intake and serum 25-hydroxyvitamin D (25(OH)D) concentrations, using a single 24-h dietary recall from the 2011–2013 Australian Health Survey (n = 12,153; ages ≥ 2 years). Multiple regression models were used to investigate predictors of vitamin D-containing supplement use in adults, and associations between dose and serum 25(OH)D concentrations/vitamin D sufficiency (≥50 nmol/L), adjusting for potential confounders. The prevalence of vitamin D-containing supplement use was 10%, 6% and 19% in children, adolescents and adults, respectively. Predictors of vitamin D-containing supplement use in adults included being female, advancing age, higher educational attainment, higher socio-economic status, not smoking, and greater physical activity. After adjusting for potential confounders, a 40 IU (1 µg) increase in vitamin D intake from supplements was associated with an increase of 0.41 nmol/L in serum 25(OH)D concentrations (95% CI 0.35, 0.47; p < 0.001). However, the prevalence of vitamin D-containing supplement use was generally low in the Australian population, particularly for single vitamin D supplements, with most supplement users obtaining only low levels of vitamin D from other supplement types. PMID:27338462

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

    PubMed

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

    2012-09-01

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

  15. Seasonal variation in the serum 25-hydroxyvitamin D levels of young and elderly active and inactive adults in São Paulo, Brazil

    PubMed Central

    Maeda, Sergio Setsuo; Saraiva, Gabriela Luporini; Hayashi, Lilian Fukusima; Cendoroglo, Maysa Seabra; Ramos, Luiz Roberto; Corrêa, Marcelo de Paula; Henrique de Mesquita, Carlos; Lazaretti-Castro, Marise

    2013-01-01

    Objective: To evaluate the 25-hydroxyvitamin D [25(OH)D] concentrations in individuals in the city of São Paulo belonging to different age groups and exhibiting specific behavioral characteristics and to correlate the 25(OH)D concentration with the level of UV radiation (UVR). Patients and Methods: A total of 591 individuals were included, distributed as follows: 177 were living in institutions (NURSING, 76.2 ± 9.0 y old), 243 were part of the community elderly (COMMUNITY, 79.6 ± 5.3 y old), 99 were enrolled in a physical activity program targeting the elderly (ACTIVE, 67.6 ± 5.4 y old) and 72 were young (YOUNG, 23.9 ± 2.8 y old). Blood samples from all individuals were collected throughout the year. UVR measurements were taken by an official meteorology institution. Results: The UVR values varied throughout the year, following a sinusoidal-like pattern. Because of the Earth’s orbit, we hypothesized that there would be cyclic patterns for the 25(OH)D and UVR values that repeat every 12 mo. The general formula is represented by the equation P1+P2⋅sin(−2⋅π12⋅(t−P3)) The mean 25(OH)D concentration and the amplitude of the variation were significantly higher for the YOUNG and ACTIVE groups than for the COMMUNITY and NURSING groups. The nadir for UVR was in June, whereas the nadir for the 25(OH)D concentration was in the spring, corresponding to a delay of one season. Conclusions: There was seasonal variation in the 25(OH)D concentration for all the groups studied; however, the amplitude of the variation was higher for the groups of young and physically active people, possibly due to the higher level of sunlight exposure for these groups. The lowest 25(OH)D concentration was detected in the spring. PMID:24494057

  16. Serum 25-hydroxyvitamin D level and incident type 2 diabetes in older men, the Osteoporotic Fractures in Men (MrOS) study.

    PubMed

    Napoli, Nicola; Schafer, Anne L; Lui, Li-Yung; Cauley, Jane A; Strotmeyer, Elsa S; Le Blanc, Erin S; Hoffman, Andrew R; Lee, Christine G; Black, Dennis M; Schwartz, Ann V

    2016-09-01

    The association between vitamin D status and diabetes risk is inconsistent among observational studies, and most of the available studies have been with women. In the present study we investigated the association between serum 25-hydroxyvitamin D (25(OH)D) levels and incident type 2 diabetes (T2D) in older men (≥65years old) who participated in the multisite Osteoporotic Fractures in Men (MrOS) study enrolled from March 2000 to April 2002. Baseline 25(OH)D levels were available in 1939 subjects without prevalent T2D. Clinical information, body mass index (BMI) and other factors related to T2D were assessed at the baseline visit. Incident diabetes, defined by self-report and medication use, was determined over an average follow-up of 6.4years. At baseline, participants were, on average, 73.3 (±5.7) years old, had a mean BMI in the overweight range (27.2kg/m(2)±3.6) and had total serum 25(OH)D of 26.1ng/ml (±8.3). Incident diabetes was diagnosed in 139 subjects. Cox regression analysis showed a trend toward a protective effect of higher 25(OH)D levels with a lower risk of T2D (HR 0.87, 95% CI: 0.73-1.04 per 1 SD increase of 25(OH)D). After adjusted for BMI and other potential confounders, the relationship between 25(OH)D levels and incident diabetes was further attenuated (HR 1.03, 95% CI 0.85-1.25). No significant difference in the incidence of diabetes emerged after analyzing study subjects according to baseline 25(OH)D quartiles. In conclusion, 25(OH)D levels were not associated with incident T2D in older men. PMID:27393241

  17. Optimal Vitamin D Supplementation Doses that Minimize the Risk for Both Low and High Serum 25-Hydroxyvitamin D Concentrations in the General Population

    PubMed Central

    Veugelers, Paul J.; Pham, Truong-Minh; Ekwaru, John Paul

    2015-01-01

    The Recommended Dietary Allowance (RDA) is the nutrient intake considered to be sufficient to meet the requirements of 97.5% of the population. Recent reports revealed a statistical error in the calculation of the RDA for vitamin D opening the question of what the recommendation should be. We took a dual approach to answer this question: (1) we aggregated 108 published estimates on vitamin D supplementation and vitamin D status; and (2) we analyzed 13,987 observations of program participants. The aggregation of published data revealed that 2909 IU of vitamin D per day is needed to achieve serum 25-hydroxyvitamin D (25(OH)D) concentrations of 50 nmol/L or more in 97.5% of healthy individuals. For normal weight, overweight and obese program participants this was 3094, 4450 and 7248 IU respectively. These supplementation doses would also result in 2.5% of normal weight, overweight and obese participants having 25(OH)D concentrations above 210, 200 and 214 nmol/L respectively. As these concentrations are high, an approach that minimizes the risk for both low and high concentrations seems desirable. With this approach we estimated, for example, that doses of 1885, 2802 and 6235 IU per day are required for normal weight, overweight and obese individuals respectively to achieve natural 25(OH)D concentrations (defined as 58 to 171 nmol/L). In conclusion, the large extent of variability in 25(OH)D concentrations makes a RDA for vitamin D neither desirable nor feasible. We therefore propose recommendations be articulated in the form of an optimal intake that minimizes the risk for both low and high serum 25(OH)D concentrations. This contribution includes body weight specific recommendations for optimal intakes for various combinations of lower and upper 25(OH)D concentration targets. PMID:26690210

  18. Serum 25-hydroxyvitamin D, vitamin D binding protein, and risk of colorectal cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

    PubMed Central

    Weinstein, Stephanie J.; Purdue, Mark P.; Smith-Warner, Stephanie A.; Mondul, Alison M.; Black, Amanda; Ahn, Jiyoung; Huang, Wen-Yi; Horst, Ronald L.; Kopp, William; Rager, Helen; Ziegler, Regina G.; Albanes, Demetrius

    2014-01-01

    The potential role of vitamin D in cancer prevention has generated substantial interest, and laboratory experiments indicate several anti-cancer properties for vitamin D compounds. Prospective studies of circulating 25-hydroxyvitamin D [25(OH)D], the accepted biomarker of vitamin D status, suggest an inverse association with colorectal cancer risk, but with some inconsistencies. Furthermore, the direct or indirect impact of the key transport protein, vitamin D binding protein (DBP), has not been examined. We conducted a prospective study of serum 25(OH)D and DBP concentrations and colorectal cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, based on 476 colorectal cancer cases and 476 controls, matched on age, sex, race, and date of serum collection. All subjects underwent sigmoidoscopic screening at baseline and once during follow-up. Conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Circulating 25(OH)D was inversely associated with colorectal cancer (OR=0.60, 95% CI 0.38-0.94 for highest versus lowest quintile, p-trend 0.01). Adjusting for recognized colorectal cancer risk factors and accounting for seasonal vitamin D variation did not alter the findings. Neither circulating DBP nor the 25(OH)D:DBP molar ratio, a proxy for free circulating 25(OH)D, was associated with risk (OR=0.82, 95% CI 0.54-1.26, and OR=0.79, 95% CI 0.52-1.21, respectively), and DBP did not modify the 25(OH)D association. The current study eliminated confounding by colorectal cancer screening behavior, and supports an association between higher vitamin D status and substantially lower colorectal cancer risk, but does not indicate a direct or modifying role for DBP. PMID:25156182

  19. The Influence of Health and Lifestyle Characteristics on the Relation of Serum 25-Hydroxyvitamin D With Risk of Colorectal and Breast Cancer in Postmenopausal Women

    PubMed Central

    Neuhouser, Marian L.; Manson, JoAnn E.; Millen, Amy; Pettinger, Mary; Margolis, Karen; Jacobs, Elizabeth T.; Shikany, James M.; Vitolins, Mara; Adams-Campbell, Lucile; Liu, Simin; LeBlanc, Erin; Johnson, Karen C.; Wactawski-Wende, Jean

    2012-01-01

    The authors’ objective was to discern whether lifestyle or health-related factors were confounders, effect modifiers, or irrelevant with regard to understanding observational associations of serum 25-hydroxyvitamin D (25(OH)D) with colorectal and breast cancer. The authors conducted nested case-control studies of colorectal cancer (310 cases, 310 controls) and breast cancer (1,080 cases, 1,080 controls) in the Women’s Health Initiative Calcium and Vitamin D Clinical Trial (1994–2005). Case-control matching factors included age, latitude, race/ethnicity, and blood collection date. Serum 25(OH)D was assayed in baseline fasting blood. Conditional logistic regression was used to estimate odds ratios for each cancer by serum 25(OH)D concentration, comparing the relative effects of successively adding body mass index, physical activity, and other health and lifestyle characteristics particular to each cancer. In models with matching factors only, low (vs. high) serum 25(OH)D was associated with a colorectal cancer odds ratio of 2.72 (95% confidence interval (CI): 1.55, 4.77) and a breast cancer odds ratio of 1.33 (95% CI: 1.02, 1.72). In multivariate-adjusted models for colorectal cancer, the association strengthened (OR = 4.45, 95% CI: 1.96, 10.10). However, in multivariate-adjusted breast cancer models, associations were no longer significant (OR = 1.06, 95% CI: 0.78, 1.43). Adjusting for health and lifestyle characteristics has differential effects depending on the cancer site; when modeling such relations, investigators should take these factors into account. PMID:22362582

  20. Both serum 25-hydroxyvitamin D and calcium levels may increase the risk of incident prostate cancer in Caribbean men of African ancestry.

    PubMed

    Jackson, Maria D; Tulloch-Reid, Marshall K; Lindsay, Carole M; Smith, Garrett; Bennett, Franklyn I; McFarlane-Anderson, Norma; Aiken, William; Coard, Kathleen C M

    2015-06-01

    Circulating 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with both higher and lower risk of prostate cancer (PCa), whereas elevated levels of circulating calcium has been related to higher risks. However, there are few studies that account for effects of both calcium and 25(OH)D concentrations on incident PCa in a black population. We examined these relationships in a case-control study of men 40-80 years old with newly diagnosed, histologically confirmed PCa in Jamaica, a tropical country. Mean serum calcium concentrations was higher among cases (2.32 ± 0.19 mmol/L) than controls, (2.27 ± 0.30 mmol/L) (P = 0.023) however, there were no differences in 25(OH)D by cancer status (cases, 33.67 ± 12.71 ng/mL; controls (32.25 ± 12.59 ng/mL). Serum calcium was not correlated with 25(OH)D (partial correlation: r, 0.06; P = 0.287). Multivariable-adjusted models showed a positive linear relationship between PCa and serum calcium (OR, 1.12; CI, 1.00-1.25 per 0.1 nmol/L). Serum 25(OH)D concentration also showed a positive association with PCa (OR, 1.23; CI, 1.01-1.49 per 10 ng/mL). The odds of PCa in men with serum 25(OH)D tertile 2 was OR, 2.18; CI, 1.04-4.43 and OR, 2.47 CI, 1.20-4.90 for tertile 3 (P(trend) = 0.013). Dietary intakes of calcium showed no relationship with PCa. Despite the strong relationship between serum calcium and vitamin D the mechanism by which each affects prostate cancer risk in men of African ancestry needs additional investigation. PMID:25858172

  1. Association between circulating ascorbic acid, α-tocopherol, 25-hydroxyvitamin D, and plasma cytokine concentrations in young adults: a cross-sectional study

    PubMed Central

    2012-01-01

    Background Inflammation and oxidative stress are associated with the development of numerous chronic diseases. Circulating ascorbic acid, α-tocopherol, and 25-hydroxyvitamin D (25(OH)D) may help reduce concentrations of pro-inflammatory cytokines through their antioxidant and anti-inflammatory properties. These micronutrients may act synergistically, and they may have different anti-inflammatory effects, but previous studies have assessed the link between each of these micronutrients and inflammation in isolation without controlling for the other micronutrients. Our objective was to examine the association between circulating concentrations of ascorbic acid, α-tocopherol, and 25(OH) D and a panel of pro-inflammatory cytokines in an ethnically diverse population of young adults. Methods Participants (n = 1,007) from the Toronto Nutrigenomics and Health study provided fasting blood samples for biomarker measurements and were subsequently categorized into tertiles for each micronutrient based on their circulating concentrations. We conducted Pearson’s correlation analyses across all micronutrients and cytokines. The associations between individual micronutrients and cytokines were examined using analysis of covariance with age, sex, waist circumference, ethnicity, physical activity, season of blood collection, total cholesterol, hormonal contraceptive use among women, and the other two micronutrients as covariates. Results We observed weak micronutrient-cytokine correlations, moderate correlations between certain cytokines, and strong correlations between specific cytokines, particularly interleukin 1- receptor antagonist (IL-1RA), interferon-γ (IFN-γ), and platelet-derived growth factor BB (PDGF-bb). After full covariate adjustment, circulating α-tocopherol was inversely associated with IFN-γ and regulated upon activation normal T-cell expressed and secreted (RANTES). We observed an unexpected positive association between ascorbic acid and IFN-γ. 25(OH)D

  2. The Relationship Between Serum 25-Hydroxyvitamin D Levels and Nuclear Cataract in the Carotenoid Age-Related Eye Study (CAREDS), an Ancillary Study of the Women's Health Initiative

    PubMed Central

    Rao, Prethy; Millen, Amy E.; Meyers, Kristin J.; Liu, Zhe; Voland, Rickie; Sondel, Sheri; Tinker, Lesley; Wallace, Robert B.; Blodi, Barbara A.; Binkley, Neil; Sarto, Gloria; Robinson, Jennifer; LeBlanc, Erin; Mares, Julie A.

    2015-01-01

    Purpose. To investigate the relationship between serum 25-hydroxyvitamin D (25[OH]D) levels and nuclear cataract among participants of the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative (WHI) Observational Study (OS). Methods. Nuclear cataract was assessed from slit lamp photographs (2001–2004) taken 6 years after collecting serum analyzed for 25(OH)D levels at WHI baseline (1994–1998) in 1278 CAREDS participants age 50 to 79 years. Multivariate (age, iris color, smoking, pulse pressure) odds ratios (ORs) for nuclear cataract (nuclear opacities > level 4 or cataract extraction) by quintiles of serum 25(OH)D were estimated using logistic regression. Results. No significant association was observed between serum 25(OH)D and nuclear cataract among women of all ages (age-adjusted OR [95% confidence interval (CI)] 0.97 [0.65–1.45]). However, there was a significant age interaction (P for interaction = 0.04). There were no significant associations in the women 70 years or older. In women younger than 70 years, we observed an inverse association between serum 25(OH)D and nuclear cataract (multivariate adjusted ORs [95% CI] 0.54 [0.29–0.99] and 0.66 [0.36–1.20] for quintiles 4 and 5 vs. 1, respectively; P = 0.03). Further adjustment for 25(OH)D determinants (body mass index, vitamin D intake, and UVB exposure) attenuated this association. Conclusions. Serum 25(OH)D levels were unrelated to nuclear opacities in this study sample. However, exploratory analyses suggest a protective association in women younger than 70 years. Further investigations of the relationship between vitamin D and nuclear lens opacities are warranted. PMID:26132781

  3. Vitamin D-fortified milk achieves the targeted serum 25-hydroxyvitamin D concentration without affecting that of parathyroid hormone in New Zealand toddlers.

    PubMed

    Houghton, Lisa A; Gray, Andrew R; Szymlek-Gay, Ewa A; Heath, Anne-Louise M; Ferguson, Elaine L

    2011-10-01

    For young children, the level of vitamin D required to ensure that most achieve targeted serum 25-hydroxyvitamin D [25(OH)D] ≥50 nmol/L has not been studied. We aimed to investigate the effect of vitamin D-fortified milk on serum 25(OH)D and parathyroid hormone (PTH) concentrations and to examine the dose-response relationship between vitamin D intake from study milks and serum 25(OH)D concentrations in healthy toddlers aged 12-20 mo living in Dunedin, New Zealand (latitude 46°S). Data from a 20-wk, partially blinded, randomized trial that investigated the effect of providing red meat or fortified toddler milk on the iron, zinc, iodine, and vitamin D status in young New Zealand children (n = 181; mean age 17 mo) were used. Adherence to the intervention was assessed by 7-d weighed diaries at wk 2, 7, 11, 15, and 19. Serum 25(OH)D concentration was measured at baseline and wk 20. Mean vitamin D intake provided by fortified milk was 3.7 μg/d (range, 0-10.4 μg/d). After 20 wk, serum 25(OH)D concentrations but not PTH were significantly different in the milk groups. The prevalence of having a serum 25(OH)D <50 nmol/L remained relatively unchanged at 43% in the meat group, whereas it significantly decreased to between 11 and 15% in those consuming fortified study milk. In New Zealand, vitamin D intake in young children is minimal. Our findings indicate that habitual consumption of vitamin D-fortified milk providing a mean intake of nearly 4 μg/d was effective in achieving adequate year-round serum 25(OH)D for most children. PMID:21832027

  4. Serum 25-hydroxyvitamin D concentrations and postmenopausal breast cancer risk: a nested case control study in the Cancer Prevention Study-II Nutrition Cohort

    PubMed Central

    McCullough, Marjorie L; Stevens, Victoria L; Patel, Roshni; Jacobs, Eric J; Bain, Elizabeth B; Horst, Ronald L; Gapstur, Susan M; Thun, Michael J; Calle, Eugenia E

    2009-01-01

    Introduction Vitamin D status measured during adulthood has been inversely associated with breast cancer risk in some, but not all, studies. Vitamin D has been hypothesized to prevent breast cancer through genomic and non-genomic actions in cell-cycle regulation. Methods A subset (n = 21,965) of female participants from the prospective Cancer Prevention Study-II (CPS-II) Nutrition Cohort provided a blood sample from 1998-2001 and were followed through 2005. We measured serum 25-hydroxyvitamin D (25(OH)D) in 516 verified incident cases and 516 controls, matched on birth date (± 6 months), date of blood draw (± 6 months) and race. Information on medical history, risk factors and lifestyle was available from repeated questionnaires. We computed multi-variable odds ratios (OR) and 95% confidence intervals (95% CI) for the association between 25(OH)D quintile and breast cancer risk using unconditional logistic regression, controlling for matching factors and additional confounders. Results We observed no association between 25(OH)D and breast cancer (OR = 1.09, 95% CI 0.70-1.68, P = 0.60) for the top vs bottom quintile. Using a priori cut-points, the OR was 0.86 (95% CI 0.59-1.26), for ≥75 vs <50 nmol/L. Results were not different when the first two years of follow-up were excluded, or in analyses stratified by season, latitude, BMI, postmenopausal hormone use, or by tumor grade or estrogen receptor status. Conclusions These results do not support an association between adulthood serum 25(OH)D and postmenopausal breast cancer. We cannot rule out an association with 25(OH)D status earlier in life. PMID:19715600

  5. Serum 25-hydroxyvitamin D, vitamin D binding protein and risk of colorectal cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

    PubMed

    Weinstein, Stephanie J; Purdue, Mark P; Smith-Warner, Stephanie A; Mondul, Alison M; Black, Amanda; Ahn, Jiyoung; Huang, Wen-Yi; Horst, Ronald L; Kopp, William; Rager, Helen; Ziegler, Regina G; Albanes, Demetrius

    2015-03-15

    The potential role of vitamin D in cancer prevention has generated substantial interest, and laboratory experiments indicate several anti-cancer properties for vitamin D compounds. Prospective studies of circulating 25-hydroxyvitamin D [25(OH)D], the accepted biomarker of vitamin D status, suggest an inverse association with colorectal cancer risk, but with some inconsistencies. Furthermore, the direct or indirect impact of the key transport protein, vitamin D binding protein (DBP), has not been examined. We conducted a prospective study of serum 25(OH)D and DBP concentrations and colorectal cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, based on 476 colorectal cancer cases and 476 controls, matched on age, sex, race and date of serum collection. All subjects underwent sigmoidoscopic screening at baseline and once during follow-up. Conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Circulating 25(OH)D was inversely associated with colorectal cancer (OR = 0.60, 95% CI 0.38-0.94 for highest versus lowest quintile, p trend 0.01). Adjusting for recognized colorectal cancer risk factors and accounting for seasonal vitamin D variation did not alter the findings. Neither circulating DBP nor the 25(OH)D:DBP molar ratio, a proxy for free circulating 25(OH)D, was associated with risk (OR = 0.82, 95% CI 0.54-1.26, and OR = 0.79, 95% CI 0.52-1.21, respectively), and DBP did not modify the 25(OH)D association. The current study eliminated confounding by colorectal cancer screening behavior, and supports an association between higher vitamin D status and substantially lower colorectal cancer risk, but does not indicate a direct or modifying role for DBP. PMID:25156182

  6. Bone mineral density and serum 25-hydroxyvitamin D level: is there any difference according to the dressing style of the female university students.

    PubMed

    Budak, Nurten; Ciçek, Betül; Sahin, Habibe; Tutus, Ahmet

    2004-11-01

    Nutrition plays a role in the etiology of osteoporosis. Two of the most important nutrients for bone health are calcium and vitamin D. Plasma 25-hydroxyvitamin D [25-(OH)D] is the most sensitive clinical index of vitamin D status and has been found to be positively related to bone mineral density (BMD) in middle-aged and elderly women, and positive relations exist between the BMD of adult women and their calcium consumption throughout life. The aim of the present study was to determine relationships between BMD, serum vitamin D levels and dietary calcium intake of female young adult students who dressed in different styles. We studied two groups of volunteer female students (total = 67). Students in the first group dressed in a style that exposed the skin to sunlight, students in the second group wore dresses completely covering the skin except for the face and hands. Serum 25-(OH)D levels were measured by radioimmunoassay, BMDs were determined at the lumbar spine and femoral neck by dual-energy X-ray absorptiometry, and calcium intakes were estimated with a 3-day food recording questionnaire. The serum 25-(OH)D level was significantly lower in the second group. There was no significant difference in BMD between the two groups. The dietary calcium intake of the two groups were lower than the adequate intake of 1000 mg daily for this age. There was a correlation between the serum 25-(OH)D level and BMD at the femoral neck in the first group. Our results indicate that vitamin D and calcium requirements for normal bone mineral accrual in young adults may advance until a certain age, and the covered dressing style causes vitamin D insufficiency and most of the students were under risk for osteoporosis in later life. PMID:16019301

  7. Including food 25-hydroxyvitamin D in intake estimates may reduce the discrepancy between dietary and serum measures of vitamin D status.

    PubMed

    Taylor, Christine L; Patterson, Kristine Y; Roseland, Janet M; Wise, Stephen A; Merkel, Joyce M; Pehrsson, Pamela R; Yetley, Elizabeth A

    2014-05-01

    The discrepancy between the commonly used vitamin D status measures-intake and serum 25-hydroxyvitamin D [25(OH)D] concentrations--has been perplexing. Sun exposure increases serum 25(OH)D concentrations and is often used as an explanation for the higher population-based serum concentrations in the face of apparently low vitamin D intake. However, sun exposure may not be the total explanation. 25(OH)D, a metabolite of vitamin D, is known to be present in animal-based foods. It has been measured and reported only sporadically and is not currently factored into U.S. estimates of vitamin D intake. Previously unavailable preliminary USDA data specifying the 25(OH)D content of a subset of foods allowed exploration of the potential change in the reported overall vitamin D content of foods when the presence of 25(OH)D was included. The issue of 25(OH)D potency was addressed, and available commodity intake estimates were used to outline trends in projected vitamin D intake when 25(OH)D in foods was taken into account. Given the data available, there were notable increases in the total vitamin D content of a number of animal-based foods when potency-adjusted 25(OH)D was included, and in turn there was a potentially meaningful increase (1.7-2.9 μg or 15-30% of average requirement) in vitamin D intake estimates. The apparent increase could reduce discrepancies between intake estimates and serum 25(OH)D concentrations. The relevance to dietary interventions is discussed, and the need for continued exploration regarding 25(OH)D measurement is highlighted. PMID:24623845

  8. Vitamin D Binding Protein Genotype Is Associated with Serum 25-Hydroxyvitamin D and PTH Concentrations, as Well as Bone Health in Children and Adolescents in Finland

    PubMed Central

    Viljakainen, Heli T.; Kokkonen, Elina; Jakobsen, Jette; Cashman, Kevin; Mäkitie, Outi; Lamberg-Allardt, Christel

    2014-01-01

    Vitamin D binding protein (DBP)/group-specific component (Gc), correlates positively with serum vitamin D metabolites, and phenotype influences serum 25-hydroxyvitamin D (S-25(OH)D) concentration. The protein isoform has been associated with decreased bone mineral density (BMD) and increased fracture risk. We examined the role of GC genotypes in S-25(OH)D status and BMD in 231 Finnish children and adolescents aged 7−19 yr. BMD was measured with DXA from lumbar spine (LS), total hip, and whole body, and for 175 subjects, radial volumetric BMD was measured with pQCT. Background characteristic and total dietary intakes of vitamin D and calcium were collected. The concentrations of 25(OH)D, parathyroid hormone (PTH), calcium and other markers of calcium homeostasis were determined from blood and urine. Genotyping was based on single-nucleotide polymorphism (rs4588) in the GC gene. The genotype distribution was: GC 1/1 68%, GC 1/2 26% and GC 2/2 6%. A significant difference emerged in 25(OH)D and PTH concentrations between the genotypes, (p = 0.001 and 0.028 respectively, ANCOVA). There was also a linear trend in: Gc 2/2 had the lowest 25(OH)D and PTH concentrations (p = 0.025 and 0.012, respectively). Total hip bone mineral content was associated with GC genotype (BMC) (p = 0.05, ANCOVA) in boys. In regression analysis, after adjusting for relevant covariates, GC genotype was associated with LS BMC and strength and strain index (SSI) Z-score in both genders, and LS BMD in boys. In conclusion, the present study demonstrates the association between GC genotypes and S-25(OH)D and PTH concentrations. The results show the influence of DBP genetic variation on bone mass accrual in adolescence. PMID:24498064

  9. Short- and Long-Term Safety of Weekly High-Dose Vitamin D3 Supplementation in School Children

    PubMed Central

    Maalouf, Joyce; Nabulsi, Mona; Vieth, Reinhold; Kimball, Samantha; El-Rassi, Rola; Mahfoud, Ziyad; El-Hajj Fuleihan, Ghada

    2008-01-01

    Background: Hypovitaminosis D is prevalent in youth worldwide, but the safety of vitamin D at doses exceeding 200 IU/d is unknown in this age group. We assessed the safety of high doses of vitamin D3 administered to apparently healthy schoolchildren. Methods: To assess short-term safety, 25 subjects randomly received placebo or vitamin D3 at doses of 14,000 IU/wk for 8 wk. To assess long-term safety, 340 subjects randomly received placebo, vitamin D3 as 1,400 IU/wk or 14,000 IU/wk for 1 yr. Biochemical variables were monitored at 0, 2, 4, 6, and 8 wk and 8 wk off therapy in the short-term study and at 0, 6, and 12 months in the long-term study. Results: In both the short- and long-term studies, mean serum calcium and 1,25-hydroxyvitamin levels did not change in any group. In the short-term study, mean 25-hydroxyvitamin concentrations increased from 44 (± 11) to 54 (± 19) ng/ml in the treated groups (P = 0.033). In the long-term study, mean 25-hydroxyvitamin D levels increased from 15 ± 8 to 19 ± 7 ng/ml (P < 0.0001) in subjects receiving 1,400 IU/wk and from 15 ± 7 to 36 ± 22 ng/ml (P < 0.0001) in the group receiving 14,000 IU/wk. No subject developed vitamin D intoxication. Conclusion: Vitamin D3 at doses equivalent to 2000 IU/d for 1 yr is safe in adolescents and results in desirable vitamin D levels. PMID:18445674

  10. A simultaneous quantitative method for vitamins A, D and E in human serum using liquid chromatography-tandem mass spectrometry.

    PubMed

    Albahrani, Ali A; Rotarou, Victor; Roche, Peter J; Greaves, Ronda F

    2016-05-01

    Non-classical roles of fat-soluble vitamins (FSVs) in many pathologies including cancer have been identified. There is also evidence of hormonal interactions between two of these vitamins, A and D. As a result of this enhanced clinical association with disease, translational clinical research and laboratory requests for FSV measurement has significantly increased. However there are still gaps in the analytical methods available for the measurement of these vitamins. This study aimed to develop a method for simultaneous quantification of 25-hydroxyvitamin-D2 (25-OHD2), 25-hydroxyvitamin-D3 (25-OHD3) and its 3-epimer (epi-25-OHD3), retinol and α-tocopherol in human serum using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The procedure was developed and validated across two LC-MS/MS platforms, using commercial calibrators referenced to certified reference materials, controls, and deuterated internal standards. The samples were prepared by liquid-liquid extraction prior to injection and LC separation (using a Pursuit-PFP column) on two Agilent MS/MS systems (6410 and 6490) in electrospray ionisation positive mode with multiple reaction monitoring. Identification and quantification of 25-OHD3 from its 3-epimer as well as 25-OHD2, retinol and α-tocopherol were achieved. The dynamic ranges were 4-160 nmol/L for 25-OHD2 and epi-25-OHD3, 4-200 nmol/L for 25-OHD3, 0.1-4.0μmol/L for retinol and 4-70μmol/L for α-tocopherol with correlation (r(2)) of 0.997-0.998. Based on participation in an external quality assurance program, the overall performance of the simultaneous methods were: imprecision (CV%) and inaccuracy (average bias) 3.0% and 3.2 nmol/L, respectively, for 25-OHD3; 5.0% and 0.04μmol/L, respectively, for retinol; and 4.7% and 0.2μmol/L, respectively, for α-tocopherol. In summary, two simple LC-MS/MS methods were successfully developed and validated for the simultaneous quantification of the three vitamin D metabolites (25-OHD2, 25-OHD3 and 3

  11. Circulating 25-Hydroxyvitamin D, IRS1 Variant rs2943641, and Insulin Resistance: Replication of a Gene–Nutrient Interaction in 4 Populations of Different Ancestries

    PubMed Central

    Zheng, Ju-Sheng; Parnell, Laurence D.; Smith, Caren E.; Lee, Yu-Chi; Jamal-Allial, Aziza; Ma, Yiyi; Li, Duo; Tucker, Katherine L.; Ordovás, José M.; Lai, Chao-Qiang

    2014-01-01

    BACKGROUND Associations of either insulin receptor substrate 1 (IRS1) variants or circulating 25-hydroxyvitamin D [25(OH)D] with type 2 diabetes (T2D) and insulin resistance (IR) are inconsistent. This study sought to determine whether circulating 25(OH)D modulates the association of a potentially functional variant at IRS1 (rs2943641) with insulin resistance. METHOD Interaction between IRS1 rs2943641 and circulating 25(OH)D on homeostasis model assessment for IR (HOMA-IR) was examined in the Boston Puerto Rican Health Study (BPRHS) (n = 1144). Replication was performed in the African-American (n = 1126), non-Hispanic white (n = 1967), and Hispanic (n = 1241) populations of the Multi-Ethnic Study of Atherosclerosis (MESA) with genotypes of 3 IRS1 variants, rs2972144, rs1515104, and rs2673142, which are tag single nucleotide polymorphisms (SNPs) and in strong linkage disequilibrium with rs2943641. RESULTS Higher circulating 25(OH)D was associated with lower risk of T2D and IR in BPRHS women homozygous for minor allele rs2943641T. Consistently, in each of 3 MESA populations, HOMA-IR and insulin decreased more evidently with higher circulating 25(OH)D in women of the rs2943641TT genotype than in carriers of the major allele (rs2943641C). Metaanalysis indicated significant and consistent interactions between circulating 25(OH)D and IRS1 variants on HOMA-IR (log transformed) [pooled β = −0.008, 95% CI: −0.016 to −0.001, P interaction = 0.004] and insulin (log transformed) (pooled β = −0.006, 95% CI: −0.011 to −0.002, P interaction = 0.023) in 3065 women of the 4 populations. CONCLUSIONS Participants with different genotypes of IRS1 rs2943641 exhibit differential benefit from high circulating 25(OH)D for the reduction of insulin resistance and T2D risk. This gene–nutrient interaction, which appears to be limited to women, warrants further examination in randomized controlled trials of vitamin D supplementation. PMID:24255076

  12. Evidence for threshold effects of 25-hydroxyvitamin D on glucose tolerance and insulin resistance in black and white obese postmenopausal women.

    PubMed

    Sorkin, John D; Vasaitis, Tadas Sean; Streeten, Elizabeth; Ryan, Alice S; Goldberg, Andrew P

    2014-05-01

    We identified normal vs. abnormal 25-hydroxyvitamin D [25(OH)D] concentrations by examining the relation of 25(OH)D to non-bone-related measures (plasma glucose, insulin resistance, lipids, blood pressure, fitness, obesity, and regional adiposity) and asking whether there is a 25(OH)D concentration above and below which the relation between 25(OH)D and outcome changes. We examined the relation between 25(OH)D and outcome by race to see whether race-specific normal ranges are needed, and we examined the role of insulin-like growth factor-1 (IGF-1) in modulating the relation between 25(OH)D and outcome. In a cross-sectional study of 239 overweight and obese, sedentary postmenopausal women without diabetes (83 black, 156 white), outcome measures included plasma lipids, glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), IGF-1, parathyroid hormone (PTH), aerobic fitness, body composition, subcutaneous abdominal and visceral fat, and blood pressure. We identified threshold effects in the association between 25(OH)D and these variables using piecewise linear regressions. We found that 25(OH)D was inversely related to fasting glucose, fasting and 2-h insulin, HOMA-IR, visceral abdominal fat, percentage fat, PTH, and triglycerides. Evidence for a threshold effect of 25(OH)D was found for 2-h glucose, 2-h insulin, fasting insulin, and HOMA-IR. There was no evidence suggesting the need for race-specific normal 25(OH)D concentrations. IGF-1 modulated the relation between 25(OH)D and outcome but only below, and not above, a threshold 25(OH)D concentration. Our findings suggest a threshold effect of 25(OH)D on glucose-insulin metabolism such that 25(OH)D ≥ ∼26 μg/L (65.0 pmol/L) supports normal glucose homeostasis and that the same cut point defining normal 25(OH)D concentration can be used in black and white women. This study was registered at clinicaltrials.gov as NCT01798030. PMID:24717362

  13. Evidence for Threshold Effects of 25-Hydroxyvitamin D on Glucose Tolerance and Insulin Resistance in Black and White Obese Postmenopausal Women12

    PubMed Central

    Sorkin, John D.; Vasaitis, Tadas Sean; Streeten, Elizabeth; Ryan, Alice S.; Goldberg, Andrew P.

    2014-01-01

    We identified normal vs. abnormal 25-hydroxyvitamin D [25(OH)D] concentrations by examining the relation of 25(OH)D to non-bone–related measures (plasma glucose, insulin resistance, lipids, blood pressure, fitness, obesity, and regional adiposity) and asking whether there is a 25(OH)D concentration above and below which the relation between 25(OH)D and outcome changes. We examined the relation between 25(OH)D and outcome by race to see whether race-specific normal ranges are needed, and we examined the role of insulin-like growth factor-1 (IGF-1) in modulating the relation between 25(OH)D and outcome. In a cross-sectional study of 239 overweight and obese, sedentary postmenopausal women without diabetes (83 black, 156 white), outcome measures included plasma lipids, glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), IGF-1, parathyroid hormone (PTH), aerobic fitness, body composition, subcutaneous abdominal and visceral fat, and blood pressure. We identified threshold effects in the association between 25(OH)D and these variables using piecewise linear regressions. We found that 25(OH)D was inversely related to fasting glucose, fasting and 2-h insulin, HOMA-IR, visceral abdominal fat, percentage fat, PTH, and triglycerides. Evidence for a threshold effect of 25(OH)D was found for 2-h glucose, 2-h insulin, fasting insulin, and HOMA-IR. There was no evidence suggesting the need for race-specific normal 25(OH)D concentrations. IGF-1 modulated the relation between 25(OH)D and outcome but only below, and not above, a threshold 25(OH)D concentration. Our findings suggest a threshold effect of 25(OH)D on glucose–insulin metabolism such that 25(OH)D ≥ ∼26 μg/L (65.0 pmol/L) supports normal glucose homeostasis and that the same cut point defining normal 25(OH)D concentration can be used in black and white women. This study was registered at clinicaltrials.gov as NCT01798030. PMID:24717362

  14. Low Circulating 25-Hydroxyvitamin D Concentrations Are Associated with Defects in Insulin Action and Insulin Secretion in Persons with Prediabetes12

    PubMed Central

    Abbasi, Fahim; Blasey, Christine; Feldman, David; Caulfield, Michael P; Hantash, Feras M; Reaven, Gerald M

    2015-01-01

    Background: Individuals with prediabetes mellitus (PreDM) and low circulating 25-hydroxyvitamin D [25(OH)D] are at increased risk of type 2 diabetes mellitus (T2DM). Objective: We aimed to determine whether low 25(OH)D concentrations are associated with defects in insulin action and insulin secretion in persons with PreDM. Methods: In this cross-sectional study, we stratified 488 nondiabetic subjects as having PreDM or normal fasting glucose (NFG) and a 25(OH)D concentration ≤20 ng/mL (deficient) or >20 ng/mL (sufficient). We determined insulin resistance by steady state plasma glucose (SSPG) concentration and homeostasis model assessment of insulin resistance (HOMA-IR) and insulin secretion by homeostasis model assessment of β-cell function (HOMA-β). We compared insulin resistance and secretion measures in PreDM and NFG groups; 25(OH)D-deficient and 25(OH)D-sufficient groups; and PreDM-deficient, PreDM-sufficient, NFG-deficient, and NFG-sufficient subgroups, adjusting for age, sex, race, body mass index, multivitamin use, and season. Results: In the PreDM group, mean SSPG concentration and HOMA-IR were higher and mean HOMA-β was lower than in the NFG group (P < 0.001 for all comparisons). In the 25(OH)D-deficient group, mean SSPG concentration was higher (P < 0.001), but neither mean HOMA-IR nor HOMA-β was significantly different from that in the 25(OH)D-sufficient group. In the PreDM-deficient subgroup, mean (95% CI) SSPG concentration was higher (P < 0.01) than in the PreDM-sufficient, NFG-deficient, and NFG-sufficient subgroups [192 (177–207) mg/dL vs. 166 (155–177) mg/dL, 148 (138–159) mg/dL, and 136 (127–144) mg/dL, respectively]. Despite greater insulin resistance, mean HOMA-β was not significantly higher in the PreDM-deficient subgroup than in the PreDM-sufficient, NFG-deficient, and NFG-sufficient subgroups [98 (85–112) vs. 91 (82–101), 123 (112–136), and 115 (106–124), respectively]. Conclusion: Subjects with PreDM and low

  15. Low 25-Hydroxyvitamin D Concentrations Predict Incident Depression in Well-Functioning Older Adults: The Health, Aging, and Body Composition Study

    PubMed Central

    Sink, Kaycee M.; Tooze, Janet A.; Atkinson, Hal H.; Cauley, Jane A.; Yaffe, Kristine; Tylavsky, Frances A.; Rubin, Susan M.; Simonsick, Eleanor M.; Kritchevsky, Stephen B.; Houston, Denise K.

    2015-01-01

    Background. Cross-sectional studies suggest that low 25-hydroxyvitamin D (25[OH]D) may be a risk factor for depression; however, there are few prospective studies. We examined the association between 25(OH)D and depressive symptoms in community-dwelling persons aged 70–79 years in the Health, Aging, and Body Composition (Health ABC) Study (n = 2598). Methods. Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression Scale (CES-D) at baseline and 2-, 3- and 4-year follow-up. Serum 25(OH)D was measured at 1-year follow-up and categorized as <20, 20–<30, and ≥30 ng/mL. Mixed models were used to examine change in CES-D scores according to 25(OH)D categories. The association between 25(OH)D categories and incident depression (CES-D short score ≥10 or antidepressant medication use) were assessed using Cox proportional hazards models. Analyses were adjusted for socio-demographic and behavioral characteristics, season, and chronic conditions. Results. Thirty-three percent of participants had 25(OH)D <20ng/mL. Serum 25(OH)D was not associated with CES-D scores at baseline (p = .51); however, CES-D scores increased over time and were significantly associated with 25(OH)D at 2-year (p = .003) and 4-year follow-up (p < .001). Among 2,156 participants free of depression at the 1-year follow-up, the cumulative incidence of depression was 26.9%. Participants with 25(OH)D <20ng/mL were at greater risk of developing depression (HR [95% CI]: 1.65 [1.23–2.22]) over 4 years of follow-up compared with those with 25(OH)D ≥30ng/mL. Conclusion. Low 25(OH)D was independently associated with a greater increase in depressive symptom scores and incident depression in community-dwelling older adults. PMID:25326643

  16. Impact of Circulating Vitamin D Binding Protein Levels on the Association Between 25-Hydroxyvitamin D and Pancreatic Cancer Risk: A Nested Case-Control Study

    PubMed Central

    Weinstein, Stephanie J.; Stolzenberg-Solomon, Rachael Z.; Kopp, William; Rager, Helen; Virtamo, Jarmo; Albanes, Demetrius

    2012-01-01

    High concentrations of circulating 25-hydroxyvitamin D [25(OH)D] have been associated with elevated pancreatic cancer risk. As this is contrary to an expected inverse association between vitamin D status and cancer, we examined whether vitamin D binding protein (DBP), the primary carrier of vitamin D compounds in circulation, plays a role in this relationship. Prediagnostic serum DBP and 25(OH)D were studied in relation to risk of pancreatic cancer in a nested case-control study of 234 pancreatic cancer cases and 234 controls in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression, and statistical tests were two-sided. We found that DBP and 25(OH)D were correlated (r=0.27; p<0.0001), and DBP was inversely associated with pancreatic cancer risk (OR=0.66, 95% CI=0.39–1.12, for the highest vs. lowest quartile; p-trend=0.02). Importantly, this association appeared to have a threshold between quartiles 2–4 and quartile 1, and was primarily evident among men with concurrent high 25(OH)D concentrations (OR=0.33, 95% CI=0.16–0.70 for highest vs. lowest quartile; p-trend=0.002), with no association in men with lower serum 25(OH)D (OR=1.28, 95% CI=0.62–2.61 for highest vs. lowest quartile, p-trend 0.63, p-interaction= 0.01). Men with higher 25(OH)D concentrations and serum DBP below the median showed greatly elevated risk of pancreatic cancer (OR=5.01, 95% CI 2.33–10.78, for highest vs. lowest quartile; p-trend < 0.0001), while risk was weakly inversely associated with serum 25(OH)D when DBP concentrations were higher (p-interaction = 0.001). Taken together, our findings indicate that higher DBP concentrations may sequester more 25(OH)D and reduce free 25(OH)D bioavailability. Simultaneous examination of DBP and 25(OH)D may be important in determining the association of vitamin D with cancer risk. PMID:22232734

  17. The Importance of Body Weight for the Dose Response Relationship of Oral Vitamin D Supplementation and Serum 25-Hydroxyvitamin D in Healthy Volunteers

    PubMed Central

    Ekwaru, John Paul; Zwicker, Jennifer D.; Holick, Michael F.; Giovannucci, Edward; Veugelers, Paul J.

    2014-01-01

    Unlike vitamin D recommendations by the Institute of Medicine, the Clinical Practice Guidelines by the Endocrine Society acknowledge body weight differentials and recommend obese subjects be given two to three times more vitamin D to satisfy their body's vitamin D requirement. However, the Endocrine Society also acknowledges that there are no good studies that clearly justify this. In this study we examined the combined effect of vitamin D supplementation and body weight on serum 25-hydroxyvitamin (25(OH)D) and serum calcium in healthy volunteers. We analyzed 22,214 recordings of vitamin D supplement use and serum 25(OH)D from 17,614 healthy adult volunteers participating in a preventive health program. This program encourages the use of vitamin D supplementation and monitors its use and serum 25(OH)D and serum calcium levels. Participants reported vitamin D supplementation ranging from 0 to 55,000 IU per day and had serum 25(OH)D levels ranging from 10.1 to 394 nmol/L. The dose response relationship between vitamin D supplementation and serum 25(OH)D followed an exponential curve. On average, serum 25(OH)D increased by 12.0 nmol/L per 1,000 IU in the supplementation interval of 0 to 1,000 IU per day and by 1.1 nmol/L per 1,000 IU in the supplementation interval of 15,000 to 20,000 IU per day. BMI, relative to absolute body weight, was found to be the better determinant of 25(OH)D. Relative to normal weight subjects, obese and overweight participants had serum 25(OH)D that were on average 19.8 nmol/L and 8.0 nmol/L lower, respectively (P<0.001). We did not observe any increase in the risk for hypercalcemia with increasing vitamin D supplementation. We recommend vitamin D supplementation be 2 to 3 times higher for obese subjects and 1.5 times higher for overweight subjects relative to normal weight subjects. This observational study provides body weight specific recommendations to achieve 25(OH)D targets. PMID:25372709

  18. Associations of maternal 25-hydroxyvitamin D in pregnancy with offspring cardiovascular risk factors in childhood and adolescence: findings from the Avon Longitudinal Study of Parents and Children

    PubMed Central

    Williams, Dylan M; Fraser, Abigail; Fraser, William D; Hyppönen, Elina; Davey Smith, George; Deanfield, John; Hingorani, Aroon; Sattar, Naveed; Lawlor, Debbie A

    2013-01-01

    Objective Lower maternal vitamin D status in pregnancy may be associated with increased offspring cardiovascular risk in later life, but evidence for this is scant. We examined associations of maternal total 25-hydroxyvitamin D (25(OH)D) in pregnancy with offspring cardiovascular risk factors assessed in childhood and adolescence. Design A longitudinal, prospective study. Setting The study was based on data from mother–offspring pairs in the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK prospective population-based birth cohort (N=4109). Outcome measures Offspring cardiovascular risk factors were measured in childhood (mean age 9.9 years) and in adolescence (mean age 15.4 years): blood pressure, lipids, apolipoproteins (at 9.9 years only), glucose and insulin (at 15.4 years only), C reactive protein (CRP), and interleukin 6 (at 9.9 years only) were measured. Results After adjustments for potential confounders (maternal age, education, body mass index (BMI), smoking, physical activity, parity, socioeconomic position, ethnicity, and offspring gestational age at 25(OH)D sampling; gender, age, and BMI at outcome assessment), maternal 25(OH)D was inversely associated with systolic blood pressure (−0.48 mm Hg difference per 50 nmol/L increase in 25(OH)D; 95% CI −0.95 to −0.01), Apo-B (−0.01 mg/dL difference; 95% CI −0.02 to −0.001), and CRP (−6.1% difference; 95% CI −11.5% to −0.3%) at age 9.9 years. These associations were not present for risk factors measured at 15.4 years, with the exception of a weak inverse association with CRP (−5.5% difference; 95% CI −11.4% to 0.8%). There was no strong evidence of associations with offspring triglycerides, glucose or insulin. Conclusions Our findings suggest that fetal exposure to 25(OH)D is unlikely to influence cardiovascular risk factors of individuals later in life. PMID:24125739

  19. Serum 25-Hydroxyvitamin D Concentrations ≥40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study

    PubMed Central

    McDonnell, Sharon L.; Baggerly, Carole; French, Christine B.; Baggerly, Leo L.; Garland, Cedric F.; Gorham, Edward D.; Lappe, Joan M.; Heaney, Robert P.

    2016-01-01

    Background Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with a lower risk of multiple cancer types across a range of 25(OH)D concentrations. Objectives To investigate whether the previously reported inverse association between 25(OH)D and cancer risk could be replicated, and if a 25(OH)D response region could be identified among women aged 55 years and older across a broad range of 25(OH)D concentrations. Methods Data from two cohorts representing different median 25(OH)D concentrations were pooled to afford a broader range of 25(OH)D concentrations than either cohort alone: the Lappe cohort (N = 1,169), a randomized clinical trial cohort (median 25(OH)D = 30 ng/ml) and the GrassrootsHealth cohort (N = 1,135), a prospective cohort (median 25(OH)D = 48 ng/ml). Cancer incidence over a multi-year period (median: 3.9 years) was compared according to 25(OH)D concentration. Kaplan-Meier plots were developed and the association between 25(OH)D and cancer risk was examined with multivariate Cox regression using multiple 25(OH)D measurements and spline functions. The study included all invasive cancers excluding skin cancer. Results Age-adjusted cancer incidence across the combined cohort (N = 2,304) was 840 cases per 100,000 person-years (1,020 per 100,000 person-years in the Lappe cohort and 722 per 100,000 person-years in the GrassrootsHealth cohort). Incidence was lower at higher concentrations of 25(OH)D. Women with 25(OH)D concentrations ≥40 ng/ml had a 67% lower risk of cancer than women with concentrations <20 ng/ml (HR = 0.33, 95% CI = 0.12–0.90). Conclusions 25(OH)D concentrations ≥40 ng/ml were associated with substantial reduction in risk of all invasive cancers combined. PMID:27049526

  20. Association between cord blood 25-hydroxyvitamin D concentrations and respiratory tract infections in the first 6 months of age in a Korean population: a birth cohort study (COCOA)

    PubMed Central

    Shin, Youn Ho; Yu, Jinho; Kim, Kyung Won; Ahn, Kangmo; Hong, Seo-Ah; Lee, Eun; Yang, Song-I; Jung, Young-Ho; Kim, Hyung Young; Seo, Ju-Hee; Kwon, Ji-Won; Kim, Byoung-Ju; Kim, Hyo-Bin; Shim, Jung Yeon; Kim, Woo Kyung; Song, Dae Jin; Lee, So-Yeon; Lee, Soo Young; Jang, Gwang Cheon; Suh, Dong In; Yang, Hyeon-Jong; Kim, Bong Sung; Choi, Suk-Joo; Oh, Soo-Young; Kwon, Ja-Young; Lee, Kyung-Ju; Park, Hee Jin; Lee, Pil Ryang; Won, Hye-Sung

    2013-01-01

    Purpose Previous studies suggest that the concentration of 25-hydroxyvitamin D [25(OH)D] in cord blood may show an inverse association with respiratory tract infections (RTI) during childhood. The aim of the present study was to examine the influence of 25(OH)D concentrations in cord blood on infant RTI in a Korean birth cohort. Methods The levels of 25(OH)D in cord blood obtained from 525 Korean newborns in the prospective COhort for Childhood Origin of Asthma and allergic diseases were examined. The primary outcome variable of interest was the prevalence of RTI at 6-month follow-up, as diagnosed by pediatricians and pediatric allergy and pulmonology specialists. RTI included acute nasopharyngitis, rhinosinusitis, otitis media, croup, tracheobronchitis, bronchiolitis, and pneumonia. Results The median concentration of 25(OH)D in cord blood was 32.0 nmol/L (interquartile range, 21.4 to 53.2). One hundred and eighty neonates (34.3%) showed 25(OH)D concentrations less than 25.0 nmol/L, 292 (55.6%) showed 25(OH)D concentrations of 25.0-74.9 nmol/L, and 53 (10.1%) showed concentrations of ≥75.0 nmol/L. Adjusting for the season of birth, multivitamin intake during pregnancy, and exposure to passive smoking during pregnancy, 25(OH)D concentrations showed an inverse association with the risk of acquiring acute nasopharyngitis by 6 months of age (P for trend=0.0004). Conclusion The results show that 89.9% of healthy newborns in Korea are born with vitamin D insufficiency or deficiency (55.6% and 34.3%, respectively). Cord blood vitamin D insufficiency or deficiency in healthy neonates is associated with an increased risk of acute nasopharyngitis by 6 months of age. More time spent outdoors and more intensified vitamin D supplementation for pregnant women may be needed to prevent the onset of acute nasopharyngitis in infants. PMID:24244212

  1. Evaluation of Vitamin D Standardization Program protocols for standardizing serum 25-hydroxyvitamin D data: a case study of the program's potential for national nutrition and health surveys12345

    PubMed Central

    Cashman, Kevin D; Kiely, Mairead; Kinsella, Michael; Durazo-Arvizu, Ramón A; Tian, Lu; Zhang, Yue; Lucey, Alice; Flynn, Albert; Gibney, Michael J; Vesper, Hubert W; Phinney, Karen W; Coates, Paul M; Picciano, Mary F; Sempos, Christopher T

    2013-01-01

    Background: The Vitamin D Standardization Program (VDSP) has developed protocols for standardizing procedures of 25-hydroxyvitamin D [25(OH)D] measurement in National Health/Nutrition Surveys to promote 25(OH)D measurements that are accurate and comparable over time, location, and laboratory procedure to improve public health practice. Objective: We applied VDSP protocols to existing ELISA-derived serum 25(OH)D data from the Irish National Adult Nutrition Survey (NANS) as a case-study survey and evaluated their effectiveness by comparison of the protocol-projected estimates with those from a reanalysis of survey serums by using liquid chromatography–tandem mass spectrometry (LC–tandem MS). Design: The VDSP reference system and protocols were applied to ELISA-based serum 25(OH)D data from the representative NANS sample (n = 1118). A reanalysis of 99 stored serums by using standardized LC–tandem MS and resulting regression equations yielded predicted standardized serum 25(OH)D values, which were then compared with LC–tandem MS reanalyzed values for all serums. Results: Year-round prevalence rates for serum 25(OH)D concentrations <30, <40, and <50 nmol/L were 6.5%, 21.9%, and 40.0%, respectively, via original ELISA measurements and 11.4%, 25.3%, and 43.7%, respectively, when VDSP protocols were applied. Differences in estimates at <30- and <40-nmol/L thresholds, but not at the <50-nmol/L threshold, were significant (P < 0.05). A reanalysis of all serums by using LC–tandem MS confirmed prevalence estimates as 11.2%, 27.2%, and 45.0%, respectively. Prevalences of serum 25(OH)D concentrations >125 nmol/L were 1.2%, 0.3%, and 0.6% by means of ELISA, VDSP protocols, and LC–tandem MS, respectively. Conclusion: VDSP protocols hold a major potential for national nutrition and health surveys in terms of the standardization of serum 25(OH)D data. PMID:23615829

  2. Sustained Increase of 25-Hydroxyvitamin D Levels in Healthy Young Women during Wintertime after Three Suberythemal UV Irradiations—The MUVY Pilot Study

    PubMed Central

    Biersack, Maria Gudrun; Hajdukiewicz, Malgorzata; Uebelhack, Ralf; Franke, Leonora; Piazena, Helmut; Klaus, Pascal; Höhne-Zimmer, Vera; Braun, Tanja; Buttgereit, Frank; Burmester, Gerd-Rüdiger; Detert, Jacqueline

    2016-01-01

    Objectives Vitamin D (VitD) deficiency is a health problem prevalent not only in the elderly but also in young adults. The primary objective of our observational pilot study “MUVY” (Mood, UVR, Vitamin D in Young women) was to test both the short-term and long-term effects of a series of three suberythemal UV radiation (UVR) exposures on the VitD status and well-being of young healthy women during winter in a repeat measure design. Methods 20 healthy young women (Fitzpatrick skin types I–III, aged 21–25 years) received three full body broad band UVR exposures with an escalating erythemally weighted dose schedule during one week in winter, and completed self-report questionnaires monitoring symptoms of depression (Beck Depression Inventory, BDI) and affective state/well-being (Profile of Mood States, POMS) at baseline and three days after the last UVR exposure. 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured in serum at baseline, and at study days 8, 36 and 50. Results Mean baseline 25(OH)D level was 54.3 nmol/L (standard deviation (s.d.) = 24.1), with seven women having VitD deficient status. Relevant symptoms of depression, as indicated by low BDI total scores (0–8), were absent. After the three UVR exposures the increment of 25(OH)D was an average of 13.9 nmol/L (95% confidence interval (CI) = 9.4–18.4) and 26.2 pmol/L (95%CI = 7.2–45.1) for 1,25(OH)2D. Δ25(OH)D, and corresponding baseline levels were significantly and inversely associated (rho = -0.493, p = 0.027). Only 25(OH)D remained significantly increased above baseline for at least six weeks after the last UVR exposure. A strong inverse correlation of the POMS subscale “Vigor/Activity” and the increment in 1,25(OH)2D was found (rho = -0.739, p<0.001) at day 8. Conclusions Three suberythemal whole body UVR exposures during one week are a simple and suitable method for improving 25(OH)D levels during winter, for at least six weeks, and especially in

  3. Both serum 25-hydroxyvitamin D and calcium levels may increase the risk of incident prostate cancer in Caribbean men of African ancestry

    PubMed Central

    Jackson, Maria D; Tulloch-Reid, Marshall K; Lindsay, Carole M; Smith, Garrett; Bennett, Franklyn I; McFarlane-Anderson, Norma; Aiken, William; Coard, Kathleen C M

    2015-01-01

    Circulating 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with both higher and lower risk of prostate cancer (PCa), whereas elevated levels of circulating calcium has been related to higher risks. However, there are few studies that account for effects of both calcium and 25(OH)D concentrations on incident PCa in a black population. We examined these relationships in a case–control study of men 40–80 years old with newly diagnosed, histologically confirmed PCa in Jamaica, a tropical country. Mean serum calcium concentrations was higher among cases (2.32 ± 0.19 mmol/L) than controls, (2.27 ± 0.30 mmol/L) (P = 0.023) however, there were no differences in 25(OH)D by cancer status (cases, 33.67 ± 12.71 ng/mL; controls (32.25 ± 12.59 ng/mL). Serum calcium was not correlated with 25(OH)D (partial correlation: r, 0.06; P = 0.287). Multivariable-adjusted models showed a positive linear relationship between PCa and serum calcium (OR, 1.12; CI, 1.00–1.25 per 0.1 nmol/L). Serum 25(OH)D concentration also showed a positive association with PCa (OR, 1.23; CI, 1.01–1.49 per 10 ng/mL). The odds of PCa in men with serum 25(OH)D tertile 2 was OR, 2.18; CI, 1.04–4.43 and OR, 2.47 CI, 1.20–4.90 for tertile 3 (Ptrend = 0.013). Dietary intakes of calcium showed no relationship with PCa. Despite the strong relationship between serum calcium and vitamin D the mechanism by which each affects prostate cancer risk in men of African ancestry needs additional investigation. PMID:25858172

  4. Sequential sampling and analysis of renal hydroxylase activities of cattle given 1 alpha-hydroxyvitamin D3.

    PubMed

    Littledike, E T; Engstrom, G W; Sachs, M

    1986-04-01

    A new method was developed for sequential sampling of bovine renal cortex. This method results in minimum hemorrhage and adhesions and provides sufficient renal cortex tissue for assay of 25-hydroxyvitamin D 1 alpha-, 24-, and 23-hydroxylase activities. Application of this procedure in calves and pregnant cows treated with 1 alpha-hydroxyvitamin D3 is described. The success of these experiments suggests these techniques could be used to follow enzyme activities that control crucial aspects of vitamin D metabolism in normal peripartum cows and cows with milk fever or other diseases of mineral metabolism. PMID:3722540

  5. Use of 1 alpha-hydroxyvitamin D3 in prevention of bovine parturient paresis. 8. Maternal and neonatal plasma calcium, parathyroid hormone, and vitamin D metabolites concentrations.

    PubMed

    Bar, A; Striem, S; Perlman, R; Sachs, M

    1988-10-01

    Thirteen Israeli Friesian cows (3.71 average calvings) in the second or later lactation, fed a daily diet containing 90 g of Ca and 50 g of P, were injected once intramuscularly with 700 micrograms 1 alpha-hydroxy-vitamin D3 in order to investigate its placental transfer and its subsequent metabolism in the neonate. The injection of the vitamin 96 to 24 h before calving slightly increased plasma Ca at parturition, whereas uninjected controls displayed a prominent hypo-calcemia. On the 10th and 20th d after calving, difference in the plasma Ca concentration of the two groups was not significant. At parturition, plasma parathyroid hormone concentration was significantly higher and plasma 1,25-dihydroxyvitamin D lower in the control than in the treated cows. At parturition the plasma concentrations of Ca, parathyroid hormone, hydroxyproline, and 24,25-hydroxyvitamin D were higher in the calves than in their dams. Plasma concentrations of 25-hydroxyvitamin D were markedly higher and 1,25-hydroxyvitamin D was slightly higher in cows than in their offsprings. PMID:3204189

  6. SUMMER AND WINTER VITAMIN D3 LEVELS IN FOUR LEMUR SPECIES HOUSED AT A BRITISH ZOO, WITH REFERENCE TO UVB LEVELS.

    PubMed

    Killick, Rowena; Saunders, Richard; Redrobe, Sharon P

    2015-09-01

    Serum samples were collected from 18 lemurs of four diurnal/cathemeral species housed with outdoor access at Bristol Zoo Gardens (United Kingdom) to test 25-hydroxy-vitamin D3 (25OHD3) levels as part of the veterinary department's preventative health care program. Samples were collected from each lemur in August 2008 (summer) and January 2009 (winter) to examine the effect of season on 25OHD3 levels. The lemurs were fed commercial primate food and a range of fruit and vegetables, and dietary levels of vitamin D3 remained the same throughout the study period. Statistical analysis showed that the lemurs' summer 25OHD3 values (range 26.7 to >150.0 μg/L) were significantly higher than their winter 25OHD3 values (range 11.4-87.1 μg/L). UVB measurements taken during the study period confirmed that UVB levels were significantly higher in summer (mean reading for 1200-1300 GMT time period 153.8 μW/cm2) compared to winter (mean reading for 1200-1300 GMT time period 19.4 μW/cm2). The 25OHD3 levels measured were generally found to be high compared to previously published values from wild (free-ranging) lemurs in Madagascar. The most likely explanation for this was the higher vitamin D3 content of the captive lemurs' diet, as UVB levels at the zoo (latitude 51° north) are substantially lower than those that occur in Madagascar (latitude 12°-26° south). No evidence of vitamin D toxicity or deficiency was found in any of the captive lemurs. The results indicate that vitamin D3 levels in lemurs housed with outdoor access in the United Kingdom and by extension, other regions of similar latitude, vary with seasonal environmental UVB levels, in a similar way to the seasonal variations in vitamin D3 observed in humans living in these regions, but that vitamin D levels in this captive lemur population were adequate compared to wild lemur levels, even in winter. PMID:26352953

  7. Association of polymorphisms in the vitamin D receptor gene and serum 25-hydroxyvitamin D levels in children with autism spectrum disorder.

    PubMed

    Coşkun, Salih; Şimşek, Şeref; Camkurt, Mehmet Akif; Çim, Abdullah; Çelik, Sercan Bulut

    2016-08-22

    Vitamin D is implicated in several aspects of human physiology, and polymorphisms in the vitamin D receptor gene (VDR) are associated with a variety of neuropsychiatric disorders. The aims of this study are to determine whether VDR polymorphisms are associated with autism spectrum disorder (ASD), to examine serum 25-hydroxyvitamin D (25(OH)D) levels in ASD, and to explore whether VDR polymorphisms influence serum 25(OH)D levels. We investigated 480 subjects (237 children with ASD and 243 healthy controls) for the following VDR polymorphisms: TaqI, BsmI, FokI, ApaI, and Cdx2.Within the same samples, 25(OH)D levels were available only for 85 patients and 82 controls. The Cdx-2 variation was shown to deviate from Hardy-Weinberg equilibrium in the controls and was therefore excluded from the study. We found that the frequency of rare FokI TT, TaqI CC, and BsmI AA genotypes differed significantly between children with ASD and the controls (p=0.042, p=0.016, p=0.038, respectively). After correction for multiple testing, only the TaqI CC genotype remained significant. Further analysis using a recessive model showed that rare genotypes of these polymorphisms were significantly higher in patients compared to controls (p=0.045, p=0.005 and p=0.031, respectively). However, no significant association was found between ApaI and ASD. We found serum 25(OH)D levels to be significantly higher in children with ASD (p<0.001) and that the FokI polymorphism had an effect on serum 25(OH)D levels in children with ASD (p=0.041). Additionally, we found the haplotype GTTT (BsmI/TaqI/FokI/ApaI) conferred an increased risk for developing ASD (p=0.022; odds ratio [95% confidence interval]=2.322 [1.105-4.879]). This is the first clinical study evaluating the association between serum 25(OH)D levels and VDR polymorphisms in children with ASD. Our results demonstrated a significant association between TaqI, BsmI, and FokI polymorphisms and ASD and showed for the first time that FokI polymorphisms

  8. Barriers to optimizing vitamin D3 intake for the elderly.

    PubMed

    Heaney, Robert P

    2006-04-01

    Available data on metabolic utilization of vitamin D3 indicate a total daily requirement of approximately 4000 international units (iu) (100 microg) or twice the current tolerable upper intake level (UL). In young individuals, most of this comes from the skin. However, cutaneous vitamin D3 synthesis declines with age, creating a need for increasing oral intake to maintain optimal serum 25-hydroxyvitamin D [25(OH)D] concentrations. Estimates of the population distribution of serum 25(OH)D values, coupled with available dose-response data, indicate that it would require input of an additional 2600 iu/d (65 microg/d) of oral vitamin D3 to ensure that 97.5% of older women have 25(OH)D values at or above desirable levels. The age-related decline in cutaneous input, taken together with the UL, creates a substantial barrier to the deployment of public health strategies to optimize vitamin D status in the elderly. PMID:16549492

  9. 25-hydroxyvitamin D circulates in different fractions of calf plasma if the parent compound is vitamin D₂ or vitamin D₃, respectively.

    PubMed

    Hymøller, Lone; Jensen, Søren K

    2016-02-01

    Vitamin D has become one of the most discussed nutrients in human nutrition, which has led to an increased interest in milk as a vitamin D source. Problems related to fortifying milk with synthetic vitamin D can be avoided by securing a high content of natural vitamin D in the milk by supplying dairy cows with sufficient vitamin D. However, choosing the most efficient route and form of supplementation requires insight into how different vitamin D metabolites are transported in the body of cattle. There are two forms of vitamin D: vitamin D2 (D2) and vitamin D3 (D3). Vitamin D2 originates from fungi on roughage. Vitamin D3 originates either from endogenous synthesis in the skin or from feed supplements. Vitamin D2 is chemically different from, and less physiologically active than, D3. Endogenous and dietary D3 is chemically similar but dietary D3 is toxic, whereas endogenous D3 appears well regulated in the body. PMID:26608575

  10. Use of 1 alpha-hydroxyvitamin D3 to prevent bovine parturient paresis. VI. Concentrations of vitamin D metabolites and vitamin D3 equivalence in milk.

    PubMed

    Bar, A; Sachs, M; Perlman, R

    1986-11-01

    Concentration of vitamin D metabolites was determined in the milk of control and 1 alpha-hydroxyvitamin D3-injected (700 micrograms) cows that calved 36 to 43 h after treatment. Milk samples were taken 60 h after calving. Concentrations of vitamin D, 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D in milk of the control cows were 372 +/- 24, 264 +/- 68, 68 +/- 26, and 21 +/- 3 ng/L, respectively. Concentrations of vitamin D metabolites in the milk of the treated cows did not differ significantly from those of controls. Concentration of 1 alpha-hydroxyvitamin D3 in milk of treated cows was less than 20 ng/L. In a second experiment, cows were injected twice, at 72-h intervals, with 350 micrograms 1 alpha-hydroxyvitamin D3. Milk was taken 60 h after parturition from cows that calved 37 to 60 h after the second injection. The vitamin D3 equivalence of the milk was 40 +/- 3 IU/L. Results indicate that injection of 700 micrograms 1 alpha-hydroxyvitamin D3 did not affect the concentration of vitamin D metabolites or the vitamin D3 equivalence of milk taken 60 h after calving. PMID:3027149

  11. Increased renal catabolism of 1,25-dihydroxyvitamin D3 in murine X-linked hypophosphatemic rickets.

    PubMed Central

    Tenenhouse, H S; Yip, A; Jones, G

    1988-01-01

    The hypophosphatemic (Hyp) mouse, a murine homologue of human X-linked hypophosphatemic rickets, is characterized by renal defects in brush border membrane phosphate transport and vitamin D3 metabolism. The present study was undertaken to examine whether elevated renal 25-hydroxyvitamin D3-24-hydroxylase activity in Hyp mice is associated with increased degradation of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] by side chain oxidation. Metabolites of 1,25(OH)2D3 were separated by HPLC on Zorbax SIL and identified by comparison with standards authenticated by mass spectrometry. Production of 1,24,25-trihydroxyvitamin D3, 24-oxo-1,25-dihydroxyvitamin D3, and 24-oxo-1,23,25-trihydroxyvitamin D3 was twofold greater in mitochondria from mutant Hyp/Y mice than from normal +/Y littermates. Enzyme activities, estimated by the sum of the three products synthesized per milligram mitochondrial protein under initial rate conditions, were used to estimate kinetic parameters. The apparent Vmax was significantly greater for mitochondria from Hyp/Y mice than from +/Y mice (0.607 +/- 0.064 vs. 0.290 +/- 0.011 pmol/mg per protein per min, mean +/- SEM, P less than 0.001), whereas the apparent Michaelis-Menten constant (Km) was similar in both genotypes (23 +/- 2 vs. 17 +/- 5 nM). The Km for 1,25(OH)2D3 was approximately 10-fold lower than that for 25-hydroxyvitamin D3 [25(OH)D3], indicating that 1,25(OH)2D3 is perhaps the preferred substrate under physiological conditions. In both genotypes, apparent Vmax for 25(OH)D3 was fourfold greater than that for 1,25(OH)2D3, suggesting that side chain oxidation of 25(OH)D3 may operate at pharmacological concentrations of substrate. The present results demonstrate that Hyp mice exhibit increased renal catabolism of 1,25(OH)2D3 and suggest that elevated degradation of vitamin D3 hormone may contribute significantly to the clinical phenotype in this disorder. PMID:3339128

  12. Photoaffinity labeling of human serum vitamin D binding protein and chemical cleavage of the labeled protein: Identification of an 11. 5-kDa peptide containing the putative 25-hydroxyvitamin D sub 3 binding site

    SciTech Connect

    Ray, R.; Holick, M.F. ); Bouillon, R.; Baelen, H.V. )

    1991-07-30

    In this paper, the authors describe photoaffinity labeling and related studies of human serum vitamin D binding protein (hDBP) with 25-hydroxyvitamin D{sub 3} 3{beta}-3{prime}-(N-(4-azido-2-nitrophenyl)amino)propyl ether (25-ANE) and its radiolabeled counterpart, i.e., 25-hydroxyvitamin D{sub 3} 3{beta}-3{prime}-(N-(4-azido-2-nitro-(3,5-{sup 3}H)phenyl)amino)propyl ether ({sup 3}H-25-ANE). They have carried out studies to demonstrate that (1) 25-ANE competes with 25-OH-D{sub 3} for the binding site of the latter in hDBP and (2) {sup 3}H-25-ANE is capable of covalently labeling the hDBP molecule when exposed ot UV light. Treatment of a sample of purified hDBP, labeled with {sup 3}H-25-ANE, with BNPS-skatole produced two Coomassie Blue stained peptide fragments, and the majority of the radioactivity was assoicated with the smaller of the two peptide fragments (16.5 kDa). On the other hand, cleavage of the labeled protein with cyanogen bromide produced a peptide (11.5 kDa) containing most of the covalently attached radioactivity. Considering the primary amino acid structure of hDBP, this peptide fragment (11.5 kDa) represents the N-terminus through residue 108 of the intact protein. Thus, the results tentatively identify this segment of the protein containing the binding pocket for 25-OH-D{sub 3}.

  13. The use of vitamin D3 and its metabolites to improve beef tenderness.

    PubMed

    Foote, M R; Horst, R L; Huff-Lonergan, E J; Trenkle, A H; Parrish, F C; Beitz, D C

    2004-01-01

    Three experiments were conducted to determine whether feeding 25-hydroxyvitamin D3 (25-OH D3) or 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3) improves the tenderness of longissimus dorsi (LD), semimembranosus (SM), and infraspinatus (IF) muscles similar to supplemental vitamin D3 without leaving residual vitamin D3 and its metabolites in muscle. In the first two experiments, 24 crossbred steers were used to determine the effects of different oral amounts of 1,25-(OH)2 D3 (Exp. 1; n = 12) and 25-OH D3 (Exp. 2; n = 12) on plasma Ca2+ concentrations. In the third experiment, crossbred steers were allotted randomly to one of four treatments: 1) control placebo (n = 7); 2) 5 x 10(6) IU of vitamin D3/d (n = 9) for 9 d and harvested 2 d after last treatment; 3) single, 125-mg dose of 25-OH D3 (n = 8) 4 d before harvest; or 4) single, 500-microg dose of 1,25-(OH)2 D3 (n = 9) 3 d before harvest. The LD and SM steaks from each animal were aged for 8, 14, or 21 d, whereas steaks from the IF were aged for 14 or 21 d. All steaks were analyzed for tenderness by Warner-Bratzler shear force and for troponin-T degradation by Western blot analysis. Supplementing steers with vitamin D3 increased (P < 0.01) the concentration of vitamin D3 and 25-OH D3 in all muscles sampled. Feeding steers 25-OH D3 increased (P < 0.05) the concentration of 25-OH D3 in meat, but to an amount less than half that of cattle treated with vitamin D3. Supplemental 1,25-(OH)2 D3 did not affect (P < 0.10) shear force values; however, there was a trend (P < 0.10) for supplemental vitamin D3 and 25-OH D3 to produce LD steaks with lower shear values after 8 and 14 d of aging, and lower (P < 0.10) shear force values for the SM aged for 21 d. Analysis of Western blots indicated that LD steaks from cattle supplemented with vitamin D3 and 25-OH D3 had greater (P < 0.05) troponin-T degradation. Antemortem supplementation of 25-OH D3 seems to increase postmortem proteolysis and tenderness in the LD and SM without

  14. 1alpha,25-dihydroxyvitamin D3 rapidly inhibits fibroblast-induced collagen gel contraction.

    PubMed

    Greiling, D; Thieroff-Ekerdt, R

    1996-06-01

    1alpha,25-Dihydroxyvitamin D3 (1,25-D3) inhibits the proliferation of fibroblasts in vitro in monolayer culture. We investigated the effect of 1,25-D3 on normal murine and human fibroblasts cultured in collagen type I gels, which more closely resembles the in vivo situation in the dermis. In this culture system 1,25-D3 had no effect on fibroblast proliferation; however, the fibroblast-induced collagen gel contraction was inhibited in a time- and concentration-dependent manner in the nanomolar concentration range. 25-Hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 were inactive. 1,25-D3 had no effect in fibroblasts lacking a functional vitamin D receptor. Pretreatment of fibroblasts in monolayer culture for 5 min was sufficient to trigger the inhibition of collagen gel contraction. Nifedipine increased collagen gel contraction and counteracted the effect of 1,25-D3. The inhibition of collagen gel contraction by 1,25-D3 is supposed to be mediated by the vitamin D receptor because a functional vitamin D receptor is required, and vitamin D metabolites with low affinity to the vitamin D receptor were inactive. Brief pretreatment of fibroblasts was sufficient to trigger the inhibitory effect of 1,25-D3, suggesting a nongenomic effect. A genomic mode of action could not be ruled out, however, because the inhibition was first measured after 24 h. The antagonism of the calcium channel antagonist nifedipine probably represents the sum of two opposite effects rather than supporting evidence for a nongenomic mode of action of 1,25-D3. In conclusion, 1,25-D3 has a specific and rapidly triggered inhibitory effect on fibroblast-induced collagen gel contraction. PMID:8752663

  15. Diminished internalization and action of 1,25-dihydroxyvitamin D3 in dermal fibroblasts cultured from New World primates

    SciTech Connect

    Adams, J.S.; Gacad, M.A.; Baker, A.J.; Kheun, G.; Rude, R.K.

    1985-06-01

    We investigated the occurrence of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3)-resistant osteomalacia in the New World primate colony of Saguinus imperator at the Los Angeles Zoo. The mean serum concentration of 1,25-(OH)2D3 was elevated 5-fold in the New World primates compared to that in their Old World counterparts. The specific internalization of 0.6 nM (/sup 3/H)1,25-(OH)2D3 by cultured dermal fibroblasts from New World primates was reduced 75% compared to that by cells from Old World primates or man. The decrease in hormone uptake resulted from a decrease in the number of high affinity intracellular binding sites for 1,25-(OH)2D3 and apparently caused a 90-95% reduction in 1,25-(OH)2D3-induced 25-hydroxyvitamin-D3-24-hydroxylase activity. There was no alteration in the capacity or avidity of New World primate serum for 1,25-(OH)2D3 compared to that of serum from Old World primates. These data suggest that the occurrence of vitamin D-resistant osteomalacia in New World primates is the result of decreased high affinity, receptor-mediated uptake of 1,25-(OH)2D3 by the target cell.

  16. The cytochrome P450scc system opens an alternate pathway of vitamin D3 metabolism

    PubMed Central

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

    2008-01-01

    We show that cytochrome P450scc (CYP11A1) in either a reconstituted system or in isolated adrenal mitochondria can metabolize vitamin D3. The major products of the reaction with reconstituted enzyme were 20-hydroxycholecalciferol and 20,22-dihydroxycholecalciferol, with yields of 16 and 4%, respectively, of the original vitamin D3 substrate. Trihydroxycholecalciferol was a minor product, likely arising from further metabolism of dihydroxycholecalciferol. Based on NMR analysis and known properties of P450scc we propose that hydroxylation of vitamin D3 by P450scc occurs sequentially and stereospecifically with initial formation of 20(S)-hydroxyvitamin D3. P450scc did not metabolize 25-hydroxyvitamin D3, indicating that modification of C25 protected it against P450scc action. Adrenal mitochondria also metabolized vitamin D3 yielding 10 hydroxyderivatives, with UV spectra typical of vitamin D triene chromophores. Aminogluthimide inhibition showed that the three major metabolites, but not the others, resulted from P450scc action. It therefore appears that non-P450scc enzymes present in the adrenal cortex to some extent contribute to metabolism of vitamin D3. We conclude that purified P450scc in a reconstituted system or P450scc in adrenal mitochondria can add one hydroxyl group to vitamin D3 with subsequent hydroxylation being observed for reconstituted enzyme but not for adrenal mitochondria. Additional vitamin D3 metabolites arise from the action of other enzymes in adrenal mitochondria. These findings appear to define novel metabolic pathways involving vitamin D3 that remain to be characterized. PMID:16098191

  17. The cytochrome P450scc system opens an alternate pathway of vitamin D3 metabolism.

    PubMed

    Slominski, Andrzej; Semak, Igor; Zjawiony, Jordan; Wortsman, Jacobo; Li, Wei; Szczesniewski, Andre; Tuckey, Robert C

    2005-08-01

    We show that cytochrome P450scc (CYP11A1) in either a reconstituted system or in isolated adrenal mitochondria can metabolize vitamin D3. The major products of the reaction with reconstituted enzyme were 20-hydroxycholecalciferol and 20,22-dihydroxycholecalciferol, with yields of 16 and 4%, respectively, of the original vitamin D3 substrate. Trihydroxycholecalciferol was a minor product, likely arising from further metabolism of dihydroxycholecalciferol. Based on NMR analysis and known properties of P450scc we propose that hydroxylation of vitamin D3 by P450scc occurs sequentially and stereospecifically with initial formation of 20(S)-hydroxyvitamin D3. P450scc did not metabolize 25-hydroxyvitamin D3, indicating that modification of C25 protected it against P450scc action. Adrenal mitochondria also metabolized vitamin D3 yielding 10 hydroxyderivatives, with UV spectra typical of vitamin D triene chromophores. Aminogluthimide inhibition showed that the three major metabolites, but not the others, resulted from P450scc action. It therefore appears that non-P450scc enzymes present in the adrenal cortex to some extent contribute to metabolism of vitamin D3. We conclude that purified P450scc in a reconstituted system or P450scc in adrenal mitochondria can add one hydroxyl group to vitamin D3 with subsequent hydroxylation being observed for reconstituted enzyme but not for adrenal mitochondria. Additional vitamin D3 metabolites arise from the action of other enzymes in adrenal mitochondria. These findings appear to define novel metabolic pathways involving vitamin D3 that remain to be characterized. PMID:16098191

  18. Kinetic studies of 25-hydroxy-19-nor-vitamin D3 and 1 alpha,25-dihydroxy-19-nor-vitamin D3 hydroxylation by CYP27B1 and CYP24A1.

    PubMed

    Urushino, Naoko; Nakabayashi, Sachie; Arai, Midori A; Kittaka, Atsushi; Chen, Tai C; Yamamoto, Keiko; Hayashi, Keiko; Kato, Shigeaki; Ohta, Miho; Kamakura, Masaki; Ikushiro, Shinichi; Sakaki, Toshiyuki

    2007-09-01

    Our previous study demonstrated that 25-hydroxy-19-nor-vitamin D(3) [25(OH)-19-nor-D(3)] inhibited the proliferation of immortalized noncancerous PZ-HPV-7 prostate cells similar to 1 alpha,25-dihydroxyvitamin D(3) [1 alpha,25(OH)(2)D(3)], suggesting that 25(OH)-19-nor-D(3) might be converted to 1 alpha,25-dihydroxy-19-nor-vitamin D(3) [1 alpha,25(OH)(2)-19-nor-D(3)] by CYP27B1 before exerting its antiproliferative activity. Using an in vitro cell-free model to study the kinetics of CYP27B1-dependent 1 alpha-hydroxylation of 25(OH)-19-nor-D(3) and 25-hydroxyvitamin D(3) [25(OH)D(3)] and CYP24A1-dependent hydroxylation of 1 alpha,25(OH)-19-nor-D(3) and 1 alpha,25(OH)(2)D(3), we found that k(cat)/K(m) for 1 alpha-hydroxylation of 25(OH)-19-nor-D(3) was less than 0.1% of that for 25(OH)D(3), and the k(cat)/K(m) value for 24-hydroxylation was not significantly different between 1 alpha,25(OH)(2)-19-nor-D(3) and 1 alpha,25(OH)(2)D(3). The data suggest a much slower formation and a similar rate of degradation of 1 alpha,25(OH)(2)-19-nor-D(3) compared with 1 alpha,25(OH)(2)D(3). We then analyzed the metabolites of 25(OH)D(3) and 25(OH)-19-nor-D(3) in PZ-HPV-7 cells by high-performance liquid chromatography. We found that a peak that comigrated with 1 alpha,25(OH)(2)D(3) was detected in cells incubated with 25(OH)D(3), whereas no 1 alpha,25(OH)(2)-19-nor-D(3) was detected in cells incubated with 25(OH)-19-nor-D(3). Thus, the present results do not support our previous hypothesis that 25(OH)-19-nor-D(3) is converted to 1 alpha,25(OH)(2)-19-nor-D(3) by CYP27B1 in prostate cells to inhibit cell proliferation. We hypothesize that 25(OH)-19-nor-D(3) by itself may have a novel mechanism to activate vitamin D receptor or it is metabolized in prostate cells to an unknown metabolite with antiproliferative activity without 1 alpha-hydroxylation. Thus, the results suggest that 25(OH)-19-nor-D(3) has potential as an attractive agent for prostate cancer therapy. PMID:17553915

  19. 24R,25-Dihydroxyvitamin D3 Protects against Articular Cartilage Damage following Anterior Cruciate Ligament Transection in Male Rats.

    PubMed

    Boyan, Barbara D; Hyzy, Sharon L; Pan, Qingfen; Scott, Kayla M; Coutts, Richard D; Healey, Robert; Schwartz, Zvi

    2016-01-01

    Osteoarthritis (OA) in humans is associated with low circulating 25-hydroxyvitamin D3 [25(OH)D3]. In vitamin D replete rats, radiolabeled 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] accumulates in articular cartilage following injection of [3H]-25(OH)D3. Previously, we showed that 24R,25(OH)2D3 blocks chondrocyte apoptosis via phospholipase D and p53, suggesting a role for 24R,25(OH)2D3 in maintaining cartilage health. We examined the ability of 24R,25(OH)2D3 to prevent degenerative changes in articular cartilage in an OA-like environment and the potential mechanisms involved. In vitro, rat articular chondrocytes were treated with IL-1β with and without 24R,25(OH)2D3 or 1α,25(OH)2D3. 24R,25(OH)2D3 but not 1α,25(OH)2D3 blocked the effects of IL-1β in a dose-dependent manner, and its effect was partially mediated through the TGF-β1 signaling pathway. In vivo, unilateral anterior cruciate ligament transections were performed in immunocompetent rats followed by intra-articular injections of 24R,25(OH)2D3 or vehicle (t = 0, 7, 14, 21 days). Tissues were harvested on day 28. Joints treated with vehicle had changes typical of OA whereas joints treated with 24R,25(OH)2D3 had less articular cartilage damage and levels of inflammatory mediators. These results indicate that 24R,25(OH)2D3 protects against OA, and suggest that it may be a therapeutic approach for preventing trauma-induced osteoarthritis. PMID:27575371

  20. Biological activities of 2alpha-substituted analogues of 1alpha,25-dihydroxyvitamin D3 in transcriptional regulation and human promyelocytic leukemia (HL-60) cell proliferation and differentiation.

    PubMed

    Takahashi, Eiji; Nakagawa, Kimie; Suhara, Yoshitomo; Kittaka, Atsushi; Nihei, Ken-ichi; Konno, Katsuhiro; Takayama, Hiroaki; Ozono, Keiichi; Okano, Toshio

    2006-11-01

    Biological activities of 2alpha-substituted 1alpha,25-dihydroxyvitamin D3 analogues were evaluated in vitro. Their binding affinity was examined with calf thymus cytosolic vitamin D receptor (VDR) and rat plasma vitamin D-binding protein (DBP). In addition, the transcriptional activity of the analogues was measured using a rat 25-hydroxyvitamin D3-24-hydroxylase gene promoter, a human osteocalcin gene promoter, and VDR-GAL4 system. This study investigated the biological activities of 2alpha-substituted analogues in comparison with 2beta-substitued analogues at the molecular level, with regard to the structural differences of alkyl, hydroxyalkyl, hydroxyalkoxy substituents at the 2-position of 1alpha,25-dihydroxyvitamin D3. PMID:17077522

  1. Incidence rate of type 2 diabetes is >50% lower in GrassrootsHealth cohort with median serum 25-hydroxyvitamin D of 41 ng/ml than in NHANES cohort with median of 22 ng/ml.

    PubMed

    McDonnell, S L; Baggerly, L L; French, C B; Heaney, R P; Gorham, E D; Holick, M F; Scragg, R; Garland, C F

    2016-01-01

    Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with lower risk of type 2 diabetes. This study compared incidence rates of type 2 diabetes among participants aged ≥20 years in two U.S. cohorts with markedly different median 25(OH)D concentrations. The median 25(OH)D concentration in the GrassrootsHealth (GRH) cohort was 41 ng/ml (N=4933) while in the 2005-6 National Health and Nutrition Examination Survey (NHANES) it was 22 ng/ml (N=4078) (P<0.0001). The adjusted annual incidence rate of type 2 diabetes was 3.7 per 1000 population (95% confidence interval=1.9, 6.6) in the GRH cohort, compared to 9.3 per 1000 population (95% confidence interval=6.7, 12.6) in NHANES. In the NHANES cohort, the lowest 25(OH)D tertiles (<17, 17-24 ng/ml) had higher odds of developing diabetes than the highest tertile (OR: 4.9, P=0.02 and 4.8, P=0.01 respectively), adjusting for covariates. Differences in demographics and methods may have limited comparability. Raising serum 25(OH)D may be a useful tool for reducing risk of diabetes in the population. PMID:26151742

  2. Benzothiadiazole (BTH) activates sterol pathway and affects vitamin D3 metabolism in Solanum malacoxylon cell cultures.

    PubMed

    Burlini, Nedda; Iriti, Marcello; Daghetti, Anna; Faoro, Franco; Ruggiero, Antonietta; Bernasconi, Silvana

    2011-11-01

    Benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH), a particularly efficient inducer of systemic acquired resistance (SAR), was developed as an immunizing agent to sensitize various crop species against pathogen infections. Recent works highlighted its activating effect on different metabolic pathways, concerning both primary and secondary metabolites. In this study, we investigated the effect of BTH treatment on sterol levels and vitamin D(3) metabolism in Solanum malacoxylon cultures. Calli of S. malacoxylon were incubated in Gamborg B5 liquid medium alone or added with 50 μM BTH for different times (one, two or three cycles of light). Histocytochemical investigations performed on our experimental system using 3,3'-diaminobenzidine (DAB) for hydrogen peroxide (H(2)O(2)) detection and phloroglucinol for lignin staining showed that BTH causes H(2)O(2) accumulation and lignin deposition in treated calli. Gas chromatographic analysis of principal cell membrane sterols (β-sitosterol, campesterol, stigmasterol) showed that BTH transiently increases their cellular levels. Callus cultures were found to contain also cholesterol, 7-dehydrocholesterol, the putative precursor of vitamin D(3), and the hydroxylated metabolites 25-hydroxyvitamin D(3) [25(OH)D(3)] and 1α,25-dihydroxyvitamin D(3) [1α,25(OH)(2)D(3)]. BTH treatment enhanced 7-dehydrocholesterol while reduced cholesterol. HPLC analysis of sample extracts showed that BTH does not affect the cell content of vitamin D(3), though results of ELISA tests highlighted that this elicitor moderately enhances the levels of 25(OH)D(3) and 1α,25(OH)(2)D(3) metabolites. In conclusion, BTH treatment not only causes cell wall strengthening, a typical plant defence response, as just described in other experimental models, but in the same time increases the cellular level of the main sterols and 7-dehydrocholesterol. PMID:21779826

  3. Dietary supplementation with high doses of regular vitamin D3 safely reduces diabetes incidence in NOD mice when given early and long term.

    PubMed

    Takiishi, Tatiana; Ding, Lei; Baeke, Femke; Spagnuolo, Isabella; Sebastiani, Guido; Laureys, Jos; Verstuyf, Annemieke; Carmeliet, Geert; Dotta, Francesco; Van Belle, Tom L; Gysemans, Conny A; Mathieu, Chantal

    2014-06-01

    High doses of the active form of vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], prevent diabetes in the NOD mouse but also elicit unwanted calcemic side effects. Because immune cells themselves can convert vitamin D3 into 1,25(OH)2D3 locally, we hypothesized that dietary vitamin D3 can also prevent disease. Thus, we evaluated whether dietary administration of high doses of regular vitamin D3 (800 IU/day) during different periods of life (pregnancy and lactation, early life [3-14 weeks of age], or lifelong [3-35 weeks of age]) safely prevents diabetes in NOD mice. We found that only lifelong treatment raised serum 25-hydroxyvitamin D3 from 173 nmol/L in controls to 290 nmol/L, without inducing signs of calcemic or bone toxicity, and significantly reduced diabetes development in both male and female NOD mice. This diabetes protection by vitamin D3 correlated with preserved pancreatic insulin content and improved insulitis scores. Moreover, vitamin D3 treatment decreased interferon-γ-positive CD8(+) T cells and increased CD4(+)(CD25(+))FoxP3(+) T cells in pancreatic draining lymph nodes. In conclusion, this study shows for the first time that high doses of regular dietary vitamin D3 can safely prevent diabetes in NOD mice when administered lifelong, although caution is warranted with regards to administering equivalently high doses in humans. PMID:24550187

  4. Influence of blanketing and season on vitamin D and parathyroid hormone, calcium, phosphorus, and magnesium concentrations in horses in New Zealand.

    PubMed

    Azarpeykan, S; Dittmer, K E; Gee, E K; Marshall, J C; Wallace, J; Elder, P; Acke, E; Thompson, K G

    2016-07-01

    The aims of the study were to determine the effect of season and blanketing on vitamin D synthesis in horses and examine the interaction between vitamin D and other analytes involved in calcium homeostasis. Twenty-one healthy horses at pasture were included; 5 were covered with standard horse blankets including neck rugs. Blood samples were collected for 13 mo and analyzed for 25-hydroxyvitamin D2 (25OHD2) and 25-hydroxyvitamin D3 (25OHD3), 1,25-dihydroxyvitamin D (1,25[OH]2D), ionized calcium (iCa), total calcium (tCa), phosphorus (P), total magnesium (tMg), and parathyroid hormone (PTH). Grass and hay samples were collected and analyzed for vitamin D, calcium, phosphorus, and magnesium. Climate data were also collected. The serum concentration of 25OHD3 in horses was either undetectable or below the detection limit of the assay, and the main form of 25OHD was 25OHD2. No differences in serum 25OHD2, 1,25(OH)2D, iCa, tCa, P, tMg, and PTH (P ≥ 0.05) concentrations were seen between the 2 groups. Associations were seen between iCa and PTH (P < 0.05), iCa and tMg (P < 0.05), and dietary vitamin D and 25OHD2 (P < 0.05). A strong seasonal trend was seen in serum 25OHD2 (P < 0.0001), which was higher during spring and summer when the amount of sunshine and UV radiation was higher. Parathyroid hormone and 1,25(OH)2D showed opposing trends with PTH higher in winter whereas 1,25(OH)2D was higher in summer. The results suggest that dietary vitamin D may be necessary for horses to fulfill their vitamin D requirements; however, further research is required to determine the contribution of vitamin D3 synthesis in the skin to the vitamin D status of the horse. PMID:27131337

  5. Metabolism of vitamin D3 in human osteoblasts: evidence for autocrine and paracrine activities of 1 alpha,25-dihydroxyvitamin D3.

    PubMed

    Atkins, Gerald J; Anderson, Paul H; Findlay, David M; Welldon, Katie J; Vincent, Cristina; Zannettino, Andrew C W; O'Loughlin, Peter D; Morris, Howard A

    2007-06-01

    Circulating 1 alpha,25-dihydroxyvitamin D(3) (1,25D) derives from renal conversion of 25-hydroxyvitamin D(3) (25D), by the 25D 1 alpha-hydroxylase (CYP27B1). Blood 25D levels, but not 1,25D levels, are the best indicator of vitamin D status and predict fracture risk in the elderly. We examined the extent to which osteoblasts can metabolize 25D. Well-characterized human primary osteoblasts and osteosarcoma (OS) cell lines were examined for the expression and regulation of genes associated with vitamin D metabolism, using real-time PCR. Primary osteoblasts and OS cell lines were found to express CYP27B1 mRNA and secreted detectable 1,25D in response to 25D. Of the OS cell lines tested, HOS expressed the most CYP27B1 mRNA and secreted the highest levels of 1,25D. All osteoblastic cells examined up-regulated expression of the catabolic regulator of 1,25D, the 25-hydroxyvitamin D-24-hydroxylase (CYP24), when incubated with either 1,25D or 25D. Exposure to physiological levels of 25D resulted in up-regulated transcription of the 1,25D responsive genes, osteocalcin (OCN), osteopontin (OPN) and RANKL. Specific knockdown of CYP27B1 in HOS cells using siRNA resulted in up to 80% reduction in both 1,25D secretion and the transcription of OCN and CYP24, strongly implying that the 25D effect in osteoblasts is preceded by conversion to 1,25D. Incubation with 25D, like 1,25D, inhibited primary osteoblast proliferation and promoted in vitro mineralization. Finally, we detected expression by osteoblasts of receptors for vitamin D binding protein (DBP), cubilin and megalin, suggesting that osteoblasts are able to internalize DBP-25D complexes in vivo. Together, our results suggest that autocrine, and perhaps paracrine, pathways of vitamin D(3) metabolism may regulate key osteoblast functions independently of circulating, kidney derived 1,25D. Our results are therefore consistent with the reported benefits of maintaining a healthy vitamin D status in the elderly to reduce the risk of

  6. Sequestration and microsomal C-25 hydroxylation of (/sup 3/H)-vitamin D3 by the rat liver

    SciTech Connect

    Gascon-Barre, M.; Elbaz, H.; Therrien-Ferland, D.

    1985-03-01

    A study of the vitamin D3 (D3) 25-hydroxylase was undertaken in an in vivo-in vitro model. (/sup 3/H)-D3 (0.7, 1.0, 10, or 100 nmol/100 g of body weight) was injected into the portal vein and the liver was excised 18 seconds later. The liver homogenate was then submitted to differential centrifugation and the amount of (/sup 3/H)-D3 incorporated in the subcellular fractions was evaluated. The microsomal fraction was also incubated in vitro and the appearance of (/sup 3/H)-25-hydroxyvitamin D3 (25(OH)D3) was determined by high performance liquid chromatography (HPLC). Results showed that the fractional liver (/sup 3/H)-D3 uptake varied between 37 percent and 48 percent of the dose injected. The intracellular distribution of (/sup 3/H)-D3 showed that most of the vitamin was incorporated into the microsomal fraction (45% to 50% of the intracellular (/sup 3/H)-D3) except at the highest dose of (/sup 3/H)-D3 where the cytosolic fraction contained the highest amount (56.4%) of the incorporated vitamin. Mathematical analysis of the intracellular (/sup 3/H)-D3 distribution showed that the microsomal fraction was the only subcellular fraction that was found to incorporate (/sup 3/H)-D3 in relation to the total liver uptake of the vitamin. The apparent Michaelis-Menten kinetics of the (/sup 3/H)-D3-25-hydroxylase showed that with substrate concentration of up to 88.5 nM, the apparent Km and Vmax were 28.2 nM and 25.8 fentomoles (fmol) X min-1 X mg microsomal pro-1, respectively, but the reaction lost considerable efficiency with higher substrate concentrations.

  7. Vitamin D(3) synthesis in the entire skin surface of dairy cows despite hair coverage.

    PubMed

    Hymøller, L; Jensen, S K

    2010-05-01

    How hair-coated animals such as dairy cows synthesize endogenous vitamin D(3) during exposure to summer sunlight has been unclear since vitamin D(3) and its relation to sunlight was discovered. The fur of fur-bearing animals is thought to be comparable to clothing in humans, which prevents vitamin D(3) synthesis in the skin during exposure to sunlight. Different scenarios have been suggested but never tested in cows; for example, that vitamin D(3) is synthesized from sebum on the hair and ingested by cows during grooming or that body areas such as the udder and muzzle that have scant hair exclusively produce the vitamin. To test different scenarios, 16 Danish Holstein dairy cows were subjected to 4 degrees of coverage of their bodies with fabric that prevented vitamin D(3) synthesis in the covered skin areas. The treatments were horse blanket (cows fitted with horse blankets), udder cover (cows fitted with udder covers, horse blanket+udder cover (cows fitted with both horse blankets and udder covers), and natural (cows without any coverage fitted). The cows were let out to pasture daily between 1000 and 1500h for 4 wk in July and August 2009. Blood samples were collected 15 times during the study and analyzed for content of 25-hydroxyvitamin D(3) [25(OH)D(3)] indicative of the animals' vitamin D(3) status. Results showed that uncovered cows had a higher 25(OH)D(3) concentration in plasma after 28 d of access to sunlight compared with covered cows and that the plasma concentration of 25(OH)D(3) was strongly inversely correlated to the body surface area covered. These results are consistent with findings in humans, wherein the vitamin D(3) status of different individuals was inversely proportional to the amount of clothing worn during exposure to artificial sunlight. Hence, it appears that human clothing and cow hair are not comparable with respect to prevention of vitamin D(3) synthesis and that cows, like humans, synthesize vitamin D(3) evenly over their body

  8. In vitro biological activities of a series of 2 beta-substituted analogues of 1 alpha,25-dihydroxyvitamin D3.

    PubMed

    Tsugawa, N; Nakagawa, K; Kurobe, M; Ono, Y; Kubodera, N; Ozono, K; Okano, T

    2000-01-01

    Biological activities of a series of 2beta-substituted analogues of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] were evaluated in vitro in terms of their binding affinity with regard to calf thymus cytosolic vitamin D receptor (VDR) and rat plasma vitamin D-binding protein (DBP). Additionally, reporter gene luciferase activities using either a rat 25-hydroxyvitamin D3-24-hydroxylase gene promoter, including two vitamin D-responsive elements (VDREs), in transfected rat osteoblast-like ROS17/2.8 cells, or a human VDR-GAL4 modified two-hybrid system in transfected human epitheloid carcinoma, cervix HeLa cells were examined. Binding affinity for VDR, transactivation potency on the target gene and VDR-mediated gene regulation of the hydroxyalkyl and hydroxyalkoxy 2beta-substituted analogues were almost comparable to those of 1alpha,25(OH)2D3, while the alkyl and alkenyl analogues were much less active than 1alpha,25(OH)2D3. This study investigated the biological evaluation of a series of 2beta-substituted analogues at the molecular level, with regard to the structural differences of alkyl, alkenyl, hydroxyalkyl, hydroxyalkoxy, alkoxy, hydroxy and chloro substituents at the 2beta-position of 1alpha,25(OH)2D3. PMID:10706413

  9. Cdx-2 polymorphism in Vitamin D Receptor gene was associated with serum 25-hydroxyvitamin D levels, bone mineral density and fracture in middle-aged and elderly Chinese women.

    PubMed

    Ling, Yan; Lin, Huandong; Aleteng, Qiqige; Ma, Hui; Pan, Baishen; Gao, Jian; Gao, Xin

    2016-05-15

    The aim of the current study was to examine the relationship between Cdx-2 polymorphism in the promoter region of the VDR gene and serum 25-hydroxyvitamin D (25(OH)D) levels, bone mineral density (BMD) and fracture in Chinese population. This was a cross-sectional study, which included 738 individuals (428 women and 310 men) aged 45 years or older. In women, the association of Cdx-2 polymorphism with serum 25(OH)D levels was significant adjusting for age, BMI, estimated glomerular filtration rate, menopausal status and season of blood collection (P = 0.002). Cdx-2 polymorphism was associated with lumbar spine BMD adjusted for age, BMI, menopausal status and serum 25(OH)D in women (P = 0.005). But it was not associated with femoral neck BMD or total hip BMD in women. In women, Cdx-2 polymorphism was also associated with fracture adjusted for age, BMI, menopausal status, serum 25(OH)D and total hip BMD (P = 0.03). Carriers of AA and AG genotypes was associated with a higher odds of fracture compared with the carriers of GG genotype (OR = 2.14, 95% CI 1.04-4.42 and OR = 1.90, 95% CI 1.03-3.51). In men, Cdx-2 polymorphism was not associated with serum 25(OH)D levels, BMD or fracture. Our results indicate that the association of Cdx-2 polymorphism in the VDR gene with serum 25(OH)D levels, BMD and fracture may have sex differences. Cdx-2 polymorphism in the VDR gene may affect the serum 25(OH)D concentrations and the risk of osteoporosis and fracture in middle-aged and elderly Chinese women. PMID:26970179

  10. Diabetes prevalence is associated with serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in US middle-aged Caucasian men and women: a cross-sectional analysis within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

    PubMed

    Brock, Kaye E; Huang, Wen-Yi; Fraser, David R; Ke, Liang; Tseng, Marilyn; Mason, Rebecca S; Stolzenberg-Solomon, Rachael Z; Freedman, D Michal; Ahn, Jiyoung; Peters, Ulrike; McCarty, Catherine; Hollis, Bruce W; Ziegler, Regina G; Purdue, Mark P; Graubard, Barry I

    2011-08-01

    Hypovitaminosis D may be associated with diabetes, hypertension and CHD. However, because studies examining the associations of all three chronic conditions with circulating 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) are limited, we examined these associations in the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (n 2465). Caucasian PLCO participants selected as controls in previous nested case-control studies of 25(OH)D and 1,25(OH)(2)D were included in this analysis. Diabetes, CHD and hypertension prevalence, risk factors for these conditions and intake of vitamin D and Ca were collected from a baseline questionnaire. Results indicated that serum levels of 25(OH)D were low (< 50 nmol/l) in 29 % and very low (< 37 nmol/l) in 11 % of subjects. The prevalence of diabetes, hypertension and CHD was 7, 30 and 10 %, respectively. After adjustment for confounding by sex, geographical location, educational level, smoking history, BMI, physical activity, total dietary energy and vitamin D and Ca intake, only diabetes was significantly associated with lower 25(OH)D and 1,25(OH)(2)D levels. Caucasians who had 25(OH)D ≥ 80 nmol/l were half as likely to have diabetes (OR 0·5 (95 % CI 0·3, 0·9)) compared with those who had 25(OH)D < 37 nmol/l. Those in the highest quartile of 1,25(OH)(2)D (≥ 103 pmol/l) were less than half as likely to have diabetes (OR 0·3 (95 % CI 0·1, 0·7)) than those in the lowest quartile (< 72 pmol/l). In conclusion, the independent associations of 25(OH)D and 1,25(OH)(2)D with diabetes prevalence in a large population are new findings, and thus warrant confirmation in larger, prospective studies. PMID:21736838

  11. The association of circulating 25-hydroxyvitamin D and calcium with cognitive performance in adolescents: cross-sectional study using data from the third National Health and Nutrition Examination Survey.

    PubMed

    Tolppanen, Anna-Maija; Williams, Dylan; Lawlor, Debbie A

    2011-01-01

    Studies in middle- and older-aged adults have shown positive associations between serum levels of 25-hydroxyvitamin D [25(OH)D] and cognitive function. Higher serum calcium levels have been associated with greater cognitive decline in older adults. There have been relatively few studies of the associations of 25(OH)D and calcium with cognitive function in adolescents. We investigated the cross sectional association between circulating levels of 25(OH)D and pH-normalised calcium with different domains of cognitive function (block design and digit span components from Wechsler Intelligence Scale for Children-revised and reading and mathematics subtests of Wide-range Achievement Test-revised) in adolescents (age 12-16.9 years) of the third National Health and Nutrition Examination Survey (NHANES III). Serum 25(OH)D was positively associated with performance in all four cognitive tests (e.g. 1 standard deviation (SD) change in digit span score per 1SD in 25(OH)D was 0.10 [95% confidence interval 0.03, 0.16]), but the association was attenuated to the null after adjusting for ethnicity/race and language used in test (1SD change in digit span per 1SD in 25(OH)D after adjusting for self-reported race/ethnicity and language used in test was 0.01[-0.06, 0.09]). pH-normalised calcium levels were not associated with any of the cognitive domains and adjustment for serum calcium levels did not alter the association between 25(OH)D and cognitive function. Thus, we found no evidence that the serum levels of 25(OH)D or calcium were associated with cognitive function in adolescents. A positive association of 25(OH)D with cognitive function was completely explained by confounding due to race/ethnicity. PMID:21133971

  12. Pro-inflammatory signaling by 24,25-dihydroxyvitamin D3 in HepG2 cells.

    PubMed

    Wehmeier, Kent; Onstead-Haas, Luisa M; Wong, Norman C W; Mooradian, Arshag D; Haas, Michael J

    2016-08-01

    The vitamin D metabolite 24,25-dihydroxyvitamin D3 (24, 25[OH]2D3) was shown to induce nongenomic signaling pathways in resting zone chondrocytes and other cells involved in bone remodeling. Recently, our laboratory demonstrated that 24,25-[OH]2D3 but not 25-hydroxyvitamin D3, suppresses apolipoprotein A-I (apo A-I) gene expression and high-density lipoprotein (HDL) secretion in hepatocytes. Since 24,25-[OH]2D3 has low affinity for the vitamin D receptor (VDR) and little is known with regard to how 24,25-[OH]2D3 modulates nongenomic signaling in hepatocytes, we investigated the capacity of 24,25-[OH]2D3 to activate various signaling pathways relevant to apo A-I synthesis in HepG2 cells. Treatment with 24,25-[OH]2D3 resulted in decreased peroxisome proliferator-activated receptor alpha (PPARα) expression and retinoid-X-receptor alpha (RXRα) expression. Similarly, treatment of hepatocytes with 50 nM 24,25-[OH]2D3 for 1-3 h induced PKCα activation as well as c-jun-N-terminal kinase 1 (JNK1) activity and extracellular-regulated kinase 1/2 (ERK1/2) activity. These changes in kinase activity correlated with changes in c-jun phosphorylation, an increase in AP-1-dependent transcriptional activity, as well as repression of apo A-I promoter activity. Furthermore, treatment with 24,25-[OH]2D3 increased IL-1β, IL-6, and IL-8 expression by HepG2 cells. These observations suggest that 24,25-[OH]2D3 elicits several novel rapid nongenomic-mediated pro-inflammatory protein kinases targeting AP1 activity, increasing pro-inflammatory cytokine expression, potentially impacting lipid metabolism and hepatic function. PMID:27234962

  13. 1,25(OH)2D3 Deficiency Induces Colon Inflammation via Secretion of Senescence-Associated Inflammatory Cytokines.

    PubMed

    Liu, Yun; Chen, Lulu; Zhi, Chunchun; Shen, Ming; Sun, Weiwei; Miao, Dengshun; Yuan, Xiaoqin

    2016-01-01

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

  14. Use of 24-F-1,25-dihydroxyvitamin D3 to prevent parturient paresis in dairy cows.

    PubMed

    Goff, J P; Horst, R L; Beitz, D C; Littledike, E T

    1988-05-01

    Forty-one aged Jersey cows were fed a high Ca diet prior to parturition to predispose them to parturient paresis. Twenty-one of the cows were treated with 24-F-1,25-dihydroxyvitamin D3, a synthetic analogue of 1,25-dihydroxyvitamin D3, 7 d before the expected parturition. Treated cows received either 100 micrograms (n = 7) or 150 micrograms (n = 14) of 24-F-1,25-dihydroxyvitamin D3, intramuscularly at 7-d intervals until the cow calved. Incidence of parturient paresis among untreated animals was 85% (17/20). Injections of 100 micrograms of 24-F-1,25-dihydroxyvitamin D3 reduced the incidence of parturient paresis to 43% (3/7), whereas 150 micrograms injections of 24-F-1,25-dihydroxyvitamin D3 reduced the incidence of parturient paresis to 29% (4/14). Plasma concentrations of hydroxyproline were not elevated prior to parturition in 24-F-1,25-dihydroxyvitamin D3-treated cows, indicating that treatment did not stimulate bone resorption and that the ability of 24-F-1,25-dihydroxyvitamin D3 to prevent parturient paresis likely resides in its ability to stimulate intestinal Ca absorption prior to parturition. Further, cows treated with 24-F-1,25-dihydroxyvitamin D3 that developed parturient paresis had lower than normal plasma concentrations of 1,25-dihydroxyvitamin D, indicating that 24-F-1,25-dihydroxyvitamin D3 treatment impairs the metabolism of 25-hydroxyvitamin D in response to hypocalcemia. These data suggest that injection of 24-F-1,25-dihydroxyvitamin D3, delivered at 7-d intervals prior to parturition, can effectively reduce incidence of parturient paresis in dairy cows. PMID:3397418

  15. Effect of 1,25-dihydroxyvitamin D3 on phospholipid metabolism in cultured bovine parathyroid cells.

    PubMed

    Sugimoto, T; Ritter, C; Slatopolsky, E; Morrissey, J

    1988-06-01

    There is evidence that 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] affects phospholipid metabolism of intestine, kidney, and bone. There are no such studies concerning the parathyroid gland, which is also a target tissue for 1,25-(OH)2D3. In this investigation we examined the effect of 1,25-(OH)2D3 on the incorporation of radiolabeled choline, inositol, serine, and ethanolamine into the phospholipids of cultured bovine parathyroid cells. Treatment with 10(-8) M 1,25-(OH)2D3 for 48 h caused a significant decrease in [14C]choline incorporation, although there were no differences in the incorporation of radiolabeled inositol, serine, or ethanolamine. Time-course and dose-response evaluations of the 1,25-(OH)2D3 effect revealed that the decrease in [14C]choline incorporation was seen within 12 h of incubation and occurred with as little as 10(-9) M, respectively. In contrast, neither 10(-7) M 25-hydroxyvitamin D3 nor 10(-7) M 24,25-(OH)2D3 caused significant changes in [14C]choline incorporation. When 5 X 10(-6) M cycloheximide was added to the medium, the inhibitory effect of 1,25-(OH)2D3 on [14C]choline incorporation was completely abolished. A significant decrease in phosphatidylcholine content was observed after treatment with 10(-8) M 1,25-(OH)2D3 for 96 h. 1,25-(OH)2D3 did not cause a dramatic change in the fatty acid composition of the phosphatidylcholine. The present studies demonstrate that in parathyroid cells 1,25-(OH)2D3 causes a decrease in [14C]choline incorporation, which could be due to a decrease in the synthesis of phosphatidylcholine or increased degradation. This effect is specific for 1,25-(OH)2D3 and requires new protein synthesis. PMID:3131114

  16. 1α,25-Dihydroxyvitamin D3 Regulates Mitochondrial Oxygen Consumption and Dynamics in Human Skeletal Muscle Cells.

    PubMed

    Ryan, Zachary C; Craig, Theodore A; Folmes, Clifford D; Wang, Xuewei; Lanza, Ian R; Schaible, Niccole S; Salisbury, Jeffrey L; Nair, K Sreekumaran; Terzic, Andre; Sieck, Gary C; Kumar, Rajiv

    2016-01-15

    Muscle weakness and myopathy are observed in vitamin D deficiency and chronic renal failure, where concentrations of the active vitamin D3 metabolite, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), are low. To evaluate the mechanism of action of 1α,25(OH)2D3 in skeletal muscle, we examined mitochondrial oxygen consumption, dynamics, and biogenesis and changes in expression of nuclear genes encoding mitochondrial proteins in human skeletal muscle cells following treatment with 1α,25(OH)2D3. The mitochondrial oxygen consumption rate (OCR) increased in 1α,25(OH)2D3-treated cells. Vitamin D3 metabolites lacking a 1α-hydroxyl group (vitamin D3, 25-hydroxyvitamin D3, and 24R,25-dihydroxyvitamin D3) decreased or failed to increase OCR. 1α-Hydroxyvitamin D3 did not increase OCR. In 1α,25(OH)2D3-treated cells, mitochondrial volume and branching and expression of the pro-fusion protein OPA1 (optic atrophy 1) increased, whereas expression of the pro-fission proteins Fis1 (fission 1) and Drp1 (dynamin 1-like) decreased. Phosphorylated pyruvate dehydrogenase (PDH) (Ser-293) and PDH kinase 4 (PDK4) decreased in 1α,25(OH)2D3-treated cells. There was a trend to increased PDH activity in 1α,25(OH)2D3-treated cells (p = 0.09). 83 nuclear mRNAs encoding mitochondrial proteins were changed following 1α,25(OH)2D3 treatment; notably, PDK4 mRNA decreased, and PDP2 mRNA increased. MYC, MAPK13, and EPAS1 mRNAs, which encode proteins that regulate mitochondrial biogenesis, were increased following 1α,25(OH)2D3 treatment. Vitamin D receptor-dependent changes in the expression of 1947 mRNAs encoding proteins involved in muscle contraction, focal adhesion, integrin, JAK/STAT, MAPK, growth factor, and p53 signaling pathways were observed following 1α,25(OH)2D3 treatment. Five micro-RNAs were induced or repressed by 1α,25(OH)2D3. 1α,25(OH)2D3 regulates mitochondrial function, dynamics, and enzyme function, which are likely to influence muscle strength. PMID:26601949

  17. Seasonal variation in vitamin D status of beef cattle reared in the central United States

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective was to measure seasonal sunshine associated variation in concentration 25-hydroxyvitamin D (25OHD) in beef cattle. Vitamin D is a key modulator of calcium homeostasis, as well as innate and adaptive immunity. Concentrations of 25OHD reflects vitamin D production/intake and vitamin D s...

  18. Seasonal variation in vitamin D status of beef cattle reared in the midwest and Fed to NRC recommendations.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective was to measure seasonal variation in concentration of circulating 25-hydroxyvitamin D (25OHD) in beef cattle reared in the Midwest and fed to NRC recommendations. The concentration of 25OHD reflects adequacy of vitamin D intake and indicates vitamin D status. Vitamin D is an important ...

  19. A Proposed Molecular Mechanism of High-Dose Vitamin D3 Supplementation in Prevention and Treatment of Preeclampsia

    PubMed Central

    Zabul, Piotr; Wozniak, Michal; Slominski, Andrzej T.; Preis, Krzysztof; Gorska, Magdalena; Korozan, Marek; Wieruszewski, Jan; Zmijewski, Michal A.; Zabul, Ewa; Tuckey, Robert; Kuban-Jankowska, Alicja; Mickiewicz, Wieslawa; Knap, Narcyz

    2015-01-01

    A randomized prospective clinical study performed on a group of 74 pregnant women (43 presenting with severe preeclampsia) proved that urinary levels of 15-F2t-isoprostane were significantly higher in preeclamptic patients relative to the control (3.05 vs. 2.00 ng/mg creatinine). Surprisingly enough, plasma levels of 25-hydroxyvitamin D3 in both study groups were below the clinical reference range with no significant difference between the groups. In vitro study performed on isolated placental mitochondria and placental cell line showed that suicidal self-oxidation of cytochrome P450scc may lead to structural disintegration of heme, potentially contributing to enhancement of oxidative stress phenomena in the course of preeclampsia. As placental cytochrome P450scc pleiotropic activity is implicated in the metabolism of free radical mediated arachidonic acid derivatives as well as multiple Vitamin D3 hydroxylations and progesterone synthesis, we propose that Vitamin D3 might act as a competitive inhibitor of placental cytochrome P450scc preventing the production of lipid peroxides or excess progesterone synthesis, both of which may contribute to the etiopathogenesis of preeclampsia. The proposed molecular mechanism is in accord with the preliminary clinical observations on the surprisingly high efficacy of high-dose Vitamin D3 supplementation in prevention and treatment of preeclampsia. PMID:26068234

  20. A Proposed Molecular Mechanism of High-Dose Vitamin D3 Supplementation in Prevention and Treatment of Preeclampsia.

    PubMed

    Zabul, Piotr; Wozniak, Michal; Slominski, Andrzej T; Preis, Krzysztof; Gorska, Magdalena; Korozan, Marek; Wieruszewski, Jan; Zmijewski, Michal A; Zabul, Ewa; Tuckey, Robert; Kuban-Jankowska, Alicja; Mickiewicz, Wieslawa; Knap, Narcyz

    2015-01-01

    A randomized prospective clinical study performed on a group of 74 pregnant women (43 presenting with severe preeclampsia) proved that urinary levels of 15-F(2t)-isoprostane were significantly higher in preeclamptic patients relative to the control (3.05 vs. 2.00 ng/mg creatinine). Surprisingly enough, plasma levels of 25-hydroxyvitamin D3 in both study groups were below the clinical reference range with no significant difference between the groups. In vitro study performed on isolated placental mitochondria and placental cell line showed that suicidal self-oxidation of cytochrome P450scc may lead to structural disintegration of heme, potentially contributing to enhancement of oxidative stress phenomena in the course of preeclampsia. As placental cytochrome P450scc pleiotropic activity is implicated in the metabolism of free radical mediated arachidonic acid derivatives as well as multiple Vitamin D3 hydroxylations and progesterone synthesis, we propose that Vitamin D3 might act as a competitive inhibitor of placental cytochrome P450scc preventing the production of lipid peroxides or excess progesterone synthesis, both of which may contribute to the etiopathogenesis of preeclampsia. The proposed molecular mechanism is in accord with the preliminary clinical observations on the surprisingly high efficacy of high-dose Vitamin D3 supplementation in prevention and treatment of preeclampsia. PMID:26068234

  1. Optimal vitamin D3 daily intake of 2000IU inferred from modeled solar exposure of ancestral humans in Northern Tanzania.

    PubMed

    Krzyścin, Janusz W; Guzikowski, Jakub; Rajewska-Więch, Bonawentura

    2016-06-01

    Recently, high serum 25-hydroxyvitamin D concentration (~110nmol/L) was found in the Hadza tribe still keeping ancient hunter-gather life style. This level could serve as optimal vitamin D level that was built during millennia of human evolution. The personal vitamin D3 effective solar exposures of the Hadza adults are estimated using radiative model simulations with input from the satellite observations over lake Eyasi (3.7°S, 35.0°E). The calculations are carried out assuming the Hadza typical clothing habits and specific scenarios of the out-door activity comprising early morning and late afternoon working time in sun and prolonged midday siesta in the shade. The modeled doses received by the Hadza are converted to the vitamin D3 effective daily doses pertaining to the lighter skinned persons. We propose a novel formula to get adequate vitamin D level - exposure of 1/3 MED around local noon to 1/3 part of the whole body during warm sub-period of the year in the low- and mid-latitude regions. Such daily solar exposure is equivalent to ~2000IU of vitamin D3 taken orally. For many contemporary humans with limited out-door activity habit achieving such daily norm requires vitamin D3 supplementation of 2000IU throughout the whole year. PMID:27043260

  2. The efficacy of a vitamin D(3) metabolite for improving the myofibrillar tenderness of meat from Bos indicus cattle.

    PubMed

    Lawrence, R W; Doyle, J; Elliott, R; Loxton, I; McMeniman, J P; Norton, B W; Reid, D J; Tume, R W

    2006-01-01

    The influence of a once only administration of a metabolite of vitamin D(3) (HY·D(®)-25-hydroxy vitamin D(3)) on myofibrillar meat tenderness in Australian Brahman cattle was studied. Ninety-six Brahman steers of three phenotypes (Indo-Brazil, US and US/European) and with two previous hormonal growth promotant (HGP) histories (implanted or not implanted with Compudose(®)) were fed a standard feedlot ration for 70d. Treatment groups of 24 steers were offered daily 10g/head HY·D(®) (125mg 25-hydroxyvitamin D(3)) for 6, 4, or 2d before slaughter. One other group of 24 steers was given the basal diet without HY·D(®). Feed lot performance, blood and muscle samples and carcass quality data were collected at slaughter. Calcium, magnesium, potassium, sodium, iron and Vitamin D(3) metabolites were measured in plasma and longissimus dorsi muscle. Warner-Bratzler (WB) shear force (peak force, initial yield) and other objective meat quality measurements were made on the longissimus dorsi muscle of each steer after ageing for 1, 7 and 14d post-mortem at 0-2°C. There were no significant effects of HY·D(®) supplements on average daily gain (ADG, 1.28-1.45kg/d) over the experimental period. HY·D(®) supplements given 6d prior to slaughter resulted in significantly higher (P<0.05) initial yield values compared to supplements given 2d prior to slaughter. Supplementation had no significant effect on meat colour, ultimate pH, sarcomere length, cooking loss, instron compression or peak force. There was a significant treatment (HY·D(®)) by phenotype/HGP interaction for peak force (P=0.028), in which Indo-Brazil steers without previous HGP treatment responded positively (increased tenderness) to HY·D(®) supplements at 2d when compared with Indo-Brazil steers previously given HGP. There were no significant effects of treatment on other phenotypes. HY·D(®) supplements did not affect muscle or plasma concentrations of calcium, potassium or sodium, but did significantly

  3. Modulation of the bovine innate immune response by production of 1alpha,25-dihydroxyvitamin D(3) in bovine monocytes.

    PubMed

    Nelson, C D; Reinhardt, T A; Thacker, T C; Beitz, D C; Lippolis, J D

    2010-03-01

    In cattle, the kidney has been the only known site for production of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] from 25-hydroxyvitamin D(3) [25(OH)D(3)] by 1alpha-hydroxylase (1alpha-OHase). Based on human studies, it was hypothesized that bovine monocytes could produce 1,25(OH)(2)D(3) upon activation and 1,25(OH)(2)D(3) would regulate expression of vitamin D-responsive genes in monocytes. First, the effects of 1,25(OH)(2)D(3) on bovine monocytes isolated from peripheral blood were tested. Treatment of nonstimulated monocytes with 1,25(OH)(2)D(3) increased expression of the gene for the vitamin D 24-hydroxylase (24-OHase) enzyme by 51+/-13 fold, but 1,25(OH)(2)D(3) induction of 24-OHase expression was blocked by lipopolysaccharide (LPS) stimulation. In addition, 1,25(OH)(2)D(3) increased the gene expression of inducible nitric oxide synthase and the chemokine RANTES (regulated upon activation, normal T-cell expressed and secreted) in LPS-stimulated monocytes 69+/-13 and 40+/-12 fold, respectively. Next, the ability of bovine monocytes to express 1alpha-OHase and produce 1,25(OH)(2)D(3) was tested. Activation of monocytes with LPS, tripalmitoylated lipopeptide (Pam3CSK4), or peptidoglycan caused 43+/-9, 17+/-3, and 19+/-3 fold increases in 1alpha-OHase gene expression, respectively. Addition of 25(OH)D(3) to LPS-stimulated monocytes enhanced expression of inducible nitric oxide synthase and RANTES and nitric oxide production in a dose-dependent manner, giving evidence that activated monocytes convert 25(OH)D(3) to 1,25(OH)(2)D(3). In conclusion, bovine monocytes produce 1,25(OH)(2)D(3) in response to toll-like receptor signaling, and 1,25(OH)(2)D(3) production in monocytes increased the expression of genes involved in the innate immune system. Vitamin D status of cattle might be important for optimal innate immune function because 1,25(OH)(2)D(3) production in activated monocytes and subsequent upregulation of inducible nitric oxide synthase and RANTES expression

  4. Supplemental vitamin D3 concentration and biological type of steers. II. Tenderness, quality, and residues of beef.

    PubMed

    Montgomery, J L; King, M B; Gentry, J G; Barham, A R; Barham, B L; Hilton, G G; Blanton, J R; Horst, R L; Galyean, M L; Morrow, K J; Wester, D B; Miller, M F

    2004-07-01

    Vitamin D3 was orally supplemented to determine the supplemental dose that improved beef tenderness in different cattle breed types. Feedlot steers (n = 142) were arranged in a 4 x 3 factorial arrangement consisting of four levels of supplemental vitamin D3 (0, 0.5, 1, and 5 million IU/steer daily) administered for eight consecutive days antemortem using three biological types (Bos indicus, Bos Taurus-Continental, and Bos Taurus-English). Warner-Bratzler shear force (WBSF) was measured at 3, 7, 10, 14, and 21 d postmortem, and trained sensory analysis was conducted at 7 d postmortem on LM, semimembranosus, gluteus medius, and supraspinatus steaks. Concentrations of vitamin D3 and the metabolites 25-hydroxyvitamin D3, and 1,25-dihydroxyvitamin D3 were determined in the LM, liver, kidney, and plasma. Biological type of cattle did not interact (P > 0.10) with vitamin D3 supplementation for sensory or tenderness traits, suggesting that feeding vitamin D3 for 8 d before slaughter affected the different biological types of cattle similarly. Supplementing steers with 0.5, 1, or 5 million IU/(steer(d) decreased (P < 0.05) LM WBSF at 7, 10, 14, and 21 d postmortem compared with controls, and vitamin D3 treatments of 0.5, 1, and 5 million IU decreased (P < 0.05) semimembranosus WBSF at 3, 7, and 14 d postmortem. In general, vitamin D3-induced improvements in WBSF were most consistent and intense in LM steaks. Sensory panel tenderness was improved (P < 0.05) by all vitamin D3 treatments in LM steaks. Sensory traits ofjuiciness, flavor, connective tissue, and off-flavor were not (P > 0.05) affected by vitamin D3 treatments. All vitamin D3 treatments decreased micro-calpain activity and increased muscle Ca concentrations (P < 0.05). Vitamin D3 concentrations were increased (P < 0.05) by supplementation in all tissues tested (liver, kidney, LM, and plasma); however, cooking steaks to 71 degrees C decreased (P < 0.05) treatment residue effects. The vitamin D metabolite 1

  5. Vitamin D3 intake modulates diaphragm but not peripheral muscle force in young mice.

    PubMed

    Ray, Andrew D; Personius, Kirkwood E; Williamson, David L; Dungan, Cory M; Dhillon, Samjot S; Hershberger, Pamela A

    2016-05-15

    Recent data support an important role for vitamin D in respiratory health. We tested the hypothesis that dietary vitamin D3 (VD3) intake modulates diaphragm (DIA) strength. Four-week-old female A/J mice (n = 10/group) were randomized to receive diets containing 100 IU VD3/kg (low), 1,000 IU VD3/kg (reference), or 10,000 IU VD3/kg (pharmacologic). After 6 wk of dietary intervention, plasma 25-hydroxyvitamin D3 (25D3) levels, DIA and extensor digitorum longus (EDL) in vitro contractile properties, and fiber cross-sectional area (CSA) were measured. Myosin heavy chain (MHC) composition and Akt/Foxo3A growth signaling were studied in the DIA and tibialis anterior. Mice fed the low, reference, and pharmacologic diets had average 25D3 levels of 7, 21, and 59 ng/ml, respectively. Maximal DIA force, twitch force, and fiber CSA were reduced 26%, 28%, and 10% (P < 0.01), respectively, in mice receiving the low-VD3 diet compared with the reference and pharmacologic diets. EDL force parameters were unaltered by diet. Effects of VD3 intake on DIA force were not observed in mice that began dietary intervention at 12 wk of age. VD3 intake did not alter the MHC composition of the DIA, indicating that decreases in force and CSA in young mice were not due to a switch in fiber type. Paradoxically, low VD3 intake was associated with activation of anabolic signaling in muscle (hyperphosphorylation of Akt and Foxo3A and decreased expression of autophagy marker LC3). These studies identify a potential role of dietary VD3 in regulating DIA development and insulin sensitivity. PMID:26968027

  6. Short communication: artificial ultraviolet B light exposure increases vitamin D levels in cow plasma and milk.

    PubMed

    Jakobsen, Jette; Jensen, Søren Krogh; Hymøller, Lone; Andersen, Elisabeth Wreford; Kaas, Poul; Burild, Anders; Jäpelt, Rie Bak

    2015-09-01

    The number of dairy cows without access to pasture or sunlight is increasing; therefore, the content of vitamin D in dairy products is decreasing. Ultimately, declining vitamin D levels in dairy products will mean that dairy products are a negligible source of natural vitamin D for humans. We tested the ability of a specially designed UVB lamp to enhance the vitamin D3 content in milk from dairy cows housed indoors. This study included 16 cows divided into 4 groups. Each group was exposed daily to artificial UVB light simulating 1, 2, 3, or 4 h of summer sun at 56°N for 24 d, and the group with simulated exposure to 2 h of summer sun daily continued to be monitored for 73 d. We found a significant increase in 25-hydroxyvitamin D3 (25OHD3) levels in plasma as well as vitamin D3 and 25OHD3 levels in milk after daily exposure for 24 d in all treatment groups. Extending daily exposure to artificial UVB light to 73 d did not lead to an increase of vitamin D3 or 25OHD3 level in the milk. In conclusion, the change in production facilities for dairy cows providing cows with no access to pasture and sunlight causes a decrease of vitamin D levels in dairy products. This decrease may be prevented by exposing cows to artificial UVB light in the stable. PMID:26117346

  7. Vitamin D supplementation in young White and African American women.

    PubMed

    Gallagher, J Christopher; Jindal, Prachi S; Smith, Lynette M

    2014-01-01

    There is limited information on the effects of vitamin D on serum 25 hydroxyvitamin D (25OHD) in young people and none on African Americans. The main objective of this trial was to measure the effect of different doses of vitamin D3 on serum 25OHD and serum parathyroid hormone (PTH) in young women with vitamin D insufficiency (serum 25OHD ≤ 20 ng/mL (50 nmol/L). A randomized double-blind placebo-controlled trial of vitamin D3 was conducted in young white and African American women, age 25 to 45 years. A total of 198 healthy white (60%) and African American (40%) women were randomly assigned to placebo, or to 400, 800, 1600, or 2400 IU of vitamin D3 daily. Calcium supplements were added to maintain a total calcium intake of 1000 to 1200 mg daily. The primary outcomes of the study were the final serum 25OHD and PTH levels at 12 months. The absolute increase in serum 25OHD with 400, 800, 1600, and 2400 IU of vitamin D daily was slightly greater in African American women than in white women. On the highest dose of 2400 IU/d, the mixed model predicted that mean 25OHD increased from baseline 12.4 ng/mL (95% confidence interval [CI], 9.2-15.7) to 43.2 ng/mL (95% CI, 38.2-48.1) in African American women and from 15.0 ng/mL (95% CI, 12.3-17.6) to 39.1 ng/mL (95% CI, 36.2-42.0) in white women. There was no significant effect of vitamin D dose on serum PTH in either race but there was a significant inverse relationship between final serum PTH and serum 25OHD. Serum 25OHD exceeded 20 ng/mL in 97.5% of whites on the 400 IU/d dose and between 800 and 1600 IU/d for African Americans. The recommended dietary allowance (RDA) suggested by the Institute of Medicine for young people is 600 IU daily. The increase in serum 25OHD after vitamin D supplementation was similar in young and old, and in white and African American women. PMID:23761326

  8. The local production of 1,25(OH)2D3 promotes osteoblast and osteocyte maturation.

    PubMed

    Turner, Andrew G; Hanrath, Maarten A; Morris, Howard A; Atkins, Gerald J; Anderson, Paul H

    2014-10-01

    Maintenance of an adequate vitamin D status, as indicated by the level of circulating 25-hydroxyvitamin D (25(OH)D), is associated with higher bone mass and decreased risk of fracture. However, the molecular actions of vitamin D hormone (1,25(OH)2D3) in bone are complex, and include stimulation of osteoclastogenesis via RANK-ligand up-regulation, as well as the inhibition of mineralisation. We hypothesise that these divergent data may be reconciled by autocrine actions of 1,25(OH)2D3 which effect skeletal maintenance, as opposed to endocrine 1,25(OH)2D3 which acts to maintain serum calcium homeostasis. We have previously described local metabolism of 1,25(OH)2D3 within osteoblasts, with effects on gene expression and cell function. The aim of the current study was to investigate potential autocrine actions of 1,25(OH)2D3 within cells that exhibit osteocyte-like properties. Late osteoblastic MLO-A5 cells were cultured in the presence of 25(OH)D for 9 days with gene expression analysed pre- and post-mineralisation. Gene expression analysis revealed maturation within this time frame to an osteocyte-like stage, evidenced by increased Dmp1 and Phex mRNA expression. Expression of Cyp27b1 in 25(OH)D treated MLO-A5 cells was associated with elevated media levels of 1,25(OH)2D3 (p<0.05), induction of Cyp24a1 (p<0.001) and elevated ratios of Opg:Rankl mRNA (p<0.01). Chronic 25(OH)D exposure also increased osteocalcin mRNA in MLO-A5 cells, which contrasted with the dose-dependent inhibition of osteocalcin mRNA observed with acute treatment in MLO-Y4 cells (p<0.01). Treatment of MLO-Y4 cells with 25(OH)D also inhibited Phex mRNA expression (p<0.05), whilst Enpp1 gene expression was induced (p<0.01). Overall, the current study demonstrates that osteocyte-like cells convert physiological levels of 25(OH)D to 1,25(OH)2D3, with changes in gene expression that are consistent with increased osteocyte maturation. Although the physiological role of local metabolism of 1,25(OH)2D3

  9. Evidence for 1,25-dihydroxyvitamin D3-independent transactivation by the vitamin D receptor: uncoupling the receptor and ligand in keratinocytes.

    PubMed

    Ellison, Tara I; Eckert, Richard L; MacDonald, Paul N

    2007-04-13

    The vitamin D endocrine system plays critical although poorly understood roles in skin. Vitamin D receptor (VDR) knock-out (VDRKO) mice have defects in hair follicle cycling and keratinocyte proliferation leading to epidermal thickening, dermal cyst formation, and alopecia. Surprisingly, skin defects are not apparent in mice lacking 25-hydroxyvitamin D 1alpha-hydroxylase, the enzyme required for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) hormone biosynthesis. These disparate phenotypes indicate that VDR effects in skin are independent of the 1,25(OH)2D3 ligand. However, cellular or molecular data supporting this hypothesis are lacking. Here, we show transcriptional activation of the vitamin D-responsive 24-hydroxylase promoter by VDR in primary keratinocytes that is independent of the 1,25(OH)2D3 ligand. This activity required functional vitamin D-responsive promoter elements as well as an intact VDR DNA binding domain and thus could not be distinguished from 1,25(OH)2D3-dependent VDR transactivation. The 1,25(OH)2D3-independent activation of VDR was also observed in keratinocytes from 1alpha-hydroxylase knock-out mice, indicating that it is not due to endogenous 1,25(OH)2D3 production. Mammalian two-hybrid studies showed strong, 1,25(OH)2D3-independent interaction between VDR and retinoid X receptors in primary keratinocytes, indicating that enhanced heterodimerization of these receptors was involved. Indeed, this 1,25(OH)2D3-independent VDR-RXR heterodimerization was sufficient to drive transactivation by VDR(L233S), an inactive ligand binding mutant of VDR that was previously shown to rescue the skin phenotype of VDR null mice. Cumulatively, these studies support the concept that transactivation by VDR in keratinocytes may be uncoupled from the 1,25(OH)2D3 ligand. PMID:17310066

  10. 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. PMID:26385608

  11. Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial

    PubMed Central

    Kamal, S. M. Mostafa; Arifuzzaman, Abu Saleh Mohammad; Rahim, Zeaur; Khan, Lamia; Haq, Md. Ahsanul; Zaman, Khaliqu; Bergman, Peter; Brighenti, Susanna; Gudmundsson, Gudmundur H.; Agerberth, Birgitta; Raqib, Rubhana

    2015-01-01

    Background Development of new tuberculosis (TB) drugs and alternative treatment strategies are urgently required to control the global spread of TB. Previous results have shown that vitamin D3 (vitD3) and 4-phenyl butyrate (PBA) are potent inducers of the host defense peptide LL-37 that possess anti-mycobacterial effects. Objective To examine if oral adjunctive therapy with 5,000IU vitD3 or 2x500 mg PBA or PBA+vitD3 to standard chemotherapy would lead to enhanced recovery in sputum smear-positive pulmonary TB patients. Methods Adult TB patients (n = 288) were enrolled in a randomized, double-blind, placebo-controlled trial conducted in Bangladesh. Primary endpoints included proportions of patients with a negative sputum culture at week 4 and reduction in clinical symptoms at week 8. Clinical assessments and sputum smear microscopy were performed weekly up to week 4, fortnightly up to week 12 and at week 24; TB culture was performed at week 0, 4 and 8; concentrations of LL-37 in cells, 25-hydroxyvitamin D3 (25(OH)D3) in plasma and ex vivo bactericidal function of monocyte-derived macrophages (MDM) were determined at week 0, 4, 8, 12 and additionally at week 24 for plasma 25(OH)D3. Results At week 4, 71% (46/65) of the patients in the PBA+vitD3-group (p = 0.001) and 61.3% (38/62) in the vitD3-group (p = 0.032) were culture negative compared to 42.2% (27/64) in the placebo-group. The odds of sputum culture being negative at week 4 was 3.42 times higher in the PBA+vitD3-group (p = 0.001) and 2.2 times higher in vitD3-group (p = 0.032) compared to placebo. The concentration of LL-37 in MDM was significantly higher in the PBA-group compared to placebo at week 12 (p = 0.034). Decline in intracellular Mtb growth in MDM was earlier in the PBA-group compared to placebo (log rank 11.38, p = 0.01). Conclusion Adjunct therapy with PBA+vitD3 or vitD3 or PBA to standard short-course therapy demonstrated beneficial effects towards clinical recovery and holds potential for host

  12. Effects of oral administration of "rumen-bypass" vitamin D3 on vitamin D and calcium metabolism in periparturient cows.

    PubMed

    Yamagishi, N; Dohmae, H; Shirato, A; Sato, J; Sato, R; Naito, Y

    2000-04-01

    Eleven late-pregnant Jersey cows were assigned to two groups; a group (PO-RBVD group) consisting of five cows treated with an oral administration of 10 million I.U. of an encapsulated form of vitamin D3 ("rumen-bypass" VD3; RBVD3) and another group (IMVD group) consisting of the other six treated with an intramuscular injection of 10 million I.U. of vitamin D3 (VD3). The cows received the RBVD3 or VD3 administration at 7 days before the expected parturition. The changes in the plasma concentrations of vitamin D metabolites, ionized Ca (Ca++) and inorganic phosphorus (iP) were evaluated. Of the vitamin D metabolites, the plasma 25-hydroxyvitamin D concentrations in PO-RBVD group increased significantly after the RBVD3 administration and remained in high levels that were significantly higher than those in IMVD group. This suggested that RBVD3 was absorbed rapidly and excellently from the post-ruminal digestive tract without the degradation by ruminal microorganisms. The plasma Ca++ and iP concentrations in PO-RBVD group tended to be higher after the administration and around parturition than those in IMVD group. From these observations, it was suggested the oral RBVD3 administration had more potent ability to prevent parturient paresis compared with the VD3 injection used widely in Japan. PMID:10823727

  13. In vivo evidence for a novel pathway of vitamin D3 metabolism initiated by P450scc and modified by CYP27B1

    PubMed Central

    Slominski, Andrzej T.; Kim, Tae-Kang; Shehabi, Haleem Z.; Semak, Igor; Tang, Edith K. Y.; Nguyen, Minh N.; Benson, Heather A. E.; Korik, Elena; Janjetovic, Zorica; Chen, Jianjun; Yates, Charles R.; Postlethwaite, Arnold; Li, Wei; Tuckey, Robert C.

    2012-01-01

    We define previously unrecognized in vivo pathways of vitamin D3 (D3) metabolism generating novel D3-hydroxyderivatives different from 25-hydroxyvitamin D3 [25(OH)D3] and 1,25(OH)2D3. Their novel products include 20-hydroxyvitamin D3 [20(OH)D3], 22(OH)D3, 20,23(OH)2D3, 20,22(OH)2D3, 1,20(OH)2D3, 1,20,23(OH)3D3, and 17,20,23(OH)3D3 and were produced by placenta, adrenal glands, and epidermal keratinocytes. We detected the predominant metabolite [20(OH)D3] in human serum with a relative concentration ∼20 times lower than 25(OH)D3. Use of inhibitors and studies performed with isolated mitochondria and purified enzymes demonstrated involvement of the steroidogenic enzyme cytochrome P450scc (CYP11A1) as well as CYP27B1 (1α-hydroxylase). In placenta and adrenal glands with high CYP11A1 expression, the predominant pathway was D3 → 20(OH)D3 → 20,23(OH)2D3 → 17,20,23(OH)3D3 with further 1α-hydroxylation, and minor pathways were D325(OH)D3 → 1,25(OH)2D3 and D3 → 22(OH)D3 → 20,22(OH)2D3. In epidermal keratinocytes, we observed higher proportions of 22(OH)D3 and 20,22(OH)2D3. We also detected endogenous production of 20(OH)D3, 22(OH) D3, 20,23(OH)2D3, 20,22(OH)2D3, and 17,20,23(OH)3D3 by immortalized human keratinocytes. Thus, we provide in vivo evidence for novel pathways of D3 metabolism initiated by CYP11A1, with the product profile showing organ/cell type specificity and being modified by CYP27B1 activity. These findings define the pathway intermediates as natural products/endogenous bioregulators and break the current dogma that vitamin D is solely activated through the sequence D325(OH)D3 → 1,25(OH)2D3.—Slominski, A. T., Kim, T.-K., Shehabi, H. Z., Semak, I., Tang, E. K. Y., Nguyen, M. N., Benson, H. A. E., Korik, E., Janjetovic, Z., Chen, J., Yates, C. R., Postlethwaite, A., Li, W., Tuckey, R. C. In vivo evidence for a novel pathway of vitamin D3 metabolism initiated by P450scc and modified by CYP27B1. PMID:22683847

  14. Expression of human CYP27A1 in B. megaterium for the efficient hydroxylation of cholesterol, vitamin D3 and 7-dehydrocholesterol.

    PubMed

    Ehrhardt, Maximilian; Gerber, Adrian; Hannemann, Frank; Bernhardt, Rita

    2016-01-20

    In the current work the ability of Bacillus megaterium to take up hydrophobic substrates and efficiently express eukaryotic membrane proteins was utilized for establishing a CYP27A1-based biocatalyst. The human mitochondrial cytochrome P450CYP27A1 was co-expressed with its redox partners adrenodoxin reductase (Adr) and adrenodoxin (Adx). CYP27A1 could be localized at the cell's polyhydroxybutyrate (PHB) granules, carbon storage serving organelle-like vesicles that can take up cholesterol, resulting in bioreactor-like structures in B. megaterium . The resulting whole cell system allowed the efficient biotechnological conversion of the CYP27A1 substrates cholesterol, 7-dehydrocholesterol (7-DHC) and vitamin D3. After 48 h, nearly 100% of cholesterol was metabolized producing a final concentration of 113.14 mg/l 27-hydroxycholesterol (27-HC). Moreover, 70% of vitamin D3 was converted into 25-hydroxyvitamin D3 (25-OH-D3) with a final concentration of 80.81 mg/l. Also more than 97% of 7-DHC were found to be metabolized into two products, corresponding to 26/27-hydroxy-7-dehydrocholesterol (P1) and 25-hydroxy-7-dehydrocholesterol (P2). To our knowledge this is the first CYP27A1-based whole-cell system, allowing the efficient and low-cost production of pharmaceutically interesting metabolites of this enzyme from relatively cheap substrates. PMID:26638999

  15. 1,25(OH)2D3 Deficiency Induces Colon Inflammation via Secretion of Senescence-Associated Inflammatory Cytokines

    PubMed Central

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

    2016-01-01

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

  16. Vitamin D3 alters Toll-like receptor 4 signaling in monocytes of pregnant women at risk for preeclampsia

    PubMed Central

    Qian, Lei; Wang, Hongyou; Wu, Fenghui; Li, Ming; Chen, Wei; LV, Lianzheng

    2015-01-01

    Vitamin D deficiency during pregnancy is thought to play a role in the development of preeclampsia; however, the underlying mechanism is not fully understood. In this study, a randomized double-blind placebo-controlled clinical trial was performed among 60 pregnant women at risk for pre-eclampsia according to abnormal uterine artery Doppler waveform. Subjects were randomly divided into 2 groups to receive a daily dose of 2000 IU vitamin D3 supplements (n=30) or receive placebo (n=30) between gestational weeks 20-32 for a total of 12 consecutive weeks. Because vitamin D3 supplementation can induce anti-inflammatory cytokine signaling, peripheral blood monocytes were investigated by flow cytometry for expression of toll-like receptor 4 (TLR4), an important mediator of innate immune response. The pro-inflammatory cytokines secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1 from monocytes, which are typically upregulated in preeclampsia, was also assessed. The incidence of preeclampsia was significantly lower in patients treated with vitamin D3 compared to the placebo group. Both the mean fluorescence intensity and the positive percentage of monocytes TLR4 in the vitamin D group were significantly lower compared to the placebo group, as well as the concentrations of secreted TNF-α, IL-6, and IL-1, while the concentration of IL-10 was higher. In the placebo group, the positive frequency of monocytes TLR4 was negatively correlated with the concentration of serum 25-hydroxyvitamin D in preeclampsia patients. Based on these results, we conclude that vitamin D3 supplementation for patients at risk of preeclampsia leads to a decrease in the expression of peripheral blood monocytes TLR4 and a subsequent decrease in pro-inflammatory cytokine secretion. Therefore, inhibiting the expression of monocytes TLR4 through vitamin D3 supplement may be a new approach to preeclampsia prevention. PMID:26770399

  17. Production and characterization of monoclonal antibodies against two haptenic derivatives of 1 alpha,25-dihydroxyvitamin D3 conjugated with bovine serum albumin through the C-3 or C-24 position.

    PubMed

    Kobayashi, N; Sato, A; Takagi, K; Shimada, K

    1997-09-01

    To develop the immunochemical methods for determining 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] in clinical samples, a variety of monoclonal anti-1,25(OH)2D3 antibodies have been generated. Two kinds of hapten-carrier conjugates, 25-hydroxyvitamin D3 3-hemisuccinate (hapten 3-HS) and 1 alpha-hydroxy-25,26,27-trinorvitamin D3 24-oic acid (hapten 24-OA) conjugated with bovine serum albumin, were used for immunization. Spleen cells from SD rats or BALB/c mice, each immunized with the conjugate of hapten 3-HS or 24-OA, were fused with P3/NS1/1-Ag4-1 myeloma cells. After screening by ELISA employing beta-galactosidase-labeled haptens, seven kinds of hybridomas secreting anti-1,25(OH)2D3 antibodies were established. Binding characteristics of these antibodies (Ka 0.73-20 x 10(9) M-1) were investigated by an RIA using tritium-labeled 1,25(OH)2D3. The data suggested that the rat monoclonal antibody 3R-1 derived from the hapten 3-HS and the mouse monoclonal antibody 24M-3 from the hapten 24-OA would be available for developing practical analytical systems. PMID:9331974

  18. Vitamin D does not increase calcium absorption in young women: a randomized clinical trial.

    PubMed

    Gallagher, J Christopher; Jindal, Prachi S; Smith, Lynette M

    2014-01-01

    It is commonly said that vitamin D should be used to increase calcium absorption. We tested this statement in a dose-response study of vitamin D on calcium absorption. A total of 198 white and African American women, aged 25 to 45 years, with vitamin D insufficiency, serum 25-hydroxyvitamin D (25OHD) <20 ng/mL, were randomized in a double-blind study to vitamin D3 400, 800, 1600, 2400 IU, or placebo. A calcium supplement was given to increase mean calcium intake at baseline from 706 mg/d to 1031 mg/d. Calcium absorption was measured at baseline and after 12 months using a single isotope method with radiocalcium45 and 100 mg of calcium. Mean baseline serum 25OHD was 13.4 ng/mL (33.5 nmol/L) and increased to 40 ng/mL (100 nmol/L) on the highest dose of 2400 IU. Using a multivariate regression analysis with significant predictors, baseline absorption, calcium intake, and weight, there was no increase in 12-month calcium absorption compared with baseline on any dose of vitamin D in either whites or African Americans. There was no significant relationship between 12-month calcium absorption and final serum 25OHD. In an analysis of calcium absorption and serum 25OHD at baseline, serum 25OHD levels were divided into groups: 0 to 5, 6 to 10, 11 to 15, or 16 to 20 ng/mL. There was no evidence of a threshold decrease in calcium absorption or serum 1,25 dihydroxyvitamin D (1,25(OH)2 D) amongst the lowest groups. Vitamin D doses up to 2400 IU daily did not increase calcium absorption. No threshold level of serum 25OHD for calcium absorption was found at baseline or in the longitudinal study, suggesting that active transport of calcium is saturated at very low serum 25OHD levels <5 ng/mL. There is no need to recommend vitamin D for increasing calcium absorption in normal subjects. Very efficient calcium absorption at very low levels of serum 25OHD explains why people do not develop osteomalacia provided that dietary intakes of calcium and phosphorus are adequate

  19. Induction of a high phagocytic capability in P388D1, a macrophage-like tumor cell line, by 1 alpha, 25-dihydroxyvitamin D3.

    PubMed

    Goldman, R

    1984-01-01

    1 alpha, 25-Dihydroxyvitamin D3 [1,25-(OH)2D3] was shown to induce a high phagocytic capability in the macrophage-like murine tumor cell line P388D1. Induction of phagocytic capability by 1,25-(OH)2D3 was dose-dependent in the range of 0.2 to 5.0 ng/ml, required the continuous presence of the secosteroid in culture, and was reversible. 25-Hydroxyvitamin D3 was an effective inducer only at about 500 ng/ml, while 24R,25-dihydroxyvitamin D3 was ineffective. The induction of the high phagocytic capability was neither accompanied by increased synthesis of lysozyme nor closely associated with an inhibitory effect on cellular proliferation. P388D1 cells bound (without ingestion) nonopsonized sheep erythrocytes (sheep RBC), and the binding increased in 1,25-(OH)2D3-treated cells. Fc-receptor-mediated binding of immunoglobulin G-coated sheep RBC was not modulated in 1,25-(OH)2D3-treated cells, but the cells acquired an Fc-receptor-mediated phagocytic capability that was expressed only when preformed P388D1-sheep RBC rosettes were further exposed to immunoglobulin G. Several differentiation agents of myeloid leukemia cells (including dexamethasone) were not effective in inducing the high-phagocytic phenotype, while retinoic acid was very effective. Different myeloid or macrophage-like tumors (WEHI-265, J774.2, PU-5, and WEHI-3) were variable in their response to 1,25-(OH)2D3. PMID:6546302

  20. Simultaneous determination of vitamins A and D3 in dairy products by liquid chromatography-tandem mass spectrometry (LC-MS/MS)

    NASA Astrophysics Data System (ADS)

    Barakat, I. S. A.; Hammouri, M. K.; Habib, I.

    2015-10-01

    A potential method for simultaneous determination of vitamin A and vitamin D3 (25- hydroxyvitamin D3) in fresh milk samples is addressed. The method is based on combination of high performance liquid chromatography and mass spectrometry during the course of analysis. The method applied for determination of vitamins A and D3 on eighteen (18) different fresh milk samples using liquid chromatography along with tandem -mass spectrometry. The work describes the suitability of the proposed method for the simultaneous determination of both vitamins using LC-MS/MS as a specific and quantitative technique. The vitamins of milk were separated by C18 Thermo gold column(100mm × 4.6mm × 5 μm) with a flow rate of 1ml/min (using an isocratic mobile phase). The method was validated using duplicate analyses, relative recovery experiment, and comparative analysis with control samples. Liquid- liquid extraction was employed as a pre-concentration step with n-hexane - dichloromethane mixture (90%:10%) as an extraction solvent. The molecular ions (m/z) appeared near 286 and 385nm and for the base peaks were appeared near 255 and 355nm for vitamins A and D3. Good correlation coefficients were obtained, 0.9999 for vitamin D3 and 0.9994 for vitamin A. The limit of detection and the limit of quantification were found to be 0.09ng/ml and 0.54ng/ml for vitamin D3 and 0.32ng/ml and 1.8ng/ml and for vitamin A. The proposed method showed excellent recoveries, about 98% for both vitamins A and D3.

  1. Prevalence of Vitamin D Deficiency in Elderly Patients Admitted to an Inpatient Rehabilitation Unit in Tropical Singapore

    PubMed Central

    Neo, Jong J.; Kong, Keng H.

    2016-01-01

    Background. Data on hypovitaminosis D in elderly patients admitted to rehabilitation units in tropical countries are scarce. Objective. To assess the prevalence of vitamin D deficiency and its associated risk factors in elderly patients admitted to a rehabilitation unit in tropical Singapore. Methods. Prospective, cohort study of 134 subjects ≥ 65 years old admitted to a tertiary rehabilitation centre. Serum 25-hydroxyvitamin D3 (25OHD3) was measured on rehabilitation admission. Results. Mean age was 72.0 ± 5.7 years, and stroke was the commonest rehabilitation diagnosis (49.3%). Low 25OHD3 levels were present in 115 patients (85.6%) and 59 patients (44%) were deemed to be vitamin D deficient. The mean PTH level was significantly higher in patients with low 25OHD3 levels. (p = 0.002) Age, gender, vitamin D supplementation, premorbid ambulatory status, and admission/discharge Functional Independence Measure scores were not significantly associated with vitamin D deficiency. Malays/Indians (p = 0.013) and recurrent fallers (p = 0.029) were at significantly higher risk of vitamin D deficiency. Conclusions. Despite the tropical weather, vitamin D deficiency is common in elderly subjects admitted to a rehabilitation unit in Singapore. Routine assessment of vitamin D levels is recommended especially in those with a history of recurrent falls and patients of Indian/Malay ethnicity. PMID:26998361

  2. Novel ring A stereoisomers of 2-methyl-1alpha,25-dihydroxyvitamin D(3) and 2-methyl-20-epi-1alpha,25-dihydroxyvitamin D(3): transactivation of target genes and modulation of differentiation in human promyelocytic leukemia (HL-60) cells.

    PubMed

    Nakagawa, K; Kurobe, M; Ozono, K; Konno, K; Fujishima, T; Takayama, H; Okano, T

    2000-03-15

    We evaluated the biological activity of two sets of ring A stereoisomers of 2-methyl-1alpha,25-dihydroxyvitamin D(3) (2-methyl-1alpha,25(OH)(2)D(3)) and 2-methyl-20-epi-1alpha, 25-dihydroxyvitamin D(3) (2-methyl-20-epi-1alpha,25(OH)(2)D(3)) in terms of the following: transactivation of a rat 25-hydroxyvitamin D(3)-24-hydroxylase gene promoter including two vitamin D response elements (VDREs) and a human osteocalcin gene promoter including a VDRE in transfected human osteosarcoma (MG-63) cells; a vitamin D receptor (VDR)-mediated response using a VDR-GAL4 one-hybrid luciferase reporter system and a retinoid X receptor alpha (RXRalpha)-mediated response using an expressed VDR/RXRalpha-GAL4 modified two-hybrid luciferase reporter system in transfected human epitheloid carcinoma, cervix (HeLa) cells; and modulation of cell surface CD11b antigen expression in human leukemia (HL-60) cells. All the diastereomers of both analogues exhibited unique biological activity profiles depending upon the configurations of the C-1 and C-3 hydroxyl groups, the C-2 methyl group in ring A, and the C-20 methyl group in the side chain. Of the eight possible diastereomers of the 2-methyl analogues, 2alpha-methyl-1alpha,25(OH)(2)D(3) was the most potent and exhibited comparable or even greater biological potency than 1alpha,25(OH)(2)D(3). Of the eight possible diastereomers of the 2-methyl-20-epi analogues, 2alpha-methyl-20-epi-1alpha,25(OH)(2)D(3) was the most potent and exhibited 100- to 200-fold higher transcriptional potencies than 1alpha,25(OH)(2)D(3) and exceptionally high cell regulatory activities. 2beta-methyl-20-epi-1alpha,25(OH)(2)D(3) was nearly as potent as its 2-epimer, 2alpha-methyl-20-epi-1alpha,25(OH)(2)D(3), whereas its 20-epimer, 2beta-methyl-1alpha,25(OH)(2)D(3), was almost completely biologically inactive. In these respects, it can be postulated that the double modification of 2-methyl substitution and 20-epimerization to 1alpha,25(OH)(2)D(3) induces remarkable changes

  3. [Active vitamin D3 analog].

    PubMed

    Takata, Shinjiro

    2015-10-01

    Vitamin D is a fat-soluble vitamin and exerts effects on skeletal and extraskeletal health in children and adults of all ages. Vitamin D insufficiency is related to low muscle strength, increasing body sway, falls in the elderly. Supplementation with vitamin D reduces risk of osteoporotic fracture, and improves muscle strength and postural balance to prevent the elderly from fall. The preferred vitamin D analog for daily supplementation is cholecalciferol (vitamin D3). The active form of vitamin D3 is 1,25-dihydroxy-vitamin D3. Alfacalcidol, calcitriol and eldecalcitol are used to treat osteoporosis in Japan. Randomized placebo-controlled, double-blinded clinical trial for osteoporotic subjects showed that eldecalcitol is more efficacious to increase bone mineral density and prevent vertebral and wrist fractures in osteoporotic patients with vitamin D sufficiency than alfacalcidol. PMID:26529933

  4. The Associations of Novel Vitamin D3 Metabolic Gene CYP27A1 Polymorphism, Adiponectin/Leptin Ratio, and Metabolic Syndrome in Middle-Aged Taiwanese Males

    PubMed Central

    Liu, Chia-Chu; Huang, Chun-Nung; Lee, Yung-Chin; Chu, Chih-Sheng; Chang, Chu-Fen; Kuo, Po-Lin; Lai, Wen-Ter

    2015-01-01

    Metabolic syndrome (MetS) confers increased risks of cardiovascular disease (CVD). Both vitamin D3 and adipocytokines (especially adiponectin and leptin) have a great impact on CVD and MetS. In vitamin D3 metabolism, the vitamin D3 25-hydroxylase (CYP27A1) and 25-hydroxyvitamin D3 1-alpha-hydroxylase (CYP27B1) are two key enzymes. This study aimed to examine the influence of vitamin D3 CYP27 single nucleotide polymorphisms (SNPs) on adipocytokines and MetS. Cross-sectional data and DNA samples were collected from male volunteers (n = 649, age: 55.7 ± 4.7 years). Two tagging SNPs, CYP27A1 rs4674344 and CYP27B1 rs10877012, were selected from the HapMap project. MetS was significantly associated with the CYP27A1 rs4674344 SNP (P = 0.04) and the ratio of adiponectin/leptin (A/L ratio) was most correlated to the CYP27A1 rs4674344 SNP, appearing to be significantly lower in T-carriers than in AA subjects (3.7 ± 4.0 versus 5.1 ± 6.0, P = 0.001) and significantly negatively associated after adjustment. For each MetS component associated with the CYP27A1 rs4674344 SNP, the A/L ratios were significantly negative in preclinical stage (condition not meeting the individual criteria), except the blood pressure. In conclusion, CYP27A1 rs4674344 SNP, A/L ratio, and MetS are significantly associated and T-carriers might have a higher risk of developing MetS due to low A/L ratios in the preclinical stage. PMID:25628655

  5. 27-Oxygenation of C27-sterols and 25-hydroxylation of vitamin D3 in kidney: cloning, structure and expression of pig kidney CYP27A.

    PubMed Central

    Postlind, H; Hosseinpour, F; Norlin, M; Wikvall, K

    2000-01-01

    This paper describes the molecular cloning of a cytochrome P450 enzyme in pig kidney that catalyses the hydroxylations of vitamin D(3) (cholecalciferol) and C(27)-sterols. DNA sequence analysis of the cDNA revealed that the enzyme belongs to the CYP27 family. The first 36 amino acids have many hallmarks of a mitochondrial signal sequence. The mature pig kidney CYP27 protein contains 498 amino acids. The M(r) of the mature protein was calculated to be 56607. The structure of pig kidney CYP27, as deduced by DNA sequence analysis, shows 77-83% identity with CYP27A in rat, rabbit and human liver. Transfection of the renal CYP27A cDNA into simian COS cells resulted in the synthesis of an enzyme that catalysed the 25-hydroxylation of vitamin D(3) and the 27-hydroxylation of 5beta-cholestane-3alpha,7alpha,12alpha-triol, and the further oxidation of the product into the corresponding C(27)-acid 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoic acid. As part of these studies, the enzymic activities of cultured human embryonic kidney cells were examined using vitamin D(3) and C(27)-sterols as substrates. The cells were found to express CYP27A mRNA and to convert the respective substrates into the same products as recombinantly expressed CYP27A, i.e. 25-hydroxyvitamin D(3) and 27-oxygenated C(27)-sterols. The results of the present study describing the structure and expression of CYP27A in kidney suggest that this enzyme is involved in the renal metabolism of vitamin D(3) and that the kidney plays a role in the metabolism of cholesterol and other C(27)-sterols. PMID:10749662

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

    PubMed Central

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

    2015-01-01

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

  7. The D3 Middleware Architecture

    NASA Technical Reports Server (NTRS)

    Walton, Joan; Filman, Robert E.; Korsmeyer, David J.; Lee, Diana D.; Mak, Ron; Patel, Tarang

    2002-01-01

    DARWIN is a NASA developed, Internet-based system for enabling aerospace researchers to securely and remotely access and collaborate on the analysis of aerospace vehicle design data, primarily the results of wind-tunnel testing and numeric (e.g., computational fluid-dynamics) model executions. DARWIN captures, stores and indexes data; manages derived knowledge (such as visualizations across multiple datasets); and provides an environment for designers to collaborate in the analysis of test results. DARWIN is an interesting application because it supports high-volumes of data. integrates multiple modalities of data display (e.g., images and data visualizations), and provides non-trivial access control mechanisms. DARWIN enables collaboration by allowing not only sharing visualizations of data, but also commentary about and views of data. Here we provide an overview of the architecture of D3, the third generation of DARWIN. Earlier versions of DARWIN were characterized by browser-based interfaces and a hodge-podge of server technologies: CGI scripts, applets, PERL, and so forth. But browsers proved difficult to control, and a proliferation of computational mechanisms proved inefficient and difficult to maintain. D3 substitutes a pure-Java approach for that medley: A Java client communicates (though RMI over HTTPS) with a Java-based application server. Code on the server accesses information from JDBC databases, distributed LDAP security services, and a collaborative information system. D3 is a three tier-architecture, but unlike 'E-commerce' applications, the data usage pattern suggests different strategies than traditional Enterprise Java Beans - we need to move volumes of related data together, considerable processing happens on the client, and the 'business logic' on the server-side is primarily data integration and collaboration. With D3, we are extending DARWIN to handle other data domains and to be a distributed system, where a single login allows a user

  8. Plasma 24,25-dihydroxyvitamin D concentration of Dahl salt-sensitive rats decreases during high salt intake

    NASA Technical Reports Server (NTRS)

    Thierry-Palmer, Myrtle; Tewolde, Teclemicael K.; Forte, Camille; Wang, Min; Bayorh, Mohamed A.; Emmett, Nerimiah L.; White, Jolanda; Griffin, Keri

    2002-01-01

    Dahl salt-sensitive rats, but not salt-resistant rats, develop hypertension in response to high salt intake. We have previously shown an inverse relationship between plasma 25-hydroxyvitamin D (25-OHD) concentration and blood pressure of Dahl salt-sensitive rats during high salt intake. In this study, we report on the relationship between high salt intake and plasma 24,25-dihydroxyvitamin D (24,25-(OH)(2)D) concentration of Dahl salt-sensitive and salt-resistant rats. Rats were fed a high salt diet (8%) and sacrificed at day 2, 7, 14, 21, and 28. Plasma 24,25-(OH)(2)D concentrations of salt-sensitive rats were reduced to 50% of that at baseline at day 2-when blood pressure and plasma 25-OHD concentration were unchanged, but 25-OHD content in the kidney was 81% of that at baseline. Plasma 24,25-(OH)(2)D concentration was reduced further to 10% of that at baseline from day 7 to 14 of high salt intake, a reduction that was prevented in rats switched to a low salt (0.3%) diet at day 7. Exogenous 24,25-dihydroxycholecalciferol (24,25-(OH)(2)D(3)), administered at a level that increased plasma 24,25-(OH)(2)D concentration to five times normal, did not attenuate the salt-induced hypertension of salt-sensitive rats. Plasma 24,25-(OH)(2)D concentration of salt-resistant rats was gradually reduced to 50% of that at baseline at day 14 and returned to baseline value at day 28 of high salt intake. We conclude that the decrease in plasma 24,25-(OH)(2)D concentration in salt-sensitive rats during high salt intake is caused by decreased 25-OHD content in the kidney and also by another unidentified mechanism.

  9. Biological activity profiles of 1alpha,25-dihydroxyvitamin D2, D3, D4, D7, and 24-epi-1alpha,25-dihydroxyvitamin D2.

    PubMed

    Tsugawa, N; Nakagawa, K; Kawamoto, Y; Tachibana, Y; Hayashi, T; Ozono, K; Okano, T

    1999-04-01

    We have synthesized several 1alpha,25-dihydroxyvitamin D [1alpha,25(OH)2D] derivatives and evaluated their biological activity in terms of their binding affinity for the vitamin D receptor (VDR) and vitamin D-binding protein (DBP), antiproliferative or differentiation-inducing effects on human promyelocytic leukemic HL-60 cells, and transcriptional activity on a rat 25-hydroxyvitamin D3-24-hydroxylase gene promoter, including two vitamin D-responsive elements (VDREs), and human osteocalcin gene promoter, including a VDRE in transfected human osteosarcoma MG-63 cells. Furthermore, human VDR- or retinoic acid X receptor alpha (RXR alpha)-mediated luciferase activities of the derivatives were also measured by a one-hybrid system in human epitheloid carcinoma, cervix HeLa cells and African green monkey kidney CV-1 cells. Binding affinity for VDR, bone-resorbing activity, antiproliferative and cell-differentiating effects, transactivation potencies on target genes and VDR- or RXR alpha-mediated gene regulations of 1alpha,25(OH)2D2 and 1alpha,25(OH)2D4 were almost comparable to the effects of 1alpha,25(OH)2D3 while 24-epi-1alpha,25(OH)2D2 and 1alpha,25(OH)2D7 were much less active than 1alpha,25(OH)2D3 in these respects. This is the first report concerning biological assessment of 1alpha,25(OH)2D2, 1alpha,25(OH)2D3, 1alpha,25(OH)2D4, 24-epi-1alpha,25(OH)2D2 and 1alpha,25(OH)2D7 at the molecular level, especially with regards to the structural differences at the 24R- or 24S-methyl group and a double bond between carbons 22 and 23 in the side chain of 1alpha,25(OH)2D derivatives. PMID:10328556

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

    PubMed

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

    2015-01-01

    A study was conducted to examine the effects of 25-hydroxyvitamin D3 (25-(OH)D3) on fecal Ca and P excretion, bone mineralization, performance and the mRNA expression of intestinal transporter genes in growing female pigs. Sixty-day old gilts (n = 24) with an average initial BW of 23.13 ± 1.49 kg were randomly allocated to a control diet (diet 1) containing wheat/corn/soybean meal and 150 IU kg(-1) of Vitamin D3, diet 1 + 50 μg of 25-(OH)D3 kg(-1) (diet 2) and diet 1 + 100 μg of 25-(OH)D3 kg(-1) (diet 3). The pigs were housed in an individual pen and had ad libitum access to feed and water for 42 days, and BWG and feed intake were measured weekly. Measures of bone mineralization and expression of Ca and P transporters mRNA were analyzed using Dual Energy X-Ray Absortiometry (DEXA) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Data were analyzed using GLM procedure of the Statistical Analysis System (SAS Institute version 9.2). Fecal Ca and P concentration were significantly reduced (P ≤ 0.05) in pigs fed diets 2 and 3 compared with the control diet. Supplementation of 25-(OH)D3 did not significantly improve bone mineralization, animal performance and intestinal transporters mRNA expression except for SLC34A1, a sodium-dependent phosphate transporter 1. In conclusion, supplementation of 25-(OH)D3 in swine nutrition may not improve animal performance but has the potential to reduce environmental pollution by increasing dietary Ca and P retention while reducing their excretion. PMID:25714461

  11. Serum 25-Hydroxyvitamin D in Patients with Major Depressive Disorder

    PubMed Central

    DANA-ALAMDARI, Leila; KHEIROURI, Sorayya; NOORAZAR, Seyed Gholamreza

    2015-01-01

    Background: We investigated the association between serum 25(OH) D levels and depressive symptoms in patients with major depressive disorder (MDD). Methods: Eighty-five adults, 44 drug free patients with MDD and 41 apparently healthy controls, participated in the study. The Hamilton Depression Rating Scale was used to assess severity of major depression. Mental health of the controls was assessed according to DSM-IV criteria. Stress level of the participants was assessed by the Holmes and Rahe stress scale. Serum 25(OH) D levels was measured by immunochemiluminescence assay. Vitamin D deficiency was defined as a serum 25(OH) D concentration of lower than 20 ng/ml. Results: Depressed patients had the higher levels of stress. There was a positive correlation between stress level and disease severity (r= 0.32, P= 0.03). In total participants, mean percentage of vitamin D deficiency was 77.6% with 75% in patients and 80.5% in the healthy subjects. There were no differences between the two groups in serum 25(OH) D levels and percentage of subjects with the vitamin deficiency. A negative correlation was observed between disease severity and serum 25(OH) D level of patients with depression episodes < 2 y (r= −0.38, P = 0.08) and winter samples (samples collected and measured from December to march, r= −0.62, P = 0.004). Conclusion: Serum 25(OH) D levels were not associated with depression. However, the inverse relationship between levels of vitamin D and depressive symptoms in current depression episodes and in sun-deprived season warrants further investigation. PMID:26284211

  12. Serum 25-hydroxyvitamin D and functional outcomes in the elderly

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this paper is to consider key evidence that treatment of vitamin D insufficiency has measurable clinical benefits for the musculoskeletal system in the elderly. The outcomes considered are increased bone mass, decreased rates of bone loss, improved muscle performance, reduced risk o...