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Micronutritional deficiencies are common in atopic children suffering from atopic dermatitis, food allergy, rhinitis, and asthma. A lack of iron, in particular, may impact immune activation with prolonged deficiencies of iron, zinc, vitamin A, and vitamin D associated with a Th2 signature, maturation of macrophages and dendritic cells (DCs), and the generation of IgE antibodies. In contrast, the sufficiency of these micronutrients establishes immune resilience, promotion of regulatory cells, and tolerance induction. As micronutritional deficiencies mimic an infection, the body’s innate response is to limit access to these nutrients and also impede their dietary uptake. Here, we summarize our current understanding of the physiological function of iron, zinc, and vitamins A and D in relation to immune cells and the clinical consequences of deficiencies in these important nutrients, especially in the perinatal period. Improved dietary uptake of iron is achieved by vitamin C, vitamin A, and whey compounds, whereas zinc bioavailability improves through citrates and proteins. The addition of oil is essential for the dietary uptake of beta-carotene and vitamin D. As for vitamin D, the major source comes via sun exposure and only a small amount is consumed via diet, which should be factored into clinical nutritional studies. We summarize the prevalence of micronutritional deficiencies of iron, zinc, and vitamins in the pediatric population as well as nutritional intervention studies on atopic diseases with whole food, food components, and micronutrients. Dietary uptake via the lymphatic route seems promising and is associated with a lower atopy risk and symptom amelioration. This review provides useful information for clinical studies and concludes/emphasizes that a healthy, varied diet containing dairy products, fish, nuts, fruits, and vegetables as well as supplementing foods or supplementation with micronutrients as needed is essential to combat the atopic march.

The 4th International Conference on Controversies in Vitamin D was held as a virtual meeting in September, 2020, gathering together leading international scientific and medical experts in vitamin D. Since vitamin D has a crucial role in skeletal and extra-skeletal systems, the aim of the Conference was to discuss improved management of vitamin D dosing, therapeutic levels and form or route of administration in the general population and in different clinical conditions. A tailored approach, based on the specific mechanisms underlying vitamin D deficiency in different diseases that were discussed, was recommended. Specifically, in comparison to healthy populations, higher levels of vitamin D and greater amounts of vitamin D were deemed necessary in osteoporosis, diabetes mellitus, obesity (particularly after bariatric surgery), and in those treated with glucocorticoids. Emerging and still open issues were related to target vitamin D levels and the role of vitamin D supplementation in COVID-19 since low vitamin D may predispose to SARS-CoV-2 infection and to worse COVID-19 outcomes. Finally, whereas oral daily cholecalciferol appears to be the preferred choice for vitamin D supplementation in the general population, and in most clinical conditions, active vitamin D analogs may be indicated in patients with hypoparathyroidism and severe kidney and liver insufficiency. Parenteral vitamin D administration could be helpful in malabsorption syndromes or in states of vitamin D resistance.Specific guidelines for desired levels of vitamin D should be tailored to the different conditions affecting vitamin D metabolism with the goal to define disease-specific normative values. ispartof: REVIEWS IN ENDOCRINE & METABOLIC DISORDERS vol:22 issue:4 pages:1201-1218 ispartof: location:Germany status: published

Objective To explore the association of both plasma vitamin D and K concentrations with all-cause mortality, cardiovascular mortality, and cardiovascular events in the general population. Methods We studied 4742 participants of the Prevention of REnal and Vascular ENd-Stage Disease (PREVEND) Study. At baseline, vitamin D and K status was determined by measurement of 25-hydroxyvitamin D [25(OH)D] and dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP), respectively. Patients were categorized into: 25(OH)D 75 nmol/L and dp-ucMGP Results Mean age was 52.6 ± 11.9 years and 2513 (53%) were female. During a median of 14.2 year follow-up, 620 participants died of which 142 were due to cardiovascular causes. Combined low vitamin D and K status was present in 970 participants (20%) and was associated with a greater risk of all-cause mortality compared to high vitamin D and high vitamin K status group (n = 1424) after adjusting for potential confounders: hazard ratio 1.46 (95% confidence intervals 1.12–1.90). We observed similar trends, albeit non-significant for cardiovascular mortality, and cardiovascular events: 1.42 (0.79–2.55), 1.28 (0.93–1.77), respectively. Conclusions Combined low vitamin D and K status are associated with increased all-cause mortality risk and possibly with cardiovascular mortality and cardiovascular events compared with adequate vitamin D and K status. Future studies should investigate the effect of combined vitamin D and K supplementation on clinical outcomes.

Context and purpose There is an urgent need to develop vitamin D dietary recommendations for dark-skinned populations resident at high latitude. Using data from randomised controlled trials (RCTs) with vitamin D3-supplements/fortified foods, we undertook an individual participant data-level meta-regression (IPD) analysis of the response of wintertime serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among dark-skinned children and adults residing at ≥ 40° N and derived dietary requirement values for vitamin D. Methods IPD analysis using data from 677 dark-skinned participants (of Black or South Asian descent; ages 5-86 years) in 10 RCTs with vitamin D supplements/fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D intake estimates across a range of 25(OH)D thresholds. Results To maintain serum 25(OH)D concentrations ≥ 25 and 30 nmol/L in 97.5% of individuals, 23.9 and 27.3 µg/day of vitamin D, respectively, were required among South Asian and 24.1 and 33.2 µg/day, respectively, among Black participants. Overall, our age-stratified intake estimates did not exceed age-specific Tolerable Upper Intake Levels for vitamin D. The vitamin D intake required by dark-skinned individuals to maintain 97.5% of winter 25(OH)D concentrations ≥ 50 nmol/L was 66.8 µg/day. This intake predicted that the upper 2.5% of individuals could potentially achieve serum 25(OH)D concentrations ≥ 158 nmol/L, which has been linked to potential adverse effects in older adults in supplementation studies. Conclusions Our IPD-derived vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25, 30 and 50 nmol/L are substantially higher than the equivalent estimates for White individuals. These requirement estimates are also higher than those currently recommended internationally by several agencies, which are based predominantly on data from Whites and derived from standard meta-regression based on aggregate data. Much more work is needed in dark-skinned populations both in the dose-response relationship and risk characterisation for health outcomes. Trail registration PROSPERO International Prospective Register of Systematic Reviews (Registration Number: CRD42018097260).

The interest in Vitamin D (Vit D) is increased after the finding of Vit D receptors in many different cells. This led to the hypothesis that Vit D may have more impact on human health than its role in bone health. Epidemiological studies found associations between low plasma levels of Vit D and the prevalence of many diseases. However, Large RCTs did not find convincing evidence for a positive effect of Vit D supplementation on cancer, cardiovascular disease, auto-immune disease and inflammatory diseases. In this review, the results are described of a literature search regarding the relationship between Vit D status and different diseases. Pubmed was used to find systematic reviews of observational studies describing the association between Vit D status, diseases (cancer, coronary heart diseases, auto-immune diseases, sepsis) and mortality. Subsequently, a search was performed for RCTs and the results of large RCTs are described. Studies with a positive intervention effect on primary or secondary outcome variables are summarized. No exclusion criteria were used. The metabolism of Vit D is reviewed, its endogenous production and the intake from food, its activation and transport in the body. The article addresses the effects of diseases on the metabolism of Vit D with special focus on the role of Vit D Binding Protein and its effects on assessing Vit D status. Studies addressing the association between vitamin D status and cancer, cardiovascular diseases, auto-immune diseases, inflammation and severe illness are reviewed. A search for RCTs with positive effects of Vit D supplementation on different diseases yielded only a few studies. The vast majority of RCTs showed no significant positive effects. The presumed high prevalence of Vit D deficiency is questioned based on these results and on altered concentrations of Vit D binding protein, leading to low Vit D levels in plasma but not to low active Vit D levels during disease related inflammation In these conditions, plasma levels of Vit D are therefore not a valid reflection of Vit D status. Reversed causality is described as a possible factor interfering with the correct assessment of the Vit D status. It is concluded that further widespread fortification of foods and stimulation of supplement use should be reconsidered. (c) 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Background: Vitamin D status may be an important determinant of health-related quality of life of colorectal cancer survivors. The current study investigated longitudinal associations between serum 25-hydroxyvitamin D3 (25OHD3) concentrations and quality of life in stage I–III colorectal cancer survivors up to 2 years after treatment. Methods: Patients with colorectal cancer (n = 261) were included upon diagnosis. Home visits (including blood sampling) were performed at diagnosis and at 6 weeks, 6 months, 1 year, and 2 years after treatment. Serum 25OHD3 concentrations were measured using LC/MS-MS and adjusted for season. Validated questionnaires were used to assess global quality of life and cognitive functioning (EORTC-QLQ-C30), fatigue (EORTC-QLQ-C30 and Checklist Individual Strength, CIS), and depression and anxiety (Hospital Anxiety and Depression Scale). Statistical analyses were performed using linear mixed models and adjusted for sex, age, time since diagnosis, therapy, comorbidities, physical activity, and body mass index. Results: At diagnosis, 45% of patients were vitamin D deficient ( Conclusions: Higher concentrations of 25OHD3 were longitudinally associated with better global quality of life and less fatigue in colorectal cancer survivors. Impact: This study suggests that higher 25OHD3 concentrations may be beneficial for colorectal cancer survivors. Future intervention studies are needed to corroborate these findings.

ObjectivesThe steroid hormone vitamin D has roles in immunomodulation and bone health. Insufficiency is associated with susceptibility to respiratory infections. We report 25-hydroxy vitamin D (25(OH)D) measurements in hospitalised people with COVID-19 and influenza A and in survivors of critical illness to test the hypotheses that vitamin D insufficiency scales with illness severity and persists in survivors.DesignCross-sectional study.Setting and participantsPlasma was obtained from 295 hospitalised people with COVID-19 (International Severe Acute Respiratory and emerging Infections Consortium (ISARIC)/WHO Clinical Characterization Protocol for Severe Emerging Infections UK study), 93 with influenza A (Mechanisms of Severe Acute Influenza Consortium (MOSAIC) study, during the 2009–2010 H1N1 pandemic) and 139 survivors of non-selected critical illness (prior to the COVID-19 pandemic). Total 25(OH)D was measured by liquid chromatography-tandem mass spectrometry. Free 25(OH)D was measured by ELISA in COVID-19 samples.Outcome measuresReceipt of invasive mechanical ventilation (IMV) and in-hospital mortality.ResultsVitamin D insufficiency (total 25(OH)D 25–50 nmol/L) and deficiency (ConclusionsVitamin D deficiency/insufficiency was present in majority of hospitalised patients with COVID-19 or influenza A and correlated with severity and persisted in critical illness survivors at concentrations expected to disrupt bone metabolism. These findings support early supplementation trials to determine if insufficiency is causal in progression to severe disease, and investigation of longer-term bone health outcomes.

Background: Vitamin D deficiency is frequently seen in patients with polycystic ovary syndrome (PCOS) and has been shown to exhibit multiple effects on the disease process. The purpose of this study was to investigate the role of vitamin D deficiency in complex PCOS pathophysiological pathways. Methods: Two hundred sixty-seven patients with PCOS were divided into two groups Group 1 with 25(OH)D3 deficiency, and Group 2 with normal 25(OH)D3. Biochemical and hormonal parameters (androgen hormones, gonadotropins, and thyroid function tests) were compared between the two groups. Results: Eighty-six percent of the patients (n=231) were in Group 1 and 14% (n=36) in Group 2. Statistically signifi- cantly higher concentrations of serum testosterone, dehydroepiandrosterone-sulfate and LH were determined in Group 1 (p

Preclinical data strongly suggest that the vitamin D endocrine system (VDES) may have extraskeletal effects. Cells of the immune and cardiovascular systems and lungs can express the vitamin D receptor, and overall these cells respond in a coherent fashion when exposed to 1,25-dihydroxyvitamin D, the main metabolite of the VDES. Supplementation of vitamin D-deficient subjects may decrease the risk of upper respiratory infections. The VDES also has broad anti-inflammatory and anti-thrombotic effects, and other mechanisms argue for a potential beneficial effect of a good vitamin D status on acute respiratory distress syndrome, a major complication of this SARS-2/COVID-19 infection. Activation of the VDES may thus have beneficial effects on the severity of COVID-19. Meta-analysis of observational data show that a better vitamin D status decreased the requirement of intensive care treatment or decreased mortality. A pilot study in Cordoba indicated that admission to intensive care was drastically reduced by administration of a high dose of calcifediol early after hospital admission for COVID-19. A large observational study in Barcelona confirmed that such therapy significantly decreased the odds ratio (OR) of mortality (OR = 0.52). This was also the conclusion of a retrospective study in five hospitals of Southern Spain. A retrospective study on all Andalusian patients hospitalized because of COVID-19, based on real-world data from the health care system, concluded that prescription of calcifediol (hazard ratio [HR] = 0.67) or vitamin D (HR = 0.75), 15 days before hospital admission decreased mortality within the first month. In conclusion, a good vitamin D status may have beneficial effects on the course of COVID-19. This needs to be confirmed by large, randomized trials, but in the meantime, we recommend (rapid) correction of 25 hydroxyvitamin D (25OHD) deficiency in subjects exposed to this coronavirus. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. ispartof: JBMR PLUS vol:5 issue:12 ispartof: location:England status: published

Many epidemiological studies have highlighted the link between vitamin D deficiency and schizophrenia. In particular, two prominent studies report an association between neonatal vitamin D deficiency and an increased risk of schizophrenia. In parallel, much has been learnt about the role of vitamin D in the developing central nervous system over the last two decades. Studies in rodent models of developmental vitamin D (DVD)-deficiency describe how brain development is altered leading to a range of neurobiological and behavioral phenotypes of interest to schizophrenia. While glutamate and gamma aminobutyric acid (GABA) systems have been little investigated in these models, alterations in developing dopamine systems are frequently reported. There have been far more studies reporting patients with schizophrenia have an increased risk of vitamin D deficiency compared to well controls. Here we have conducted a systematic review and meta-analysis that basically confirms this association and extends this to first-episode psychosis. However, patients with schizophrenia also have poorer general health, poorer diets, are frequently less active and also have an increased risk of other medical conditions, all factors which reduce circulating vitamin D levels. Therefore, we would urge caution in any causal interpretation of this association. We also summarize the inconsistent results from existing vitamin D supplementation trials in patients with schizophrenia. In respect to animal models of adult vitamin D deficiency, such exposures produce subtle neurochemical alterations and effects on cognition but do not appear to produce behavioral phenotypes of relevance to schizophrenia. We conclude, the hypothesis that vitamin D deficiency during early life may increase the risk of schizophrenia remains plausible and warrants ongoing research.

Context: Vitamin D deficiency in obesity has been linked to insulin resistance. However, studies that examined the association between plasma 25-hydroxyvitamin D-3 [25(OH)D-3] as well as plasma 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] and tissue-specific insulin sensitivity are scarce. Furthermore, vitamin D receptor (VDR) and vitamin D-metabolizing enzymes [cytochrome 450 (CYP)] expression in adipose tissue (AT) might affect AT insulin sensitivity.Objective: To investigate the association between body mass index (BMI) and plasma 25(OH)D-3 and 1,25(OH)(2)D-3, AT VDR; between plasma 25(OH)D-3, 1,25(OH)(2)D-3, AT VDR, and tissue-specific insulin sensitivity in individuals with overweight/obesity.Design and Patients: This analysis included 92 adult individuals (BMI, >25 kg/m(2)). A two-step hyperinsulinemic-euglycemic clamp with a [6,6-2H(2)]-glucose tracer was performed to assess tissue-specific insulin sensitivity. Abdominal subcutaneous AT (SAT) mRNA expression of VDR and CYP was determined by using quantitative RT-PCR.Setting: University medical center.Main Outcome Measures: Plasma 25(OH)D-3, 1,25(OH)(2)D-3, 1,25(OH)(2)D-3/25(OH)D-3 ratio, SAT VDR and CYPs mRNA, and tissue-specific insulin sensitivity.Results: BMI was inversely associated with plasma 25(OH)D-3 (beta = 20.274; P = 0.011) but not with plasma 1,25(OH)(2)D-3. Plasma 25(OH)D-3 was not related to CYPs or VDR expression in SAT. Plasma 1,25(OH)(2)D-3 and 25(OH)D-3 were not related to tissue-specific insulin sensitivity. Interestingly, SAT VDR mRNA was negatively associated with AT insulin sensitivity (b = 20.207; P = 0.025).Conclusions: BMI was inversely associated with 25(OH)D-3 concentrations, which could not be explained by alterations in SAT VDR and CYP enzymes. Plasma vitamin D metabolites were not related to tissue-specific insulin sensitivity. However, VDR expression in SAT was negatively associated with AT insulin sensitivity.

Studies on the relationship between vitamin D (VitD) and glucose homeostasis usually consider either total VitD or 25OHD3 but not 25OHD2 and epimers. We aimed to evaluate the cross-sectional association of VitD compounds with glucose homeostasis measurements in pregnant women with overweight/obesity participating in the Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus Prevention study. Methods: The analysis included 912 women. Inclusion criteria

Objective: Late neonatal hypocalcemia (LNH) is a common metabolic problem associated with hypoparathyroidism, high phosphate intake and vitamin D deficiency, often presenting with seizures. In this cross-sectional study, we aimed to evaluate the role of vitamin D deficiency in LNH in Turkey and to describe the characteristics of affected newborns. Methods: Conducted with a cross-sectional design and with the participation of 61 neonatal centers from December 2015 to December 2016, the study included term neonates with LNH (n=96) and their mothers (n=93). Data were registered on the FAVOR Web Registry System. Serum samples of newborns and mothers were analyzed for calcium, phosphate, magnesium, albumin, alkaline phosphatase, intact parathyroid hormone (iPTH) and 25 hydroxyvitamin D [25(OH)D] levels. Results: The median (range) onset time of hypocalcemia was 5.0 (4.0-8.0) days of age, with a male preponderance (60.4%). The median (range) serum 25(OH)D levels of the neonates and their mothers were 6.3 (4.1-9.05) and 5.2 (4.7-8.8) ng/mL, respectively. The prevalence of vitamin D deficiency (, Kocaeli University Scientific Research Fund, This study was supported by Kocaeli University Scientific Research Fund.

Background Childhood hypertension is a growing public health problem. Simultaneously, hypovitaminosis D is widespread in this population and could be associated with hypertension. This study systematically reviewed the literature on the relationship between vitamin D status and blood pressure (BP) in children and adolescents. Methods Following the PRISMA guidelines, PUBMED, MEDLINE, CINAHL, EMBASE, Cochrane Library, and ClinicalTrials.gov and the gray literature without language or time restrictions were searched. We included observational studies, assessed their risk of bias, and extracted data on population characteristics, vitamin D status and BP measurements, and the association between the two variables. A narrative analysis of the studies was performed. Results In total, 85 studies were included. Prospective cohort studies showed no association between vitamin D and BP, and generally, they were flawed. Also, the majority of non-prospective cohort studies (cross-sectional, retrospective, case-control) did not report an association between vitamin D and BP. They were mostly flawed regarding BP measurement and adjusting to potential confounders. Conclusion The results on the relationship between vitamin D status and BP in children and adolescents varied between the studies, and mainly pointed towards lack of association.

Background: Childhood hypertension is a growing public health problem. Simultaneously, hypovitaminosis D is widespread in this population and could be associated with hypertension. This study systematically reviewed the literature on the relationship between vitamin D status and blood pressure (BP) in children and adolescents.Methods: Following the PRISMA guidelines, PUBMED, MEDLINE, CINAHL, EMBASE, Cochrane Library, and and the gray literature without language or time restrictions were searched. We included observational studies, assessed their risk of bias, and extracted data on population characteristics, vitamin D status and BP measurements, and the association between the two variables. A narrative analysis of the studies was performed.Results: In total, 85 studies were included. Prospective cohort studies showed no association between vitamin D and BP, and generally, they were flawed. Also, the majority of non-prospective cohort studies (cross-sectional, retrospective, case-control) did not report an association between vitamin D and BP. They were mostly flawed regarding BP measurement and adjusting to potential confounders.Conclusion: The results on the relationship between vitamin D status and BP in children and adolescents varied between the studies, and mainly pointed towards lack of association.

Purpose of review Observational studies have shown that serum 25-OH vitamin D [25(OH)D] is inversely associated with overall cancer risk in many malignancies. We performed a systematic literature review to determine whether vitamin D deficiency is related to head and neck cancer (HNC) etiology and outcome. Recent findings The search yielded five prospective studies reporting 25(OH)D levels prior to cancer diagnosis and their effect on the risk of HNC. Eight studies were cross-sectional or case-control studies, in which 25(OH)D levels were only measured after cancer diagnosis. Two studies found an inverse association between 25(OH)D level and HNC risk, while two other prospective cohort studies demonstrated no connection between 25(OH)D and HNC risk. Several studies reported cancer patients to have significantly lower 25(OH)D levels than controls. Associations between 25(OH)D and prognosis and mortality were variable. Summary The link between vitamin D and HNC has so far only been investigated in a few observational, prospective, and case-control studies. Vitamin D deficiency may be more common in HNC patients than in the healthy population. There is no evidence for a causal relationship. Further studies are needed to evaluate whether low 25(OH)D concentrations play a role in the development or outcome of HNCs.

In Pakistan, there is limited evidence for the levels and relationship of 25 (OH) Vitamin D (25(OH)D) status in pregnant women and their newborns, while the association between maternal 25(OH)D and newborn anthropometric measurements remains unexplored. Sociodemographic data were collected from 213 pregnant mothers during their visit to a tertiary care hospital at the time of childbirth. Anthropometric measurements were performed on all mothers and their newborns and blood samples collected from both for 25(OH)D levels. Participants were classified into two groups according to their 25(OH)D status: sufficient (25(OH)D ≥50 nmol L−1) and deficient (25(OH)D 0.05). Our study shows a high prevalence of 25(OH)D deficiency in pregnant women and their newborns and a strong positive association between maternal and newborn 25(OH)D levels. Findings of this study indicate the importance of maintaining sufficient 25(OH)D levels during pregnancy.

Recurrent wheezing (RW) in infancy is one of the most frequent reasons for parents to consult health care providers and creates a significant global burden. Clinical course of RW is difficult to predict, also which infants will progress to asthma, since no valid biomarkers have been established. Identification of those infants with RW who are at risk of further recurrences and/or severe acute respiratory tract infection (ARTI) could help pediatricians to improve their therapeutic decisions. Increasing research interest is focused on the extra-skeletal actions of vitamin D (VD) and the clinical impact of VD insufficiency/deficiency. As VD deficiency could be a risk factor for causing RW in children, measurement of their serum level of 25-hydroxycholecalciferol [25(OH)D] is recommended. In the case of deficiency, VD administration is recommended in age-appropriate doses for at least 6 weeks, until achievement of normal blood 25(OH)D level, followed by supplementation as long as exposure to sun is inadequate. Higher doses of VD given in an attempt to prevent asthma development appear to be of no additional benefit. In children with severe ARTI, VD level is recommended to be assess.

Context The relationship of maternal and infant 25-hydroxyvitamin D concentration [25(OH)D] with infant growth is unclear. Objective Our objective was to explore whether 25(OH)D in pregnancy, umbilical cord blood (UCB), or in infancy was associated with infant growth. Design This study involved 798 healthy infants and their mothers in Finland. We assessed 25(OH)D during pregnancy, from UCB at birth, and from the infant at the age of 12 months. Main Outcome Measures Infant length, weight, length-adjusted weight, and head circumference at 6 and 12 months and midupper-arm circumference at 12 months. Results Of the mothers and infants, 96% and 99% were vitamin D sufficient [25(OH)D ≥50 nmol/L], respectively. Mothers with pregnancy 25(OH)D >125 nmol/L had the shortest, lightest (in weight), and thinnest (in length-adjusted weight) infants at 6 months (P for all < 0.05). For each 10 nmol/L higher UCB 25(OH)D, the infants were 0.03 SD score (SDS) shorter at 6 months (95% CI −0.05 to −0.01), adjusted for birth size, infant 25(OH)D, and parental height. Higher UCB 25(OH)D associated with smaller head circumference at 6 and 12 months (P for all 125 nmol/L had the thinnest infants at 12 months (P = 0.021). For each 10 nmol/L higher infant 25(OH)D, the infants were 0.03 SDS lighter (−0.05 to −0.01) and 0.03 SDS thinner (−0.05 to 0.00) at 12 months. Conclusions Our results suggest that high pregnancy, cord blood, and infant vitamin D concentration may have disadvantageous effects on infant growth.

Aims To study the effects of metformin, as compared to placebo, on serum levels of vitamin D (25-hydroxyvitamin D [25(OH)D]) in patients with advanced type 2 diabetes.Materials and Methods In the HOME trial, a randomized placebo-controlled trial, 390 insulin-treated patients with type 2 diabetes were treated with 850 mg metformin or placebo thrice daily for 52 months. In a post-hoc analysis, we examined changes in the combined levels of 25(OH)D-2 and 25(OH)D-3 at 4 and 16 months during the study.Results Mean combined 25(OH)D at baseline was 68.2 nmoL/L (95% confidence interval [CI]: 65.5-71.1). In mixed model analysis, metformin, as compared to placebo, had no effect on 25(OH)D levels during 16 months (coefficient: 1.002 per month, multiplicative model; 95% CI: 0.998-1.006, P=.30). Metformin was associated with a small increase of 25(OH)D-2 (coefficient: 1.012 per month; 95% CI: 1.003-1.021, P=.008). However, 25(OH)D-2 is only a very small fraction (3%) of 25(OH)D. Seasonal variation had the biggest impact on 25(OH)D levels. Vitamin B12 levels were not associated with the levels of 25(OH)D.Conclusion Metformin had no effect on serum 25(OH)D during 16 months in the setting of a clinical randomized controlled trial in patients with type 2 diabetes. Our results show that metformin doesn't lead to vitamin D deficiency.

People with psychotic disorders have an increased metabolic riskand their mean life expectancy is reduced with circa 28 years (Olfsonet al., 2015).Predictors of this increased metabolic risk are genetic predisposition (Liu et al., 2013), lifestyle factors such as unhealthy diet,physical inactivity and smoking (Bobes et al., 2010), and the side effectsof antipsychotic medication (Werner and Coveñas, 2014;Chadda et al.,2013). Low vitamin D status might also contribute to an increased metabolicrisk (Ginde et al., 2009;Kendrick et al., 2009;Kilkkinen et al.,2009;Ford et al., 2009) and all-cause mortality by promoting atherosclerosis,hypertension, inflammation and activation of the renin-angiotensinsystem (Wang et al., 2012;Garland et al., 2014;Lee et al., 2008). Also,one review demonstrated cardiovascular mortality rates in the generalpopulation were higher during winter than in summer (Zittermann etal., 2005).Vitamin D interacts with dopaminergic, cholinergic and noradrenergicneurotransmitter systems, which have all been implicated inSchizophrenia Research 195 (2018) 513–518⁎ Corresponding author at: University Medical Center Groningen, University Center for Psychiatry, Rob Giel Research center, P.O. Box 30.001 (CC72), 9700 RB Groningen, The Netherlands.E-mail addresses: j.bruins@lentis.nl (J. Bruins), f.jorg@umcg.nl (F. Jörg),e.r.v.d.heuvel@tue.nl (E.R. van den Heuvel), a.a.bartels@umcg.nl (A.A. Bartels-Velthuis),e.corpeleijn@umcg.nl (E. Corpeleijn), f.a.j.muskiet@umcg.nl (F.A.J. Muskiet),g.h.m.pijnenborg@rug.nl (G.H.M. Pijnenborg), r.bruggeman@umcg.nl (R. Bruggeman).experiencing psychotic symptoms (Eyles et al., 2013). When vitaminD is low, dopamine signalling in the brain appears to decrease (Eyleset al., 2013;Cui et al., 2015;Cui et al., 2013;Groves et al., 2014), whichin its turn could lead to more severe negative symptoms of psychosis(Buchanan et al., 2007). Indeed, several studies found that vitamin D insufficiencywas strongly associated with negative symptoms of psychosis(Graham et al., 2015;Yüksel et al., 2014;Cieslak et al., 2014;OttesenBerg et al., 2010).Vitamin D is thus associated with both metabolic risk and negativesymptom severity. Negative symptoms have also been shown to interferewith patients' ability to be physically active and make healthy lifestylechoices, which can increase their metabolic risk (Bergqvist et al.,2013). Negative symptom severity may therefore mediate the associationbetween low vitamin D and increased metabolic risk in peoplewith a psychotic disorder.Vitamin D is mostly produced in the skin by exposure to ultravioletBradiation in sunlight (Brown et al., 1999;Holick, 2007). Absorption ofvitamin D and levels of circulation differ among individuals and can beinfluenced by determinants such as latitude, season, time of day, skincolor (Holick et al., 2011), bodyweight, age, calcium intake(Zittermann et al., 2014), diet and genetics (Mazahery and von Hurst,2015).Vitamin D shows a natural fluctuation throughout the year, with vitaminD insufficiency more likely to occur during winter than in summer(Rosecrans and Dohnal, 2014). A recent study suggestsseasonality may also affect clinical symptoms of schizophrenia, althoughthe underlying mechanism is unknown (Byrne et al., 2015).In this study we aim to investigate whether vitamin D levels are associatedwith metabolic risk in people with psychotic disorders andwhether this effect was mediated by negative symptoms. We hypothesizethat vitamin D levels may influence the severity of metabolic disturbancesand negative symptoms. As vitamin D levels naturally fluctuatethroughout the seasons (Rosecrans and Dohnal, 2014), we examinewhether metabolic risk and negative symptom severity follow a similarseasonal fluctuation pattern. Furthermore, we investigate whether thehttp://dx.doi.org/10.1016/j.schres.2017.08.0590920-9964/© 2017 Elsevier B.V. All rights reserved.Contents lists available at ScienceDirectSchizophrenia Researchjournal homepage: www.elsevier.com/locate/schresseverity of metabolic risk and negative symptoms differ between patientsusing and patients not using vitamin D supplementation. In thiscross-sectional study, seasonal patterns and differences with regard tosupplementation may indicate an interdependent and potentially causalconnection between vitamin D, metabolic risk and negative symptomseverity

Breast-fed infants are susceptible to vitamin D deficiency rickets. The current vitamin D ‘adequate intake’ (AI) for 0–6-month-old infants is 10 µg/d, corresponding with a human milk antirachitic activity (ARA) of 513 IU/l. We were particularly interested to see whether milk ARA of mothers with lifetime abundant sunlight exposure reaches the AI. We measured milk ARA of lactating mothers with different cultural backgrounds, living at different latitudes. Mature milk was derived from 181 lactating women in the Netherlands, Curaçao, Vietnam, Malaysia and Tanzania. Milk ARA and plasma 25-hydroxyvitamin D (25(OH)D) were analysed by liquid-chromatography-MS/MS; milk fatty acids were analysed by GC-flame ionisation detector (FID). None of the mothers reached the milk vitamin D AI. Milk ARA (n; median; range) were as follows: Netherlands (n 9; 46 IU/l; 3–51), Curaçao (n 10; 31 IU/l; 5–113), Vietnam: Halong Bay (n 20; 58 IU/l; 23–110), Phu Tho (n 22; 28 IU/l; 1–62), Tien Giang (n 20; 63 IU/l; 26–247), Ho-Chi-Minh-City (n 18; 49 IU/l; 24–116), Hanoi (n 21; 37 IU/l; 11–118), Malaysia–Kuala Lumpur (n 20; 14 IU/l; 1–46) and Tanzania-Ukerewe (n 21; 77 IU/l; 12–232) and Maasai (n 20; 88 IU/l; 43–189). We collected blood samples of these lactating women in Curaçao, Vietnam and from Tanzania–Ukerewe, and found that 33·3 % had plasma 25(OH)D levels between 80 and 249·9 nmol/l, 47·3 % between 50 and 79·9 nmol/l and 19·4 % between 25 and 49·9 nmol/l. Milk ARA correlated positively with maternal plasma 25(OH)D (range 27–132 nmol/l, r 0·40) and milk EPA+DHA (0·1–3·1 g%, r 0·20), and negatively with latitude (2°S-53°N, r −0·21). Milk ARA of mothers with lifetime abundant sunlight exposure is not even close to the vitamin D AI for 0–6-month-old infants. Our data may point at the importance of adequate fetal vitamin D stores.

Calcium and vitamin-D (Ca/VitD) deficiency is a major risk factor for osteoporosis. It may also contribute to the compromised bone healing frequently observed in osteoporotic patients, since calcium is essential for fracture-callus mineralization. Additionally, clinical data suggest systemic bone loss following fracture, which may aggravate osteoporosis and thus increase the risk for fragility fractures in osteoporotic patients further. However, the role of Ca/VitD in fracture healing and posttraumatic bone turnover has to date been poorly investigated. Here, we studied bone regeneration and posttraumatic bone turnover in C57BL/6 J mice with ovariectomy-induced osteoporosis. Mice were fed a standard or a Ca/VitD-deficient diet. Notably, fracture healing was only marginally disturbed in Ca/VitD-deficient mice. However, deficient mice displayed significantly increased serum parathyroid hormone levels and osteoclast activity, as well as reduced bone mass in the intact skeleton post-fracture, suggesting considerably enhanced calcium mobilization from the intact skeleton during bone regeneration. Ca/VitD supplementation initiated post-fracture prevented posttraumatic bone loss by reducing bone resorption and furthermore improved bone repair. These results imply that adequate Ca/VitD supply post-fracture is essential to provide sufficient calcium for callus-mineralization in order to prevent posttraumatic bone loss and to reduce the risk for secondary fractures in osteoporotic patients with Ca/VitD deficiency., publishedVersion

AimTo test whether a low serum 25-hydroxyvitamin D level explains the greater prevalence of depression among people with Type 2 diabetes.MethodsWe performed a cross-sectional analysis of 527 people, aged 60-87 years, who participated in a population-based cohort study. Type 2 diabetes, impaired glucose tolerance, impaired fasting glucose and normal glucose tolerance were defined according to the 2006 WHO criteria. The Centre for Epidemiologic Studies Depression questionnaire was administered, using a cut-off score of 16 to determine clinically relevant depressive symptoms.ResultsLogistic regression analysis confirmed that women with impaired glucose tolerance/impaired fasting glucose and people with Type 2 diabetes did have a higher risk of depressive symptoms [unadjusted odds ratios 3.66 (95% CI 1.59 to 8.43) and 3.04 (95% CI 1.57 to 5.88), respectively], compared with people with normal glucose tolerance. Serum 25-hydroxyvitamin D level was not a mediating factor in the association between impaired glucose tolerance/impaired fasting glucose or Type 2 diabetes and depressive symptoms [unstandardized indirect effect 0.001 (95% CI -0.063 to 0.079) and 0.004 (95% CI -0.025 to 0.094), respectively].ConclusionsThe study found no evidence that low vitamin D levels are a contributing factor to higher depression scores in people with Type 2 diabetes.

Background Higher circulating 25-hydroxyvitamin-D [25(OH)D] concentrations are consistently inversely associated with colorectal cancer (CRC) risk in observational studies. However, it is unknown whether this association depends on the functional GC-rs4588*A (Thr436Lys) variant encoding the vitamin D–binding protein-2 (DBP2) isoform, which may affect vitamin D status and bioavailability. Methods We analyzed data from 1710 incident CRC cases and 1649 incidence-density–matched controls nested within three prospective cohorts of mostly Caucasians. Study-specific incidence rate ratios (RRs) for associations of prediagnostic, season-standardized 25(OH)D concentrations according to DBP2 isoform with CRC were estimated using multivariable unconditional logistic regression and were pooled using fixed-effects models. All statistical significance tests were two-sided. Results The odds of having 25(OH)D concentrations less than 50 nmol/L (considered insufficient by the Institute of Medicine) were 43% higher for each DBP2-encoding variant (rs4588*A) inherited (per DBP2 odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.27 to 1.62, Ptrend = 1.2 × 10−8). The association of 25(OH)D concentrations with CRC risk differed by DBP2: 25(OH)D concentrations considered sufficient (≥ 50 nmol/L), relative to deficient ( Conclusions Our results suggest that the 25(OH)D-CRC association may differ by DBP isoform, and those with a DBP2-encoding genotype linked to vitamin D insufficiency may particularly benefit from adequate 25(OH)D for CRC prevention.

The obese insulin-resistant state is often associated with low circulating concentration of vitamin D 25-hydroxyvitamin D3 [25(OH)D3]. Fat sequestration of vitamin D in the expanded obese adipose tissue mass has been pointed out as a plausible explanation for this circulating vitamin D deficiency. However, the putative mechanisms behind this hypovitaminosis D remain to be elucidated. The presence of vitamin D receptor and vitamin D-metabolizing enzymes in insulin-sensitive organs suggests that vitamin D may be involved in glucose and lipid metabolism and may be related to insulin sensitivity. Indeed, mainly in vitro studies support a role of vitamin D in regulating glucose and lipid metabolism in several insulin-sensitive tissues including adipose tissue, skeletal muscle, liver, as well as pancreatic insulin secretion. A potential role of vitamin D in gut barrier function and metabolism has also been suggested. This review summarizes recent knowledge on vitamin D deficiency in the aetiology of obesity-related insulin resistance and discusses potential underlying mechanisms. Finally, the role of vitamin D supplementation on insulin sensitivity and glycaemic control is discussed.

The obese insulin-resistant state is often associated with low circulating concentration of vitamin D 25-hydroxyvitamin D3 [25(OH)D3 ]. Fat sequestration of vitamin D in the expanded obese adipose tissue mass has been pointed out as a plausible explanation for this circulating vitamin D deficiency. However, the putative mechanisms behind this hypovitaminosis D remain to be elucidated. The presence of vitamin D receptor and vitamin D-metabolizing enzymes in insulin-sensitive organs suggests that vitamin D may be involved in glucose and lipid metabolism and may be related to insulin sensitivity. Indeed, mainly in vitro studies support a role of vitamin D in regulating glucose and lipid metabolism in several insulin-sensitive tissues including adipose tissue, skeletal muscle, liver, as well as pancreatic insulin secretion. A potential role of vitamin D in gut barrier function and metabolism has also been suggested. This review summarizes recent knowledge on vitamin D deficiency in the aetiology of obesity-related insulin resistance and discusses potential underlying mechanisms. Finally, the role of vitamin D supplementation on insulin sensitivity and glycaemic control is discussed.

Objective The effect of vitamin D at the transcriptome level is poorly understood, and furthermore, it is unclear if it differs between obese and normal-weight subjects. The objective of the study was to explore the transcriptome effects of vitamin D supplementation. Design and methods We analysed peripheral blood gene expression using GlobinLock oligonucleotides followed by RNA sequencing in individuals participating in a 12-week randomised double-blinded placebo-controlled vitamin D intervention study. The study involved 18 obese and 18 normal-weight subjects (of which 20 males) with mean (±s.d.) age 20.4 (±2.5) years and BMIs 36 (±10) and 23 (±4) kg/m2, respectively. The supplemental daily vitamin D dose was 50 µg (2000 IU). Data were available at baseline, 6- and 12-week time points and comparisons were performed between the vitamin D and placebo groups separately in obese and normal-weight subjects. Results Significant transcriptomic changes were observed at 6 weeks, and only in the obese subjects: 1724 genes were significantly upregulated and 186 genes were downregulated in the vitamin D group compared with placebo. Further analyses showed several enriched gene categories connected to mitochondrial function and metabolism, and the most significantly enriched pathway was related to oxidative phosphorylation (adjusted P value 3.08 × 10−14). Taken together, our data suggest an effect of vitamin D supplementation on mitochondrial function in obese subjects. Conclusions Vitamin D supplementation affects gene expression in obese, but not in normal-weight subjects. The altered genes are enriched in pathways related to mitochondrial function. The present study increases the understanding of the effects of vitamin D at the transcriptome level.

Beyond its impact on bone health, numerous studies have investigated the immune-regulatory properties of vitamin D and shown how its deficiency can affect outcomes in allogeneic hematopoietic stem cell transplantation (HSCT), particularly in acute or chronic graft-versus-host disease. This survey, carried out by the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation (EBMT), describes the current clinical practice discrepancies across the EBMT HSCT programs. We therefore recommend the development of evidence-based guidelines to standardize evaluation criteria and to harmonize the management of vitamin D deficiency in patients undergoing allogeneic HSCT. ispartof: Biology Of Blood And Marrow Transplantation vol:25 issue:10 pages:2079-2085 ispartof: location:United States status: published

Different laboratory approaches have been exploited to analyze an effect of vitamin D-3 supplements on T cell cytokine profiles in multiple sclerosis, with poorly reproducible results. We assessed the correlation between intra-cellular flowcytometry analysis of CD4 T cell-enriched CD3(+)CD8(-) lymphocytes after PMA/ionomycin stimulation directly ex-vivo or after 72 h pre-stimulation with anti-CD3, and cytokine levels excreted in culture supernatants. Pre-stimulation with anti-CD3 resulted in higher proportions of cells positive for IFN-gamma, IL-17A, IL-4, IL-10 and GM-CSF (all P

Vitamin D insufficiency is common in the healthy population. Recent insights addressed the role of vitamin D in serotonin and melatonin regulation, suggesting that increasing vitamin D status may be helpful for improving mood and sleep. This literature review covers the current state of evidence regarding potential effects of vitamin D on mood and sleep indicators in healthy people. In total, 11 observational studies were found for sleep, and 54 studies on mood (including ten RCTs). These studies revealed mixed results for both sleep and mood. The findings were interpreted based on the previously proposed serotonergic pathway of vitamin D. Implications and challenges for future research regarding the timing of blood sampling, timing and dosage of supplement intake and investigating the response dynamics are discussed.

Background: Vitamin D (Vit D) is suggested to play a role in the regulation of physical function as well as in depression. Since, Vit D deficiency is common in patients with heart failure (HF), this study aims to explore if Vit D levels are associated with depressive symptoms and if this association is mediated by the patients' physical function.Method: 506 HF patients (mean age 71, 38% women) were investigated. Depressive symptoms and physical function were measured with the Centre for Epidemiological Studies Depression Scale and the physical function scale from the RAND-36. Vit D was measured in blood samplesResults: At baseline there was no relationship between depressive symptoms and Vit D levels. However, at 18 months follow-up 29% of patients with Vit D 50 nmol/l (p Conclusion: In HF patients with Vit D 50 nmol/l. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Vitamin D deficiency can lead to musculoskeletal diseases such as rickets and osteomalacia, but vitamin D supplementation may also prevent extraskeletal diseases such as respiratory tract infections, asthma exacerbations, pregnancy complications and premature deaths. Vitamin D has a unique metabolism as it is mainly obtained through synthesis in the skin under the influence of sunlight (i.e., ultraviolet-B radiation) whereas intake by nutrition traditionally plays a relatively minor role. Dietary guidelines for vitamin D are based on a consensus that serum 25-hydroxyvitamin D (25[OH]D) concentrations are used to assess vitamin D status, with the recommended target concentrations ranging from >= 25 to >= 50 nmol/L (>= 10->= 20 ng/mL), corresponding to a daily vitamin D intake of 10 to 20 mu g (400-800 international units). Most populations fail to meet these recommended dietary vitamin D requirements. In Europe, 25(OH)D concentrations < 30 nmol/L (12 ng/mL) and < 50 nmol/L (20 ng/mL) are present in 13.0 and 40.4% of the general population, respectively. This substantial gap between officially recommended dietary reference intakes for vitamin D and the high prevalence of vitamin D deficiency in the general population requires action from health authorities. Promotion of a healthier lifestyle with more outdoor activities and optimal nutrition are definitely warranted but will not erase vitamin D deficiency and must, in the case of sunlight exposure, be well balanced with regard to potential adverse effects such as skin cancer. Intake of vitamin D supplements is limited by relatively poor adherence (in particular in individuals with low-socioeconomic status) and potential for overdosing. Systematic vitamin D food fortification is, however, an effective approach to improve vitamin D status in the general population, and this has already been introduced by countries such as the US, Canada, India, and Finland. Recent advances in our knowledge on the safety of vitamin D treatment, the dose-response relationship of vitamin D intake and 25(OH)D levels, as well as data on the effectiveness of vitamin D fortification in countries such as Finland provide a solid basis to introduce and modify vitamin D food fortification in order to improve public health with this likewise cost-effective approach.

Background Pregnant women are at increased susceptibility to vitamin D deficiency. Hence, there is continuing interest in determining how vitamin D influences pregnancy health. We aimed to compare vitamin D status in two distinct populations of pregnant women in Australia and New Zealand and to investigate the relationship between vitamin D status and pregnancy outcome. This included evaluating possible effect measure modifications according to fetal sex. Methods Serum 25-hydroxy vitamin D (25(OH)D) was measured at 15 ± 1 weeks’ gestation in 2800 women from Adelaide and Auckland who participated in the multi-centre, prospective cohort SCreening fOr Pregnancy Endpoints (SCOPE) study. Results Mean serum 25(OH)D in all women was 68.1 ± 27.1 nmol/L and 28% (n = 772) were considered vitamin D deficient ( 81 nmol/L) “standardised” vitamin D status when compared to moderate-high (63–81 nmol/L, aRR, 0.47; 95% CI: 0.23, 0.96). Marginal sex-specific differences occurred between vitamin D status and GDM: women carrying a female fetus had a 56% decreased risk for GDM in those with low-moderate levels of standardised vitamin D (44–63 nmol/L) compared to moderate-high levels (aRR: 0.44; 95% CI: 0.20, 0.97), whilst in women carrying a male fetus, a 55% decreased risk of GDM was found with high standardised vitamin D when compared to moderately-high vitamin D, but this was not statistically significant (aRR: 0.45; 95% CI: 0.15, 1.38). Conclusions High serum 25(OH)D at 15 ± 1 weeks’ gestation was shown to be protective against the development of GDM. A possible association between fetal sex, vitamin D status and GDM provides further questions and encourages continual research and discussion into the role of vitamin D in pregnancy, particularly in vitamin D replete populations. Electronic supplementary material The online version of this article (10.1186/s12884-018-1887-x) contains supplementary material, which is available to authorized users.

BACKGROUND: Vitamin D has health benefits in many respiratory diseases but the evidence in CF is unclear. Induction of the antimicrobial peptides cathelicidin (LL37) and human-beta-defensin-2 (HBD-2) may be the mechanism of any benefit. We hypothesised that antimicrobial peptide levels would be decreased, and airway infection and inflammation greater, in CF children with vitamin D deficiency. The objective of the study was to explore relationships between vitamin D, LL37 and HBD-2, and airway infection, inflammation and physiology in children with CF. METHODS: Bronchoalveolar lavage (BALF) and blood were obtained from children undergoing fibreoptic bronchoscopy. Serum vitamin D, BALF HBD-2 and LL37, cultured bacteria and inflammatory markers were measured. Clinical parameters were recorded. RESULTS: 113 patients with CF, 23 with non-CF chronic suppurative lung disease (CSLD) and 6 healthy controls were included. We found no relationship between serum vitamin D and BALF HBD-2 or LL-37. There were no differences in infective or inflammatory markers between vitamin D sufficient and deficient groups. Vitamin D deficient patients (

Background. The effects of vitamin D on sexual function are very unclear. Therefore, we aimed at evaluating the possible association between vitamin D and sexual function and at assessing the influence of vitamin D administration on sexual function. Methods. We retrospectively studied 114 men by evaluating clinical, biochemical, and sexual parameters. A subsample (n=41) was also studied longitudinally before and after vitamin D replacement therapy. Results. In the whole sample, after performing logistic regression models, higher levels of 25(OH) vitamin D were significantly associated with high values of total testosterone and of all the International Index of Erectile Function (IIEF) questionnaire parameters. On the other hand, higher levels of total testosterone were positively and significantly associated with high levels of erectile function and IIEF total score. After vitamin D replacement therapy, total and free testosterone increased and erectile function improved, whereas other sexual parameters did not change significantly. At logistic regression analysis, higher levels of vitamin D increase (Δ-) were significantly associated with high values of Δ-erectile function after adjustment for Δ-testosterone. Conclusions. Vitamin D is important for the wellness of male sexual function, and vitamin D administration improves sexual function.

Vitamin D deficiency can lead to musculoskeletal diseases such as rickets and osteomalacia, but vitamin D supplementation may also prevent extraskeletal diseases such as respiratory tract infections, asthma exacerbations, pregnancy complications and premature deaths. Vitamin D has a unique metabolism as it is mainly obtained through synthesis in the skin under the influence of sunlight (i.e., ultraviolet-B radiation) whereas intake by nutrition traditionally plays a relatively minor role. Dietary guidelines for vitamin D are based on a consensus that serum 25-hydroxyvitamin D (25[OH]D) concentrations are used to assess vitamin D status, with the recommended target concentrations ranging from >= 25 to >= 50 nmol/L (>= 10->= 20 ng/mL), corresponding to a daily vitamin D intake of 10 to 20 mu g (400-800 international units). Most populations fail to meet these recommended dietary vitamin D requirements. In Europe, 25(OH)D concentrations

Vitamin D is a key hormone in the regulation of calcium and phosphorus metabolism and plays a pivotal role in bone health, particularly during pediatric age when nutritional rickets and impaired bone mass acquisition may occur. Great interest has been placed in recent years on vitamin D's extraskeletal actions. However, while recent data suggest a possible role of vitamin D in the pathogenesis of several pathological conditions, including infectious and autoimmune diseases, the actual impact of vitamin D status on the global health of children and adolescents, other than bone, remains a subject of debate. In the meantime, pediatricians still need to evaluate the determinants of vitamin D status and consider vitamin D supplementation in children and adolescents at risk of deficiency. This review is the result of an expert meeting that was held during the congress "Update on vitamin D and bone disease in childhood" convened in Pisa, Italy, in May 2013.Conclusion: The collaboration of the international group of experts produced this "state of the art" review on vitamin D in childhood and adolescence. After dealing with vitamin D status and its determinants, the review outlines the current debate on vitamin D's health benefits, concluding with a practical approach to vitamin D supplementation during childhood and adolescence.

Context: Vitamin D deficiency is common in renal transplant recipients (RTR). The long-term implications of vitamin D deficiency in RTR remain unclear.Objective: We investigated whether 25(OH) or 1,25(OH)(2) vitamin D levels are associated with mortality, renal function decline, and graft failure in stable RTR.Design: Observational study with longitudinal design. Followup was 7.0, interquartile range (IQR) 6.2-7.5 years.Setting: Single-center outpatient clinic.Participants: 435 stable RTR (51% men, mean age 52 +/- 12 years) were included at a median [IQR] of 6 [3-12] years after kidney transplantation.Main Outcome Measures: All-cause mortality, annual change of estimated glomerular filtration rate (eGFR), and graft failure.Results: Mean 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were 21.6 +/- 9.1 ng/ml and 45.2 +/- 19.0 pg/ml, respectively. During followup, 99 patients (22.8%) died and 44 patients (10.1%) developed graft failure. In univariable analysis, both 25(OH)D and 1,25(OH)(2)D were significantly associated with mortality (hazard ratio [HR], 0.64; 95% confidence interval (CI), 0.51-0.81; P Conclusions: Low 25(OH) D is independently associated with an increased risk of all-cause mortality and 25(OH) D

There is a growing body of evidence that links nutrition to muscle mass, strength and function in older adults, suggesting that it has an important role to play both in the prevention and management of sarcopenia. This review summarises the discussions of a working group [ESCEO working group meeting 8th September 2016] that met to review current evidence and to consider its implications for preventive and treatment strategies. The review points to the importance of 'healthier' dietary patterns that are adequate in quality in older age, to ensure sufficient intakes of protein, vitamin D, antioxidant nutrients and long-chain polyunsaturated fatty acids. In particular, there is substantial evidence to support the roles of dietary protein and physical activity as key anabolic stimuli for muscle protein synthesis. However, much of the evidence is observational and from high-income countries. Further high-quality trials, particularly from more diverse populations, are needed to enable an understanding of dose and duration effects of individual nutrients on function, to elucidate mechanistic links, and to define optimal profiles and patterns of nutrient intake for older adults. (C) 2017 The Authors. Published by Elsevier Ltd.

Background Low circulating vitamin D levels have been associated with risk of asthma, atopic dermatitis, and elevated total immunoglobulin E (IgE). These epidemiological associations, if true, would have public health importance, since vitamin D insufficiency is common and correctable. Methods and findings We aimed to test whether genetically lowered vitamin D levels were associated with risk of asthma, atopic dermatitis, or elevated serum IgE levels, using Mendelian randomization (MR) methodology to control bias owing to confounding and reverse causation. The study employed data from the UK Biobank resource and from the SUNLIGHT, GABRIEL and EAGLE eczema consortia. Using four single-nucleotide polymorphisms (SNPs) strongly associated with 25-hydroxyvitamin D (25OHD) levels in 33,996 individuals, we conducted MR studies to estimate the effect of lowered 25OHD on the risk of asthma (n = 146,761), childhood onset asthma (n = 15,008), atopic dermatitis (n = 40,835), and elevated IgE level (n = 12,853) and tested MR assumptions in sensitivity analyses. None of the four 25OHD-lowering alleles were associated with asthma, atopic dermatitis, or elevated IgE levels (p ≥ 0.2). The MR odds ratio per standard deviation decrease in log-transformed 25OHD was 1.03 (95% confidence interval [CI] 0.90–1.19, p = 0.63) for asthma, 0.95 (95% CI 0.69–1.31, p = 0.76) for childhood-onset asthma, and 1.12 (95% CI 0.92–1.37, p = 0.27) for atopic dermatitis, and the effect size on log-transformed IgE levels was −0.40 (95% CI −1.65 to 0.85, p = 0.54). These results persisted in sensitivity analyses assessing population stratification and pleiotropy and vitamin D synthesis and metabolism pathways. The main limitations of this study are that the findings do not exclude an association between the studied outcomes and 1,25-dihydoxyvitamin D, the active form of vitamin D, the study was underpowered to detect effects smaller than an OR of 1.33 for childhood asthma, and the analyses were restricted to white populations of European ancestry. This research has been conducted using the UK Biobank Resource and data from the SUNLIGHT, GABRIEL and EAGLE Eczema consortia. Conclusions In this study, we found no evidence that genetically determined reduction in 25OHD levels conferred an increased risk of asthma, atopic dermatitis, or elevated total serum IgE, suggesting that efforts to increase vitamin D are unlikely to reduce risks of atopic disease., In a Mendelian randomization analysis, J. Brent Richards and colleagues investigate possible relations between genetic elements associated with vitamin D levels and atopic susceptibility., Author summary Why was this study done? Observational epidemiological studies have reported associations of low vitamin D levels with risk of asthma, atopic dermatitis, and elevated immunoglobulin E (IgE) levels. However, these studies are susceptible to confounding and reverse causation, and thus it remains unclear whether these associations are genuine. The randomized controlled trials published to date on this topic have been inconclusive. If vitamin D insufficiency did cause atopic diseases, this would be of clinical relevance, since vitamin D insufficiency is common and safely correctable. What did the researchers do and find? We applied a Mendelian randomization study design, which greatly limits bias due to confounding and prevents bias due to reverse causation, to understand if vitamin D levels are associated with a higher risk of adult and pediatric asthma, atopic dermatitis, or elevated IgE levels. Despite high statistical power, our study showed no evidence of an unconfounded association between vitamin D and the studied outcomes. What do these findings mean? Our findings suggest that the previous epidemiological associations between vitamin D and atopic diseases could be due to confounding. Efforts to increase vitamin D levels will probably not result in decreased risk of adult and pediatric asthma, atopic dermatitis, or elevated IgE levels.

The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, pcurvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life. © The Author(s) 2017. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Studies monitoring vitamin D status in athletes are seldom conducted for a period of 12 months or longer, thereby lacking insight into seasonal fluctuations. The objective of the current study was to identify seasonal changes in total 25-hydroxyvitamin D (25(OH)D) concentration throughout the year. Fifty-two, mainly Caucasian athletes with a sufficient 25(OH)D concentration (>75 nmol/L) in June were included in this study. Serum 25(OH)D concentration was measured every three months (June, September, December, March, June). In addition, vitamin D intake and sun exposure were assessed by questionnaires at the same time points. Highest total 25(OH)D concentrations were found at the end of summer (113 ± 26 nmol/L), whereas lowest concentrations were observed at the end of winter (78 ± 30 nmol/L). Although all athletes had a sufficient 25(OH)D concentration at the start of the study, nearly 20% of the athletes were deficient (

Objectives: The aim of this study was to further investigate the prevalence of Vitamin D deficiency in diabetes mellitus (DM) patients, as well as the association between hypovitaminosis D and the microvascular complications of type 2 (T2) DM. Methods: This was a cross-sectional, case-control study of 206 T2DM patients and 34 healthy control subjects. Participants were evaluated for the presence of diabetic retinopathy, nephropathy, and neuropathy. Results: The level of serum 25-hydroxyvitamin D (25(OH) D) was significantly lower in the T2DM patients (11.16 +/- 3.99 ng/mL vs. 15.58 +/- 3.16 ng/mL; p

BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk.METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium.FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002).INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.FUNDING: British Heart Foundation, UK Medical Research Council, and Academy of Finland.

On September 29, 2011, acknowledged experts in the field of vitamin D, mainly European, were brought together in order to discuss the recent scientific advances in relation to vitamin D: the current requirements and associations with various health outcom