Adverse Effects Of Vitamin Research Articles

The effect of maternal vitamin D deficiency during pregnancy on glycolipid metabolism of offspring rats and the improvement of vitamin D intervention after weaning.

Vitamin D deficiency during pregnancy is common, but whether maternal vitamin D status affects glycolipid metabolism of offspring remains unclear. To evaluate the effect of maternal vitamin D deficiency during pregnancy on the glycolipid metabolism of offspring at different life-cycles (from birth to adulthood) and to explore the improvement of different dosages of vitamin D supplementation. Sprague-Dawley rats were fed vitamin D-deprived (VDD group) or standard vitamin D diets (SC group) during pregnancy, and their diets were changed to standard vitamin D diets during lactation (the offspring were sorted into VDDoffspring and SCoffspring groups). After weaning, rats in the VDDoffspring group were randomly assigned to the VDDoffspring, VDDoffspring-S3300 and VDDoffspring-S10000 groups with diets containing standard, medium and high dosages of vitamin D for 12 wk. Serum was collected for biochemical analyses at postnatal Day 21, postnatal Day 56 and postnatal Day 84. Oral glucose tolerance test (OGTT) was performed at postnatal Day 70. Compared to SCoffspring, rats in the VDDoffspring group had significantly lower birth weight with faster weight gain and higher levels of lipid metabolism in early life. After near adulthood, the differences in weight and lipid metabolism between the two groups disappeared. OGTT showed significantly higher blood glucose levels in the VDDoffspring group at 30 min, 60 min, and 90 min. The continuation of vitamin D supplementation at medium and high dosages after weaning did not cause any obvious changes in weight or glycolipid metabolism (except for postprandial hyperglycemia). OGTT demonstrated that the glucose levels in the VDDoffspring-S3300 group were lowest at all the time points and that those in the VDDoffspring-S10000 group were the highest at 30 min, 60 min, and 90 min among the three groups. The adverse effects of vitamin D deficiency during pregnancy on glycolipid metabolism in offspring vary in different stages. Over a long time period, adequate vitamin D supplementation is beneficial to glycolipid metabolism for the offspring of subjects with vitamin D deficiency during pregnancy; however, further improvement is required.

Beneficial and adverse effects of vitamin E on the kidney.

This article reviews the beneficial and adverse effects of high-dose vitamin E supplementation on the vitamin E status and renal function in human and rodent studies. The high doses of vitamin E, which can cause renal effects, were compared to upper limits of toxicity (UL) as established by various authorities worldwide. In recent mice studies with higher doses of vitamin E, several biomarkers of tissue toxicity and inflammation were found to be significantly elevated. In these biomarker studies, the severity of inflammation and the increased levels of the biomarkers are discussed together with the need to re-evaluate ULs, given the toxic effects of vitamin E on the kidney and emphasizing oxidative stress and inflammation. The controversy in the literature about vitamin E effects on the kidney is mainly caused by the dose-effects relations that do not give a clear view, neither in human nor animals studies. In addition, more recent studies on rodents with new biomarkers of oxidative stress and inflammation give new insights into possible mechanisms. In this review, the controversy is shown and an advice given on the vitamin E supplementation for renal health.

Reduced Time to Procedure for Gastrointestinal Bleeding After Warfarin Reversal With Four-Factor Complex Concentrate as Compared to Plasma.

Bleeding is a serious adverse effect of vitamin K antagonists (VKAs). Anticoagulation reversal is required in some acute cases. This is usually accomplished by plasma transfusion or four-factor prothrombin complex concentrate (4F-PCC). The aim of this study was to gain insight into the clinical course of patients with gastrointestinal (GI) bleeding who require VKA reversal. Medical records were collected from two centers from patients who presented to the emergency department (ED) for GI bleeding and received 4F-PCC or plasma for VKA reversal between January 2015 and December 2020. ED, hospital, intensive care unit (ICU) length of stay (LOS) as well as time from admission to GI procedure were determined. 4F-PCC patients (n = 49) as compared to plasma (n = 63) patients were found to have a greater number of comorbidities (average of 4.2 vs. 2.7 comorbidities/patient) and more ICU admissions (47% vs. 21%). Time to GI procedure was significantly decreased in the 4F-PCC group (median (interquartile range (IQR)) 19.47 (9.23 - 30.25) vs. 27.88 (21.38 - 45.00) h; P = 0.01). When adjusting for comorbidities, differences in time to GI procedures were also significant in favor of 4F-PCC regardless of any comorbidities (P = 0.014), in atrial fibrillation (P = 0.045) and in hypertension (P = 0.02). The 4F-PCC patients had shorter LOS in the ED and ICU. Our study demonstrated that compared to plasma, 4F-PCC was utilized in more acutely ill patients with higher rates of comorbidities and ICU admission. Nevertheless, the patients who received 4F-PCC had faster access to GI procedure and shorter ED and ICU LOS.

Забезпеченість вітаміном D та вплив його дефіциту на перебіг алергічних захворювань у дітей

The prevalence of allergic pathology is increasing significantly in both adults and children, and at the same time, the problem of vitamin D deficiency remains relevant. Recent studies have revealed a close connection between vitamin D deficiency and the development of allergic diseases in children. In addition to its role in bone and calcium metabolism, recent observations have shown its possible role as an immunomodulator in allergic diseases. This is due to the presence of vitamin D receptors in most cells of the human body. One of the most important functions of vitamin D is to modulate the response of the immune system, both innate and adaptive. Currently, there is no consensus on the possible mechanisms of vitamin D involvement in the pathogenesis of allergies. It is believed that the role of vitamin D in the pathogenesis of allergic diseases is due to its regulatory effect on the immune system, participation in antimicrobial protection and ensuring the barrier function of the skin and mucous membranes. In this regard, considerable attention is paid to the study of the role of vitamin D in the development and course of allergic diseases in children. Purpose - to summarize the literature data on the biological role of vitamin D and the impact of its deficiency on the course of allergic diseases in children. Results and conclusions. In most scientific studies, the adverse effect of vitamin D deficiency on the allergic process has been established - an insufficient level of 25(OH)D in blood serum was found in children with asthma, allergic rhinitis, atopic dermatitis and food allergies. Also, a number of authors found a connection between the status of vitamin D and the risk of development and exacerbation of an allergic disease or indicators of a severe course. Although other researchers deny such relationship. Despite the inconsistencies in the literature, it is possible to note the important role of vitamin D in the development and course of allergic diseases in children. No conflict of interests was declared by the authors.

The effect of vitamin D on recurrence of uterine fibroids: A randomized, double-blind, placebo-controlled pilot study

Backgroundand purpose: A deficiency of vitamin D has been suggested as one of the principal risk factors for uterine fibroids (UFs). We aimed to investigate the effect of vitamin D supplementation on the recurrence of UFs. Materials and methodsIn a randomized, double-blind, placebo-controlled pilot study, women who had undergone hysteroscopic myomectomy from November 2017 to June 2020 were randomly given either vitamin D (1000 IU tablet; n = 55), or placebo (n = 54) daily for 12 months. Both groups were followed and compared in regard of the primary outcomes of the study, which were recurrence rates, size, and numbers of UFs based on three-dimensional transvaginal ultrasound investigation (3D-TVS). Data analysis was performed by the intention-to-treat (ITT) approach. ResultsThe mean age of the study participants was 37.9 ± 6.5 years. The two groups did not differ significantly in terms of demographic and pre-intervention clinical characteristics. The administration of vitamin D supplements for one year reduced recurrence rates of UFs by 50% (p = 0.17). Vitamin D also reduced the size of recurrent UFs in the intervention group compared to controls (−7.7 mm), the difference was statistically different (p < 0.001). No adverse effect of vitamin D was reported in the present study. ConclusionBased on these results, vitamin D appears to be a promising and safe agent in the prevention of recurrence and reduction of the size of recurrent UFs, although further well-designed and appropriately powered studies are required to demonstrate a significant difference in the size and number of recurrent UFs.

Clinical Role of Oral Vitamin C and E Therapy in Skin and Hair Disorders

Clinical Role of Oral Vitamin C and E Therapy in Skin and Hair Disorders

Effect of serum 25-hydroxyvitamin D concentrations on skeletal mineralization in black and white women

There is controversy over the adverse effect of vitamin D deficiency on bone mineralization. The purpose of this study was to determine the ethnical differences in vitamin D and bone mineralization as well as the association between vitamin D deficiency and bone mineralization defects. We examined serum 25-hydroxyvitamin D (25(OH)D) levels and transiliac bone biopsies in 92 healthy black and white women, aged 20-73 years. The major bone mineralization indices include osteoid volume per bone volume (OV/BV), osteoid surfaces per bone surface (OS/BS), osteoid thickness (O.Th) and mineralization lag time (Mlt). 25(OH)D levels were significantly lower and prevalence of 25(OH)D deficiency was significantly higher in blacks than in whites. However, none of the mineralization indices showed significant difference between the two groups. In addition, there was no significant correlation between 25(OH)D levels and mineralization indices in both black and white cohorts. Only one case had O.Th marginally greater than 12.5 µm, which is the cutoff value for identifying bone mineralization defects. OV/BV and OS/BS, but not O.Th, were significantly positively correlated with activation frequency (Ac.f). Our study indicated: (1) vitamin D deficiency is common, but bone mineralization is not impaired in black women, and (2) there are no significant correlations between serum 25(OH)D levels and bone mineralization indices, suggesting that vitamin D deficiency may not be an independent factor contributing to bone mineralization defects and osteomalacia.

Oral Vitamin D Therapy in Patients with Psoriasis

Vitamin D treatment is effective when applied topically to the skin for plaque-type psoriasis. Oral vitamin D supplementation might be effective as an adjuvant treatment option in psoriasis. This umbrella review aimed to highlight the current knowledge regarding the use of oral vitamin D for treatment of patients with psoriasis. We performed a literature search and identified 107 eligible full-text articles that were relevant to the research interest. Among these, 10 review articles were selected, and data were extracted. A data synthesis showed that only a few studies monitored oral vitamin D efficacy in patients with psoriasis. No studies investigated the optimal dose of systemic vitamin D in psoriasis. However, most studies did not observe side effects for doses within a relatively narrow range (0.25 to 2 μg/day). These results suggest that more large-scale studies are needed to determine the efficacy, optimal dose, and adverse effects of vitamin D administration in patients with psoriasis.

Role of vitamin D in oxidative stress modulation in end-stage renal disease patients: A double-blind randomized clinical trial.

Oxidative stress is considered as important actor in uremia-associated morbidity and mortality in hemodialysis (HD) patients. We aimed to evaluate the role of vitamin D supplementation on oxidative stress parameters in this group. This double-blind randomized clinical trial was conducted on HD patients who were randomly allocated into intervention (n = 40) or control groups (n = 38) for 10 weeks. Blood samples were taken before and at the end of the trial to measure serum 25-hydroxyvitamin D (25(OH)D), malondialdehyde (MDA), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). Data were analyzed using SPSS, and P value <0.05 was considered to be statistically significant. Out of the 78 patients with a mean age of 44.7 ± 13.0 years, 55.1% were men. At the commencement of the study, there was no difference with respect to serum 25(OH)D levels in our groups (P = 0.575), but during the study it was significantly elevated in the intervention group (18.1 ± 9.1 vs. 31.7 ± 12.9, P < 0.0001). Serum antioxidative enzymes activity (GPx, CAT, and SOD) had significantly increased after vitamin D supplementation in the intervention group (P < 0.05). Furthermore, MDA levels was significantly reduced only in the intervention group (31.7 ± 18.0 vs. 24.7 ± 7.7, P = 0.018). Regular consumption of vitamin D can increase the GPx, CAT, SOD, and reduce the MDA plasma levels in HD patients. Since no adverse effects of vitamin D supplementation was reported by the patients; hence, it can be prescribed for HD patients.

The Effect of Vitamin D Supplementation on Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objective: A systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to assess the benefits and harms of vitamin D supplementation for attention-deficit/hyperactivity disorder (ADHD) patients. Methods: We followed the standard methodological procedures of the Cochrane Handbook for Systematic Reviews of Intervention. PubMed, Embase, the Cochrane Central Register of Controlled Trials, Science and Conference Proceedings Citation Index-Social Science and Humanities (Web of Science), ClincalTrials.gov, and World Health Organization's International Clinical Trials Registry Platform were searched for RCTs in January 2019. Independently, two authors (J.G., T.X.) extracted data, assessed the risk of bias, combined the data, and graded evidence quality using the Grading of Recommendations Assessment, Development, and Evaluation approach. Our primary outcomes were assessed through rating scales of ADHD severity. Secondary outcomes measured were the possible adverse effects of vitamin D supplementation and vitamin D status after supplementation for ADHD. Results: We included four RCTs with 256 children addressing vitamin D supplementation as adjunctive therapy to methylphenidate on ADHD symptoms. Vitamin D supplementation demonstrated a small but statistically significant improvement in ADHD total scores, inattention scores, hyperactivity scores, and behavior scores. The improvement was likely limited due to the low to very low quality of evidence in the literature. There was no statistically significant improvement in oppositional scores. Reported adverse events in the vitamin D group were mild and not significantly different from the control group. Vitamin D supplementation increased serum vitamin D levels and the ratio of patients with sufficient vitamin D levels. Conclusions: Vitamin D supplementation as adjunctive therapy to methylphenidate appeared to reduce ADHD symptoms without serious adverse events, associated with improved vitamin D status. However, considering the generally low strength of evidence, well-designed RCTs are needed to determine the efficacy and safety of vitamin D supplementation for both children and adults with ADHD, especially in the setting of a combination of vitamin D and other ADHD treatments.

Evaluation of Tolerable Upper Intake Levels for Vitamin D in Children and Adolescents

In 2012, the European Food Safety Authority (EFSA) suggested a tolerable upper intake level (UL) for vitamin D at 100 µg/day for adults based on the risk of hypercalcaemia. EFSA concluded that consumption of up to 50 µg/day does not lead to hypercalcaemia in children and adolescents (10-17 years). Furthermore, EFSA stated that there is no reason to assume that children and adolescents in the phase of rapid bone formation and growth have a lower tolerance for vitamin D compared to adults, and a UL of 100 µg/day for adolescents aged 11-17 years and 50 µg/day in children 1-10 years, taking the smaller body size into account, was proposed.&#x0D; The Norwegian Food Safety Authority (NFSA) is currently revising the national regulation of maximum limits in food supplements (not yet harmonised in the European Economic Area (EEA)), including maximum limits for vitamin D. NFSA has therefore requested the Norwegian Scientific Committee for Food Safety (VKM) to evaluate the assumption in the EFSA opinion that children and adolescents can tolerate the same amount of vitamin D as adults due to rapid bone formation and growth. In children and adolescents with lower weight than adults, this assumption actually implies that adolescents can tolerate more vitamin D per kg body weight than adults. VKM is therefore requested to evaluate if there is scientific evidence that a UL at 50 µg/day for children (1-10 years) and 100 µg/day for adolescents (11-17 years) is safe.&#x0D; The present statement is prepared by members of the Panel on Nutrition, Dietetic Products and Novel Food and Allergy in VKM.&#x0D; Three literature searches were performed to find new relevant studies investigating high intakes of vitamin D in children and adolescents and the role of vitamin D in bone formation and growth.&#x0D; No studies supporting a higher tolerance to vitamin D in children and adolescents due to rapid bone formation and growth were retrieved in the literature search. Moreover, there is apparently no firm association between bone formation and vitamin D levels in children during their growth period into adolescence and adulthood. &#x0D; No studies investigating high intakes of vitamin D in children 1-10 years were found. Furthermore, no studies that have examined safety issues and/or adverse effects of vitamin D supplementation in doses above 50 µg/day in adolescents were identified. It can therefore not be concluded that the UL at 50 µg/day in children (1-10 years) and 100 µg/day in adolescents (11-17 years) is safe.&#x0D; In the 2002 report from European Scientific Committee on Food (SCF), a UL was set at 25 µg/day for children aged 2-10 years, and 50 µg/day for adolescents aged 11-17 years (corresponding to the UL for adults at that time). To the best of knowledge no serious, harmful effects have been reported for these doses of vitamin D.

Vitamin A supplementation to prevent mortality and short- and long-term morbidity in very low birth weight infants.

Vitamin A is necessary for normal lung growth and the integrity of respiratory tract epithelial cells. Preterm infants have low vitamin A status at birth and this has been associated with an increased risk of developing chronic lung disease. To evaluate supplementation with vitamin A on the incidence of death or neonatal chronic lung disease and long-term neurodevelopmental disability in very low birth weight (VLBW) infants compared with a control (placebo or no supplementation), and to consider the effect of the supplementation route, dose, and timing. For the original review and subsequent updates, we searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, Science Citation Index, and the Oxford Database of Perinatal Trials. The reference lists of relevant trials, paediatric and nutrition journals, and conference abstracts and proceedings were handsearched up to 2010.For the 2016 update, we used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 4), MEDLINE via PubMed (1 May 2016), EMBASE (1 May 2016), and CINAHL (1 May 2016). We also searched clinical trials' databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised controlled trials comparing vitamin A supplementation with a control (placebo or no supplementation) or other dosage regimens in VLBW infants (birth weight ≤ 1500 grams or less than 32 weeks' gestation). Two review authors screened the search results, extracted data, and assessed the trials for risk of bias. Results were reported as risk ratios (RR), risk differences (RD), and number needed to treat to benefit (NNTB), all with 95% confidence intervals (CI). Trialists were contacted for additional data. Eleven trials met the inclusion criteria. Ten trials (1460 infants) compared vitamin A supplementation with a control and one (120 infants) compared different regimens of vitamin A supplementation. Compared to the control group, vitamin A appeared to have a small benefit in reducing the risk of death or oxygen requirement at one month of age (typical RR 0.93, 95% CI 0.88 to 0.99; typical RD -0.05, 95% CI -0.10 to -0.01; NNTB 20, 95% CI 10 to 100; 6 studies, 1165 infants) and the risk of chronic lung disease (oxygen requirement) at 36 weeks' postmenstrual age (typical RR 0.87, 95% CI 0.77 to 0.99; typical RD -0.07, 95% CI -0.13 to -0.01; NNTB 11, 95% CI 6 to 100; 5 studies, 986 infants) (moderate-quality evidence). There was a marginal reduction of the combined outcome of death or chronic lung disease (typical RR 0.92, 95% CI 0.84 to 1.01; typical RD -0.05, 95% CI -0.11 to 0.01; 4 studies, 1089 infants). Neurodevelopmental assessment of 88% of the surviving infants in the largest trial showed no difference between the groups at 18 to 22 months of age, corrected for prematurity (low-quality evidence). There is no evidence to support different vitamin A dosing regimens. No adverse effects of vitamin A supplementation were reported, but it was noted that intramuscular injections of vitamin A were painful. Whether clinicians decide to utilise repeat intramuscular doses of vitamin A to prevent chronic lung disease may depend upon the local incidence of this outcome and the value attached to achieving a modest reduction in the outcome balanced against the lack of other proven benefits and the acceptability of the treatment. Information on long-term neurodevelopmental status suggests no evidence of either benefit or harm from the intervention.

No Effect of High-Dose Vitamin D Treatment on β-Cell Function, Insulin Sensitivity, or Glucose Homeostasis in Subjects With Abnormal Glucose Tolerance: A Randomized Clinical Trial.

There has been conflicting evidence regarding the potential role of vitamin D in glucose homeostasis. This study was designed to investigate the effect of high-dose vitamin D3 treatment on β-cell function, insulin sensitivity, and glucose tolerance in subjects with prediabetes or diet-treated type 2 diabetes. Subjects (n = 44) were randomized to 30,000 IU vitamin D3 once weekly or placebo for 8 weeks. Hyperglycemic clamp assessed first-phase (0-12 min) and second-phase (12-120 min) insulin response, insulin sensitivity, and disposition index (DI). An oral glucose tolerance test assessed glucose tolerance and glycosylated hemoglobin assessed glycemic control. A total of 21 (vitamin D) and 22 (placebo) subjects completed the study, respectively. Season-adjusted 25-OH-vitamin D [25(OH)D] levels were doubled in the active treated group (43-82 nmol/L). No effect of vitamin D treatment, compared with placebo, was seen on first-phase or second-phase insulin secretion. There were no group differences in insulin sensitivity, DI, or any measures of glycemic control. No hypercalcemia or other adverse effects of vitamin D treatment were seen compared with placebo. Subgroup analyses of those with the lowest basal and greatest increase in 25(OH)D levels did not change these results. This study gives no support for any substantial effect of high-dose vitamin D treatment for 8 weeks in prediabetes or diet-treated type 2 diabetes on β-cell function, insulin sensitivity, or glycemic control.

Vitamin D Deficiency: "At Risk" Patient Populations and Potential Drug Interactions

Vitamin D is known to play an essential role in calcium homeostasis; however, excessive amounts can have harmful effects. Calcium and vitamin D levels are known to be influenced by drug interactions and pathology ranging from cancer to cardiovascular disease. Vitamin D supplementation has become widespread, and it is important for clinicians to understand the way that certain conditions and medications interact with vitamin D and calcium homeostasis. The purpose of this review is to outline the benefits and adverse effects of vitamin D and how its levels are affected by certain pathologic and pharmacologic interactions.

Dietary Supplement Therapies for Inflammatory Bowel Disease: Crohn's Disease and Ulcerative Colitis.

Inflammatory bowel disease (IBD) including ulcerative colitis and Crohn's disease are chronic relapsing and remitting chronic diseases for which there is no cure. The treatment of IBD frequently requires immunosuppressive and biologic therapies which carry an increased risk of infections and possible malignancy. There is a continued search for safer and more natural therapies in the treatment of IBD. This review aims to summarize the most current literature on the use of dietary supplements for the treatment of IBD. Specifically, the efficacy and adverse effects of vitamin D, fish oil, probiotics, prebiotics, curcumin, Boswellia serrata, aloe vera and cannabis sativa are reviewed.

Adverse effects of vitamin D deficiency on the Pi3k/Akt pathway and pancreatic islet morphology in diet-induced obese mice.

To investigate the impact of vitamin D deficiency on insulin resistance and abnormal glucose homeostasis in obesity. Sixty male C57BL/6 mice (3 months old) were fed a control diet (C-10% energy as fat) or a high-fat diet (HF-50% energy as fat), with or without vitamin D, for 8 weeks. There was no difference in body mass between the HF and HF/VitD- groups. Vitamin D deficiency (VitD) in the diet-induced obese mice increased hyperinsulinemia (p = 0.04), hyperleptinemia (p = 0.0002), insulin resistance (HOMA-IR, p = 0.04), and islet changes, including alpha and beta cell disarray. In the insulin signaling pathway, insulin receptor substrate 2 expression was upregulated in the C/VitD- group (p = 0.001) and downregulated in the HF/VitD- group (p = 0.009). Interestingly, forkhead box protein O1 expression was higher in the HF/VitD- group than in the HF group (p = 0.03), and pancreatic and duodenal homeobox 1 expression was lower in the HF/VitD-group than in the HF group (p = 0.025), indicating that the HF diet and vitamin D deficiency influenced the downregulation of the expression of these proteins (two-way ANOVA, p < 0.0001). Vitamin D deficiency exacerbated the adverse structural and physiological remodeling of pancreatic islets due to obesity, contributing to abnormal glucose homeostasis.

Global summary of maternal and newborn vitamin D status - a systematic review.

Pregnant women and newborns are at increased risk of vitamin D deficiency. Our objective was to create a global summary of maternal and newborn vitamin D status. We completed a systematic review (1959-2014) and meta-analysis of studies reporting serum 25-hydroxyvitamin D [25(OH)D] concentration in maternal and newborn populations. The 95 identified studies were unevenly distributed by World Health Organization (WHO) region: Americas (24), European (33), Eastern Mediterranean (13), South-East Asian (7), Western Pacific (16) and African (2). Average maternal 25(OH)D concentrations (nmol L(-1) ) by region were 47-65 (Americas), 15-72 (European), 13-60 (Eastern Mediterranean), 20-52 (South-East Asian), 42-72 (Western Pacific) and 92 (African). Average newborn 25(OH)D concentrations (nmol L(-1) ) were 35-77 (Americas), 20-50 (European), 5-50 (Eastern Mediterranean), 20-22 (South-East Asian), 32-67 (Western Pacific) and 27-35 (African). The prevalences of 25(OH)D <50 and <25 nmol L(-1) by WHO region in pregnant women were: Americas (64%, 9%), European (57%, 23%), Eastern Mediterranean (46%, 79%), South-East Asian (87%, not available) and Western Pacific (83%, 13%). Among newborns these values were: Americas (30%, 14%), European (73%, 39%), Eastern Mediterranean (60%, not available), South-East Asian (96%, 45%) and Western Pacific (54%, 14%). By global region, average 25(OH)D concentration varies threefold in pregnant women and newborns, and prevalence of 25(OH)D <25 nmol L(-1) varies eightfold in pregnant women and threefold in newborns. Maternal and newborn 25(OH)D concentrations are highly correlated. Addressing vitamin D deficiency in pregnant women and newborns should be a global priority. To protect children from the adverse effects of vitamin D deficiency requires appropriate interventions during both pregnancy and childhood.

Adverse Effects of Vitamin D Deficiency on Outcomes of Patients With Chronic Hepatitis B

Vitamin D is an immunomodulator that might be involved in the pathogenesis of viral hepatitis. We investigated the effects of vitamin D deficiency on long-term outcomes of patients with chronic hepatitis B (CHB). We performed a prospective cohort study of 426 patients with CHB (65% male; mean age, 41 ± 13 years), who were enrolled from 1997 through 2000. Serum levels of 25-hydroxycholecalciferol (25(OH)D3) were measured on study enrollment (baseline). Patients were followed for 159 ± 46 months until last clinic visit or death; approximately 33% received antiviral therapy during the follow-up period. The primary outcome was a clinical event (hepatocellular carcinoma, complications of cirrhosis, or death). At baseline, the patients' mean serum level of hepatitis B virus DNA was 5.0 ± 2.1 log10 IU/mL; their mean level of 25(OH)D3 was 24.3 ± 9.4 ng/mL, and 348 patients (82%) had vitamin D deficiency (<32 ng/mL). Serum levels of 25(OH)D3 did not correlate with cirrhosis or viral load. Ninety-seven patients (22.8%) developed clinical events by a mean time of 118 ± 60 months after study enrollment. Patients who developed clinical events had lower baseline serum levels of 25(OH)D3 (23.2 ± 10.4 ng/mL) than patients who did not (28.2 ± 9.3 ng/mL, P < .001). Low baseline serum 25(OH)D3 was an independent factor associated with clinical events after adjustment for sex, age, and cirrhosis. The adjusted hazard ratio of vitamin D deficiency for clinical events was 1.90 (95% confidence interval [CI], 1.06-2.43; P = .04). The 15-year cumulative incidence rate of clinical events among patients with vitamin D deficiency was 25.5% (95% CI, 23.1%-27.9%), compared with 11.1% (95% CI, 7.4%-14.8%) in patients with normal serum levels of 25(OH)D3. Vitamin D deficiency is common among patients with CHB and is associated with adverse clinical outcomes.

Decreased Levels Of Procoagulant Phospholipids In Bleeding Patients With Overcoagulation By Vitamin K Antagonists

Background The major adverse effect of vitamin K antagonists (VKA) is the increased risk for bleeding complications. In addition to well-identified risk factors such as age, prior gastrointestinal tract bleeding, or hypertension, the intensity of anticoagulation evaluated by the International Normalized Ratio (INR) measurement is a major determinant of VKA-induced bleeding. However, for the same degree of VKA overcoagulation and comorbidities, some patient will bleed, whereas others remain asymptomatic. Therefore, identifying specific biological markers that identify patients at high risk of bleeding would have great clinical impact. Microparticles, derived from different cellular origins (endothelium, red blood cells, leukocytes, platelets or apoptotic tissues), can be detected in plasma and express procoagulant phospholipids (PPL). The presence of PPL has been associated with various diseases complicated by an hypercoagulable state. Therefore, we hypothesize that the procoagulant activity of PPL could protect against haemorrhage in patients with VKA overcoagulation. Patients and methods 53 consecutive patients who were referred to the emergency department of our institution and with an INR &gt; 5 were enrolled in the study: 22 (10 females; 12 males, median age 82 years) were symptomatic (20 cases of minor bleeding, 2 cases of non-fatal major bleeding), whereas 31 (18 females, 13 males, median age 78 years) were asymptomatic. Median INR was 7.36 (range: 5 – 22.6) and 6.3 (range: 5 – 10.7) in symptomatic and asymptomatic patients, respectively (p = 0.17, not significant). PPL were evaluated using a factor Xa-based coagulation assay (STA-Procoag-PPL, Diagnostica Stago) in which shortened clotting times are associated with increased levels of PPL. We also quantified thrombomodulin (TM) by an ELISA assay (Asserachrom Thrombomodulin, Diagnostica Stago) and by a functional assay based on the ability of TM to activate Protein C in the presence of thrombin, since high plasma levels of TM were previously identified as a predictor of bleeding complications. Results Clotting times were significantly lower in asymptomatic patients than in bleeding patients [respective median values 36.5 seconds (range: 27.1 – 72.2) and 47.2 seconds (range : 30.5 – 72.8); p = 0.03. In contrast, there were no significant differences for TM levels, whatever the assay used (functional or immunological). Conclusion Increased PPL could contribute to decrease the haemorrhagic risk of patients treated by VKA. It is not clear if the decrease of PPL is directly responsible of the hemorrhagic syndrom, or if PPL are decreased because of a consumption during the hemorrhagic episode. In order to answer this question, it could be of interest to analyse if a prospective follow-up of this parameter could help to identify patients with an increased hemorrhagic risk when treated by VKA. Disclosures: No relevant conflicts of interest to declare.

Vitamin D supplementation reduces airway hyperresponsiveness and allergic airway inflammation in a murine model

Asthma is a chronic disease associated with airway hyperresponsiveness (AHR), airway obstruction and airway remodelling. NF-κB is a transcriptional factor that regulates and co-ordinates the expression of various inflammatory genes. The NF-κB subunits, p50 and Rel-A, are translocated to the nucleus by importin α3 and importin α4. There is growing evidence that vitamin D is a potent immunomodulator. However, the evidence for beneficial or adverse effects of vitamin D in asthma is still unclear. In this study, we examined the effect of vitamin D status on AHR, airway inflammation and cytokines in the bronchoalveolar lavage fluid (BALF) in a murine model of allergic asthma. Female BALB/c mice were fed with special vitamin D-deficient or vitamin D-sufficient (2000 IU/kg) or vitamin D-supplemented (10,000 IU/kg) diet for 13 weeks. Mice were sensitized and challenged with ovalbumin (OVA). The effect of vitamin D on lung histology, AHR, T regulatory cells (Tregs) and BALF cytokines was examined. The expression of importin-α3 and Rel-A in the lung of OVA-sensitized mice was analysed using immunofluorescence. Vitamin D deficiency was associated with higher AHR in OVA-sensitized and challenged mice than those in vitamin D-sufficient mice. This was accompanied with marked signs of airway remodelling, high BALF eosinophilia, increased BALF pro-inflammatory cytokines, reduced BALF IL-10 levels, reduced blood Tregs, increased expression of importin-α3 and Rel-A in the lung tissue. Vitamin D supplementation attenuated the pro-inflammatory effects, but did not completely reverse the features of allergic airway inflammation. Vitamin D could be beneficial as an adjunct therapy in the treatment of allergic asthma.