High-Dose Vitamin D Supplementation Does Not Prevent Allergic Sensitization of Infants

Abstract

Objective To investigate the effect of vitamin D supplementation dose on allergic sensitization and allergic diseases in infants, and to evaluate whether vitamin D status in pregnancy and at birth are associated with infant allergy outcomes. Study design Altogether, 975 infants participated in a randomized, controlled trial of daily vitamin D supplementation of 10 mg (400 IU) or 30 mg (1200 IU) from the age of 2 weeks. At 12 months of age, food and aeroallergen IgE antibodies were measured, and the occurrence of allergic diseases and wheezing were evaluated. Results We found no differences between the vitamin D supplementation groups in food (OR, 0.98; 95% CI, 0.66-1.46) or aeroallergen sensitization at 12 months (OR, 0.76; 95% CI,0.34-1.71). Allergic diseases or wheezing did not differ between groups, except for milk allergy which occurred more often in infants administered 30 mg vitamin D compared with the 10 mg dose (OR, 2.23; 95% CI, 1.00-4.96). Infants with high cord blood 25-hydroxyvitamin D (³100 nmol/L) had a higher risk of food allergen sensitization compared with those with lower 25(OH)D concentration (75-99.9 nmol/L; OR, 2.00; 95% CI, 1.19-3.39). Conclusions High-dose vitamin D supplementation did not prevent allergic sensitization, allergic diseases, or wheezing during the first year of life. In contrast, we observed an increased risk of milk allergy in infants randomized to higher vitamin D supplementation, and an increased risk of allergic sensitization in infants with high cord blood vitamin D status, indicating a possible adverse effect of high concentrations of vitamin D.

In “High-Risk” Infants with Sufficient Vitamin D Status at Birth, Infant Vitamin D Supplementation Had No Effect on Allergy Outcomes: A Randomized Controlled Trial

“…Our finding of no statistically significant effect between vitamin D supplementation and medically diagnosed allergic disease over the first 2.5 years of age is consistent with other intervention trials which have been performed investigating the effect of maternal vitamin D supplementation during pregnancy and offspring allergic disease outcomes [15][16][17][18]. Even more importantly, our findings are also consistent with those in the recent infant RCT by Rosendahl et al [25], where they also found no statistically significant differences in allergic disease outcomes at 1 year between two groups of infants supplemented daily with either 10 (400 IU) or 30 µg (1200 IU) vitamin D from the age of 2 weeks. While our trial investigated the effect of the Australian recommended dose (400 IU) [26] for vitamin D supplementation in infancy versus placebo on allergy outcomes in early childhood, the study by Rosendahl et al was based on a secondary analysis comparing two different supplemental doses of vitamin D on allergy outcomes in the first year of life.…”

“…In our RCT and in that of Rosendahl et al [25], both involving infants born at term gestation, we did not find any significant benefit of infant vitamin D supplementation on reducing the incidence of medically diagnosed wheeze at 1 year of age. This contrasts with the results at 1 year of age from a recently published paper by Hibbs et al [29], where preterm black infants (mean gestational age of 33 weeks) were randomized to vitamin D supplementation of 400 IU/day until 6 months of age, and were found to have reduced recurrent wheezing (relative risk 0.66; 95% CI 0.47 to 0.94) compared with a placebo.…”

“…While our trial investigated the effect of the Australian recommended dose (400 IU) [ 26 ] for vitamin D supplementation in infancy versus placebo on allergy outcomes in early childhood, the study by Rosendahl et al was based on a secondary analysis comparing two different supplemental doses of vitamin D on allergy outcomes in the first year of life. Rosendahl et al [ 25 ] found no statistically significant differences between the vitamin D supplementation groups for any food allergy (OR 1.35; 95% CI 0.75–2.46), atopic eczema (OR 0.72; 95% CI 0.49–1.01) or wheeze (OR 0.94; 95% CI 0.58–1.50) outcomes at 1 year of age. Furthermore, and of concern, Rosendahl et al [ 25 ] found a higher incidence of cow’s milk allergy in infants administered 30 μg (1200 IU) vitamin D compared with the 10 μg (400 IU) dose (OR 2.23; 95% CI 1.00–4.96), indicating a possible adverse effect of high doses of infant vitamin D supplementation.…”

“…Rosendahl et al [ 25 ] found no statistically significant differences between the vitamin D supplementation groups for any food allergy (OR 1.35; 95% CI 0.75–2.46), atopic eczema (OR 0.72; 95% CI 0.49–1.01) or wheeze (OR 0.94; 95% CI 0.58–1.50) outcomes at 1 year of age. Furthermore, and of concern, Rosendahl et al [ 25 ] found a higher incidence of cow’s milk allergy in infants administered 30 μg (1200 IU) vitamin D compared with the 10 μg (400 IU) dose (OR 2.23; 95% CI 1.00–4.96), indicating a possible adverse effect of high doses of infant vitamin D supplementation. This has also been identified in the Japanese RCT by Norizoe et al [ 21 ], where maternal vitamin D supplementation (800 IU/day) during early lactation was found to increase the risk of food allergy at 2 years of age.…”

Insufficient Sun Exposure Has Become a Real Public Health Problem

“…Some trials have also reported reduced development of wheeze or asthma, but not respiratory tract infections, in offspring of pregnant women supplemented with vitamin D; this effect was independent of starting 25(OH)D levels. The outcomes of trials of vitamin D supplementation to prevent allergic sensitization in infants are, however, controversial, with some trials reporting no significant benefits [ 47 ].…”