Introduction and Objectives Meta-analysis of clinical trials of vitamin D supplementation for the prevention of acute respiratory infection (ARI) shows a protective effect in the general population, but there is controversy regarding the optimal dosing regimen. Low-dose vitamin D supplementation is already recommended in older adults for prevention of fractures and falls, but clinical trials investigating whether higher doses could provide additional protection against ARI are lacking.
Methods We conducted a double-blind cluster-randomised placebo-controlled trial of high- vs. low-dose vitamin D supplementation in residents and staff of sheltered accommodation schemes in London, UK. 108 schemes were allocated to receive the intervention (vitamin D3 2.4 mg 2-monthly + 10 μg daily for residents; 3 mg 2-monthly for staff) or control (vitamin D3 10 μg daily for residents, nil for staff) over the course of one year. The primary endpoint of the trial was time from first dose of study medication to date of first ARI, determined by a validated acute respiratory symptom score recorded prospectively in a symptom diary. Secondary outcomes included time to first upper / lower respiratory infections (URI/LRI) and mean serum 25-hydroxyvitamin D (25[OH]D) concentration.
Results 240 participants were included in the intention-to-treat analysis (137 participants in 54 schemes allocated to intervention, mean baseline 25[OH]D 43.8 nmol/L vs. 103 participants in 54 schemes allocated to control, mean baseline 25[OH]D 43.8 nmol/L). Median time to ARI was 203 days in the intervention arm and 227 days in the control arm (adjusted HR 1.18, 95% CI 0.80 to 1.74, p = 0.42). Allocation to the intervention arm of the trial was associated with increased risk of URI (adjusted HR 1.48, 95% CI 1.02 to 2.16, p = 0.04), but not with altered risk of LRI (adjusted HR 1.12, 95% CI 0.73 to 1.70, p = 0.61). Mean serum 25(OH)D concentration at 1 year was 84.8 nmol/L vs. 58.5 nmol/L in intervention vs. control arms (p < 0.0001).
Conclusions Addition of intermittent bolus-dose vitamin D supplementation to a daily low-dose regimen improved vitamin D status in older adults and their carers, but it did not influence risk of ARI, and was less effective at preventing URI.