Association between urinary arsenic species and vitamin D deficiency: a cross-sectional study in Chinese pregnant women.

Background: An increasing number of studies suggest that environmental pollution may increase the risk of vitamin D deficiency (VDD). However, less is known about arsenic (As) exposure and VDD, particularly in Chinese pregnant women. Objectives: This study examines the correlations of different urinary As species with serum 25 (OH) D and VDD prevalence. Methods: We measured urinary arsenite (As3+), arsenate (As5+), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) levels and serum 25(OH)D2, 25(OH)D3, 25(OH) D levels in 391 pregnant women in Tianjin, China. The diagnosis of VDD was based on 25(OH) D serum levels. Linear relationship, Logistic regression, and Bayesian kernel machine regression (BKMR) were used to examine the associations between urinary As species and VDD. Results: Of the 391 pregnant women, 60 received a diagnosis of VDD. Baseline information showed significant differences in As3+, DMA, and tAs distribution between pregnant women with and without VDD. Logistic regression showed that As3+ was significantly and positively correlated with VDD (OR: 4.65, 95% CI: 1.79, 13.32). Meanwhile, there was a marginally significant positive correlation between tAs and VDD (OR: 4.27, 95% CI: 1.01, 19.59). BKMR revealed positive correlations between As3+, MMA and VDD. However, negative correlations were found between As5+, DMA and VDD. Conclusion: According to our study, there were positive correlations between iAs, especially As3+, MMA and VDD, but negative correlations between other As species and VDD. Further studies are needed to determine the mechanisms that exist between different As species and VDD.

Separation and identification of monoglucuronides of vitamin D3 metabolites in urine by derivatization-assisted LC/ESI-MS/MS using a new Cookson-type reagent.

A liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) method was developed using a new Cookson-type reagent, 4-[4-(1-pipelidinyl)phenyl]-1,2,4-triazoline-3,5-dione (PIPTAD), to analyze the monoglucuronides (Gs) of vitamin D3 metabolites in human urine. The G of 23S,25-dihydroxyvitamin D3 [23,25(OH)2D3] was previously found as a major metabolite of vitamin D3 in the urine, but its conjugation position remained undetermined. Determination of the position was an important research issue to clarify the whole picture of the excretion of surplus 25-hydroxyvitamin D3 [25(OH)D3, the circulating form of vitamin D3] in humans. After the pretreated urine sample was derivatized with PIPTAD, the peak corresponding to the G of 23,25(OH)2D3 was satisfactorily separated from the urine-derived interfering substances on reversed-phase LC, which could not be achieved by using the previous analogous reagent, DAPTAD. The PIPTAD-derivatized Gs of the vitamin D3 metabolites provided characteristic product ions useful for identifying the conjugation positions during the MS/MS. Accordingly, we successfully determined the glucuronidated position of 23,25(OH)2D3 to be the C23-hydroxy group. The developed method also enabled the simultaneous detection of Gs of 25(OH)D3 and 24R,25-dihydroxyvitamin D3 as well as 23,25(OH)2D3-23-G without interference from the urine components.

Examination of potential novel biochemical factors in relation to prostate cancer incidence and mortality in UK Biobank.

BACKGROUND: Although prostate cancer is a leading cause of cancer death, its aetiology is not well understood. We aimed to identify novel biochemical factors for prostate cancer incidence and mortality in UK Biobank. METHODS: A range of cardiovascular, bone, joint, diabetes, renal and liver-related biomarkers were measured in baseline blood samples collected from up to 211,754 men at recruitment and in a subsample 5 years later. Participants were followed-up via linkage to health administrative datasets to identify prostate cancer cases. Hazard ratios (HRs) and 95% confidence intervals were calculated using multivariable-adjusted Cox regression corrected for regression dilution bias. Multiple testing was accounted for by using a false discovery rate controlling procedure. RESULTS: After an average follow-up of 6.9 years, 5763 prostate cancer cases and 331 prostate cancer deaths were ascertained. Prostate cancer incidence was positively associated with circulating vitamin D, urea and phosphate concentrations and inversely associated with glucose, total protein and aspartate aminotransferase. Phosphate and cystatin-C were the only biomarkers positively and inversely, respectively, associated with risk in analyses excluding the first 4 years of follow-up. There was little evidence of associations with prostate cancer death. CONCLUSION: We found novel associations of several biomarkers with prostate cancer incidence. Future research will examine associations by tumour characteristics.

Seasonal variations in urinary calcium, volume, and vitamin D in kidney stone formers

ABSTRACT Objectives: To investigate the seasonal variations in urinary calcium, serum vitamin D, and urinary volume in patients with a history of nephrolithiasis. Materials and Methods: Patients included were those who completed a 24-hour urine metabolic evaluation on two occasions; one in summer (June-Aug) and one in winter (Nov-Jan), and who had not started any medications or been instructed on dietary modifications in the interval between the two tests that may have impacted the results. Patients were excluded if they were on thiazide diuretics or were taking calcium and / or Vitamin D supplementation. Welch's t-test was used to compare the difference in average summer and winter values. Unpaired Student t-test was used to compare baseline parameters (age, BMI), and Paired Student t-test was used to compare average seasonal measurements in men vs. women. Results: 136 patients were identified who were not taking calcium or vitamin D supplements or thiazide diuretics, and who were not instructed on dietary modifications in the interval between the two measured parameters. No significant differences were observed when comparing male to female baseline parameters of age or BMI (Table-1). Average 24-hour urine calcium was higher (226.60) in the winter than in summer (194.18) and was significant in males (p = 0.014) and females (p < 0.001). No significant seasonal difference was seen in 24-hour urine volume or serum vitamin D levels. Conclusions: Urinary calcium is higher in winter months compared to summer months. As such, tailoring medical preventative strategies to the time of year may be helpful.

Seasonal variations in urinary calcium, volume, and vitamin d in kidney stone formers.

OBJECTIVES: To investigate the seasonal variations in urinary calcium, serum vitamin D, and urinary volume in patients with a history of nephrolithiasis. MATERIALS AND METHODS: Patients included were those who completed a 24-hour urine metabolic evaluation on two occasions; one in summer (June-Aug) and one in winter (Nov-Jan), and who had not started any medications or been instructed on dietary modifications in the interval between the two tests that may have impacted the results. Patients were excluded if they were on thiazide diuretics or were taking calcium and / or Vitamin D supplementation. Welch's t-test was used to compare the difference in average summer and winter values. Unpaired Student t-test was used to compare baseline parameters (age, BMI), and Paired Student t-test was used to compare average seasonal measurements in men vs. women. RESULTS: 136 patients were identified who were not taking calcium or vitamin D supplements or thiazide diuretics, and who were not instructed on dietary modifications in the interval between the two measured parameters. No significant differences were observed when comparing male to female baseline parameters of age or BMI (Table-1). Average 24-hour urine calcium was higher (226.60) in the winter than in summer (194.18) and was significant in males (p = 0.014) and females (p < 0.001). No significant seasonal difference was seen in 24-hour urine volume or serum vitamin D levels. CONCLUSIONS: Urinary calcium is higher in winter months compared to summer months. As such, tailoring medical preventative strategies to the time of year may be helpful.

Vitamin A and D intake in pregnancy, infant supplementation, and asthma development: the Norwegian Mother and Child Cohort.

Background: Western diets may provide excess vitamin A, which is potentially toxic and could adversely affect respiratory health and counteract benefits from vitamin D. Objective: The aim of this study was to examine child asthma at age 7 y in relation to maternal intake of vitamins A and D during pregnancy, infant supplementation with these vitamins, and their potential interaction. Design: We studied 61,676 school-age children (born during 2002-2007) from the Norwegian Mother and Child Cohort with data on maternal total (food and supplement) nutrient intake in pregnancy (food-frequency questionnaire validated against biomarkers) and infant supplement use at age 6 mo (n = 54,142 children). Linkage with the Norwegian Prescription Database enabled near-complete follow-up (end of second quarter in 2015) for dispensed medications to classify asthma. We used log-binomial regression to calculate adjusted RRs (aRRs) for asthma with 95% CIs. Results: Asthma increased according to maternal intake of total vitamin A [retinol activity equivalents (RAEs)] in the highest (≥2031 RAEs/d) compared with the lowest (≤779 RAEs/d) quintile (aRR: 1.21; 95% CI: 1.05, 1.40) and decreased for total vitamin D in the highest (≥13.6 µg/d) compared with the lowest (≤3.5 µg/d) quintile (aRR: 0.81; 95% CI: 0.67, 0.97) during pregnancy. No association was observed for maternal intake in the highest quintiles of both nutrients (aRR: 0.99; 95% CI: 0.83, 1.18) and infant supplementation with vitamin D or cod liver oil. Conclusions: Excess vitamin A (≥2.5 times the recommended intake) during pregnancy was associated with increased risk, whereas vitamin D intake close to recommendations was associated with a reduced risk of asthma in school-age children. No association for high intakes of both nutrients suggests antagonistic effects of vitamins A and D. This trial was registered at http://www.clinicaltrials.gov as NCT03197233.

Vitamin D and renal outcome: the fourth outcome of CKD-MBD? Oshima Award Address 2015.

Bone fracture, cardiovascular events, and mortality are three outcomes of chronic kidney disease-mineral and bone disorder (CKD-MBD), and the umbrella concept originally described for dialysis patients. The reported association of serum phosphorus or fibroblast growth factor 23 (FGF23) levels with renal outcome suggests that the fourth relevant outcome of CKD-MBD in predialysis patients is renal outcome. We found that proteinuria of 2+ or greater with a dipstick test was associated with low vitamin D status due to urinary loss of 25-hydroxyvitamin D (25D). Moreover, active vitamin D or its analogues decrease proteinuria. Given our finding that maxacalcitol does not repress renin, the reduction of proteinuria by this agent is likely due to direct upregulation of the nephrin and podocin in podocytes. Moreover, this agent downregulates the mesenchymal marker desmin in podocytes and blocks transforming growth factor-beta autoinduction, leading to attenuation of renal fibrosis in a unilateral ureteral obstructive (UUO) model. These facts are reminiscent of the suppression of epithelial-mesenchymal transition (EMT) by vitamin D. EMT blockage may explain our finding that vitamin D prescription in renal transplant recipients is associated with a lower incidence of cancer. We also reported that low vitamin D status and high FGF23 levels predict a worse renal outcome. However, administration of massive doses of 25D exacerbates renal fibrosis in UUO kidneys in 1alpha-hydroxylase knockout mice. Moreover, FGF23 inhibits 1alpha-hydroxylase in proximal tubules and monocytes. Taken together, local 1,25(OH)2D in the kidney tissue but not 25D seems to protect the kidney.

Effects of cholecalciferol supplementation on serum and urinary vitamin D metabolites and binding protein in HIV-infected youth.

Vitamin D insufficiency is widespread in HIV-infected patients. HIV and/or antiretroviral therapy (ART), particularly efavirenz (EFV), may interfere with vitamin D metabolism. However, few data from randomized, controlled trials exist. Here, we investigate changes in vitamin D metabolites and binding protein (VDBP) after 6 months of supplementation in a randomized, active-control, double-blind trial investigating 2 different monthly cholecalciferol (vitamin D3) doses [60,000 (medium) or 120,000 (high) IU/month] vs. a control arm of 18,000 IU/month in 8-25year old HIV-infected youth on ART with HIV-1 RNA <1000 copies/mL and baseline 25-hydroxycholecalciferol (25(OH)D3) ≤30ng/mL. A matched healthy uninfected group was enrolled in a similar parallel study for comparison. Changes after 6 months were analyzed as intent-to-treat within/between groups [control group (low dose) vs. combined supplementation doses (medium+high)]. At 6 months, 55% vs. 82% of subjects in control and supplementation groups, respectively, reached 25(OH)D3 ≥30ng/mL (P=0.01) with no difference between medium and high doses (both 82% ≥30ng/mL). There were few differences for those on EFV vs. no-EFV, except serum VDBP decreased in EFV-treated subjects (both within- and between-groups P≤0.01). There were no significant differences between the HIV-infected vs. healthy uninfected groups. The major finding of the present study is that cholecalciferol supplementation (60,000 or 120,000 IU/month) effectively raises serum 25(OH)D3 in the majority of HIV-infected subjects, regardless of EFV use. Notably, response to supplementation was similar to that of uninfected subjects.

Analysis of vitamin D deficiency in calcium stone-forming patients.

PURPOSE: The aim of this study is to analyse the percentage of hypovitaminosis D, as well as its relationship with the various parameters of calcium-phosphate metabolism. METHODS: A case control study was conducted on 366 patients, divided into two groups: Group 1: 127 non-stone-forming patients, and Group 2: 239 calcium stone forming. A study was performed on calcium-phosphate metabolism and urinary lithogenic factors. The percentage of vitamin D deficiency (25-OH-vitamin D levels <20 ng/ml) between the groups was analysed and compared. The SPSS 20.0 statistics program was used for the analysis, with a p ≤ .05 being considered significant. RESULTS: The mean age of Group 1 was 52.1 years compared to 49.6 years in Group 2, with no significant differences (p = .07). Vitamin D levels were lower in Group 2 compared to Group 1 (25.7 vs. 28.4 ng/ml, p = .02). A vitamin D deficiency was observed in 28 % of the Group 2 stone-forming patients versus 15.7 % in Group 1 (p = .009), with an odds ratio (OR) of 2.09 (95 % CI; 1.19-3.63). In the stone-forming patients with a vitamin D deficiency, the only difference observed was the higher levels of iPTH compared to those stone-formers with a normal vitamin D (56.9 vs. 45.5 pg/ml, respectively; p = .0001). CONCLUSION: Calcium stone-forming patients have lower mean levels of vitamin D and a higher percentage of hypovitaminosis D than in non-stone-forming patients. This was only related to increased iPTH levels, with urine calcium and other lithogenic parameters having no obvious effect.

Calcium and phosphorus metabolism and lithogenic factors in patients with osteoporotic fracture.

OBJECTIVES: To demonstrate the attendance of mineral metabolism disorders and lithogenic factors in patients' urine with osteoporotic fracture without previously known stones MATERIAL AND METHODS: 67 patients with osteoporotic fractures surgically treated in trauma service are included. The area of the fracture site, fracture mechanism and the presence of osteoporosis were the factors taken into account to diagnose osteoporotic fracture. Mineral metabolism, calciuria, oxaluria, uricosuria and citraturia in 24hours urine were analyzed. The presence of abnormal calcium and phosphorus metabolism was proved comparing hypercalciuria patients with normocalciuria ones. RESULTS: 12 men and 55 women with mean age 68.8±14.5 years old were included. Mean Body Mass Index (BMI) was 27.4±4.1kg/m2. 42% of patients showed hypercalciuria, 34% hyperoxaluria, 34% hypocitraturia and 7% hyperuricosuria. Statistically significant differences were observed only in fasting calcium/creatinine ratio (0.17 vs. 0.08; P<.0001) when comparing patients with hypercalciuria with those with normocalciuria. CONCLUSIONS: Patients with osteoporotic fractures show different lithogenic factors in urine, mainly hypercalciuria, always in fasting conditions.

Analysis of urinary vitamin D3 metabolites by liquid chromatography/tandem mass spectrometry with ESI-enhancing and stable isotope-coded derivatization.

The determination of the urinary vitamin D3 metabolites might prove helpful in the assessment of the vitamin D status. We developed a method for the determination of trace vitamin D3 metabolites, 25-hydroxyvitamin D3 [25(OH)D3] and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], in urine using liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) combined with derivatization using an ESI-enhancing reagent, 4-(4'-dimethylaminophenyl)-1,2,4-triazoline-3,5-dione (DAPTAD), and its isotope-coded analogue, (2)H4-DAPTAD (d-DAPTAD). The urine samples were treated with ß-glucuronidase, purified with an Oasis hydrophilic-lipophilic balanced (HLB) cartridge, and then subjected to the derivatization. The DAPTAD derivatization enabled the highly sensitive detection (detection limit, 0.25 fmol on the column), and the use of d-DAPTAD significantly improved the assay precision [the intra- (n = 5) and inter-assay (n = 3) relative standard deviations did not exceed 9.5%]. The method was successfully applied to urine sample analyses and detected the increases of the urinary 25(OH)D3 and 24,25(OH)2D3 levels due to vitamin D3 administration.

Dietary resistant starch prevents urinary excretion of vitamin D metabolites and maintains circulating 25-hydroxycholecalciferol concentrations in Zucker diabetic fatty rats.

BACKGROUND: Type 2 diabetes (T2D) is the leading cause of nephropathy in the United States. Renal complications of T2D include proteinuria and suboptimal serum 25-hydroxycholecalciferol (25D) concentrations. 25D is the major circulating form of vitamin D and renal reabsorption of the 25D-vitamin D-binding protein (DBP) complex via megalin-mediated endocytosis is believed to determine whether 25D can be activated to 1,25-dihydroxycholecalciferol (1,25D) or returned to circulation. We previously demonstrated that excessive urinary excretion of 25D-DBP and albuminuria occurred in rats with type 1 diabetes (T1D) and T2D. Moreover, feeding rats with T1D high-amylose maize partially resistant to digestion [resistant starch (RS)] prevented excretion of 25D-DBP without significantly affecting hyperglycemia. OBJECTIVE: We used Zucker diabetic fatty (ZDF) rats, a model of obesity-related T2D, to determine whether feeding RS could similarly prevent loss of vitamin D and maintain serum 25D concentrations. METHODS: Lean control Zucker rats (n = 8) were fed a standard semi-purified diet (AIN-93G) and ZDF rats were fed either the AIN-93G diet (n = 8) or the AIN-93G diet in which cornstarch was replaced with RS (550 g/kg diet; 35% resistant to digestion) (n = 8) for 6 wk. RESULTS: RS attenuated hyperglycemia by 41% (P < 0.01) and prevented urinary DBP excretion and albuminuria, which were elevated 3.0- (P < 0.01) and 3.6-fold (P < 0.01), respectively, in control diet-fed ZDF rats. Additionally, urinary excretion of 25D (P = 0.01) and 1,25D (P = 0.03) was higher (89% and 97%, respectively), whereas serum 25D concentrations were 31% lower (P < 0.001) in ZDF rats fed the control diet compared with RS-fed ZDF rats. Histopathologic scoring of the kidney revealed that RS attenuated diabetes-mediated damage by 21% (P = 0.12) despite an ∼50% decrease in megalin protein abundance. CONCLUSIONS: Taken together, these data provide evidence that suggests vitamin D balance can be maintained by dietary RS through nephroprotective actions in T2D, which are independent of vitamin D supplementation and renal expression of megalin.

Role of 1,25-dihydroxy vitamin D3 and parathyroid hormone in urinary calcium excretion in calcium stone formers.

PURPOSE: To find out the possible role of 1,25(OH)2 vitamin D3 [1,25(OH)2D3] and parathyroid hormone (PTH) as intrinsic factors in urinary calcium stone formers (SFs), we investigated their relationship with serum and urinary biochemical parameters. MATERIALS AND METHODS: A total of 326 calcium SFs (male: 204, female: 122) were enrolled and underwent outpatient metabolic evaluations including 1,25(OH)2D3 and PTH as well as serum and 24-hour urinary biochemical parameters. As control, 163 age- and sex-matched (2:1) individuals (non-SFs) who have never urinary stone episode were included. RESULTS: 1,25(OH)2D3 level was positively correlated with urinary calcium excretion (r=0.347, p<0.001). The hypercalciuric group and recurrent SFs had higher serum 1,25(OH)2D3 levels than the normocalciuric group (p<0.001) and first SFs (p=0.050). In the adjusted multiple linear regression analysis, serum 1,25(OH)2D3 level (ß=0.259, p<0.001) and serum PTH level (ß=-0.160, p<0.001) were significantly correlated with urinary calcium excretion. The patients in highest tertile of 1,25(OH)2D3 had a more than 3.1 fold risk of hypercalciuria than those in the lowest tertile (odds ratio=3.14, 95% confidence interval: 1.431-6.888, p=0.004). No correlation was observed between PTH and 1,25(OH)2D3 (R=0.005, p=0.929) in calcium SFs, while a negative correlation was found in controls (R=-0.269, p=0.001). CONCLUSION: 1,25(OH)2D3 was closely correlated with urinary calcium excretion, and high 1,25(OH)2D3 levels were detected in the hypercalciuric group and in recurrent SFs. However, 1,25(OH)2D3 was not correlated with PTH in calcium SFs. These findings suggest that 1,25(OH)2D3 might be important intrinsic factor for altered calcium regulation in SFs.

Activation of FGF-23 mediated vitamin D degradative pathways by cholecalciferol.

CONTEXT: The optimal circulating concentration of 25(OH) vitamin D is controversial. OBJECTIVE: The aim was to investigate if FGF-23 and 24,25(OH)2D can guide cholecalciferol replacement. DESIGN: Oral cholecalciferol (10,000 IU weekly) administered to subjects with 25(OH)D levels < 20 ηg/mL and eGFR > 60 mL/min/1.73 m(2) (n = 25), chronic kidney disease (CKD) (n = 27), or end stage renal disease (ESRD) (n = 14). SETTING: The study was conducted at the Veterans Affairs clinics. MAIN OUTCOME MEASURE: Serum FGF-23, PTH, 25(OH)D, 1,25(OH)2D, 24,25(OH)2D, calcium, and phosphorous concentrations, and urinary excretion of calcium and phosphorus at baseline and after 8 weeks of treatment. RESULTS: Cholecalciferol treatment increased concentrations of serum 25(OH)D by (19.3 ± 8 ηg/mL, P = .001; 12.2 ± 9 ηg/mL, P = .0001) and 24,25(OH)2D (1.14 ± 0.89 ηg/mL, P = .0024; 1.0 ± 0.72 ηg/mL P = .0002), and reduced serum PTH (-11 ± 21 pg/mL, P = .0292; -42 ± 68 pg/mL, P = .0494) in normal and CKD subjects, respectively. Cholecalciferol increased serum FGF-23 levels only in normal subjects (44 ± 57 ηg/mL, P = .01). Increments in serum 25(OH)D positively correlated with serum FGF-23 and 24,25(OH)2D and negatively correlated with PTH. In ESRD, cholecalciferol administration increased 25(OH)D by (16.6 ± 6.6 ηg/mL P ≤ .05) without changing 24,25(OH)2D, FGF-23 or PTH levels. CONCLUSION: Modest elevations of serum 25(OH)D levels after cholecalciferol treatment are sufficient to induce compensatory degradative pathways in patients with sufficient renal reserves, suggesting that optimal circulating 25(OH)D levels are approximately 20 ηg/mL. In addition, catabolism of 25(OH)D may also contribute to the low circulating vitamin D levels in CKD, since elevations of FGF-23 in CKD are associated with increased 24,25(OH)2D after cholecalciferol administration.

LC-MS/MS in endocrinology: what is the profit of the last 5 years?

Currently, chromatography (GC but more commonly HPLC) is the analytical method of choice for several hormones, either because the immunoassays suffer from extensive crossreactivity or because chromatography permits simultaneous measurements of hormones. However, sometimes the conventional detection systems with HPLC methods do not meet desired specificity. With the increase of robust and affordable LC-MS/MS systems, the next step forward in specificity was taken. LC-MS/MS is rapidly being incorporated in the endocrine laboratories. To be useful in the clinical diagnostic practice, it is of utmost importance that methods are both analytically and clinically vaidated, as until now, the majority of applications of LC-MS/MS in the clinical laboratories are 'home-made' methods, therefore special case must be taken. This review aims to focus on Clinical and Laboratory Standards Institute or comparable validated LC-MS/MS methods for targeted hormone analysis used for diagnostic purposes in human samples, published in the last 5 years.

An approach for quantitative analysis of vitamins D and B9 and their metabolites in human biofluids by on-line orthogonal sample preparation and sequential mass spectrometry detection.

An approach for quantitative analysis of two vitamins with different polarities (vitamins D and B9) and their metabolites is presented here. The approach is based on an experimental setup based on hyphenation of an automated workstation for preparation of liquid samples and an LC-MS/MS system with a triple quadrupole mass spectrometer. This configuration enabled development of an orthogonal protocol for sequential SPE retention of analytes with different polarities for subsequent elution and chromatographic separation prior to detection. The resulting method was validated by application to three human biofluids. Estimation of recovery factors in the SPE step led to values from 85.2 to 100% for vitamin D and metabolites and from 93.1 to 100% for vitamin B9 and metabolites (folic acid and folates). The influence of sample matrix variability by analysis of human serum, urine and breast milk was minimized with a complete optimization of the SPE step. The utility of the proposed configuration is shown by the sensitivity and precision of the method, expressed as limits of detection (between 0.2 and 0.30 ng mL(-1) or 4 and 60 pg on-column) and within-laboratory reproducibility (lower than 6.7%, as relative standard deviation). The present application represents an example of determination methods involving targeted analysis of compounds with different polarities using a single aliquot of the sample.

Urinary environmental chemical concentrations and vitamin D are associated with vision, hearing, and balance disorders in the elderly.

BACKGROUND: Acute exposure to environmental chemicals can result in loss of consciousness and upon recovery neurological symptoms, but little evidence exists in large epidemiological human studies. Hence, it was aimed to determine the relationships between urinary environmental chemicals (including heavy metals, environmental bisphenols, pesticides, arsenic, and phthalates) concentrations and vision, hearing, and balance disorders in a national population-based setting. METHODS: United States National Health and Nutrition Examination Surveys is a national population-based multi-year cross-sectional study. Information on demographics and vision, hearing, and balance disorders was obtained by household interview using questionnaires in the 2003-2004 cohort (aged 50 and above). Urinary environmental chemicals were detected by mass spectrometry in selected but representative people. Analyses involved logistic regression models. RESULTS: Urinary cadmium, molybdenum, and tungsten concentrations, which are commonly associated with heart disease, were associated with vision disorder. Urinary 2,4,5-trichlorophenol and arsenic acid concentrations and circulating mono-n-butyl phthalate, mono-benzyl phthalate, and mono-(3-carboxypropyl) phthalate metabolites were significantly associated with hearing disorder. Moreover, urinary barium and 4-tert-octyl-phenol concentrations were associated with balance disorder. People who had ears ringing, roaring, or buzzing in the past year tended to have higher urinary barium, 2,4-dichlorophenol, and mono-benzyl phthalate concentrations. DISCUSSION: Significant correlations were observed in urinary environmental chemicals and neurobehavioural impairment for the first time. However, the causation cannot be established due to its cross-sectional study design. Future studies with a longitudinal aspect and/or in clinical trials are warranted to clearly understand the biological mechanism along the pathway before drawing a firm conclusion on these relationships.

Serum vitamin D increases with weight loss in obese subjects 6 months after Roux-en-Y gastric bypass.

BACKGROUND: Malabsorptive surgical procedures lead to deficiencies in fat-soluble vitamins. However, results concerning serum vitamin D (25OHD) after gastric bypass (GBP) are controversial. The aim of the study was to assess the influence of GBP on 25OHD and calcium metabolism. METHODS: Parameters of calcium metabolism were evaluated in 202 obese subjects before and 6 months after GBP. Thirty of them were matched for age, gender, weight, skin color, and season with 30 subjects who underwent sleeve gastrectomy (SG). A multivitamin preparation that provides 200 to 500 IU vitamin D3 per day was systematically prescribed after surgery. RESULTS: In the 202 patients after GBP, serum 25OHD significantly increased from 13.4 ± 9.1 to 22.8 ± 11.3 ng/ml (p < 0.0001), whereas parathyroid hormone (PTH) did not change. Despite a decrease in calcium intake (p < 0.0001) and urinary calcium/creatinine ratio (p = 0.015), serum calcium increased after GBP (p < 0.0001). Preoperatively, 91 % of patients had 25OHD insufficiency (< 30 ng/ml), 80% deficiency (< 20 ng/ml), and 19% secondary hyperparathyroidism (> 65 pg/ml) vs. 76, 44, and 17%, respectively, following GBP. Serum 25OHD was negatively correlated with BMI at 6 months after GBP (R = -0.299, p < 0.0001). In the two groups of 30 subjects, serum 25OHD and PTH did not differ at 6 months after GBP or SG. CONCLUSIONS: At 6 months after GBP, serum 25OHD significantly increased in subjects supplemented with multivitamins containing low doses of vitamin D. These data suggest that weight loss at 6 months after surgery has a greater influence on vitamin D status than malabsorption induced by GBP.

Vitamin D is a major determinant of bone mineral density at school age.

BACKGROUND: Vitamin D insufficiency in children may have long-term skeletal consequences as vitamin D affects calcium absorption, bone mineralization and bone mass attainment. METHODOLOGY/PRINCIPAL FINDINGS: This school-based study investigated vitamin D status and its association with vitamin D intake and bone health in 195 Finnish children and adolescents (age range 7-19 years). Clinical characteristics, physical activity and dietary vitamin D intake were evaluated. Blood and urine samples were collected for serum 25-hydroxyvitamin D (25-OHD) and other parameters of calcium homeostasis. Bone mineral density (BMD) and body composition were measured with dual-energy X-ray absorptiometry (DXA). Altogether 71% of the subjects were vitamin D insufficient (25-OHD <50 nmol/L). The median 25-OHD was 41 nmol/L for girls and 45 nmol/L for boys, and the respective median vitamin D intakes 9.1 µg/day and 10 µg/day. In regression analysis, after adjusting for relevant factors, 25-OHD concentration explained 5.6% of the variance in lumbar BMD; 25-OHD and exercise together explained 7.6% of the variance in total hip BMD and 17% of the variance in whole body BMD. S-25-OHD was an independent determinant of lumbar spine and whole body BMD and in magnitude surpassed the effects of physical activity. CONCLUSIONS/SIGNIFICANCE: Vitamin D insufficiency was common even when vitamin D intake exceeded the recommended daily intake. Vitamin D status was a key determinant of BMD. The findings suggest urgent need to increase vitamin D intake to optimize bone health in children.