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Context Chronic obstructive lung disease (COPD) is a progressive lung disease characterized by persistent airflow limitation. An increasing amount of evidence suggests an effect of dietary quality on the risk of COPD in the general population and pulmonary function decline in patients with COPD. Objective The association of dietary intake and nutrient status with COPD risk and onset, as well as pulmonary function decline (change in forced expiratory volume in 1 second, forced vital capacity, or the ratio of the former to the latter) in patients with COPD was investigated in this systematic review. Data Sources The PubMed database was searched by combining terms of pulmonary function or COPD with diet, nutrient status, or nutritional supplementation. Data Extraction Original studies and systematic reviews and meta-analyses were included. Articles obtained were independently screened for relevance on the bases of title and abstract by 2 researchers. Eventually, 89 articles were included in the analysis. Results The unhealthy Western-style diet is associated with an increased risk of COPD and an accelerated decline of pulmonary function. Intake of fruit, vegetables, dietary fibers, vitamins C and E, polyphenols, and β-carotene were individually associated with lower COPD risk, whereas consumption of processed meat was associated with higher COPD risk. Data on the effect of dietary quality on pulmonary function decline in patients with COPD are limited and inconsistent. Strong evidence for beneficial effects on pulmonary function decline was found only for vitamin D supplementation. Conclusion Considering the increasing burden of COPD, more attention should be given to dietary quality as a modifiable factor in disease development and progression in patients with COPD. Systematic Review Registration PROSPERO registration no. CRD42021240183.

Summary: Introduction: Vitamin D is obtained from dermal synthesis and dietary sources. The serum concentration of 25-hydroxyvitamin D [25(OH)D], may be used to evaluate vitamin D status, and this has been related to different dietary patterns (DPs) in previous studies. The bioavailability of vitamin D may be affected by adiposity. We aimed to investigate the relationship between dietary patterns and serum 25(OH)D in an Iranian population sample with abdominal obesity. Methods: This cross-sectional study was undertaken in 215 adults who were 30–50 years old, and comprised students and employees of Mashhad University of Medical Sciences (MUMS), who had abdominal obesity. Serum 25(OH)D was measured using an enzyme-linked immunoassay method. A 65-item validated food frequency questionnaire (FFQ) and a principal components factor analysis (PCA) method were used to determine major dietary patterns. Results: Two major dietary patterns were identified among the study population using PCA, and were termed “healthy” and “unhealthy”. The healthy dietary pattern was characterized by a high intake of fruits, green leafy vegetables, other vegetables, honey, dairy products, olive oil, nuts, poultry, legumes, and soup and low intake of sugar, tea and solid fats. An unhealthy dietary pattern was characterized by high consumption of carbonated beverages, processed meat, fast foods, snacks, mayonnaise, seafood, red meat, refined grains, pickled foods, coffee, mineral water, potato, liquid fats, and egg. Serum concentrations of 25(OH)D were directly associated with adherence to the healthy dietary pattern (r: 0.170, p

Background Vitamin D is a steroid hormone that exerts its actions through ligation of the vitamin D receptor (VDR), a transcription factor of the nuclear receptor family. VDR has not only physiologic actions in calcium metabolism but also several other cellular effects through extensive binding to the DNA and modification of genome expression. In cancer, it has neoplasia-suppressive effects and various mechanisms of action mediating cancer cell inhibition have been described. Vitamin D deficiency has been linked to increased risk of breast cancer. A role of the vitamin once the disease has been diagnosed is also probable. Methods A systematic review and meta-analysis of studies that report on vitamin D levels (in the form of its main circulating metabolite, 25-hydroxyvitamin D [25-OHD]) in patients with newly diagnosed breast cancer was performed. Outcomes of interest included the levels of serum 25-OHD in patients with breast cancer, those of matched controlled, in studies that included controls, as well as respective percentages of patients and controls with deficient and insufficient 25-OHD levels. Results A total of 25 studies (10 with controls and 15 without controls) provided data on the outcomes of interest. Populations from all continents, besides Australia, were represented in the studies. The mean level of 25-OHD in patients with breast cancer was 26.88 ng/mL (95% CI 22.8–30.96 ng/mL) and the mean level of 25-OHD in control patients was 31.41 ng/mL (95% CI 19.31–43.5 ng/mL). In the patients with breast cancer group, 45.28% (95% CI 24.37%–53.51%) had levels of 25-OHD below 20 ng/mL, whereas this percentage was 33.71% (95% CI 21.61%–45.82%) in controls. Similarly, 67.44% (95% CI 48.32%–86.55%) of patients with breast cancer had a baseline level of 25-OHD below 30 ng/mL, whereas this percentage was 33.71% (95% CI 21.61%–45.82%) in controls. Conclusion A high prevalence of vitamin D insufficiency is observed in patients with newly diagnosed breast cancer and may be linked pathophysiologically with breast cancer development or progression. Therapeutic benefits may be provided by manipulation of the vitamin D pathway in breast cancer.

Background: Worldwide, vitamin D deficiency is a public health issue and the prevalence of obesity and non-alcoholic fatty liver disease (NAFLD) are rapidly increasing. There are a limited number of studies assessing the association between serum levels of 25-hydroxyvitamin D (25(OH)D) and NAFLD risk in obese population. Objective: We evaluated the associations between serum 25(OH)D levels and risk of suspected NAFLD after stratification by obesity using data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2008–2014. Methods: This study included 25,755 subjects without significant alcohol consumption for the serum alanine aminotransferase (ALT) and hepatic steatosis index (HSI) analyses (8922 subjects for the serum gamma-glutamyl transferase (GGT) and fatty liver index (FLI) analyses), based on a cross-sectional study design. Serum 25(OH)D levels were measured using a Gamma counter with radioimmunoassay. A survey logistic regression model was applied to estimate ORs and 95% CIs. Restricted cubic smoothing splines were applied to evaluate nonlinear associations. Results: The risk of suspected NAFLD was reduced per unit of natural log-transformed serum 25(OH)D concentration in obese individuals (OR [95% (CI)], for ALT, 0.80 [0.67, 0.96], for GGT, 0.70 [0.49, 0.99, for FLI, 0.68 [0.47, 1.01], for HSI, 0.70 [0.56, 0.87]). The ORs [95% CI] of suspected NAFLD changed across the quartiles: for serum ALT, from 1.02 [0.85, 1.23] to 0.72 [0.59, 0.87], for serum GGT, from 0.79 [0.56, 1.13] to 0.64 [0.44, 0.92], for FLI, from 0.98 [0.67, 1.44] to 0.70 [0.48, 1.02], and for HSI, from 0.91 [0.73, 1.14] to 0.65 [0.52, 0.81] with dose–response relationships (all p for trend &lt, 0.01). Conclusions: This study suggests that vitamin D sufficiency for public health should be emphasized in order to prevent adverse health effects in obese populations.

One in five Canadians are first-generation immigrants. Evidence suggests the baseline risk for vitamin D (vitD) deficiency is increased among immigrants who move from equatorial to northern countries. We investigated the prevalence and determinants of vitD deficiency/insufficiency among first-generation immigrants compared with native-born Canadians and identified explanatory covariables. We used a cross-sectional design with data from the national Canadian Health Measures Survey (Cycles 3 and 4) (11,579 participants aged 3–79 years). We assessed serum 25-hydroxyvitamin D (S-25(OH)D) levels, sociodemographic and environmental factors, immigration status, length of time in Canada, vitD-rich food intake, ethnicity, and place of birth. Immigrants had lower mean S-25(OH)D than non-immigrants (51.23 vs. 62.72 nmol/L, p &lt, 0.001). Those with younger age at the time of immigration (&lt, 18 years) had a high risk for low vitD, and S-25(OH)D levels increased with the length of time they had lived in Canada. The highest deficiency levels were in immigrants born in Morocco, India, and Lebanon compared with native-born Canadians. Ethnicity was the factor most strongly associated with S-25(OH)D. Compared with the white ethnic grouping, the Japanese had the highest level of vitD deficiency, followed by Arabs and Southeast Asians. Ethnic variations, dietary intake, and lifestyle factors are the main predictors of/explanatory factors for vitD status among Canadian immigrants.

ContextSingle nucleotide polymorphisms (SNPs) of the vitamin D binding protein encoding the GC (group component) gene affect 25-hydroxyvitamin D (25OHD) concentrations, but their influence on vitamin D status and response to vitamin D supplementation in infants is unknown.ObjectiveTo study GC genotype–related differences in 25OHD concentrations and the response to supplementation during a vitamin D intervention study in infants.DesignIn this randomized controlled trial, healthy term infants received vitamin D3 (10 or 30 μg/d) from 2 weeks to 24 months of age. GC SNPs rs2282679, rs4588, rs7041, and rs1155563 were genotyped. rs4588/7041 diplotype and haplotypes of rs2282679, rs4588, and rs7041 (Haplo3SNP) and of all four SNPs (Haplo4SNP) were determined.Main Outcome Measures25OHD measured in cord blood at birth and at 12 and 24 months during intervention.ResultsA total of 913 infants were included. Minor allele homozygosity of all studied GC SNPs, their combined haplotypes, and rs4588/rs7041 diplotype 2/2 were associated with lower 25OHD concentrations at all time points in one or both intervention groups [analysis of covariance (ANCOVA) P < 0.043], with the exception of rs7041, which did not affect 25OHD at birth. In the high-dose supplementation group receiving 30 μg/d vitamin D3, but not in those receiving 10 µg/d, genotype of rs2282679, rs4588, and rs7041; diplotype; and Haplo3SNP significantly affected intervention response (repeated measurement ANCOVA Pinteraction < 0.019). Minor allele homozygotes had lower 25OHD concentrations and smaller increases in 25OHD throughout the intervention.ConclusionsIn infants, vitamin D binding protein genotype affects 25OHD concentration and efficiency of high-dose vitamin D3 supplementation.

Clinical assessment of arterial stiffness relies on noninvasive measurements of regional pulse wave velocity or local distensibility. However, arterial stiffness measures do not discriminate underlying changes in arterial wall constituent properties (e.g., in collagen, elastin, or smooth muscle), which is highly relevant for development and monitoring of treatment. In arterial stiffness in recent clinical-epidemiological studies, we systematically review clinical-epidemiological studies (2012–) that interpreted arterial stiffness changes in terms of changes in arterial wall constituent properties (63 studies included of 514 studies found). Most studies that did so were association studies (52 of 63 studies) providing limited causal evidence. Intervention studies (11 of 63 studies) addressed changes in arterial stiffness through the modulation of extracellular matrix integrity (5 of 11 studies) or smooth muscle tone (6 of 11 studies). A handful of studies (3 of 63 studies) used mathematical modeling to discriminate between extracellular matrix components. Overall, there exists a notable gap in the mechanistic interpretation of stiffness findings. In constitutive model-based interpretation, we first introduce constitutive-based modeling and use it to illustrate the relationship between constituent properties and stiffness measurements (“forward” approach). We then review all literature on modeling approaches for the constitutive interpretation of clinical arterial stiffness data (“inverse” approach), which are aimed at estimation of constitutive properties from arterial stiffness measurements to benefit treatment development and monitoring. Importantly, any modeling approach requires a tradeoff between model complexity and measurable data. Therefore, the feasibility of changing in vivo the biaxial mechanics and/or vascular smooth muscle tone should be explored. The effectiveness of modeling approaches should be confirmed using uncertainty quantification and sensitivity analysis. Taken together, constitutive modeling can significantly improve clinical interpretation of arterial stiffness findings.

ObjectiveMaternal vitamin D level in pregnancy may have implications for both the mother and fetus. Deficiency of vitamin D has been linked to several pregnancy complications and fetal skeletal health. Smoking has been associated with reduced serum level of the vitamin D metabolite, 25-hydroxyvitamin D (25(OH)D).DesignA nested case–control study within the Finnish Maternity Cohort, a population-based cohort which includes first-trimester sera from 98 % of pregnancies in Finland since 1987. The selection consisted of women with uncomplicated pregnancies. We studied serum concentration of 25(OH)D in 313 non-smoking and forty-six self-reported smoking pregnant women.SettingWe hypothesize that pregnant smokers may have an increased risk of low 25(OH)D levels especially during winter months.ParticipantsA control group from an unpublished pregnancy complication study consisting of 359 uncomplicated pregnancies. Individuals who reported that they do not smoke were considered ‘non-smokers’ (n 313) and those who reported continued smoking after the first trimester of pregnancy were considered ‘smokers’ (n 46).ResultsSmokers had significantly lower levels of 25(OH)D irrespective of sampling time (PConclusionsExpectant mothers who smoke have an increased risk of vitamin D deficiency during low sun-exposure months in northern regions. Further studies are needed to assess the associated risks for maternal and fetal health as well as possible long-term implications for the infant.

Summary The association between serum 25-hydroxyvitamin D level and post-fracture mortality indicates beneficial relatively high serum 25-hydroxyvitamin D concentrations. A 1-year cohort study on 245 hip fracture patients in Finland indicated the lowest 3-year mortality and highest survival among patients with serum 25-hydroxyvitamin D level of 50–74 nmol/L. Purpose To explore pre-fracture serum 25-hydroxyvitamin D level as a factor associated with post-fracture survival among a cohort of hip fracture patients in Finland. Methods A prospectively collected cohort of hip fracture patients (n = 245, 70% women) from two hospitals was followed for 3.2 post-hip fracture years. Serum 25-hydroxyvitamin D was measured in admission to the hospital and classified

Vitamin D, sunshine and UVB phototherapy were first reported in the early 1900s to control psoriasis, cure rickets and cure tuberculosis (TB). Vitamin D also controlled asthma and rheumatoid arthritis with intakes ranging from 60,000 to 600,000 International Units (IU)/day. In the 1980s, interest in treating psoriasis with vitamin D rekindled. Since 1985 four different oral forms of vitamin D (D2, D3, 1-hydroxyvitaminD3 (1(OH)D3) and 1,25-dihydroxyvitaminD3 (calcitriol)) and several topical formulations have been reported safe and effective treatments for psoriasis—as has UVB phototherapy and sunshine. In this review we show that many pre-treatment serum 25(OH)D concentrations fall within the current range of normal, while many post-treatment concentrations fall outside the upper limit of this normal (100 ng/mL). Yet, psoriasis patients showed significant clinical improvement without complications using these treatments. Current estimates of vitamin D sufficiency appear to underestimate serum 25(OH)D concentrations required for optimal health in psoriasis patients, while concentrations associated with adverse events appear to be much higher than current estimates of safe serum 25(OH)D concentrations. Based on these observations, the therapeutic index for vitamin D needs to be reexamined in the treatment of psoriasis and other diseases strongly linked to vitamin D deficiency, including COVID-19 infections, which may also improve safely with sufficient vitamin D intake or UVB exposure.

Recent evidence suggests that breastfeeding may increase the risk of vitamin D deficiency in offspring. However, it is unclear whether increased risk results from breastfeeding alone, or whether it is associated together with other risk factors. This study surveyed 208 infant–mother dyads recruited by stratified random sampling in different districts of Hong Kong. Mothers were asked to complete a questionnaire on their demographics, history of risk behavior, and feeding practices. Peripheral blood samples were collected from infants to determine their vitamin D status. Among all infant participants, 70 were vitamin D insufficient or deficient. Being breastfed, being a girl, having a multiparous mother, and the use of sun cream were found to be the strongest risk factors for vitamin D insufficiency during infancy (all p &lt, 0.05), after mutual adjustment. The cumulative risk model displayed a dose–response pattern between the number of risk factors and the risk of vitamin D insufficiency during this period. Our findings indicate the risk profile of infants with insufficient vitamin D. Guidelines and recommendations on healthy diet and lifestyle should be provided to mothers during the early stage of pregnancy to increase the likelihood of adequate levels of vitamin D in their offspring.

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: During the coronavirus disease 2019 (COVID-19) pandemic, the implementation of social distancing and home confinement measures may elevate the risk of vitamin D deficiency particularly for infants. This study aimed to quantify changes in vitamin D level among infants and toddlers in Hong Kong after the COVID-19 outbreak. Methods: We recruited 303 infants and toddlers aged 2–24 months by stratified random sampling from 1 June 2019 to November 30, 2020. Regression models were used to estimate the effect of time on infants’ serum 25-hydroxyvitamin D (25(OH)D) level overall and by age groups before and after the outbreak. Interrupted time series (ITS) analysis was performed to examine the sustained effect of COVID-19 on their serum 25(OH)D level. Results: The ITS results showed no immediate reduction in serum 25(OH)D level among infants, but a decreasing trend was observed in the subsequent months post-outbreak at a monthly decline rate of −6.32 nmol/L. When analyzed by age group, the magnitude of post-outbreak reduction in 25(OH)D was stronger among younger infants (aged 2–6 months). Conclusion: Guidelines and recommendations should be given to pregnant women and mothers to ensure sufficient vitamin D level in their infants during the COVID-19 period.

Hypovitaminosis D has been linked to several non-bone diseases. Relation between 25-hydroxyvitamin D [25(OH)D] and lung function and lung diseases has received little attention at the global level. Cross-sectional data from three National Health and Nutrition Examination Surveys, 2007–2008, 2009–2010, and 2011–2012 were used to investigate the relationship between serum 25(OH)D concentrations and lung function makers [forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)] and lung diseases (asthma, emphysema, and chronic bronchitis) with multivariate regression models (n = 11,983; men, 6,010; women, 5,973). Serum 25(OH)D concentrations were directly associated with FVC and FEV1 (P for trend

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.

ObjectiveTo investigate serum 25-hydroxyvitamin D (S-25(OH)D) concentration in a multi-ethnic population of northern Norway and determine predictors of S-25(OH)D, including Sami ethnicity.DesignCross-sectional data from the second survey of the Population-based Study on Health and Living Conditions in Regions with Sami and Norwegian Populations (the SAMINOR 2 Clinical Survey, 2012–2014). S-25(OH)D was measured by the IDS-iSYS 25-Hydroxy Vitamin Dˢ assay. Daily dietary intake was assessed using an FFQ. BMI was calculated using weight and height measurements.SettingTen municipalities of northern Norway (latitude 68°–70°N).ParticipantsMales (n 2041) and females (n 2424) aged 40–69 years.ResultsMean S-25(OH)D in the study sample was 64·0 nmol/l and median vitamin D intake was 10·3 µg/d. The prevalence of S-25(OH)DConclusionsThere were many modifiable risk factors related to S-25(OH)D, however no clear ethnic differences were found. Even in winter, the low prevalence of vitamin D deficiency found among participants with non-Sami, multi-ethnic Sami and Sami self-perceived ethnicity was likely due to adequate vitamin D intake.

Smell and taste decline with aging, and markedly deteriorate when nutritional deficiencies occur. This study aims to examine the associations between Vitamin D (VD) deficiency and smell and taste impairments among adults. This paper details a cross-sectional study utilizing data from the US National Health and Nutrition Examination Survey (NHANES, 2013&ndash, 2014.). Smell impairment was assessed by the Pocket Smell Test and defined as failing to correctly identify six or more of the eight odors. Taste impairment was defined as failing to correctly identify quinine or sodium chloride. VD was measured as serum 25-hydroxyvitamin. Multivariable weighted logistic regressions were utilized. Adjusted odds ratio (OR) and 95% confidence interval (CI) were presented. Overall, 2216 (smell sample) and 2636 (taste sample) participants were included, aged between 40 and 80 years old. Of those, 18.3% had taste impairment, 12.2% had smell impairment, and 20% had VD deficiency (&lt, 20 ng/mL). Compared to participants with sufficient VD (&gt, 30 ng/mL), those with VD deficiency were more likely by 39% to report a higher prevalence of smell impairment (OR = 1.39, 95%CI: 1.02&ndash, 1.89), and only participants aged 70&ndash, 80 years with VD inadequacy (20&ndash, 30 ng/mL) were more likely by 96% to report a higher prevalence of taste impairment (OR = 1.96, 95%CI: 1.35&ndash, 1.85). VD may have a significant role in age-related smell impairment in adults aged 40 years or older, and in age-related taste impairment in the elderly aged 70&ndash, 80 years.

Background The incidence of osteoporotic fractures has increased rapidly, and because of the poor prognosis and high mortality associated with osteoporotic fractures, they remain a prospective research area globally. One way to reduce their incidence is to investigate their intervention risk factors in the elderly. Hence, this study explores the correlation between serum 25-hydroxyvitamin D [25(OH)D] levels and osteoporotic fractures in elderly patients through a meta-analysis. Methods We conducted our literature search mainly in PubMed and Embase for identifying studies that investigated the relationship between serum 25(OH)D levels and the risk for osteoporotic fractures. We performed categorical analysis, heterogeneity checks, publication bias analysis, and subgroup analyses. Results In total, 20 studies were included, of which 4 were case-cohort studies and 16 were cohort studies. A total of 41,738 patients from 20 studies were included in the meta-analysis, of which 5916 had fractures, including 3237 hip fractures. By combining the lowest and highest categories of relative risks (RRs) and 95% confidence intervals (CIs), it was suggested that lower serum 25-hydroxyvitamin D levels may be a risk factor for fractures. RR (95% CI) for total and hip fractures were 1.11 (0.99, 1.24) and 0.89 (0.80, 0.98) after adjustments. Conclusions Our study showed that compared to low serum 25(OH)D levels, high serum 25(OH)D levels reduce the risk of hip fractures in the patients aged 60 years or older. In contrast, serum 25(OH)D has no significant relationship with total fracture risk.

Background: Although animal studies show evidence for a role of vitamin D during brain development, data from human studies show conflicting signals. Objective: We aimed to explore associations between maternal and neonatal vitamin D status with childhood neurodevelopmental outcomes. Methods: Comprehensive clinical, demographic, and lifestyle data were collected prospectively in 734 maternal-infant dyads from the Cork BASELINE Birth Cohort Study. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were quantified at 15 weeks of gestation and in umbilical cord sera at birth via a CDC-accredited liquid chromatography-tandem mass spectrometry method. Children were assessed at age 5 y through the use of the Kaufman Brief Intelligence Test (2nd Edition, KBIT-2) and the Child Behaviour Checklist (CBCL). Linear regression was used to explore associations between 25(OH)D and neurodevelopmental outcomes. Results: 25(OH)D concentrations were

BACKGROUND Vitamin D has been suggested to affect peripheral insulin sensitivity. Evidence regarding the effect of vitamin D supplementation on insulin sensitivity is still conflicting. PURPOSE This meta-analysis aimed to assess the effect of vitamin D supplementation on insulin sensitivity in humans with or at risk for insulin resistance. DATA SOURCES AND STUDY SELECTION PubMed, Web of Science, Embase, CINAHL, and Cochrane Library were systematically searched for randomized controlled trials (RCTs) from 1980 until 31 December 2018 reporting treatment effects of vitamin D supplementation on insulin sensitivity. DATA EXTRACTION The main outcome of interest was the change in insulin sensitivity, derived from the gold standard hyperinsulinemic-euglycemic clamp or the Matsuda index derived from the oral glucose tolerance test and insulin sensitivity index from intravenous glucose tolerance test. We extracted data on the standardized mean difference between the vitamin D treatment and placebo groups in change from baseline insulin sensitivity. DATA SYNTHESIS Eighteen RCTs were included in this meta-analysis comparing vitamin D supplementation (n = 612) with placebo (n = 608). Vitamin D supplementation had no effect on insulin sensitivity (standardized mean difference −0.01, 95% CI −0.12, 0.10; P = 0.87, I2 = 0%). Visual inspection of funnel plot symmetry did not suggest potential publication bias. LIMITATIONS The number of individuals who participated in the included studies was relatively small, possibly due to the invasive character of the measurement (e.g., clamp). CONCLUSIONS This meta-analysis provides no evidence that vitamin D supplementation has a beneficial effect on peripheral insulin sensitivity in people with or at risk for insulin resistance.

Background Vitamin D deficiency has been shown to be closely associated with peritoneal dialysis (PD)-related peritonitis. The aim of this study is to examine the feasibility of conducting a large, powered randomized controlled trial to determine the effects of vitamin D supplementation on the risk of PD-related peritonitis in patients who have already experienced an episode of peritonitis. Methods This prospective, open-label randomized controlled pilot trial with blinded end-points aims to determine the feasibility of oral vitamin D supplementation and to explore its effects on the risk of subsequent PD-related peritonitis among PD patients who have recovered from a recent episode of peritonitis. Eligible patients will be randomized 1:1 to either oral vitamin D supplementation (2000 IU per day; intervention group) or no vitamin D supplementation (control group) in addition to usual care according to International Society for Peritoneal Dialysis guidelines. The sample size will be 30 patients for both groups. All participants will be followed for 12 months. The primary outcome is the assessment of feasibility (recruitment success, retention, adherence, safety) and fidelity (change in serum 25-hydroxyvitamin D level during follow-up) for a large, powered randomized controlled trial to determine the effects of vitamin D on the risk of PD-related peritonitis in the future. Secondary outcomes include time to peritonitis occurrence, recovery of peritonitis, peritonitis-related transition to hemodialysis, and peritonitis-related death (defined as death within 30 days of peritonitis onset). Discussion This is the first randomized controlled trail investigating the effects of vitamin D supplementation on the risk of subsequent PD-related peritonitis among patients on PD. The findings for this pilot study will determine the feasibility of conducting a full-scale randomized controlled trail, which may provide a new strategy for preventing PD-related peritonitis among PD patients. Trial registration Clinicaltrails.gov, NCT03264625. Registered on 29 August 2017.

Highlights • Hypovitaminosis D is prevalent in Saudi women with polycystic ovarian syndrome (PCOS). • Serum 25(OH)D of PCOS patients were correlated positively with adiponectin and FSH. • Serum 25(OH)D of PCOS patients was correlated negatively with markers of insulin resistance. • Serum 25(OH)D of PCOS patients was correlated negatively with follistatin, LH, and androgens. • Hypovitaminosis D, with low adiponectin and excess follistatin, is being a risk in PCOS., Aims The association between vitamin D and polycystic ovary syndrome (PCOS) is an active area of growing research. However, data in Saudi Arabia are scarce. This study aimed to define serum 25-hydroxyvitamin D (25(OH)D) levels among Saudi women with naïve PCOS, and to investigate the associations of their 25(OH)D status with their serum adiponectin and follistatin levels, along with indices of insulin resistance and hormonal deteriorations. Methods In this case-control observational study, 63 women with PCOS and 65 age-and body mass index (BMI)-matched control women were assessed. PCOS was diagnosed based on the revised criteria of Rotterdam. Fasting serum levels of 25(OH)D, adiponectin, follistatin, insulin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), androgen (Δ4-androstenedione), estradiol, progesterone, along with fasting plasma glucose (FPG), homeostasis model assessment-insulin resistance (HOMA-IR) index and lipid profile were measured in both groups. Results The prevalence of hypovitaminosis D (serum 25(OH)D

Background: Vitamin D is associated with musculoskeletal function in our body, and its deficiency is a common health problem all over the world. Low back pain (LBP) is an important health problem in terms of low quality of life, loss of work power, and cost of diagnosis and treatment approaches. Aims: The purpose of this study is to investigate the relationship between pain severity and Vitamin D deficiency in patients who applied to pain polyclinic with LBP. Settings and Design: This was a retrospective, observational study. Subjects and Methods: The files of patients aged between 18 and 70 years who applied to our hospital between January and February 2018 were examined retrospectively by a specialist. Serum 25-hydroxyvitamin D (25(OH)D) level, Visual Analogue Scale (VAS), age, education level, marital status, working status, and body mass index (BMI) values recorded in patient files were included in the study. The limit value of Vitamin D was accepted as 20 ng/mL. Patients were divided into two groups according to their levels of Vitamin D. Patients with serum 25(OH)D levels below 20 ng/mL were considered as the deficiency of Vitamin D (Group 1) and patients with 20 ng/mL and over 20 ng/mL values were considered as normal in terms of Vitamin D (Group 2). Statistical Analysis Used: Descriptive statistical data were presented as mean, standard deviation, numbers, and percentage. There was no difference between the normally distributed group and the non-normally distributed group in terms of vitamin D levels. To compare the frequencies, the Chi-square test was used. To define the linear association between independent variables and Vitamin D level, Spearman's rho correlation coefficients were calculated. Results: The level of Vitamin D was measured in 98 patients aged 18–70 years who applied to our hospital's polyclinic due to LBP during the study period. The deficiency of vitamin was detected in 84 (85.7%) of the patients, while Vitamin D was found in 14 (14.3%) as normal. Groups were similar in terms of age, gender, BMI, educational level, marital status and working status (p> 0.05); however, there was a statistically significant difference between the two groups in terms of VAS score and levels of Vitamin D (P < 0.001 and P < 0.001, respectively). While there was a negative correlation between D vitamin level and VAS score (r = −0.594, P < 0.001), there was no correlation between age, gender, BMI, education level, marital status, and working status (P > 0.05). Conclusions: The deficiency of Vitamin D is often asymptomatic, and also, it can cause bone and muscle pain. In our study, we determined that the severity of pain increased in patients with LBP as the deficiency of Vitamin D increased. For this reason, we recommend to be evaluated the level of Vitamin D in patients with LBP.

Background: Vitamin D supplementation is proposed as a potential treatment strategy to counteract functional decline in older adults. However, data from randomized trials are either limited or inconsistent. Objective: This study investigated the effect of daily supplementation with 25-hydroxycholecalciferol [25(OH)D3] or cholecalciferol (vitamin D3) on muscle strength and physical performance in older adults. Methods: This was a randomized, double-blind, placebo-controlled trial of 6 mo including 78 prefrail or frail (according to the Fried criteria), community-dwelling older adults (n = 43 men) aged ≥65 y, with a baseline 25-hydroxyvitamin D [25(OH)D] concentration between 20 and 50 nmol/L. Participants were supplemented daily with 10 µg 25(OH)D3, 20 µg vitamin D3, or a placebo capsule. Serum 25(OH)D was measured by liquid chromatography–tandem mass spectrometry. The primary outcome was maximal isometric knee-extension strength (Biodex System 4); secondary outcomes included knee-flexion and hand grip strength, Short-Physical Performance Battery score, Timed Up and Go score, postural sway, muscle mass (dual-energy X-ray absorptiometry), and muscle fiber type and size. Results: The mean baseline serum 25(OH)D concentration was 37.7 nmol/L (95% CI: 35.4, 39.9 nmol/L). After 6 mo of supplementation, concentrations increased to 98.7 nmol/L (95% CI: 93.1, 104.4 nmol/L) in the 25(OH)D3 group and to 72.0 nmol/L (95% CI: 66.1, 77.8 nmol/L) in the vitamin D3 group, compared with 47.5 nmol/L (95% CI: 41.8, 53.3 nmol/L) in the placebo group (P-interaction < 0.01). Knee-extension strength did not significantly change in the 25(OH)D3group (5.9 Nm; 95% CI: −6.2, 18.0 Nm), in the vitamin D3 group (5.5 Nm; 95% CI: −6.8, 17.8 Nm), or in the placebo group (1.8 Nm; 95% CI: −10.7, 14.4 Nm) (P-interaction = 0.74). Furthermore, mean changes in physical performance tests, muscle mass, and muscle fiber type and size did not differ between the groups. Conclusion: Increasing the serum 25(OH)D concentration over a period of 6 mo did not significantly change muscle strength and physical performance in prefrail and frail older adults. This trial was registered at www.clinicaltrials.gov as NCT02349282.

ObjectiveTo understand the relationship between vitamin D intake and serum 25-hydroxyvitamin D (25(OH)D) levels in a sample of Portuguese adolescents.DesignCross-sectional evaluation carried out in the 2003/2004 school year. Vitamin D intake was assessed by an FFQ and 25(OH)D was measured in a fasting blood sample.SettingPublic and private schools in Porto, Portugal.SubjectsAdolescents aged 13 years (n 521) enrolled at school (EPITeen cohort).ResultsBoth mean (sd) intake and serum 25(OH)D level were far below the recommended, 4·47 (2·49) µg/d and 16·5 (5·7) ng/ml, respectively. A significant difference in serum level was found according to season, with lower values in winter than summer (14·8 (4·6) v. 17·3 (5·9) ng/ml, P<0·001). Vitamin D intake was weakly correlated with serum 25(OH)D (r=0·056, P=0·203).ConclusionsDietary vitamin D and serum 25(OH)D levels were positively but weakly correlated and the error was higher among those with higher serum 25(OH)D concentration. Our results support the need for strategies that promote increase of the most important food sources of vitamin D to reduce the high prevalence of low vitamin D status.

// Qing-Bo Lv 1 , Xiang Gao 1 , Xiang Liu 1 , Zhen-Xuan Shao 1 , Qian-Hui Xu 1 , Li Tang 1 , Yong-Long Chi 1 and Ai-Min Wu 1 1 Department of Orthopedics, Bone Research Institute, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Second Medical School of Wenzhou Medical University, Wenzhou, Zhejiang, China Correspondence to: Ai-Min Wu, email: // Keywords : serum 25-hydroxyvitamin D, hip fracture, meta-analysis, dose-response Received : December 14. 2016 Accepted : February 13, 2017 Published : March 17, 2017 Abstract Hip fracture has increasingly become a social and economic burden. The relationship between serum 25-hydroxyvitamin D levels and the risk of hip fracture reported by previous studies remains controversial. We searched Pubmed and Embase to identify studies reporting the relationship between serum 25-hydroxyvitamin D levels and risk of hip fracture. Fifteen prospective cohort studies with a total of 51239 participants and 3386 hip fracture cases were included. By pooling the Relative Risk of the lowest vs. the highest categories indicated that lower levels of serum 25-hydroxyvitamin D were more likely to be a risk factor for hip fracture with adjusted Relative Risk (95%Confidence Interval) of 1.58 (1.41, 1.77). Subgroup meta-analysis examining the stability of the primary results achieved the same results. A dose-response meta-analysis showed that the risk of hip fracture was a descending curve below the line of RR=1. The descending trend was obvious when serum 25-hydroxyvitamin D levels were less than 60 nmol/L and was flat when serum 25-hydroxyvitamin D levels were more than 60 nmol/L. We found that individuals with low levels of serum 25-hydroxyvitamin D have an increased risk of hip fracture, and this effect was evident when the serum 25-hydroxyvitamin D levels were less than 60 nmol/L.

Vitamin D is important for bone mass accrual during growth. Additionally, it is considered a requirement for a multitude of processes associated with, for example, the development of immunity. Many countries apply vitamin D supplementation strategies in infants, but the guidelines are not based on scientific evidence and aim at prevention of rickets. It remains unclear whether the recommended doses are sufficient for the wide array of other effects of vitamin D. The VIDI trial performed in Finland is the first large randomised controlled study for evaluation of the effects of different vitamin D supplemental doses in infancy on: VIDI, a randomised controlled double-blinded single-centre intervention study is conducted in infants from the age of 2 weeks to 24 months. Participants, recruited at Helsinki Maternity Hospital, are randomised to receive daily either 10 μg (400 IU) or 30 μg (1 200 IU) of vitamin D3 supplementation. Both groups are assessed at 6 months of age for calcium homeostasis, and at 12 and 24 months of age for parameters associated with bone strength, growth, developmental milestones, infections, immunity, atopy-related diseases, and genetic factors involved in these functions. The study enables evaluation of short and long term effects of supplemental vitamin D on growth, immune functions and skeletal and developmental parameters in infants, and the effects of genetic factors therein. The results enable institution of evidence-based guidelines for vitamin D supplementation in infancy. ClinicalTrials.gov, NCT01723852 , registration date 6.11.2012.

PURPOSE To investigate the relationship between vitamin D and glaucoma. METHODS This retrospective, cross-sectional study included subjects who underwent a health screening at the Health Screening Center of Kangbuk Samsung Hospital from August 2012 to July 2013. All fundus photographs were reviewed by ophthalmologists. The ophthalmologists determined if an eye was glaucomatous based on the criteria set forth by the International Society of Geographical and Epidemiological Ophthalmology and by the appearance of the retinal nerve fiber layer and optic disc. If the subjects previously underwent an ophthalmologic examination, they were enrolled based on the documented history. In addition to fundus photographs, each participant underwent a systemic examination including blood sampling and sociodemographic and behavioral questionnaires. The subjects were divided into five groups according to serum 25-hydroxyvitamin D (25(OH)D) level. Multivariate logistic regression models were constructed to assess possible associations between elevated glaucoma risk and systemic factors with a p < 0.2 on univariate analysis. RESULTS Of the 169,208 subjects older than 20 years, 123,331 were eligible for the study. There was no difference in the prevalence of glaucoma according to quintile of serum 25(OH)D level based on sex (p = 0.412 for males, p = 0.169 for females). According to the multivariable-adjusted logistic analysis, the odds ratio of glaucoma for the fourth quintile was significantly lower than that of the first quintile in females (odds ratio, 0.713; 95% confidence interval, 0.520 to 0.979). CONCLUSIONS Lower 25(OH)D level was significantly associated with an elevated risk of glaucoma in females compared with higher 25(OH)D level. Further evaluation is needed to investigate the relationship between glaucoma and vitamin D.

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.

Purpose To assess the possible association between keratoconus (KC) and serum levels of 25-hydroxyvitamin D (25OHD), Selenium (Se), Zinc (Zn), and Copper (Cu) and to compare it with age-matched healthy subjects. Methods One hundred patients with KC and 100 normal subjects were included. The two groups were compared for serum 25OHD and serum levels of three trace elements: Se, Zn, and Cu. These factors were also compared between groups with different KC stages. Results Serum levels of vitamin D, Zn, Cu, and Se were significantly different between the KC and normal groups (P = 0.006, P = 0.015, P = 0.004, and P = 0.038, respectively). Although a lower level of 25OHD was found in severe stages of KC, it was not significantly different among different KC groups (P = 0.441). KC stage groups were not significantly different for mean serum Zn, Cu, and Se (P = 0.130, P = 0.98, P = 0.113, respectively). Although the Cu/Zn ratio was higher in cases than in controls, there was no significant difference between the two groups and between KC stages (P = 0.168, P = 0.143, respectively). Conclusion Lower serum 25OHD, Cu, Zn, and Se were found in the KC group compared to the control group. The results of this study suggest that a lower antioxidative activity may be involved in the possible etiology of KC.

Previous prospective studies assessing the relationship between circulating concentrations of vitamin D and prostate cancer risk have shown inconclusive results, particularly for risk of aggressive disease. In this study, we examine the association between prediagnostic concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and the risk of prostate cancer overall and by tumor characteristics. Principal investigators of 19 prospective studies provided individual participant data on circulating 25(OH)D and 1,25(OH)2D for up to 13,462 men with incident prostate cancer and 20,261 control participants. ORs for prostate cancer by study-specific fifths of season-standardized vitamin D concentration were estimated using multivariable-adjusted conditional logistic regression. 25(OH)D concentration was positively associated with risk for total prostate cancer (multivariable-adjusted OR comparing highest vs. lowest study-specific fifth was 1.22; 95% confidence interval, 1.13–1.31; P trend < 0.001). However, this association varied by disease aggressiveness (Pheterogeneity = 0.014); higher circulating 25(OH)D was associated with a higher risk of nonaggressive disease (OR per 80 percentile increase = 1.24, 1.13–1.36) but not with aggressive disease (defined as stage 4, metastases, or prostate cancer death, 0.95, 0.78–1.15). 1,25(OH)2D concentration was not associated with risk for prostate cancer overall or by tumor characteristics. The absence of an association of vitamin D with aggressive disease does not support the hypothesis that vitamin D deficiency increases prostate cancer risk. Rather, the association of high circulating 25(OH)D concentration with a higher risk of nonaggressive prostate cancer may be influenced by detection bias. Significance: This international collaboration comprises the largest prospective study on blood vitamin D and prostate cancer risk and shows no association with aggressive disease but some evidence of a higher risk of nonaggressive disease.

An increasing aging population worldwide accounts for a growing share of noncommunicable diseases (NCDs) of the overall social and economic burden. Dietary and nutritional approaches are of paramount importance in the management of NCDs. As a result, nutrition programs are increasingly integrated into public health policies. At present, programs aimed at reducing the burden of NCDs have focused mostly on the excess of unhealthy nutrient intakes whereas the importance of optimizing adequate essential and semi-essential nutrient intakes and nutrient-rich diets has received less attention. Surveys indicate that nutrient intakes of the aging population are insufficient to optimally support healthy aging. Vitamin and mineral deficiencies in older adults are related to increased risk of NCDs including fatigue, cardiovascular disease, and cognitive and neuromuscular function impairments. Reviewed literature demonstrates that improving intake for certain nutrients may be important in reducing progress of NCDs such as musculoskeletal disorders, dementia, loss of vision, and cardiometabolic diseases during aging. Current knowledge concerning improving individual nutrient intakes to reduce progression of chronic disease is still emerging with varying effect sizes and levels of evidence. Most pronounced benefits of nutrients were found in participants who had low nutrient intake or status at baseline or who had increased genetic and metabolic needs for that nutrient. Authorities should implement ways to optimize essential nutrient intake as an integral part of their strategies to address NCDs.

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 and objectives: To examine the frequency of endocrinopathies in children with systemic lupus erythematosus (SLE) and juvenile idiopathic arthritis (JIA). Design and setting: A cross-sectional study. Patients and methods: A study was conducted in Saudi children with SLE and JIA who were seen at King Faisal Specialist Hospital and Research Centre, Riyadh, between September 2013 and April 2015. All enrolled patients completed the clinical evaluation, which included information about family history of autoimmune disease, growth parameters and tanner stage, as well as the following assessments: vitamin D profile (parathyroid hormone and 25-OH vitamin D levels), TSH, FT4 and total T3, thyroglobulin antibodies, thyroperoxidase antibodies, random blood sugar, HbA1C, IGF1, IGFBP-3, LH, and FSH. Results: A total of 42 patients, 22 with JIA and 20 with SLE, were included in the study. The mean participant age was 12.2 ± 5.3 years with a mean disease duration of 3.2 ± 3.4 years. Female gender was predominant (17 SLE, 13 JIA) in the patient population. Fifteen patients (35.7%) presented with a family history of autoimmune disease. The most frequently detected endocrinopathies were vitamin D insufficiency (35%) and thyroid disease (31%). Eight JIA patients and 7 SLE patients exhibited low vitamin D levels; 10 patients presented with hyperparathyroidism. Thyroid dysfunction was observed in 13 patients (8 SLE, 5 JIA), and 2 patients were found to be euthyroid (normal TSH, FT4) with positive thyroid autoantibodies. Furthermore, 7 patients presented with subclinical hypothyroidism (high TSH, normal FT4), and 4 patients presented with overt hypothyroidism (high TSH, low FT4). Seven patients (4 SLE and 3 JIA) presented with short stature due to growth hormone insufficiency (low IGF1, IGFBP-3). Two patients exhibited delayed puberty accompanied by low LH levels. Diabetes mellitus was more frequently observed in patients with JIA (4 patients) than in patients with SLE (1 patient). Conclusion: Our findings demonstrated that coexistence of endocrinopathies is not uncommon in children diagnosed with JIA and SLE. Abnormal thyroid function occurs frequently and at a similar rate in children diagnosed with SLE and JIA. Thus, screening for endocrinopathies, namely thyroid disease, during the assessment of childhood SLE and JIA is worth consideration.

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.

Higher serum 25–hydroxyvitamin D [25(OH)D] concentrations have been associated with lower risk of type 2 diabetes. This study compared incidence rates of type 2 diabetes among participants aged ≥20 years in two U.S. cohorts with markedly different median 25(OH)D concentrations. The median 25(OH)D concentration in the GrassrootsHealth (GRH) cohort was 41ng/ml (N=4933) while in the 2005–6 National Health and Nutrition Examination Survey (NHANES) it was 22ng/ml (N=4078) (P

Low circulating 25-hydroxyvitamin D [25(OH)D] and high sodium intake are both associated with progressive albuminuria and renal function loss in CKD. Both vitamin D and sodium intake interact with the renin-angiotensin-aldosterone system. We investigated whether plasma 25(OH)D or 1,25-dihydroxyvitamin D [1,25(OH)2D] is associated with developing increased albuminuria or reduced renal function and whether these associations depend on sodium intake.Baseline plasma 25(OH)D and 1,25(OH)2D were measured by liquid chromatography tandem mass spectrometry, and sodium intake was assessed by 24-hour urine collections in the general population-based Prevention of Renal and Vascular End-Stage Disease cohort (n=5051). Two primary outcomes were development of urinary albumin excretion30 mg/24 h and eGFR (creatinine/cystatin C-based CKD Epidemiology Collaboration)60 ml/min per 1.73 m(2). Participants with CKD at baseline were excluded. In Cox regression analyses, we assessed associations of vitamin D with developing increased albuminuria or reduced eGFR and potential interaction with sodium intake.During a median follow-up of 10.4 (6.2-11.4) years, 641 (13%) participants developed increased albuminuria, and 268 (5%) participants developed reduced eGFR. Plasma 25(OH)D was inversely associated with increased albuminuria (fully adjusted hazard ratio [HR] per SD higher, 0.86; 95% confidence interval [95% CI], 0.78 to 0.95; P=0.003) but not reduced eGFR (HR, 0.99; 95% CI, 0.87 to 1.12; P=0.85). There was interaction between 25(OH)D and sodium intake for risk of developing increased albuminuria (P interaction =0.03). In participants with high sodium intake, risk of developing increased albuminuria was inversely associated with 25(OH)D (lowest versus highest quartile: adjusted HR, 1.81; 95% CI, 1.20 to 2.73, P0.01), whereas this association was nonsignificant in participants with low sodium intake (HR, 1.29; 95% CI, 0.94 to 1.77; P=0.12). Plasma 1,25(OH)2D was not significantly associated with increased albuminuria or reduced eGFR.Low plasma 25(OH)D is associated with higher risk of developing increased albuminuria, particularly in individuals with high sodium intake, but not of developing reduced eGFR. Plasma 1,25(OH)2D is not associated with risk of developing increased albuminuria or reduced eGFR.

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.

Purpose Ultraviolet-B (UVB) light exposure is the major risk factor for developing a pterygium, and serum 25-hydroxyvitamin D (25(OH)D) level is an objective measure of UVB light exposure. In this study, we investigated the association between pterygium, sun exposure, and serum 25(OH)D. Methods This population-based, cross-sectional study comprised 12,258 adults (aged ≥19 years) participating in the fifth annual Korea National Health and Nutrition Examination Survey from 2010 to 2012. The enrolled subjects underwent interviews, clinical examinations, and laboratory investigations. The serum 25(OH)D levels were measured, and pterygium was examined by using a slit lamp. We used three adjusted logistic regression models and selected covariates as potential confounders. Results The overall prevalence of pterygium was 7.09, and 53.1% of these subjects were women. The prevalence of pterygium was higher in elderly subjects and those who lived at low latitudes. In multivariate analysis with adjustment for confounding factors, subjects with a serum 25(OH)D level > 30 ng/mL, 25–30 ng/mL, and 15–20 ng/mL had an odds ratio (OR) (95% confidence interval [CI]) of 1.565 (1.035–2.366), 1.545 (1.086–2.198), 1.8 (1.358–2.386), and 1.535 (1.216–1.938), respectively, compared to those with a serum 25(OH)D level 5 h had an OR (95% CI) of 1.761 (1.395–2.223) compared to subjects with a daily sun exposure

We assessed the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and community-acquired pneumonia (CAP) among Chinese children. This observational study examined children aged 3 days to 14 years (n = 1582) from the Capital Institute of Pediatrics in 2009 to 2011. There were 797 children in the CAP group and 785 controls. The CAP group was divided into 2 groups: a pneumonia group and pneumonia-induced sepsis group. The serum 25(OH)D level was estimated using micro whole blood chemiluminescence. The average serum 25(OH)D level in all samples was 25.32 ± 14.07 ng/mL, with the CAP group showing a lower value than the control group (P

Evidence indicates that Vitamin D deficiency may be associated with increased risk of cardiovascular disease, although findings on risk of heart failure (HF) are controversial. We investigated the relationship between serum Vitamin D and the incidence of hospitalization for HF in a large prospective cohort of Italian adults.19,092 (49% men, age range 35-99 years) HF-free individuals from the Moli-sani study, with complete data on serum Vitamin D (25-hydroxyvitamin) levels and incident hospitalized HF, were analysed. The cohort was followed up for a median of 6.2 years. Baseline serum Vitamin D levels were categorized in deficient (10 ng/mL), insufficient (10-29 ng/mL), and normal (≥30 ng/mL) Incident cases of hospitalization for HF were identified by linkage with the regional hospital discharge registry. Hazard ratios (HRs) were calculated using Cox-proportional hazard models. The prevalence of normal, insufficient or deficient levels of Vitamin D was 12.2%, 79.6% and 8.2%, respectively. During follow-up, 562 admissions to hospital for HF were identified. The incidence of HF was 1.6%, 2.9% and 5.3%, respectively in subjects with normal, insufficient and deficient levels of Vitamin D. After multivariable analysis, individuals with deficiency of Vitamin D had a higher risk of hospitalization for HF (HR: 1.61, 95%CI: 1.06-2.43) than those with normal levels. Further adjustment for subclinical inflammation did not substantially change the association between Vitamin D deficiency and HF.Deficiency of Vitamin D was associated, independently of known HF risk factors, with an increased risk of hospitalization for HF in an Italian adult population.

Background. The kidney plays a central role in the regulation of vitamin D metabolism. It is not clear, however, whether vitamin D influences kidney function. Previous studies have reported conflicting results, which may have been influenced by reverse causation and residual confounding. We conducted a Mendelian randomization (MR) study to obtain unconfounded estimates of the association between genetically instrumented vitamin D metabolites and estimated glomerular filtration rate (eGFR) as well as the urinary albumin: creatinine ratio (UACR).Methods. We performed a two-sample MR study based on three single nucleotide variants associated with 25(OH)D levels: rs2282679, rs10741657 and rs12785878, related to the genes GC, CYP2R1 and DHCR7, respectively. Estimates of the allele-dependent effects on serum 25(OH)D and eGFR/UACR were obtained from summary statistics of published genome-wide association meta-analyses. Additionally, we performed a one-sample MR analysis for both 25(OH)D and 1,25(OH)2D using individual-level data from six cohorts.Results. The combined MR estimate supported a negative causal effect of log transformed 25(OH)D on log transformed eGFR (beta = -0.013, P = 0.003). The analysis of individual-level data confirmed the main findings and also revealed a significant association of 1,25(OH)2D on eGFR (beta = -0.094, P = 0.008). These results show that a 10% increase in serum 25(OH)D levels causes a 0.3% decrease in eGFR. There was no effect of 25(OH)D on UACR (beta = 0.032, P = 0.265).Conclusion. Our study suggests that circulating vitamin D metabolite levels are negatively associated with eGFR. Further studies are needed to elucidate the underlying mechanisms.

Background: Diabetes is one of the most common diseases around the world and its prevalence is continuously increasing. It is seen that many patients of diabetes with mild cognitive impairment (MCI) have low serum level of Vitamin D. The aim of the study is to identify the correlation between serum levels of 25-hydroxyvitamin D (25(OH)D) and MCI in patients with type 2 diabetes mellitus. This cross-sectional study was conducted at P.B.M. Hospital, Bikaner, Rajasthan, India. Method: In this study, 100 type 2 diabetic patients were enrolled in which 47 were male and 53 were female. For measuring the cognitive impairment in patients, we used montreal cognitive assessment (MoCA) test. After evaluating all the patients with MoCA test, 43 patients were found to have MCI with MoCA score

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.

Study Objectives: Our group and others have reported a high rate of vitamin D deficiency in obstructive sleep apnea (OSA), where vitamin D levels (25(OH) D) correlate negatively with OSA severity and some of its associated metabolic alterations. Data regarding vitamin D supplementation in OSA are lacking. We wanted to evaluate the effect of vitamin D-3 supplementation on OSA symptoms and metabolic parameters. Methods: We conducted a pilot, double-blind, randomized, placebo-controlled trial of daily supplementation with 4,000 IU vitamin D-3 (D3) or placebo (PL). We studied 19 Caucasian adults (14 male, mean age 55 y, mean body mass index [BMI] 30.4 kg/m(2)) with OSA. Fifteen patients were stable on continuous positive airways pressure (CPAP) therapy, whereas four were CPAP naive. Assessments were completed at baseline and after 15 weeks of supplementation. Outcomes included sleepiness (Epworth Sleepiness Scale), quality of life (Sleep Apnea Quality of Life Inventory), fatigue (fatigue severity scale) and neuropsychological function (trail making test and Connor's Continuous Performance Test II). In addition, we assessed biochemical indices of vitamin D status (25(OH)D, calcium), inflammation (high sensitivity C-reactive protein, and lipoprotein- associated phospholipase A2), lipids (total cholesterol [low-density and high-density lipoprotein]) and glycemic indices (fasting glucose, oral glucose tolerance test). Results: There was no change in BMI, medication, or CPAP usage. Although there was no change in neuropsychological or quality of life indices, we observed a significant increase in 25(OH)D (p = 0.00001) and significant decreases in both low-density lipoprotein (p = 0.04) and lipoprotein-associated phospholipase A2 (p = 0.037) as well as trends toward decreased fasting glucose (p = 0.09) and increased high-density lipoprotein (p = 0.07) in the D-3 group compared to PL. Conclusions: Vitamin D-3 supplementation increased vitamin D levels and decreased metabolic markers compared to placebo. Larger trials are required.

Introduction: Optimal vitamin D status promotes skeletal health and is recommended with specific treatment in individuals at high risk for fragility fractures. A growing body of literature has provided indirect and some direct evidence for possible extraskeletal vitamin D-related effects. Purpose and Methods: Members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis have reviewed the main evidence for possible proven benefits of vitamin D supplementation in adults at risk of or with overt chronic extra-skeletal diseases, providing recommendations and guidelines for future studies in this field. Results and conclusions: Robust mechanistic evidence is available from in vitro studies and in vivo animal studies, usually employing cholecalciferol, calcidiol or calcitriol in pharmacologic rather than physiologic doses. Although many cross-sectional and prospective association studies in humans have shown that low 25-hydroxyvitamin D levels (i.e., < 50 nmol/L) are consistently associated with chronic diseases, further strengthened by a dose-response relationship, several meta-analyses of clinical trials have shown contradictory results. Overall, large randomized controlled trials with sufficient doses of vitamin D are missing, and available small to moderate-size trials often included people with baseline levels of serum 25-hydroxyvitamin D levels > 50 nmol/L, did not simultaneously assess multiple outcomes, and did not report overall safety (e.g., falls). Thus, no recommendations can be made to date for the use of vitamin D supplementation in general, parental compounds, or non-hypercalcemic vitamin D analogs in the prevention and treatment of extra-skeletal chronic diseases. Moreover, attainment of serum 25-hydroxyvitamin D levels well above the threshold desired for bone health cannot be recommended based on current evidence, since safety has yet to be confirmed. Finally, the promising findings from mechanistic studies, large cohort studies, and small clinical trials obtained for autoimmune diseases (including type 1 diabetes, multiple sclerosis, and systemic lupus erythematosus), cardiovascular disorders, and overall reduction in mortality require further confirmation.

Objective : Assessment of serum 25-hydroxyvitamin D (25(OH) D) correlations with clinical parameters and evaluation of the efficacy of standard oral supplementation in systemic sclerosis (SSc) patients. Methods : 154 SSc patients were recruited, in all seasons. Serum 25(OH) D concentrations were evaluated using LIAISON 25-OH (Diasorin, Italy). Medsger disease severity scale (DSS), nailfold videocapillaroscopy (NVC) and all instrumental exam contemplated by international guidelines were performed. Drug assumption, including oral colecalciferol, was evaluated. Nonparametric tests were used for statistical analysis. Results : Average 25(OH) D serum concentration was 18.7 +/- 9 ng/ml (

African American men have higher incidence rates of aggressive prostate cancer, where high levels of calcium and serum vitamin D deficient levels play a role in the racial differences in incidence. In this study, we examined associations of serum vitamin D with aggressive prostate cancer to improve our understanding of higher susceptibility of aggressive disease in this racial cohort. From Howard University Hospital, 155 African American men with clinically-identified prostate cancer were identified; 46 aggressive cases, and 58 non-aggressive cases. Serum vitamin D was assessed from fasting blood samples, and total calcium intake was assessed using the Block Food Frequency Questionnaire. Vitamin D receptor polymorphisms from three different loci were genotyped; rs731236, rs1544410, and rs11568820. Multivariate logistic regression models were used to determine odds ratios (OR) and 95% confidence intervals (CI) comparing aggressive to non-aggressive prostate cancer. Vitamin D deficiency (

The hypothesized effect of vitamin D on C-reactive protein (CRP) has received substantial attention as a potential means to alleviate the risk for cardiovascular disease. However, observational studies have been inconsistent in their reporting of associations between serum 25-hydroxyvitamin D (25(OH)D) and CRP concentrations, and trials and meta analyses have been inconsistent in their conclusions regarding the effect of vitamin D supplementation on CRP concentrations. These supplementation trials were mostly conducted among patients with more or less inflammatory complications and did not consider potential distinctive effects by weight status. To further our understanding of the potential influences of vitamin D on CRP, we analyzed longitudinal observations of 6755 participants of a preventative health program. On average, serum 25(OH)D concentrations increased from 88.3 to 121.0 nmol/L and those of CRP decreased from 1.7 to 1.6 mg/L between baseline and follow up. Relative to obese participants without temporal increases in 25(OH)D, those who showed improvements of

Objective To investigate the effect of vitamin D supplementation dose on allergic sensitization and allergic diseases in infants, and to evaluate whether vitamin D status in pregnancy and at birth are associated with infant allergy outcomes. Study design Altogether, 975 infants participated in a randomized, controlled trial of daily vitamin D supplementation of 10 mu g (400 IU) or 30 mu g (1200 IU) from the age of 2 weeks. At 12 months of age, food and aeroallergen IgE antibodies were measured, and the occurrence of allergic diseases and wheezing were evaluated. Results We found no differences between the vitamin D supplementation groups in food (OR, 0.98; 95% CI, 0.66-1.46) or aeroallergen sensitization at 12 months (OR, 0.76; 95% CI,0.34-1.71). Allergic diseases or wheezing did not differ between groups, except for milk allergy which occurred more often in infants administered 30 mu g vitamin D compared with the 10 mu g dose (OR, 2.23; 95% CI, 1.00-4.96). Infants with high cord blood 25-hydroxyvitamin D (>= 100 nmol/L) had a higher risk of food allergen sensitization compared with those with lower 25(OH)D concentration (75-99.9 nmol/L; OR, 2.00; 95% CI, 1.19-3.39). Conclusions High-dose vitamin D supplementation did not prevent allergic sensitization, allergic diseases, or wheezing during the first year of life. In contrast, we observed an increased risk of milk allergy in infants randomized to higher vitamin D supplementation, and an increased risk of allergic sensitization in infants with high cord blood vitamin D status, indicating a possible adverse effect of high concentrations of vitamin D.