Urashima and colleagues gave 334 Japanese school children vitamin D₃ 1,200 IU daily or placebo (Urashima et al. 2010). There was a 50 % reduction in children who were diagnosed with influenza A (primary outcome). However, if one combines the number of cases of influenza A and influenza B, there was no reduction in total influenza infections between the vitamin D treated and the control group. Laaksi and colleagues supplemented 164 young Finnish men with only 400 IU/day of vitamin D₃. Absence from duty due to respiratory tract infection and number of days absent was lower in the treated group. The proportion of subjects without any days absent was slightly higher in the vitamin D supplementation group (Laaksi et al. 2010). Martineau and colleagues used high-dose vitamin D₃ in the treatment of pulmonary TB (Martineau et al. 2011). The number of people who had upper respiratory tract infection symptoms was recorded. One of seventy-one patients receiving at least one dose of vitamin D₃ as compared to 6 of 70 receiving at least one dose of placebo reported symptoms. This secondary outcome was of borderline statistical significance (p = 0.06). In a recent RCT of 247 Mongolian children with vitamin D deficiency in winter, vitamin D supplementation halved the risk of upper respiratory infections (Camargo et al. 2012).

In the randomized controlled trial (RCT) where Japanese children were given 1,200 IU daily or placebo, children with a previous diagnosis of asthma, there was also a significant reduction in number of asthma attacks (Urashima et al. 2010); only 2 asthmatic children taking vitamin D and 12 taking placebo had “asthma attacks.” Recently, Majak and colleagues reported in an RCT on the role of vitamin D supplementation (vitamin D₃ 500 IU daily) vs placebo for 6 months in Polish children with newly diagnosed asthma (Majak et al. 2011); the investigators observed a significant reduction in asthma exacerbations due to acute upper respiratory tract infections (p = 0.029).

Vitamin D deficiency has been linked to an increased incidence of atopy including allergic rhinitis (Ehlayel et al. 2011). However, Hyppönen and colleagues have reported that regular vitamin D supplementation (≥2,000 IU/day) of Finnish infants increases the risk of developing allergic rhinitis and asthma at the age of 31 (Hyppönen et al. 2004). In a separate study in the UK, they also linked deficient (<25 nmol/L) and excessively high (>135 nmol/L) serum 25(OH)D levels with elevated serum IgE levels (Hyppönen et al. 2009). The relationships of vitamin D with allergy appear complex, but a possible “U” shape relationship exists with both low and high 25(OH)D levels predisposing to atopy (Bartley 2010).

A number of RCTs are currently underway worldwide investigating the role of vitamin D supplementation in upper respiratory infection and allergic disease (Bartley 2010). While preliminary data appears promising, optimal 25(OH)D levels and vitamin D treatment regimens for the prevention and/or management of respiratory infections remain to be determined.