Monthly high-dose vitamin D supplementation failed to reduce the number of upper respiratory tract infections in healthy adults of European extraction who already had adequate serum 25-hydroxyvitamin D levels, according to a report in the Oct. 3 issue of JAMA.
The treatment also failed to reduce the severity or duration of URTIs, or the number of days patients missed work, said Dr. David R. Murdoch of the department of pathology, University of Otago, Christchurch, New Zealand, and his associates (JAMA 2012;308:1333-9).
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Epidemiologic and observational studies have reported an association between low vitamin D levels and a high rate of a variety of respiratory tract infections.
However, it is still possible that monthly high-dose vitamin-D supplementation may prevent or ameliorate URTIs in other populations, the authors noted, particularly those with a high prevalence of vitamin D deficiency. And different regimens with smaller, steadier dosing might prove effective, they added.
Epidemiologic and observational studies have reported an association between low vitamin D levels and a high rate of a variety of respiratory tract infections. But the few clinical trials to examine the issue have been hampered by small study populations, short durations, and low doses of vitamin D.
This large, randomized, double-blind, placebo-controlled clinical trial was designed to overcome those drawbacks, the investigators said.
Dr. Murdoch and his colleagues assessed 322 healthy adults with a mean age of 47 years, of whom 75% were women. The patients were randomly assigned to receive either oral vitamin D3 or matching placebo tablets every month for 18 months, and were followed closely for signs and symptoms of URTIs. Nasopharyngeal swabs were collected and analyzed for the presence of 20 viruses whenever a patient developed a runny nose, nasal stuffiness, sore throat, or cough that was not attributed to allergy.
The active-treatment group received a loading dose of 200,000 IU of vitamin D3 for months 1 and 2, then a maintenance dose of 100,000 IU for the remainder of the study. A total of 91% of the patients completed the study, and there were only three missed appointments throughout.
Serum levels of 25-hydroxyvitamin D rose dramatically in the patients who received active treatment but not in those who received placebo.
The main outcome measure of this study was the number of URTIs that developed during follow-up.
There were 593 URTIs in the vitamin D group, with a mean of 3.7 infections per person, and 611 URTIs in the placebo group, with a mean of 3.8 infections per person. This was not a statistically significant difference, the investigators said.
The results didn’t change when the data were categorized according to patients’ scores on the Wisconsin Upper Respiratory Symptom Survey 24, which measures the severity and functional impact of URTIs. Nor were outcomes altered by an analysis based on patients’ serum vitamin D levels at baseline.
The lack of a treatment effect also persisted across one summer and two winter seasons, even though the number of URTIs nearly doubled during the winter. The mean number of URTIs was 1.3 for both study groups in summer, and 2.5 and 2.3 in winter for the placebo and treatment groups, respectively.
There also was no difference in URTI severity between patients who received vitamin D and those who received placebo. The number of URTIs associated with positive nasopharyngeal swabs also was not significantly different between the two groups.
Another measure of URTI severity – the percentage of patients who missed at least 1 day of work when sick with a cold – also was exactly the same, at 41% in both groups.
There were no cases of asymptomatic hypercalcemia and no other adverse events attributed to vitamin D supplementation. The number of serious adverse events was not significantly different between the active-treatment and placebo groups.
"Further research is required to clarify whether there is benefit from supplementation in other populations and with other dosing regimens," Dr. Murdoch and his associates concluded.
The study was supported by the Health Research Council of New Zealand. The researchers reported no conflicts of interest.