In 2017, a meta-analysis of data from 25 randomized controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infections (ARIs) found a protective effect of this intervention. The same group of researchers led by Dr. David A. Jolliffe, Barts and The London School of Medicine and Dentistry, Queen Mary University, London, has now taken another look at this issue and examined the relationship in more detail in an updated meta-analysis.
Compared with the 2017 work, this updated meta-analysis [1] includes data from an additional 18 studies completed since December 2015. In total, data from 48 488 participants from 43 studies were included. As a result, researchers were able to report a small but significant protective effect of vitamin D supplementation on the risk of one or more ARIs compared with placebo (OR 0.92; 95% CI 0.86-0.99): A total of 61.3% of participants taking vitamin D experienced one or more acute respiratory infections, compared with 62.3% in the placebo group (Table 1).
Unlike four years ago, no improved protection from baseline was observed in participants with the lowest 25(OH)D concentrations. However, there was evidence that the efficacy of vitamin D supplementation-depending on dosing regimen, study duration, and age of participants at inclusion-was associated with protective effects associated with daily administration of doses of 400-1000 IU vitamin D (taken for 12 months or less and aged 1.00-15.99 years at intake) varies. An exploratory analysis limited to data from five trials that met these design criteria showed a greater protective effect of vitamin D supplementation versus placebo (OR 0.56; 95% CI 0.38-0.82) compared with the main analysis, without significant heterogeneity between trials.
Overall, the magnitude of the protective effect of vitamin D supplementation on ARI risk appears low in the current analysis (OR 0.92 [95%-KI 0,86–0,99]), similar to those individual participant-level data (adjusted OR 0.88 [95%-KI 0,81–0,96]) in the previous meta-analysis. Consistent with the previous study, the estimate for this effect was lower in participants with baseline 25(OH)D concentrations of less than 25 nmol/l than in those with concentrations greater than 25 nmol/l. However, in contrast to the previous results, no significant protective effect of vitamin D was observed in participants with the lowest 25(OH)D concentrations at baseline. This difference reflects the inclusion of null data from four new RCTs in which vitamin D was administered at daily dose equivalents of 2000 IU/day or more at weekly or monthly intervals for 2-5 years.
Lower doses protect better
The null results of these studies contrast with the protective effects reported in previous studies in which smaller daily doses of vitamin D were administered for shorter periods of time. This may suggest that frequency, dose, and duration of vitamin D supplementation may be the key factor in its protective effect against ARI, the authors write. Consistent with this hypothesis, in their meta-analysis, significant protective effects of vitamin D supplementation versus placebo were observed in studies in which vitamin D was administered daily in doses of 400-1000 IU/day and for 12 months or less. The stronger protective effects of lower vs. higher doses of vitamin D might reflect the deleterious effects of higher-dose vitamin D on its own metabolism, for example. Head-to-head studies in individuals randomized to different regimens of vitamin D supplementation are needed to examine this issue in more detail, experts said.
Qualifyingly, Jolliffe et al. to consider that due to the evolving COVID-19 pandemic, a rapid update was needed and therefore the authors meta-analyzed aggregated study-level data rather than data on an individual participant basis. This allowed it to proceed quickly without the delays that would have resulted from having to enter into multiple data sharing agreements. Thus, however, information was lacking to examine race or ethnicity and obesity as potential effect modifiers. Also, no other factors could be considered that might influence the protective effect of vitamin D supplementation in preventing ARIs, such as taking the vitamin with or without food.
Literature:
- Jolliffe DA, et al: Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials. Lancet Diabetes Endocrinol 2021; 9(5): 276-292; doi: 10.1016/S2213-8587(21)00051-6.
InFo PNEUMOLOGY & ALLERGOLOGY 2021; 3(3): 32-33.
