Applicability of the results
Three of the reviews consistently showed a benefit of vitamin D supplementation for preventing respiratory tract infection mainly in children younger than 16 years (10–12). Two of the reviews also reported that the protective effect is observed only when single daily doses are used but not when bolus doses are given (10, 12). One review further showed that doses of 800 IU or less were protective of respiratory tract infections, but not higher doses (12). However, this protective role was not seen for pneumonia, as reported by Yakoob et al. (9) from only two trials.
It is important to note that most reviews reported significant heterogeneity, which may make the generalizability of the results difficult. This heterogeneity may be due to several reasons, including some publication bias, but also methodological issues, such as low numbers of trials, vitamin D supplementation regime used and heterogeneity of participants’ characteristics. With respect of vitamin D supplementation regime, these reviews showed that the size of the dose and the administration intervals might modify the effects of vitamin D supplementation on respiratory tract infections. Daily smaller doses were more effective than single large boluses of vitamin D. In fact, studies have shown that large boluses may in some cases increase the risk of adverse outcomes, such as increased risk of pneumonia, suppressed proliferative responses of peripheral blood monocytes, suppressed inflammation, and greater positive sputum cultures (13–16). With respect to participant’s characteristics, body mass index as well as baseline vitamin D status may modify the 25-hydroxyvitamin D response to vitamin D supplementation (15, 17, 18).
Implementation in settings with limited resources
Vitamin D supplementation for preventing respiratory tract infection is not routinely done. For this intervention to be effective, it should be done continuously, before the respiratory tract infection starts. This could be a major challenge in many under-resourced settings, as programme managers and policy-makers will have to plan for procurement of the preparation, storage, distribution, quality-control, and compliance assurance of vitamin D supplements for children on a routine basis. Failures in implementation of this intervention have been attributed in many instances to inadequate infrastructure and poor compliance, particularly in developing countries. Intermittent vitamin D supplementation would reduce some of these challenges, although results from these trials show that bolus doses are not effective. Future studies could evaluate the effectiveness of different dosing schemes on respiratory tract infections, such as once a week, which may be easier to implement.“