Dataset Information

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

ABSTRACT: Context: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. Objectives: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). Design: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. Results: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. Conclusion: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.

SUBMITTER: Kanhere M

PROVIDER: S-EPMC5800825 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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

Kanhere Mansi M He Jiabei J Chassaing Benoit B Ziegler Thomas R TR Alvarez Jessica A JA Ivie Elizabeth A EA Hao Li L Hanfelt John J Gewirtz Andrew T AT Tangpricha Vin V

The Journal of clinical endocrinology and metabolism 20180201 2

<h4>Context</h4>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.<h4>Objectives</h4>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).<h4>Design</h4>Forty-on ...[more]

PMID: 29161417

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Project description:OBJECTIVE: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. DESIGN, SETTING AND PATIENTS:Randomized controlled trial (clinicaltrials.govNCT01240265) in 40 lactating women. INTERVENTIONS: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. MAIN OUTCOME MEASURE:Temporal changes in the serum 24,25(OH)2D3/25(OH)D3 ratio. RESULTS: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. CONCLUSIONS: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.

Project description:BackgroundVitamin D deficiency is associated with obesity; whether repletion supports weight loss and changes obesity-related biomarkers is unknown.ObjectiveWe compared 12 mo of vitamin D3 supplementation with placebo on weight, body composition, insulin, and C-reactive protein (CRP) in postmenopausal women in a weight-loss intervention.DesignA total of 218 overweight/obese women (50-75 y of age) with serum 25-hydroxyvitamin D [25(OH)D] ≥10 ng/mL but <32 ng/mL were randomly assigned to weight loss + 2000 IU oral vitamin D3/d or weight loss + daily placebo. The weight-loss intervention included a reduced-calorie diet (10% weight loss goal) and 225 min/wk of moderate-to-vigorous aerobic activity. Mean 12-mo changes in weight, body composition, serum insulin, CRP, and 25(OH)D were compared between groups (intent-to-treat) by using generalized estimating equations.ResultsA total of 86% of participants completed the 12-mo measurements. The mean (95% CI) change in 25(OH)D was 13.6 (11.6, 15.4) ng/mL in the vitamin D3 arm compared with -1.3 (-2.6, -0.3) ng/mL in the placebo arm (P < 0.0001). Changes in weight [-7.1 (-8.7, -5.7) compared with -7.4 (-8.1, -5.4) kg], body mass index (in kg/m(2): both -2.8), waist circumference [-4.9 (-6.7, -2.9) compared with -4.5 (-5.6, -2.6) cm], percentage body fat [-4.1 (-4.9, -2.9) compared with -3.5 (-4.5, -2.5)], trunk fat [-4.1 (-4.7, -3.0) compared with -3.7 (-4.3, -2.9) kg], insulin [-2.5 (-3.4, -1.7) compared with -2.4 (-3.3, -1.4) μU/mL], and CRP [-0.9 (-1.2, -0.6) compared with -0.79 (-0.9, -0.4) mg/L] [corrected] were similar between groups (all P > 0.05). Compared with women who achieved 25(OH)D <32 ng/mL, women randomly assigned to vitamin D who became replete (ie, 25(OH)D ≥32 ng/mL) lost more weight [-8.8 (-11.1, -6.9) compared with -5.6 (-7.2, -5.0) kg; P = 0.05], waist circumference [-6.6 (-9.3, -4.3) compared with -2.5 (-4.6, -2.0) cm; P = 0.02], and percentage body fat [-4.7 (-6.1, -3.5) compared with -2.6 (-3.9, -2.2); P = 0.04]. Among women with complete pill counts (97% adherence), the mean decrease in CRP was 1.18 mg/mL (46%) in the vitamin D arm compared with 0.46 mg/mL (25%) in the placebo arm (P = 0.03).ConclusionsVitamin D3 supplementation during weight loss did not increase weight loss or associated factors compared with placebo; however, women who became replete experienced greater improvements. This trial was registered at clinicaltrials.gov as NCT01240213.

Project description:While vitamin D inadequacy occurs worldwide, there is a lack of consensus internationally on the optimum plasma levels of 25(OH)D to maximally suppress the level of parathyroid hormone toward reducing bone loss. This study aimed to investigate the response of intact parathyroid hormone (iPTH) to vitamin D3 supplementation among Malaysian women of reproductive age in a randomised double-blind placebo-control trial [NMRR-15-479-25680]. A total of 106 women who fulfilled the study inclusion criteria were randomly assigned to receive daily one of these three supplement doses (i) 600 IU vitamin D3 + 500 mg calcium; (ii) 1200 IU vitamin D3 + 500 mg calcium; or (iii) 4000 IU vitamin D3 + 500 mg calcium. The placebo group received daily 500 mg calcium. The outcome examined was change in plasma iPTH concentration in response to daily vitamin D3 supplementation for 16 weeks. Fasting blood sample was obtained at baseline and post-supplementation. A total of 78 subjects (73.6%) completed the intervention. None of the supplementation groups brought about any detectable suppression of iPTH concentration post-supplementation. Vitamin D3 supplementation resulted in overall increase in plasma 25(OH)D levels, but only the 4000 IU/day group showed a significant dose effect post-supplementation (mean 49.7 ± 26.5 nmol/L) compared to placebo (29.3 ± 13.3 nmol/L). The lack of iPTH suppression is attributed to high prevalence of vitamin D insufficiency at baseline and the supplementation regimen was inadequate to raise the 25(OH)D level to cause PTH suppression. Inadequate calcium intake of the participants was also a likely contributing factor to the result. As prolonged vitamin D insufficiency and hypocalcaemia could lead to a compensatory rise in PTH resulting in accelerated bone loss, as well as posing increasing risks of non-skeletal morbidities, further clinical trials with an adequately powered sample size should be undertaken over an appropriate study duration to verify the results obtained in this study.

Project description:BackgroundCystic fibrosis (CF) is a multi-organ disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Individuals with CF often have gastrointestinal (GI) dysbiosis due to chronic inflammation and antibiotic use. Previous studies suggested a role for vitamin D in reversing the GI dysbiosis found in CF.ObjectiveTo explore the potential role of a combination of high-dose oral cholecalciferol (vitamin D3) and fermentable dietary fiber, inulin, to impact bacterial composition, richness, and diversity of intestinal and airway microbiota in adults with CF.MethodsThis was a 2 × 2 factorial, double-blinded, placebo-controlled, randomized, pilot clinical trial in which adults with CF received oral cholecalciferol (vitamin D3) (50,000 IU/week) and/or inulin (12 g/day) for 12 weeks. Thus, there were 4 study groups (n = 10 subjects per group); 1) placebo 2) vitamin D3 3) inulin 4) vitamin D3 plus inulin. Stool and sputum samples were collected at baseline (just before) and after the intervention and were analysed using 16S ribosomal RNA gene sequencing for gut and airway microbiota composition. Statistical analyses assessed alpha and beta diversity to evaluate microbial community changes.ResultsOf a total of 254 screened participants, 40 eligible participants were randomized to one of the 4 treatment arms. Participants receiving vitamin D3 plus inulin exhibited greater changes in microbiome indexes in both intestinal and airway relative to those in the other study groups. Specific taxonomic changes supported the potential beneficial influence of this combination to mitigate both intestinal and airway dysbiosis in adults with CF.ConclusionThis pilot study established that the combination of oral vitamin D3 and the prebiotic inulin was well tolerated over 12 weeks in adults with CF and altered gut and airway bacterial communities. Future research appear warranted to define clinical outcomes and the role of microbiota changes therein with this approach.

Dataset Information

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

Publications

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

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