Vitamin D in early life: good or bad for food allergies?

There is controversial evidence for an influence of 25Hydroxyvitamin D3 (25-OHD) levels and nutritional vitamin D supplementation, respectively, on the development of allergic diseases during childhood. We have read with great interest the paper by Weisse et al. who analyzed data of a subgroup of the prospective German LINA cohort study, including 378 mother–child pairs (1). The authors describe a positive association of 25-OH-D3 levels, in both maternal and cord blood, with parent-reported doctor diagnosis of food allergy in the second year of life, but not in the first year. In addition, maternal 25-OH-D3 levels were positively associated with the child’s serum level of IgE specific for food allergens (but not inhalant allergens) at the age of two. We believe that unfortunately, this study suffers from some major limitations that do not allow the drawing of the published conclusions. Most importantly, food allergy was diagnosed by parental report of a doctor diagnosis and not by an oral food challenge test. Although the authors have mentioned this limitation, we would like to point out that the prevalence of parentor self-reported food allergy differs markedly when compared with objective measures. This has been shown in a meta analysis by Rona et al. and a systematic review by Zuidmeer et al. (2, 3). Therefore, a number of expert panels from various organizations have published consensus documents on the appropriate diagnosis of food allergies highlighting the importance of oral food challenges for diagnosing food allergy (4, 5). Thus, the authors used an outcome definition for food allergy that has not been validated. It does not allow the conclusion to be drawn that high vitamin D levels increase the risk of food allergy. Furthermore, the authors had not prioritized their primary outcome and secondary outcomes. Multiple testing of 30 outcomes increases the finding of statistically significant associations by chance. This is acceptable if the results are clearly interpreted as explorative and are used as the basis for planning future studies. It is not acceptable for advice in favor of or against vitamin D supplements. Also, vitamin D deficiency is strongly associated with low birth weight (6). By not regarding birth weight as an important clinical parameter in this setting, the authors have missed the chance to clarify a potential association of birth weight and atopic disease. Finally, the authors falsely concluded that cord blood vitamin D levels are correlated with regulatory T cells. This does not correspond to the scatter plot (Fig. 4) or the correlation coefficient of r = 0.17. It is a misinterpretation of their results based on only interpreting the P-value but ignoring the low correlation coefficient, which is close to zero (equal to no correlation) and far away from 1 (equal to best correlation). Therefore, the last sentence of the Results section in the abstract as well as the last two sentences of the Results in the main text could mislead the readers. Thus, the suggestion that Treg numbers in cord blood might mediate the effect of vitamin D levels on atopic outcomes remains hypothetical.