Research in context
Evidence before this study
Observational studies have shown a consistent link between serum 25-hydroxy vitamin D (25[OH]D) concentration and the risk or severity of acute respiratory tract infection. There have been several meta-analyses of randomised controlled trials that have assessed the effect of vitamin D supplementation on the risk and severity of these infections. However, the results were inconsistent in terms of the overall effect on the risk, and whether the effect is influenced by baseline 25(OH)D concentration or dosing regimen. We recently published a meta-analysis of observational studies and identified a consistent link between low 25(OH)D concentration and increased risk (n=78,127). Martineau and colleagues published two meta-analyses of randomised controlled trials, one in 2017 and one in July, 2020. The pooled effect estimate reported in the most recent meta-analysis was 0·89 (95% CI 0·81 to 0·98) for the overall risk of acute respiratory tract infection. However, there was high heterogeneity (I2 40·0%, p=0·009); there have been few truly population-based studies and questions remain about interactions with dosing regimen and baseline 25(OH)D concentration. There has been limited exploration of the effect of vitamin D on duration and severity of symptoms.
Added value of this study
Our results suggest that supplementing the general population with vitamin D is unlikely to reduce the risk of developing an acute respiratory tract infection. The observed reduction in duration of symptoms, and in the number of days with severe symptoms, is of unclear clinical significance, but suggests a potential impact of vitamin D on the immune response to infection. This is the second-largest trial to have reported on the effect of vitamin D supplementation on acute respiratory tract infections to date and thus makes an important contribution to the literature.
Implications of all the available evidence
The evidence, in its totality, suggests that vitamin D supplementation of adult populations that are largely vitamin D replete is unlikely to have a clinically significant effect on the risk or duration of acute respiratory tract infections.