Fructose-Containing Dietary Exposures and Pediatric Atopic Disease: A Review of Epidemiologic Evidence

Background: Mechanistic evidence increasingly implicates fructose exposures as contributors to the development and exacerbation of asthma and other atopic diseases. Proposed mechanisms include gut dysbiosis, impaired epithelial barrier integrity in the gut and airways, metabolic endotoxemia, and amplification of type 2 immune responses. However, epidemiologic findings linking fructose intake with asthma and atopic disorders remain heterogeneous. Objective: To conduct a review of epidemiologic studies evaluating associations between dietary fructose-containing exposures and atopic outcomes in pediatric populations. Methods: A systematic search of PubMed and Embase identified cohort, case-control, cross-sectional, and randomized feeding studies assessing fructose exposure in relation to asthma and atopic outcomes in pediatric populations. Eligibility screening, data extraction, and risk-of-bias assessment were conducted by one reviewer and confirmed by the other. Results: Seventeen epidemiologic studies met criteria. Multiple cohorts (e.g., BRISA, PIAMA) reported modest to moderate associations between higher sugar-sweetened beverage (SSB) intake and pediatric asthma or "asthma traits." Cross-sectional analyses from NHANES and the National Children's Study showed stronger associations, with greater fructose exposures linked to two- to five-fold higher odds of asthma. High fructose beverage consumption demonstrated the most consistent positive associations. Large ISAAC-based studies reported largely null findings, reflecting broad dietary exposure categories and limited specificity for fructose-rich beverages. Evidence for rhinitis, eczema, and sensitization was directionally consistent. Conclusions: Despite heterogeneity, the convergence of mechanistic plausibility with epidemiologic signals supports a potential contributory role of high fructose exposure in pediatric atopic disease. More rigorous longitudinal studies with biomarker-based exposure assessment are needed to refine causal inference.