Effectiveness of Vitamin D Supplementation on Preventing Acute Respiratory Infections

Effectiveness of Vitamin D Supplementation on Preventing Acute Respiratory Infections
Sami Russo, PharmD, Goodrich Pharmacy

Background: There have been heterogeneous results when studying the use of vitamin D supplementation to reduce the risk of acute respiratory infections (ARIs). The past findings have shown vitamin D metabolites support immune response to respiratory viruses. Additionally, this hypothesis has been supported by observational studies that have reported an association between low concentrations of the biomarker for vitamin D, 25-hydroxyvitamin D (25[OH]D) and an increased risk of ARI. 

Purpose: This systematic review and meta-analysis aimed to evaluate the effects of vitamin D supplementation on ARI risk, considering such factors as baseline 25[OH]D levels, vitamin D dosing regimen, and age. 

Study DesignA systematic review and meta-analysis was completed using MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov, with studies from database inception to 2020. The earliest study included was in 2009. Studies included randomized, double-blind, trials of vitamin D supplementation with a placebo control group that reported the incidence of ARI. Studies were only included if ARI was studied prospectively and listed as an efficacy outcome. The primary outcome was the proportion of participants with one or more ARI, which was defined as an upper respiratory infection, lower respiratory infection, or location unclassified. Secondary outcomes focused on a lower or upper respiratory infection, emergency medical attention or hospital admission for an ARI, death associated with an ARI, or antibiotic use for an ARI. Forty six studies were eligible out of 1528 studies assessed in the database search, which included 75,541 randomized participants. 

Results: The results of the primary outcome showed a significantly lower proportion of participants taking vitamin D having one or more ARIs compared to placebo (OR 0.92 [95% CI 0.86-0.99]). Further evaluation of this effect explored baseline 25[OH]D concentration, age, and vitamin D dosing. There was no significant effect of vitamin D supplementation on ARIs for patients with a baseline 25[OH]D less than 25 nmol/L (0.81 [ 0.57-1.15]), 25-49.9 nmol/L (1.04 [0.94-1.15]), 50-74.9 nmol/L (0.88 [0.76-1.02]), or more than 75nmol/L (1.00 [0.85-1.58]). A significant protective effect of vitamin D on ARI was seen for participants 1.00-15.99 years old (0.71 [0.57-0.90]), but not significant in participants less than 1 year old (0.95 [0.82-1.10]), 16 to 64.99 years (0.97 [0.93-1.09]), or over 65 years (0.96 [0.90-1.02]). The protective effect of vitamin D was seen when vitamin D was given daily (0.78 [0.65-0.94]), but not when given weekly (0.97 [0.88-1.06]). Doses of vitamin D also had an effect of the significance of the protective effect, finding doses of 400-1000IU daily (0.70 [0.55-0.89]) was protective against ARI, while doses less than 400IU were not (0.65 [0.31-1.37]). Interestingly, doses of 1000-2000IU daily (0.97 [0.93-1.02]) were also insignificant. The results of the secondary outcomes did not find significance. 

Conclusions: Despite heterogeneity across trials evaluated, it was concluded that vitamin D supplementation significantly reduced the risk of ARI compared with placebo. Protection was significant with daily doses of 400-1000IU vitamin D daily at ages of 1.00-15.99 years. The magnitude of this effect was small (0.92 [0.86-0.99]) and was less for those with a baseline 25[OH]D concentration less than 25 nmol/L. 

Key Point: Vitamin D supplementation can reduce the risk of ARI at doses of 400-1000IU daily for patients 1.00-15.99 years old.



  1. Jolliffe DA, Camargo CA Jr, Sluyter JD, et.al. Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials. Lancet Diabetes Endocrinol. 2021; 9: 276-92.