S102 Vitamin d supplementation to prevent acute respiratory infections: systematic review and meta-analysis of individual participant data

Abstract

Introduction and objectivesRandomised controlled trials of vitamin D to prevent acute respiratory infection have yielded mixed results. We conducted an individual patient data (IPD) meta-analysis to identify factors that may explain this heterogeneity.MethodsWe performed an IPD meta-analysis of 25 trials of vitamin D supplementation with incidence of acute respiratory infection as a pre-specified outcome (total 11,321 participants, aged 0 to 95 years). We used one-step logistic regression with random effects adjusting for age, sex, study duration and clustering by study. Pre-specified sub-group analyses were done to determine whether effects of vitamin D on risk of acute respiratory infection varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration or dosing regimen.ResultsIPD were obtained for 10,933/11,321 (96.6%) participants. Vitamin D supplementation reduced risk of acute respiratory infection among all participants (adjusted Odds Ratio [aOR] 0.88, 95% CI: 0.81 to 0.96, P = 0.003; P for heterogeneity < 0.001). Sub-group analysis revealed a strong protective effect among individuals with baseline 25(OH) D < 25 nmol/L (aOR 0.62, 95% CI: 0.45 to 0.83, P = 0.002), not seen among those with higher levels (aOR 0.91, 95% CI: 0.78 to 1.05; Pinteraction = 0.01). A protective effect was also seen in individuals receiving daily or weekly vitamin D without additional bolus doses (aOR 0.81, 95% CI: 0.72 to 0.91, P < 0.001), but not in those receiving one or more bolus doses (aOR 0.97, 95% CI: 0.86 to 1.10, Pinteraction = 0.05). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (aOR 0.98, 95% CI: 0.80 to 1.20, P = 0.83). The body of evidence contributing to these analyses was assessed as being of high quality.ConclusionsVitamin D supplementation was safe, and it protected against acute respiratory infection overall. Very deficient individuals and those not receiving bolus doses experienced the most benefit.

Vitamins C, D and Zinc: Synergistic Roles in Immune Function and Infections

“…Finally, vitamin D stimulates the expression of potent antimicrobial peptides, synthesized in neutrophils, monocytes, NK cells and in epithelial cells lining the respiratory tract where they play a major role in protecting the lung from infection [40]. It's therefore not surprising that low serum 25(OH)D levels are associated with an increased risk of respiratory infections [9] and a recent meta-analysis showed a 12% decrease in the risk of acute respiratory tract infections following vitamin D supplementation [60].…”

“…Finally, a systematic review and meta-analysis of individual participant data from randomized controlled studies was published in 2016 [60] and identified 25 eligible trials with a total of 11'321 participants (aged 0 to 95 years). Overall, vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants by 12%.…”

“…The most common respiratory tract infection is the common cold, but others include bronchitis, pneumonia, and infections of the sinuses or ears. At least 70% of the population gets one or more respiratory infection in any given year [60].…”

Impact of Serum 25(OH) Vitamin D Level on Mortality in Patients with COVID-19 in Turkey

“…Through several different but additive mechanisms, vitamin D produces anti-viral effects (8). Although not all included studies supported its conclusion, a meta-analysis found a protective effect of vitamin D supplementation against upper respiratory tract viral infections (9). First reports with respect to the role of vitamin D serum levels on contraction of SARS-CoV2 revealed that patients with PCR-proven COVID-19 had significantly lower serum 25(OH) D levels compared with patients without COVID-19, even after controlling for the effect of age (10).…”

Effects of vitamin D supplementation and seasonality on circulating cytokines in adolescents: analysis of data from a feasibility trial in Mongolia

“…linking the observed cytokine changes with the recent meta-analysis findings indicating that 25 nmol/L is a critical threshold of vitamin D deficiency associated with elevated risk for acute respiratory infection(7). Interestingly, in May the placebo group had higher 25(OH)D 3 concentrations compared to November, although these levels were still under the critical threshold of 25 nmol/L (Figure Comparedto baseline, six months of cholecalciferol supplementation resulted in a cumulative shift toward elevation for a majority (~%86) of measured cytokines.…”