Vitamin D3 Supplementation In Patients Research Articles

Safety and efficacy of Vitamin D3 supplementation with Imatinib in Chronic Phase- Chronic Myeloid Leukaemia: an Exploratory Randomized Controlled Trial

ObjectivesThe study aimed to compare early molecular response (EMR) rates at 3 months of imatinib therapy with and without vitamin D3 supplementation in patients newly diagnosed with chronic-phase chronic myeloid...

Effects of repeated infections with non-typeable Haemophilus influenzae on lung in vitamin D deficient and smoking mice

BackgroundIn chronic obstructive pulmonary disease (COPD), exacerbations cause acute inflammatory flare-ups and increase the risk for hospitalization and mortality. Exacerbations are common in all disease stages and are often caused by bacterial infections e.g., non-typeable Heamophilus influenzae (NTHi). Accumulating evidence also associates vitamin D deficiency with the severity of COPD and exacerbation frequency. However, it is still unclear whether vitamin D deficiency when combined with cigarette smoking would worsen and prolong exacerbations caused by repeated infections with the same bacterial strain.MethodsVitamin D sufficient (VDS) and deficient (VDD) mice were exposed to nose-only cigarette smoke (CS) for 14 weeks and oropharyngeally instilled with NTHi at week 6, 10 and 14. Three days after the last instillation, mice were assessed for lung function, tissue remodeling, inflammation and immunity. The impact of VDD and CS on inflammatory cells and immunoglobulin (Ig) production was also assessed in non-infected animals while serum Ig production against NTHi and dsDNA was measured in COPD patients before and 1 year after supplementation with Vitamin D3.ResultsVDD enhanced NTHi eradication, independently of CS and complete eradication was reflected by decreased anti-NTHi Ig’s within the lung. In addition, VDD led to an increase in total lung capacity (TLC), lung compliance (Cchord), MMP12/TIMP1 ratio with a rise in serum Ig titers and anti-dsDNA Ig’s. Interestingly, in non-infected animals, VDD exacerbated the CS-induced anti-NTHi Ig’s, anti-dsDNA Ig’s and inflammatory cells within the lung. In COPD patients, serum Ig production was not affected by vitamin D status but anti-NTHi IgG increased after vitamin D3 supplementation in patients who were Vitamin D insufficient before treatment.ConclusionDuring repeated infections, VDD facilitated NTHi eradication and resolution of local lung inflammation through production of anti-NTHi Ig, independently of CS whilst it also promoted autoantibodies. In COPD patients, vitamin D supplementation could be protective against NTHi infections in vitamin D insufficient patients. Future research is needed to decipher the determinants of dual effects of VDD on adaptive immunity.Trail registrationClinicalTrials, NCT00666367. Registered 23 April 2008, https://www.clinicaltrials.gov/ct2/show/study/NCT00666367.

Vitamin D3 Attenuates Viral-Induced Inflammation and Fibrotic Responses in Bronchial Smooth Muscle Cells.

Toll-like receptor 3 (TLR3) activation by viral infections plays a key role in promoting inflammatory immune responses that contribute to pulmonary fibrosis in chronic inflammatory respiratory diseases. Vitamin D3 has been shown to be beneficial to patients with asthma and chronic obstructive pulmonary disease (COPD) through its anti-inflammatory and anti-fibrotic properties. Smooth muscle cells are one of the major contributors to airway remodeling in asthma and COPD. We therefore aimed to investigate the effect of vitamin D3 treatment on viral-induced TLR3 responses in Bronchial Smooth Muscle Cells (BSMCs) as a mechanism contributing to pulmonary fibrosis in asthma and COPD. Primary BSMCs from patients with asthma (n=4), COPD (n=4), and healthy control subjects (n=6) were treated with polyinosinic: polycytidylic acid (polyI:C), TLR3 agonist in the presence or absence of vitamin D3 (1,25D3). Here we report the mRNA expression and protein levels of pro-inflammatory and pro-fibrotic markers (IL-6, IFN-β1, CCL2/MCP-1, fibronectin 1 and type I collagen) among BSMCs groups: asthma, COPD, and healthy controls. We show that at the baseline, prior to polyI:C stimulation, asthma and COPD BSMCs presented increased pro-inflammatory and pro-fibrotic state compared to healthy control subjects, as measured by quantitative PCR and immunoassays (ELISA/Flow Cytometry. Ligation of TLR3 by polyI:C in BSMCs was associated with increased TLR3 mRNA expression, and 1,25D3 treatment significantly reduced its expression. In addition, 1,25D3 decreased the expression of IL-6, IFN-β1, CCL2, FN1 and COL1A1 induced by polyI:C in BSMCs. The regulatory effect of 1,25D3 treatment on polyI:C-stimulated BSMCs was further confirmed at protein levels. Our findings suggest that vitamin D3 attenuates TLR3 agonist-induced inflammatory and fibrotic responses in BSMCs and support the clinical relevance of vitamin D3 supplementation in patients with viral infections having chronic respiratory diseases, such as asthma and COPD.

Effect of vitamin D3 supplementation upon the metabolic and DNA methylation profile of cystic fibrosis patients

Background: Cystic fibrosis (CF) is a genetic disease that affects the transmembrane conductance regulator gene responsible for modulating chloride ion transportation in the cell membrane. Hypovitaminosis D is frequently observed among fibrocystic disease patients. Therefore, this study was aimed to evaluate the effect of vitamin D3 supplementation in patients with CF concerning their metabolic and deoxyribonucleic acid (DNA) methylation profiles. Methodology: A clinical trial involving 12 CF patients was carried out in Joao Pessoa. After assessment of hypovitaminosis D prevalence in the studied population, four patients with vitamin D3 insufficiency/deficiency were administered cholecalciferol megadose supplementation in addition to biochemical examinations and analysis of inflammatory and epigenetic indicators. The DNA methylation profile of the studied genes' promoter regions was determined through a qualitative methylation restriction enzyme technique. Data were analyzed using the Statistical Package for the Social Sciences 25.0 software for T-tests, Mann-Whitney, and Wilcoxon test calculations. Results: Hypovitaminosis D was observed in 58%, 33% of the studied individuals. Patients with hypovitaminosis D reported blood sugar, glutamic-pyruvic transaminase (ALT), and uric acid levels significantly higher (p = 0.02; p = 0.05; p = 0.02, respectively) compared to individuals with sufficient 25-hydroxyvitamin D (25(OH)D), as well as elevated inflammatory values. Supplementation did not influence epigenetic nor metabolic parameters significantly, although the mean 25(OH)D serum concentration value increased from 18.3 ng/dl to 34.1 ng/dl (p = 0.06). Conclusion: Cholecalciferol megadose elevated 25(OH)D serum levels, although it did not alter inflammatory, glycemic, or epigenetic parameters. This encourages future studies on the matter since significant differences were found in blood sugar, uric acid, and ALT serum levels for the vitamin D3 insufficiency/deficiency group despite this study�s small sample size.

Study of Role of Vitamin D3 Supplementation in Patients Suffering from Dry Eye Syndrome (DES) Attending in Tertiary Care Hospital, at S.K.M.C.H. Muzaffarpur, Bihar

Study of Role of Vitamin D3 Supplementation in Patients Suffering from Dry Eye Syndrome (DES) Attending in Tertiary Care Hospital, at S.K.M.C.H. Muzaffarpur, Bihar

Vitamin D Deficiency and Immune Disorders in Combined Endocrine Pathology.

Introduction: Combined endocrine pathology is a serious healthcare problem in Ukraine. This prospective study assessed the blood levels of 25-hydroxyvitamin D [25(OH)D] and markers of immune function in response to vitamin D intervention in patients with type 1 and type 2 diabetes mellitus (T1DM and T2DM, respectively) and autoimmune thyroiditis (AIT).Objective: This study evaluated the relationship between the metabolic and immune status of DM + AIT patients with respect to their vitamin D status and changes after vitamin D3 supplementation.Material and Methods: Patients with type 1 or type 2 DM in combination with AIT and decreased circulating levels of 25(OH)D were divided into two groups of 30 patients each. All patients with AIT were euthyroid and receiving hormonal replacement therapy. The levels of carbohydrate and fat metabolism markers, Immunologic markers, namely, Th1-type cytokines [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-6, IL-12], Th2-type cytokines (IL-4, IL-5), IL-10, and IL-17 were measured before and after vitamin D3 supplementation. The vitamin D status was assessed according to the level of 25(OH)D.Results: Patients with combined endocrine disorders (DM and AIT) with a decreased vitamin D status had significantly increased background concentrations of Th1-type cytokines and reduced concentrations of Th2-type cytokines (IL-4 and IL-5), IL-10, and IL-17. The results of our study showed that vitamin D3 supplementation in patients with T1DM and T2DM reduced the concentrations of the inflammatory Th1-type cytokines and increased the levels of Th2-type cytokines.Conclusion: The presence of two endocrine diseases, aggravated by decreased circulating levels of 25(OH)D, leads to disorders wherein the immune status is markedly changed. These decreased levels of 25(OH)D contribute to an autoimmune inflammatory process and to the progression of complications in addition to the metabolic disorders. A vitamin D intervention resulted in significant changes in the blood levels of 25(OH)D that are related to parameters of autoimmunity and glucose metabolism. Vitamin D3 supplementation should be considered for the prevention and treatment of combined endocrine pathology.

Impact of High-Dose Vitamin D3 Supplementation in Patients with Crohn's Disease in Remission: A Pilot Randomized Double-Blind Controlled Study.

To assess the tolerability and efficacy of high-dose vitamin D3 in patients with Crohn's disease (CD). This was a randomized, double-blind placebo-controlled trial of high-dose vitamin D3 at 10,000IU daily (n=18) compared to 1000IU daily (n=16) for 12months in patients with CD in remission. The primary outcome was change in serum 25-hydroxy-vitamin D levels. Secondary outcomes included clinical relapse rates and changes in mood scores. High-dose vitamin D3 at 10,000IU daily significantly improved 25-hydroxy-vitamin D levels from a mean of 73.5nmol/L [standard deviation (SD) 11.7nmol/L] to 160.8nmol/L (SD 43.2nmol/L) (p=0.02). On an intention-to-treat basis, the rate of relapse was not significantly different between patients receiving low- and high-dose vitamin D3 (68.8 vs 33.3%, p=0.0844). In per-protocol analysis, clinical relapse of Crohn's disease was less frequently observed in patients receiving a high dose (0/12 or 0%) compared to those receiving a low dose of 1000IU daily (3/8 or 37.5%) (p=0.049). Improvement in anxiety and depression scores and a good safety profile were observed in both groups treated with vitamin D3. Oral supplementation with high-dose vitamin D3 at 10,000IU daily significantly improved serum 25-hydroxy-vitamin D levels. Rates of clinical relapse were similar between both groups. Larger studies using high-dose vitamin D3 for treatment of inflammatory bowel diseases are warranted. CLINICALTRIALS. NCT02615288.

The Role of Calcium and Vitamin D3 Supplementation in Patients with Fracture of Bones

The Role of Calcium and Vitamin D3 Supplementation in Patients with Fracture of Bones

Analysis of Adequacy of 25-Hydroxi vitamin D3 Supplementation in Patients on Hemodialysis and Parathormone, Calcium and Phosphorus Level in the Blood of These Patients.

Introduction:Appropriate vitamin D turnover is essential for many physiological function. Knowledge of it’s function was improved in last two decades with enlargement of scientific confirmation and understanding of overall importance. In addition to classical (skeletal) roles of vitamin D, many other function (no classical), out of bone and calcium-phosphate metabolism, are well defined today.Aim:To analyze vitamin D level in the blood in dialysis and pre dialysis patients and evaluate efficacy of supplementation therapy with vitamin D supplements.Methods:Vitamin D3 level in form of 25-hydroxivitamin D3 was measured in dialysis and pre dialysis patients, using combination of enzyme immunoassay competition method with final fluorescent detection (ELFA). Parathormone was measured by ELISA method. Other parameters were measured by colorimetric methods. Statistical analysis was done by nonparametric methods, because of dispersion of results of Vitamin D and parathormone.Results:In group of dialysis patients 38 were analyzed. Among them 35 (92%) presented vitamin D deficiency, whether they took supplementation or not. In only 3 patients vitamin D deficiency was not so severe. Vitamin D form were evaluated in 42 pre dialysis patients. Out of all 19 patients (45 %) have satisfied level, more than 30 ng/ml. Moderate deficiency have 16 patients (38%), 5 of all (12%) have severe deficiency, and two patients (5%) have very severe deficiency, less than 5 ng/ml. Parathormone was within normal range (9.5-75 pg/mL) in 13 patients (34 %), below normal range (2 %) in one subject, and in above normal range in 24 (63 %).Conclusion:Vitamin D3 deficiency was registered in most hemodialysis patients; nevertheless supplemental therapy was given regularly or not. It is to be considered more appropriate supplementation of Vitamin D3 for dialyzed patients as well as for pre dialysis ones. In pre dialysis patient moderate deficiency is shown in half of patients but sever in only two.

Vitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial

Patients with chronic obstructive pulmonary disease (COPD) often have vitamin D deficiency, which is associated with increased susceptibility to upper respiratory infection-a major precipitant of exacerbation. Multicentre trials of vitamin D supplementation for prevention of exacerbation and upper respiratory infection in patients with COPD are lacking. We therefore investigated whether vitamin D3 (colecalciferol) supplementation would reduce the incidence of moderate or severe COPD exacerbations and upper respiratory infections. We did a randomised, double-blind, placebo-controlled trial of vitamin D3 supplementation in adults with COPD in 60 general practices and four Acute National Health Service Trust clinics in London, UK. Patients were allocated to receive six 2-monthly oral doses of 3 mg vitamin D3 or placebo over 1 year in a 1:1 ratio using computer-generated permuted block randomisation. Participants and study staff were masked to treatment assignment. Coprimary outcomes were time to first moderate or severe exacerbation and first upper respiratory infection. Analysis was by intention to treat. A prespecified subgroup analysis was done to assess whether effects of the intervention on the coprimary outcomes were modified by baseline vitamin D status. This trial is registered with ClinicalTrials.gov, number NCT00977873. 240 patients were randomly allocated to the vitamin D3 group (n=122) and placebo group (n=118). Vitamin D3 compared with placebo did not affect time to first moderate or severe exacerbation (adjusted hazard ratio 0·86, 95% CI 0·60-1·24, p=0·42) or time to first upper respiratory infection (0·95, 0·69-1·31, p=0·75). Prespecified subgroup analysis showed that vitamin D3 was protective against moderate or severe exacerbation in participants with baseline serum 25-hydroxyvitamin D concentrations of less than 50 nmol/L (0·57, 0·35-0·92, p=0·021), but not in those with baseline 25-hydroxyvitamin D levels of at least 50 nmol/L (1·45, 0·81-2·62, p=0·21; p=0·021 for interaction between allocation and baseline serum 25-hydroxyvitamin D status). Baseline vitamin D status did not modify the effect of the intervention on risk of upper respiratory infection (pinteraction=0·41). Vitamin D3 supplementation protected against moderate or severe exacerbation, but not upper respiratory infection, in patients with COPD with baseline 25-hydroxyvitamin D levels of less than 50 nmol/L. Our findings suggest that correction of vitamin D deficiency in patients with COPD reduces the risk of moderate or severe exacerbation. UK National Institute for Health Research.

Effect of Vitamin D3on Asthma Treatment Failures in Adults With Symptomatic Asthma and Lower Vitamin D Levels

In asthma and other diseases, vitamin D insufficiency is associated with adverse outcomes. It is not known if supplementing inhaled corticosteroids with oral vitamin D3 improves outcomes in patients with asthma and vitamin D insufficiency. To evaluate if vitamin D supplementation would improve the clinical efficacy of inhaled corticosteroids in patients with symptomatic asthma and lower vitamin D levels. The VIDA (Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma) randomized, double-blind, parallel, placebo-controlled trial studying adult patients with symptomatic asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL was conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute's AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by January 2014. After a run-in period that included treatment with an inhaled corticosteroid, 408 patients were randomized. Oral vitamin D3 (100,000 IU once, then 4000 IU/d for 28 weeks; n = 201) or placebo (n = 207) was added to inhaled ciclesonide (320 µg/d). If asthma control was achieved after 12 weeks, ciclesonide was tapered to 160 µg/d for 8 weeks, then to 80 µg/d for 8 weeks if asthma control was maintained. The primary outcome was time to first asthma treatment failure (a composite outcome of decline in lung function and increases in use of β-agonists, systemic corticosteroids, and health care). Treatment with vitamin D3 did not alter the rate of first treatment failure during 28 weeks (28% [95% CI, 21%-34%] with vitamin D3 vs 29% [95% CI, 23%-35%] with placebo; adjusted hazard ratio, 0.9 [95% CI, 0.6-1.3]). Of 14 prespecified secondary outcomes, 9 were analyzed, including asthma exacerbation; of those 9, the only statistically significant outcome was a small difference in the overall dose of ciclesonide required to maintain asthma control (111.3 µg/d [95% CI, 102.2-120.4 µg/d] in the vitamin D3 group vs 126.2 µg/d [95% CI, 117.2-135.3 µg/d] in the placebo group; difference of 14.9 µg/d [95% CI, 2.1-27.7 µg/d]). Vitamin D3 did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency. These findings do not support a strategy of therapeutic vitamin D3 supplementation in patients with symptomatic asthma. clinicaltrials.gov Identifier: NCT01248065.

High vitamin D3diet administered during active colitis negatively affects bone metabolism in an adoptive T cell transfer model

Decreased bone mineral density (BMD) represents an extraintestinal complication of inflammatory bowel disease (IBD). Vitamin D₃ has been considered a viable adjunctive therapy in IBD. However, vitamin D₃ plays a pleiotropic role in bone modeling and regulates the bone formation-resorption balance, depending on the physiological environment, and supplementation during active IBD may have unintended consequences. We evaluated the effects of vitamin D₃ supplementation during the active phase of disease on colonic inflammation, BMD, and bone metabolism in an adoptive IL-10-/- CD4⁺ T cell transfer model of chronic colitis. High-dose vitamin D₃ supplementation for 12 days during established disease had negligible effects on mucosal inflammation. Plasma vitamin D₃ metabolites correlated with diet, but not disease, status. Colitis significantly reduced BMD. High-dose vitamin D₃ supplementation did not affect cortical bone but led to a further deterioration of trabecular bone morphology. In mice fed a high vitamin D₃ diet, colitis more severely impacted bone formation markers (osteocalcin and bone alkaline phosphatase) and increased bone resorption markers, ratio of receptor activator of NF-κB ligand to osteoprotegrin transcript, plasma osteoprotegrin level, and the osteoclast activation marker tartrate-resistant acid phosphatase (ACp5). Bone vitamin D receptor expression was increased in mice with chronic colitis, especially in the high vitamin D₃ group. Our data suggest that vitamin D₃, at a dose that does not improve inflammation, has no beneficial effects on bone metabolism and density during active colitis or may adversely affect BMD and bone turnover. These observations should be taken into consideration in the planning of further clinical studies with high-dose vitamin D₃ supplementation in patients with active IBD.

Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomised and double-blind intervention study

BackgroundLow serum levels of 25-hydroxyvitamin D3 are associated with an increased risk of respiratory tract infections (RTIs). Clinical trials with vitamin D3 against various infections have been carried out but...