Vitamin D for the Immune System in Cystic Fibrosis (DISC): a double-blind, multicenter, randomized, placebo-controlled clinical trial.

BACKGROUND: Patients with cystic fibrosis (CF) have increased risk of vitamin D deficiency owing to fat malabsorption and other factors. Vitamin D deficiency has been associated with increased risk of pulmonary exacerbations of CF. OBJECTIVES: The primary objective of this study was to examine the impact of a single high-dose bolus of vitamin D3 followed by maintenance treatment given to adults with CF during an acute pulmonary exacerbation on future recurrence of pulmonary exacerbations. METHODS: This was a multicenter, double-blind, placebo-controlled, intent-to-treat clinical trial. Subjects with CF were randomly assigned to oral vitamin D3 given as a single dose of 250,000 International Units (IU) or to placebo within 72 h of hospital admission for an acute pulmonary exacerbation, followed by 50,000 IU of vitamin D3 or an identically matched placebo pill taken orally every other week starting at 3 mo after random assignment. The primary outcome was the composite endpoint of the time to next pulmonary exacerbation or death within 1 y. The secondary outcomes included circulating concentrations of the antimicrobial peptide cathelicidin and recovery of lung function as assessed by the percentage of predicted forced expiratory volume in 1 s (FEV1%). RESULTS: A total of 91 subjects were enrolled in the study. There were no differences between the vitamin D3 and placebo groups in time to next pulmonary exacerbation or death at 1 y. In addition, there were no differences in serial recovery of lung function after pulmonary exacerbation by FEV1% or in serial concentrations of plasma cathelicidin. CONCLUSIONS: Vitamin D3 initially given at the time of pulmonary exacerbation of CF did not alter the time to the next pulmonary exacerbation, 12-mo mortality, serial lung function, or serial plasma cathelicidin concentrations. This trial was registered at clinicaltrials.gov as NCT01426256.

Serum 25-hydroxyvitamin D but not dietary vitamin D intake is associated with hemoglobin in women of reproductive age in rural northern Vietnam.

BACKGROUND AND OBJECTIVES: Hypovitaminosis D and anemia are both prevalent in Vietnam, and low vitamin D status may be a risk factor for anemia. This study aimed to 1) describe vitamin D intake and its determinants, and 2) examine the associations of vitamin D intake and serum 25(OH)D concentrations with hemoglobin and anemia. METHODS AND STUDY DESIGN: We used data from the baseline survey of a pre-conceptual micronutrient supplementation trial in women of reproductive age (WRA) in Thai Nguyen, Vietnam (N = 4961). Vitamin D intake was estimated using a semi-quantitative food frequency questionnaire (FFQ). Multivariable regression models were used for the analyses. RESULTS: Median vitamin D intake was 0.2 µg/d (8.0 IU) [IQR: 0.4]. Age, being a farmer, food insecurity, and body mass index (BMI) were inversely associated with vitamin D intake, while socioeconomic status (SES), total energy intake, and education were positively associated with vitamin D intake. Vitamin D intake was not associated with hemoglobin concentration or anemia after adjusting for age, BMI, total energy intake, transferrin receptor, C-reactive protein, α1-acid glycoprotein, SES, occupation, education, ethnicity, and food insecurity (P = 0.56 and P = 0.65 for hemoglobin and anemia, respectively). Controlling for the same covariates, 25(OH)D <50 nmol/L (vs. ≥50 nmol/L) was associated with decreased hemoglobin concentrations (ß = -0.91 (SE:0.42), P = 0.03), but not with anemia (P = 0.11). CONCLUSIONS: Low vitamin D status may be linked to reduced hemoglobin concentrations, but the role of diet in this association was not evident in this population of WRA in Vietnam where dietary vitamin D intake was very low.

Plasma metabolomics in adults with cystic fibrosis during a pulmonary exacerbation: A pilot randomized study of high-dose vitamin D3 administration.

BACKGROUND: Cystic fibrosis (CF) is a chronic catabolic disease often requiring hospitalization for acute episodes of worsening pulmonary exacerbations. Limited data suggest that vitamin D may have beneficial clinical effects, but the impact of vitamin D on systemic metabolism in this setting is unknown. OBJECTIVE: We used high-resolution metabolomics (HRM) to assess the impact of baseline vitamin D status and high-dose vitamin D3 administration on systemic metabolism in adults with CF with an acute pulmonary exacerbation. DESIGN: Twenty-five hospitalized adults with CF were enrolled in a randomized trial of high-dose vitamin D3 (250,000IU vitamin D3 bolus) versus placebo. Age-matched healthy subjects served as a reference group for baseline comparisons. Plasma was analyzed with liquid chromatography/ultra-high resolution mass spectrometry. Using recent HRM bioinformatics and metabolic pathway enrichment methods, we examined associations with baseline vitamin D status (sufficient vs. deficient per serum 25-hydroxyvitamin D concentrations) and the 7-day response to vitamin D3 supplementation. RESULTS: Several amino acids and lipid metabolites differed between CF and healthy control subjects, indicative of an overall catabolic state. In CF subjects, 343 metabolites differed (P<0.05) by baseline vitamin D status and were enriched within 7 metabolic pathways including fatty acid, amino acid, and carbohydrate metabolism. A total of 316 metabolites, which showed enrichment for 15 metabolic pathways-predominantly representing amino acid pathways-differed between the vitamin D3- and placebo-treated CF subjects over time (P<0.05). In the placebo group, several tricarboxylic acid cycle intermediates increased while several amino acid-related metabolites decreased; in contrast, little change in these metabolites occurred with vitamin D3 treatment. CONCLUSIONS: Numerous metabolic pathways detected by HRM varied in association with vitamin D status and high-dose vitamin D3 supplementation in adults with CF experiencing a pulmonary exacerbation. Overall, these pilot data suggest an anti-catabolic effect of high-dose vitamin D3 in this clinical setting.