Background Low serum levels of 25-hydroxyvitamin D₃ are associated with an increased risk of respiratory tract infections (RTIs). Clinical trials with vitamin D₃ 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 D₃ on infections.

Objective To investigate if supplementation with vitamin D₃ 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 D₃ (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 D₃, 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 D₃ may reduce disease burden in patients with frequent RTIs.