Vitamin D supplementation to prevent asthma exacerbations: a systematic review and meta-analysis of individual participant data.

Double-blind, placebo-controlled randomized trials of vitamin D supplementation in people with asthma; seven RCTs with individual participant data (IPD) from 955 participants; ages 1.6–85 years; included both children and adults across multiple countries.

Oral supplementation with vitamin D (vitamin D3 or vitamin D2) in varying regimens: daily doses from 500 IU/day to 2000 IU/day; bolus dosing of 100,000 IU every 2 months; or a combination of bolus plus daily dosing (e.g., 100,000 IU bolus followed by 400–4000 IU/day). Study durations ranged from 15 weeks to 12 months.

Vitamin D supplementation reduced the rate of asthma exacerbations requiring systemic corticosteroids (adjusted incidence rate ratio 0.74; 95% CI 0.56–0.97; p=0.03; 955 participants). No significant effects on the proportion with at least one exacerbation or time to first exacerbation overall. In participants with baseline 25-hydroxyvitamin D <25 nmol/L, protective effect was stronger (aIRR 0.33; 95% CI 0.11–0.98; p=0.046). In participants with baseline 25(OH)D ≥25 nmol/L, reduction was not statistically significant (aIRR 0.77; 95% CI 0.58–1.03; p=0.08). Vitamin D did not increase hypercalcemia or renal stones; serious adverse events were not increased. Two-step IPD meta-analysis yielded similar results. Overall, vitamin D safely reduces rate of severe asthma exacerbations requiring systemic corticosteroids, particularly in those with very low baseline vitamin D, though evidence for differential effects across subgroups is not definitive.

Not IPD available for one eligible trial; one trial had unclear risk of bias due to loss to follow-up; dosing regimens and vitamin D forms varied (D2 vs D3; daily vs bolus vs mixed); definitions of exacerbation varied across trials; subgroup analyses were underpowered due to small sample sizes; some trials had very few events, limiting precision.