Vitamin D Supplementation and the Risk of Colds in Patients with Asthma

Abstract

Rationale: Restoration of vitamin D sufficiency may reduce asthma exacerbations, events that are often associated with respiratory tract infections and cold symptoms.

Objectives: To determine whether vitamin D supplementation reduces cold symptom occurrence and severity in adults with mild to moderate asthma and vitamin D insufficiency.

Methods: Colds were assessed in the AsthmaNet VIDA (Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness) trial, in which 408 adult patients were randomized to receive placebo or cholecalciferol (100,000 IU load plus 4,000 IU/d) for 28 weeks as add-on therapy. The primary outcome was cold symptom severity, which was assessed using daily scores on the 21-item Wisconsin Upper Respiratory Symptom Survey.

Measurements and main results: A total of 203 participants experienced at least one cold. Despite achieving 25-hydroxyvitamin D levels of 41.9 ng/ml (95% confidence interval [CI], 40.1-43.7 ng/ml) by 12 weeks, vitamin D supplementation had no effect on the primary outcome: the average peak WURSS-21 scores (62.0 [95% CI, 55.1-68.9; placebo] and 58.7 [95% CI, 52.4-65.0; vitamin D]; P = 0.39). The rate of colds did not differ between groups (rate ratio [RR], 1.2; 95% CI, 0.9-1.5); however, among African Americans, those receiving vitamin D versus placebo had an increased rate of colds (RR, 1.7; 95% CI, 1.1-2.7; P = 0.02). This was also observed in a responder analysis of all subjects achieving vitamin D sufficiency, regardless of treatment assignment (RR, 1.4; 95% CI, 1.1-1.7; P = 0.009).

Conclusions: Our findings in patients with mild to moderate asthma undergoing an inhaled corticosteroid dose reduction do not support the use of vitamin D supplementation for the purpose of reducing cold severity or frequency.

Keywords: WURSS-21; asthma; upper respiratory tract infection; vitamin D.

Figure 1.

Number of colds per calendar month during the VIDA (Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness) trial. This histogram includes multiple colds per subject.

Figure 2.

Impact of the cold on asthma control. (Left) Changes in Asthma Control Test (ACT) scores. Subjects’ baseline measurements were subtracted from the ACT measurement taken at the next scheduled study visit for those with colds or from the ACT value at the end of the trial for those without colds. Error bars represent SE. (Right) Proportion of subjects with a decline in ACT score that was greater than 2, the minimal important difference. CI = confidence interval; OR = odds ratio.

Figure 3.

Cold symptom scores. (A) The sum of the Wisconsin Upper Respiratory Symptom Survey (WURSS)-21 cold scores on Days 1 and 2, Days 1–4, and Days 1–7 are shown, stratified by treatment assignment. Dark gray, placebo; light gray, vitamin D. (B) These scores were reported daily for the time courses shown during the first 14 days after the start of the cold. The number of observations for each day is included, with an expected decrease in sample size due to the resolution of some colds before the 14-day period was completed. In addition to the peak scores for single-day measurements, data are presented as mean ± SE.

Figure 4.

Number of colds per person-year, stratified by 25-hydroxyvitamin D level data collected at baseline (light gray bars) or after completing 12 of 28 weeks of treatment (dark gray bars).