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Vitamin D is an essential nutrient to be consumed in the habitual dietary intake, whose deficiency is associated with various disturbances. This study represents a validation of vitamin D status estimation using a semi-quantitative FFQ, together with data from additional physical activity and lifestyle questionnaires. This information was combined to forecast the serum vitamin D status. Different statistical methods were applied to estimate the vitamin D status using predictors based on diet and lifestyle. Serum vitamin D was predicted using linear regression (with leave-one-out cross-validation) and random forest models. Intraclass correlation coefficients, Lin's agreement coefficients, Bland-Altman plots and other methods were used to assess the accuracy of the predicted v . observed serum values. Data were collected in Spain. A total of 220 healthy volunteers aged between 18 and 78 years were included in this study. They completed validated questionnaires and agreed to provide blood samples to measure serum 25-hydroxyvitamin D (25(OH)D) levels. The common final predictors in both models were age, sex, sunlight exposure, vitamin D dietary intake (as assessed by the FFQ), BMI, time spent walking, physical activity and skin reaction after sun exposure. The intraclass correlation coefficient for the prediction was 0·60 (95 % CI: 0·52, 0·67; P < 0·001) using the random forest model. The magnitude of the correlation was moderate, which means that our estimation could be useful in future epidemiological studies to establish a link between the predicted 25(OH)D values and the occurrence of several clinical outcomes in larger cohorts.

Previous studies of the effect of vtamin D on serum levels of fibroblast growth factor- 23 (FGF-23) have yeilded an inconsistent findings. This systematic review and meta-analysis of randomized controlled trials (RCTs) sought to investigate the effect of vitamin D supplementation on serum levels of FGF-23. PubMed, Scopus, ISI Web of Science, and the Cochrane Library were searched, from database inception to November 2020, for RCTs that evaluated the effects of native or active vitamin D supplementation on serum levels of FGF-23 in adults. Weighted mean difference (WMD) were calculated and random effects meta-analysis was used to estimate the overall effects. Twenty-seven trials were included in the meta-analysis. Supplementation with native vitamin D (23 studies, n = 2247 participants; weighted mean difference [WMD] = 0.5 pg/mL, 95 % CI: -0.52 to 1.51, P = 0.33; I 2 = 29.9 %), and active vitamin D (5 studies, n = 342 participants, WMD = 29.45 pg/mL, 95 % CI: -3.9 to 62.81, P = 0.08; I 2 = 99.3%) had no significant effects on serum FGF-23 concentration. In subgroup analyses, supplementation with ergocalciferol (3 studies, n = 205 participants; WMD = 18.27 pg/mL, 95 % CI: 5.36-31.17, P = 0.006), and daily dosing regimens (9 studies, n = 1374 participants; WMD = 0.41 pg/mL, 95 % CI: 0.22 to 0.59, P < 0.001) increased serum FGF-23 levels compared to control. Overall, our findings revealed no significan effect of vitamin D supplementation on serum FGF-23 concentration. However, further high quality, large-scale studies are needed to better elucidate this relationship., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Widespread prevalence of vitamin D deficiency has been documented globally. Commonly used interventions to address this deficiency include supplementation and/or fortification with either ergocalciferol (vitamin D 2 ) or cholecalciferol (vitamin D 3 ), but the relative efficacy of these two vitamers is unclear. The current study aimed to evaluate the relative efficacy of ergocalciferol (vitamin D 2 ) and cholecalciferol (vitamin D 3 ) for raising the serum levels of vitamin D metabolites and functional indicators including serum parathyroid (PTH) levels, isometric muscle strength, hand grip strength and bone mineral density., Methods: Randomized and non-randomized controlled studies evaluating relative efficacy of ergocalciferol and cholecalciferol were systematically reviewed to synthesize quantitative and qualitative evidence as per the recommendations of according to "Preferred Reporting Items for Systematic reviews and Meta-analysis" guidelines. Search terms were constructed on the basis of the "participants", "intervention", "control", "outcome" and "study type" (PICOS) strategy to systematically search the popular electronic databases. Relevant data from studies meeting inclusion and exclusion criteria were extracted and analyzed. Meta-regression, subgroup and sensitivity analyses were performed to investigate the influence of study-level characteristics including intervention dosage, frequency of dosing, interval between the last dose and test for outcome assessment, participant characteristics and analytical methods., Results: Apparently healthy human participants ( n = 1277) from 24 studies were included for meta-analysis. The quantitative analysis suggested higher efficacy of cholecalciferol than ergocalciferol in improving total 25(OH)D (mean difference: 15.69, 95%CI: 9.46 to 21.93 nmol/L) and reducing PTH levels, consistently across variable participant demographics, dosage and vehicle of supplementation. Meta-regression suggested smaller differences in the efficacy of cholecalciferol and ergocalciferol at lower doses. Average daily dose was the single significant predictor of effect size, as revealed by multivariate meta-regression analysis., Conclusions: Compared to ergocalciferol, cholecalciferol intervention was more efficacious in improving vitamin D status (serum levels of total 25(OH)D and 25(OH)D 3 ) and regulating PTH levels, irrespective of the participant demographics, dosage and vehicle of supplementation.

The objective of this study was to determine the impact of calcium sensing receptor (CASR) A990G genetic polymorphism on parathyroid hormone (PTH) lowering response to cinacalcet treatment when controlling for significant influencing clinical factors. This retrospective study was conducted on 135 Thai hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). CASR A990G genotypes were determined. The patients were identified as either G carriers (heterozygous or homozygous CASR 990G allele carriers) or noncarriers (homozygous CASR 990A carriers). Tested covariates were baseline PTH level (bPTH), baseline serum phosphate (bPhos), baseline serum calcium (bCa), baseline calcitriol equivalent dose (bCtriol), baseline ergocalciferol dose (bErgo), and age. The ANCOVA showed that intact PTH levels after 12 weeks of cinacalcet treatment (PTHw12) was significantly lower among G carriers compared with noncarriers after controlling for bPTH, bPhos, bCtriol, and bErgo (F(1, 127) = 15.472, p < 0.001), with the adjusted mean difference of 253.7 pg/mL. The logistic regression analysis revealed that the odds of a G carrier achieving 30% PTH reduction after 12-week cinacalcet treatment were 3.968 times greater than the odds for a noncarrier after adjusting for bPhos, bCtriol, and age. In conclusion, the CASR A990G polymorphism significantly influences cinacalcet response in HD patients with SHPT., (© 2021. The Author(s).)

Vitamin D deficiency is a global problem with many health consequences, and it is currently recommended to supplement vitamin D. Change of diet should also be considered to ensure adequate vitamin D in the human body. The aim of this study was to assess the concentration of vitamin D metabolites in two different groups: one group on the low-carbohydrate-high-fat (LCHF) diet and the other group on the Eastern European (EE) diet. In the first stage, 817 participants declaring traditional EE diet or LCHF diet were investigated. Nutrition (self-reported 3-day estimated food record) and basic anthropometric parameters were assessed. After extra screening, 67 participants on the EE diet and 41 on the LCHF diet were qualified for the second stage. Plasma 25-hydroxycholecalciferol (25(OH)D 3 ) and (25(OH)D 2 ) concentration was measured by the validated HPLC-MS/MS method. Plasma 25(OH)D 3 concentration was significantly higher in the group on the LCHF diet (34.9 ± 15.9 ng/mL) than in the group on the EE diet (22.6 ± 12.1 ng/mL). No statistical differences were observed in plasma 25(OH)D 2 concentration between the study groups ( p > 0.05). Women had a higher plasma 25(OH)D 2 concentration than men regardless of diet type. The LCHF diet had a positive influence on plasma vitamin D concentration. However, long-term use of the LCHF diet remains contentious due to the high risk of cardiovascular disease. This study confirmed that the type of diet influences the concentration of vitamin D metabolites in the plasma.

(1) Background: Vitamin D, a well-established regulator of calcium and phosphate metabolism, also has immune-modulatory functions. An uncontrolled immune response and cytokine storm are tightly linked to fatal courses of COVID-19. The present retrospective study aimed to inves-tigate vitamin D status markers and vitamin D degradation products in a mixed cohort of 148 hospitalized COVID-19 patients with various clinical courses of COVID-19. (2) Methods: The serum concentrations of 25(OH)D 3 , 25(OH)D 2 , 24,25(OH) 2 D 3 , and 25,26(OH) 2 D 3 were determined by a validated liquid-chromatography tandem mass-spectrometry method in leftover serum samples from 148 COVID-19 patients that were admitted to the University Hospital of the Medical Uni-versity of Graz between April and November 2020. Anthropometric and clinical data, as well as outcomes were obtained from the laboratory and hospital information systems. (3) Results: From the 148 patients, 34 (23%) died within 30 days after admission. The frequency of fatal outcomes did not differ between males and females. Non-survivors were significantly older than survivors, had higher peak concentrations of IL-6 and CRP, and required mechanical ventilation more frequently. The serum concentrations of all vitamin D metabolites and the vitamin D metabolite ratio (VMR) did not differ significantly between survivors and non-survivors. Additionally, the need for res-piratory support was unrelated to the serum concentrations of 25(OH)D vitamin D and the two vitamin D catabolites, as well as the VMR. (4) Conclusion: The present results do not support a relevant role of vitamin D for the course and outcome of COVID-19.

The influence of energy restriction (ER) on muscle is controversial, and the mechanisms are not well understood. To study the effect of ER on skeletal muscle phenotype and the influence of vitamin D, rats ( n = 34) were fed a control diet or an ER diet. Muscle mass, muscle somatic index (MSI), fiber-type composition, fiber size, and metabolic activity were studied in tibialis cranialis (TC) and soleus (SOL) muscles. Plasma vitamin D metabolites and renal expression of enzymes involved in vitamin D metabolism were measured. In the ER group, muscle weight was unchanged in TC and decreased by 12% in SOL, but MSI increased in both muscles ( p < 0.0001) by 55% and 36%, respectively. Histomorphometric studies showed 14% increase in the percentage of type IIA fibers and 13% reduction in type IIX fibers in TC of ER rats. Decreased size of type I fibers and reduced oxidative activity was identified in SOL of ER rats. An increase in plasma 1,25(OH) 2 -vitamin D (169.7 ± 6.8 vs. 85.4 ± 11.5 pg/mL, p < 0.0001) with kidney up-regulation of CYP27b1 and down-regulation of CYP24a1 was observed in ER rats. Plasma vitamin D correlated with MSI in both muscles ( p < 0.001), with the percentages of type IIA and type IIX fibers in TC and with the oxidative profile in SOL. In conclusion, ER preserves skeletal muscle mass, improves contractile phenotype in phasic muscles (TC), and reduces energy expenditure in antigravity muscles (SOL). These beneficial effects are closely related to the increases in vitamin D secondary to ER.

Background: Prevalence of vitamin D insufficiency/deficiency has been noted in athletic populations, although less is known about recreationally active individuals. Biofortification of natural food sources (e.g. UV radiated mushrooms) may support vitamin D status and is therefore of current scientific and commercial interest. The aim of this study was to assess the impact of a mushroom-derived food ingredient on vitamin D status in recreationally active, healthy volunteers., Methods: Twenty-eight participants were randomly assigned to either: 25 μg (1000 IU) encapsulated natural mushroom-derived vitamin D 2 ; matched-dose encapsulated vitamin D 3 or placebo (PL) for 12 weeks. Venous blood samples were collected at baseline, week 6 and 12 for analysis of serum 25(OH)D 2 and 25(OH)D 3 using liquid chromatography mass spectrometry. Habitual dietary intake and activity were monitored across the intervention., Results: Vitamin D status (25(OH)D TOTAL ) was significantly increased with vitamin D 3 supplementation from 46.1 ± 5.3 nmol·L - 1 to 88.0 ± 8.6 nmol·L - 1 (p < 0.0001) across the intervention, coupled with an expected rise in 25(OH)D 3 concentrations from 38.8 ± 5.2 nmol·L - 1 to 82.0 ± 7.9 nmol·L - 1 (p < 0.0001). In contrast, D 2 supplementation increased 25(OH)D 2 by + 347% (7.0 ± 1.1 nmol·L - 1 to 31.4 ± 2.1 nmol·L - 1 , p < 0.0001), but resulted in a - 42% reduction in 25(OH)D 3 by week 6 (p = 0.001). A net + 14% increase in 25(OH)D TOTAL was established with D 2 supplementation by week 12 (p > 0.05), which was not statistically different to D 3 . Vitamin D status was maintained with PL, following an initial - 15% reduction by week 6 (p ≤ 0.046 compared to both supplement groups)., Conclusions: The use of a UV radiated mushroom food ingredient was effective in maintaining 25(OH)D TOTAL in healthy, recreationally active volunteers. This may offer an adjunct strategy in supporting vitamin D intake. However, consistent with the literature, the use of vitamin D 3 supplementation likely offers benefits when acute elevation in vitamin D status is warranted.

Objective: This study aimed to assess the serum levels of vitamin D in an Egyptian cohort of children with allergic rhinitis (AR) and to evaluate any correlation of vitamin D status with the disease severity. Patient and methods: One hundred twenty children with AR and 100 healthy children were included in our study. We studied the serum levels of vitamin D 25(OH)D and 1,25(OH)2D in all participants. The associations between vitamin D levels and clinical characteristics of AR were examined. Results: In AR group, the serum levels of calcium, (25(OH)D and 1,25(OH)2D levels were significantly lower ( p < .0001, p < .001, and p < .0001, respectively) in AR children than in controls. Furthermore, the mean 25-OHD3 levels in patients with moderate/severe AR were significantly lower than those with mild AR ( p < .001). We found significant negative correlations between mean 25(OH)D levels and total nasal symptom score ( r = -.62, p = .002) and total immunoglobulin E levels ( r = -.27, p = .013) in AR group. Conclusions: Vitamin D deficiency is a frequent finding among Egyptian children with AR when compared to the healthy group. A significant inverse association was observed between vitamin D levels and AR disease severity.

Background: Vitamin D3 (vit. D3) deficiency is considered as one of the main factors involved in the development of type 2 diabetes (T2D). We assessed insulin resistance (IR), β-cell functional activity and metabolic profile according to 25(OH) vit. D3 status in patients with T2D., Methods: The study included 109 patients with T2D, divided in 3 groups: group 1 (N.=11) with normal levels of vit. D3 (>30 ng/mL); group 2 (N.=38) with vit. D3 insufficiency (21-29 ng/mL); and group 3 (N.=60) with vit. D3 deficiency (<20 ng/mL). IR and β-cell functional activity were assessed as change in C-peptide concentration and homeostasis model assessment-estimated (HOMA) β-cell function which was calculated using HOMA2 calculator., Results: Patients with vit. D3 deficiency presented significantly higher C-peptide concentration compared to other groups. HOMA2 (3.29±1.89 vs. 2.12±0.71; P=0.049) and hemoglobin (H8b)A1c (9.11±1.63 vs. 7.75±1.06; P=0.016) levels changed significantly only in patients with vit. D3 deficiency compared to diabetics with normal vit. D3 levels. Furthermore, in univariate Pearson's correlation analysis, we observed significant association between vit. D3 levels and C-peptide, insulin sensitivity, HOMA2, triglyceride-glucose index, HbA1c and Body Mass Index, only in the vit. D3 deficiency group. In multivariate logistic regression analysis, poor glycemic control, as defined by HbA1c levels, was independent from metformin use while high density lipoprotein-cholesterol levels were associated with vit. D3 deficiency., Conclusions: Our study demonstrated that vit. D3 deficiency in patients with T2D was associated with more severe IR, poor glycemic control and obesity compared to normal status or vit. D3 insufficiency.

Aims: Vitamin D measurement is a composite of vitamin D 2 (25(OH)D 2 ) and D 3 (25(OH)D 3 ) levels, and its deficiency is associated with the development of type 2 diabetes (T2DM) and diabetic complications; vitamin D deficiency may be treated with vitamin D 2 supplements. This study was undertaken to determine if vitamin D 2 and D 3 levels differed between those with and without T2DM in this Middle Eastern population, and the relationship between diabetic microvascular complications and vitamin D 2 and vitamin D 3 levels in subjects with T2DM . METHODS: Four hundred ninety-six Qatari subjects, 274 with and 222 without T2DM participated in the study. Plasma levels of total vitamin D 2 and D 3 were measured by LC-MS/MS analysis., Results: All subjects were taking vitamin D 2 and none were taking D 3 supplements. Vitamin D 2 levels were higher in diabetics, particularly in females, and higher levels were associated with hypertension and dyslipidemia in the diabetic subjects (p < 0.001), but were not related to diabetic retinopathy or nephropathy. Vitamin D 3 levels measured in the same subjects were lower in diabetics, particularly in females (p < 0.001), were unrelated to dyslipidemia or hypertension, but were associated with retinopathy (p < 0.014). Neither vitamin D 2 nor vitamin D 3 were associated with neuropathy. For those subjects with hypertension, dyslipidemia, retinopathy or neuropathy, comparison of highest with lowest tertiles for vitamin D 2 and vitamin D 3 showed no difference., Conclusions: In this Qatari cohort, vitamin D 2 was associated with hypertension and dyslipidemia, whilst vitamin D 3 levels were associated with diabetic retinopathy. Vitamin D 2 levels were higher, whilst vitamin D 3 were lower in diabetics and females, likely due to ingestion of vitamin D 2 supplements.

Introduction: Body stores of vitamin D are measured as "total" serum 25-hydroxy vitamin D (25(OH)D). Its largest component is protein bound and lost in urine in nephrotic syndrome (NS). Our study investigates whether "free" 25(OH)D levels are a better guide to bone health and need for vitamin D supplementation in patients with steroid-sensitive NS (SSNS)., Methods: A cross-sectional study was performed in children with SSNS and healthy controls. Blood was tested for albumin, creatinine, calcium, phosphate, ALP, total and free (by direct ELISA) 25(OH)D, iPTH, and urine for protein-creatinine ratio., Results: Seventy-nine NS patients (48 in relapse, 31 in remission) and 60 healthy controls were included. The levels of total 25(OH)D were significantly different (lowest in NS relapse and highest in controls) (p < 0.001). Corrected calcium and phosphate levels were normal, and there were no differences in free 25(OH)D, ALP, or iPTH levels between groups. Only total and not free 25(OH)D correlated significantly and negatively with urinary protein creatinine ratios (r s = - 0.42 vs. 0.04). Free 25(OH)D values of 3.75 and 2.85 pg/ml corresponded to total 25(OH)D levels of 20 and 12 ng/ml, respectively, in healthy controls., Conclusion: These results confirm that total 25(OH)D levels are low in NS and related to degree of proteinuria. However levels of free 25(OH)D, ALP, and iPTH did not change in relapse or remission in comparison with healthy controls. Our results suggest that in proteinuric renal diseases, free 25(OH)D rather than total 25(OH)D levels should be used to diagnose vitamin D deficiency and guide therapy.

Several hyperthyroidism misdiagnoses cases have been recently described due to biotin intake. Biotin used in immuno-analysis assays which rely on biotin/streptavidin binding properties. In these assays, high plasmatic biotin levels can lead to major analytical interferences resulting in falsely higher (competition tests) or falsely reduced determinations (for sandwiches assays). We performed a simulation test of biotin intake with patient's samples. We studied the effect of biotin on cardiac troponin I and total vitamin D (D 2 +D 3 ) assays that are using biotin-streptavidin binding on Dimension EXL®. Increasing doses of biotin were added (28 samples for each parameter) before the assays. The results evidenced a significant negative interference of biotin on cardiac troponin I determinations for concentrations of 100 ng/mL and above, with a total loss of signal for higher biotin additions. Such interference may lead to inappropriate therapeutic decisions. Positive interferences were observed on total vitamin D (D 2 +D 3 ) with less impact for therapeutic decisions.

Vitamin D (VitD) insufficiency is common in multiple sclerosis (MS). VitD has possible anti-inflammatory effects on the immune system. The ratio between VitD metabolites in MS patients and the severity of the disease are suggested to be related. However, the exact effect of the bone-derived hormone fibroblast-growth-factor-23 (FGF23) and VitD binding protein (VDBP) on this ratio is not fully elucidated yet. Therefore, the aim is to study differences in total, free, and bioavailable VD metabolites and FGF23 between MS patients and healthy controls (HCs). FGF23, vitD (25(OH)D), active vitD (1,25(OH) 2 D), inactive 24,25(OH)D, and VDBP were measured in 91 MS patients and 92 HCs. Bioavailable and free concentrations were calculated. No difference in FGF23 ( p = 0.65) and 25(OH)D/24.25(OH) 2 D ratio ( p = 0.21) between MS patients and HCs was observed. Bioavailable 25(OH)D and bioavailable 1.25(OH) 2 D were lower ( p < 0.01), while VDBP concentrations were higher in MS patients ( p = 0.02) compared with HCs, specifically in male MS patients ( p = 0.01). In conclusion, FGF23 and 25(OH)D/24.25(OH) 2 D did not differ between MS patients and HCs, yet bioavailable VitD concentrations are of potential clinical relevance in MS patients. The possible immunomodulating role of VDBP and gender-related differences in the VD-FGF23 axis in MS need further study.

24,25(OH) 2 D and the 25OHD/24,25(OH) 2 D ratio have recently been shown to be useful for screening for hypercalcemia caused by CYP24A1 mutations. However, no population-based data on 24,25(OH) 2 D have been published for Chinese populations, and few studies evaluated the sources of variation on 24,25(OH) 2 D levels and the 25OHD/24,25(OH) 2 D ratio. Hence, in 2018, we enrolled 1211 apparently healthy adults without systematic diseases from six representative cities in China (Beijing, Dongying, Guiyang, Urumqi, Shenzhen, and Qiqihar). 24,25(OH) 2 D and 25OHD levels were measured using isotope dilution liquid chromatography tandem mass spectrometry. Multiple regression analysis showed that sex contributed the most to variations in 24,25(OH) 2 D, 25OHD, and 25OHD/24,25(OH) 2 D (rp= -0.255, -0.253, and 0.141, respectively), and age also contributed to variations in 25OHD but not 24,25(OH) 2 D or 25OHD/24,25(OH) 2 D. Men had significantly higher 24,25(OH) 2 D and 25OHD levels than women, but had significantly lower 25OHD/24,25(OH) 2 D values. Individuals from Dongying had the highest 24,25(OH) 2 D and 25OHD values, whereas individuals from Urumqi had the lowest values. The median(2.5-97.5%) values for 24,25(OH) 2 D, 25OHD, and 25OHD/24,25(OH) 2 D were 1.2(0.36-2.65) ng/mL, 18.9(8.6-32.5) ng/mL, and 16.0 (9.8-30.8), respectively. 24,25(OH) 2 D was significantly correlated with 25OHD (r = 0.838, p <  0.001), and 25OHD/24,25(OH) 2 D was significantly negatively correlated with 24,25(OH) 2 D (r = -0.758, P < 0.001) and 25OHD (r = -0.310, P < 0.001). In conclusion, in this nationwide, multicenter, cross-sectional study, we evaluated the levels of 24,25(OH) 2 D and the 25OHD/24,25(OH) 2 D ratio in the Chinese population. Sex contributed the most to variations in 24,25(OH) 2 D, 25OHD, and 25OHD/24,25(OH) 2 D., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease have been linked to vitamin D-deficiency. Using a dextran sodium sulphate (DSS)-induced model of IBD we have shown previously that mice raised on vitamin D-deficient diets from weaning have lower serum 25-hydroxyvitamin D (25OHD) levels and develop more severe colitis compared to vitamin D-sufficient counterparts. We have also shown in vitro that immune responses to 25OHD may depend on 'free' rather than total serum concentrations of 25OHD. To investigate the possible effects of free versus total 25OHD on anti-inflammatory immune responses in vivo we have studied DSS-induced colitis in wild type C57BL/6 mice raised from weaning on diets containing vitamin D2 (D2) or vitamin D3 (D3) only (both 1000 IU/kg feed). 25OHD2 has lower binding affinity for the vitamin D binding protein than 25OHD3 which results in higher levels of free 25OHD2 relative to free 25OHD3 in mice raised on a D2-only diet. Total serum 25OHD concentrations, measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS), showed that D2 mice had significantly lower levels of 25OHD than D3 mice (6.85 ± 2.61 nmol/L vs. 49.16 ± 13.8 nmol/L for D2 and D3 respectively). Despite this, direct ELISA measurement showed no difference in free serum 25OHD levels between D2 and D3 mice (13.62 ± 2.26 pmol/L vs. 14.11 ± 2.24 pmol/L for D2 and D3 respectively). Analysis of DSS-induced colitis also showed no difference in weight loss or disease progression between D2 and D3 mice. These data indicate that despite D2-fed mice being vitamin D-deficient based on serum total 25OHD concentrations, these mice showed no evidence of increased inflammatory colitis disease relative to vitamin D-sufficient D3 mice. We therefore propose that free, rather than total serum 25OHD, may be a better marker of immune responses to vitamin D in vivo., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

This study establishes and validates a rapid method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) without derivatization steps to simultaneously measure of 24,25(OH) 2 D 2 , 24,25(OH) 2 D 3 , 25OHD 2 , and 25OHD 3 , while efficiently separating the 3-epi analogs. Samples were prepared by precipitation and liquid-liquid extraction. The linearity, precision, accuracy, recovery and matrix effect of the method were thoroughly evaluated according to the Clinical & Laboratory Standards Institute guidelines. Additionally, the four vitamin D metabolites in the serum of 38 apparently healthy Chinese volunteers were evaluated. The total analysis time was 8.0 min, with efficient separation of 3-epi 24,25(OH) 2 D 3 and 3-epi 25OHD 3 , without interference from isomers such as 23,25(OH) 2 D 3 or 1,25(OH) 2 D 2 , 1,25(OH) 2 D 3 . Good reproducibility was obtained for all four metabolites with within-run coefficient variations (CVs) of 4.07%-6.55%, 4.26%-7.84%, 2.46%-7.21%, and 4.90%-6.87% for 25OHD 3 , 25OHD 2 , 24,25(OH) 2 D 3 , and 24,25(OH) 2 D 2 , respectively, and the total CVs were 4.29%-6.64%, 6.14%-7.84%, 4.33%-7.21%, 5.82%-9.90%, respectively. The limit of quantification was 0.625 ng/mL for 25OHD 3 and 25OHD 2 , and 0.5 ng/mL for 24,25(OH) 2 D 3 and 24,25(OH) 2 D 2 . The relative bias of the LC-MS/MS method compared to the certified results of SRM 972a for 25OHD 3 , 25OHD 2 and 24,25(OH) 2 D 3 was -2.21% to 1.01%, 3.38% to 6.73%, and -7.72% to -3.9%, respectively. The mean±SD values for 25OHD, 24,25(OH) 2 D and 25OHD/24,25(OH) 2 D in the volunteers were 13.5±4.4 ng/mL(range:7.6-27.5 ng/mL), 0.84±0.42 ng/mL (range:0.26-2.1 ng/mL), and 18±7(range:8-37), respectively. Thus, a simple, precise LC-MS/MS method for appropriate retention and separation of vitamin D metabolites and their epi analogs was developed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Vitamin-D2 (D2) treatment has been associated with a decrease in 25-hydroxy (25(OH)) vitamin-D3 (D3) level, suggesting that D3 treatment would be preferred to raise total 25(OH) vitamin-D (D) level. We postulated that D2 treatment-associated decrease in 25(OH)D3 level is related to the increase in 25(OH)D level rather than being D2-specific, and thus there would be a similar D3 treatment-associated decrease in 25(OH)D2 level., Methods: Fifty volunteers were block-randomized to 50,000 IU D2 or placebo orally once (study-1) and fifty volunteers received 50,000 IU D2 orally once and 4 days later block-randomized to 50,000 IU D3 or placebo orally once (study-2). Interventions were concealed from volunteers and research coordinators and blindly-administered. Serum 25(OH)D2 and 25(OH)D3 levels were blindly-determined at baseline and days 14, 28, 42, and 56, post-randomization by high performance liquid chromatography assay. Results of 97 participants were analyzed. Primary outcome measure was day-28 D2-associated change in 25(OH)D3 level in study-1 and D3-associated change in 25(OH)D2 level in study-2, adjusted for baseline levels., Results: Mean (95% confidence interval) difference between the active and placebo arms in the decrease in day-28 25(OH)D3 (study-1) and 25(OH)D2 (study-2) levels was 13.2 (9.7 to 16.6) and 9.8 (5.2 to 14.4) nmol/L, respectively. Corresponding differences at day-56 were 10.8 (6.8 to 14.8) and 1.7 (- 7.6 to 11.1) nmol/L, respectively. The difference between the placebo and active arms in area-under-the-curve at day-28 (AUC 28 ) and day-56 (AUC 56 ) were 262.3 (197.8 to 326.7) and 605.1 (446.3 to 784.0) for 25(OH)D3 (study-1) and 282.2 (111.2 to 453.3) and 431.2 (179.3 to 683.2) nmol.d/L for 25(OH)D2 (study-2), respectively. There were significant correlations between day-28 changes in 25(OH)D2 and 25(OH)D3 levels in study-1 (rho = - 0.79, p < 0.001) and study-2 (rho = - 0.36, p = 0.01), and between day-28 changes in 25(OH)D2 level and baseline 25(OH)D level in study-2 (rho = - 0.42, p = 0.003)., Conclusions: Compared to placebo, D3 treatment is associated with a decrease in 25(OH)D2 level similar in magnitude to D2-treatment associated decrease in 25(OH)D3 level; however, the D3-placebo difference in 25(OH)D2 level is shorter-lasting. Changes in 25(OH)D2 and 25(OH)D3 levels are correlated with each other and with baseline 25 (OH) D levels, suggesting a common regulatory mechanism., Trial Registration: ClinicalTrial.gov identifier: NCT03035084 (registered January 27, 2017).

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.

Ultraviolet-irradiated yeast (Saccharomyces cerevisiae) can be used to biofortify bakery products with vitamin D, but in bread, it was not effective in increasing serum 25-hydroxyvitamin D [25(OH)D] in humans, possibly because of the low digestibility of the yeast matrix. We investigated the effects of vitamin D 2 -rich intact yeast cells and their separated fraction, yeast cell walls, which we hypothesized to provide vitamin D 2 in a more bioavailable form, on serum 25(OH)D and its metabolites in growing female Sprague-Dawley rats (n = 54) compared to vitamin D 2 and D 3 supplements (8 treatment groups: 300 or 600 IU vitamin D/d, and a control group, 8-week intervention). The D 3 supplement groups had the highest 25(OH)D concentrations, and the vitamin D 2 supplement at the 600-IU dose increased 25(OH)D better than any yeast form (P < .001 for all, analysis of covariance, adjusted for body weight). There were no significant differences between the yeast forms at the same dose (P > .05). Serum 24,25-dihydroxyvitamin D (a vitamin D catabolite) concentrations and the trend in the differences between the groups were in line with 25(OH)D (P < .001 for all). The 24,25-dihydroxyvitamin D to 25(OH)D ratio between the D 2 supplement and the yeast groups did not differ (P > .05). These findings do not support the hypothesis: the ability of the different ultraviolet-treated vitamin D 2 -containing yeast forms to increase 25(OH)D did not differ, and the poor bioavailability of vitamin D 2 in the yeasts compared D 3 or D 2 supplements could not be explained by the increased vitamin D catabolism in the yeast-treated groups., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was (1) to elucidate any reciprocal seasonal relationship that might exist between red cell folate (RCF) and serum vitamin D 3 Levels; (2) to explore whether folate-related gene variants that influence/alter DNA-thymidylate and methyl group biosynthesis modify any associations detected in objective 1; and (3) to consider whether these processes might influence reproductive success consistent with the "folate-vitamin D-UV hypothesis of skin pigmentation" evolutionary model., Methods: A large (n = 649) Australian cross-sectional study population was examined. Polymerase chain reaction (PCR)/Restriction fragment length polymorphism (RFLP) analysis was used to genotype C677T-MTHFR, C1420T-SHMT, T401C-MTHFD and 2R > 3R-TS. RCF was measured by chemiluminescent immunoassay and vitamin D 2 and D 3 by HPLC., Results: RCF and photosynthesized vitamin D 3 , but not RCF and dietary vitamin D 2 , exhibit a significant reciprocal association in spring and summer. Three folate genes (C677T-MTHFR, C1420T-SHMT, and 2R > 3R-TS) strengthen this effect in spring, and another (T401C-MTHFD) in summer. Effects are seasonal, and do not occur over the whole year., Conclusions: Findings are consistent with what might be required for the "folate-vitamin D-UV hypothesis of skin pigmentation" model. It suggests genetic influence in provision of one-carbon units by 5,10-methylene-H 4 folate, may be an important factor in what appears to be a clear seasonal relationship between vitamin D 3 and folate status., (© 2018 Wiley Periodicals, Inc.)

Rationale: Sufficient levels of vitamin D seem to be essential for proper immune function, and low levels might be associated to disease activity in Rheumatoid Arthritis (RA). Most studies investigate only 25OHD and not the physiologically active vitamin D metabolite, 1,25(OH) 2 D., Objective: To investigate associations between serum level of vitamin D metabolites and disease activity parameters in 160 inflammatory active and treatment naïve early RA patients. Serum level of vitamin D metabolites (25OHD 2 , 25OHD 3 and 1,25(OH) 2 D) was measured by isotope dilution mass spectrometry and radio-immunoassays at baseline. Disease characteristics were gender, number of tender joints, number of swollen joints, DAS28-CRP, HAQ, VAS-scores, CRP, erosive status (Total Sharp Score; TSS), ACPA and IgM-RF-status. Associations were evaluated using Spearman's and Wilcoxon rank-sum tests. The study was registered in clinical trials; trial registration number: NCT00209859., Findings: Statistically significant inverse associations were found between the active metabolite 1,25(OH) 2 D and DAS28-CRP (P = 0.004, rho = -0.23), HAQ (P = 0.005, rho = -0.22), CRP (P = 0.001, rho = -0.25), VAS patient-pain (P = 0.008, rho = -0.21), and a positive association was found to ACPA-status (P = 0.04)., Conclusion: The vitamin D metabolite 1,25(OH) 2 D was inversely associated with disease activity and positively associated with ACPA in treatment naïve and inflammatory active early RA. The results indicate that in RA, both the degree of inflammatory activity, and the diagnostic sensitivity and specificity might affect-or might be affected by the level of vitamin 1,25(OH) 2 D., (© 2018 The Foundation for the Scandinavian Journal of Immunology.)

Background & Aims: While vitamin D deficiency is common in patients with end stage renal disease on dialysis and treatment with Vitamin D 2 and Vitamin D 3 is becoming increasingly common in these patients, little is known about 24,25(OH) 2 D 3 metabolite production. Some authors report that the CYP24A1 enzyme is upregulated in CKD, but reports of low serum levels of 24,25(OH) 2 D 3 in these patients bring this into question. Lack of substrate or increased clearance of the metabolite have been proposed as possible causes. We report serum 24,25(OH) 2 D 3 levels from three controlled trials of Vitamin D 2 and Vitamin D 3 supplementation which reached adequate levels of 25(OH)D in patients with end stage renal disease on dialysis., Methods: 680 samples from three controlled trials of Vitamin D 2 or Vitamin D 3 supplementation in CKD Stage 5D were available for analysis. The trials used single doses of 50,000 IU Vitamin D 3 , or 50,000 IU Vitamin D 2 , or weekly doses of 10,000 IU or 20,000 IU Vitamin D 3 . Blood samples were drawn at baseline and frequently over the ensuing 3-4 months. Serum 25(OH)D and 24,25(OH) 2 D 3 levels were measured using a novel, very sensitive LC-MS/MS-based method involving derivatization with DMEQ-TAD. Linear mixed effect regression models were used to compare the 3 studies and the interventions within studies over time., Results: The subjects given Vitamin D 3 had significant increases in 25(OH)D levels. Serum 24,25(OH) 2 D 3 levels were low at baseline in the renal patients and rose slightly with native vitamin D supplementation, but these levels were lower than reports of 24,25(OH) 2 D 3 in healthy populations., Conclusions: We conclude that the enzymatic activity of CYP24A1 is abnormal in end stage renal patients on dialysis. These trials were registered on clinicaltrials.govNCT00511225 on 8/1/2007; NCT01325610 on 1/17/2011; and NCT01675557 on 8/28/2012., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Purpose: To characterize the physiological changes in 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH) 2 D] throughout pregnancy., Methods: Prospective cohort of 229 apparently healthy pregnant women followed at 5th-13th, 20th-26th, and 30th-36th gestational weeks. 25(OH)D and 1,25(OH) 2 D concentrations were measured by LC-MS/MS. Statistical analyses included longitudinal linear mixed-effects models adjusted for parity, season, education, self-reported skin color, and pre-pregnancy BMI. Vitamin D status was defined based on 25(OH)D concentrations according to the Endocrine Society Practice Guideline and Institute of Medicine (IOM) for adults., Results: The prevalence of 25(OH)D <75 nmol/L was 70.4, 41.0, and 33.9%; the prevalence of 25(OH)D <50 nmol/L was 16.1, 11.2, and 10.2%; and the prevalence of 25(OH)D <30 nmol/L was 2, 0, and 0.6%, at the first, second, and third trimesters, respectively. Unadjusted analysis showed an increase in 25(OH)D (β = 0.869; 95% CI 0.723-1.014; P < 0.001) and 1,25(OH) 2 D (β = 3.878; 95% CI 3.136-4.620; P < 0.001) throughout pregnancy. Multiple adjusted analyses showed that women who started the study in winter (P < 0.001), spring (P < 0.001), or autumn (P = 0.028) presented a longitudinal increase in 25(OH)D concentrations, while women that started during summer did not. Increase of 1,25(OH) 2 D concentrations over time in women with insufficient vitamin D (50-75 nmol/L) at baseline was higher compared to women with sufficient vitamin D (≥75 nmol/L) (P = 0.006)., Conclusions: The prevalence of vitamin D inadequacy varied significantly according to the adopted criteria. There was a seasonal variation of 25(OH)D during pregnancy. The women with insufficient vitamin D status present greater longitudinal increases in the concentrations of 1,25(OH) 2 D in comparison to women with sufficiency.

Introduction: Post-transplant diabetes mellitus (PTDM) occurs most frequently during the first year after transplantation. We focused on parameters of calcium-phosphate metabolism and proteinuria as possible new risk factors for PTDM after kidney transplantation., Materials and Methods: We have prospectively identified risk factors for post-transplant diabetes mellitus with follow-up of 12 months in a set of 167 patients after kidney transplantation. Patients with diabetes mellitus type 1 and type 2 as well as patients using ciclosporin A or mTOR inhibitor have been excluded from the monitoring. From the perspective of immunosuppression it was a homogeneous set of patients., Results: We identified the following independent risk factors for PTDM in our set: average proteinuria > 0.300 g/24 h (HR 3.0785, (95 % CI 1.6946-5.5927), p=0.0002), level of vitamin D<20 ng/ml (HR 5.4517, (95 % CI 2.3167-11.8209), p1.45 mmol/l (HR0.0821, (95 % CI0.0042-1.5920), p=0.0439). The lowest occurrence of PTDM and proteinuria was recorded in patients whose treatment included paricalcitol (p<0.0001) and these patients had at the same time the highest level of vitamin D (p<0.0001)., Conclusion: Deficit of vitamin D, proteinuria and hyperphosphatemia have been independent risk factors for the development of PTDM in our set. We identified the usage of paricalcitol as protective factor with regard to the PTDM development (Tab. 6, Fig. 4, Ref. 29).

In the UAE and the Gulf region in general, there are several intricate public health issues in the context of vitamin D deficiency that needs to be addressed. Changes in lifestyle such as diet, lack of exercise, cultural habits, avoiding sun exposure due to excessive heat, and other risk factors predispose those who live in GULF countries, such as Emiratis likely to becoming vitamin D deficient. Consequently, the prevalence of vitamin D deficiency is high, and new guidelines are needed to overcome this major public health issue. Peer-reviewed papers related to guidelines and those vitamin D-related papers relevant to the Middle-Eastern region were extracted from multiple research databases using key words according to the general guidelines from the Preferred Reporting Items for Systematic Analysis. This guideline was prepared focusing on the United Arab Emirate and the Gulf populations, to overcome the high incidence of vitamin D deficiency and to improve overall health. We recommend the following vitamin D supplementations for different groups of people: (A) Breastfed infants supplement with 400 IU/day up to age 6 months, and 400-600 IU/day between 6 and 12 months, depending on daily intake of total vitamin D and sun exposure; (B) for children and adolescents of age 1-18 years supplement with 600-1000 IU/day depending on the body weight; (C) adults greater than 18 years', supplementation with 1000-2000 IU/day is recommended, while, (D) the elderly (over 65 years) should be supplemented with 2000 IU/day, throughout the year; (E) pregnant and breast feed women, 2000 IU/day from the first trimester of pregnancy. (F) Premature infants, supplementation of 400-800 IU/daystart from the first days of life. (G) For obese, individuals and those with metabolic syndrome, supplementation of 2000 IU/day (H) For individuals with dark skin complexions and for night workers, supplementation of 1000-2000 IU/day (25-50μg/day), throughout the year, depending on body weight. The goal of supplementation is to achieve and longer term maintenance of serum 25(OH)D concentration of 30-50ng/mL., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The Vitamin D External Quality Assessment Scheme (DEQAS) was launched in 1989 and monitors the performance of 25-hydroxyvitamin D (25-OHD) and 1,25- dihydroxyvitamin D (1,25(OH) 2 D) assays. In April 2015 a pilot scheme for 24,25-dihydroxyvitamin D (24,25(OH) 2 D) was introduced. The 25-OHD scheme is accuracy - based with target values assigned by the NIST Reference Measurement Procedure (RMP) for 25-OHD 2 and 25-OHD 3 . A similar method is used to assign values for 3-epi-25-OHD. Five samples of human serum are distributed quarterly to over 1000 participants in 58 countries (April 2016) and clinical laboratories are expected to submit results within approximately 5 weeks. Research laboratories with assays run less frequently are not given a deadline. Archived samples with NIST- assigned values are also available. Performance is assessed on the first four samples with the fifth reserved for investigations e.g. recovery experiments or to assess the influence of other serum constituents such as lipids. DEQAS provides rapid feedback, with an on-line preliminary report available immediately after a participant submits results and a comprehensive report soon after the results deadline. In 2015, DEQAS investigations revealed that several 25-OHD immunoassays under-recovered 25-OHD 2 and 25-OHD results were falsely low on a sample with a modestly raised triglyceride concentration. An RMP for 1,25 (OH) 2 D is not yet available and results are judged against the Method Mean. Free advice is available from the DEQAS Advisory Panel which includes experts on methodology and biostatistics. DEQAS collaborates closely with the Vitamin D Standardization Program (VDSP) and both organizations have successfully worked with participants and manufacturers to improve the accuracy of vitamin D assays., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: There are conflicting views in the literature as to whether vitamin D 2 and vitamin D 3 are equally effective in increasing and maintaining serum concentrations of 25-hydroxyvitamin D [25(OH)D], particularly at lower doses of vitamin D. Objective: We aimed to investigate whether vitamin D 2 or vitamin D 3 fortified in juice or food, at a relatively low dose of 15 μg/d, was effective in increasing serum total 25(OH)D and to compare their respective efficacy in South Asian and white European women over the winter months within the setting of a large randomized controlled trial. Design: A randomized, double-blind, placebo-controlled food-fortification trial was conducted in healthy South Asian and white European women aged 20-64 y ( n = 335; Surrey, United Kingdom) who consumed placebo, juice supplemented with 15 μg vitamin D 2 , biscuit supplemented with 15 μg vitamin D 2 , juice supplemented with 15 μg vitamin D 3 , or biscuit supplemented with 15 μg vitamin D 3 daily for 12 wk. Serum 25(OH)D was measured by liquid chromatography-tandem mass spectrometry at baseline and at weeks 6 and 12 of the study. Results: Postintervention in the 2 ethnic groups combined, both the vitamin D 3 biscuit and the vitamin D 3 juice groups showed a significantly greater absolute incremental change (Δ) in total 25(OH)D when compared with the vitamin D 2 biscuit group [Δ (95% CI): 15.3 nmol/L (7.4, 23.3 nmol/L) ( P < 0.0003) and 16.0 nmol/L (8.0, 23.9 nmol/L) ( P < 0.0001)], the vitamin D 2 juice group [Δ (95% CI): 16.3 nmol/L (8.4, 24.2 nmol/L) ( P < 0.0001) and 16.9 nmol/L (9.0, 24.8 nmol/L) ( P < 0.0001)], and the placebo group [Δ (95% CI): 42.3 nmol/L (34.4, 50.2 nmol/L) ( P < 0.0001) and 42.9 nmol/L (35.0, 50.8 nmol/L) ( P < 0.0002)]. Conclusions: With the use of a daily dose of vitamin D relevant to public health recommendations (15 μg) and in vehicles relevant to food-fortification strategies, vitamin D 3 was more effective than vitamin D 2 in increasing serum 25(OH)D in the wintertime. Vitamin D 3 may therefore be a preferential form to optimize vitamin D status within the general population. This trial was registered at www.controlled-trials.com as ISRCTN23421591., (© 2017 American Society for Nutrition.)

The aim of the preclinical investigation was to obtain single dose pharmacokinetics in dogs from 2 different oral cholecalciferol formulations using corrective measures to overcome the interference of endogenous cholecalciferol. 6 dogs were fasted overnight and the following day received 60 000 IU dose cholecalciferol [reference, Eris ® , vs. test, Sunbless ® ] by oral dosing. Blood samples were collected on day 0 (baseline establishment) and after dosing on day 1 up to 28 days. The serum samples were extracted using protein precipitation/solid phase extraction and analysed to determine cholecalciferol by LC-MS/MS assay with calibrators prepared from cholecalciferol free serum. Standard pharmacokinetic analysis was carried out to assess pharmacokinetic parameters. An un-paired t-test was employed for comparing statistical significance between formulations. Serum cholecalciferol concentration vs. time profiles for the 2 formulations was almost superimposable. None of the pharmacokinetic parameters showed statistically significant differences (p>0.05) between the 2 treatments. For example: C max (ng/mL) and AUC inf (ng.h/mL) derived after the baseline corrections were 708.65 and 38 877.18 for reference and 743.71 and 40 665.51 for test, respectively. Pharmacokinetics of cholecalciferol was comparable between reference vs. test formulations. The procedures, baseline correction and employment of cholecalciferol devoid serum, can be readily adopted in future pharmacokinetic studies in animals or humans., Competing Interests: Conflict of interest: All the authors are employees of Cadila Healthcare Limited. The authors have no conflict of interest to declare on the content of this research work (ZRC publication no. 499)., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Disturbances in vitamin D metabolism are common in patients with end-stage renal disease and may contribute to vascular dysfunction., Study Design: Cross-sectional., Setting & Participants: We evaluated 558 of 602 participants at baseline of the Hemodialysis Fistula Maturation (HFM) Study, a 7-center prospective cohort study of a cohort of patients with chronic kidney disease awaiting arteriovenous fistula (AVF) creation surgery., Factor: 4 vitamin D metabolites measured with liquid chromatography-tandem mass spectroscopy from samples obtained within 4 weeks prior to AVF surgery., Outcomes: Vasodilator functions and measurements of arterial stiffness., Measurements: Trained HFM Study personnel measured brachial artery flow-mediated dilation, nitroglycerin-mediated dilation, and carotid-femoral and carotid-radial pulse wave velocities (PWVs) prior to AVF creation. We evaluated associations after basic adjustment for sex, age, and clinical site and more fully adjusted additionally for baseline education, smoking, body mass index, diabetes, dialysis status, and medication use., Results: Mean participant age was 55±13 (SD) years and 65% were receiving maintenance dialysis. None of the vitamin D metabolites were significantly associated with flow-mediated dilation, carotid-femoral PWV, or carotid-radial PWV in basic or fully adjusted analyses. Higher serum concentrations of bioavailable vitamin D and 1,25-dihydroxyvitamin D were associated with 0.62% and 0.58% greater nitroglycerin-mediated dilation values, respectively, in basic models; however, these associations were no longer statistically significant with full adjustment. There were no significant associations of vitamin D metabolites with carotid-femoral or carotid-radial PWV in fully adjusted analyses., Limitations: Cross-sectional ascertainment of vitamin D metabolites and vascular functions late during the course of kidney disease., Conclusions: Serum concentrations of vitamin D metabolites are not associated with vasodilator functions or vascular stiffness at baseline in a cohort study of patients with chronic kidney disease awaiting AVF creation surgery. Laboratory measurements of vitamin D metabolites are unlikely to provide useful information regarding vascular functions in this setting., (Copyright © 2017 National Kidney Foundation, Inc. All rights reserved.)

Vitamin D is a fat-soluble vitamin that is naturally found in very few food sources. It is produced endogenously from ultraviolet light from the sun striking the skin and then triggering vitamin D synthesis and activation. Vitamin D helps promote calcium absorption in the gut, maintains adequate serum calcium and phosphate levels, promotes bone growth, modulates cell growth, and has many other roles. There have been an increasing number of people, especially in older adults, with vitamin D deficiency. This is in part a result of a reduction of sun exposure as people age, increase in use of sunscreen, and other factors. This article highlights the roles of cholecalciferol (vitamin D3) versus ergocalciferol (vitamin D2) supplementation for practicing pharmacists.

Objective: Variability in 25-hydroxyvitamin D (25(OH)D) change following vitamin D supplementation exists. Vitamin D metabolite measurement might assist in predicting 25(OH)D response and also contribute to defining vitamin D adequacy. This study assessed utility of vitamin D metabolite measurements to predict 25(OH)D response and explored the relationship between parathyroid hormone (PTH) and a "vitamin D composite index" comprised of the sum of serum 25(OH) D, cholecalciferol (vitamin D 3 ) and 24,25 dihydroxyvitamin D (24,25(OH) 2 D)., Methods: Sixty-two postmenopausal women were randomized to daily vitamin D 3 1,800 IU or placebo for 4 months. Blood was drawn at baseline and after 1 and 4 months. Serum 25(OH)D, vitamin D 3 , and 24,25(OH) 2 D were measured by liquid chromatography tandem mass spectroscopy. Free 25(OH)D and PTH were measured by enzyme-linked immunosorbent assay. Repeated measures analysis of variance and regression analyses were performed., Results: Baseline 25(OH)D was positively correlated (P<.05) with vitamin D3, 24,25(OH) 2 D and free 25(OH) D. Daily vitamin D supplementation increased all metabolites (P<.001). Substantial individual variability in 25(OH) D change at 4 months was observed but was unrelated to baseline vitamin D 3 , 25(OH)D or 24,25(OH) 2 D. Only body mass index, body weight, and body fat mass was associated with 25(OH)D change at 4 months. The vitamin D composite score was associated with serum PTH, but this association was similar to that observed with 25(OH) D alone., Conclusion: This study does not support measurement of vitamin D metabolites in a composite index to assist in prediction of 25(OH)D response to supplementation. Overweight individuals have less robust 25(OH) D response to supplementation, but variability precludes prediction of the result following daily supplementation., Abbreviations: BMI = body mass index DXA = dual-energy X-ray absorptiometry LC-MS/MS = liquid chromatography tandem mass spectroscopy 25(OH)D = 25-hydroxyvitamin D 24,25(OH) 2 D = 24,25 dihydroxyvitamin D PTH = parathyroid hormone vitamin D 3 = cholecalciferol.

In cattle, there are 2 significant forms of vitamin D: ergocalciferol (ERG) from fungi on roughage and cholecalciferol (CHO) from vitamin supplements or endogenous synthesis in the skin. The hypothesis of the present study is that vitamin D from the 3 sources is transported in different plasma fractions in the body. This is hypothesized to explain the lower efficiency of ERG compared to CHO in securing a sufficient plasma status of 25-hydroxyvitamin D and explain the inefficient excretion of dietary CHO into milk compared to endogenous CHO. Twenty vitamin D-depleted cows were assigned to 5 treatments: D2, housed indoor and fed 625-μg/d (25.000 IU) ERG; D3, housed indoor and fed 625-μg/d CHO; D2+D3, housed indoor and fed 625-μg/d ERG and 625-μg/d CHO; SUN, let out for daily pasture to facilitate CHO synthesis from sunlight; and D2+SUN, fed 625-μg/d ERG and let out for daily pasture. Blood samples were taken twice weekly and plasma fractionated by ultracentrifugation into 3 fractions: light lipoprotein (LLP), heavy lipoprotein (HLP), and protein and analyzed for content of ERG and CHO and their liver derived metabolites 25-hydroxyergocalciferol (25ERG) and 25-hydroxycholecalciferol (25CHO), respectively. Liver biopsies were taken on the last day of the study to asses gene expression related to vitamin D metabolism. During 4 wk of study, the vitamin D status in plasma increased to 19.3 to 22.8 ng/mL 25ERG in ERG-treated cows with the highest concentration in D2 (P ≤ 0.05) and to 25.0 to 33.4 ng/mL 25CHO in pasture or CHO-treated cows with the highest concentration in SUN (P ≤ 0.01). In plasma fractions, CHO was mainly found in the HLP fraction, whereas 25CHO was almost exclusively found in the protein fraction, probably due to its reported high binding affinity to vitamin D-binding protein. About 70% to 90% of 25ERG was found in the protein fraction and the remaining 25ERG was found in HLP, whereas ERG was found in both HLP and LLP fractions. In liver tissue, the expression of vitamin D-25-hydroxylase was lower in D2+D3 (P ≤ 0.05) and SUN (P ≤ 0.05) than that in the remaining groups, and the vitamin D receptor was expressed in the liver to a larger extent in D2+SUN than that in D2+D3 (P ≤ 0.05) and SUN (P ≤ 0.05). In conclusion, different plasma transport mechanisms may explain the lower physiological efficiency of ERG compared to CHO in securing the vitamin D status in plasma but do not explain the lower efficiency of synthetic CHO compared to endogenous CHO from sunlight or UV light in securing a high CHO content in milk., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Vitamin D deficiency (<20 ng/mL) and insufficiency (20-29 ng/mL) are common among patients with chronic kidney disease (CKD) or undergoing dialysis. In addition to nutritional and sunlight exposure deficits, factors that affect vitamin D deficiency include race, sex, age, obesity and impaired vitamin D synthesis and metabolism. Serum 1,25(OH)₂D levels also decrease progressively because of 25(OH)D deficiency, together with impaired availability of 25(OH)D by renal proximal tubular cells, high fibroblast growth factor (FGF)-23 and decreased functional renal tissue. As in the general population, this condition is associated with increased morbidity and poor outcomes. Together with the progressive decline of serum calcitriol, vitamin D deficiency leads to secondary hyperparathyroidism (SHPT) and its complications, tertiary hyperparathyroidism and hypercalcemia, which require surgical parathyroidectomy or calcimimetics. Kidney Disease Outcomes Quality Initiative (KDOQI) and Kidney Disease Improving Global Outcomes (KDIGO) experts have recognized that vitamin D insufficiency and deficiency should be avoided in CKD and dialysis patients by using supplementation to prevent SHPT. Many vitamin D supplementation regimens using either ergocalciferol or cholecalciferol daily, weekly or monthly have been reported. The benefit of native vitamin D supplementation remains debatable because observational studies suggest that vitamin D receptor activator (VDRA) use is associated with better outcomes and it is more efficient for decreasing the serum parathormone (PTH) levels. Vitamin D has pleiotropic effects on the immune, cardiovascular and neurological systems and on antineoplastic activity. Extra-renal organs possess the enzymatic capacity to convert 25(OH)D to 1,25(OH)₂D. Despite many unanswered questions, much data support vitamin D use in renal patients. This article emphasizes the role of native vitamin D replacement during all-phases of CKD together with VDRA when SHPT persists.

When using vitamin D, the most important clinical problems are hypercalcemia, hyperphosphatemia, and vascular calcification. VS-105 is a novel vitamin D receptor (VDR) analog. In the present study, we compared the effects of VS-105 and paricalcitol on chronic kidney disease-mineral bone disorder (CKD-MBD) in a CKD rat model. We used male Sprague-Dawley (SD) rats and performed 5/6 nephrectomy at 8-9 weeks. At 10 weeks, the rats were classified into five groups and administered vehicle, low-dose paricalcitol (LP, 0.1μg/kg), high-dose paricalcitol (HP, 0.3μg/kg), low-dose VS-105 (LV, 0.2μg/kg), and high-dose VS-105 (HV, 0.6 μg/kg) three times a week for 10 weeks. There were no significant differences in blood pressure or renal function among the five groups. Alhough serum calcium levels were comparable between the LP and LV groups, they were higher in the HP group than in the HV group. Serum phosphate levels were higher in the paricalcitol-treated groups than in the VS-105-treated groups and paticularly higher in the HP group than in the other groups. The urinary excretion of phosphate was greater in the VS-105-treated groups than in the paricalcitol-treated groups. Serum parathyroid hormone (PTH) levels decreased and serum fibroblast growth factor-23 (FGF23) levels were elevated after administering paricalcitol and VS-105; however, serum FGF23 levels were remarkably elevated in the paricalcitol-treated groups. Further biochemical analyses revealed that the calcium content of the aorta was higher in the paricalcitol-treated groups than in the VS-105-treated group. VDR and Klotho expression in the kidney was significantly higher in the VS-105-treated groups than in the paricalcitol-treated groups although both agents increased these expressions. Our data suggest that VS-105 had a lesser effect on CKD-MBD than paricalcitol except in the case of serum PTH levels. The mechanism appears to be associated with the difference in VDR and Klotho expression., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Hypovitaminosis D exists postburn. However, evidence-based guidelines for vitamin D repletion are unknown. This investigation examined differences between D 2 and D 3 supplementation on outcome in children with burn injuries., Methods: Fifty patients with total body surface area burn of 55.7% ± 2.6% and full-thickness injury of 40.8% ± 3.8% were enrolled, ranging in age from 0.7-18.4 years. All participants received multivitamin supplementation per standardized clinical protocol. In addition, 100 IU/kg D 2 , D 3 , or placebo was administered daily during hospitalization using a randomized, double-blinded study design. Assay of total 25-hydroxyvitamin D (D25), 1,25-dihydroxyvitamin D (D1,25), 25-hydroxyvitamin D 2 (25-OH-D 2 ), 25-hydroxyvitamin D 3 (25-OH-D 3 ), and parathyroid hormone (PTH) was performed at 4 preplanned time intervals (baseline, midpoint, discharge, and 1 year postburn). Differences in vitamin D status were compared over time and at each specific study interval., Results: There were no significant differences in serum vitamin D levels between groups, but >10% of patients had low D25 at discharge, and percent deficiency worsened by the 1-year follow up for the placebo (75%), D 2 (56%), and D 3 (25%) groups. There were no statistical differences in PTH or clinical outcomes between treatment groups, although vitamin D supplementation demonstrated nonsignificant but clinically relevant decreases in exogenous insulin requirements, sepsis, and scar formation., Conclusions: The high incidence of low serum D25 levels 1 year following serious thermal injury indicates prolonged compromise. Continued treatment with vitamin D 3 beyond the acute phase postburn is recommended to counteract the trajectory of abnormal serum levels and associated morbidity.

Patients with chronic kidney disease (CKD) demonstrate complex mineral metabolism derangements and a high prevalence of vitamin D deficiency. However, the optimal method of 25-hydroxyvitamin D (25(OH)D) repletion is unknown, and trials analysing the comparative efficacy of cholecalciferol and ergocalciferol in this population are lacking. We conducted a randomised clinical trial of cholecalciferol 1250μg (50 000 IU) weekly v. ergocalciferol 1250μg (50 000 IU) weekly for 12 weeks in forty-four non-dialysis-dependent patients with stage 3-5 CKD. The primary outcome was change in total 25(OH)D from baseline to week 12 (immediately after therapy). Secondary analyses included the change in 1,25-dihydroxyvitamin D (1,25(OH)2D), parathyroid hormone (PTH), D2 and D3 sub-fractions of 25(OH)D and 1,25(OH)2D and total 25(OH)D from baseline to week 18 (6 weeks after therapy). Cholecalciferol therapy yielded a greater change in total 25(OH)D (45·0 (sd 16·5) ng/ml) v. ergocalciferol (30·7 (sd 15·3) ng/ml) from baseline to week 12 (P<0·01); this observation partially resulted from a substantial reduction in the 25(OH)D3 sub-fraction with ergocalciferol. However, following cessation of therapy, no statistical difference was observed for total 25(OH)D change from baseline to week 18 between cholecalciferol and ergocalciferol groups (22·4 (sd 12·7) v. 17·6 (sd 8·9) ng/ml, respectively; P=0·17). We observed no significant difference between these therapies with regard to changes in serum PTH or 1,25(OH)2D. Therapy with cholecalciferol, compared with ergocalciferol, is more effective at raising serum 25(OH)D in non-dialysis-dependent CKD patients while active therapy is ongoing. However, levels of 25(OH)D declined substantially in both arms following cessation of therapy, suggesting the need for maintenance therapy to sustain levels.

Background: To assess a patient's vitamin D status the precursor metabolite 25-hydroxyvitamin D can be determined. However, measurement of 1,25-dihydroxyvitamin D is required when disorders of 1a-hydroxylation, extrarenal 1a-hydroxylation, or vitamin D receptor defects are suspected., Methods: The aim of this study was to determine reference values for 1,25-dihydroxyvitamin D 3 and D 2 using a 2D ID-UPLC-MS/MS method., Results: The LC-MS/MS method, able to measure picomolar concentrations of both 1,25-dihydroxyvitamin D 3 and D 2 in human serum, was extensively validated. Intra-assay variations were <5% and 8.5% and <7.5% and 11%, for 1,25-dihydroxyvitamin D 3 and D 2 , respectively, over the whole dynamic range (3.1-376 and 3.1-652pmol/L). Limit of quantitation was 3.4pmol/L for both compounds. Our method correlated well with a published LC-MS/MS method (r=0.87) and with the average 1,25-dihydroxyvitamin D 3 results of the vitamin D External Quality Assessment Scheme (DEQAS) determined with LC-MS/MS (r=0.93). Reference ranges, determined in 96 plasma samples of healthy volunteers were 59-159pmol/L and <17pmol/L for respectively 1,25-dihydroxyvitamin D 3 and D 2 . The female part of the reference group showed a statistically significant decrease of 1,25-dihydroxyvitamin D 3 concentrations with age. The presence of significantly higher average 1,25-dihydroxyvitamin D 3 levels in premenopausal women taking oral contraceptive pills compared to postmenopausal women suggests that this effect is estrogen-related, as estrogens lead to a higher vitamin D binding protein., Conclusions: The major finding of the present study is a reference interval of 59-159pmol/L for 1,25-dihydroxyvitamin D 3 determined with a highly sensitive and precise LC-MS/MS method., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To establish the impact the chronic kidney disease stage has in the native vitamin D levels in patients not undergoing dialysis treatment., Methods: A study performed in Manizales, Colombia, a city located 2,200 meters above sea level, without important stational variations. Patients with 18 years of age or more, with chronic kidney disease stages 2 to 5 and not undergoing dialysis treatment were recruited for this study. Demographic and anthropometric variations were evaluated as well as solar exposure, CKD etiology and laboratory variables related to bone and mineral diseases. For each CKD clinical stage, correlations were evaluated for vitamin D levels, laboratory results for bone and mineral diseases, solar exposure and ethnicity., Results: Three hundred thirty-three patients were evaluated with a median age of 71 years, most of them mestizo (71%), 173 were women. The main CKD etiology was hypertensive nephropathy (32.2%). 21.1% of patients had normal vitamin D levels, 70.1% were within insufficient range and 8.8% were in deficit. A negative correlation was found between the levels of vitamin 25 (OH) D and the values for: creatinine, phosphorous, calcium x phosphorous product, PTH, 24 hours urine protein and BMI. A positive relationship was found for calcium and albumin. Positive significant statistical correlation was found for vitamin 25(OH) D levels and solar exposure for stages 3b and 4 of CKD., Conclusions: It is common to find low levels of vitamin 25(OH) D in patients with CKD; these can contribute to the appearance of secondary hyperparathyroidism., Objetivo: Establecer el impacto del estadio clínico en los niveles de vitamina D nativa en pacientes con enfermedad renal crónica (ERC) sin diálisis., Métodos: Estudio realizado en Manizales, Colombia, una ciudad tropical ubicada a 2,200 metros de altura sobre el nivel del mar, sin variaciones estacionales importantes a lo largo del año. Se incluyeron pacientes mayores de 18 años, con enfermedad renal crónica estadio 2 a 5 sin tratamiento dialítico. En ellos se evaluaron variables demográficas, antropométricas, grado de exposición solar, etiología de la enfermedad, y variables de laboratorio relacionadas con desórdenes óseos y minerales. Para cada estadío clínico se evaluó la correlación entre los niveles de vitamina D y los resultados de las pruebas de laboratorio relacionadas con desordenes óseos y minerales, exposición solar y etnia., Resultados: Se evaluaron 331 pacientes, con una edad media de 71 años, la mayoría mestizos (71%), 173 mujeres. La principal etiología de ERC fue nefropatía hipertensiva (33.2%). El 21.1% de los pacientes tenían niveles normales de vitamina D, fueron insuficientes en 70.1% y 8.8% en déficit. Se detectó correlación negativa, entre los niveles de vitamina 25(OH)D y los valores de creatinina, fósforo, producto calcio x fósforo, PTH, proteínas en orina de 24 horas e IMC. Correlación positiva para el calcio y la albumina. Se encontró significancia estadística positiva entre los niveles de vitamina 25(OH)D y la exposición solar para los estadios 3b y 4., Conclusiones: En pacientes con ERC es comun detectar bajos niveles de 25(OH)D, los cuales pueden contribuir a la generación de hiperparatiroidismo secundario., Competing Interests: Conflict of interest:The authors state no conflict of interest

Vitamin D plays important roles in skeletal metabolism and many other diseases, including chronic renal failure, hypoparathyroidism, sarcoidosis and rickets. 1α,25-dihydroxy vitamin D (1α,25(OH)2D), the active form of vitamin D, exhibits an extremely low serum concentration, which makes its quantification very challenging. High performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) is considered to be the "gold standard" for the determination of these chemicals, which are found in low concentrations in the serum, but conventionally, it needs tedious sample pretreatment procedures, such as solid phase extraction and derivatization. Herein, we describe a simple and rapid HPLC-MS/MS method for the simultaneous quantification of 1α,25-dihydroxy vitamin D3 (1α,25(OH)2D3) and 1α,25-dihydroxy vitamin D2 (1α,25(OH)2D2). The analytes were extracted from the matrix by liquid-liquid extraction, centrifuged to dryness and reconstituted with 75% methanol. Lithium acetate was employed to improve the ionization efficiency of 1α,25(OH)2D. The assay was sensitive with a low limit of quantitation of 10.0pg/mL for both 1α,25(OH)2D3 and 1α,25(OH)2D2 using a 0.5mL sample aliquot. Linearity was obtained over the range of 10.0pg/mL to 500pg/mL. Both the inter-assay and intra-assay precisions were <15%, and the analytical recoveries were within 100±5%. The performance evaluation of this assay demonstrated that it was a practical, sensitive and specific method for measuring the serum 1α,25(OH)2D3 and 1α,25(OH)2D2 concentrations., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The determination of both the water-soluble and lipid-soluble vitamin D compounds in human biological fluids is necessary to illuminate potentially significant biochemical mechanisms. The lack of analytical methods to quantify the water-soluble forms precludes studies on their role and biological functions; currently available liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods are able to determine only a single sulfated form of Vitamin D. We describe here a highly sensitive and specific LC-MS/MS method for the quantification of four sulfated forms of vitamin D: vitamins D2- and D3-sulfate (D2-S and D3-S) and 25-hydroxyvitamin D2- and D3-sulfate (25(OH)D2-S and 25(OH)D3-S). A comparative evaluation showed that the ionization efficiencies of underivatized forms in negative ion mode electrospray ionisation (ESI) are superior to those of the derivatized (using 4-phenyl-l,2,4-triazoline-3,5-dione (PTAD)) forms in positive ion mode ESI. Separation was optimised to minimise co-elution with endogenous matrix compounds, thereby reducing ion suppression/enhancement effects. Isotopically labelled analogues of each compound were used as internal standards to correct for ion suppression/enhancement effects. The method was validated and then applied for the analysis of breastmilk and human serum. The detection limits, repeatability standard deviations, and recoveries ranged from 0.20 to 0.28fmol, 2.8 to 10.2%, and 81.1 to 102%, respectively., (Copyright © 2015 Elsevier B.V. All rights reserved.)

1,25-Dihydroxyvitamin D is the active form of vitamin D and plays a critical role in the maintenance of calcium and phosphorous metabolism of the human body. Measurement of 1,25-dihydroxyvitamin D in serum can aid in clinical diagnosis and/or management of renal disease, sarcoidosis, and rare inherited diseases. We present here an effective and accurate method for measuring 1,25-dihydroxyvitamin D3 and 1,25-dihydroxyvitamin D2 by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) after immunoaffinity extraction. The MS/MS is operated in multiple reaction mode with positive electrospray. Quantification is based on peak area ratios of the analytes to respective deuterated internal standards. This method offered a linear range from 4.0 to 160.0 pg/mL with analytical recovery of 89.9-115.5 % for both 1,25-dihydroxyvitamin D3 and 1,25-dihydroxyvitamin D2.

Background and Purpose: Low 25-hydroxyvitamin D [25(OH)D] levels correlate with higher disease activity in patients with multiple sclerosis (MS). However, it is not clear whether low 25(OH)D levels directly contribute to increased disease activity or merely represent a consequence of reduced endogenous vitamin D synthesis in more disabled MS patients. Furthermore, recent data suggest that bioavailable vitamin D, which also integrates the levels of vitamin D binding proteins and albumin, could be a biologically more relevant parameter than 25(OH)D., Methods: Measured de-seasonalized 25(OH)D3 and vitamin D binding protein and calculated bioavailable and free vitamin D were compared in the baseline serum samples of 76 patients with clinically isolated syndrome enrolled in a longitudinal observational study and in 76 age- and sex-matched healthy controls (HC)., Results: 25(OH)D3 levels were lower in patients with clinically isolated syndrome (P = 0.002) than in HC, and more patients (8/76, 10.5%) than HC (1/76, 1.3%) had 25(OH)D3 levels <25 nmol/l (P = 0.03). In contrast, levels of 25(OH)D2, vitamin D binding protein and calculated levels of free and bioavailable vitamin D did not differ between the two groups., Conclusions: Lower 25(OH)D3 levels already in the earliest phase of disease and in clinically hardly affected patients suggest that low 25(OH)D3 levels are rather a risk factor for than a consequence of MS. Nevertheless, because bioavailable vitamin D levels did not differ between the two groups, the mechanism underlying the association of 25(OH)D3 and MS does not appear to be related to reduced bioavailability of vitamin D., (© 2015 EAN.)

Vitamin D levels of pregnant women and their neonates tend to be related; however, it is unknown whether there are any subgroups in which they are not related. 25-Hydroxyvitamin D [25(OH)D] was measured in prenatal maternal and child cord blood samples of participants (n = 241 pairs) in a birth cohort. Spearman correlations were examined within subgroups defined by prenatal and delivery factors. Cord blood as a percentage of prenatal 25(OH)D level was calculated and characteristics compared between those who did and did not have ≥25% and ≥50% of the maternal level and those who did and did not have a detectable 25(OH)D level. The correlation among Black children was lower than in White children. When the maternal 25(OH)D level was <15 ng/mL, the overall correlation was r = 0.16. Most children had a 25(OH)D cord blood level less than half of their mother's; 15.4% had a level that was <25% of their mother's. Winter birth and maternal level were associated with the level being less than 25%. Children with undetectable levels were more likely to be Black and less likely to be firstborn. These data suggest mothers may reduce their contribution to the fetus's 25(OH)D supply once their own level becomes low.

Objective: To investigate the effects of vitamin D supplement for three months on anthropometric and glucose homeostatic measures in Thai adults with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT)., Material and Method: Forty-seven IFG and/or IGT subjects enrolled in the study. Subjects were randomized into three groups, control (n = 18), vitamin D₂ (20,000 IU weekly, n = 19) or vitamin D₃ (15,000 IU weekly, n = 10). Anthropometric variables were obtained at baseline and at 3-month. Oral glucose tolerance test was performed at baseline and at 3-month. Total serum 25(OH)D, 25(OH)D₃, and 25(OH)D2 were measured by LC-MS/MS. Insulin resistance (HOMA-IR) and insulin secretion index (HOMA%B) were calculated by the homeostasis model assessment., Results: The total 25(OH)D levels significantly increased from baseline in both the vitamin D₂ and the vitamin D₃ groups, while there was no change in the control group. D₃ supplementation raised 25(OH)D₃ significantly (+13.7 ± 4.9 ng/mL, p < 0.01) while D2 increased 25(OH)D2 levels (+25.9?4.2 ng/mL, p<0.001) but with a decrease in 25(OH)D3 (-13.1?3.1 ng/mL, p<0. 001). Subjects were classified into two groups, i.e., control (n = 18) and D₂ or D₃ supplementations (n = 29). After three months, waist circumference (WC) significantly decreased in subjects of vitamin D supplementation group. Body weight (BW p = 0.05), systolic blood pressure (SBP, p = 0.05), body mass index (BM, p = 0.06), and HOMA-IR (p = 0.09) also tended to decrease. Subjects with an increase of total 25(OH)D levels > 10 ng/mL (23 of 29 subjects) had significant decrease in HOMA-IR and increase in disposition index. Using robust regression analysis, we found the use of D3 was associated with a larger decrease in WC (coefficient = -3.5, p < 0.001) independent of the change in total 25(OH)D and baseline BMI. No difference between D₂ and D₃ was observed for other metabolic measures., Conclusion: Weekly supplementations of vitamin D₂ (20,000 IU) or vitamin D₃ (15,000 IU) improve metabolic phenotypes in subjects with prediabetes. D₃ supplement may decrease waist circumference more than D₂ supplement.

Many methods for routine total plasma/serum 25-hydroxyvitamin D (25OHD) measurements are available from automated immunoassays to the most specific LC-MS/MS techniques. These last ones are nowadays numerous, still perfectible but more powerful than immunoassays in specific illnesses. We presented a robust method for simple quantification of 25-hydroxyvitamin D(2) (25OHD(2)) and 25-hydroxyvitamin D(3) (25OHD(3)) in human plasma by LC-APCI-MS/MS. This method is reliable and easy to perform for clinical measurements as we report a 4-year of clinical laboratory use. A brief off-line sample pretreatment (protein precipitation with addition of the internal standard) was realized then the supernatant was loaded into 96-well plates and analyzed by an online SPE-LC/MS/MS method on an APCI mode. 25OHD(2) and 25OHD(3) were both measured. The chromatographic system was thought and optimized for providing a dedicated line for this measurement on a shared instrument. The linearity was tested up to 380 nmol/L for both 25OHD(2) and 25OHD(3). The limit of quantification (LOQ) was 7 and 8 nmol/L for 25OHD3 and 25OHD(2), respectively. Routine imprecision and bias were found in agreement with recommended limits for routine testing, CV≤10% and bias≤5%. Since July 2010, our participation to DEQAS was successfully validated. This simple robust online SPE-LC/MS/MS method is suitable for routine measurement of 25OHD(2) and 25OHD(3) in human adult plasma. The assay operates for 4 years and has performed more than 40,000 patient samples on a shared instrument., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A highly sensitive, specific and rapid LC-ESI-MS/MS method has been developed and validated for the quantification of paricalcitol (PAR) in human plasma (500 μL) using paricalcitol-d6 (PAR-d6 ) as an internal standard (IS) as per regulatory guidelines. A liquid-liquid extraction method was used to extract the analyte and IS from human plasma. Chromatography was achieved on Zorbax SB C18 column using an isocratic mobile phase in a gradient flow. The total chromatographic run time was 6.0 min and the elution of PAR and PAR-d6 occurred at ~2.6 min. A linear response function was established for the range of concentrations 10-500 pg/mL in human plasma. The intra- and inter-day accuracy and precision values for PAR met the acceptance criteria. The validated assay was applied to quantitate PAR concentrations in human plasma following oral administration of 4 µg capsules to humans., (Copyright © 2014 John Wiley & Sons, Ltd.)

Background: Despite living in a sunny country, hypovitaminosis D is common in women of reproductive age in Al Ain, United Arab Emirates (UAE)., Aims and Objectives: To establish the prevalence of hypovitaminosis D in adolescent female Emirati nationals and its risk factors., Methods: This was an analytical prospective cohort study of 350 female Emirati nationals aged 11-18 years attending public schools in Al Ain. Socio-economic status, diet and amount of sun exposure were evaluated by face-to-face interviews. Serum total 25 (OH) vitamin D (D2 + D3) levels were measured by electrochemiluminescence assay. The prevalence of hypovitaminosis D was calculated and the association with risk factors analysed., Results: Data were complete for 293 girls. Only one girl [prevalence 0.3%, 95% confidence interval (CI) 0.01-1.9] had vitamin D sufficiency (serum vitamin D levels >75 nmol/L). Three girls (1.0%, 95% CI 0.2-2.9) had vitamin D insufficiency (50-75 nmol/L), 58 (19.8%, 95% CI 15.0-25.5) were deficient (27.5-50 nmol/L) and 231 (78.8%, 95% CI 68.9-89.6) had severe deficiency (<27.5 nmol/L). Serum vitamin D levels declined between the ages of 11 and 13 years before progressively rising until the age of 18 years but without regaining the levels they were at the age of 11. There was no statistically significant difference between the vitamin D status groups in age, body mass index, accommodation type, family income, percentage of surface area unexposed to the sun when outdoors, consumption of oily fish or total vitamin D intake., Conclusion: The finding of a high prevalence of hypovitaminosis D in adolescent females in UAE is of serious concern for their health and that of their infants during their reproductive lives. Adolescent girls with a similar social and cultural background currently living in less sunny, industrialised countries might also be at risk.

Unlabelled: Bile acid amidation defects were predicted to present with fat/fat soluble vitamin malabsorption with minimal cholestasis. We identified and treated five patients (one male, four females) from four families with defective bile acid amidation due to a genetically confirmed deficiency in bile acid CoA:amino acid N-acyl transferase (BAAT) with the conjugated bile acid, glycocholic acid (GCA). Fast atom bombardment-mass spectrometry analysis of urine and bile at baseline revealed predominantly unconjugated cholic acid and absence of the usual glycine and taurine conjugated primary bile acids. Treatment with 15 mg/kg GCA resulted in total duodenal bile acid concentrations of 23.3 ± 19.1 mmol/L (mean ± SD) and 63.5 ± 4.0% of the bile acids were secreted in bile in the conjugated form, of which GCA represented 59.6 ± 9.3% of the total biliary bile acids. Unconjugated cholic acid continued to be present in high concentrations in bile because of partial intestinal deconjugation of orally administered GCA. Serum total bile acid concentrations did not significantly differ between pretreatment and posttreatment samples and serum contained predominantly unconjugated cholic acid. These findings confirmed efficient intestinal absorption, hepatic extraction, and biliary secretion of the administered GCA. Oral tolerance tests for vitamin D2 (1,000 IU vitamin D2/kg) and tocopherol (100 IU/kg tocopherol acetate) demonstrated improvement in fat-soluble vitamin absorption after GCA treatment. Growth improved in 3/3 growth-delayed prepubertal patients., Conclusion: Oral glycocholic acid therapy is safe and effective in improving growth and fat-soluble vitamin absorption in children and adolescents with inborn errors of bile acid metabolism due to amidation defects., (© 2014 by the American Association for the Study of Liver Diseases.)