Current estimates suggest that acute respiratory tract infections are responsible for about 2.7 million deaths[1] worldwide and are the most common reason[2] for doctor visits and antibiotic prescription in the United States. Respiratory infections include, but are not limited to the common cold, sinus infections, and ear infections[3].

These diseases are highly opportunistic and often manifest themselves in people with reduced immune function. Low levels of vitamin D have been associated with worse immune function[4] and increased rates[5] of acute respiratory infection, possibly due to its role in regulating the immune system (as outlined in Figure 1). For example, it has been well documented that low levels of vitamin D in countries with suboptimal sunlight (about 32-42o N or S of the equator[6]) as well as a genetic predisposition for low vitamin D status are both associated with increased[7] rates of acute respiratory tract infections. This observation has also appeared in the United States[8]. These data suggest that adequate vitamin D status might be a protective factor against acute respiratory tract infections.

Adapted from: Lang et al. Osteoporos Int. 2013 May

There is also genetic data demonstrating a link between vitamin D status and acute respiratory infections. Genetic polymorphisms that result in a reduction in the total number of vitamin D receptors in the human body are associated with an increased risk[9] of acute respiratory tract infections) in children, further supporting a role for vitamin D in immune regulation.

The most recent meta-analysis[10] of controlled trials investigating the effect of vitamin D supplementation on the risk of developing respiratory tract infections found that vitamin D supplementation did not have a significant effect. However, heterogeneity was high and there was a marginally significant benefit in people who were deficient and in people who took vitamin D daily rather than in weekly boluses.

By examining individual patient data (IPD), it may be possible to overcome inconsistencies at the trial level. IPD can be used to determine whether specific treatments are effective for what kinds of people and under which circumstances. In addition to allowing for conduct subgroup analysis on consistently defined criteria, utilizing IPD data overcomes several key issues with trial-level meta-analyses that use aggregate data. Trial-level meta-analyses ignore the effect of missing data and omit important correlational structures, which are overcomed by IPD analyses[11]. Recently, IPD-based meta-analysis methods were utilized to compile data across vitamin D intervention trials and examine patient level data to determine which patients would benefit from vitamin D supplementation and which dosing strategies were effective for lowering risk of acute respiratory tract infection.

Vitamin D has well-established immunomodulatory properties and there is some evidence to suggest that vitamin D levels are linked to infections. It has been well documented that lower levels of vitamin D, either genetically or due to environment, are associated with higher levels of acute respiratory tract infections. The current study was a meta-analysis of individual participant data that sought to determine whether vitamin D supplementation can lower ones’ risk of acute respiratory tract infections, as well as identify people that might benefit from supplementation and those that might not.