A recent meta-analysis published in the British Medical Journal found that people who received weekly or daily, but not monthly, vitamin D supplements reduced their risk of acute respiratory infections (ARTIs).
ARTI is an infection that may interfere with breathing. It may only affect the upper respiratory system, which begins at the sinuses and ends at the vocal chords. It can also only affect the lower respiratory system, which begins at the vocal chords and ends at the lungs.
ARTIs are responsible for 10% of doctor visits in the United States and an estimated 2.65 million deaths worldwide in 2013.
Researchers have hypothesized that vitamin D plays a role in ARTIs due to vitamin D’s ability to increase proteins that kill bacteria, known as anti-microbial peptides. This has prompted multiple randomized controlled trials (RCTs), the gold standard of research.
Five aggregate data meta-analyses have reviewed the findings of RCTs. However, two reported statistically significant protective effects of vitamin D, while the other three reported no statistically significant effects.
Two of the three meta-analyses with insignificant findings reported significant heterogeneity. Heterogeneity describes excessive variation between study design, which can skew results. This has led researchers to conduct yet another meta-analysis, but this time, using individual participant data as opposed to aggregate data.
Individual participant data refers to the data recorded for each participant in a study. In this scenario, the individual participant data consists of the pre-treatment and post-treatment vitamin D levels, incidence of ARTIs and important baseline clinical characteristics such as age and sex. Whereas, aggregate data refers to the averaging information across all individuals in a study such as the average reduction in incidence of ARTIs for those given vitamin D.
Individual participant data meta-analyses offer many potential advantages over aggregate data meta-analyses. Individual participant data reduces the heterogeneity between studies by allowing researchers to study subgroups of participants. Baseline characteristics can be adjusted for consistently throughout all studies. Furthermore, the researchers can use the same statistical analyses across all studies.
The meta-analysis included 25 RCTs, totaling 11,321 participants. Here is what the researchers found:
- The odds of experiencing an ARI was 12% lower in those who received vitamin D compared to those who did not (p = 0.003).
- In the subgroup analysis, vitamin D supplementation on a daily or weekly basis provided protection from ARTIs (p < 0.001), but monthly vitamin D supplementation did not protect against ARTIs (p = 0.67).
- The protective effects of weekly and daily vitamin D supplementation were stronger in those with baseline vitamin D levels below 10 ng/ml compared to those with baseline vitamin D levels above 10 ng/ml.
The researchers concluded,
“In this individual participant data meta-analysis of randomized controlled trials, vitamin D supplementation reduced the risk of experiencing at least one acute respiratory tract infection. Subgroup analysis revealed that daily or weekly vitamin D supplementation without additional bolus doses protected against acute respiratory tract infections, whereas regimens containing large bolus doses did not.”
The study did not only highlight the importance of vitamin D for the prevention of ARTIs but also the importance of daily and weekly supplementation opposed to bolus dosing.
The researchers discussed why bolus dosing may be ineffective in the prevention of ARTIs. They stated that it likely relates to the wide fluctuations in vitamin D levels seen with the use of bolus doses but not with daily or weekly supplementation. The high vitamin D levels from bolus doses may chronically dysregulate the activity of proteins responsible for the synthesis and breakdown of active vitamin D. This results in reduced availability of active vitamin D for cells. Therefore, this effect may weaken the ability of vitamin D to strengthen the immune system in response to ARTIs.
While critically assessing the results of a study, keep in mind whether the researchers used daily, weekly or bolus dosing. Insignificant results are more likely to occur from bolus dosing. Also, as the researchers pointed out, the greatest benefits were observed in patients with deficient baseline levels. This is another important factor to consider while evaluating a study’s findings.
Tovey, A. & Cannell, JJ. Research finds daily or weekly vitamin D supplements reduce risk of acute respiratory tract infections. The Vitamin D Council Blog & Newsletter, April 25, 2017.
Martineau, A. Jolliffe, D. Hooper, R. et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. British Medical Journal, 2017