Markers of vitamin D exposure and oesophageal cancer risk: a systematic review and meta-analysis.

Vitamin D has been associated with reduced risk of many cancers, but evidence for oesophageal cancer is mixed. To clarify the role of Vitamin D, we performed a systematic review and meta-analysis to evaluate the association of Vitamin D exposures and oesophageal neoplasia, including adenocarcinoma, squamous cell carcinoma (SCC), Barrett's oesophagus and squamous dysplasia. Ovid MEDLINE, EMBASE and Web of Science were searched from inception to September 2015. Fifteen publications in relation to circulating 25-hydroxyvitamin D (n=3), Vitamin D intake (n=4), UVB exposure (n=1), and genetic factors (n=7) were retrieved. Higher 25-OHD was associated with increased risk of cancer (adenocarcinoma or SCC, OR=1.39;95%CI:1.04-1.74), with the majority of participants coming from China. No association was observed between Vitamin D intake and risk of cancer overall (OR=1.03;0.65-1.42); however, a non-significantly increased risk for adenocarcinoma (OR=1.45;0.65-2.24) and non-significantly decreased risk for SCC (OR=0.80;0.48-1.12) were observed. One study reported a decreased risk of adenocarcinoma with higher UVB exposure. A decreased risk was found for VDR haplotype rs2238135(G)/rs1989969(T) carriers, OR=0.45;0.00-0.91, and a suggestive association was observed for rs2107301. No consistent associations were observed between Vitamin D exposures and occurrence of oesophageal lesions. Further adequately powered, well-designed studies are needed before conclusions can be made.

« Et ils prophétiseront » : la prophétie de Jl 3,1-5 reprise en Ac 2, 17-21 : clé d'interprétation du phénomène pentecostal

Cette présente recherche vise à défendre le point de vue selon lequel le don de l’Esprit dans le récit de la Pentecôte (Ac 2, 1-13) s’interprète principalement comme l’investissement d’une puissance habilitant au témoignage. À cette fin, nous posons l’hypothèse que le contenu d’Ac 2, 17-21 est un axe fondamental de la théologie pneumatique de l’œuvre lucanienne, lequel interprète la manifestation pentecostale dans une perspective prophétique. La démonstration se fait par le biais d’une analyse rédactionnelle d’Ac 2, 17-21, une citation de Jl 3,1-5 insérée dans un discours explicatif de Pierre du phénomène pentecostal. Nous examinons d’abord le lieu d’inscription de ce passage dans l’œuvre lucanienne afin d’évaluer la valeur stratégique de son emplacement (chapitre 1). Nous étudions ensuite l’interprétation que fait Luc de cette prophétie pour en venir à la conclusion qu’il envisage l’intervention de l’Esprit essentiellement dans une perspective d’habilitation à la prophétie (chapitre 2). Nous vérifions cette première conclusion dans l’Évangile de Luc (chapitre 3); puis ensuite dans les Actes des Apôtres (chapitre 4). Nous en arrivons ainsi à établir un parallélisme entre les étapes initiatiques du ministère de Jésus dans le troisième évangile et celui des disciples dans les Actes, pour y découvrir que, dans les deux cas, l’effusion de l’Esprit habilite à l’activité prophétique. Le ministère des disciples s’inscrit de la sorte dans le prolongement de celui du Maître. Nous soutenons, en fait, que tout le discours pneumatique de l’Évangile de Luc converge vers l’effusion initiale de l’Esprit sur les disciples dans le récit pentecostal, d’une part, et que cette effusion jette un éclairage sur l’ensemble de l’œuvre missionnaire des Actes, d’autre part. Bref, le passage explicatif du phénomène pentecostal, en l’occurrence Ac 2, 17-21, met en lumière un axe central des perspectives de Luc sur l’Esprit : Il s’agit de l’Esprit de prophétie. Dans cette optique, l’effusion de l’Esprit à la Pentecôte s’interpréterait essentiellement comme l’investissement du croyant d’une puissance en vue du témoignage.

Niveles de vitamina d y prevalencia de déficit de vitamina d en mujeres postmenopáusicas mayores de 50 años en Bogotá

Objetivo: Describir los niveles de vitamina D y calcular prevalencia de déficit de vitamina D en mujeres postmenopáusicas mayores de 50 años que asisten a consulta de medicina general en una muestra en de la ciudad de Bogotá durante el periodo 2013-2014. Pacientes y métodos: Realizamos un estudio descriptivo para estimar el déficit de VD en mujeres postmenopáusicas entre 50 y 80 años en la ciudad de Bogotá y la prevalencia de hipovitaminosis D. Durante el periodo octubre 2013 a octubre 2014 se analizaron 320 muestras, se identificaron las características socio-demográficas, patológicas y la exposición a radiación ultravioleta de cada participante. Se realizó un análisis descriptivo de las variables, se estableció su asociación con el déficit de vitamina D su aporte estadístico con al mismo. Resultados :El promedio de edad en la muestra fue de 61 años y el promedio de edad en la que reportaron la ultima menstruación fue a los 43 años. Con respecto a las características socio-demográficas 50% de las mujeres pertenecieron a los estratos 3 y 4, únicamente 11% de los pacientes realizaron una carrera universitaria y 73% de la mujeres fueron amas de casa. Con respecto a los niveles de vitamina D, 81% de los pacientes presentaron niveles anormales y el promedio de 25(OH)D en la población estudio fue de 19,81ng/ml. Conclusión: La prevalencia de déficit de vitamina D en mujeres bogotanas postmenopáusicas es significativo. Se requiere incrementar la exposición solar o dar suplencia con vitamina D para disminuir el riesgo de fracturas.

Down-regulation of the CSLF6 gene results in decreased (1,3;1,4)-beta-D-glucan in endosperm of wheat

(1,3;1,4)-beta-d-Glucan (beta-glucan) accounts for 20% of the total cell walls in the starchy endosperm of wheat (Triticum aestivum) and is an important source of dietary fiber for human nutrition with potential health benefits. Bioinformatic and array analyses of gene expression profiles in developing caryopses identified the CELLULOSE SYNTHASE-LIKE F6 (CSLF6) gene as encoding a putative beta-glucan synthase. RNA interference constructs were therefore designed to down-regulate CSLF6 gene expression and expressed in transgenic wheat under the control of a starchy endosperm-specific HMW subunit gene promoter. Analysis of wholemeal flours using an enzyme-based kit and by high-performance anion-exchange chromatography after digestion with lichenase showed decreases in total beta-glucan of between 30% and 52% and between 36% and 53%, respectively, in five transgenic lines compared to three control lines. The content of water-extractable beta-glucan was also reduced by about 50% in the transgenic lines, and the M(r) distribution of the fraction was decreased from an average of 79 to 85 x 10(4) g/mol in the controls and 36 to 57 x 10(4) g/mol in the transgenics. Immunolocalization of beta-glucan in semithin sections of mature and developing grains confirmed that the impact of the transgene was confined to the starchy endosperm with little or no effect on the aleurone or outer layers of the grain. The results confirm that the CSLF6 gene of wheat encodes a beta-glucan synthase and indicate that transgenic manipulation can be used to enhance the health benefits of wheat products.

Pharmacological analysis of a dopamine D-2Short: G(alpha o) fusion protein expressed in Sf9 cells

A dopamine D-2Short receptor:G(alphao) fusion protein was expressed in Sf9 cells using the baculovirus expression system. [H-3]Spiperone bound to D-2Short:G(alphao) with a pK(d) approximate to 10. Dopamine stimulated the binding of [S-35]guanosine-5'-O-(3-thio)triphosphate (GTPgammaS) to D-2Short:G(alphao) expressed with Gbeta(1)gamma(2) (E-max > 460%; pEC(50) 5.43 +/- 0.06). Most of the putative D-2 antagonists behaved as inverse agonists (suppressing basal [S-35]GTPgammaS binding) at D-2Short:G(alphao)/Gbeta(1)gamma(2) although (-)-suipiride and ziprasidone were neutral antagonists. Competition of [H-3]spiperone binding by dopamine and 10,11-dihydroxy-N-n-propylnorapo-morphine revealed two, binding sites of different affinities, even in the presence of GTP (100 muM). The D-2Short:G(alphao) fusion protein is therefore a good model for characterising D-2 receptors. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

Solar ultraviolet-B radiation and vitamin D: a cross-sectional population-based study using data from the 2007 to 2009 Canadian Health Measures Survey

Background: Exposure to solar ultraviolet-B (UV-B) radiation is a major source of vitamin D3. Chemistry climate models project decreases in ground-level solar erythemal UV over the current century. It is unclear what impact this will have on vitamin D status at the population level. The purpose of this study was to measure the association between ground-level solar UV-B and serum concentrations of 25-hydroxyvitamin D (25(OH)D) using a secondary analysis of the 2007 to 2009 Canadian Health Measures Survey (CHMS). Methods: Blood samples collected from individuals aged 12 to 79 years sampled across Canada were analyzed for 25(OH)D (n=4,398). Solar UV-B irradiance was calculated for the 15 CHMS collection sites using the Tropospheric Ultraviolet and Visible Radiation Model. Multivariable linear regression was used to evaluate the association between 25(OH)D and solar UV-B adjusted for other predictors and to explore effect modification. Results: Cumulative solar UV-B irradiance averaged over 91 days (91-day UV-B) prior to blood draw correlated significantly with 25(OH)D. Independent of other predictors, a 1 kJ/m 2 increase in 91-day UV-B was associated with a significant 0.5 nmol/L (95% CI 0.3-0.8) increase in mean 25(OH)D (P =0.0001). The relationship was stronger among younger individuals and those spending more time outdoors. Based on current projections of decreases in ground-level solar UV-B, we predict less than a 1 nmol/L decrease in mean 25(OH)D for the population. Conclusions: In Canada, cumulative exposure to ambient solar UV-B has a small but significant association with 25(OH)D concentrations. Public health messages to improve vitamin D status should target safe sun exposure with sunscreen use, and also enhanced dietary and supplemental intake and maintenance of a healthy body weight.

Causal relationship between obesity and vitamin D status: bi-directional mendelian randomization analysis of multiple cohorts

BACKGROUND: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. METHODS AND FINDINGS: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH)D (p = 6.52×10⁻²⁷). The BMI allele score was associated both with BMI (p = 6.30×10⁻⁶²) and 25(OH)D (-0.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p≤8.07×10⁻⁵⁷ for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores). CONCLUSIONS: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency.

Prevalence of Vitamin D Insufficiency in Brazilian Adolescents

Background/Aims: Cutaneous sun exposure and dietary vitamin D intake are important determinants of vitamin D status. The objective of the present study was to evaluate the vitamin D status of a group of healthy adolescent students living in Brazil. Methods: One hundred and thirty-six adolescents, 64 boys and 72 girls, aged 16-20 years old, living in a rural town in the state of Sao Paulo, Brazil, participated in this study. Results: The mean dietary vitamin D intake was 140 (120-156) IU/day [3.5 (3.0-3.9) mu g/day]. Only 14.9% of the students met the daily adequate intake recommendation of vitamin D. Only 27.9% practice physical activity outdoors and 17.6% of the adolescents apply sunscreen daily. The mean 25(OH)D concentration was 73.0 (22.0) nmol/l [29.2 (8.8) ng/ml]. Vitamin D insufficiency was observed in 60% of adolescents. Conclusions: The present study suggests that even in a sunny climate like Brazil the prevalence of vitamin D insufficiency in adolescents is high. Most likely this is due to low intakes of vitamin D in this group. Due to the limited extent of natural dietary sources of vitamin D, a policy of vitamin D food fortification should be considered in the future, and in the meantime greater use of vitamin D supplements in this population group should be encouraged to provide the increased amounts of this essential nutrient for optimal health. Copyright (C) 2009 S. Karger AG, Basel

Estimation of the dietary requirement for vitamin D in healthy adults

Background: Knowledge gaps have contributed to considerable variation among international dietary recommendations for vitamin D.

Objective: We aimed to establish the distribution of dietary vitamin D required to maintain serum 25-hydroxyvitamin D [25(OH)D] concentrations above several proposed cutoffs (ie, 25, 37.5, 50, and 80 nmol/L) during wintertime after adjustment for the effect of summer sunshine exposure and diet.

Design: A randomized, placebo-controlled, double-blind 22-wk intervention study was conducted in men and women aged 20–40 y (n = 238) by using different supplemental doses (0, 5, 10, and 15 µg/d) of vitamin D3 throughout the winter. Serum 25(OH)D concentrations were measured by using enzyme-linked immunoassay at baseline (October 2006) and endpoint (March 2007).

Results: There were clear dose-related increments (P < 0.0001) in serum 25(OH)D with increasing supplemental vitamin D3. The slope of the relation between vitamin D intake and serum 25(OH)D was 1.96 nmol·L–1·µg–1 intake. The vitamin D intake that maintained serum 25(OH)D concentrations of >25 nmol/L in 97.5% of the sample was 8.7 µg/d. This intake ranged from 7.2 µg/d in those who enjoyed sunshine exposure, 8.8 µg/d in those who sometimes had sun exposure, and 12.3 µg/d in those who avoided sunshine. Vitamin D intakes required to maintain serum 25(OH)D concentrations of >37.5, >50, and >80 nmol/L in 97.5% of the sample were 19.9, 28.0, and 41.1 µg/d, respectively.

Conclusion: The range of vitamin D intakes required to ensure maintenance of wintertime vitamin D status [as defined by incremental cutoffs of serum 25(OH)D] in the vast majority (>97.5%) of 20–40-y-old adults, considering a variety of sun exposure preferences, is between 7.2 and 41.1 µg/d.

Is this D vitamin to worry about? Vitamin D insufficiency in an inpatient sample

Objective: The aim of the present study was to investigate the relationship between reduced serum vitamin D levels and psychiatric illness.

Method: This study was an audit of serum 25-hydroxyvitamin D (25-OHD) levels measured routinely in a sample of 53 inpatients in a private psychiatric clinic. These levels were compared with those of controls without psychiatric illness.

Results: The median levels of serum 25-OHD were 43.0 nmol L⁻¹ (range 20–102 nmol L⁻¹) in the patient population, 46.0 nmol L⁻¹ (range 20–102 nmol L⁻¹) in female patients (n =33) and 41.5 nmol L⁻¹ (range 22–97 nmol L⁻¹) in male patients (n =20). The proportion of vitamin D insufficiency (serum 25-OHD ≤50 nmol L⁻¹) in this patient population was 58%. Furthermore, 11% had moderate deficiency (serum 25-OHD ≤25 nmol L⁻¹). There was a 29% difference between mean levels in the patient population and control sample (geometric mean age- and season-adjusted levels: 46.4 nmol L⁻¹ (95% confidence interval (CI) =38.6–54.9 nmol L⁻¹) vs 65.3 nmol L⁻¹ (95%CI =63.2–67.4 nmol L⁻¹), p <0.001).

Conclusion: Low levels of serum 25-OHD were found in this patient population. These data add to the literature suggesting an association between vitamin D insufficiency and psychiatric illness, and suggest that routine monitoring of vitamin D levels may be of benefit given the high yield of clinically relevant findings.

Vitamin D, obesity, and obesity-related chronic disease among ethnic minorities : a systematic review

Objective : To assess the association between 25-hydroxyvitamin D (25[OH]D) status and obesity, cardiovascular diseases (CVDs), the metabolic syndrome, and type 2 diabetes mellitus (T2DM) in ethnic minorities.

Methods : Databases searched were CINHAL with full text, Global Health, MEDLINE with full text, and PsycINFO from 1980 through 2010 (February). Studies were included if they 1) targeted immigrants from low- to high-income countries or ethnic minorities, 2) focused primarily on 25(OH)D and its relation to obesity, T2DM, and/or CVDs, and 3) were published in peer-reviewed journals. The influences of key confounders such as age, gender, and ethnicity on any observed relations were also assessed. Due to the heterogeneity of study characteristics, only a narrative synthesis was undertaken.

Results : Ethnic minorities had significantly higher rates of vitamin D insufficiency (25[OH]D <50 nmol/L; children 43.6–48.7% versus 10%; adults 30.3–53% versus 13.7–26%) than their white counterparts. None of the studies reported a prevalence of obesity stratified by ethnicity. There was evidence supporting links between vitamin D deficiency and obesity-related chronic diseases, with 14 of 14 studies reporting a statistically significant result with a measurement of obesity, four of five for T2DM, four of five for CVDs, and one of one for the metabolic syndrome. However, the strength of the association varied across ethnic groups depending on the index used to measure adiposity, T2DM, and CVDs. Because most of the included studies were cross-sectional and there were variations in outcome measurements, it was not possible to determine the relative contributions of obesity or vitamin D insufficiency to CVD risk and risk of T2DM or which is the initial driver It is possible both have a role to play.

Conclusion : Further research specific to migrant populations using randomized controlled trials are required to establish whether causal links between 25(OH)D and obesity-related chronic disease exist, and whether vitamin D supplementation could be valuable in the prevention or treatment of obesity-related diseases.

Prevalence of vitamin D insufficiency and risk factors for type 2 diabetes and cardiovascular disease among African migrant and refugee adults in Melbourne

Migration to industrialised countries poses a “double whammy” for type 2 diabetes among sub-Saharan African migrant and refugee adults. This population group has been found to be at an increased risk of obesity and type 2 diabetes, which may be further aggravated by inadequate vitamin D status. Thus, this study aimed to describe the demographics of vitamin D insufficiency, obesity, and risk factors for type 2 diabetes among sub-Saharan African migrants and refugees aged 20 years or older living in Melbourne, Australia (n=49). Data were obtained by a questionnaire, medical assessment, and fasting blood samples. The mean serum 25-hydroxyvitamin D level was 27.3 nmol/L (95% CI: 22.2, 32.4 nmol/L); with 25-hydroxyvitamin D levels <50 nmol/L occurring in 88% of participants. Participants displayed a cluster of risk factors for type 2 diabetes and cardiovascular disease: 62% were overweight or obese, 47% had insulin resistance (HOMA-IR ≥2), 25% had low density lipoprotein cholesterol levels ≥3.5 mmol/L, 24.5% had high density lipoprotein cholesterol levels ≤1.03 mmol/L, 34.6% had borderline or high levels of total cholesterol (≥5.2 mmol/L), 18.2% had borderline or high levels of triglyceride (≥1.7 mmol/L), and 16% had hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg). These findings suggest that sub-Saharan African migrants and refugees may be at risk of type 2 diabetes and atherosclerosis-related diseases such as ischemic heart disease, stroke, and peripheral vascular disease. Well-designed vitamin D interventions that incorporate lifestyle changes are urgently needed in this sub-population.

Seasonal periodicity of serum vitamin D and parathyroid hormone, bone resorption, and fractures : the Geelong Osteoporosis Study

In this population-based study, seasonal periodicity was seen with reduced serum vitamin D, increased serum PTH, and increased bone resorption in winter. This was associated with an increased proportion of falls resulting in fracture and an increased risk of wrist and hip fractures.

Introduction: In a population of women who reside in a temperate climate and do not generally receive dietary vitamin D supplementation, we investigated whether seasonal vitamin D insufficiency is associated with increased risk of fracture.

Materials and Methods: An observational, cross-sectional, population-based study set in southeastern Australia (latitude 38–39° S). Participants were drawn from a well-defined community of 27,203 women ≥55 years old: 287 randomly selected from electoral rolls, 1635 with incident fractures, and 1358 presenting to a university hospital with falls. The main outcome measures were annual periodicities of ultraviolet radiation, serum 25-hydroxyvitamin D [25(OH)D], serum parathyroid hormone (PTH), serum C-telopeptide (CTx), BMD, falls, and fractures.

Results: Cyclic variations in serum 25(OH)D lagged 1 month behind ultraviolet radiation, peaking in summer and dipping in winter (p < 0.001). Periodicity of serum PTH was the inverse of serum 25(OH)D, with a phase shift delay of 1 month (p = 0.004). Peak serum CTx lagged peak serum PTH by 1–2 months. In late winter, a greater proportion of falls resulted in fracture (p < 0.001). Seasonal periodicity in 439 hip and 307 wrist fractures also followed a simple harmonic model (p = 0.078 and 0.002, respectively), peaking 1.5–3 months after the trough in 25(OH)D.

Conclusions: A fall in 25(OH)D in winter is accompanied by increases in (1) PTH levels, (2) bone resorption, (3) the proportion of falls resulting in fracture, and (4) the frequency of hip and wrist fracture. Whether vitamin D supplementation in winter can reduce the population burden of fractures requires further investigation.

Vitamin D status of women in the Geelong Osteoporosis Study : association with diet and casual exposure to sunlight

Objective: To assess vitamin D intake and casual exposure to sunshine in relation to serum 25-hydroxyvitamin D (25OHD) levels.

Design: Cross-sectional study of a population-based, random sample of women aged 20-92 years, assessed between 1994 and 1997.

Setting and participants: 861 women from the Barwon Statistical Division (population, 218 000), which includes the city of Geelong (latitude 38° south) in Victoria.

Main outcome measures: Vitamin D intake; serum 25OHD level; season of assessment; exposure to sunshine.

Results: Median intake of vitamin D was 1.2 μg/day (range, 0.0-11.4 μg/day). Vitamin D supplements, taken by 7.9% of participants, increased intake by 8.1% to 1.3 μg/day (range, 0.0-101.2 μg/day) (P < 0.001). A dose-response relationship in serum 25OHD levels was observed for sunbathing frequency before and after adjusting for age (P < 0.05). During winter (May-October), serum 25OHD levels were dependent on vitamin D intake (partial r2 = 0.01; P < 0.05) and were lower than during summer (November-April) (age-adjusted mean, 59 nmol/L [95% CI, 57-62] v 81 nmol/L [95% CI, 78-84]; P < 0.05). No association was detected between serum 25OHD and vitamin D intake during summer. The prevalences of low concentrations of serum 25OHD were, for <28 nmol/L, 7.2% and 11.3% overall and in winter, respectively; and, for <50 nmol/L, 30.0% and 43.2% overall and in winter, respectively.

Conclusions: At latitude 38° south, the contribution of vitamin D from dietary sources appears to be insignificant during summer. However, during winter vitamin D status is influenced by dietary intake. Australia has no recommended dietary intake (RDI) for vitamin D, in the belief that adequate vitamin D can be obtained from solar irradiation alone. Our results suggest that an RDI may be needed.