Study Title:

Vitamin D3 supplementation in patients with frequent respiratory tract infections

Study Abstract

BACKGROUND:

Low serum levels of 25-hydroxyvitamin D(3) are associated with an increased risk of respiratory tract infections (RTIs). Clinical trials with vitamin D(3) against various infections have been carried out but data are so far not conclusive. Thus, there is a need for additional randomised controlled trials of effects of vitamin D(3) on infections.

OBJECTIVE:

To investigate if supplementation with vitamin D(3) could reduce infectious symptoms and antibiotic consumption among patients with antibody deficiency or frequent RTIs.

DESIGN:

A double-blind randomised controlled trial.

SETTING:

Karolinska University Hospital, Huddinge.

PARTICIPANTS:

140 patients with antibody deficiency (selective IgA subclass deficiency, IgG subclass deficiency, common variable immune disorder) and patients with increased susceptibility to RTIs (>4 bacterial RTIs/year) but without immunological diagnosis.

INTERVENTION:

Vitamin D(3) (4000 IU) or placebo was given daily for 1 year. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was an infectious score based on five parameters: symptoms from respiratory tract, ears and sinuses, malaise and antibiotic consumption. Secondary endpoints were serum levels of 25-hydroxyvitamin D(3), microbiological findings and levels of antimicrobial peptides (LL-37, HNP1-3) in nasal fluid.

RESULTS:

The overall infectious score was significantly reduced for patients allocated to the vitamin D group (202 points) compared with the placebo group (249 points; adjusted relative score 0.771, 95% CI 0.604 to 0.985, p=0.04).

LIMITATIONS:

A single study centre, small sample size and a selected group of patients. The sample size calculation was performed using p=0.02 as the significance level whereas the primary and secondary endpoints were analysed using the conventional p=0.05 as the significance level.

CONCLUSIONS:

Supplementation with vitamin D(3) may reduce disease burden in patients with frequent RTIs.

From press release:

Treating infection-prone patients over a 12-month period with high doses of vitamin D reduces their risk of developing respiratory tract infection -- and consequently their antibiotic requirement. This according to a new study by researchers at Karolinska Institutet and Karolinska University Hospital published in the online scientific journal 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," says Peter Bergman, researcher at Karolinska Institutet's Department of Laboratory Medicine and doctor at Karolinska University Hospital's Immunodeficiency Unit. "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."

Vitamin D is synthesised in the skin through exposure to sunlight and obtained through certain foods. In Sweden there is a seasonal variation in vitamin D in the blood, the trough coming during the darker half of the year. Studies have shown that low levels of vitamin D can increase the risk of infection, and it has long been known that the vitamin can also activate the immune defence.

For the present study now published in BMJ Open the researchers examined whether treatment with vitamin D can prevent and relieve respiratory tract infections in particularly infection-prone patients. All the 140 participants from the Immunodeficiency Unit had symptoms of disease in their respiratory tracts for at least 42 days prior to the study. The patients were randomly divided into two groups, one of which received vitamin D in relatively high doses, the other a placebo. They were also asked to keep a diary recording their state of health every day during the year-long study period.

The results show that symptoms of respiratory tract infection declined by almost a quarter and the use of antibiotics by almost half. Vitamin D treatment was also tolerated well by all patients and gave no serious side-effects.

The effect of vitamin D on respiratory tract infection is controversial, and a major study from New Zeeland published recently in the scientific journal JAMA found that it did not reduce the incidence or severity of viral respiratory tract infections. However, the present study differs from the JAMA study in several important respects, which could explain their different results. The JAMA study examined a group of healthy people with initially normal levels of vitamin D in the blood, and used bolus dose administration (i.e. large doses on fewer occasions), which is thought to be less effective that daily doses.

"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," says Dr Anna-Carin Norlin, doctoral student and co-lead author of the study along with Dr Bergman. "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."

Study Information

Bergman P, Norlin AC, Hansen S, Rekha RS, Agerberth B, Björkhem-Bergman L, Ekström L, Lindh JD, Andersson J.
Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomised and double-blind intervention study
BMJ Open.
2012 December
Department of Laboratory Medicine, Clinical Microbiology, Karolinska Institutet, Stockholm, Sweden.

Full Study

http://bmjopen.bmj.com/content/2/6/e001663.long