Abstract
- Background
A 2017 meta-analysis of data from 25 randomized controlled trials ($\text{RCTs}$) of vitamin D supplementation for the prevention of acute respiratory infections ($\text{ARIs}$) revealed a protective effect. We aimed to examine the link between vitamin D supplementation and prevention of $\text{ARIs}$ in an updated systematic review and meta-analysis.
- Methods
We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov from database inception to May 1, 2020. Eligible studies were double-blind $\text{RCTs}$ of vitamin $\text{D}_3$, vitamin $\text{D}_2$, or $25$-hydroxyvitamin D ($25(\text{OH})\text{D}$) supplementation versus placebo or low-dose control, where $\text{ARI}$ incidence was prospectively collected and prespecified as an efficacy outcome. Aggregated study-level data stratified by baseline $25(\text{OH})\text{D}$ concentration and age were analyzed using random-effects meta-analysis to obtain pooled odds ratios ($\text{ORs}$) and $95\%$ confidence intervals ($\text{CIs}$). Subgroup analyses evaluated baseline $25(\text{OH})\text{D}$ level, dose, frequency, trial duration, age, and presence of airway disease. The study was registered with PROSPERO (CRD42020190633).
- Results
We identified 46 eligible $\text{RCTs}$ ($75,541\text{ participants}$). Data for the primary outcome were obtained for 48,488 ($98.1\%$) of 49,419 participants (aged $0\text{--}95\text{ years}$) across 43 studies. Vitamin D supplementation significantly reduced the proportion of participants experiencing one or more $\text{ARIs}$ compared to placebo ($14,332\text{ [}61.3\%\text{] of }23,364$ vs. $14,217\text{ [}62.3\%\text{] of }22,802$; $\text{OR} = 0.92$, $95\%\text{ CI} = 0.86\text{ to }0.99$; 37 studies; $I^2 = 35.6\%$, $p_{\text{heterogeneity}} = 0.018$). No significant interaction was observed across subgroups defined by baseline $25(\text{OH})\text{D}$ concentration. However, protective effects were observed in trials utilizing daily dosing regimens ($\text{OR} = 0.78$, $95\%\text{ CI} = 0.65\text{ to }0.94$), daily dose equivalents of $400\text{--}1000\text{ IU}$ ($\text{OR} = 0.70$, $95\%\text{ CI} = 0.55\text{ to }0.89$), trial durations $\le 12\text{ months}$ ($\text{OR} = 0.82$, $95\%\text{ CI} = 0.72\text{ to }0.93$), and in participants aged $1.00\text{--}15.99\text{ years}$ ($\text{OR} = 0.71$, $95\%\text{ CI} = 0.57\text{ to }0.90$). Serious adverse events did not differ significantly between groups ($\text{OR} = 0.97$, $95\%\text{ CI} = 0.86\text{ to }1.07$).
- Conclusions
Vitamin D supplementation was safe and overall reduced the risk of $\text{ARIs}$ compared with placebo, although the risk reduction was small. Protection was associated with daily doses of $400\text{--}1000\text{ IU}$ for up to 12 months and in individuals aged $1.00\text{--}15.99\text{ years}$.
https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00051-6/fulltext