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OBJECTIVES: Evidence suggests a beneficial effect of vitamin D on perinatal health; however, low vitamin D status is prevalent in pregnant women and neonates. The objective was to determine factors that are associated with vitamin D status of mothers in early pregnancy and neonates. METHODS: The study comprised 1,635 pregnant women from Quebec City and Halifax, Canada, 2002-2010. Vitamin D status was based on the concentration of 25-hydroxy-vitamin D [25(OH)D] determined with a chemiluminescence immunoassay in maternal sera collected at a median of 15 weeks' gestation and in neonatal cord sera at delivery. A questionnaire with information on potential determinants was completed midpregnancy. RESULTS: A total of 44.8% of mothers and 24.4% of neonates had 25(OH)D concentrations CONCLUSION: This study suggests that vitamin D status of pregnant women and/or neonates might be improved through supplementation, adequate dairy intake, a move towards a healthy pre-pregnancy body weight, and participation in physical activity. Controlled studies are needed to determine the effectiveness of interventions aimed at these factors. KEY WORDS: Pregnancy; newborn; vitamin D; lifestyle; epidemiology; Canada OBJECTIFS : Les donnees semblent indiquer que la vitamine D a un effet benefique sur la sante perinatale, mais un faible statut en vitamine D prevaut chez les femmes enceintes et les nouveau-nes. Nous avons voulu determiner les facteurs associes au statut en vitamine D de meres en debut de grossesse et de nouveau-nes. METHODE : L'etude a compris 1 635 femmes enceintes de Quebec et de Halifax, au Canada, de 2002 a 2010. Le statut en vitamine D etait fonde sur la concentration de 25-hydroxyvitamine D [25(OH)D], determinee grace a un immunoessai par chimiluminescence dans le serum maternel preleve a la duree mediane de 15 semaines de grossesse et dans le serum du cordon ombilical des nouveau-nes a l'accouchement. Au milieu de leur grossesse, les femmes ont rempli un questionnaire donnant de l'information sur les determinants potentiels. RESULTATS : En tout, 44,8 % des meres et 24,4 % des nouveau-nes avaient des concentrations de 25(OH)D CONCLUSION : Notre etude indique que le statut en vitamine D des femmes enceintes et/ou des nouveau-nes pourrait etre ameliore par la supplementation, par un apport suffisant en produits laitiers, par un effort pour atteindre un poids-sante avant la grossesse et par la participation a l'activite physique. Il faudrait mener des etudes controlees pour determiner l'efficacite des interventions ciblant ces facteurs. MOTS CLES : grossesse; nouveau-ne; vitamine D; style de vie; epidemiologie; Canada La traduction du resume se trouve a la fin de l'article. Can J Public Health 2016;107(4-5):e410-e416 doi: 10.17269/CJPH.107.5629, Vitamin D has long been known to be essential for calcium-phosphorus homeostasis and bone health. The recognition that vitamin D metabolites influence other physiologic processes has prompted the examination of [...]

BACKGROUND/OBJECTIVES: To determine the interrelationships between body composition, glycemic control and vitamin D status in an ambulatory population with diabetes (DM) and chronic kidney disease (CKD). SUBJECTS/METHODS: Adult (18-80 years) patients (n = 60) with DM and stage 1-4 CKD were recruited from the Northern Alberta Renal Program. Outcome variables included body composition (absolute/regional fat (FM)/lean soft tissue/total mass, percent fat/ lean/fat-free (FFM) mass), glycemic control (glycated hemoglobin (HbA1c)), vitamin D intake (dietary/supplemental) and vitamin D status (25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25[(OH).sub.2]D)) measured by validated methodologies. Sarcopenia was determined as an appendicular skeletal mass/[height.sup.2] less than 7.26 kg/[m.sup.2] (males) and 5.45 kg/[m.sup.2] (females). RESULTS: Suboptimal HbA1c (>7%), 25(OH)D (< 50 nmol/l) and 1,25[(OH).sub.2]D (< 43 pmol/l) concentrations were present in 57, 8 and 11% of participants. Ten percent of subjects had sarcopenia. Gender/age/DM type, not CKD, significantly influenced regional/ whole body composition. Females, older participants and those with type 2 DM had higher %FM. No significant interrelationships between vitamin D status and glycemic control were observed (P>0.05). Serum 25(OH)D concentrations were inversely associated with arm lean soft tissue/FFM/total mass, weight, appendicular skeletal mass, lean soft tissue/[height.sup.2], FFM/[height.sup.2], appendicular skeletal mass/[height.sup.2] and body mass index (P < 0.05). Sarcopenia occurred more frequently in patients with 25(OH)D concentrations [greater than or equal to] 100 nmol/l. Regional/whole body %FM was inversely related to 1,25[(OH).sub.2]D, not 25(OH)D. CONCLUSIONS: Body composition, not glycemic control, is associated with vitamin D status in an ambulatory population of adults with DM and CKD. European Journal of Clinical Nutrition (2016) 70, 743-749; doi:10.1038/ejcn.2015.185; published online 4 November 2015, INTRODUCTION Known for its classical role in calcium/bone homeostasis, vitamin D has been receiving renewed attention for its extraskeletal/ pleiotropic effects. Vitamin D acts as a transcription factor, through the [...]

BACKGROUND/OBJECTIVES: The long-term chronology of the association between low serum concentrations of 25-hydroxy vitamin D (25(OH)D) and weight status is unclear. We examined whether lower 25(OH)D in middle-aged women drives upwards the weight, body mass index (BMI) and waist-hip ratio (WHR) over the next 32 years, and whether higher 25(OH)D might predict less decline in the mid- to late-life height trajectory. SUBJECTS/METHODS: The Population Study of Women in Gothenburg started in 1968-1969 (the baseline) in 38-60-year-old women residing in Gothenburg, Sweden. Anthropometric measures were taken at baseline and 4 re-examinations until 2000- 2003. Levels of 25(OH)D were analyzed in serum stored since baseline in 1227 (84%) women. Repeated measures analyses were used to model associations between 25(OH)D (dichotomized, cut point 51.45 nmol/l) at baseline and anthropometric trajectories, adjusting for fixed and time-dependent covariates. RESULTS: At baseline, mean BMI was 25.2 kg/[m.sup.2] in women with low 25(OH)D and 23.8 kg/[m.sup.2] in the remaining women (P < 0.001), but this difference did not increase over 32 years and longitudinal differences were explained by the baseline BMI. Similar results were observed for weight and WHR. In contrast, no association was seen for height at baseline or longitudinally. CONCLUSIONS: No relationship was observed between 25(OH)D height trajectory, but lower 25(OH)D was associated with higher BMI, weight and WHR differences that were maintained over three decades. This provides no evidence for the direction of causality, but for a life-long difference in adiposity-related measures according to the 25D level in middle-aged women. European Journal of Clinical Nutrition (2016) 70, 709-714; doi:10.1038/ejcn.2016.11; published online 24 February 2016, INTRODUCTION Lower serum 25-hydroxy vitamin D (25(OH)D) levels (hereafter referred to as 25D) are well known to be associated with obesity, but the direction of causality remains unclear as summarized [...]

BACKGROUND/OBJECTIVES: Maternal vitamin D deficiency during pregnancy may influence offspring kidney health. We aimed to examine the associations of 25-hydroxyvitamin D (25(OH)D) blood levels during fetal life with kidney outcomes at school age. SUBJECTS/METHODS: This study was embedded in a population-based prospective cohort study among 4212 mother-child pairs. We measured maternal second trimester (18-25 weeks) and fetal cord blood (at birth) 25(OH)D levels. At a median age of 6.0 years, we measured children's combined kidney volume, glomerular filtration rate (eGFR) from creatinine and cystatin C serum levels, and microalbuminuria from albumin and creatinine urine levels. RESULTS: Of all mothers, 21.9% had severely deficient levels (25(OH)D < 25.0 nmol/l), 25.7% had deficient levels (25.0-49.9 nmol/l), 25% had sufficient levels (50.0-74.9 nmol/l) and 27.4% had optimal levels (≥ 75.0 nmol/l). Maternal 25(OH)D levels were not consistently associated with childhood combined kidney volume. Higher maternal 25(OH)D levels were associated with lower childhood eGFR (difference -0.94 ml/min per 1.73 [m.sup.2] (95% confidence interval, -1.73;-0.15) per 1 standard deviation (s.d.) increase in 25(OH)D). Maternal 25(OH)D levels were not associated with microalbuminuria. Cord blood 25(OH)D levels were not associated with childhood kidney outcomes. The associations of maternal 25(OH)D levels with childhood eGFR were partly explained by childhood vitamin D status. CONCLUSIONS: Our findings suggest that maternal 25(OH)D levels during pregnancy may influence childhood kidney outcomes. These results should be considered hypothesis generating. Further studies are needed to replicate the observations, to examine the underlying mechanisms and to identify the long-term clinical consequences. European Journal of Clinical Nutrition (2016) 70, 629-634; doi: 10.1038/ejcn.2015.216; published online 23 December 2015, INTRODUCTION Vitamin D deficiency is related to various adverse health outcomes in early and later life. (1-4) An accumulating body of evidence suggests that vitamin D status during pregnancy may [...]

BACKGROUND/OBJECTIVES: Seasonal variation may reduce the validity of 25-hydroxyvltamln D (25OHD) as a blomarker of vitamin D status. Here we aimed to identify potential determinants of seasonal variation in 25OHD concentrations and to evaluate cosinor modelling as a method to adjust single 25OHD measurements for seasonal variation. SUBJECTS/METHODS: In Caucasian cardiovascular patients (1999-2004), we measured 25OHD by liquid chromatography tandem mass spectrometry in 4116 baseline and 528 follow-up samples. To baseline values, we fitted a cosinor model for monthly concentrations of 25OHD. Using the model, we estimated each patient's adjusted annual 25OHD value. Further, we studied how covariates affected the annual mean 25OHD concentration and seasonal variation of the study cohort. To evaluate the model, we predicted follow-up measurements with and without covariates and compared accuracy with carrying forward baseline values and linear regression adjusting for season, common approaches in research and clinical practice, respectively. RESULTS: The annual mean (59.6 nmol/l) was associated with participants' age, gender, smoking status, body mass, physical activity level, diabetes diagnosis, vitamin D supplement use and study site (adjusted models, P < 0.05). Seasonal 25OHD variation was 15.8 nmol/l, and older age (>62 years) was associated with less variation (adjusted model, P = 0.025). Prediction of follow-up measurements was more accurate with the cosinor model compared with the other approaches (P < 0.05). Adding covariates to cosinor models did not improve prediction (P>0.05). CONCLUSIONS: We find cosinor models suitable and flexible for analysing and adjusting for seasonal variation in 25OHD concentrations, which is influenced by age. European Journal of Clinical Nutrition (2016) 70, 517-522; doi: 10.1038/ejcn.2015.200; published online 25 November 2015, INTRODUCTION In countries located increasingly distant from the Earth's equator, the population concentration of 25-hydroxyvitamin D (25OHD) tends to follow changes in the ultraviolet B radiation from the sun. (1-6) [...]

BACKGROUND/OBJECTIVES: Previous studies have suggested that serum 25-hydroxyvitamin D (25(OH)D) is associated with hypertension. However, the effects of age and sex on the relation between serum 25(OH)D and hypertension has not been examined. The present study examined the relationship between serum 25(OH)D and hypertension by age and sex in the general Korean population, considering potential confounders for hypertension. SUBJECTS/METHODS: We conducted a population-based, cross-sectional study. Twenty thousand four hundred and forty adults aged 19 years or older, who participated in the 2009-2012 Korean National Health and Nutrition Examination Surveys, were selected for the present study. Hypertension was defined as a systolic blood pressure [greater than or equal to] 140mmHg, diastolic blood pressure [greater than or equal to] 90 mm Hg or current use of antihypertensive medication. RESULTS: We found that serum 25(OH)D levels are inversely associated with hypertension in young and middle-aged adults, but not in the elderly population. In young and middle-aged adults, the adjusted odds ratios (ORs) for hypertension tended to decrease according to the quartiles of serum 25(OH)D after adjustment for potential confounders, although it was only significant in women (OR = 0.73, 95% confidence interval (CI) = 0.58-0.91, P for trend =0.0349). There was no association between serum 25(OH)D concentration and hypertension in elderly subjects of either sex. CONCLUSIONS: A higher serum 25(OH)D level was strongly associated with a lower prevalence of hypertension in young and middle-aged Korean women, but not in elderly adults. European Journal of Clinical Nutrition (2016) 70, 326-332; doi: 10.1038/ejcn.2015.115; published online 15 July 2015, INTRODUCTION Vitamin D in the body is derived from dietary intake or supplementation and from endogenous production of vitamin D in the skin following sun exposure. (1) The primary physiological [...]

Background Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk. Methods and findings We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. For each case, we randomly selected four controls from among contacts who did not develop TB disease, matching on gender and year of age. We also conducted a one-stage individual-participant data (IPD) meta-analysis searching PubMed and Embase to identify prospective studies of vitamin D and TB disease until June 8, 2019. We included studies that assessed vitamin D before TB diagnosis. In the primary analysis, we defined vitamin D deficiency as 25-(OH)D 75nmol/L. We estimated the association between baseline vitamin D status and incident TB using conditional logistic regression in the Lima cohort and generalized linear mixed models in the meta-analysis. We further defined severe vitamin D deficiency as 25-(OH)D < 25 nmol/L and performed stratified analyses by HIV status in the IPD meta-analysis. In the Lima cohort, we analyzed 180 cases and 709 matched controls. The adjusted odds ratio (aOR) for TB risk among participants with baseline vitamin D deficiency compared to sufficient vitamin D was 1.63 (95% CI 0.75-3.52; p = 0.22). We included seven published studies in the meta-analysis and analyzed 3,544 participants. In the pooled analysis, the aOR was 1.48 (95% CI 1.04-2.10; p = 0.03). The aOR for severe vitamin D deficiency was 2.05 (95% CI 0.87-4.87; p trend for decreasing 25-(OH)D levels from sufficient vitamin D to severe deficiency = 0.02). Among 1,576 HIV-positive patients, vitamin D deficiency conferred a 2-fold (aOR 2.18, 95% CI 1.22-3.90; p = 0.01) increased risk of TB, and the aOR for severe vitamin D deficiency compared to sufficient vitamin D was 4.28 (95% CI 0.85-21.45; p = 0.08). Our Lima cohort study is limited by the short duration of follow-up, and the IPD meta-analysis is limited by the number of possible confounding covariates available across all studies. Conclusion Our findings suggest vitamin D predicts TB disease risk in a dose-dependent manner and that the risk of TB disease is highest among HIV-positive individuals with severe vitamin D deficiency. Randomized control trials are needed to evaluate the possible role of vitamin D supplementation on reducing TB disease risk., Author(s): Omowunmi Aibana 1, Chuan-Chin Huang 2, Said Aboud 3, Alberto Arnedo-Pena 4, Mercedes C. Becerra 2, Juan Bautista Bellido-Blasco 4, Ramesh Bhosale 5, Roger Calderon 6, Silvia Chiang 7, [...]

Byline: Amal. Mohamed, Ahmed. Aref, Soha. Talima, Reham. A Elshimy, Shawkat. Gerges, Mohamed. Meghed, Fawkia. Zahran, Eman. EL-Adawy, Sherief. Abd-Elsalam BACKGROUND AND AIMS: Pancreatic cancer (PC) is the fourth most [...]

BACKGROUND/OBJECTIVES: Prenatal vitamin-D deficiency may be associated with increased risk of obesity later in life. Using two national vitamin-D fortification programs as the setting for a societal experiment, we investigated whether exposure to vitamin-D from fortified margarine and low-fat milk during foetal life was associated with body size at 7 years of age. SUBJECTS/METHODS: Vitamin-D fortification of margarine was mandatory in Denmark from 1961 to 1985, and voluntary fortification of low-fat milk was permitted from 1972 to 1976. Using information on body mass index (BMI) Z-score at the age of 7 years of 54 270 children, who were measured during the mandatory Copenhagen School Health examination, we compared children according to whether the mothers were pregnant during the fortification programs or not. The comparisons were performed for children born just before and after initiation or termination of margarine and milk fortification periods, respectively. In total four sets of analyses were performed. RESULTS: We observed no difference in mean BMI Z-score between children exposed to vitamin-D fortification in utero and non-exposed children. Similar results were observed for overweight and obesity. CONCLUSIONS: Prenatal exposure to vitamin-D from fortification of margarine and low-fat milk showed no association with body size at 7 years. doi:10.1038/ejcn.2015.55; published online 8 April 2015, INTRODUCTION Vitamin-D deficiency is common at northern latitudes because vitamin-D is available from few food sources naturally and synthesis in the skin is limited to half of the year when [...]

Maternal hypovitaminosis D during pregnancy has been associated with a plethora of adverse health effects on the offspring. Maternal vitamin D status during pregnancy is affected by local climatic conditions. The aim of this article was to report on difficulties related to the heterogeneity of studies available in current literature on vitamin D status during pregnancy and discuss the incorporation of geophysical data in future studies, in an attempt to optimize their design and facilitate their interpretation. We focused on current vitamin D trials during pregnancy and their association with local regional climatic condition in geographical regions such as the Mediterranean basin based on our perspective on the field. Conduction of studies from areas with similar geophysical conditions is necessary, in order to extend our knowledge with respect to the question of which populations and under which circumstances would benefit most from vitamin D supplementation. Future vitamin D studies could benefit from the adoption of a unified concept minimizing these variations by selecting populations residing in areas with similar geophysical conditions adjusting also for their social and dietary habits. European Journal of Clinical Nutrition (2015) 69, 874-877; doi: 10.1038/ejcn.2015.33; published online 18 March 2015, INTRODUCTION Public health surveillance is considered as an integral part of an effective health-care system worldwide. (1) Two of the essential uses of public health surveillance, coordinated globally by World [...]

OBJECTIVES: To study the effect of Vitamin [D.sub.3] supplementation on metabolic control in an obese type 2 diabetes Emirati population. METHODS: This randomized double-blind clinical trial was conducted with 87 vitamin D-deficient obese, type 2 diabetic participants. The vitamin D-group (n = 45) and the placebo group (n = 42) were matched for gender, age, HbA1c and 25- hydroxy vitamin D (25(OH) D) at the baseline. The study was divided into two phases of 3 months each;in phase 1, the vitamin D- group received 6000 IU vitamin [D.sub.3]/day followed by 3000 IU vitamin [D.sub.3]/day in phase 2, whereas the placebo group (n = 42) received matching placebo. RESULTS: After supplementation, serum 25(OH) D peaked in the vitamin D-group in phase 1 (77.2 ±30.1 nmol/l, P = 0.003) followed by a decrease in the phase 2 (61.4± 18.8 nmol/l, P = 0.006), although this was higher compared with baseline. In the placebo group, no difference was observed in the serum 25(OH) D levels throughout the intervention. Relative to baseline serum, parathyroid hormone decreased 24% (P = 0.003) in the vitamin D-group in phase 2, but remained unchanged in the placebo group. No significant changes were observed in blood pressure, fasting blood glucose, HbA1c, C-peptide, creatinine, phosphorous, alkaline phosphatase, lipids, C-reactive protein or thyroid stimulating hormone concentrations compared with baseline in either group. CONCLUSIONS: Six months of vitamin [D.sub.3] supplementation to vitamin D-deficient obese type 2 diabetes patients in the UAE normalized the vitamin D status and reduced the incidence of eucalcemic parathyroid hormone elevation but showed no effect on the metabolic control. European Journal of Clinical Nutrition (2015) 69, 707-711; doi: 10.1038/ejcn.2014.251; published online 19 November 2014, INTRODUCTION Vitamin D role in calcium homeostasis and bone metabolism is well established. (1) However, in recent years, there has been numerous non-skeletal disease associations reported with vitamin D deficiency [...]

The active form of vitamin [D.sub.3], 1α,25-dihydroxyvitamin [D.sub.3] (1α,25[(OH).sub.2][D.sub.3] or calcitriol), is known to inhibit the proliferation and invasiveness of many types of cancer cells, including breast, colon, pancreatic, prostate, and liver cancer cells. These findings support the use of 1α,25 [(OH).sub.2][D.sub.3] for the treatment of these types of cancer. However, 1α,25[(OH).sub.2][D.sub.3] can cause hypercalcemia, so analogs of 1α,25[(OH).sub.2] [D.sub.3] that are less calcemic but exhibit more potent anti-tumor activity would be good candidates as therapeutic agents. Therefore, a series of 19-norvitamin D analogs, in which the methylidene group on C19 is replaced with 2 hydrogen atoms, have been synthesized by several laboratories. In our laboratory, we have designed and synthesized a series of 2α-functional group substituted 19-norvitamin [D.sub.3] analogs and examined their anti-proliferative activity. Among them, 2α- and 2β-(3-hydroxypropyl)-1α,25-dihydroxy-19-norvitamin [D.sub.3] (MART-10 and MART-11) were found to be the most promising. Here, we review the rationale and approaches for the synthesis of different 19-norvitamin D analogs, and the pre-clinical studies using these analogs in breast cancer cells, in particular, we chose MART-10 for its potential application to the prevention and treatment of breast cancer. Key words: 1α,25-dihydroxyvitamin [D.sub.3], vitamin D receptor, MART-10, synthesis, CYP24A1. Resume : On sait que la forme active de la vitamine [D.sub.3], la 1α,25-dihydroxyvitamine [D.sub.3] (1α,25[(OH).sub.2][D.sub.3] ou calcitriol), inhibe la proliferation et le potentiel invasif de plusieurs types de cellules cancereuses, y compris celles des cancers du sein, du colon, du pancreas, de la prostate et du foie. Ces resultats viennent appuyer l'utilisation de la 1α,25[(OH).sub.2][D.sub.3] pour le traitement de ces types de cancer. Toutefois, la 1α,25[(OH).sub.2][D.sub.3] peut causer une hypercalcemie. Aussi, les analogues de la 1α,25[(OH).sub.2][D.sub.3] qui augmentent moins les taux de calcium, mais qui ont des effets anti-tumoraux plus puissants pourraient etre de bons agents therapeutiques candidats. Par consequent, une serie d'analogues 19-nor de la vitamine D, dans lesquels le groupement methylidene du carbone 19 est remplace par deux atomes d'hydrogene, ont ete synthetises dans plusieurs laboratoires. Dans notre laboratoire, nous avons concu et synthetise une serie d'analogues de la 19-norvitamine [D.sub.3] avec substitution du groupement fonctionnel en position 2a, puis examine leurs effets anti-proliferatifs. Nous avons observe que la 2α- et la 2β-(3-hydroxypropyl)-1α,25-dihydroxy-19-norvitamine [D.sub.3] (MART-10 et MART-11) etaient les plus prometteurs d'entre eux. Ici, nous examinons le raisonnement et les approches en vue de la synthese de differents analogues de la 19-norvitamine D, ainsi que les etudes precliniques portant sur l'utilisation de ces analogues pour le traitement du cancer du sein, en particulier de MART-10 en raison de son application eventuelle a des strategies de prevention et de traitement du cancer du sein. [Traduit par la Redaction] Mots-cles : 1α,25-dihydroxyvitamine [D.sub.3], recepteur de la vitamine D, MART-10, synthese, CYP24A1., Introduction Long before the discovery of vitamin D by McCollum in 1922 (McCollum et al. 1922), Sniadecki, a physician from Warsaw, had already suspected that an anti-rachitic principle must be [...]

Vitamin D supplementation is recommended whenever patients are given therapeutic drugs for osteoporosis, to make their calcium (Ca) balance positive. Vitamin D is converted to 25-hydroxyvitamin D in the liver, and then activated to become 1α,25-dihydroxyvitamm D in the kidneys. The active vitamin D acts in the intestine to stimulate Ca absorption and maintain the Ca balance. 2β-(3-Hydroxypropyloxy)-1α, 25-dihydroxyvitamm [D.sub.3] (eldecalcitol) and 2-methylene-19-nor-(20S)-1a,25-dihydroxyvitamm [D.sub.3] (2MD) are newly developed vitamin D analogs, with a substitution at the 2 position of 1α,25-dihydroxyvitamm [D.sub.3] (calcitriol). Eldecalcitol and 2MD share common structural and biological characteristics. Both compounds increase serum Ca levels more markedly than calcitriol, increase bone mineral density (BMD), and improve bone strength in ovariectomized (OVX) rats. In a randomized, placebo controlled, double-blind, 1 year clinical trial, eldecalcitol dose-dependently increased lumbar and hip BMD and suppressed bone turnover markers in patients with osteoporosis. Whereas, 2MD markedly increased the bone turnover markers, but it did not change the BMD of postmenopausal women with osteopenia in a 1 year clinical trial. After a randomized, double-blind, 3 year fracture prevention trial comparing it with alfacalcidol, eldecalcitol was approved for the treatment of osteoporosis in Japan. On the other hand, the manufacturer discontinued the clinical development of 2MD. In this review, we discuss the similarities and differences between these 2 compounds, and the reasons why different outcomes resulted from their clinical trials. Key words: eldecalcitol, 2MD, vitamin D receptor ligand, vitamin-D-binding protein, mini-modeling. Une supplementation en vitamine D est recommandee, meme si les patients sont traites avec des medicaments contre l'osteoporose afin de rendre leur balance en calcium (Ca) positive. La vitamine D est convertie en 25-hydroxyvitamine D dans le foie, et est ensuite activee pour devenir la 1α,25-dihydroxyvitamine D dans les reins. La vitamine D active agit dans l'intestin afin de stimuler l'absorption du Ca et maintenir la balance en Ca. La 2β-(3-hydroxypropyloxy)-1α, 25-dihydroxyvitamine [D.sub.3] (eldecalcitol) et la 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamine [D.sub.3] (2MD) sont deux analogues de la vitamine D recemment developpes, qui portent une substitution en position 2 de la 1α,25-dihydroxyvitamine [D.sub.3] (calcitriol). L'eldecalcitol et la 2MD partagent des caracteristiques structurales et biologiques. Les deux composes accroissent les niveaux seriques de Ca de facon plus marquee que le calcitriol, et augmentent la densite minerale osseuse (DMO) et ameliorent la force de l'os chez des rates ovariectomisees. L'eldecalcitol augmentait la DMO lombaire et de la hanche en fonction de sa concentration, et reprimait les marqueurs du turnover osseux chez les patients atteints d'osteoporose lors d'essais cliniques aleatoires a double insu controles par placebo d'une duree d'un an. Alors que la 2MD accroissait de facon marquee les marqueurs du turnover osseux, elle ne changeait par la DMO de femmes post-menopausees avec osteopenie lors d'un test clinique d'un an. L'eldecalcitol a ete approuvee dans le traitement de l'osteoporose au Japon a la suite d'un essai clinique aleatoire a double insu d'une duree de trois ans qui visait la prevention de fractures et qui la comparait a l'alfacalcidol. Par contre, le manufacturier a cesse le developpement clinique de la 2MD. Dans cet article de synthese, les auteurs discutent des similarites et des differences entre ces deux composes, et des raisons qui expliquent les differents resultats de leurs essais cliniques. [Traduit par la Redaction] Mots-cles : eldecalcitol, 2MD, ligand du recepteur de la vitamine D, proteine liant la vitamine D, mini-modelisation., Introduction Vitamin D is regarded as an essential nutrient required for increasing intestinal calcium (Ca) and phosphate ([P.sub.i]) absorption. Vitamin D is converted by 25-hydroxylase in the liver to 25-hydroxyvitamin [...]

Tuberculosis (TB) is a major global health problem and often coincides with vitamin D deficiency. High doses of vitamin D were widely used to treat TB during the pre-antibiotic era. Vitamin D exerts its action through vitamin D receptor (VDR), and VDR gene polymorphisms are associated with susceptibility or resistance to tuberculosis as well as sputum smear and culture conversion during anti-TB treatment. In-vitro studies have revealed that 1,25-dihydroxyvitamin [D.sub.3] enhances innate immunity by increased expression of various antimicrobial peptides, including cathelicidin, and induction of autophagy of the infected cells thus restricts the intracellular growth of Mycobacterium tuberculosis in macrophages. On the other hand, vitamin D has been shown to suppress the pro-inflammatory cytokine response and enhance the anti-inflammatory response. Supplementation with vitamin D in concert with treatment for TB may be beneficial with respect to minimizing the excessive tissue damage that occurs during the active stage of tuberculosis disease. Several clinical trials have evaluated vitamin D supplementation as an adjunct therapy in the treatment for tuberculosis. However, results are conflicting, owing to variations in dose regimens and outcomes. Further investigations are needed to find the optimal concentration of vitamin D for supplementation with standard anti-TB drugs to optimize treatment, which could help to effectively manage both drug-sensitive and drug-resistant tuberculosis. Key words: 1,25-dihydroxyvitamin [D.sub.3], vitamin D receptor, antimicrobial peptides, immunity, clinical trials. La tuberculose (TB) est un probleme de sante mondial qui coincide souvent avec une deficience en vitamine D. Des doses elevees de vitamine D etaient largement utilisees pour traiter la TB avant l'ere des antibiotiques. La vitamine D exerce son action par l'intermediaire du recepteur de la vitamine D (VDR), et les polymorphismes du gene du VDR sont associes a la susceptibilite ou la resistance a la tuberculose de meme qu'a la conversion des cultures d'expectoration pendant le traitement anti-TB. Des etudes in vitro ont revele que la 1,25-dihydroxyvitamine [D.sub.3] accroit l'immunite innee en augmentant l'expression de differents peptides antimicrobiens, incluant la cathelicidine, et l'induction de l'autophagie des cellules infectees, ce qui restreint alors la croissance intracellulaire de Mycobacterium tuberculosis dans les macrophages. En revanche, on a montre que la vitamine D supprime la reponse des cytokines pro-inflammatoires et accroit la reponse anti-inflammatoire. La supplementation en vitamine D durant le traitement anti-TB peut etre benefique en minimisant le dommage tissulaire excessif durant le stade actif de la maladie. Plusieurs essais cliniques ont evalue la supplementation en vitamine D comme therapie d'appoint durant la traitement anti-TB. Cependant les resultats sont contradictoires fi cause des variations sur le plan des doses administrees et des mesures des resultats. Des recherches plus approfondies sont requises afin de trouver une concentration optimale de supplement de vitamine D a administrer parallelement aux medicaments anti-TB standard, afin de raccourcir la duree du traitement, ce qui pourrait aider a gerer efficacement tant la tuberculose sensible aux medicaments que la tuberculose resistante. [Traduit par la Redaction] Mots-cles : 1,25-dihydroxyvitamine [D.sub.3], recepteur de la vitamine D, peptides antimicrobiens, immunite, essais cliniques., Introduction Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), continues to be a major threat to public health. Results from various epidemiological studies have unveiled the association between vitamin D deficiency [...]

Vitamin D has been described as an essential element for maintaining the homeostasis of mineral content in the body and bone architecture. However, our view of the physiological functions of this micronutrient has radically changed, owing to the vast number of properties, not calcium-related, mediated by its nuclear receptor. This receptor has been found in a variety of cells, including the immune cells, where many of the functions performed by vitamin D are related to inflammation. Although the effect of vitamin D has been widely studied in many diseases caused by viruses or bacteria, very little is known about its role in parasitic diseases, such as leishmaniasis, which is a vector-borne disease caused by different species of the intracellular parasite Leishmania spp. This disease occurs as a spectrum of different clinical syndromes, all of them characterized by a large amount of tissue damage, sometimes leading to necrosis. Owing to the involvement of vitamin D in inflammation and wound healing, its role in leishmaniasis must be relevant, and could be used as an adjuvant for the control of this parasitic disease, opening a possibility for a therapeutic application. Key words: 1,25[(OH).sub.2][D.sub.3], leishmaniasis, inflammation, cytokines, immunoregulation, wound healing. On considere que la vitamine D constitue un element essentiel au maintien de l'homeostasie du contenu en mineraux du corps et a l'architecture des os. Cependant, notre vision des fonctions physiologiques de ce micronutriment a radicalement change a cause du grand nombre de proprietes, non reliees au calcium, qui sont relayees par son recepteur nucleaire. Ce recepteur est present dans une variete de cellules incluant les cellules immunitaires, dans lesquelles plusieurs des fonctions exercees par la vitamine D sont reliees a l'inflammation. Meme si l'effet de la vitamine D a ete largement etudie dans plusieurs maladies causees par des virus ou des bacteries, on sait peu de choses de son role dans les maladies parasitaires comme la leishmaniose, une maladie fi transmission vectorielle causee par differentes especes du parasite intracellulaire Leishmania. Cette maladie se manifeste en un spectre de differents symptomes cliniques, tous caracterises par un dommage tissulaire important, conduisant souvent a la necrose. A cause de l'implication de la vitamine D dans l'inflammation et la cicatrisation, son role dans la leishmaniose devrait etre pertinent et elle pourrait etre utilisee comme adjuvant pour controler cette maladie parasitaire, ouvrant une possibilite d'application therapeutique. [Traduit par la Redaction] Mots-cles : 1,25[(OH).sub.2][D.sub.3], leishmaniose, inflammation, cytokines, immunoregulation, cicatrisation., Introduction The use of vitamin D as a treatment for infections started approximately 150 years ago, although the mechanisms behind this practice were not understood. Over a hundred years ago, [...]

Vitamin D and calcium are well-established regulators of keratinocyte proliferation and differentiation. Therefore, it was not a great surprise that deletion of the vitamin D receptor (VDR) should predispose the skin to tumor formation, and that the combination of deleting both the VDR and calcium sensing receptor (CaSR) should be especially pro-oncogenic. In this review I have examined 4 mechanisms that appear to underlie the means by which VDR acts as a tumor suppressor in skin. First, DNA damage repair is curtailed in the absence of the VDR, allowing mutations in DNA to accumulate. Second and third involve the increased activation of the hedgehog and [beta]-catenin pathways in the epidermis in the absence of the VDR, leading to poorly regulated proliferation with reduced differentiation. Finally, VDR deletion leads to a shift in the expression of long noncoding RNAs toward a more oncogenic profile. How these different mechanisms interact and their relative importance in the predisposition of the VDR null epidermis to tumor formation remain under active investigation. Key words: calcium, epidermis, DNA damage repair, hedgehog, catenin, LncRNA. La vitamine D et le calcium sont des regulateurs bien etablis de la proliferation et de la differenciation des keratinocytes. Ainsi, il n'est pas surprenant de constater que la deletion du recepteur de la vitamine D (VDR) predispose fi la formation de tumeurs cutanees, et que la combinaison de la deletion du VDR et du recepteur de detection de calcium (CaSR ; Calcium sensing receptor) soit particulierement pro-oncogenique. Dans cet article de revue, l'auteur a examine quatre mecanismes qui semblent sous-tendre les moyens par lesquels le VDR agit comme suppresseur de tumeurs cutanees. D'abord, la reparation du dommage fi l'ADN est restreinte par l'absence du VDR, permettant aux mutations dans l'ADN de s'accumuler. Les deuxieme et troisieme mecanismes impliquent l'activation accrue des voies hedgehog et [beta]-catenine dans l'epiderme en absence de VDR, conduisant a une proliferation faiblement regulee et une differenciation reduite. Finalement, la deletion du VDR mene fi un changement de l'expression de longs ARN non codants vers un profil plus oncogenique. La recherche se poursuit activement afin de comprendre comment ces differents mecanismes interagissent, ainsi que leur relative importance dans la predisposition de l'epiderme depourvu de VDR a la formation tumorale. [Traduit par la Redaction] Mots-cles : calcium, epiderme, reparation du dommage a l'ADN, hedgehog, catenine, long ARNnc., Introduction Over 1 million skin cancers occur annually in the United States, 80% of which are basal cell carcinomas (BCC), 16% squamous cell carcinomas (SCC), and 4% melanomas, making skin [...]

Background To examine the relationship of serum 25-hydroxyvitamin D (25OHD) concentrations with serum parathyroid hormone (PTH) levels, body mass index (BMI), and environmental factors in a population of Caucasian children living at latitude 43[degrees]N. Methods Cross-sectional study on 288 children aged 1 month to 13 years who presented to a pediatric emergency unit during a 21-month period. Results Mean (SD) serum 25OHD concentrations were 40.6 (17.6), 30.9 (12.0), and 26.4 (9.9) ng/ml (1 ng/ml = 2.5 nmol/ l), in children aged 0-1, 2-5, and [greater than or equal to] 6 years, respectively. Serum PTH levels were 26.6 (13.6), 24.3 (11.9), and 32.7 (12.1) pg/ml in the same groups. Infants had 25OHD concentrations significantly higher. PTH levels were significantly higher in children aged [greater than or equal to] 6 years. There was no significant correlation between serum 25OHD and PTH concentrations. Totals of 15.6% and 2.1% of children had 25OHD values less than 20 and 10 ng/ml, respectively, but none had elevated serum PTH or clinical manifestations related with vitamin D deficiency. Age (inverse correlation) and season (higher values in summer), but not BMI, sex, and time spent outdoors, influenced serum 25OHD concentrations. Conclusions Our results raise doubt on the assumption of only a serum 25OHD threshold as indicative of vitamin D deficiency in children. Keywords 25OHD * PTH * Deficiency * Correlation * Threshold * Children, Introduction Vitamin D is essential for health. Its major physiologic function is related to the homeostasis of mineral metabolism by maintaining serum calcium and phosphorus levels within the normal physiologic [...]

BACKGROUND/OBJECTIVES: The objectives were to evaluate the effects of improvement of vitamin D status on biomarkers of oxidative stress (OS) in type 2 diabetic (T2D) subjects and whether vitamin D receptor (VDR)-FokI polymorphisms could modulate the response to vitamin D3 intake. SUBJECTS/METHODS: Subjects with T2D were allocated to one of the two groups to receive either plain doogh (PD; containing 150 mg calcium and no vitamin D/250 ml, [n.sub.1] = 50) or vitamin D3-fortified doogh (FD; containing 500 IU/250 ml, [n.sub.1] = 50) twice a day for 12 weeks. Outcomes were changes in serum 25-hydroxyvitamin D (25(OH)D), superoxide dismutase, glutathione (GSH), total antioxidant capacity (TAC) and malondialdehyde (MDA). VDR genotypes in 140 T2D subjects in FD were determined by FokI restriction enzyme. RESULTS: After 12 weeks, serum 25(OH)D increased significantly in FD (from 38.5 ± 202.2 to 72.0 ± 23.5, P < 0.001) as compared with PD (from 38.8 ± 22.8 to 33.4 ± 22.8, P = 0.28). Comparisons between FD and PD revealed significant differences in changes of serum MDA (-0.54 ± 0.82 µmol/l vs +0.17 ± 1 µmol/l, P < 0.001), GSH (+8.4 ± 40.1 ng/l vs - 13.1 ± 29.4 ng/l, P = 0.002) and TAC (+0.14 ± 0.43 mmol/l vs +0.02 ± 0.45 mmol/l bovine serum albumin equivalent, P = 0.03). Although there was no significant association between FokI genotypes and OS biomarkers, ff variant subgroup showed the weakest response to vitamin D. CONCLUSIONS: Improvement of vitamin D status via daily intake of FD ameliorates OS biomarkers in T2D subjects and the interactive effect of FokI genotypes cannot be ruled out. European Journal of Clinical Nutrition (2015) 69, 216-222; doi: 10.1038/ejcn.2014.240; published online 26 November 2014, INTRODUCTION There is mounting interest in the role of vitamin D in type 2 diabetes (T2D) and its complications. (1) Cardiovascular disease is the leading cause of morbidity and mortality [...]

BACKGROUND/OBJECTIVES: Although single, high doses of vitamin D effectively maintain vitamin D sufficiency in several populations, no studies have evaluated healthy adults over winter, during which vitamin D status declines. This study investigated whether high-dose vitamin [D.sub.3] given once to healthy adults before winter will (1) prevent the wintertime decline in vitamin D status, (2) promote vitamin D sufficiency 1 year following the dose and (3) prevent the rise of parathyroid hormone (PTH) concentrations. SUBJECTS/METHODS: In this double-blind, placebo-controlled trial, we assessed plasma 25(OH)D and PTH concentrations at baseline, 5, 90 and 365 days after drug administration in 28 healthy adults. In all, >80% of subjects returned at each time point. RESULTS: At baseline, the young, healthy participants had a mean plasma 25(OH)D concentration of 17.5 ± 6.1 ng/ml. Only two subjects exhibited plasma 25(OH)D concentrations >30 ng/ml. At 5 days, subjects randomized to vitamin [D.sub.3] had a higher mean plasma 25(OH)D concentration compared with the placebo group (39.1 vs 19.1 ng/ml, P < 0.001). Plasma 25(OH)D concentrations returned to baseline at 90 and 365 days in the vitamin [D.sub.3] group and remained unchanged in the placebo group. PTH and calcium concentrations were unrelated to changes in 25(OH)D levels and similar between groups over time. CONCLUSIONS: A dose of 250 000 IU of vitamin [D.sub.3] given once in November resulted in a robust increase in plasma 25(OH)D after 5 days, but it was unable to sustain this increase after 90 days. A larger or more frequent dosing regimen may be needed for long-term vitamin D sufficiency. European Journal of Clinical Nutrition (2015) 69, 193-197;doi:10.1038/ejcn.2014.209;published online 1 October 2014, INTRODUCTION Vitamin D status is best assessed by measurement of the serum 25-hydroxyvitamin D (25(OH)D) concentration, the major circulating form of vitamin D. (1) Exposure to ultraviolet-B (UVB) radiation from [...]