How much is too much? Threshold dose distributions for 5 food allergens

Barbara K. Ballmer-Weber, Montserrat Fernandez-Rivas, Kirsten Beyer, Marianne Defernez, Matthew Sperrin, Alan R. Mackie, Louise J. Salt, Jonathan O'B. Hourihane, Riccardo Asero, Simona Belohlavkova, Marek Kowalski, Frederic de Blay, Nikolaos G. Papadopoulos, Michael Clausen, Andre C. Knulst, Graham Roberts, Ted Popov, Aline B. Sprikkelman, Ruta Dubakiene, Stefan ViethsRonald van Ree, Rene Crevel, E. N. Clare Mills*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

151 Citations (Scopus)


Background: Precautionary labeling is used to warn consumers of the presence of unintended allergens, but the lack of agreed allergen thresholds can result in confusion and risk taking by patients with food allergy. The lack of data on threshold doses below which subjects are unlikely to react is preventing the development of evidence-based allergen management strategies that are understood by clinician and patient alike.

Objective: We sought to define threshold dose distributions for 5 major allergenic foods in the European population. Methods: Patients with food allergy were drawn from the EuroPrevall birth cohort, community surveys, and outpatient clinic studies and invited to undergo a food challenge. Low-dose, double-blind, placebo-controlled food challenges were undertaken with commercially available food ingredients (peanut, hazelnut, celery, fish, and shrimp) blinded into common matrices. Dose distributions were modeled by using interval-censoring survival analysis with 3 parametric approaches.

Results: Of the 5 foods used for challenge, 4 produced similar dose distributions, with estimated doses eliciting reactions in 10% of the allergic population (ED10), ranging from 1.6 to 10.1 mg of protein for hazelnut, peanut, and celery with overlapping 95% CIs. ED10 values for fish were somewhat higher (27.3 mg of protein), although the CIs were wide and overlapping between fish and plant foods. Shrimp provided radically different dose distributions, with an ED10 value of 2.5 g of protein.

Conclusion: This evidence base will contribute to the development of reference doses and action levels for allergens in foods below which only the most sensitive subjects might react.

Original languageEnglish
Pages (from-to)964-971
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Issue number4
Publication statusPublished - Apr-2015
Externally publishedYes


  • Food
  • allergy
  • threshold
  • peanut
  • hazelnut
  • celeriac
  • fish
  • shrimp
  • EuroPrevall

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