COMMENTARY

High-Dose Vitamin D and Upper Respiratory Infections in Children

William T. Basco, Jr., MD, MS

Disclosures

October 16, 2017

High-Dose Vitamin D and Upper Respiratory Tract Infections

Some observational studies have suggested that low levels of 25–hydroxyvitamin D (vitamin D) are associated with an increased risk for respiratory tract infections, but prospective, randomized data with adequate power to test whether supplementation with vitamin D can prevent respiratory tract infections are lacking. There are biological reasons to suspect that vitamin D might be protective in that it increases antimicrobial peptides in the respiratory epithelium.

A recent trial by Aglipay and colleagues[1] was conducted in Toronto to determine whether daily oral supplementation with vitamin D at 2000 IU/day or a standard dose of 400 IU/day was effective in reducing viral upper respiratory tract infections (URIs). The children were randomly assigned in a 1:1 allocation during respiratory seasons from 2011 to 2015. The children were 1-5 years old and were enrolled at eight primary care clinics that were part of a local research network. Children were only enrolled in the trial for one respiratory season, generally running from September through May. The vitamin D was administered as a single drop orally each day.

At enrollment, demographic and clinical information were collected on the patient and parent, including measures of physical activity, time outdoors, skin pigmentation, and estimates of sun exposure. Parents maintained daily symptom checklists and were instructed on how to collect a nasal swab specimen every time their child experienced aURI. Couriers picked up the samples from the study households. Vitamin D levels were measured at enrollment and at the end of the respiratory season.

The outcome of interest was the number of laboratory-confirmed viral URIs. The study enrolled 703 eligible children, with approximately 350 in each group. Only four children were lost to follow-up. Treatment was discontinued in 7.9% of the children, but all were able to complete the follow-up study. Overall, the children took the study agent for a mean of 6.2 months. The mean age of recruitment was 2.7 years, and approximately 42% of the children were girls.

In the high-dose group, the mean baseline serum vitamin D level was 35.9 ng/mL compared with 36.9 ng/mL among children in the standard-dose group. No laboratory-confirmed URIs occurred in 46% of the children during the study season. The mean number of URIs per child was 1.03 in the standard-dose group and 1.05 in the high-dose group, resulting in a between-group difference of 0.02 (95% confidence interval [CI], –0.17 to 0.21). The rate ratio for infection among the high-dose children compared with the low-dose children was 0.97, with a 95% CI of 0.80-1.16, meaning that the difference was not statistically significant. Similarly, the number of parental-reported URIs was not different between the two groups (1.91, standard dose; 1.97, high dose).

The vitamin D level was higher at the end of the study in the treatment group by about 12 ng/mL, but this difference was not statistically significant.

Looking at specific virus infections, influenza infections were reduced in the high-dose group by about 50%. However, influenza infections represented less than 10% of the viral infections in either group.

The investigators concluded that supplementation with high-dose vitamin D did not reduce all-cause viral respiratory infections in young children.

Viewpoint

Last year, I reviewed two international trials that evaluated the potential preventive effects of high-dose vitamin D supplementation in pregnant women, attempting to lower the risk for asthma or atopic illness in the offspring. Those trials were disappointing, to say the least.

I suspect that many providers would be just as disappointed with the findings of this trial, given how ubiquitous viral URIs are among children. The investigators note that the finding of a lower risk for influenza has to be interpreted with caution, given the relatively few influenza cases in the study. In addition, they admit that it was a secondary outcome, suggesting that the question of high-dose vitamin D supplementation and influenza prevention would be best tested in a very active flu season.

In the meantime, they conclude that we should not be routinely supplementing children with high-dose vitamin D if the goal is only to prevent URIs. It certainly would be appropriate to wait to see whether the potential effects on influenza reduction can be replicated in other trials before recommending it strongly as an influenza prevention method.

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