Vitamin D May Reduce Respiratory Infection Symptoms

Laurie Barclay, MD

December 19, 2012

In patients with increased frequency of respiratory tract infections, supplementation with 4000 IU vitamin D3 for 1 year reduced symptoms and antibiotic use, according to findings of a randomized controlled trial published online December 13 in BMJ Open.

"Our research can have important implications for patients with recurrent infections or a compromised immune defence, such as a lack of antibodies, and can also help to prevent the emerging resistance to antibiotics that come from overuse," lead author Peter Bergman, MD, PhD, from Karolinska Institutet's Department of Laboratory Medicine and Karolinska University Hospital's Immunodeficiency Unit in Stockholm, Sweden, said in a news release. "On the other hand, there doesn't seem to be anything to support the idea that vitamin D would help otherwise healthy people with normal, temporary respiratory tract infections."

The impetus for this study included recent evidence regarding significant extraskeletal effects of vitamin D3, including anti-inflammatory activity and induction of antimicrobial peptides strengthening mucosal immunity. Observational studies have also shown an increased risk for respiratory tract infections in patients with low 25-hydroxyvitamin D3 levels. To date, however, there have been few randomized controlled trials of the protective effect of vitamin D3 against respiratory tract infections, and the findings have been inconclusive.

The goal of this double-blind, randomized controlled trial was to determine whether vitamin D3 supplementation in patients with antibody deficiency or frequent respiratory tract infections would be associated with lower rates of infectious symptoms and antibiotic use.

At Karolinska University Hospital, 140 participants were assigned to receive 4000 IU vitamin D3 or placebo daily for 1 year. Participants included patients with antibody deficiency (selective immunoglobulin A deficiency, immunoglobulin G subclass deficiency, common variable immunodeficiency) or with more than 4 bacterial respiratory tract infections per year but without immunological diagnosis. All participants had respiratory symptoms for at least 42 days before randomization.

The main study outcome was an infectious score calculated from 5 clinical characteristics that the patients recorded in a daily diary: respiratory symptoms, ear symptoms, sinus symptoms, malaise, and antibiotic use. Secondary outcomes included 25-hydroxyvitamin D3 serum levels, microbiological characteristics, and nasal fluid levels of antimicrobial peptides (cathelicidin, human neutrophil peptides 1 - 3).

Compared with the placebo group, the vitamin D group had a significantly lower overall infectious score (202 points vs 249 points; adjusted relative score, 0.771; 95% confidence interval, 0.604 - 0.985; P = .04). In the vitamin D group, symptoms of respiratory tract infection decreased by nearly 25%. The odds of taking antibiotics during the study period decreased by 63.5% in the vitamin D group, and the absolute number of days on antibiotics decreased by 50% (from 33 days in the placebo group to 16 days in the vitamin D group).

All patients tolerated vitamin D treatment well, with no serious adverse effects.

"The main conclusion is that vitamin D3 supplementation reduces symptoms and antibiotic consumption among patients with an increased frequency of respiratory tract infections," the study authors write. "Thus, vitamin D3 supplementation may be an alternative strategy to reduce antibiotic use among patients with recurrent respiratory tract infections."

Limitations of this study include its location at a single center, small sample size, reliance on patient-reported symptoms, and use of a selected patient group. Although the sample size calculation used P = .02 as the significance level, analysis of the primary and secondary endpoints used a conventional significance level of P = .05.

A recent study from New Zealand showed that vitamin D was not associated with lower incidence or severity of viral respiratory tract infections. Differences from the present study include use of healthy participants with initially normal vitamin D blood levels and use of bolus dose administration.

"However, the most important difference is probably due to the fact that our participants had much lower initial levels of vitamin D than those in the New Zealand study," coauthor Anna-Carin Norlin, MD, from the Department of Laboratory Medicine, Clinical Immunology, Karolinska Institutet, and Karolinska University Hospital, Clinical Immunology, Immunodeficiency Unit, said in the news release. "There is evidence from previous studies that vitamin D supplements are only effective in patients who fall well below the recommended level, which also suggests that it would be wise to check the vitamin D levels of patients with recurrent infections."

Karolinska Institutet, the Stockholm County Council, and the Swedish Foundation for Strategic Research supported this study, along with grants from the Swedish Heart and Lung foundation, Magnus Bergwall and Åke Wiberg foundations. Merck KGaA provided vitamin D3 and placebo oil. The authors have disclosed no relevant financial relationships.

BMJ Open. Published online December 13, 2012. Full text