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 (250,000 IU 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.

BACKGROUND Anemia, iron deficiency and hypovitaminosis D are well-known comorbidities in inflammatory bowel disease (IBD). Epidemiologic studies have linked vitamin D deficiency with increased risk of anemia, and in vitro studies suggest that vitamin D may improve iron recycling through down-regulatory effects on hepcidin and pro-inflammatory cytokines. DESIGN/METHODS We aimed to investigate the association of vitamin D status with inflammation, iron biomarkers, and anemia in pediatric IBD. Cross-sectional data was obtained from N=69 IBD patients aged 5 to <19y. Iron biomarkers [ferritin, soluble transferrin receptor (sTfR)], 25-hydroxyvitamin D (25(OH)D), inflammatory biomarkers [C-reactive protein (CRP), α1-acid glycoprotein (AGP)], hepcidin, and hemoglobin were collected. Iron biomarkers were regression corrected for inflammation. Multivariable logistic/linear models were used to examine the associations of 25(OH)D with inflammation, iron status, hepcidin, and anemia. RESULTS ~ 50% of subjects were inflamed (CRP>5 mg/L or AGP>1 g/L). Iron deficiency prevalence (inflammation-corrected ferritin < 15 μg/L or sTfR > 8.3mg/L) was 67%; anemia was 36%, vitamin D insufficiency (25(OH)D < 30 ng/mL) was 77%. In linear regression models, vitamin D insufficiency was associated with increased hepcidin levels (β(SE)=0.6(0.2), P=0.01) and reduced hemoglobin (β(SE)= −0.9 (0.5), P=0.046), controlling for age, sex, race, insurance status, body mass index-for-age, inflammation, disease diagnosis (ulcerative colitis vs. Crohn’s) and disease duration, compared to 25(OH)D ≥ 30 ng/mL. CONCLUSIONS Our results suggest that concentrations of 25(OH)D ≥ 30 ng/mL are associated with lower hepcidin and higher hemoglobin levels. Further research is needed to clarify the association of vitamin D with inflammation, iron status and anemia in pediatric IBD.

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.

Background and objectivesHypovitaminosis 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 designWe 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.ResultsMedian 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 (β = −0.91 (SE:0.42), P = 0.03), but not with anemia (P = 0.11).ConclusionsLow 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.

The authors regret there was an error in Fig. 2C. The metabolite L-Alanine is incorrectly colored as green. It should be yellow as shown here. The authors would like to apologize for any inconvenience caused.