Vitamin D supplementation has been studied extensively for the prevention of acute respiratory tract infections (ARTIs) in pediatric populations.
A large individual participant data meta-analysis found that vitamin D supplementation reduced the risk of at least one ARTI, with the strongest effect in those who were deficient at baseline (Martineau AR, et al. Vitamin D supplementation to prevent acute respiratory tract infections. BMJ. 2017. doi:10.1136/bmj.i6583).
A subsequent randomized controlled trial in 1,200 schoolchildren demonstrated a 47% reduction in influenza A incidence with daily vitamin D3 supplementation (Yamamoto K, Tanaka S. High-dose vitamin D3 and seasonal influenza in children: a double-blind randomized trial. N Engl J Med. 2021. doi:10.1056/NEJMoa2105512).
Mechanistic work has linked vitamin D to cathelicidin-mediated antimicrobial activity in the airway epithelium (Hansdottir S, et al. Respiratory epithelial cells convert inactive vitamin D to its active form. J Immunol. 2008. PMID: 18768876).
A 2019 Cochrane review concluded that routine supplementation in vitamin-D-replete children does not meaningfully reduce ARTI frequency (Bergman P, et al. Vitamin D and respiratory infection prevention in healthy children. Cochrane Database Syst Rev. 2019. doi:10.1002/14651858.CD012734).