Low 25OHD Research Articles

The acute effects of ultraviolet radiation on the blood transcriptome are independent of plasma 25OHD3

The molecular basis of many health outcomes attributed to solar ultraviolet radiation (UVR) is unknown. We tested the hypothesis that they may originate from transcriptional changes in blood cells. This was determined by assessing the effect of fluorescent solar simulated radiation (FSSR) on the transcriptional profile of peripheral blood pre- and 6h, 24h and 48h post-exposure in nine healthy volunteers. Expression of 20 genes was down-regulated and one was up-regulated at 6h after FSSR. All recovered to baseline expression at 24h or 48h. These genes have been associated with immune regulation, cancer and blood pressure; health effects attributed to vitamin D via solar UVR exposure. Plasma 25-hydroxyvitamin D3 [25OHD3] levels increased over time after FSSR and were maximal at 48h. The increase was more pronounced in participants with low basal 25OHD3 levels. Mediation analyses suggested that changes in gene expression due to FSSR were independent of 25OHD3 and blood cell subpopulations.

The Association of Maternal Asthma and Early Pregnancy Vitamin D with Risk of Preeclampsia: An Observation From Vitamin D Antenatal Asthma Reduction Trial (VDAART)

Maternal asthma, uncontrolled asthma, and low vitamin D levels during pregnancy have been individually linked to increased risk of preeclampsia. To investigate the association of history of physician-diagnosed asthma and uncontrolled asthma status during pregnancy with the risk of preeclampsia and the effects of early pregnancy vitamin D concentrations on this relationship. A total of 816 subjects with available pregnancy outcome data and risk factors of interest were analyzed. A group of experienced obstetricians and gynecologists from 3 study centers validated the preeclampsia diagnoses. Vitamin D was measured using the DiaSorin method at 10 to 18 weeks of gestation. The Pregnancy-Asthma Control Test was used to assess asthma control during pregnancy. Criterion-based stepwise variable selection algorithm was applied to investigate the relationships of risk factors of interest (history of asthma diagnosis, uncontrolled asthma during pregnancy, and vitamin D) to preeclampsia. The incidence of preeclampsia was not related to the presence of asthma diagnosis (8.9% with vs 7.4% without). The adjusted odds of preeclampsia controlled for maternal serum 25-hydroxyvitamin D (25OHD) concentrations was higher for women with a higher proportion of uncontrolled asthma months per visit during pregnancy (adjusted odds ratio, 3.55; 95% CI, 1.15-13.0). Adjusting for asthma control status during pregnancy, an additional decrease in the associated preeclampsia risk by 7% was observed for a 10-unit (ng/mL) increase in early pregnancy 25OHD levels (adjusted odds ratio10-unit, 0.60; 95% CI, 0.43-0.82) as compared with the previous risk estimate of preeclampsia associated with low maternal 25OHD unadjusted for asthma control status. Uncontrolled asthma during pregnancy is associated with an increased risk of preeclampsia. Early pregnancy 25OHD contributes to the association of uncontrolled asthma status with preeclampsia.

Evaluation of Vitamin D, Vitamin D Binding Protein Gene Polymorphism with Oxidant - Antioxidant Profiles in Chronic Obstructive Pulmonary Disease.

SummaryBackgroundThe aim was to evaluate the association of plasma 25-hydroxyvitamin D (25-OHD) and vitamin D binding protein (VDBP or Gc-globin) gene polymorphism with oxidant-antioxidant profiles in patients with chronic obstructive pulmonary disease (COPD), and their role as biomarker risk factors in susceptibility and severity of COPD.MethodsEighty patients diagnosed with COPD (mild, moderate and severe according to lung function tests; FEV 1%) and 80 healthy controls were included in the study. Serum nitric oxide (NO) and lipid peroxide (LP), plasma reduced glutathione (RGSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activity, 25-OHD and VDBP polymorphism were analyzed in all subjects.ResultsCOPD patients had significantly decreased serum NO, plasma SOD, RGSH, GSH-Px, CAT and 25-OHD versus controls, but had significantly increased serum LP. In COPD patients, 25-OHD levels were significantly lower (41.49± 13.65 ng/mL) versus controls, but more lower in severe COPD patients (30.54±9.09 ng/mL; sensitivity 79.2%; spe - cificity 73.2%, p<0.001) versus mild and moderate COPD. VDBP genotypes frequencies were Gc1S-1S=23.8%, Gc1F-1S=28.8%, Gc1F-1F=15%, Gc1S-2=20%, Gc1F-2=11.3% and Gc2-2=1.3%. Also, VDBP variants frequencies were Gc1S=48.1%, Gc1F=35% and Gc2=16.6%. How ever, Gc1F-1S genotypes and Gc1F variants were significantly higher than in controls (10%, 12.5%; p=0.009, p=0.001, respectively). Moreover, in severe COPD patients, Gc1F-1S genotype was significantly higher than in mild COPD (41.7% vs 31.3%, p=0.04).ConclusionCOPD patients had significantly lower plasma 25-OHD and were associated with significantly higher VDBP Gc1F-1S genotypes and Gc1F variants frequencies than controls. Low vitamin D levels and VDBP polymorphism may be important as diagnostic risk factors in the susceptibility to and severity of COPD.

Randomized supplementation of 4000\xa0IU vitamin D3 daily vs placebo on the prevalence of anemia in advanced heart failure: the EVITA trial

BackgroundLow 25-hydroxyvitamin D (25OHD) levels (< 75 nmol/l) are inversely associated with anemia prevalence. Since anemia and low 25OHD levels are common in patients with heart failure (HF), we aimed to investigate whether vitamin D supplementation can reduce anemia prevalence in advanced HF.MethodsEVITA (Effect of Vitamin D on Mortality in Heart Failure) is a randomized, placebo-controlled clinical trial in patients with initial 25OHD levels < 75 nmol/l. Participants received either 4000 IU vitamin D3 daily or a matching placebo for 36 months. A total of 172 patients (vitamin D group: n = 85; placebo group: n = 87) were investigated in this pre-specified secondary data analysis. Hemoglobin (Hb) and other hematological parameters were measured at baseline and study termination. Assessment of between-group differences in anemia prevalence and Hb concentrations was performed at study termination, while adjusting for baseline differences.ResultsIn the vitamin D and placebo group, baseline proportions of patients with anemia (Hb < 12.0 g/dL in females and < 13.0 g/dL in males) were 17.2% and 10.6%, respectively (P = 0.19). At study termination, the proportion of patients with anemia in the vitamin D and placebo groups was 32.2% and 31.8%, respectively (P > 0.99). There was no between-group difference in change in the Hb concentrations (− 0.04 g/dL [95%CI:-0.53 to 0.45 g/dL]; P = 0.87). Results regarding anemia risk and Hb concentrations were similar in the subgroup of patients with chronic kidney disease (vitamin D group: n = 26; placebo group: n = 23). Moreover, results did not differ substantially when data analysis was restricted to patients with deficient baseline 25OHD levels.ConclusionsA daily vitamin D supplement of 4000 IU did not reduce anemia prevalence in patients with advanced HF. Data challenge the clinical relevance of vitamin D supplementation to increase Hb levels.Trial registrationThe study was registered at EudraCT (No. 2010–020793-42) and clinicaltrials.gov (NCT01326650).

Is primary hyperparathyroidism a cause of endothelial dysfunction?

Symptomatic primary hyperparathyroidism (PHPT) is thought to be related to increased cardiovascular morbidity and mortality. In our study, we aimed to investigate endothelial dysfunction and markers of subclinical atherosclerosis in patients with PHPT. Also we aimed to demonstrate the effect of vitamin D supplementation on these parameters. Twenty-nine patients followed by medical treatment (A), 25 preoperative (B) and 23 postoperative patients with PHPT (C), and 26 normocalcaemic subjects (D) were included. Groups were assessed by measurements of flow-mediated dilation (FMD), carotid intima-media thickness (CIMT), serum levels of sCD40L, high-sensitivity CRP (hs-CRP) and interleukin-8 (IL-8). Thirteen patients with low levels of 25-hydroxy-vitamin D (25OHD) in the medical treatment group were assessed before and 3months after vitamin D replacement. The median FMD was 5% in group A, 5.1% in group B, 7.6% in group C and 7.7% in group D. The FMD measurement in group A was significantly lower than groups C and D (P=.02) and was similar to the FMD measurement in group B. FMD measurements of group B were not significantly lower than groups C and D. In 13 patients with low 25OHD in group A, the median FMD increased to 7.07% from 4.71% after vitamin D replacement (P=.02). Flow-mediated dilation was impaired in patients with PHPT, particularly in the medically observed group. Vitamin D supplementation seems to provide improvements in FMD in medically observed PHPT patients with low 25OHD levels, and this was the novel observation of our study.

Season and vitamin D status are independently associated with glucose homeostasis in pregnancy

BackgroundVitamin D status and season are intrinsically linked, and both have been proposed to be associated with glucose homeostasis in pregnancy, with conflicting results. We aimed to determine if exposure to winter and low maternal 25 hydroxyvitamin D (25OHD) in early pregnancy were associated with maternal glucose metabolism.MethodsThis is a secondary data analysis of 334 pregnant women enrolled in the ROLO study, Dublin. Serum 25OHD, fasting glucose, insulin and insulin resistance (HOMA-IR) were measured in early (12 weeks’ gestation) and late pregnancy (28 weeks’ gestation). Season of first antenatal visit was categorised as extended winter (November–April) or extended summer (May–October). Multiple linear regression models, adjusted for confounders, were used for analysis.ResultsThose who attended their first antenatal visit in extended winter had lower 25OHD compared to extended summer (32.9 nmol/L vs. 44.1 nmol/L, P < 0.001). Compared to those who attended their first antenatal visit during extended summer, extended winter was associated with increased HOMA-IR in early-pregnancy (46.7%) and late pregnancy (53.7%), independent of 25OHD <30 nmol/L and confounders. Early pregnancy 25OHD <30 nmol/L and extended winter were independently associated with significantly higher fasting glucose in late pregnancy (B = 0.15 and 0.13, respectively).ConclusionsWomen who attended their first antenatal visit during the months of extended winter were more likely to have raised insulin resistance in early pregnancy, which had a lasting association to 28 weeks, and was independent of 25OHD. Our novel findings imply that seasonal variation in insulin resistance may not be fully explained by differences in vitamin D status. This could reflect circannual rhythm or seasonal lifestyle behaviours, and requires further exploration.Trial registrationISRCTN registry, ISRCTN54392969, date of registration: 22/04/2009, retrospectively registered.

Correlation between serum vitamin D status and immunological changes in children affected by gastrointestinal food allergy

BackgroundLow vitamin D status is linked to increased incidence of food allergy and intestinal inflammation. Whether vitamin D status is associated with immunological changes in children with gastrointestinal food allergy (GFA) remains unclear. MethodsForty-nine GFA children (aged 2–11 years old) were enrolled in this study. Serum 25-hydroxyvitamin D (25OHD) level, total immunoglobulin E (IgE), specific IgE against allergens, circulating regulatory T lymphocytes (Tregs), and blood eosinophil numbers were measured. ResultsLevels of serum 25OHD in the GFA children ranged 35.5–156.4nmol/L, with a mean value similar to that of the healthy controls. Compared to those with normal 25OHD (≥75nmol/L), GFA children with low 25OHD (<75nmol/L) had increased total IgE (84% vs. 54%, P<0.05), persistent blood eosinophilia (56% vs. 25%, P<0.05), and delayed resolution of symptoms after food allergen elimination (odds ratio 3.51, 95% CI 1.00–12.36, P<0.05). Among the GFA children with elevated total IgE, those with low 25OHD had lower circulatory Tregs (8.79±2.4% vs. 10.21±1.37%, P<0.05), higher total IgE (1197.5±1209.8 vs. 418.5±304.6kU/L, P<0.05), and persistent eosinophilia (0.61±0.52 vs. 0.31±0.15×109cells/L, P<0.05) compared to those with normal 25OHD. In addition, serum 25OHD concentrations inversely correlated with total IgE (R=−0.434, P<0.05), and positively with Treg population (R=0.356, P<0.05). ConclusionLow serum vitamin D status correlates with stronger allergic immune response in GFA children.

Vitamin D levels in childhood and adolescence and cardiovascular risk factors in a cohort of healthy Australian children

As the prevalence of obesity appears to be increasing in Australia’s youth the overall objective of this study was to examine serum 25-hydroxyvitamin D (25OHD) concentrations in a cohort of 8-year-olds (n=249) followed up at age 15 (n=162) and explore associations between 25OHD with cardiovascular disease (CVD) risk factors in these populations. This was done in two stages: the first, two cross-sectional analyses (at ages 8 and 15); and the second, a prospective analysis from age 8 to 15. At both ages data on 25OHD, blood lipids, and anthropometry were measured. Date of blood draw was used as a surrogate of sunlight exposure. Results were then analysed by multivariate linear analyses taking into account interaction and confounding. Mean 25OHD concentrations decreased from 94±25nmol/L to 63±16nmol/L between age 8 and 15 years (p<0.001). On cross-sectional analysis of 8year olds, no CVD risk factor was found to be significantly associated with 25OHD concentrations. On cross-sectional analysis of 15year olds lower 25OHD levels were significantly associated with higher body fat (adjusted β=−0.24, p=0.003). Prospectively, lower 25OHD levels in 8-year-old boys, but not girls, were significantly associated with higher blood total cholesterol (adjusted β=−0.28, p=0.040) and triglyceride levels (adjusted β=−0.33, p=0.030) at age 15. The limitation of these data is the relatively small sample sizes, however these results suggest that low 25OHD in childhood needs to be further investigated in larger cohort studies as there may be later cardiovascular consequences in adolescence.

Non-skeletal health effects of vitamin D supplementation: A systematic review on findings from meta-analyses summarizing trial data.

BackgroundA large number of observational studies have reported harmful effects of low 25-hydroxyvitamin D (25OHD) levels on non-skeletal outcomes. We performed a systematic quantitative review on characteristics of randomized clinical trials (RCTs) included in meta-analyses (MAs) on non-skeletal effects of vitamin D supplementation.Methods and findingsWe identified systematic reviews (SR) reporting summary data in terms of MAs of RCTs on selected non-skeletal outcomes. For each outcome, we summarized the results from available SRs and scrutinized included RCTs for a number of predefined characteristics. We identified 54 SRs including data from 210 RCTs. Most MAs as well as the individual RCTs reported null-findings on risk of cardiovascular diseases, type 2 diabetes, weight-loss, and malignant diseases. Beneficial effects of vitamin D supplementation was reported in 1 of 4 MAs on depression, 2 of 9 MAs on blood pressure, 3 of 7 MAs on respiratory tract infections, and 8 of 12 MAs on mortality. Most RCTs have primarily been performed to determine skeletal outcomes, whereas non-skeletal effects have been assessed as secondary outcomes. Only one-third of the RCTs had low level of 25OHD as a criterion for inclusion and a mean baseline 25OHD level below 50 nmol/L was only present in less than half of the analyses.ConclusionsPublished RCTs have mostly been performed in populations without low 25OHD levels. The fact that most MAs on results from RCTs did not show a beneficial effect does not disprove the hypothesis suggested by observational findings on adverse health outcomes of low 25OHD levels.

Suboptimal vitamin D status in Korean adolescents: a nationwide study on its prevalence, risk factors including cotinine-verified smoking status and association with atopic dermatitis and asthma

ObjectiveTo determine the prevalence and risk factors for suboptimal vitamin D status in Korean adolescents and to assess its relationship with atopic dermatitis (AD) and asthma at a national level.DesignThis...

Abstract 3268: Obesity, circulating 25-hydroxyvitamin D, and C-reactive protein levels in cancer survivors

Abstract Aim: Circulating 25-hydroxyvitamin D (25-OHD) levels may be associated with cancer prognosis. It is, however, unclear if low 25-OHD levels in cancer survivors is a surrogate for obesity, which also influences cancer prognosis. To address this, we evaluated the associations of body mass index (BMI) with circulating 25-OHD levels among cancer survivors using data from the National Health and Nutrition Examination Survey (NHANES). Further, we determined if this association is modified by inflammation, as determined by circulating C-reactive protein (CRP) levels, since obesity is a pro-inflammatory state and vitamin D deficiency is associated with higher inflammatory markers. Method: Data on cancer survivors in five waves of NHANES (2001-2010) were aggregated. Multiple linear regression models were used to evaluate the associations of BMI with circulating 25-OHD levels, adjusting for confounders (age, gender, race, smoking status, and season of blood draw). We stratified our analyses by CRP levels into low &amp;lt;1mg/L, moderate 1.1-3.0mg/L and high &amp;gt;3.1-9.9mg/L. Results: There were 1,306 cancer survivors (mean age=60.8 years, mean BMI=28.0 kg/m2) with detailed data for analyses. The prevalent cancer types were breast (19.6%), prostate (19.6%), cervix (10.0%), and colon (8.9%). Circulating 25-OHD levels were 7.43 nmol/L lower (95%CI: 3.06 to 11.81) among obese cancer survivors (BMI ≥30kg/m2) compared to those with BMI &amp;lt;25kg/m2. In analyses stratified by CRP levels, we observed no such association among cancer survivors with low CRP levels. However, among those with moderate and high CRP levels, obese cancer survivors had statistically significantly lower 25-OHD levels compared to those with BMI &amp;lt;25kg/m2; (-8.87, 95%CI: -16.28 to -1.24) among those with moderate CRP levels and -9.85, (95% CI: -17.00 to -2.71) among those with high CRP levels. Conclusion: Obesity is associated with lower circulating 25-OHD levels in cancer survivors. This appears, however, to be limited to those with evidence of systemic inflammation. Table 1.Multivariable-adjusted associations between BMI and ciruclating 25-OHD levels among cancer survivors in the NHANES 2001-2010 (n=1306); stratified by CRP levels.Circulating 25-OHD (nmol/L)BMI category (kg/m2)Beta-coefficient (95% CI)p*Overall, n=1306&amp;lt;25reference25.0 – 29.9-2.91 (-7.49 to 1.37)0.18≥ 30-7.43 (-11.81 to -3.06)&amp;lt;.001Low CRP levels (&amp;lt;1.0 mg/L), n=348&amp;lt;25reference25.0 – 29.9-0.64 (-9.09 to 7.91)0.88≥ 30-4.00 (-11.59 to 3.59)0.3Moderate CRP levels (1.1-3.0 mg/L), n=498&amp;lt;25reference25.0 – 29.9-2.44 (-9.27 to 4.38)0.48≥ 30-8.76 (-16.28 to -1.24)0.02High CRP levels (3.1-9.9 mg/L), n=460&amp;lt;25reference25.0 – 29.9-7.63 (-13.94 to -1.33)0.02≥ 30-9.85 (-17.00 to -2.71)0.008*Adjusted for age, gender, race, body mass index, and smoking status. Citation Format: Lin Yang, Adetunji T. Toriola. Obesity, circulating 25-hydroxyvitamin D, and C-reactive protein levels in cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3268. doi:10.1158/1538-7445.AM2017-3268

Associations Between Vitamin D Levels and Depressive Symptoms in Later Life: Evidence From the English Longitudinal Study of Ageing (ELSA).

BackgroundA possible role of vitamin D in depression has received considerable attention, especially given the significant disability, mortality, and healthcare costs associated to depression and the high prevalence of vitamin D deficiency.MethodsWe investigated the cross-sectional associations between serum 25-hydroxyvitamin D (25OHD) levels and depressive symptoms (CES-D) in 5,607 older adults from the English Longitudinal Study of Ageing (ELSA).ResultsOverall, there was a significant association between low 25OHD levels and elevated depressive symptoms (odds ratio [OR] = 1.58, 95% confidence interval [CI] = 1.20–2.07 for the lowest quartile; OR = 1.45, 95% CI = 1.15–1.83 for <30 nmol/L cut-off and OR = 1.34, 95% CI = 1.10–1.62 for the ≤50 nmol/L cut-off) after adjustment for a wide range of covariates of clinical significance. Fully adjusted models showed that women in the lowest (OR = 1.67, 95% CI = 1.20–2.34) and second lowest (OR = 1.68, 95% CI = 1.20–2.35) quartiles of 25OHD as well as those with 25OHD levels <30 nmol/L (OR = 1.40, 95% CI = 1.06–1.86) and ≤50 nmol/L (OR = 1.35, 95% CI = 1.07–1.72) were more likely to report elevated depressive symptoms. For men, however, this association only remained significant for those with 25OHD levels of <30 nmol/L (OR = 1.60, 95% CI = 1.06–2.42) in the fully adjusted models.ConclusionsThe independent and inverse association found between low 25OHD levels and elevated depressive symptoms suggests that vitamin D deficiency may be a risk factor for late-life depression, particularly among women. Whether our findings have any clinical meaning or not, additional data are needed from well-designed randomized controlled trials of vitamin D for the prevention and treatment of late-life depression.

Vitamin D status is inversely associated with markers of risk for type 2 diabetes: A population based study in Victoria, Australia.

A growing body of evidence suggests a protective role of vitamin D on the risk of type 2 diabetes mellitus (T2DM). We investigated this relationship in a population sample from one Australian state. The data of 3,393 Australian adults aged 18–75 years who participated in the 2009–2010 Victorian Health Monitor survey was analyzed. Socio-demographic information, biomedical variables, and dietary intakes were collected and fasting blood samples were analyzed for 25, hydroxycholecalciferol (25OHD), HbA1c, fasting plasma glucose (FPG), and lipid profiles. Logistic regression analyses were used to evaluate the association between tertiles of serum 25OHD and categories of FPG (<5.6 mmol/L vs. 5.6–6.9 mmol/L), and HbA1c (<5.7% vs. 5.7–6.4%). After adjusting for social, dietary, biomedical and metabolic syndrome (MetS) components (waist circumference, HDL cholesterol, triglycerides, and blood pressure), every 10 nmol/L increment in serum 25OHD significantly reduced the adjusted odds ratio (AOR) of a higher FPG [AOR 0.91, (0.86, 0.97); p = 0.002] and a higher HbA1c [AOR 0.94, (0.90, 0.98); p = 0.009]. Analysis by tertiles of 25OHD indicated that after adjustment for socio-demographic and dietary variables, those with high 25OHD (65–204 nmol/L) had reduced odds of a higher FPG [AOR 0.60, (0.43, 0.83); p = 0.008] as well as higher HbA1c [AOR 0.67, (0.53, 0.85); p = 0.005] compared to the lowest 25OHD (10–44 nmol/L) tertile. On final adjustment for other components of MetS, those in the highest tertile of 25OHD had significantly reduced odds of higher FPG [AOR 0.61, (0.44, 0.84); p = 0.011] and of higher HbA1c [AOR 0.74, (0.58, 0.93); p = 0.041] vs. low 25OHD tertile. Overall, the data support a direct, protective effect of higher 25OHD on FPG and HbA1c; two criteria for assessment of risk of T2DM.

Association of baseline plasma levels of 25OH vitamin D and breast cancer risk in a chemoprevention trial.

1546 Background: Observational studies have shown a correlation of higher serum 25-hydroxyvitamin D (25OHD) concentrations and reduced cancer risk, including breast cancer (BC). We assessed the association of 25OHD and Vitamin D Receptor (VDR) polymorphisms (SNPs) with breast cancer events within a chemoprevention trial in premenopausal women at risk for BC. Methods: Premenopausal women with history of intraepithelial neoplasia (IEN) or at risk women according to the Gail model were included in a 4 arm phase II prevention trial (low dose tamoxifen vs fenrerinide vs their combination vs placebo). Level of 25OHD were measured at baseline. VDR SNPs ( FokI, BsmI, TaqI, ApaI, and Cdx2) were determined using the Applied Biosystems’ Taqman Allelic Discrimination Assay according to manufacturer’s instructions. Survival analysis for breast cancer events was performed using competing risk models, adjusted for BMI, age, season and risk strata. Results: Plasma samples were available for 228 subjects. At baseline the median plasma 25OHD concentrations were slightly higher in 53 unaffected women, 19.6 ng/ml (IQR 12.7-27.3 ng/mL) than in 175 women with IEN, 18.8 ng/ml (11.7-25.8). After a median follow up of 15 years, 79 women developed a breast cancer event, 12 had different neoplastic events. The median level of 25OHD was 19.7 ng/ml (IQR 12.8-26.1) in subjects free from oncological events and 17.8 ng/ml (9.7-23.9) in subjects with breast events. Women in the lowest 25OHD quartile (≤12 ng/ml) had an increased risk of breast cancer events: HR = 1.79 (95%CI, 1.07-2.99, p = 0.03). Considering all cancer events, the associations with 25OHD were confirmed (P = 0.005). Among the VDR SNPs the ApaI variant in homozygote or heterozygote versus wild type showed an HR of 1.83 (95%CI, 1.04-3.21 p = 0.03). Conclusions: Our results support a role of plasma vitamin D levels in breast cancer risk. Subjects in the lowest quartile had a two-fold increased risk of a cancer event. Our findings support trials of 25OHD supplementation to prevent breast cancer in 25OHD insufficient subjects.

Longitudinal Assessment of PTH in Community-Dwelling Older Women-Elevations Are Not Associated With Mortality.

Context:In older women, the magnitude of elevated parathyroid hormone (PTH) and its consequence is unclear.Objective:To describe normal PTH profiles over time and the association with mortality.Design and Participants:There were 1044 community-dwelling women in the Malmö Osteoporosis Prospective Risk Assessment cohort (OPRA) who attended baseline (age 75 years). Follow-ups were attended by 715 (age 80 years) and 382 (age 85 years).Main Outcome Measures:PTH, estimated glomerular filtration rate (eGFR), 25-hydroxyvitamin D (25OHD) and mortality.Results:At age 75 years, PTH levels for most (n = 877, 88%) were within the normal reference range (NRR) (i.e., <6.9 pmol/L). Longitudinally, between ages 75 and 80 years, PTH increased in 60% of all women (n = 390) but increases of up to 50% above baseline values (64%; n=250) still resulted in PTH levels within the NRR. These women had lower 25OHD levels (74 vs 83 nmol/L, P = 0.001). Only when increases were >50% was PTH elevated beyond the NRR (mean 7.1 ± 3.3). Here, a pronounced decline in eGFR (56 vs 61 mL/min/1.73 m2, P = 0.002) was found, despite no further changes in 25OHD. Extending the observational period until age 85 years gave similar results. Baseline PTH levels above NRR were associated with mortality (hazard ratio, 1.4; 95% confidence interval (CI), 1.1-1.8; P = 0.007), although not after adjustment for covariates (P = 0.082).Conclusions:Most women remained within normal PTH ranges despite large increases of up to 50%. PTH elevated above normal is not independently associated with mortality; impaired kidney function and low 25OHD status may be more prognostic in the very old.

Vitamin D status of White pregnant women and infants at birth and 4months in North West England: A cohort study.

The prevalence of vitamin D deficiency in pregnant white-skinned women (WSW) and their infants has not been investigated at northern latitudes in a developed county. A 2-year observational cohort study was undertaken in the North West of England to determine 25-hydroxyvitamin D (25OHD) levels in WSW and their infants during pregnancy and 4months postdelivery and to explore factors associated with these levels. Nutritional and lifestyle questionnaires were completed and 25OHD levels measured at 28weeks and 4months postdelivery. Twenty-seven percent and 7% of WSW had insufficient and deficient levels of 25OHD during pregnancy and 48% and 11% four months postdelivery. WSW with Fitzpatrick skin-type I (FST I) have significantly lower 25OHD than other skin types after controlling for time spent outside and vitamin D intake. Twenty-four percent and 13% of infants had insufficient and deficient 25OHD levels at 4months. Unsupplemented breast-fed infants have the highest level of insufficiency (67%) compared with formula-fed infants (2%). Factors associated with infant serum 25OHD levels at 4months included breast feeding, supplementation, and time outside. WSW have a high prevalence of insufficiency and deficiency during pregnancy which doubles 4months after birth. Breast-fed infants of WSW are rarely considered at risk of vitamin D insufficiency but have high rates compared with formula-fed infants. This is the first study to show the finding that FST I WSW have significantly lower levels of 25OHD than those with FST II-IV (difference adjusted for diet and time outside 14 (95%CI 7-21) nmol/L).

Association of vitamin D deficiency, season of the year, and latent tuberculosis infection among household contacts.

ObjectivesVitamin D (VD) enhances the immune response against Mycobacterium tuberculosis in vitro, and VD deficiency has been described in patients with active tuberculosis (TB). However, the role of hypovitaminosis D in the pathogenesis of early TB infection acquisition is unclear. We aimed to evaluate the association of VD deficiency, season of the year, and latent TB infection in household contacts (HHC), given that this is a potentially modifiable condition often related to nutritional deficiencies and lack of sun exposure.MethodsWe prospectively enrolled new pulmonary TB cases (n = 107) and their HHC (n = 144) over a 2-year period in Santiago, Chile. We compared plasma 25-hydroxycholecalciferol (25OHD) levels and examined the influence of season, ethnic background, living conditions, and country of origin.ResultsOver 77% of TB cases and 62.6% of HHC had VD deficiency (<20 ng/ml). Median 25OHD concentration was significantly lower in TB cases than in HHC (11.7 vs. 18.2 ng/ml, p<0.0001). Migrants HHC had lower 25OHD levels than non-migrants (14.6 vs. 19.0 ng/ml, p = 0.026), and a trend towards a higher burden of latent TB infection (52.9% vs. 35.2%, p = 0.066). Multivariate analysis found VD deficiency in HHC was strongly associated with being sampled in winter/spring (adOR 25.68, 95%CI 7.35–89.7), corresponding to the seasons with lowest solar radiation exposure. Spring enrollment–compared with other seasons–was the chief risk factor for latent TB infection in HHC (adOR 3.14, 95%CI 1.28–7.69).ConclusionsHypovitaminosis D was highly prevalent in TB cases and also in HHC. A marked seasonality was found for both VD levels and latent TB in HHC, with winter being the season with lowest VD levels and spring the season with the highest risk of latent TB infection.

Pregnancy and cord vitamin D status and symptoms of autism spectrum disorders in toddlers: An Odense child cohort study

IntroductionVitamin D deficiency is widespread globally in pregnant women and is suggested to contribute to offspring risk of symptoms of autism spectrum disorders (ASD), but findings are inconsistent.ObjectivesTo investigate whether low prenatal 25OHD exposure and 25OHD status in early life increase risk of early symptoms of ASD.AimsTo investigate early signs of ASD.MethodsFrom the prospective birth cohort, Odense child cohort (n = 2.549), Denmark, we included singletons with their mothers with available serum concentrations of 25OHD at early pregnancy (n = 1.231), late pregnancy (n = 1.361), and birth (n = 2.082). ASD symptoms were rated by parents on the pervasive developmental problem (PDP) scale of the Child behavior checklist for ages 1½-5 (CBCL 1½-5). Associations between 25OHD and PDP score were analyzed by multiple linear and logistic regression models. A priori included covariates were gestational age, child gender, birth weight, season of birth, parity, parental psychiatric diagnoses, maternal age, smoking habits, alcohol consumption, education level, vitamin D supplementation, and pre-gestational BMI.ResultsMeans (SD) of 25OHD for early pregnancy, late pregnancy, and cord were 65.5 (21.5), 78.7 (27.0), and 47.0 (21.7) nmol/L, respectively. PDP data were obtained at a mean (SD) of 2.7 (0.6) years of age. Data from the regression analyses are pending.ConclusionsIn this well-off cohort with relatively high levels of cord 25OHD, power calculations allows us to detect a true change of 0.02 PDP scores per 10 nmol/L change in 25OHD. Further studies will clarify whether early PDP scores track later ASD diagnosis.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Hypovitaminosis D in patients with heart failure: effects on functional capacity and patients' survival.

Chronic heart failure is a major cause of morbidity and mortality, but its prognosis remains poor. Vitamin D hormone has many extra-skeletal functions including a positive impact on the cardiovascular system, and has been proposed for mortality risk evaluation in heart failure patients. The aim of the present study was to evaluate vitamin D status in heart failure patients, measured by high performance liquid chromatography coupled with mass spectrometry and to correlate serum 25 hydroxy-vitamin D (25OHD) levels with functional (peak VO2%) and mortality (Metabolic Exercise Cardiac Kidney Index) heart failure parameters. We enrolled 261 consecutive patients diagnosed with heart failure; all patients underwent a comprehensive clinical and biochemical characterization, and serum 25OHD levels were measured by high performance liquid chromatography coupled with mass spectrometry. Cardiopulmonary test parameters and Metabolic Exercise Cardiac Kidney Index of mortality risk were measured in all patients. Serum 25OHD levels ranged between 2 and 45 ng/ml (mean 17 ± 9 ng/ml); most patients (87%) showed hypovitaminosis D, and 25% showed severe vitamin D deficiency (serum 25OHD < 10 ng/ml). Patients with 25OHD < 10 ng/ml had significantly lower cardiopulmonary test VO2/kg, peak VO2% and significantly higher N-terminalproBrain natriuretic peptide and Metabolic Exercise Cardiac Kidney Index, than patients with 25OHD > 10 ng/ml. Patients with peak VO2% < 50% showed significantly lower 25OHD compared to those with peak VO2% > 50%. There was a significant, positive correlation (r = 0.16, p = 0.008) between 25OHD levels and peak VO2%, and an inverse correlation with Metabolic Exercise Cardiac Kidney Index (r = -0.21, p < 0.001), even when adjusted for age, Body Mass Index, MDRD, N-terminalproBrain natriuretic peptide. In conclusion, our findings show that vitamin D levels are associated with functional and mortality heart failure prognosis parameters.

Nephrolithiasis in Primary Hyperparathyroidism: A Comparison Between Silent and Symptomatic Patients

To characterize primary hyperparathyroidism (PHPT) patients with renal stones and to compare silent with symptomatic stone formers. We reviewed clinical data from 234 patients with PHPT, comparing those with and without renal stones (n = 109 and 125, respectively), and among stone formers those symptomatic versus silent (n = 93 and 16, respectively). Stone formers were younger, had higher urinary calcium levels and higher estimated glomerular filtration rates (eGFRs) compared to patients without stones. Patients with silent stones had higher parathyroid hormone (PTH) and lower 25OH-vitamin D (25OHD) levels and more frequently experienced microlithiasis than patients with symptomatic renal stones. Nephrolithiasis is a common complication of PHPT. Most patients with silent renal stones have microlithiasis, associated to some features of more severe disease. Lower 25OHD levels in silent stone formers raise the hypothesis that vitamin D status can influence the clinical expression of nephrolithiasis in PHPT patients. BMI = body mass index Ca = serum total calcium DM = diabetes mellitus eGFR = estimated glomerular filtration rate HOMA-IR = Homeostasis Model Assessment-Insulin Resistance 25OHD = 25OH-vitamin D PHPT = primary hyperparathyroidism PTH = parathyroid hormone UCa = 24-h urine for calcium US = ultrasound.