Vitamin D(3) and gargling for the prevention of upper respiratory tract infections: a randomized controlled trial

BACKGROUND: We undertook a 2X2 factorial, randomized controlled trial (RCT) to assess whether vitamin D(3) supplementation (10,000 international units per week) versus placebo and gargling versus no gargling could prevent viral, clinical upper respiratory tract infection (URTI) in university students. METHODS: We randomized 600 students into 4 treatment arms: 1) vitamin D(3) and gargling, 2) placebo and gargling, 3) vitamin D(3) and no gargling, and 4) placebo and no gargling. Students completed weekly electronic surveys and submitted self-collected mid-turbinate nasal flocked swabs during September and October in 2010 or 2011. Symptomatic students also completed an electronic symptom diary. The primary and secondary outcomes were the occurrence of symptomatic clinical URTI and laboratory confirmed URTI respectively. RESULTS: Of 600 participants, 471 (78.5%) completed all surveys while 43 (7.2%) completed none; 150 (25.0%) reported clinical URTI. Seventy participants (23.3%) randomized to vitamin D(3) reported clinical URTI compared to 80 (26.7%) randomized to placebo (RR:0.79, CI(95):0.61-1.03, p = 0.09). Eighty-five participants (28.3%) randomized to gargling reported clinical URTI compared to 65 participants (21.7%) randomized to the no gargling arm (RR:1.3, CI(95):0.92-1.57, p = 0.19). Laboratory testing identified 70 infections (46.7 per 100 URTIs). Vitamin D(3) treatment was associated with a significantly lower risk for laboratory confirmed URTI (RR: 0.54, CI(95):0.34-0.84, p = 0.007) and with a significantly lower mean viral load measured as log(10) viral copies/mL (mean difference: -0.89, CI(95:) -1.7, -0.06, p = 0.04). Fewer students assigned to gargling experienced laboratory confirmed URTI, however this was not statistically significant (RR:0.82, CI(95):0.53-1.26, p = 0.36). CONCLUSIONS: These results suggest that vitamin D(3) is a promising intervention for the prevention of URTI. Vitamin D(3) significantly reduced the risk of laboratory confirmed URTI and may reduce the risk of clinical infections. TRIAL REGISTRATION: Clinical Trials Registration: NCT01158560.