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Aims To measure total 25-hydroxyvitamin D levels in women in mid-pregnancy who participated in the Belfast centre of the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) observational study, and to investigate the associations between levels of 25-hydroxyvitamin D and markers of gestational diabetes mellitus and lipid biomarkers. Methods A total of 1585 pregnant women had serum samples available for measurement. Participants were recruited from the Royal Jubilee Maternity Hospital, Belfast, Northern Ireland, at 24-32 weeks' gestation, as part of the HAPO study. 25-hydroxyvitamin D concentrations were measured using liquid chromatography tandem mass spectrometry. Glucose, C-peptide and lipid levels were previously analysed in a central laboratory. Statistical analysis was performed. Results The median (interquartile range) 25-hydroxyvitamin D concentration during pregnancy was 38.6 (24.1-60.7) nmol/l, with 65.8% of women being vitamin D-deficient (≤50 nmol/l). In regression analysis, the association between maternal 25-hydroxyvitamin D and fasting plasma glucose levels approached significance [regression coefficient -0.017 (95% CI -0.034 to 0.001); P=0.06], and a significant positive association was observed between maternal 25-hydroxyvitamin D and β-cell function [1.013 (95% CI 1.001 to 1.024); P=0.031]. Maternal 25-hydroxyvitamin D level was positively associated with HDL [0.047 (95% CI 0.021 to 0.073) P≤ 0.001] and total cholesterol [0.085 (95% CI 0.002 to 0.167); P=0.044] in regression analysis. Conclusions These results indicate a high prevalence of vitamin D deficiency during pregnancy, which requires identification and treatment; however, only weak associations were observed between 25-hydroxyvitamin D level and markers of glucose and insulin metabolism. This would suggest that these are of doubtful clinical significance.

Objective: In the past decades, an increased interest in the roles of vitamin D and K has become evident, in particular in relation to bone health and prevention of bone fractures. The aim of the current study was to evaluate vitamin D and K status in children with low-energy fractures and in children without fractures. Methods: The study group of 20 children (14 boys, 6 girls) aged 5 to 15 years old, with radiologically confirmed low-energy fractures was compared with the control group of 19 healthy children (9 boys, 10 girls), aged 7 to 17 years old, without fractures. Total vitamin D (25(OH)D3 plus 25(OH)D2), calcium, BALP (bone alkaline phosphatase), NTx (N-terminal telopeptide), and uncarboxylated (ucOC) and carboxylated osteocalcin (cOC) serum concentrations were evaluated. Ratio of serum uncarboxylated osteocalcin to serum carboxylated osteocalcin ucOC:cOC (UCR) was used as an indicator of bone vitamin K status. Logistic regression models were created to establish UCR influence for odds ratio of low-energy fractures in both groups. Results: There were no statistically significant differences in the serum calcium, NTx, BALP, or total vitamin D levels between the two groups. There was, however, a statistically significant difference in the UCR ratio. The median UCR in the fracture group was 0.471 compared with the control group value of 0.245 (p &lt, 0.0001). In the logistic regression analysis, odds ratio of low-energy fractures for UCR was calculated, with an increased risk of fractures by some 78.3 times. Conclusions: In this pilot study, better vitamin K status expressed as the ratio of ucOC:cOC-UCR&mdash, is positively and statistically significantly correlated with lower rate of low-energy fracture incidence.

Multiple sclerosis (MS) is a neurodegenerative autoimmune disease resulting from a complex interaction of genetic and environmental factors. Hypovitaminosis D seems to contribute to MS susceptibility as both an environmental and a genetic risk factor. The aim of our study was to investigate the association of SNPs in CYP27A1, CYP24A1, and RXR- α genes, vitamin D status, and MS risk. We performed a nested case-control study on patients with multiple sclerosis and healthy controls. Serum 25(OH)D3 levels and genotyping of CYP27A1, CYP24A1, and RXR-α -SNPs were investigated both in MS patients and in healthy controls. Serum 25(OH)D3 levels were measured by a high-performance liquid chromatography (HPLC). Molecular analysis was performed by real-time PCR. The distribution of genotypic and allelic frequencies was not significantly different between patients and controls, except for rs2248137 CYP24A1. In particular, CC genotype (C minor allele) showed a higher frequency in MS patients in comparison to healthy controls. Moreover, we observed significantly lower serum 25(OH)D3 levels in MS patients with CC genotype in comparison to MS patients with GG and GC genotype. The findings of our study suggest a role of rs2248137 CYP24A1 in multiple sclerosis risk.

Vitamin D deficiency is known to cause increased predisposition to various infectious diseases and the addition of vitamin D to antimicrobial treatment may improve treatment responses. However, the relationship between vitamin D and Helicobacter pylori (H. pylori) remains to be determined. To assess the association between vitamin D deficiency and H. pylori infection. This cross-sectional study included patients aged 65 and over, who underwent gastroscopy and had gastric biopsy performed between 2010 and 2017. Of the 441 patients, 254 had available 25-hydroxyvitamin D level results and were included in the analyses. Patients were categorized into H. pylori (+) and H. pylori (−) groups, according to histopathological examination results of gastric biopsies. Serum 25(OH) vitamin D levels less than 20 ng/mL were defined as vitamin D deficiency. Of all patients, 43 were H. pylori (+) and 211 were H. pylori (−). More patients had vitamin D deficiency (

Vitamin D has previously been quantified in some plants and algae, particularly in leaves of the Solanaceae family. We measured the vitamin D content of Australian native food plants and Australian-grown edible seaweed. Using liquid chromatography with triple quadrupole mass spectrometry, 13 samples (including leaf, fruit, and seed) were analyzed in duplicate for vitamin D2, vitamin D3, 25-hydroxyvitamin D2, and 25-hydroxyvitamin D3. Five samples contained vitamin D2: raw wattleseed (Acacia victoriae) (0.03 &micro, g/100 g dry weight (DW)), fresh and dried lemon myrtle (Backhousia citriodora) leaves (0.03 and 0.24 &micro, g/100 g DW, respectively), and dried leaves and berries of Tasmanian mountain pepper (Tasmannia lanceolata) (0.67 and 0.05 &micro, g/100 g DW, respectively). Fresh kombu (Lessonia corrugata) contained vitamin D3 (0.01 &micro, g/100 g DW). Detected amounts were low, however, it is possible that exposure to ultraviolet radiation may increase the vitamin D content of plants and algae if vitamin D precursors are present.

The teleological purpose of an ongoing pregnancy is to fulfill its fundamental role of a successful, uncomplicated delivery, in conjunction with an optimal intrauterine environment for the developing fetus. Vitamin D metabolism is adapted to meet both these demands during pregnancy; first by stimulation of calcium absorption for adequate intrauterine bone mineral accrual of the fetus, and second, by enhancing systemic and local maternal tolerance to paternal and fetal alloantigens. Vitamin D-binding protein (VDBP) is one of the key biomolecules that optimize vitamin D homeostasis and also contributes as an immune regulator for a healthy, ongoing pregnancy. In this regard, recent results indicate that dysregulation of VDBP equilibrium could be a risk factor for adverse fetal, maternal, and neonatal outcomes, including preeclampsia, preterm birth, and gestational diabetes. Moreover, it has been hypothesized to be also implicated in the interpretation of vitamin D status in the pregnant state. The aim of this review is to assess available literature regarding the association of VDBP with clinical outcomes during pregnancy, as a potential biomarker for future clinical practice, with a discourse on current knowledge gaps and future research agenda.

BACKGROUND & AIMS Fatty liver disease is an important complication associated with liver transplantation, and the cytochrome P-450 system of the donor liver may be involved in its pathogenesis. To explore the effects of the CYP27A1, CYP27B1, CYP2R1, and vitamin D receptor pathways on vitamin D maintenance after living donor liver transplantation, we investigated the interplay between serum 25(OH)D and common variants in 60 paired donors and recipients who underwent living donor liver transplantation. METHODS We prospectively collected 60 donor/recipient pairs from our liver transplantation programmes and extracted serum DNA to evaluate single nucleotide polymorphisms in CYP27A1 rs4674344, CYP27B1 rs10877012, CYP2R1 rs10741657, and VDR rs2228530 alleles using real-time polymerase chain reaction. We measured serum 25(OH)D concentrations of donors (D-D0) and recipients before (R-D0) and after (R-D30) living donor liver transplantation for comparison with repeated-measures analysis of variance in generalized estimating equations analysis. RESULTS Fatty liver disease was noted in 28.3% of the cases after living donor liver transplantation, and the graft rejection rate was 25%. There were significant differences in low serum 25(OH)D concentrations between D-D0 and R-D0 and between R-D0 and R-30 groups. Significant associations were observed for serum CYP27A1 rs4674344 in recipients and donors as well as for graft liver tissue with VDR rs2228530. There was no significant relationship with serum CYP27B1 rs10877012 in recipients and donors or with graft liver tissue with CYP2R1 rs10741657. CONCLUSIONS Donor/recipient CYP27A1 rs4674344 and graft VDR rs2228570 may be related to low serum 25(OH)D and may play a major role in the development of fatty liver disease in recipients after living donor liver transplantation.

Background Previous in vitro and in vivo studies indicate that enzymes that synthesize and metabolize vitamin D are magnesium dependent. Recent observational studies found that magnesium intake significantly interacted with vitamin D in relation to vitamin D status and risk of mortality. According to NHANES, 79% of US adults do not meet their Recommended Dietary Allowance of magnesium. Objectives The aim of this study was to test the hypothesis that magnesium supplementation differentially affects vitamin D metabolism dependent on baseline 25-hydroxyvitamin D [25(OH)D] concentration. Methods The study included 180 participants aged 40-85 y and is a National Cancer Institute independently funded ancillary study, nested within the Personalized Prevention of Colorectal Cancer Trial (PPCCT), which enrolled 250 participants. The PPCCT is a double-blind 2 × 2 factorial randomized controlled trial conducted in the Vanderbilt University Medical Center. Doses for both magnesium and placebo were customized based on baseline dietary intakes. Subjects were randomly assigned to treatments using a permuted-block randomization algorithm. Changes in plasma 25-hydroxyvitamin D3 [25(OH)D3], 25-hydroxyvitamin D2 [25(OH)D2], 1,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D2, and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] were measured by liquid chromatography-mass spectrometry. Results The relations between magnesium treatment and plasma concentrations of 25(OH)D3, 25(OH)D2, and 24,25(OH)2D3 were significantly different dependent on the baseline concentrations of 25(OH)D, and significant interactions persisted after Bonferroni corrections. Magnesium supplementation increased the 25(OH)D3 concentration when baseline 25(OH)D concentrations were close to 30 ng/mL, but decreased it when baseline 25(OH)D was higher (from ∼30 to 50 ng/mL). Magnesium treatment significantly affected 24,25(OH)2D3 concentration when baseline 25(OH)D concentration was 50 ng/mL but not 30 ng/mL. On the other hand, magnesium treatment increased 25(OH)D2 as baseline 25(OH)D increased. Conclusion Our findings suggest that optimal magnesium status may be important for optimizing 25(OH)D status. This trial was registered at clinicaltrials.gov as NCT03265483.

The main purposes of the study were (i) to evaluate serum vitamin D concentration in the forms of 25(OH)DA total of 200 postmenopausal women were recruited from November 2012 to March 2014. To control for seasonal ultraviolet exposure time differences in serum 25(OH)D, laboratory tests were performed only from November to March when vitamin D is not synthesized. Independent relationships between 25(OH)DThe mean serum 25(OH)DBoth 25(OH)D

To explore subclinical fatty liver disease (FLD) in donors as a possible mechanism leading to FLD in recipients of living donor liver transplantation (LDLT), we extracted thirty donor-recipient pairs’ serum DNA and explored the presence of CYP2R1 single nucleotide polymorphism (SNP) rs10741657 and vitamin D receptor (VDR) SNP rs2228530 A/G alleles using real-time polymerase chain reaction. We measured the serum 25(OH)D concentrations and investigated the CYP2R1 and VDR genotypes of the donors and recipients before and after LDLT for comparison with the histological findings from the donors on wedge biopsy, the recipients’ removed native liver, and selective liver biopsy after LDLT. There was a significant difference in low serum 25(OH)D concentration between the donors and recipients before LDLT and in the recipients before versus after LDLT (13.90±8.85 versus 47.9±14.88 versus 11.82±10.36, P<0.001), and significant difference in FLD was detected on wedge biopsy from the donors and the native liver from the recipients as well as the native liver and follow-up biopsy from the recipients (P<0.001). CYP2R1 and VDR genotype were predominant, both for the AG and for the GG alleles. For the donor VDR SNP rs2228570, low serum 25(OH)D was significantly different between genotypes AA and AG (P=0.024) as well as between genotypes AA and AG plus GG (P=0.042). Our data suggest that donors’ VDR rs2228570 AA alleles may play a major role in low serum 25(OH)D regarding pathological FLD in recipients after LDLT.

Vitamin D deficiency/insufficiency is currently considered to be a re-emerging public health problem globally. This study was designed to determine the prevalence of vitamin D deficiency and insufficiency and to investigate its trend from 2001 to 2013 in a longitudinal study of Iranian adults. This study was part of a population-based, longitudinal ongoing study of Iranian healthy adults aged 35 y and older at baseline. Serum vitamin D level was assessed in a sub-sample of 370 subjects, who were apparently healthy at the time of recruitment in 2001 and were free from MetS, in three phases (2001, 2007 and 2013) during the 12-y study period. Adjusted prevalence and trend of vitamin D deficiency were calculated. Mean serum vitamin D levels increased over the time of the study (52.12, 54.27 and 62.28 nmol/L, respectively) and the prevalence of vitamin D deficiency decreased (30.5, 27.0 and 24.4, respectively). However, the prevalence of vitamin D insufficiency did not change over this time period. The risk of vitamin D deficiency decreased significantly in 2007 [OR: 0.73 (95% CI: 0.53, 0.99)] and 2013 [OR: 0.50 (95% CI: 0.36, 0.70)] compared to the baseline. The present study demonstrated some improvement in serum vitamin D levels, while the prevalence of vitamin D inadequacy was still high. Considering the possible health consequences of vitamin D deficiency, there is an urgent need for developing population-wide strategies, such as supplementation and fortification, to prevent or control vitamin D deficiency.

Background Ongoing studies in the Middle East, particularly in the Arabian Gulf countries, have reported extremely low levels of serum vitamin D across age and gender. In Kuwait, vitamin D deficiency is prevalent in adolescent girls and in adult women. A number of risk factors have been reported, among which gender, age, and obesity are a few. Because adequate vitamin D status is necessary to promote bone mineral accrual in childhood, and because low vitamin D levels have been associated with a wide range of health problems, there is concern that growing children with low vitamin D may be at higher risk for developing diseases. The aim of this study was to assess vitamin D levels in elementary schoolchildren. Methods Kuwaiti schoolchildren were recruited and assessed for their serum vitamin D, 25(OH)D, parathyroid hormone (PTH) and adjusted serum calcium (adj-Ca). Anthropometric measurements and data on lifestyle and health status were recorded during an interview. Results In a total of 199 schoolchildren, median (IQR) age was 8.5 (7.0–9.5 years), 25(OH)D was 30 (22–39 nmol/L), PTH was 4.7 (3.8–5.9 pmol/L), and adj-Ca was 2.39 (2.33–2.44 mmol/L). Boys had higher levels of 25(OH)D (18.3% vs 6.6% had levels ≥50 nmol/L) and lower levels of PTH (94.6% vs 80.2% had levels

Background: Vitamin D and iron deficiencies frequently co-exist. It is now appreciated that mechanistic interactions between iron and vitamin D metabolism may underlie these associations. Objective: We examined interrelations between iron and vitamin D status and their regulatory hormones in pregnant adolescents, who are a group at risk of both suboptimal vitamin D and suboptimal iron status. Design: The trial was a prospective longitudinal study of 158 pregnant adolescents (aged #18 y). Maternal circulating biomarkers of vitamin D and iron were determined at midgestation (w25 wk) and delivery (w40 wk). Linear regression was used to assess associations between vitamin D and iron status indicators. Bivariate and multivariate logistic regressions were used to generate the OR of anemia as a function of vitamin D status. A mediation analysis was performed to examine direct and indirect relations between vitamin D status, hemoglobin, and erythropoietin in maternal serum. Results: Maternal 25-hydroxyvitamin D [25(OH)D] was positively associated with maternal hemoglobin at both midgestation and at delivery (P , 0.01 for both). After adjustment for age at enrollment and race, the odds of anemia at delivery was 8 times greater in adolescents with delivery 25(OH)D concentrations ,50 nmol/L than in those with 25(OH)D concentrations $50 nmol/L (P ,0.001). Maternal 25(OH)D was inversely associated with erythropoietin at both midgestation (P ,0.05) and delivery (P ,0.001). The significant relation observed between 25(OH)D and hemoglobin could be explained by a direct relation between 25(OH)D and hemoglobin and an indirect relation that was mediated by erythropoietin. Conclusions: In this group of pregnant adolescents, suboptimal vitamin D status was associated with increased risk of iron insufficiency and vice versa. These findings emphasize the need for screening for multiple nutrient deficiencies during pregnancy and greater attention to overlapping metabolic pathways when selecting prenatal supplementation regimens. Am J Clin Nutr doi: 10.3945/ajcn.115.116756.

In a prospective cohort study, the association between maternal vitamin D status during pregnancy and offspring forearm fractures during childhood and adolescence was analysed in 30 132 mother and child pairs recruited to the Danish National Birth Cohort between 1996 and 2002. Data on characteristics, dietary factors and lifestyle factors were collected on several occasions during pregnancy. We analysed the association between predicted vitamin D status, based on a subsample with 25-hydroxyvitamin D (25(OH)D) biomarker measurements (n 1497) from gestation week 25, and first-time forearm fractures among offspring between birth and end of follow-up. Diagnoses were extracted from the Danish National Patient Register. Multivariable Cox regression models using age as the underlying time scale indicated no overall association between predicted vitamin D status (based on smoking, season, dietary and supplementary vitamin D intake, tanning bed use and outdoor physical activity) in pregnancy and offspring forearm fractures. Likewise, measured 25(OH)D, tanning bed use and dietary vitamin D intake were not associated with offspring forearm fractures. In mid-pregnancy, 91 % of the women reported intake of vitamin D from dietary supplements. Offspring of women who took >10 µg/d in mid-pregnancy had a significantly increased risk for fractures compared with the reference level of zero intake (hazard ratios (HR) 1·31; 95 % CI 1·06, 1·62), but this was solely among girls (HR 1·48; 95 % CI 1·10, 2·00). Supplement use in the peri-conceptional period exhibited similar pattern, although not statistically significant. In conclusion, our data indicated no protective effect of maternal vitamin D status with respect to offspring forearm fractures.

Background: To enable food-based strategies for the prevention of vitamin D deficiency to be evidence-based, there is a need to develop integrated predictive models of population serum 25-hydroxyvitamin D [25(OH)D] that are responsive to both solar and dietary inputs of vitamin D. Objectives: The objectives of this work were to develop and validate an integrated mathematical model with the use of data on UVB availability, exposure, and dietary intake to predict serum 25(OH)D concentrations in a nationally representative sample of adults, and then test the models performance with the use of 3 hypothetical fortification scenarios as exemplars. Methods: Data on UVB availability and hours of sunlight in Ireland were used in a mathematical model to predict serum 25 (OH)D in Irish adults aged 18‐64 y. An equation from our dose-related vitamin D supplementation trial in adults was developed and integrated into the model, which allowed us to predict the impact of changes in dietary vitamin D to the contribution to annual serum 25(OH)D concentrations, accounting for seasonality of UVB availability. Recently published estimates of the impact of 3 vitamin D food fortification scenarios on vitamin D intake in a representative sample of Irish adults were used in the model as a test. Results: The UVB- and vitamin D intake‐serum 25(OH)D components of the integrated model were both validated with the use of independent data. The model predicted that the percentage vitamin D deficiency [serum 25(OH)D

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

Objectives: Epidemiological studies have reported that vitamin D deficiency is associated with inflammatory disease. Smoking is a well-known risk factor for inflammation. However, few studies have investigated the interactive effect of vitamin D deficiency and smoking on inflammation. This study aims to investigate the interaction of vitamin D and smoking with inflammatory markers in the urban elderly. Methods: We used data from the Korean Elderly Environmental Panel Study, which began in August 2008 and ended in August 2010, and included 560 Koreans ≥60 years old living in Seoul. Data was collected via questionnaires that included items about smoking status at the first visit. Vitamin D levels, high-sensitivity C-reactive protein (hs-CRP), and white blood cell (WBC) counts were repeatedly measured up to three times. Results: The association of vitamin D and hs-CRP was significant after adjusting for known confounders (β=-0.080, p=0.041). After separate analysis by smoking status, the association of vitamin D deficiency and hs-CRP in smokers was stronger than that in nonsmokers (smokers: β=-0.375, p=0.013; non-smokers: β=-0.060, p=0.150). Smoking status was an effect modifier that changed the association between vitamin D deficiency and hs-CRP (interaction estimate: β=-0.254, p=0.032). Vitamin D was not significantly associated with WBC count (β=0.003, p=0.805). Conclusions: Vitamin D deficiency was associated with hs-CRP in the urban elderly. Smoking status was an effect modifier of this association. Vitamin D deficiency was not significantly associated with WBC count.

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.

Increasing evidence demonstrates that reactive oxygen species plays important roles in sepsis-induced acute kidney injury. This study investigated the effects of VitD3 pretreatment on renal oxidative stress in sepsis-induced acute kidney injury. Mice were intraperitoneally injected with lipopolysaccharide (LPS, 2.0mg/kg) to establish an animal model of sepsis-induced acute kidney injury. In VitD3+LPS group, mice were orally pretreated with three doses of VitD3 (25 μg/kg) at 1, 24 and 48 h before LPS injection. As expected, oral pretreatment with three daily recommended doses of VitD3 markedly elevated serum 25(OH)D concentration and efficiently activated renal VDR signaling. Interestingly, LPS-induced renal GSH depletion and lipid peroxidation were markedly alleviated in VitD3-pretreated mice. LPS-induced serum and renal nitric oxide (NO) production was obviously suppressed by VitD3 pretreatment. In addition, LPS-induced renal protein nitration, as determined by 3-nitrotyrosine residue, was obviously attenuated by VitD3 pretreatment. Further analysis showed that LPS-induced up-regulation of renal inducible nitric oxide synthase (inos) was repressed in VitD3-pretreated mice. LPS-induced up-regulation of renal p47phox and gp91phox, two NADPH oxidase subunits, were normalized by VitD3 pretreatment. In addition, LPS-induced down-regulation of renal superoxide dismutase (sod) 1 and sod2, two antioxidant enzyme genes, was reversed in VitD3-pretreated mice. Finally, LPS-induced tubular epithelial cell apoptosis, as determined by TUNEL, was alleviated by VitD3 pretreatment. Taken together, these results suggest that VitD3 pretreatment alleviates LPS-induced renal oxidative stress through regulating oxidant and antioxidant enzyme genes.

To find out the effect in increase in serum 25(OH) vitamin D levels aftersupplementation with 1000 IU/day of vitamin D in patients with low vitamin D levels and otherfactors which may affect the increase in vitamin D levels. Study Design: Retrospective study.Period: January 2013 and June 2014. Setting: Ch. Rehmat Ali Trust Teaching Hospital in theLahore. Methods: The study included patients > 50 years with a low-energy fracture and avitamin D level < 25 nmol/l. Results: 85 patients were included, mean basal 25(OH) vitamin Dlevel was 22 nmol/l. After a mean of 10 weeks, the mean increase in vitamin D was 49.5 nmol/l.Only 45.1% reached the target level of > 50 nmol/l. The increase was correlated with the basallevel of vitamin D (p < 0.05), and the time interval between the two vitamin D measurements(p < 0.05) and was inversely related to body weight (p < 0.05), but was not related to age,gender or renal function. Conclusions: We found that the generally recommended dosage of1000 IU of vitamin D per day resulted in suboptimal serum levels after ten weeks of treatment inmore than half of the patients. The increase in vitamin D levels was higher in patients with lowbody weight and in patients with very low basal vitamin D levels. These data suggest that thesepatients should initially be treated with higher dosages of vitamin D. If not possible, vitamin Dmeasurements should be performed after at least six months of supplementation with dosageadjustment.

Decreased bone density secondary to osteoporosis and osteomalacia represents a significant risk factor for bony fracture and spinal instrumentation failure. We evaluated the incidence of vitamin D deficiency in patients undergoing elective spinal instrumentation to investigate which patient-level risk factors are associated with deficient vitamin D levels.Serum 25-OH vitamin D levels were evaluated postoperatively (72 hours) in patients undergoing elective spinal fusion from 2011 through 2012. Patients18 years with a diagnosis of degenerative spinal spondylosis or spinal instability treated with spinal fusion were included. Risk factors for vitamin D deficiency (20 ng/mL) were analyzed using univariate and multiple logistic regression to identify independent predictors of deficiency.The mean preoperative neck and Oswestry disability indexes of the 230 consecutive patients (mean, 57 ± 13.9 years) were 21.0 ± 9.8 and 22.2 ± 8.5, respectively. Mean 25-OH vitamin D level was 25.9 ± 12.4 ng/mL (range, 6-77 ng/mL). Sixty-nine (30.0%) patients had laboratory-confirmed vitamin D deficiency and 89 (38.9%) had laboratory-confirmed vitamin D insufficiency (20-30 ng/mL). The risk of vitamin D deficiency was greater in men (odds ratio [OR] 2.53; P = 0.009), patients aged 40-60 years (OR 2.45; P = 0.018), and those who had body mass index40 (OR 7.55; P = 0.004), an existing diagnosis of diabetes (OR 3.29; P = 0.019), or no vitamin D supplementation (OR 4.96; P = 0.043).Vitamin D deficiency was common in patients with degenerative spondylosis undergoing spinal fusion. Middle-aged patients, men, the morbidly obese, those with a history of diabetes, and those with no history of supplementation had a higher incidence of vitamin D deficiency.

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 replicates per mean). NIST-certified mass fractions (ng/g) ± U 95 from the Certificates of Analysis.

We investigated the vitamin D status of Korean women during pregnancy and assessed the effects of vitamin D deficiency on two pregnancy outcomes, preterm births and the births of small for gestational age. We measured the serum 25-hydroxyvitamin D levels in 220 pregnant Korean women who were recruited prospectively and compared these levels with those of 500 healthy non-pregnant women. We analyzed vitamin D status according to patient demographics, season, and obstetrical characteristics, moreover, we also assessed pregnancy outcomes. The overall prevalence of vitamin D deficiency(&lt, 20 ng/mL) in pregnant women and healthy non-pregnant women was 77.3% and 79.2%, respectively, and the prevalence of severe vitamin D deficiency (&lt, 10 ng/mL) was 28.6% and 7.2%, respectively (p &lt, 0.05). Vitamin D deficiency was more prevalent in the winter (100%) than in the summer (45.5%) in pregnant Korean women. A higher risk of vitamin D deficiency was observed in the first trimester than in the third trimester (adjusted OR 4.3, p &lt, 0.05). No significant association was observed between vitamin D deficiency and any of the pregnancy outcomes examined. Further research focusing on the long-term consequences of vitamin D deficiency during pregnancy in Korean women is warranted.

Background and aims: Vitamin D deficiency has been associated with increased risk for cardiovascular (CV) disease, but the possible effects of Vitamin D on cardiac structure and function are not well characterized. Methods and results: The correlation between 25-hydroxyvitamin D levels and metabolic and car- diac echocardiographic parameters was studied in ARTEMIS study population including 831dia- betic and 659 non-diabetic patients with stable coronary artery disease (CAD). Low levels of Vitamin D were associated with high BMI (p < 0.001), high total and LDL cholesterol and triglyc- eride levels (p < 0.001 for all) in both diabetics and non-diabetics. Among non-diabetic patients, low Vitamin D was also associated independently with elevated systolic and diastolic blood pres- sure (p < 0.005). Low Vitamin D levels were independently associated with reduced left ventric- ular (LV) ejection fraction (p < 0.005) and increased left atrial diameter (p < 0.03) measured by cardiac ultrasound by 2-dimensional echo. In the non-diabetic group, low Vitamin D levels were associated with impaired LV filling (high E/E 0 )( p< 0.03) and low E/A mitral flow pattern measured by Doppler echocardiography (p < 0.05). Among diabetics, low Vitamin D levels were also related to increased LV end-systolic diameter (p < 0.05) and right ventricular diameter (p < 0.005). The association between LV diastolic filling (E/E 0 ) and Vitamin D levels was signifi- cant (p < 0.01) after adjustment for the commonly recognized risk factors of diastolic dysfunc- tion in linear regression analysis. Conclusions: Low Vitamin D is associated with several major cardiovascular risk factors and car- diac structural changes including impaired systolic and diastolic function, which together may explain the association of low Vitamin D to worse cardiovascular outcome.

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

Summary Objectives: vitamin D is important for muscle function and it affects different aspects of muscle metabolism. This study aim to determine whether serum 25(OH) D levels are related to lung functions, physical performance and balance in patients with chronic obstructive pulmonary disease (COPD). Methods: in 90 patients with COPD and 57 healthy controls lung function tests, physical performance tests (time up and go, gait velocity test, sit-to-stand test, isometric strength, isokinetic strength), static (functional reach test) and dynamic (time up and go) balance tests and the association of 25(OH)D levels with lung functions, physical performance and balance were evaluated. Results: the COPD patients had significantly more deficit in physical function and balance parameters, and in dynamic balance test (p

BACKGROUND/OBJECTIVES: The superiority of cholecalciferol (D3) over ergocalciferol (D2) in sustaining serum 25-hydroxy vitamin D (25OHD) levels is controversial. To compare D2 with D3 we performed a single-blind, placebo-controlled randomized trial spanning 11 weeks. SUBJECTS/METHODS: Healthy volunteers (n=33, aged 33.4±6 years) were divided into three groups (n=11, each): D2, D3 and placebo. Treatment started with a loading dose (100,000 IU) followed by 4800 IU/day (d) between d7 and d20 and follow-up until d77. Serum samples were obtained at baseline and at days 3, 7, 14, 21, 35, 49, 63 and 77. RESULTS: Baseline 25OHD values in the D2 group were lower than those in the D3 and placebo groups (P

Background/Aim: Dietary phosphate intake and vitamin D receptor activator (VDRA) regulate fibroblast growth factor 23 (FGF23); iron may modulate FGF23 metabolism. We aimed to determine whether oral iron supplementation influences serum FGF23 concentration in hemodialysis (HD) patients, while excluding the effect of dietary phosphate intake. Methods: This prospective study enrolled 27 maintenance HD patients with iron deficiency and hyperphosphatemia treated with sevelamer-HCl. The phosphate binder was changed from sevelamer-HCl to ferric citrate hydrate (FCH) to maintain constant phosphate levels. VDRA, other phosphate binders, and cinacalcet HCl were not changed. Serum intact FGF23, C-terminal FGF23 (C-term FGF23), intact parathyroid hormone (PTH), 1,25(OH)2D and other parameters were monitored for 12 weeks. Results: Serum phosphate levels (5.89 ± 1.45 mg/dl at baseline, 5.54 ± 1.35 mg/dl at 12 weeks) and 1,25(OH)2D levels were unchanged. Serum ferritin levels increased from 25.6 ± 24.3 ng/ml at baseline to 55.8 ± 33.5 ng/ml at 12 weeks with FCH administration. Serum intact FGF23 and C-term FGF23 levels significantly decreased at 12 weeks compared with baseline (2,000 (1,300.0-3,471.4) to 1,771.4 (1,142.9-2,342.9) pg/ml, p = 0.01, and 1,608.7 (634.8-2,308.7) to 1,165.2 (626.1-1,547.8) RU/ml, p = 0.007, respectively); serum intact PTH levels significantly increased (96 (65-125) to 173 (114-283) pg/ml, p < 0.001). Conclusions: Oral FCH administration decreased serum intact FGF23 and C-term FGF23 levels and increased intact PTH levels; phosphate and 1,25(OH)2D levels were unchanged. Oral FCH administration to treat iron deficiency is a possible strategy for reducing serum FGF23 levels independent of phosphate and VDRA.

Objective Fatigue is a common, disabling symptom of multiple sclerosis ( MS), but little is known about fatigue in patients with clinically isolated syndrome ( CIS), often the presenting symptom of MS. We aimed to investigate the prevalence and severity of fatigue in patients with CIS, and its association with a diagnosis of clinically definite MS ( CDMS). Methods 127 patients were consecutively included in our ongoing prospective CIS study. At baseline, clinical, demographic, laboratory and MRI data were collected, and fatigue severity was assessed using Krupp's Fatigue Severity Scale ( FSS); fatigue was defined as FSS >= 5.0. Fatigue scores were compared with scores of 113 healthy controls and with scores from the literature. The association of fatigue with CDMS was calculated using Cox regression models. Results The mean FSS of patients with CIS was 4.3, similar to MS patients, and significantly higher than that of healthy individuals ( p

Lower 25-hydroxyvitamin D2 /D3 levels at melanoma diagnosis are associated with thicker primaries and poorer survival. We postulated that this might relate to the deleterious effect of systemic inflammation as 25-hydroxyvitamin D2 /D3 levels are inversely associated with levels of C-reactive protein. 2,182 participants in the Leeds Melanoma Cohort (median follow-up 7.98 years) provided data on drug exposure, comorbidities and a serum 25-hydroxyvitamin D2 /D3 level at recruitment. Factors reported to modify systemic inflammation (low vitamin D levels, high body mass index, use of aspirin or nonsteroidal anti-inflammatory drugs or smoking were tested as predictors of microscopic ulceration (in which primary tumors are inflamed) and melanoma-specific survival (MSS). Ulceration was independently associated with lower 25-hydroxyvitamin D2 /D3 levels (odds ratio (OR) = 0.94 per 10 nmol/L, 95% CI 0.88-1.00, p = 0.05) and smoking at diagnosis (OR = 1.47, 95% CI 1.00-2.15, p = 0.04). In analyses adjusted for age and sex, a protective effect was seen of 25-hydroxyvitamin D2 /D3 levels at diagnosis on melanoma death (OR = 0.89 per 10 nmol/L, 95% CI 0.83-0.95, p0.001) and smoking increased the risk of death (OR = 1.13 per 10 years, 95% CI 1.05-1.22, p = 0.001). In multivariable analyses (adjusted for tumor thickness) the associations with death from melanoma were low 25-hydroxyvitamin D2 /D3 level at recruitment (20 nmol/L vs. 20-60 nmol/L, hazard ratio (HR) = 1.52, 95% CI 0.97-2.40, p = 0.07) and smoking duration at diagnosis (HR = 1.11, 95% CI 1.03-1.20, p = 0.009). The study shows evidence that lower vitamin D levels and smoking are associated with ulceration of primary melanomas and poorer MSS. Further analyses are necessary to understand any biological mechanisms that underlie these findings.

This double-blind, randomized, controlled study assessed the effect of esterified propoxylated glycerol (EPG) on fat-soluble vitamins and select nutrients in human subjects. For 8 weeks, 139 healthy volunteers consumed a core diet providing adequate caloric and nutrient intakes. The diet included items (spread, muffins, cookies, and biscuits) providing EPG (10, 25, and 40 g/day) vs. margarine alone (control). EPG did not significantly affect circulating retinol, α-tocopherol, or 25-OH D2, but circulating β-carotene and phylloquinone were lower in the EPG groups, and PIVKA-II levels were higher; 25-OH D3 increased but to a lesser extent than the control. The effect might be related to EPG acting as a lipid “sink” during gastrointestinal transit. No effects were seen in secondary endpoint measures (physical exam, clinical pathology, serum folate, RBC folate, vitamin B12, zinc, iron, calcium, phosphorus, osteocalcin, RBP, intact PTH, PT, PTT, cholesterol, HDL-C, LDL-C, triglycerides). Gastrointestinal adverse events (gas with discharge; diarrhea; oily spotting; oily evacuation; oily stool; liquid stool; soft stool) were reported more frequently by subjects receiving 25 or 40 g/day of EPG. In general, the incidence and duration of these symptoms correlated directly with EPG dietary concentration. The results suggest 10 g/day of EPG was reasonably well tolerated.

This article presents an overview of the most recent scientific evidence of the role of maternal vitamin D on pregnancy outcomes, with a particular emphasis on those articles in the English-language literature published between 1 January 2013 and 1 July 2014 in PubMed.Low levels of vitamin D status, as measured by 25-hydroxyvitamin D [25(OH)D], are common in pregnant women. Meta-analysis of observational studies has demonstrated positive associations between vitamin D status and adverse pregnancy outcomes such as preeclampsia, gestational diabetes mellitus, preterm birth and small-for-gestational age. There was heterogeneity among studies in terms of design, population, geographic location, definitions of exposure and outcome, gestational age at sampling, confounding factors and approach to analyses. Randomized controlled trials (RCTs) indicate that vitamin D supplementation during pregnancy optimizes maternal and neonatal vitamin D status.Recent evidence supports that low maternal vitamin D status is associated with an increased risk of adverse pregnancy outcomes. Interventional studies demonstrate that vitamin D supplementation during pregnancy optimizes maternal and neonatal vitamin D status. Large, well designed, multicentre RCTs are required to determine whether vitamin D supplementation in pregnant women with low vitamin D status reduces the risk of adverse pregnancy outcomes.

OBJECTIVE Carotid intima media thickness (IMT), a predictor of cardiovascular events, is reported to be higher in African-American (AA) vs White (AW) individuals. We investigated whether racial differences in IMT in obese adolescents could be explained by differences in 25 hydroxy-vitamin D [25(OH)D]. RESEARCH DESIGN AND METHODS A total of 63 obese adolescents had 25(OH)D levels, determination of IMT, body composition, insulin sensitivity (IS) by hyperinsulinemic-euglycemic clamp, lipids and blood pressure (BP). RESULTS IMT was higher and 25(OH)D lower in AA vs AW. IMT correlated with 25(OH)D level (r = -0.38, P = .002) but not with IS. In multiple regression analysis, race, HbA1c, BP and age, and not 25(OH)D, BMI or IS, were the significant determinants of IMT (R2 = 0.44, P < .001). Without race in the model, 25(OH)D (β = -0.36, P = .009) contributed to the variance in IMT (R2 = 0.32, P = .007). CONCLUSION Obese AA adolescents vs AW, have higher IMT, explained by race, BP, and HbA1c. Although 25(OH)D levels contribute to the variance in IMT, the observed racial difference in IMT could be mediated through other unknown race-related factors besides 25(OH)D.

Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre‐diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case‐control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord‐Trøndelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n = 626; HUNT2 n = 112; median follow‐up = 6.9 years) were matched to 738 controls. Vitamin D [25(OH)D2 and 25(OH)D3 combined] concentrations were determined using isotope‐dilution liquid chromatography‐tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42–1.20); 0.94 (0.72–1.22); 1.12 (0.82–1.53) and 1.26 (0.79–2.01) for clinically pre‐defined categories of ≤25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend = 0.09). Corresponding analyses by quintiles of season‐standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend = 0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre‐diagnostic concentrations of vitamin D, they are not statistically significant., What's new? Living at lower latitude and increased ultraviolet light exposure are inversely correlated with pancreatic cancer (PC) risk, supporting a model where vitamin D may protect from this devastating cancer. Here, the authors performed the largest combination of European studies to date and find that higher vitamin D concentrations are not associated with a lower risk of PC. They recommend caution before guidelines to increase vitamin D concentrations for the prevention of cancer can be recommended.

This study investigated the effects of synthetic and natural sources of vitamin D biofortification in pig diets on pork vitamin D activity and pork quality. One hundred and twenty pigs (60 male, 60 female) were assigned to one of four dietary treatments for a 55 d feeding period. The dietary treatments were (1)50 μg vitamin D₃/kg of feed; (2)50 μg of 25-hydroxvitamin D₃/kg of feed (25-OH-D₃); (3)50 μg vitamin D₂/kg of feed; (4)50 μg vitamin D₂-enriched mushrooms/kg of feed (Mushroom D₂). The pigs offered the 25-OH-D₃ diet exhibited the highest (P < 0.001) serum total 25-hydroxyvitamin D concentration and subsequently exhibited the highest (P < 0.05) Longissimus thoracis (LT) total vitamin D activity. Mushroom D2 and 25-OH-D3 supplementation increased pork antioxidant status. The vitamin D₂-enriched mushrooms improved (P < 0.05) pig performance, carcass weight and LT colour. In conclusion, 25-OH-D₃ is the most successful source for increasing pork vitamin D activity, while Mushroom D2 may be a new avenue to improve animal performance and pork quality. Department of Agriculture, Food and the Marine European Commission - Seventh Framework Programme (FP7)

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

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

In 2010, the dietary guidelines for vitamin D for Canadians and Americans aged 1–70 years were revised upward. It is unknown whether the vitamin D status of Canadian children improved after 2010. We compared the prevalence of vitamin D sufficiency (25-hydroxy vitamin D (25(OH)D) concentration of ≥50 nmol/L), 25(OH)D concentration and the frequency of consuming vitamin D-rich foods among children aged 6–18 years-old using data from the nationally representative 2007/2009 and 2012/2013 Canadian Health Measures Surveys. Associations of sociodemographic, anthropometric, seasonal, and regional variables with achieving vitamin D sufficiency, 25(OH)D concentration, and consumption of vitamin D-rich foods were assessed using multiple logistic and linear regression models. 79% and 68% of children in 2007/2009 and 2012/2013 respectively, were vitamin D sufficient. The main dietary source of vitamin D was milk. Between 2007/2009 and 2012/2013, the frequency of milk and fish consumption declined, but egg and red meat consumption was unchanged. Age, income, weight status, season and ethnicity were associated with 25(OH)D concentration and vitamin D sufficiency. Vitamin D status declined after the upward revision of dietary guidelines for vitamin D, consequently, dietary intake was inadequate to meet sufficiency. Public health initiatives to promote vitamin D-rich foods and supplementation for Canadian children are needed.

Estimation of the parathyroid hyperplasia prevalence after the ChNPP accident in adults exposed to ion izing radiation and their descendants using the diagnostic ultrasound and its methodology elaboration.The pilot prospective study of the prevalence of parathyroid hyperplasia among the Chornobyl Nuclear Power Plant (ChNPP) accident adult survivors (n=686) and their descendants (54 children) was performed using diagnostic ultrasound examination of thyroid and parathyroids. Among the study subjects there were 339 ChNPP accident clean up workers (ACUW), 32 persons were evacuated from the 30 km exclusion zone and 224 ones were included to the control group. Diagnostic ultrasound of thyroid and parathyroids was performed according to the standard method. Additionally, in children with parathyroid hyperplasia an additional assay of 25 hydroxyvitamin D levels in serum was performed. In calculating the statistical significance, its level p0.05 was considered statistically significant.Parathyroids are a few small but critically important endocrine glands that synthesize parathyroid hormone, regulating mainly phosphoric calcium metabolism. Insufficient (hypoparathyroidism) or excessive (hyperparathy roidism) function of parathyroids is harmful to the patients affecting the state of nervous and cardiovascular sys tem. Parathyroidss can accumulate isotopes of cesium, strontium and radioactive iodine. The available data testify to an increased incidence of clinically significant hyperplasia of parthyroids (more than 9 mm in adults and more than 5 mm in children) among persons exposed toionizng radiation as a result of the accident at the ChNPP (28.64%) and their descendants (23.8-70.6%). First of all are concerned those adults who live in contaminated areas in comparison with the control group (24.15% in not irradiated). Evacuees from the 30 km exclusion zone being the category of people who were exposed to the absorbed iodine isotopes in the first days of the Chernobyl accident are the another risk group. These data demonstrate sensitivity of parathyroidss to the impact of incorpo rated isotopes (iodine, cesium and strontium), which in the long term exposure create conditions for structural and functional changes in regulation of phosphorous calcium metabolism being the basis for a significant prevalence of osteopenia and osteoporosis in irradiated individuals and their descendants. A number of further studies are required to clarify the findings and to disclose the hormonal mechanisms of radiation effects on parathyroids.Parathyroid glands are radiosensitive and susceptible to effects of strontium, cesium and iodine iso topes, which cause parathyroid irradiation and subsequent structural and functional changes, being a prerequisite for development of osteopenia and osteoporosis in the ChNPP accident survivors and their descendants. High inci dence of parathyroid hypertrophy is found in the inhabitants of the radiation contaminated territories (long term irradiation by cesium isotopes), as well as in evacuated from the 30 km exclusion zone (irradiation by iodine iso topes in the early days of the accident).Meta. Vyznachennia poshyrenosti giperplaziy̆ pryshchytopodibnykh zaloz u oprominenykh vnaslidok avariï na ChAES do roslykh ta ïkh nashchadkiv pry skryningovomu ul'trazvukovomu doslidzheni ta vidpratsiuvaty y̆ogo metodologiiu. Materialy ta metody. Pilotne prospektyvne doslidzhennia poshyrenosti giperplaziï PShchPZ sered osib, postrazh dalykh vnaslidok avariï na Chornobyl's'kiy̆ atomniy̆ elektrostantsiï (ChAES) doroslogo viku (686 osib) ta ïkh na shchadkiv (54 ditey̆) provedeno UZD ShchPZ ta PShchPZ, z iakykh 339 vidnosylysia do uchasnykiv likvidatsiï naslidkiv avariï na ChAES, 32 osoby – evakuy̆ovani z 30 km zony vidchuzhennia ta 224 osib z grupy kontroliu. Provedeno ul'trazvu kove doslidzhennia shchytopodibnoï ta pryshchytopodibnykh zaloz za standartnoiu metodykoiu. Dodatkovo u ditey̆ z giperplaziieiu pryshchytopodibnykh zaloz provodylos' vybirkove doslidzhennia rivnia 25 gidroksyvitaminu D u syro vattsi krovi. Pry rozrakhunku statystychnoï znachushchosti, ïï riven' r0,05 vvazhaly statystychno dostovirnym. Rezul'taty. Pryshchytopodibni zalozy – tse dekil'ka nevelykykh ale vplyvovykh endokrynnykh zaloz, shcho syntezu iut' paratgormon, reguliuiut', golovnym chynom, fosforno kal'tsiievyy̆ obmin. Nedostatnia (gipoparatyreoz) abo nadlyshkova (giperparatyreoz) funktsiia pryshchytopodibnykh zaloz ie shkidlyvymy dlia patsiientiv, vplyvaie na stan nervovoï ta sertsevo sudynnoï systemy. Pryshchytopodibni zalozy mozhut' nakopychuvaty izotopy tseziiu, strontsiiu i radioaktyvnogo y̆odu. Otrymani dani svidchat' pro pidvyshchennia chastoty klinichno znachushchykh giperplaziy̆ pryshchyto podibnykh zaloz (ponad 9 mm u doroslykh, bil'she 5 mm u ditey̆) sered oprominenykh osib vnaslidok avariï na ChAES (28,64 %) ta ïkh nashchadkiv (23,8–70,6 %), persh za vse tykh, iaki meshkaiut' na zabrudnenykh terytoriiakh doroslogo viku v porivnianni z kontrol'noiu grupoiu (neopromineni – 24,15 %). Inshoiu grupoiu ryzyka buly evakuy̆ovani z 30 km zony vidchuzhennia – kategoriia osib, iaka zaznala diï poglynutykh izotopiv y̆odu v pershi dni avariï na ChAES.Tsi dani demonstruiut' chutlyvist' pryshchytopodibnykh zaloz do diï inkorporovanykh izotopiv (y̆odu, tseziiu i strontsiiu), shcho u viddaleni terminy oprominennia stvoriuiut' umovy dlia strukturno funktsional'nykh zmin u systemi reguliatsiïfosforno kal'tsiievogoobminu,iepidґruntiamdlia znachnoïposhyrenostiosteopeniïtaosteoporozuuop rominenykh osib ta ïkh nashchadkiv. Neobkhidno provesty nyzku doslidzhen' dlia podal'shogo utochnennia otrymanykh da nykh ta rozkryttia gormonal'nykh mekhanizmiv vplyvu ionizuiuchogo vyprominennia na pryshchytopodibnykh zaloz. Vysnovky. Pryshchytopodibni zalozy ie radiatsiy̆no chutlyvymy do diï izotopiv strontsiiu, tseziiu ta y̆odu, iaki obumov liuiut' ïkh oprominennia ta nastupni strukturno funktsional'ni zminy, shcho ie peredumovoiu rozvytku osteopeniï ta osteoporozu v osib, iaki postrazhdaly vnaslidok avariï na ChAES ta ïkh nashchadkiv. Vysoka chastota giperplaziï pry shchytopodibnykh zaloz vyiavlena v meshkantsiv radiatsiy̆no zabrudnenykh terytoriy̆ (dovgotryvale oprominennia izo topamy tseziiu), a takozh u evakuy̆ovanykh z 30 km zony vidchuzhennia (oprominennia izotopamy y̆odu v pershi dni avariï).

A simple and economical method has been developed for simultaneous determination of human serum 25-hydroxyvitamin D

Background: Resting metabolic rate (RMR) used to prognosticate and measure the amount of energy required. Vitamin D is known as a new predictor of RMR. The aim of this study is to investigate the relationship between vitamin D effects on RMR in connection with the vitamin D receptor (VDR) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) gene expression. Methods: We enrolled 298 overweight and obese adults in this cross-sectional study. Body mass index (BMI), fat mass, fat-free mass, insulin level, visceral fat, and vitamin D status were assessed. RMR was measured by means of indirect calorimetry. The real-time polymerase chain reaction using specific primer pairs for VDR and PGC-1α was performed. Results: There were significant differences in terms of fat free mass, fat percentage, insulin levels, RMR/kg body weight, and RMR/BMI, VDR, and PGC-1α among participants were categorized based on the vitamin D status. But after using general linear model for adjusting, all significant results missed their effectiveness except RMR/kg body weight and VDR. Linear regression analysis used to show the mediatory role of VDR and PGC-1α on the RMR/kg body weight and vitamin D status relationship. Our results showed that VDR had a mediatory effect on the relationship between RMR/kg body weight and vitamin D status (β = 0.38, 95% CI –0.48 to 1.60; β = –1.24, 95% CI –5.36 to 1.70). However, PGC-1α did not affect the relationship between RMR/kg body weight and vitamin D status (β = 0.50, 95% CI = –0.02 to 3.42; β = 0.59, 95% CI 0.14–3.90). Conclusion: Our study showed the mediatory effect of VDR gene expression in the association of 25(OH)2D plasma levels and resting metabolic rate among obese individuals.

Rickets is failure in mineralization of growing bone and cartilage due to extreme vitamin D deficiency (VDD). The study aimed to identify rickets among vitamin D deficient children and determine any relationship between clinical findings and paraclinical evidence.This study was conducted in two stages. In the first stage, blood was drawn from 406 children aged 30-72 months for measurement of 25(OH)D level. Of these children, 108 had 25(OH)D levels of20 ng/dL and were evaluated physically for signs and symptoms scores (0-1) of VDD and rickets. Biochemical analysis and radiography of the child's left wrist and hand was performed.Of the 119 children (29.67%) with 25(OH)D levels of20 ng/dL, 42 (10.3%) had vitamin D levels of ≤15 ng/dL. There was no correlation between serum 25(OH)D level and levels of calcium (Ca) (r = -0.16), alkaline phosphatase (ALP) (r = -0.12), P (r = 0.13), and parathyroid hormone (PTH) (r = -0.15,) in children with VDD. The mean of signs and symptoms scores had no significant difference between children with (1.59 ± 0.8) and without (1.73 ± 1.01) VDD (P = 0.3). None of the children with VDD had radiographic evidence of rickets. Radiographic data showed that 69.2% (72), 10.6% (11), and 20.2% (21) of the children had delayed, normal, and advanced bone age, respectively.Abnormal radiological findings of rickets were not found on wrist X-rays. Thus, this investigation is not necessary within the range of vitamin D levels described in the current study.

A large number of evidence supports the role of vitamin D insufficiency in both women and men infertility. However, no studies have evaluated the rate of concordance of vitamin D status between the partners. This finding might open new scenarios in the interpretation of the available data linking vitamin D insufficiency and infertility. In the present cross-sectional study, 103 consecutive infertile couples were recruited between April and May 2014. Both partners concomitantly provided a serum sample for the assessment of 25-hydroxy-vitamin D [25-(OH)-D]. Vitamin D insufficiency was defined as serum 25-(OH)-D 20 ng/ml. One hundred-fifty subjects (73 women and 77 males) were 25-(OH)-D insufficient, corresponding to a rate of 73%. Overall, concordance was observed in 73 couples (71%), thus higher than the expected 61% (0.732 + 0.272) based on chance (p = 0.007). The Pearson coefficient of correlation R2 between the partners of the couples was 0.52 (p 0.001). No statistically significant differences emerged when evaluating the rate of 25-(OH)-D insufficiency according to the causes of infertility. Serum 25-(OH)-D correlates within the partners of infertile couples. Further evidence is warranted to determine the clinical relevance and possible clinical applications of this finding.

Vitamin D deficiency is associated with wide range of pathologies. Some evidences have shown that low vitamin D circulating levels in children and adolescent are related to fat mass and obesity. The objectives of the present study were to characterize vitamin D status in children and adolescents and to determine if serum 25-hydroxyvitamin D (25(OH)D) concentration is related to adiposity assessed by body mass index (BMI). Serum 25(OH)D levels were measured by LIAISON method in 471 children and adolescents (2 to 18 years age) and analyzed according to gender, pubertal period, age, and BMI. An overall prevalence of 25(OH)D insufficiency and deficiency was present in the 67.1%. Lower 25(OH)D levels were found in females (25.56 ± 14.03 vs 29.71 ± 17.10 ng ml−1; P = 0.004) and pubertal children (25.52 ± 13.97 vs 29.21 ± 16.83 ng ml−1; P = 0.011). In addition, an inverse relation of BMI and age on 25(OH)D concentrations was observed in children. In conclusion, low vitamin D status was highly prevalent among children and adolescents. Of note, a non-lineal regression model showed that 39.6% of vitamin D levels variability was explained by BMI. These results indicate that adiposity assessed by BMI impacts vitamin D status.

We investigated associations between serum 25-hydroxyvitamin D (25(OH)D) in pregnancy and birth weight and other neonatal anthropometric measures. The present study was a population-based, multiethnic cohort study of 719 pregnant women (59 % ethnic minorities) in Oslo, Norway, delivering a singleton neonate at term and with birth weight measurements. In a representative sample, anthropometric measurements were taken. Maternal 25(OH)D was measured at gestational weeks 15 and 28. Women with 25(OH)D 3 supplementation. Separate linear regression analyses were performed to model the associations between 25(OH)D and each of the outcomes: birth weight, crown–heel length, head circumference, abdominal circumference, sum of skinfolds, mid-upper arm circumference and ponderal index. In early pregnancy, 51 % of the women were vitamin D deficient (25(OH)DPPfor interaction

Low plasma 25-hydroxy-vitamin D (25OHD) and high levels of parathyroid hormone (PTH) are associated with obesity and could play a role in the occurrence of complications such as insulin resistance. The objective of the study was to evaluate whether the relationship between 25OHD status and phosphocalcic parameters differs between metabolically healthy obese (MHO) and insulin-resistant obese (IRO). This cross-sectional study included 158 consecutive adults (121 females) with obesity (body mass index (BMI) 35.15 ± 2.8 kg/m2), aged 43.21 ± 13.6 years. Serum 25OHD, calcemia, phosphatemia, PTH, plasma lipids, fasting plasma glucose, insulin levels, and body composition were measured. Participants were classified as MHO (n = 65) or IRO (n = 93) based on homeostatic model assessment insulin-resistance value. IRO patients had a higher BMI (p = 0.001), waist circumference (p = 0.03), and trunk fat mass (p = 0.007) than MHO patients. Mean HbA1c (p = 0.03), triglycerides (p = 0.02), and hsCRP (p = 0.04) plasmatic levels were increased in the IRO group. No between-group difference was found on 25OHD, PTH, calcium, or phosphorus plasmatic levels. Only age-predicted 25OHD levels were identified among IRO participants, whereas no factors were identified in MHO. No predictive factors of PTH plasmatic level were identified in the IRO and MHO groups. Although MHO and IRO patients have different metabolic profiles, we did not detect any difference regarding either 25OHD or PTH. Insulin resistance was not a predictive factor of vitamin D status. Our results confirm the absence of link between vitamin D status and insulin resistance in moderate obesity.

The relationship between 25 hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and metabolic traits appear to differ among ethnicities and may be influenced by obesity. The aim of the study was to examine the association of serum 25(OH)D or PTH with metabolic syndrome (MetS) while controlling for adiposity in black women. Using a cross-sectional study design, 209 urban black women aged ≥ 43 years from the North West Province, South Africa, were included. Multiple regression models were used to explore the relationship between 25(OH)D or PTH and body composition. To explore the association between 25(OH)D or PTH and MetS, a separate variable was created including at least 3 of the MetS criteria, but excluding elevated waist circumference as a diagnostic criterion in a logistic regression model. The majority of the women (69.9%) were overweight or obese and 65.5% of the women had excessive adiposity using the age-specific cut-off points for body fat percentage. All body composition variables were positively associated with PTH, whereas body mass index and waist circumference, but not body fat percentage, had negative associations with 25(OH)D also after adjusting for confounders. Before and after adjusting for age, body fat, habitual physical activity, tobacco use, season of data collection, and estimated glomerular filtration rate, neither 25(OH)D nor PTH showed significant associations with MetS. Although PTH was positively associated and 25(OH)D was negatively associated with adiposity in black women, there was no association between either 25(OH)D or PTH and MetS in this study population, nor did adiposity influence these relationships.

BACKGROUND Three immunochemical methods for the determination of 25-(OH)-vitamin D and validated HPLC method for the determination of 25-(OH)-vitamin D3 and 25-(OH)-vitamin D2 were compared. 62 patient samples from postmenopausal women were measured and the results obtained by all these methods were compared. METHODS We used three chemiluminescent assays for determination of 25-(OH)-vitamin D. 25-(OH)-vitamin D3 and 25-(OH)-vitamin D2 were determined by HPLC with UV detection (Agilent 1200). The chemiluminescent assays were performed using the Abbott Architect i4000SR analyzer (Abbott Laboratories, Germany), the ADVIA Centaur (Siemens, USA), and the Liaison XL (DiaSorin Inc, USA). The statistical evaluation was done using GraphPad Prism 6.0. RESULTS The data were tested by Tukey's multiple comparison test. All methods showed significant differences in comparison with the immunochemical method from DiaSorin (p < 0.001 for Abbott, p < 0.05 for Siemens, and p < 0.0001 for HPLC). The comparison of the immunochemical method from Siemens with HPLC was also significant, p < 0.05. The mean of DiaSorin measurements was 38% lower than the mean of HPLC measurements. The non-significant difference was shown by the comparison of Abbott with HPLC and also Abbott with Siemens. Means for the 25-(OH)-vitamin D methods used were: Abbott 70.2 ± 24.2 nmol/L, Siemens 67.6 ± 27.9 nmol/L, DiaSorin 53.5 ± 17.1, and HPLC 82.4 ± 40.0 nmol/L. CONCLUSIONS The comparison of the DiaSorin immunochemical assay with other tested methods showed the greatest deviation. The mean of DiaSorin measurements was 38% lower than the mean of HPLC measurements. According to the results of the DiaSorin method, most patients treated with vitamin D would not achieve the optimal level of 25-(OH)-vitamin D and this could negatively affect the clinical decision.