Association Between Folate Metabolites and the Development of Food Allergy in Children

Background Studies on the association between folate/folic acid exposure and the development of allergic disease have yielded inconsistent results, which may be due, in part, to lack of data distinguishing folate from folic acid exposure. Objective To examine the association between total folate, 5-methyltetrahydrofolate (5-MTHF), and unmetabolized folic acid (UMFA) concentrations at birth and in early childhood and the development of food sensitization (FS) and food allergy (FA). Methods A nested case control study was performed in the Boston Birth Cohort (BBC). Total folate, 5-MTHF, and UMFA were measured at birth and in early childhood. Based on food-specific IgE (sIgE) levels, diet, and clinical history, children were classified as FS (sIgE ≥0.35 kU/L), FA, or non-FS/FA (controls). Folate concentrations were divided into quartiles, and multiple logistic regression was used to estimate ORs and 95%CIs. Results Of a total of 1,394 children, 507 FS and 78 FA children were identified. While mean total folate concentrations at birth were lower among those who developed FA (30.2 vs. 35.3 nmol/L; p=0.02), mean concentrations of the synthetic folic acid derivative, UMFA, were higher (1.7 vs. 1.3 nmol/L, p=0.001). Higher quartiles of UMFA at birth were associated more strongly with FA (OR 8.50; 95%CI 1.7-42.8; test for trend p=0.001). Neither early childhood concentrations of 5-MTHF nor UMFA were associated with the development of FS or FA. Conclusion Among children in the BBC, higher concentrations of UMFA at birth were associated with the development of FA, which may be due to increased exposure to synthetic folic acid in utero or underlying genetic differences in synthetic folic acid metabolism.