Cracking walnut reaction threshold (Nut CRACKER Study)
Published online May 30, 2025
Walnuts are a major global food allergen, yet detailed information about the amount required to trigger an allergic reaction in walnut allergic patients is missing. Without these data, food manufacturers often label products with overly cautious warnings, such as “may contain walnuts/tree nuts,” even if the actual risk of contamination is minimal. This creates unnecessary dietary restrictions for walnut allergic patients and diminishes their quality of life.
In a study published in The Journal of Allergy and Clinical Immunology: In Practice, Nachshon et al. from Israel’s Shamir Medical Center and collaborating researchers from the Netherlands Organization for Applied Scientific Research, TNO, analyzed data from 626 walnut oral food challenges (OFCs) performed between 2014 and 2023. Data were derived from standard protocol diagnostic OFCs and from slow protocol OFCs performed at the beginning of oral immunotherapy, OIT. Of those, a total of 415 positive OFCs that triggered objective allergic reactions were used to estimate the threshold doses that are expected to elicit symptoms in 1% (ED01) and 5% (ED05) of the walnut-allergic population. An additional 295 validation OFCs were conducted under a “safe-dose” protocol using extended time intervals to confirm doses unlikely to cause a reaction. The association between patients' characteristics, allergic background, co-allergy to pecan, or challenge protocol type and the threshold dose was examined.
The discrete dose of walnut protein eliciting symptoms in 1% (ED01) and in 5% (ED05) of the study population were 0.8 (range 0.3–24) mg and 3.8 (1.1–96.4) mg, respectively. No objective reactions were observed to doses of ≤1 mg protein in the “safe-dose” OFCs group, supporting this amount as a reliable safety threshold. Key factors associated with lower threshold included younger age, co-allergy to pecan, and undergoing a slow OFC protocol designed for threshold detection at the beginning of OIT. While some participants reported mild subjective symptoms (mostly oral discomfort) even to the first OFC protocol dose of 0.1 mg, these symptoms were not linked to objective allergic reactions and often did not recur. In summary, the data provided in the current study, on walnut reaction threshold from a large Israeli population, could be used to determine threshold for food labeling and has the potential to reduce unnecessary warnings and improve quality of life of walnut-allergic individuals.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.
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