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Objective: In-stent restenosis (ISR) is the narrowing of a stented coronary artery lesion. A considerable number of patients undergoing percutaneous coronary intervention (PCI) are affected by ISR. The predominant mechanism in the development of ISR is an inflammatory response to vessel wall injury during PCI. Vitamin D is reported to have anti-inflammatory properties, so it may also be related with ISR. Therefore, in this study the relationship between vitamin D receptor (VDR), vitamin D binding protein (VDBP) gene variations and ISR were investigated.Methods: Fifty-eight ISR patients who have chest pain, underwent angiography and were found to have restenosis in the previously inserted stent were included in the patient group and thirty-five patients who have chest pain and were not found to have restenosis in their previous stent in coronary angiography were included in the control group. rs7041 and rs4588 variations in VDBP; rs1544410 and rs2228570 variations in VDR were investigated by real-time polymerase chain reaction (RT-PCR).Results were evaluated statistically. Results: The CC genotype of rs2228570 variation of VDR and the CA genotype of rs4588 variation of VDBP were found statistically high in patient group. rs7041 variation was found statistically high in patients who had myocardial infarction history before stent implantation. Additionally, it was demonstrated that vitamin D deficiency (vitamin D level

Objective: The aim of this study was to investigate the role of vitamin D replacement therapy on advanced glycation end-products in prediabetes and type 2 diabetes mellitus patients with vitamin D deficiency. Methods: One hundred twenty subjects with serum 25-hydroxyl vitamin D levels less than 20 ng/mL were included in the study. Forty type 2 diabetes mellitus patients (type 2 diabetes mellitus group), 40 prediabetes patients (prediabetes group), and 40 non-diabetes controls (non-diabetes group) were given oral vitamin D3 50 000 units/week for 8 weeks as loading and followed by 1500 U/day as a maintenance dose. We measured serum 25-hydroxyl vitamin D, glycated hemoglobin, carboxymethyl lysine levels, and skin autofluorescence before and on the fourth month of the therapy. Results: Basal serum carboxymethyl lysine and skin autofluorescence measurement in type 2 diabe-tes mellitus and prediabetes groups were significantly higher than the non-diabetes group. While no difference was found between glycated hemoglobin and skin autofluorescence, serum carboxy-methyl lysine levels were significantly elevated for each group following vitamin D replacement. Conclusions: Vitamin D loading did not affect skin advanced glycation end-product levels and gly-cated hemoglobin but was associated with increased serum carboxymethyl lysine levels in all groups.

Sunlight exposure is an essential source of vitamin D for many humans. However, hypovitaminosis D is a global public health problem. This study aimed to develop and validate a sun exposure score (SES) and correlate it with serum 25-hydroxyvitamin D levels in women of childbearing age. One hundred and sixty women aged 18 to 45 years residing in Meknes, Morocco, were included. A questionnaire estimating the sun exposure score and blood analysis of serum 25-OHD concentration were performed. The questionnaire's reliability and construct validity were evaluated using Cronbach's alpha and factor analysis. Spearman's test was used to assess the correlation between SES and 25-OHD levels. The score's reliability and construct validity were good, with Cronbach's alpha values >0.70 and factorial saturation ranging from 0.696 to 0.948. Serum 25-OHD levels were significantly associated with the total sun exposure score, and all SES domains (Rho was 0.615 (p < 0.0001), 0.307 (p < 0.0001), 0.605 (p < 0.0001), and 0.424 (p < 0.0001) for total SES, indoor exposure domain, outdoor exposure domain, and sun protection practice domain, respectively). In addition, median 25-OHD levels increased significantly when sun exposure was changed from insufficient to sufficient (p < 0.0001). The results suggest that the sun exposure score could be used as a clinical tool to assess vitamin D levels in women of childbearing age. ispartof: NUTRIENTS vol:15 issue:3 ispartof: location:Switzerland status: published

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

Vitamin D deficiency is a common finding in overweight/obese pregnant women and is associated with increased risk for adverse pregnancy outcome. Both maternal vitamin D deficiency and maternal obesity contribute to metabolic derangements in pregnancy. We aimed to assess the effects of vitamin D3 supplementation in pregnancy versus placebo on maternal and fetal lipids. Main inclusion criteria were: women

Vitamin D is an important factor in bone metabolism. Animal studies have shown a positive effect of vitamin D-3 supplementation on fracture healing, but evidence from clinical trials is inconclusive. A randomized controlled trial was performed to assess the effects of vitamin D-3 supplementation on fracture healing using HR-pQCT-based outcome parameters. Thirty-two postmenopausal women with a conservatively treated distal radius fracture were included within 2 weeks postfracture and randomized to a low-dose (N = 10) and a high-dose (N = 11) vitamin D intervention group receiving a 6-week bolus dose, equivalent to 700 and 1800 IU vitamin D-3 supplementation per day, respectively, in addition to a control group (N = 11) receiving no supplementation. After the baseline visit 1-2 weeks postfracture, follow-up visits were scheduled at 3-4, 6-8, and 12 weeks postfracture. At each visit, HR-pQCT scans of the fractured radius were performed. Cortical and trabecular bone density and microarchitectural parameters and microfinite element analysis-derived torsion, compression, and bending stiffness were assessed. Additionally, serum markers of bone resorption (CTX) and bone formation (PINP) were measured. Baseline serum levels of 25OHD(3) were

Vitamin D has shown to play a role in multiple diseases due to its skeletal and extraskeletal actions. Furthermore, vitamin D deficiency has become a worldwide health issue. Few supplementation guidelines mention calcifediol treatment, despite being the direct precursor of calcitriol and the biomarker of vitamin D status. This 1-year, phase III-IV, double-blind, randomized, controlled, multicenter clinical trial assessed the efficacy and safety of calcifediol 0.266 mg soft capsules in vitamin D-deficient postmenopausal women, compared to cholecalciferol. Results reported here are from a prespecified interim analysis, for the evaluation of the study's primary endpoint: the percentage of patients with serum 25-hydroxyvitamin D (25(OH)D) levels above 30 ng/ml after 4 months. A total of 303 patients were enrolled, of whom 298 were included in the intention-to-treat (ITT) population. Patients with baseline levels of serum 25(OH)D

Objective: This study investigates the relationship between pathological findings of prostate biopsy and serum 25 (OH) D levels. Materials and Methods: Demographic, clinical and pathological data of 147 eligible patients were included in the study. All patients underwent transrectal ultrasound-guided prostate biopsy. Patients were divided into two groups; those with biopsy-proven prostate cancer (group 1) and those with only benign pathological findings (group 2). Later, two subgroups were formed among the patients diagnosed with prostate cancer (group 1); patients with serum 25 (OH) D levels above and below 20 ng/mL. All groups and subgroups were compared regarding clinical and pathological parameters. Finally, patients were divided according to International Society of Urological Pathology (ISUP) grade groups. Results: Serum 25 (OH) D level of patients with prostate cancer (group 1: 15.6 +/- 7.0 ng/mL) was slightly lower than the non-cancer group (group 2: 16.0 +/- 9.2 ng/mL) (p=0.38). On analysis of variance, there was a statistically significant difference between ISUP grade 1, grade 2-3 and grade 4-5 (p=0.012). Patients with clinically insignificant prostate cancer (ISUP grade 1) had significantly higher serum 25 (OH) D levels than other prostate cancer patients (p=0.023). There was a weak negative correlation between serum 25 (OH) D levels and ISUP grades (r=-0.319, p=0.01). Conclusion: There was no association between the diagnosis of prostate cancer and vitamin D deficiency. However, promising results have been obtained in favour of prostate cancer aggressiveness in vitamin D deficiency.

Background: Vitamin D deficiency is today acknowledged as a pandemic. Vitamin D deficiency and insufficiency are associated with many chronic diseases, including common cancers, cardiovascular diseases, metabolic syndrome, and infectious and autoimmune diseases. Objective: This study aims to investigate the relationship between the cotinine level in urine and Vitamin D. Methods: This study employed a descriptive and relational screening design. It was conducted with 74 smoking university students between January 2019 and March 2020. Data were collected through socio-demographic form and Fagerstrom test for nicotine dependence. Besides, the participating students' blood and urine samples were taken in a suitable environment. Results: The average age of the participating students was 21.50 +/- 2.09. Of all the students, 71.6% were males, 62.2% were exposed to the sun between 12 p.m. and 2 p.m., and the average number of cigarettes smoked daily was 13.52 +/- 8.22. The average Vitamin D level in blood was 32.4 +/- 15.3 (ng/mL), and the average cotinine level in urine was 1.60 +/-.32 (ng/L). No statistically significant relationships were found between the Vitamin D level and the cotinine level (p, Agri Ibrahim Cecen University Scientific Research Projects Unit [SYO.18.004], This research was funded by Agri Ibrahim Cecen University Scientific Research Projects Unit (SYO.18.004).

Key points Reduced vitamin D receptor (VDR) expression prompts skeletal muscle atrophy.Atrophy occurs through catabolic processes, namely the induction of autophagy, while anabolism remains unchanged.In response to VDR‐knockdown mitochondrial function and related gene‐set expression is impaired. In vitro VDR knockdown induces myogenic dysregulation occurring through impaired differentiation.These results highlight the autonomous role the VDR has within skeletal muscle mass regulation. Abstract Vitamin D deficiency is estimated to affect ∼40% of the world's population and has been associated with impaired muscle maintenance. Vitamin D exerts its actions through the vitamin D receptor (VDR), the expression of which was recently confirmed in skeletal muscle, and its down‐regulation is linked to reduced muscle mass and functional decline. To identify potential mechanisms underlying muscle atrophy, we studied the impact of VDR knockdown (KD) on mature skeletal muscle in vivo, and myogenic regulation in vitro in C2C12 cells. Male Wistar rats underwent in vivo electrotransfer (IVE) to knock down the VDR in hind‐limb tibialis anterior (TA) muscle for 10 days. Comprehensive metabolic and physiological analysis was undertaken to define the influence loss of the VDR on muscle fibre composition, protein synthesis, anabolic and catabolic signalling, mitochondrial phenotype and gene expression. Finally, in vitro lentiviral transfection was used to induce sustained VDR‐KD in C2C12 cells to analyse myogenic regulation. Muscle VDR‐KD elicited atrophy through a reduction in total protein content, resulting in lower myofibre area. Activation of autophagic processes was observed, with no effect upon muscle protein synthesis or anabolic signalling. Furthermore, RNA‐sequencing analysis identified systematic down‐regulation of multiple mitochondrial respiration‐related protein and genesets. Finally, in vitro VDR‐knockdown impaired myogenesis (cell cycling, differentiation and myotube formation). Together, these data indicate a fundamental regulatory role of the VDR in the regulation of myogenesis and muscle mass, whereby it acts to maintain muscle mitochondrial function and limit autophagy., Key points Reduced vitamin D receptor (VDR) expression prompts skeletal muscle atrophy.Atrophy occurs through catabolic processes, namely the induction of autophagy, while anabolism remains unchanged.In response to VDR‐knockdown mitochondrial function and related gene‐set expression is impaired. In vitro VDR knockdown induces myogenic dysregulation occurring through impaired differentiation.These results highlight the autonomous role the VDR has within skeletal muscle mass regulation.

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

BackgroundThe association between schizophrenia and decreased vitamin D levels is well documented. Low maternal and postnatal vitamin D levels suggest a possible etiological mechanism. Alternatively, vitamin D deficiency in patients with schizophrenia is presumably (also) the result of disease-related factors or demographic risk factors such as urbanicity.MethodsIn a study population of 347 patients with psychotic disorder and 282 controls, group differences in vitamin D concentration were examined. Within the patient group, associations between vitamin D, symptom levels and clinical variables were analyzed. Group × urbanicity interactions in the model of vitamin D concentration were examined. Both current urbanicity and urbanicity at birth were assessed.ResultsVitamin D concentrations were significantly lower in patients (B = −8.05; 95% confidence interval (CI) −13.68 to −2.42; p = 0.005). In patients, higher vitamin D concentration was associated with lower positive (B = −0.02; 95% CI −0.04 to 0.00; p = 0.049) and negative symptom levels (B = −0.03; 95% CI −0.05 to −0.01; p = 0.008). Group differences were moderated by urbanicity at birth (χ2 = 6.76 and p = 0.001), but not by current urbanicity (χ2 = 1.50 and p = 0.224). Urbanicity at birth was negatively associated with vitamin D concentration in patients (B = −5.11; 95% CI −9.41 to −0.81; p = 0.020), but not in controls (B = 0.72; 95% CI −4.02 to 5.46; p = 0.765).ConclusionsLower vitamin D levels in patients with psychotic disorder may in part reflect the effect of psychosis risk mediated by early environmental adversity. The data also suggest that lower vitamin D and psychopathology may be related through direct or indirect mechanisms.

Vitamin D plays a key role in the maintenance of calcium/phosphate homeostasis and elicits biological effects that are relevant to immune function and metabolism. It is predominantly formed through UV exposure in the skin by conversion of 7-dehydrocholsterol (vitamin D3). The clinical biomarker, 25-hydroxyvitamin D (25-(OH)-D), is enzymatically generated in the liver with the active hormone 1,25-dihydroxyvitamin D then formed under classical endocrine control in the kidney. Vitamin D metabolites are measured in biomatrices by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In LC-MS/MS, chemical derivatization (CD) approaches have been employed to achieve the desired limit of quantitation. Recently, matrix-assisted laser desorption/ionization (MALDI) has also been reported as an alternative method. However, these quantitative approaches do not offer any spatial information. Mass spectrometry imaging (MSI) has been proven to be a powerful tool to image the spatial distribution of molecules from the surface of biological tissue sections. On-tissue chemical derivatization (OTCD) enables MSI to image molecules with poor ionization efficiently. In this technical report, several derivatization reagents and OTCD methods were evaluated using different MSI ionization techniques. Here, a method for detection and spatial distribution of vitamin D metabolites in murine kidney tissue sections using an OTCD-MALDI-MSI platform is presented. Moreover, the suitability of using the Bruker ImagePrep for OTCD-based platforms has been demonstrated. Importantly, this method opens the door for expanding the range of other poor ionizable molecules that can be studied by OTCD-MSI by adapting existing CD methods.

Jing Gao,1,* Tanja Törölä,1,* Chuan-Xing Li,2 Steffen Ohlmeier,3 Tuula Toljamo,4 Pentti Nieminen,5 Noboru Hattori,6 Ville Pulkkinen,1 Hiroshi Iwamoto,6 Witold Mazur1 1Heart and Lung Centre, Department of Pulmonary Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; 2Pulmonomics Group, Respiratory Medicine Unit, Department of Medicine & Centre for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; 3Proteomics Core Facility, Biocentre Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland; 4Department of Pulmonary Medicine, Lapland Central Hospital, Rovaniemi, Finland; 5Medical Informatics and Statistics Group, University of Oulu, Oulu, Finland; 6Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan*These authors contributed equally to this workCorrespondence: Jing GaoHeart and Lung Centre, Department of Pulmonary Medicine, University of Helsinki and Helsinki University Hospital, FinlandTel +358417071559Email jing.gao@helsinki.fi, HelsinkiIntroduction: The vitamin D binding protein (VDBP, also known as GC-globulin) and vitamin D deficiency have been associated with chronic obstructive pulmonary disease (COPD). rs7041 and rs4588 are two single nucleotide polymorphisms of the VDBP gene, including three common allelic variants (GC1S, GC1F and GC2). Previous studies primarily assessed the serum levels of vitamin D and VDBP in COPD. However, less is known regarding the impact of the local release of VDBP on COPD lung function. Thus, we examined the association of sputum and plasma VDBP with lung function at baseline and at four years, and examined potential genetic polymorphism interactions.Methods: The baseline levels of sputum VDBP, plasma VDBP and plasma 25-OH vitamin D, as well as the GC rs4588 and rs7041 genotypes, were assessed in a 4-year Finnish follow-up cohort (n = 233) of non-smokers, and smokers with and without COPD. The associations between the VDBP levels and the longitudinal decline of lung function were further analysed.Results: High frequencies of the haplotypes in rs7041/rs4588 were homozygous GC1S/1S (42.5%). Higher sputum VDBP levels in stage I and stage II COPD were observed only in carriers with GC1S/1S genotype when compared with non-smokers (p = 0.034 and p = 0.002, respectively). Genotype multivariate regression analysis indicated that the baseline sputum VDBP and FEV1/FVC ratio at baseline independently predicted FEV1% at follow-up.Discussion and Conclusion: The baseline sputum VDBP expression was elevated in smokers with COPD among individuals with the GC1S/1S genotype, and predicted follow-up airway obstruction. Our results suggest that the GC polymorphism should be considered when exploring the potential of VDBP as a biomarker for COPD.Keywords: vitamin D binding protein, VDBP, genotype, COPD, prospective study, sputum

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

Purpose: The aim of this study was to determine the possible role of vitamin D on the clavicle fracture in the newborn.Materials and Methods: This retrospective cross-sectional study was conducted between 2018-2020. Infants who were admitted to neonatal intensive care unit due to the clavicle fracture were included. Infants who did not have a fracture, but were admitted to the hospital for reasons instead of exclusion criteria were included as the control group. Birth weight, height, head circumference, gender, gestational week, delivery type, other clinical findings such as brachial plexus paralysis in the infant, maternal age, number of pregnancies, risk factors time to diagnosis were recorded. According to the serum 25-OH vitamin D levels, newborns were classified as having normal vitamin D status (>30 ng/mL), vitamin D insufficient (between 20-30 ng/mL), or deficiency (, Amaç: Bu çalışmada yenidoğan döneminde klavikula kırığı üzerine D vitamininin olası rolünün belirlenmesi amaçlanmıştır.Gereç ve Yöntem: Bu retrospektif kesitsel çalışma 2018-2020 yılları arasında yapılmıştır. Klavikula kırığı nedeniyle yenidoğan yoğun bakım ünitesinde izlenen bebekler çalışmaya alındı. Kontrol grubu kırığı olmayan ancak dışlama kriterleri dışındaki nedenlerle hastaneye başvuran bebeklerden oluşturuldu. Doğum ağırlığı, boyu, baş çevresi, cinsiyeti, gebelik haftası, doğum şekli, bebekte brakiyal pleksus felci gibi diğer klinik bulgular, anne yaşı, gebelik sayısı, tanı zamanı ve risk faktörleri kaydedildi. Yenidoğanlar serum 25-OH D vitamini düzeylerine göre D vitamini düzeyi normal (>30 ng/mL), D vitamini yetersiz (20-30 ng/mL) veya eksikliği olanlar (

Vitamin D supplementation can prevent and cure nutritional rickets in infants and children. Preclinical and observational data suggest that the vitamin D endocrine system has a wide spectrum of skeletal and extra-skeletal activities. There is consensus that severe vitamin D deficiency (serum 25-hydroxyvitamin D (25OHD) concentration 50 nmol/l for optimal bone health in older adults. However, the causal link between vitamin D and many extra-skeletal outcomes remains unclear. The VITAL, ViDA and D2d randomized clinical trials (combined number of participants >30,000) indicated that vitamin D supplementation of vitamin D-replete adults (baseline serum 25OHD >50 nmol/l) does not prevent cancer, cardiovascular events, falls or progression to type 2 diabetes mellitus. Post hoc analysis has suggested some extra-skeletal benefits for individuals with vitamin D deficiency. Over 60 Mendelian randomization studies, designed to minimize bias from confounding, have evaluated the consequences of lifelong genetically lowered serum 25OHD concentrations on various outcomes and most studies have found null effects. Four Mendelian randomization studies found an increased risk of multiple sclerosis in individuals with genetically lowered serum 25OHD concentrations. In conclusion, supplementation of vitamin D-replete individuals does not provide demonstrable health benefits. This conclusion does not contradict older guidelines that severe vitamin D deficiency should be prevented or corrected. This Review highlights results from large randomized clinical trials performed during the period 2017–2020 and Mendelian randomization studies on vitamin D levels. Together, findings indicate that vitamin D supplementation alone in vitamin D-replete adults does not provide health benefits; however, vitamin D deficiency should always be corrected.

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

Objective: Obesity is a risk factor for vitamin D deficiency, which is reported to be detected differently in each population. This study aimed to evaluate the 25(OH) vitamin D (25(OH)D) levels, intact parathormone (iPTH) levels, and their relationship with body mass index (BMI) in obese patients, screened prior to bariatric surgery. Material and Methods: This retrospective study comprised of 1.082 obese patients (41 +/- 10 years, female/male: 823/259) who were candidates for bariatric surgery. BMI, waist circumference (WC), serum 25(OH)D, iPTH, calcium, phosphorus values of these patients were recorded from patient files. Results: BMI, WC, iPTH, and 25(OH)D levels were 48 +/- 8.9 kg/m(2), 128 +/- 11.9 cm, 64 +/- 36 pg/mL, and 15 +/- 18 ng/mL, respectively. Mean 25(OH)D level of 79.1% of the patients belonged to the deficiency range. Very low 25(OH) vitamin D levels (

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

BACKGROUND Worldwide, many newborns who are preterm, small or large for gestational age, or born to mothers with diabetes are screened for hypoglycemia, with a goal of preventing brain injury. However, there is no consensus on a treatment threshold that is safe but also avoids overtreatment. METHODS In a multicenter, randomized, noninferiority trial involving 689 otherwise healthy newborns born at 35 weeks of gestation or later and identified as being at risk for hypoglycemia, we compared two threshold values for treatment of asymptomatic moderate hypoglycemia. We sought to determine whether a management strategy that used a lower threshold (treatment administered at a glucose concentration of

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.

Eren, Erdal/0000-0002-1684-1053; yilmaz, gulay can/0000-0003-0525-1231; Demir, Korcan/0000-0002-8334-2422; UCAKTURK, Seyit Ahmet/0000-0001-8666-4454; Kara, Cengiz/0000-0002-8989-560X WOS: 000469271100005 PubMed: 30396880 Objective: No large study has been conducted to date to compare the effectiveness of prednisolone, alendronate and pamidronate as first-line treatment in children with hypercalcemia due to vitamin D intoxication. The aim was to perform a multicenter, retrospective study assessing clinical characteristics and treatment results. Methods: A standard questionnaire was uploaded to an online national database system to collect data on children with hypercalcemia (serum calcium level > 10.5 mg/dL) due to vitamin D intoxication [serum 25-hydroxyvitamin D (25(OH)D) level > 150 ng/mL] who were treated in pediatric endocrinology clinics. Results: Seventy-four children [median (range) age 1.06 (0.65-1.60) years, 45 males (61 %) from II centers] were included. High-dose vitamin D intake was evident in 77% of the cases. At diagnosis, serum calcium, phosphorus, alkaline phosphatase, 25(OH)D and parathyroid hormone concentrations were 15 +/- 3.2 mg/dl., 5.2 +/- 1.2 mg/dL, 268 +/- 132 IU/L, 322 (236-454) ng/ml, and 5.5 (3-10.5) pg/mL, respectively. Calcium levels showed moderate correlation with 25(OH)D levels (r(s) = 0.402, p

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

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

Vitamin D [1,25(OH)2D—calcitriol] is basically a steroid hormone with pleiotropic biologic effects, and its impact on the regulation of immune system may influence several clinical conditions. Calcidiol (25OHD), as precursor of calcitriol, derives, for the most part (80%), from cutaneous cholesterol (7-dehydrocholesterol) under the action of UV-B (sunlight). Consequently, serum concentrations fluctuate during the year following the circannual rhythm of sun exposition. We will update about the available evidence regarding the complex influence of seasonal vitamin D changes on two different chronic connective tissue diseases, namely rheumatoid arthritis (RA) and systemic sclerosis (SSc). Notably, RA is an emblematic model of autoimmune disease with prevalent joint inflammatory features, while SSc is mainly an autoimmune progressive pro-fibrotic disease. However, in both conditions, low serum concentrations of 25OHD are involved in the pathogenesis of the diseases, and emerging data report their impact on clinical manifestations.

BACKGROUND: Vitamin D has relationships with pathogenesis and inflammation pathways in many diseases. Its deficiency may make clinicians think not only of supplementation but also of presence of other diseases. OBJECTIVE: To investigate the relationship between vitamin D levels and deep vein thrombosis (DVT), given that reduced levels are related to increased risk of cardiovascular diseases. DESIGN AND SETTING: Case-control study conducted in the cardiovascular surgery and family medicine departments of a hospital in Turkey. METHODS: A total of 280 participants were included: 140 each in the DVT and control groups. Basic clinical characteristics, comorbidities and serum 25-hydroxyvitamin D (25(OH)D) levels were recorded and then compared between the groups. Serum 25(OH)D levels were also evaluated separately in three subgroups (sufficient, insufficient and deficient). RESULTS: Serum 25(OH)D levels were significantly lower in the DVT group than in the controls (P < 0.001). Females in the DVT group had lower 25(OH)D levels than those in the control group (P = 0.002). Nonetheless, the median 25(OH)D level (16.41 ng/ml) of the control group was still below the reference value. Logistic regression analysis showed that 25(OH)D was a significant predictor of DVT. Weight, height and body mass index, which all presented interaction, were significant in the logistic regression analysis but not in individual analyses. CONCLUSION: The serum vitamin D levels of DVT patients were lower than those of controls. If the results obtained from our study are supported by further large-scale randomized controlled trials, vitamin D replacement may be brought into the agenda for protection against DVT.

OBJECTIVES: To evaluate the prevalence of low vitamin D levels among well treated pregnant women living with HIV (WLWH) on combination antiretroviral therapy in Denmark, to identify risk factors of low vitamin D levels, and to assess the association between vitamin D status and birth outcomes.DESIGN: Nationwide cohort study.METHODS: All WLWH in Denmark giving birth from 2000 to 2018 with a vitamin D measurement during pregnancy were identified. Risk factors for low vitamin D (deficiency or insufficiency) were assessed using log-binomial regression models, both univariate and adjusted for maternal and HIV factors. The association between vitamin D status and birth outcomes was assessed using linear regression models for continuous outcomes and log-binomial models for binary outcomes.RESULTS: Among 208 WLWH, the prevalence of vitamin D deficiency was 13%, insufficiency 34%, and sufficiency 53%. Being of African origin (RR 2.68, P = 0.01), Asian origin (RR 3.38, P = CONCLUSION: Low vitamin D level was prevalent among well treated pregnant WLWH in Denmark, especially among women of African or Asian origin, and women with detectable viral loads. Vitamin D deficiency was associated with an increased risk of preterm birth and SGA.

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

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

Background Genetic factors modify serum 25-hydroxyvitamin D [25(OH)D] concentration and can affect the optimal intake of vitamin D. Objectives We aimed to personalize vitamin D supplementation by applying knowledge of genetic factors affecting serum 25(OH)D concentration. Methods We performed a genome-wide association study of serum 25(OH)D concentration in the Finnish Health 2011 cohort (n = 3339) using linear regression and applied the results to develop a population-matched genetic risk score (GRS) for serum 25(OH)D. This GRS was used to tailor vitamin D supplementation for 96 participants of a longitudinal Digital Health Revolution (DHR) Study. The GRS, serum 25(OH)D concentrations, and personalized supplementation and dietary advice were electronically returned to participants. Serum 25(OH)D concentrations were assessed using immunoassays and vitamin D intake using FFQs. In data analyses, cross-sectional and repeated-measures statistical tests and models were applied as described in detail elsewhere. Results GC vitamin D-binding protein and cytochrome P450 family 2 subfamily R polypeptide 1 genes showed genome-wide significant associations with serum 25(OH)D concentration. One single nucleotide polymorphism from each locus (rs4588 and rs10741657) was used to develop the GRS. After returning data to the DHR Study participants, daily vitamin D supplement users increased from 32.6% to 60.2% (P = 6.5 x 10(-6)) and serum 25(OH)D concentration from 64.4 +/- 20.9 nmol/L to 68.5 +/- 19.2 nmol/L (P = 0.006) between August and November. Notably, the difference in serum 25(OH)D concentrations between participants with no risk alleles and those with 3 or 4 risk alleles decreased from 20.7 nmol/L to 8.0 nmol/L (P = 0.0063). Conclusions We developed and applied a population-matched GRS to identify individuals genetically predisposed to low serum 25(OH)D concentration. We show how the electronic return of individual genetic risk, serum 25(OH)D concentrations, and factors affecting vitamin D status can be used to tailor vitamin D supplementation. This model could be applied to other populations and countries.

Background Diabetes, osteoporosis, and Vitamin D deficiency are interrelated. The association of the Vitamin D receptor (VDR) gene with bone density is not established in different populations. This study analyze the association between five VDR gene polymorphisms (Fok1 (rs2228570), Taq1 (rs731236), Bsm1 (rs1544410), Apa1 (rs7975232), and EcoRV (rs4516035)) and the occurrence of low bone density (LBD)/osteopenia/osteoporosis in Iranian type 2 diabetics (T2D).Methods This study contained 165 patients with T2D. Separated for gender and polymorphism, crude and adjusted (for age and BMI), logistic regression analysis provided odds ratios (ORs). The most common haplotype was used as the reference for each type of VDR gene polymorphism.Results The occurrence of T2D was 13.03% (165/1266) for the people dwelling in the city of Sanandaj in 2012, until 2013. 13.92% and 81.29% of participants with T2D had osteoporosis and vitamin D deficiency, respectively. In women, tt genotype significantly decreased the risk of LBD/osteopenia/osteoporosis versus Tt genotype, after adjusting for BMI and age (OR=0.18, CI: 0.03-0.97). Conversely, the EE genotype increased the risk of LBD/osteopenia/osteoporosis versus Ee genotype (OR=7.64, CI: 2.03-28.72).Conclusions Among the patients with T2D, Vitamin D deficiency and osteoporosis were prevalent, and some genetic variations in VDR were significantly associated with osteoporosis. In women, a weak protective role in LBD/osteopenia/osteoporosis was found for tt variant of TaqI polymorphism. More importantly, EE variant of EcoRV polymorphism had a strong significant association with increasing the risk of LBD/osteopenia/osteoporosis. Further ethnicity-based cohort studies based on a large study group of T2D patients are recommended.

Background Vitamin D supplementation lowers exacerbation frequency in severe vitamin D-deficient patients with COPD. Data regarding the effect of vitamin D on elastin degradation are lacking. Based on the vitamin's anti-inflammatory properties, we hypothesised that vitamin D supplementation reduces elastin degradation, particularly in vitamin D-deficient COPD patients. We assessed the effect of vitamin D status and supplementation on elastin degradation by measuring plasma desmosine, a biomarker of elastin degradation. Methods Desmosine was measured every 4 months in plasma of 142 vitamin D-naïve COPD patients from the Leuven vitamin D intervention trial (100 000 IU vitamin D3 supplementation every 4 weeks for 1 year). Results No significant association was found between baseline 25-hydroxyvitamin D (25(OH)D) and desmosine levels. No significant difference in desmosine change over time was found between the placebo and intervention group during the course of the trial. In the intervention arm, an unexpected inverse association was found between desmosine change and baseline 25(OH)D levels (p=0.005). Conclusions Vitamin D supplementation did not have a significant overall effect on elastin degradation compared to placebo. Contrary to our hypothesis, the intervention decelerated elastin degradation in vitamin D-sufficient COPD patients and not in vitamin D-deficient subjects., Vitamin D supplementation does not have a significant overall effect on elastin degradation. Vitamin D decelerates elastin degradation in vitamin D-sufficient, but not in vitamin D-deficient, COPD patients. https://bit.ly/2A9H9P7

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

Background/objectives: To investigate (1) the association of four VDR polymorphisms (TaqI/rs731236, ApaI/rs7975232, FokI/rs10735810, and Bsml/rs1544410) with markers of adiposity and tissue-specific insulin resistance at baseline, after weight loss and weight maintenance; (2) the effect of the VDR polymorphisms in the SAT transcriptome in overweight/obese Caucasians of the DiOGenes cohort. Methods: We included 553 adult obese individuals (mean BMI 34.8 kg/m 2), men (n = 197) and women (n = 356) at baseline, following an 8-week weight loss intervention and 26 weeks weight maintenance. Genotyping was performed using an Illumina 660W-Quad SNP chip on the Illumina iScan Genotyping System. Tissue-specific IR was determined using Hepatic Insulin Resistance Index (HIRI), Muscle Insulin Sensitivity Index (MISI), and Adipose Tissue Insulin Resistance Index (Adipo-IR). Expression quantitative trait loci (eQTL) analysis was performed to determine the effect of SNPs on SAT gene expression. Results: None of the VDR polymorphisms were associated with HIRI or MISI. Interestingly, carriers of the G allele of VDR FokI showed higher Adipo-IR (GG + GA 7.8 ± 0.4 vs. AA 5.6 ± 0.5, P = 0.010) and higher systemic FFA (GG + GA: 637.8 ± 13.4 vs. AA: 547.9 ± 24.7 µmol/L, P = 0.011), even after adjustment with age, sex, center, and FM. However, eQTL analysis showed minor to no effect of these genotypes on the transcriptional level in SAT. Also, VDR polymorphisms were not related to changes in body weight and IR as result of dietary intervention (P > 0.05 for all parameters). Conclusions: The VDR Fokl variant is associated with elevated circulating FFA and Adipo-IR at baseline. Nevertheless, minor to no effect of VDR SNPs on the transcriptional level in SAT, indicating that putative mechanisms of action remain to be determined. Finally, VDR SNPs did not affect dietary intervention outcome in the present cohort.

Environmental factors such as sunshine hours, temperature and UV radiation (UVR) are known to influence seasonal fluctuations in vitamin D concentrations. However, currently there is poor understanding regarding the environmental factors or individual characteristics that best predict neonatal 25-hydroxyvitamin D (25(OH)D) concentrations. The aims of this study were to (1) identify environmental and individual determinants of 25(OH)D concentrations in newborns and (2) investigate whether environmental factors and individual characteristics could be used as proxy measures for neonatal 25(OH)D concentrations. 25-Hydroxyvitamin D3 (25(OH)D3) was measured from neonatal dried blood spots (DBS) of 1182 individuals born between 1993 and 2002. Monthly aggregated data on daily number of sunshine hours, temperature and UVR, available from 1993, were retrieved from the Danish Meteorological Institute. The individual predictors were obtained from the Danish National Birth register, and Statistics Denmark. The optimal model to predict 25(OH)D3 concentrations from neonatal DBS was the one including the following variables: UVR, temperature, maternal education, maternal smoking during pregnancy, gestational age at birth and parity. This model explained 30 % of the variation of 25(OH)D3 in the neonatal DBS. Ambient UVR in the month before the birth month was the best single-item predictor of neonatal 25(OH)D3, accounting for 24 % of its variance. Although this prediction model cannot substitute for actual blood measurements, it might prove useful in cohort studies ranking individuals in groups according to 25(OH)D3 status.

Serum vitamin D levels negatively correlate with obesity and associated disorders such as non-alcoholic steatohepatitis (NASH). However, the mechanisms linking low vitamin D (VD) status to disease progression are not completely understood. In this study, we analyzed the effect of VD treatment on NASH in mice. C57BL6/J mice were fed a high-fat/high-sugar diet (HFSD) containing low amounts of VD for 16 weeks to induce obesity, NASH and liver fibrosis. The effects of preventive and interventional VD treatment were studied on the level of liver histology and hepatic/intestinal gene expression. Interestingly, preventive and to a lesser extent also interventional VD treatment resulted in improvements of liver histology. This included a significant decrease of steatosis, a trend towards lower non-alcoholic fatty liver disease (NAFLD) activity score and a slight non-significant decrease of fibrosis in the preventive treatment group. In line with these changes, preventive VD treatment reduced the hepatic expression of lipogenic, inflammatory and pro-fibrotic genes. Notably, these beneficial effects occurred in conjunction with a reduction of intestinal inflammation. Together, our observations suggest that timely initiation of VD supplementation (preventive vs. interventional) is a critical determinant of treatment outcome in NASH. In the applied animal model, the improvements of liver histology occurred in conjunction with reduced inflammation in the gut, suggesting a potential relevance of vitamin D as a therapeutic agent acting on the gut-liver axis.

Purpose Children with acute lymphoblastic leukemia (ALL) are at increased risk of vitamin D deficiency, which might make them more susceptible to developing adverse events. Previous studies showed that low vitamin D levels were associated with an increased inflammatory mucosal state and impaired mucosal tissue barriers. We examined the prevalence of vitamin D deficiency and studied the association between vitamin D levels and methotrexate (MTX)-induced oral mucositis in pediatric ALL. Methods We assessed 25-hydroxyvitamin D (25(OH)D3) and 24,25-dihydroxyvitamin D (24,25(OH)2D3) levels in 99 children with ALL before the start of 4 × 5 g/m2 high-dose methotrexate (HD-MTX) (T0) and in 81/99 children after discontinuation of HD-MTX (T1). Two cutoff values for vitamin D deficiency exist: 25(OH)D3 levels 4 years of age as compared to children between 1 and 4 years of age. A decrease in 25(OH)D3 levels during HD-MTX therapy was associated with developing severe oral mucositis (OR 1.6; 95% CI [1.1–2.4]). 25(OH)D3 and 24,25(OH)2D3 levels at T0 and the change in 24,25(OH)2D3 levels during therapy were not associated with the development of severe oral mucositis. Conclusions This study showed that vitamin D deficiency occurs frequently in pediatric ALL patients above the age of 4 years. A decrease in 25(OH)D3 levels during MTX therapy was observed in children with ALL that developed severe oral mucositis. Electronic supplementary material The online version of this article (10.1007/s00520-018-4312-0) contains supplementary material, which is available to authorized users.

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

RATIONALE: Vitamin D deficiency is common in patients with asthma and COPD. Low 25-hydroxyvitamin D (25[OH]D) levels may represent a cause or a consequence of these conditions. OBJECTIVE: To determine whether vitamin D metabolism is altered in asthma or COPD. METHODS: We conducted a longitudinal study in 186 adults to determine whether the 25(OH)D response to six oral doses of 3 mg vitamin D3, administered over one year, differed between those with asthma or COPD vs. controls. Serum concentrations of vitamin D3, 25(OH)D3 and 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3) were determined pre- and post-supplementation in 93 adults with asthma, COPD or neither condition, and metabolite-to-parent compound molar ratios were compared between groups to estimate hydroxylase activity. Additionally, we analyzed fourteen datasets to compare expression of 1α,25[OH]2D3-inducible gene expression signatures in clinical samples taken from adults with asthma or COPD vs. controls. MEASUREMENTS AND MAIN RESULTS: The mean post-supplementation 25(OH)D increase in participants with asthma (20.9 nmol/L) and COPD (21.5 nmol/L) was lower than in controls (39.8 nmol/L; P=0.001). Compared with controls, patients with asthma and COPD had lower molar ratios of 25(OH)D3-to-vitamin D3 and higher molar ratios of 1α,25(OH)2D3-to-25(OH)D3 both pre- and post-supplementation (P≤0.005). Inter-group differences in 1α,25[OH]2D3-inducible gene expression signatures were modest and variable where statistically significant. CONCLUSIONS: Attenuation of the 25(OH)D response to vitamin D supplementation in asthma and COPD associated with reduced molar ratios of 25(OH)D3-to-vitamin D3 and increased molar ratios of 1α,25(OH)2D3-to-25(OH)D3 in serum, suggesting that vitamin D metabolism is dysregulated in these conditions.

Ultraviolet-irradiated yeast (Saccharomyces cerevisiae) can be used to biofortify bakery products with vitamin D, but in bread, it was not effective in increasing serum 25-hydroxyvitamin D [25(OH)D] in humans, possibly because of the low digestibility of the yeast matrix. We investigated the effects of vitamin D-2-rich intact yeast cells and their separated fraction, yeast cell walls, which we hypothesized to provide vitamin D-2 in a more bioavailable form, on serum 25(OH)D and its metabolites in growing female Sprague-Dawley rats (n = 54) compared to vitamin D-2 and D-3 supplements (8 treatment groups: 300 or 600 IU vitamin D/d, and a control group, 8-week intervention). The D-3 supplement groups had the highest 25(OH)D concentrations, and the vitamin D-2 supplement at the 600-IU dose increased 25(OH)D better than any yeast form (P .05). Serum 24,25-dihydroxyvitamin D (a vitamin D catabolite) concentrations and the trend in the differences between the groups were in line with 25 (OH)D (P .05). These findings do not support the hypothesis: the ability of the different ultraviolet-treated vitamin D-2-containing yeast forms to increase 25(OH)D did not differ, and the poor bioavailability of vitamin D-2 in the yeasts compared D-3 or D-2 supplements could not be explained by the increased vitamin D catabolism in the yeast-treated groups. (C) 2018 Elsevier Inc. All rights reserved.

Vitamin D supplementation is often used in the prevention and treatment of osteoporosis, but the role of vitamin D has lately been questioned. We aimed to investigate the effect of 3 months of daily vitamin D3 supplementation (70 µg [2800 IU] vs. placebo) initiated in winter months on bone health. This study is a double-blinded placebo-controlled randomized trial. Bone health was assessed by bone turnover markers, DXA, HRpQCT, and QCT scans. The participants were 81 healthy postmenopausal women with low 25(OH)D ( 6.9 pmol/l) at screening. Vitamin D3 supplementation significantly increased levels of 25(OH)D and 1,25(OH)2D by 59 nmol/l and 19 pmol/l, respectively, whereas PTH was reduced by 0.7 pmol/l (all p

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

Background and objective: Chronic obstructive pulmonary disease and low vitamin D status predict mortality, but their combined effect on mortality remains inconclusive. We aimed to investigate a joint effect of airway obstruction and vitamin D status on mortality in a nationally representative cohort. Methods: We analysed data of 6676 Finnish adults participating between 1978 and 1980 in a national health examination survey, undergoing spirometry and having all necessary data collected. We followed them up in national registers through record linkage until 31 December 2011. We categorised the subjects with obstruction using the lower limit of normal (LLN) and the measured serum 25-hydroxyvitamin-D (s-25(OH)D) into tertiles. Results: Both obstruction and low s-25(OH) D independently predicted mortality in a multivariate model adjusted also for age, sex, smoking, education, leisure physical activity, body mass index, asthma and serum C-reactive protein. However, a statistically significant (p = 0.007) interaction emerged: the adjusted mortality HRs (95% CI's) for s-25(OH)D in tertiles among the subjects without and with obstruction were 1.00 (lowest), 0.96 (0.87-1.05) and 0.89 (0.81-0.98); and 1.00, 0.96 (0.71-1.31) and 0.57 (0.40-0.80), respectively. Conclusions: In conclusion, obstruction and low s-25(OH)D predict mortality independently of each other. Our findings suggest that low vitamin D status might be particularly detrimental among subjects with obstruction.