High-dose Vitamin D3 Research Articles

Effects of Vitamin D3 Supplementation on Muscle Strength, Mass, and Physical Performance in Women with Vitamin D Insufficiency: A Randomized Placebo-Controlled Trial.

Vitamin D insufficiency and hyperparathyroidism have been associated with reduced muscle strength, physical performance, postural stability, well-being, and quality of life. In a double-blinded, randomized placebo-controlled trial, we aimed to investigate effects of vitamin D3 supplementation on above-mentioned outcomes in healthy community-dwelling postmenopausal women with plasma levels of 25-hydroxyvitamin D (25(OH)D) below < 50nmol/l and high parathyroid hormone (PTH) levels. Participants (N = 81) were 1:1 treated with vitamin D3, 70µg(2800 IU)/day or identical placebo for three months during wintertime (56°N). Vitamin D3 supplementation increased levels of 25(OH)D and 1,25(OH)2D by 230% (95% CI 189 to 272)%, p < 0.001 and 58% (190 to 271%), p < 0.001, respectively, and reduced PTH by 17% (- 23 to - 11%), p < 0.001. Compared with placebo, vitamin D3 significantly reduced maximal handgrip strength by 9% (- 15 to - 3%; p < 0.01) and knee flexion strength by 13% (- 24 to - 2%; p = 0.02) and increased the time spent on performing the Timed Up and Go test by 4.4%; (0.1-8.6%; p < 0.05). Levels of physical activity, total lean body mass, appendicular lean mass index, postural stability, well-being, and quality of life did not change in response to treatment. Compared with placebo, a daily supplement with a relatively high dose of vitamin D3 had no beneficial effects on any outcomes. In some measures of muscle strength and physical performance, we even saw a small unfavorable effect. Our data call for caution on use of relatively high daily doses of vitamin D3 in the treatment of vitamin D insufficiency.

Placebo-controlled, randomized clinical trial of high-dose cholecalciferol in renal dialysis patients: effect on muscle strength and quality of life.

BackgroundThe importance of vitamin D sufficiency in deficient dialysis patients is uncertain. This study aimed to determine if high-dose cholecalciferol for 1-year affected symptoms, muscle strength, blood pressure (BP), cardiac ischaemia, parathyroid hormone, calcium or phosphate.MethodsThis was a randomized, double-blind, placebo-controlled trial with 1-year follow-up that enrolled dialysis patients with 25-hydroxy-vitamin D [25(OH)D] concentration <50 nmol/L. Consenting patients were randomized to 50 000 U/week oral cholecalciferol or matching placebo. Dosage was adjusted at 3- and 6-month study visits, targeting a 25(OH)D concentration >80 nmol/L. The primary objectives were to assess the effect of supplementation on renal-specific symptoms and on hand-grip strength. Symptoms were assessed using the Kidney Disease Quality of Life Short Form and muscle strength with a hand grip-strength dynamometer. Hypothesis testing was by two-group t-test and Wilcoxon rank-sum on an intention-to-treat basis.ResultsIn all, 68 participants were randomized and received study medication. Median 12-month plasma 25(OH)D concentration was 119 nmol/L and 37 nmol/L in the cholecalciferol and placebo groups, respectively. There was no statistical difference in primary outcomes at 12 months. Mean symptom scores at 12 months were two lower in the cholecalciferol group (95% confidence interval −10 to 6) and geometric mean grip-strength was 27 kg in both groups. Symptoms, strength, BP, plasma mineral bone parameters and adverse events were not different between the groups at follow-up.ConclusionsHigh-dose cholecalciferol in a deficient dialysis population had no effect on muscle strength or symptoms but appears safe.

High-dose vitamin D3 in the treatment of severe acute malnutrition: a multicenter double-blind randomized controlled trial

Vitamin D deficiency is common in children with severe acute malnutrition, in whom it is associated with severe wasting. Ready-to-use therapeutic food (the standard treatment) contains modest amounts of vitamin D that do not reliably correct deficiency. The aim of this study was to determine whether high-dose oral vitamin D3 enhances weight gain and development in children with uncomplicated severe acute malnutrition. We conducted a randomized placebo-controlled trial of high-dose vitamin D3 supplementation in children aged 6-58 mo with uncomplicated severe acute malnutrition in Pakistan. Participants were randomly assigned to receive 2 oral doses of 200,000 IU vitamin D3 or placebo at 2 and 4 wk after starting ready-to-use therapeutic food. The primary outcome was the proportion of participants gaining >15% of baseline weight at 8 wk after starting ready-to-use therapeutic food (the end of the study). Secondary outcomes were mean weight-for-height or -length z score and the proportion of participants with delayed development at the end of the study (assessed with the Denver Development Screening Tool II), adjusted for baseline values. Of the 194 randomly assigned children who started the study, 185 completed the follow-up and were included in the analysis (93 assigned to intervention, 92 to control). High-dose vitamin D3 did not influence the proportion of children gaining >15% of baseline weight at the end of the study (RR: 1.04; 95% CI: 0.94,1.15, P=0.47), but it did increase the weight-for-height or -length z score (adjusted mean difference: 1.07; 95% CI: 0.49,1.65, P<0.001) and reduce the proportion of participants with delayed global development [adjusted RR (aRR): 0.49; 95% CI: 0.31, 0.77, P=0.002], delayed gross motor development (aRR: 0.29; 95% CI: 0.13, 0.64, P=0.002), delayed fine motor development (aRR: 0.59; 95% CI: 0.38, 0.91, P=0.018), and delayed language development (aRR: 0.57; 95% CI: 0.34, 0.96, P=0.036). High-dose vitamin D3 improved the mean weight-for-height or -length z score and developmental indexes in children receiving standard therapy for uncomplicated severe acute malnutrition in Pakistan. This trial was registered at clinicaltrials.gov as NCT03170479.

The Engagement Between Vitamin D and the Immune System: Is Consolidation by a Marriage to Be Expected?

The Engagement Between Vitamin D and the Immune System: Is Consolidation by a Marriage to Be Expected?

A case of hypercalcemia with normal 25-OH vitamin D levels, post-treatment with high dose cholecalciferol for low vitamin D levels

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Fluctuations in clinical symptoms with changes in serum 25(OH) vitamin D levels in autistic children: Three cases report

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder caused by complicated interactions between genetic and environmental factors. Clinical trials, including case reports, case–control studies, and a double-blinded randomized clinical study, have suggested that high-dose vitamin D3 regimens may ameliorate the core symptoms of ASD. Vitamin D3 supplementation was effective in about three-quarters of children with ASD. To further investigate the relationship between vitamin D and ASD symptoms in vitamin D-responsive autistic children, changes in symptoms were assessed in three children with ASD who were given vitamin D3 supplementation followed by a long interruption. The core symptoms of ASD were remarkably improved during the vitamin D3 supplementation period when serum 25-hydroxyvitamin D [25(OH)]D levels reached over 40.0 ng/mL. However, symptoms reappeared after the supplementation was stopped, when serum 25(OH)D levels fell below 30.0 ng/mL but were again improved with re-administration of vitamin D3 after the interruption, when serum 25(OH)D levels exceeded 40.0 ng/mL. Overall, these results showed that the core symptoms of ASD fluctuated in severity with changes in serum 25(OH)D levels in children, indicating that maintaining a responsive 25(OH)D level is important for treating ASD. Maintaining a serum 25(OH)D level between 40.0 and 100.0 ng/ml may be optimal for producing therapeutic effects in vitamin D-responsive individuals with ASD.

Comparison of the effect of daily versus bolus dose maternal vitamin D3 supplementation on the 24,25-dihydroxyvitamin D3 to 25-hydroxyvitamin D3 ratio.

Supplementing lactating mothers with high doses of vitamin D3 can adequately meet vitamin D requirements of the breastfed infant. We compared the effect of bolus versus daily vitamin D3 dosing in lactating mothers on vitamin D3 catabolism. We hypothesized that catabolism of 25(OH)D3 to 24,25(OH)2D3 would be greater in the bolus than in the daily dose group. Randomized controlled trial (clinicaltrials.govNCT01240265) in 40 lactating women. Subjects were randomized to receive vitamin D3 orally, either a single dose of 150,000IU or 5000IU daily for 28days. Vitamin D metabolites were measured in serum and breast milk at baseline, 1, 3, 7, 14 and 28days. Temporal changes in the serum 24,25(OH)2D3/25(OH)D3 ratio. The concentration of serum 24,25(OH)2D3 was directly related to that of 25(OH)D in both groups (r2=0.63; p<0.001). The mean (±SD) 24,25(OH)2D3/25(OH)D3 ratio remained lower at all time points than baseline values in the daily dose group (0.093±0.024, 0.084±0.025, 0.083±0.024, 0.080±0.020, 0.081±0.023, 0.083±0.018 at baseline, 1, 3, 7, 14, and 28days, respectively). In the single dose group, the increase in 24,25(OH)2D3 lagged behind that of 25(OH)D, but the 24,25(OH)2D3/25(OH)D3 values (0.098±0.032, 0.067±0.019, 0.081±0.017, 0.092±0.024, 0.103±0.020, 0.106±0.024, respectively) exceeded baseline values at 14 and 28days and were greater than the daily dose group at 14 and 28days (p=0.003). The 24,25(OH)2D3/25(OH)D3 ratio remained in the normal range with both dosing regimens. Greater breast milk vitamin D3 values in the single dose group were inversely associated with the 24,25(OH)2D3/25(OH)D3 ratio (r2=0.14, p<0.001), but not with daily dosing. After a 14-day lag, a single high dose of vitamin D led to greater production of 24,25(OH)2D3, presumably via induction of the 24-hydroxylase enzyme (CYP24A1), relative to the 25(OH)D3 value than did daily vitamin D supplementation, and this effect persisted for at least 28days after vitamin D administration. A daily dose of vitamin D may have more lasting effectiveness in increasing 25(OH)D3 with lesser diversion of 25(OH)D3 to 24,25(OH)2D3 than does larger bolus dosing.

Baseline characteristics of participants in the VITamin D and OmegA-3 TriaL (VITAL): Effects on Bone Structure and Architecture

Vitamin D supplements are often used to benefit skeletal health, although data on effects of daily high-dose vitamin D alone on bone density and structure are lacking. The ongoing VITamin D and OmegA-3 TriaL (VITAL) is a double-blind, randomized, placebo-controlled trial testing effects of high-dose supplemental vitamin D3 (cholecalciferol; 2000 IU/day) and/or omega-3 fatty acids (FAs; 1 g/day) for the primary prevention of cancer and cardiovascular disease. The study has a mean treatment period of 5 years among 25,874 U.S. men ≥50 years and women ≥55 years old from all 50 states. The ancillary study, VITAL: Effects on Bone Structure and Architecture, is testing effects of vitamin D3 and/or omega-3 FAs on musculoskeletal outcomes and body composition in a subcohort of 771 participants. At in-person visits at the Harvard Catalyst Clinical and Translational Science Center (CTSC), participants completed bone density/architecture, body composition, and physical performance assessments at baseline and two-year follow-up. Baseline characteristics were evenly distributed among treatment groups, suggesting that any uninvestigated confounders will be evenly distributed; sex differences were also analyzed. Future analyses of the two-year follow-up visits will elucidate whether daily high-dose, supplemental vitamin D3 and/or omega-3 FAs improve musculoskeletal outcomes, helping to advance clinical and public health recommendations.Clinical trial registration number: NCT01747447.

399 - Single High-Dose Oral Vitamin D3 (Stoss Dose) in Lieu of Daily Dosing is Reliably Effective for Treatment of Vitamin D Insufficiency/Deficiency in Pediatric Hematopoetic Stem Cell Transplant (HSCT) Recipients

Background: It is estimated as many as 70% of children in the United States have deficient or insufficient vitamin D levels. Pediatric HSCT recipients are particularly at high risk for deficiency due to sun avoidance and sunscreen use, malabsorption, and increased catabolism due to steroid and/or calcineurin inhibitor use. It has also been postulated that maintaining adequate vitamin D levels can impact outcomes such as engraftment, graft-versus-host disease, and rejection. Given their complex medication regimens, addition of a daily vitamin D maintenance dose may lead to non-adherence and an inability to achieve adequate levels. Methods: This was a retrospective single-center analysis of pediatric HSCT recipients that received single high-dose oral vitamin D therapy beginning in May 2014. Vitamin D deficiency was defined as a 25-hydroxyvitamin D (25(OH) D) level below 20 ng/mL and insufficiency as a level of 21-29 ng/mL. The patients received doses according to dosing guidelines established in the pediatric Cystic Fibrosis population at this institution, adapted from the study by Shepherd et al in 2013. (Table 1)Table 125-OH Vit D Level (ng/mL)<3 yrs3-12 yrs>12 yrs≤ 10200,000 units400,000 units600,000 units10-20150,000 units350,000 units500,000 units20-30100,000 units200,000 units300,000 units Open table in a new tab Results: There were 14 patients identified as having received vitamin D stoss therapy and 20 doses administered. All patients evaluated had received allogeneic HSCT. In patients for whom follow-up levels were available (n = 17), an average increase in 25(OH) D level of 21 ng/mL was observed. In patients that received multiple doses, (n = 3) there was an average of 90.6 days between administrations. Two patients in the study group had follow-up levels decrease following stoss therapy, likely attributed to critical illness at the time of administration. No toxicities associated with high-dose vitamin D administration were observed. Conclusion: Single high-dose oral vitamin D therapy is an effective method for restoring and maintaining adequate vitamin D levels in this patient population. This approach reduces the need for the addition of a daily maintenance medication and allows for controlled, periodic dosing and monitoring.

Effect of vitamin D supplementation on serum sclerostin levels in chronic kidney disease

Vitamin D deficiency, cardiovascular disease and abnormal bone mineral metabolism are common in chronic kidney disease (CKD). Abnormal bone mineral metabolism has been linked to vascular calcification in CKD. Sclerostin has emerged as an important messenger in cross talk between bone-vascular axis. We analyzed sclerostin in subjects who participated in the randomized, double blind, placebo controlled trial investigating the effect of cholecalciferol supplementation on vascular function in non­diabetic CKD stage G3-4 and vitamin D ≤ 20 ng/ml [CTRI/2013/05/003648]. Patients were randomized (1:1) to receive either two directly observed oral doses of 300,000 IU of cholecalciferol or matching placebo at baseline and 8 weeks. Of the 120 subjects enrolled, 58 in the cholecalciferol group and 59 in the placebo group completed the study. At baseline, serum levels of sclerostin were similar in both groups (cholecalciferol - median;190pg/ml, IQR;140–260 pg/ml and placebo - median;180 pg/ml, IQR; 140–240 pg/ml, p = 0.67). 16 weeks after cholecalciferol supplementation, there was no change in level of sclerostin (mean change;1.10 pg/ml, 95%CI; −27.34 to 29.34 pg/ml, p = 0.25). However, a significant decrease in sclerostin level was noted in the placebo group (mean change; −31.94 pg/ml, 95%CI; −54.76 to −9.13 pg/ml, p = 0.002). Change (Δ) in sclerostin level at 16 weeks correlated negatively with Δ eGFR (r = −0.20, p = 0.03) and positively with Δuric acid (r = 0.37, p < 0.001) but not with Δ25(OH) D (r = 0.06, p = 0.54), Δ iPTH (r = − 0.03, p = 0.78) ΔFGF23 (r = − 0.08, p = 0.38) and Δ125 (OH)2 D (r = − 0.04, p = 0.65). In conclusion, high dose cholecalciferol supplementation did not change sclerostin levels in non-diabetic stage 3–4 CKD subjects.

High-Dose Vitamin D3 Intake Is Associated with Decreased Symptoms of Multiple Sclerosis

Multiple sclerosis (MS) is one of the most widespread disabling autoimmune neurological conditions of adults between the ages of 20 and 40 globally. Medical researchers do not completely understand the possible causes of MS, nor have they determined the rate of progression. A limited number of clinical trials conducted in recent years have explored the link between vitamin D deficiency and MS with vitamin D supplementation as a possible element in the treatment of this disease. The primary goal of this review was to synthesize the evidence regarding the link between vitamin D3 levels and the symptoms of MS. A PubMed search was conducted using keywords Vitamin D, multiple sclerosis, MS, RRMS, prevention, treatment and cause. 1153 articles and sources were found using the key phrase “multiple sclerosis and vitamin D,” but these were narrowed to 11 based on publication dates between 2013 and 2018, clinical trials were included, while reviews were excluded and the relevance of the goals to this review. Study designs included experimental clinical trials where pretest/posttest data were presented. Articles were excluded if they were not peer reviewed or only described the method and were awaiting results. Although not all studies found uniform results, the majority of the evidence suggests that high intakes of vitamin D may be associated with improved quality of life through the reduction of certain symptoms of MS. This was especially evident in patients who started the studies with a vitamin D deficiency. It may be too early to prescribe an increase in daily supplementation of vitamin D with the hope of reducing the development of or in the treatment of MS, but recent studies indicate that high doses of vitamin D could decrease the probability of some symptoms of the disease and possibly give favorable results in treatment. Further studies are needed before specific recommendations can be made.

Oxidative stress in critically ill ventilated adults: effects of vitamin D3 and associations with alveolar macrophage function.

BackgroundDisruptions in redox balance lead to oxidative stress, a promoter of morbidity in critical illness. This study aimed to: 1) characterize the plasma and alveolar thiol/disulfide redox pools, 2) examine their associations with alveolar macrophage phagocytosis, and 3) determine the effect of high dose vitamin D3 on plasma thiol/disulfide redox.MethodsSubjects were 30 critically ill, ventilated adults in a double-blind randomized trial of high-dose (250 000 or 500 000 IU) vitamin D3 or placebo. Baseline bronchoalveolar lavage fluid (BALF) samples were analyzed for determination of alveolar phagocytosis index (PI) and for concentrations of glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), cystine (CySS), and their respective redox potentials (EhGSSG and EhCySS). Plasma redox outcomes were assessed at baseline and days 7 and 14.ResultsBaseline plasma Cys was inversely associated with alveolar PI (ρ = −0.69, P=0.003), and EhCySS was positively associated with PI (ρ = 0.61, P=0.01). Over time, among all subjects there was an increase in plasma GSH levels and a decrease in EhGSSG (P<0.01 for both), with no difference by treatment group. Vitamin D3 decreased oxidized plasma GSSG to a more normal state (P for group × time=0.009).ConclusionsOxidative stress indicators were positively associated with alveolar macrophage phagocytic function in acutely ill ventilated adults. High-dose vitamin D3 decreased plasma GSSG concentrations, which suggests that vitamin D can possibly improve the oxidative stress environment.

Effect of high dose vitamin D3 therapy on serum vitamin D3 levels in vitamin D insufficient adults with cystic fibrosis

The effect of a high dose oral cholecalciferol repletion strategy in Vitamin D insufficient adults with CF is still unknown. Therefore, we assessed the effectiveness of our current approach, giving oral vitamin D3 supplementation at a dose of 10,000IU from Monday to Friday for a total of 50,000IU D3 weekly in vitamin D insufficient adult with CF. We performed a retrospective chart review of all 59 adult CF patients between the ages of 17 and 64 years routinely followed at the CF Adult Program of Winnipeg Health Sciences Centre. Through consultation with the endocrinologist, our clinic vitamin D repletion protocol for treating CF adult patients who have serum 25-hydroxyvitamin D (25-OHD)<30ng/ml (<75nmol/L) was to prescribe vitamin D3 10,000IU orally from Monday to Friday (or the weekly equivalent of 50,000IU) for 12 weeks in addition to their regular CF vitamin that supplied from 800 to 2000IU vitamin D3 daily. Cholecalciferol was conveniently administered orally as either one capsule (oil-based) 10,000IU or one tablet (powder-based) 10,000IU. All patients were instructed to obtain follow-up serum 25-OHD levels post completion of treatment. Of the 59 adult patients at our CF Clinic, 35 patients (59%) had below optimal serum 25-OHD levels. Of the 35 patients identified, 10 patients with insufficient serum 25-OHD levels between 10 and 30ng/ml (25-75nmol/L) fulfilled the inclusion criteria. A significant increase in serum 25-OHD levels was observed (P<0.01) from mean value of 21.6±5.9ng/ml (54.1±14.8nmol/L) at baseline to 31.7±9.1ng/ml (79.3±22.8nmol/L)≥2 months post intervention. The current treatment approach was successful in treating Vitamin D insufficiency in 70% of the patients with low 25-OHD levels. The results of this study demonstrate that a large number of adults attending Winnipeg Health Sciences Centre CF Clinic have serum 25-OHD levels below 30ng/ml (75nmol/L). This supports the need for dedicated and individualized approach to manage this condition. High dose therapy of vitamin D3, although a more aggressive treatment approach, may result in achieving optimal levels of serum 25-OHD in adults with CF.

High-Dose Vitamin D3 Administration Is Associated With Increases in Hemoglobin Concentrations in Mechanically Ventilated Critically Ill Adults: A Pilot Double-Blind, Randomized, Placebo-Controlled Trial.

Anemia and vitamin D deficiency are highly prevalent in critical illness, and vitamin D status has been associated with hemoglobin concentrations in epidemiologic studies. We examined the effect of high-dose vitamin D therapy on hemoglobin and hepcidin concentrations in critically ill adults. Mechanically ventilated critically ill adults (N = 30) enrolled in a pilot double-blind, randomized, placebo-controlled trial of high-dose vitamin D3 (D3 ) were included in this analysis. Participants were randomized to receive placebo, 50,000 IU D3 , or 100,000 IU D3 daily for 5 days (totaling 250,000 IU D3 and 500,000 IU D3 , respectively). Blood was drawn weekly throughout hospitalization for up to 4 weeks. Linear mixed-effects models were used to assess change in hemoglobin and hepcidin concentrations by treatment group over time. At enrollment, >75% of participants in all groups had plasma 25-hydroxyvitamin D (25(OH)D) concentrations <30 ng/mL, and >85% of participants across groups were anemic. In the 500,000-IU D3 group, hemoglobin concentrations increased significantly over time (Pgroup × time = .01) compared with placebo but did not change in the 250,000-IU D3 group (Pgroup × time = 0.59). Hepcidin concentrations decreased acutely in the 500,000-IU D3 group relative to placebo after 1 week (P = .007). Hepcidin did not change significantly in the 250,000-IU D3 group. In these critically ill adults, treatment with 500,000 IU D3 was associated with increased hemoglobin concentrations over time and acutely reduced serum hepcidin concentrations. These findings suggest that high-dose vitamin D may improve iron metabolism in critical illness and should be confirmed in larger studies.

High-dose vitamin D in Addison's disease regulates T-cells and monocytes: A pilot trial

On the basis of the immunomodulatory actions of vitamin D (VD), we investigated the effects of high-dose VD therapy over a 3 mo period on the immune response in patients with Addison's disease (AD). This randomized, controlled, crossover trial included 13 patients with AD who received either cholecalciferol (4000 IU/d) for 3 mo followed by 3 mo placebo oil or the sequential alternative placebo followed by verum. Glucocorticoid replacement doses remained stable. The primary outcome measures were changes in 25-hydroxyvitamin D3 (25(OH)D3) levels and immune cells including T helper cells (Th; CD3+CD4+), late-activated Th cells (CD3+CD4+HLA-DR+), regulatory T cells (CD3+CD4+CD25brightCD127dim/neg), cytotoxic T cells (Tc; CD3+CD8+), late-activated Tc cells (CD3+CD8+HLA-DR+), and monocytes. The explorative analysis included the correlation of changes with VD-related gene polymorphisms and 21-hydroxylase antibody titers. Ten of 13 patients (77%) were VD deficient. Median 25(OH)D3 concentrations increased significantly to 41.5 ng/ml (median changes: 19.95 ng/ml; P = 0.0005) after 3 mo of cholecalciferol treatment. Within the T-cells, only the late-activated Th (median changes: 1.6%; P = 0.02) and late-activated Tc cells (median changes: 4.05%; P = 0.03) decreased, whereas monocytes (median changes: 1.05%; P = 0.008) increased after VD therapy. T-cell changes were associated with two polymorphisms (CYP27B1-rs108770012 and VDR-rs10735810), but no changes in the 21-hydroxylase antibody titers were observed. Three months of treatment with cholecalciferol achieved sufficient 25(OH)D3 levels and can regulate late-activated T-cells and monocytes in patients with AD. Explorative analysis revealed potential genetic contributions. This pilot trial provides novel insights about immunomodulation in AD.

Bolus Weekly Vitamin D3 Supplementation Impacts Gut and Airway Microbiota in Adults With Cystic Fibrosis: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

Disruption of gut microbiota may exacerbate severity of cystic fibrosis (CF). Vitamin D deficiency is a common comorbidity in patients with CF that may influence composition of the gut microbiota. Compare microbiota of vitamin D-sufficient and -insufficient CF patients and assess impact of a weekly high-dose vitamin D3 bolus regimen on gut and airway microbiome in adults with CF and vitamin D insufficiency (25-hydroxyvitamin D < 30 ng/mL). Forty-one subjects with CF were classified into two groups: vitamin D insufficient (n = 23) and vitamin D sufficient (n = 18). Subjects with vitamin D insufficiency were randomized to receive 50,000 IU of oral vitamin D3 or placebo weekly for 12 weeks. Sputum and stool samples were obtained pre- and postintervention and 16S ribosomal RNA genes sequenced using Illumina MiSeq technology. Gut microbiota differed significantly based on vitamin D status with Gammaproteobacteria, which contain numerous, potentially pathogenic species enriched in the vitamin D-insufficient group. Principal coordinates analysis showed differential gut microbiota composition within the vitamin D-insufficient patients following 12 weeks treatment with placebo or vitamin D3 (permutation multivariate analysis of variance = 0.024), with Lactococcus significantly enriched in subjects treated with vitamin D3, whereas Veillonella and Erysipelotrichaceae were significantly enriched in patients treated with placebo. This exploratory study suggests that vitamin D insufficiency is associated with alterations in microbiota composition that may promote inflammation and that supplementation with vitamin D has the potential to impact microbiota composition. Additional studies to determine the impact of vitamin D on microbiota benefit clinical outcomes in CF are warranted.

Prenatal vitamin D supplementation reduces risk of asthma/recurrent wheeze in early childhood: A combined analysis of two randomized controlled trials.

BackgroundWe recently published two independent randomized controlled trials of vitamin D supplementation during pregnancy, both indicating a >20% reduced risk of asthma/recurrent wheeze in the offspring by 3 years of age. However, neither reached statistical significance.ObjectiveTo perform a combined analysis of the two trials and investigate whether maternal 25-hydroxy-vitamin D (25(OH)D) level at trial entry modified the intervention effect.MethodsVDAART (N = 806) and COPSAC2010. (N = 581) randomized pregnant women to daily high-dose vitamin D3 (4,000 IU/d and 2,400 IU/d, respectively) or placebo. All women also received a prenatal vitamin containing 400 IU/d vitamin D3. The primary outcome was asthma/recurrent wheeze from 0-3yrs. Secondary end-points were specific IgE, total IgE, eczema and lower respiratory tract infections (LRTI). We conducted random effects combined analyses of the treatment effect, individual patient data (IPD) meta-analyses, and analyses stratified by 25(OH)D level at study entry.ResultsThe analysis showed a 25% reduced risk of asthma/recurrent wheeze at 0-3yrs: adjusted odds ratio (aOR) = 0.74 (95% CI, 0.57–0.96), p = 0.02. The effect was strongest among women with 25(OH)D level ≥30ng/ml at study entry: aOR = 0.54 (0.33–0.88), p = 0.01, whereas no significant effect was observed among women with 25(OH)D level <30ng/ml at study entry: aOR = 0.84 (0.62–1.15), p = 0.25. The IPD meta-analyses showed similar results. There was no effect on the secondary end-points.ConclusionsThis combined analysis shows that vitamin D supplementation during pregnancy results in a significant reduced risk of asthma/recurrent wheeze in the offspring, especially among women with 25(OH)D level ≥ 30 ng/ml at randomization, where the risk was almost halved. Future studies should examine the possibility of raising 25(OH)D levels to at least 30 ng/ml early in pregnancy or using higher doses than used in our studies.Trial registrationCOPSAC2010: ClinicalTrials.gov NCT00856947; VDAART: ClinicalTrials.gov NCT00920621

Effects of vitamin D3 on endoplasmic reticulum stress in adipose tissue and insulin resistance induced by high fat diet in mice

Objective To study the effect of vitamin D3 on adipose tissue endoplasmic reticulum stress and insulin resistance induced by high fat diet in mice. Methods Eighty male C57BL/6 mice were divided into control group(n=20)and experimental group(n=60), fed with common food and high fat diet, respectively. After the establishment of the obesity model, the experimental mice were divided into control group, low-dose(50 IU/kg)vitamin D3 group(VitD-L), and high-dose(250 IU/kg)vitamin D3 group(VitD-H). After the mice were fed for 1 week, Western blot was used to detect the expressions of immunoglobulin heavy chain-binding protein(Bip), phosphorylated inositol-requiring enzyme 1(p-IRE1), phosphorylated protein kinase R(PKR)-like endoplasmic reticulum kinase(p-PERK), and NF-κB protein in adipose tissue. Serum levels of TNF-α, IL-6, serum 25-hydroxyvitamin D, fasting plasma glucose, HbA1C, triacylglyceride, and fasting insulin were measured and the insulin resistance index was calculated. Results Vitamin D3 down-regulated the expressions of endoplasmic reticulum stress key genes including Bip, p-IRE1, and p-PERK; and decreased the protein expression of NF-κB and the serum levels of TNF-α and IL-6(P<0.05). Vitamin D3 also significantly reduced the levels of fasting blood glucose, HbA1C, triacylglyceride, and fasting insulin in obese mice(P<0.05), while alleviated the insluin resistance in obese mice. Conclusion Vitamin D3 may significantly improve inflammatory response and insulin resistance via inhibiting endoplasmic reticulum stress in adipose tissue of obese mice. (Chin J Endocrinol Metab, 2017, 33: 861-864) Key words: Obesity; Vitamin D3; Endoplasmic reticulum stress; Insulin resistance

Adipose Tissue Remodeling by Prolonged Administration of High Dose of Vitamin D3 in Rats Treated to Prevent Sarcopenia

To examine the effect of high dose vitamin D3 treatment on visceral adipose tissue, we used vitamin D deficient male Wistar rats (18 months old) as a model of sarcopenia. The aging process is not only responsive for the losing muscle mass but also for redistribution of lipid resulting in altered fatty acid storage and dysdifferentiation of mesenchymal precursors. The effect of aging and vitamin D treatment (weekly oral gavage with 0.125 mg vitamin D3 (5000 IU)/100g body weight) on the omental adipose tissue were histological examinated. At the end of the experiment (9 monhs), adaptive changes to the reduction of adipogenesis and increased apoptosis in response to long-term treatment with vitamin D consisted of smaller size of adipocyte and moderate macrophage infiltrate.

Efficacy of high dose vitamin D supplementation in improving serum 25-hydroxyvitamin D among laboratory personnel working at the Nepal National Center for Rheumatic Diseases.

Vitamin D deficiency is a highly prevalent condition worldwide. However, few studies have been conducted to examine the vitamin D status of laboratory personnel and the correlation between vitamin D deficiency and working conditions. The aim of the present study was to assess changes in serum 25-hydroxyvitamin D [25(OH)D] concentration with a weekly dose of oral cholecalciferol (60,000 IU) for two months. The prospective, open-label, interventional study was conducted from January 2016 to March 2016 at the National Centre for Rheumatic Diseases, Kathmandu, Nepal. The serum level of 25(OH)D in 19 healthy laboratory volunteers was measured at baseline and following the 2-month regimen with cholecalciferol supplement at 60,000 IU (1,500 µg)/week in oral tablet form. At baseline the mean serum 25(OH)D level was 10.31±7.78 ng/ml, which was increased following completion of the course of oral cholecalciferol to 59.78±14.74 ng/ml. This difference in the mean serum level of 25(OH)D compared with baseline was significant to P<0.001. These results indicate that vitamin D deficiency is prevalent among laboratory workers, and that high dose vitamin D3 (60,000 IU cholecalciferol) in tablet form may be effective in achieving sufficient serum 25(OH)D among laboratory personnel who tend to have lower baseline serum 25(OH)D. In conclusion, vitamin D deficiency may be common among laboratory workers, and guidelines should be formulated to implement vitamin D supplementation among laboratory personnel, as well as indoor workers, in Nepal.