Walnut Threshold Dose Distribution and Safe Dose in Allergic Patients (Nut CRACKER Study)

Background: Walnut is a significant global food allergen, but data relating to population reaction thresholds are limited. This hampers the ability of industry and regulators to undertake allergen risk assessment, increases use of allergen labeling, and impairs patients’ quality of life. Objective: To describe reaction eliciting doses (EDs) in a large walnut-allergic population. Methods: A retrospective cohort study including all reactive walnut oral food challenges (OFCs) was performed between July 2014 and May 2023 at Shamir Medical Center. OFCs were performed for either diagnostic reasons or at the beginning of oral immunotherapy. Objective signs were used as stopping criteria. Confirmatory safe-dose OFCs with dose intervals of 90 minutes or more were also analyzed. Results: Overall, 415 walnut OFCs were analyzed, with no left- or right-censored data. Corresponding estimated ED01 and ED05 (amount of protein eliciting an objective reaction in 1% and 5% of the walnut-allergic population, respectively) were 0.8 mg (range, 0.3-24) and 3.8 mg (range, 1.1-96.4) for discrete and 1.2 mg (range, 0.4-29.4) and 5.9 mg (range, 1.7-140.5) for cumulative dosing. Doses less than or equal to 1 mg elicited subjective reactions (in 12.5% of patients), but no objective reactions during the 295 safe-dose OFCs performed. Factors associated with a lower reaction threshold to walnut included a younger age, oral immunotherapy-OFC protocol, and coallergy to pecan (P < .001 for all). Conclusions: This is the largest published data set to inform EDs to walnut, with greater certainty of ED with the inclusion of safe-dose OFCs. These data address an evidence gap in the global Codex efforts to improve evidence-based allergen risk assessment for walnut.