The effect of a single, large bolus of vitamin D in healthy adults over the winter and following year: a randomized, double-blind, placebo-controlled trial.

BACKGROUND/OBJECTIVES: Although single, high doses of vitamin D effectively maintain vitamin D sufficiency in several populations, no studies have evaluated healthy adults over winter, during which vitamin D status declines. This study investigated whether high-dose vitamin D3 given once to healthy adults before winter will (1) prevent the wintertime decline in vitamin D status, (2) promote vitamin D sufficiency 1 year following the dose and (3) prevent the rise of parathyroid hormone (PTH) concentrations. SUBJECTS/METHODS: In this double-blind, placebo-controlled trial, we assessed plasma 25(OH)D and PTH concentrations at baseline, 5, 90 and 365 days after drug administration in 28 healthy adults. In all, >80% of subjects returned at each time point. RESULTS: At baseline, the young, healthy participants had a mean plasma 25(OH)D concentration of 17.5±6.1 ng/ml. Only two subjects exhibited plasma 25(OH)D concentrations >30 ng/ml. At 5 days, subjects randomized to vitamin D3 had a higher mean plasma 25(OH)D concentration compared with the placebo group (39.1 vs 19.1 ng/ml, P<0.001). Plasma 25(OH)D concentrations returned to baseline at 90 and 365 days in the vitamin D3 group and remained unchanged in the placebo group. PTH and calcium concentrations were unrelated to changes in 25(OH)D levels and similar between groups over time. CONCLUSIONS: A dose of 250,000 IU of vitamin D3 given once in November resulted in a robust increase in plasma 25(OH)D after 5 days, but it was unable to sustain this increase after 90 days. A larger or more frequent dosing regimen may be needed for long-term vitamin D sufficiency.

Effects of high-dose cholecalciferol on serum markers of inflammation and immunity in patients with early chronic kidney disease.

BACKGROUND/OBJECTIVES: Vitamin D has anti-inflammatory and immune-regulating properties. We aimed to determine if high-dose cholecalciferol supplementation for 1 year in subjects with early chronic kidney disease (CKD) improved circulating markers of inflammation and immunity. SUBJECTS/METHODS: In this double-blind, randomized, placebo-controlled trial, 46 subjects with early CKD (stages 2 and 3) were supplemented with oral cholecalciferol (50 000 IU weekly for 12 weeks followed by 50 000 IU every other week for 40 weeks) or a matching placebo for 1 year. Serum tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1 (MCP-1), interferon gamma-induced protein-10 and neutrophil gelatinase-associated lipocalin were measured at baseline, 12 weeks and 1 year. Serum cathelicidin (LL-37) was measured at baseline and 12 weeks. An in vitro experiment was performed to investigate the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment on MCP-1 secretion in THP-1 monocytes activated with lipopolysaccharide (LPS) and Pseudomonas aeruginosa. RESULTS: By 12 weeks, serum MCP-1 decreased in the cholecalciferol group (66.2±2.5 to 60.8±2.6 pg/ml, group-by-time interaction P=0.02) but was not different from baseline at 1 year. Other markers of inflammation and immunity did not change. In vitro, LPS- and Pseudomonas-activated monocytes treated with 1,25(OH)2D3 had significantly less MCP-1 secretion compared with untreated cells. CONCLUSIONS: High-dose cholecalciferol decreased serum MCP-1 concentrations by 12 weeks in patients with early CKD, although the decrease was not maintained for the remainder of the year. In vitro results confirm an MCP-1-lowering effect of vitamin D. Future studies should determine if vitamin D-mediated reductions in MCP-1 concentrations reflect improved clinical outcomes.

Impact of vitamin D supplementation on markers of inflammation in adults with cystic fibrosis hospitalized for a pulmonary exacerbation.

Patients with cystic fibrosis (CF) suffer from chronic lung infection and inflammation leading to respiratory failure. Vitamin D deficiency is common in patients with CF, and correction of vitamin D deficiency may improve innate immunity and reduce inflammation in patients with CF. We conducted a double-blinded, placebo-controlled, randomized clinical trial of high-dose vitamin D to assess the impact of vitamin D therapy on antimicrobial peptide concentrations and markers of inflammation. We randomized 30 adults with CF hospitalized with a pulmonary exacerbation to 250,000 IU of cholecalciferol or placebo, and evaluated changes in plasma concentrations of inflammatory markers and the antimicrobial peptide LL-37 at baseline and 12 weeks post intervention. In the vitamin D group, there was a 50.4% reduction in tumor necrosis factor-α (TNF-α) at 12 weeks (P<0.01), and there was a trend for a 64.5% reduction in interleukin-6 (IL-6) (P=0.09). There were no significant changes in IL-1ß, IL-8, IL-10, IL-18BP and NGAL (neutrophil gelatinase-associated lipocalin). We conclude that a large bolus dose of vitamin D is associated with reductions in two inflammatory cytokines, IL-6 and TNF-α. This study supports the concept that vitamin D may help regulate inflammation in CF, and that further research is needed to elucidate the potential mechanisms involved and the impact on clinical outcomes.

An update on the screening, diagnosis, management, and treatment of vitamin D deficiency in individuals with cystic fibrosis: evidence-based recommendations from the Cystic Fibrosis Foundation.

OBJECTIVE: The objective was to develop evidence-based clinical care guidelines for the screening, diagnosis, management, and treatment of vitamin D deficiency in individuals with cystic fibrosis (CF). PARTICIPANTS: The guidelines committee was comprised of physicians, registered dietitians, a pharmacist, a nurse, a parent of an individual with CF, and a health scientist, all with experience in CF. PROCESS: Committee members developed questions specific to vitamin D health in individuals with CF. Systematic reviews were completed for each question. The committee reviewed and graded the available evidence and developed evidence-based recommendations and consensus recommendations when insufficient evidence was available. Each consensus recommendation was voted upon by an anonymous process. CONCLUSIONS: Vitamin D deficiency is common in CF. Given the limited evidence specific to CF, the committee provided consensus recommendations for most of the recommendations. The committee recommends yearly screening for vitamin D status, preferably at the end of winter, using the serum 25-hydroxyvitamin D measurement, with a minimal 25-hydroxyvitamin D concentration of 30 ng/ml (75 nmol/liter) considered vitamin D sufficient in individuals with CF. Recommendations for age-specific vitamin D intake for all individuals with CF, form of vitamin D, and a stepwise approach to increase vitamin D intake when optimal vitamin D status is not achieved are delineated.