Determination of Milk Allergen Threshold Doses with Dedicated Challenge

Rationale: Allergic reactions to traces of milk proteins in patients with cow's milk allergy (CMA) have led to regulatory and voluntary precautionary allergy labeling (PAL) practices.  These practices increase the inconvenience to patients and paradoxically may increase risk-taking and disregard in other patients. Therefore determination of minimal threshold doses is of critical importance for patients, industry and clinicians.  Previous data on the lowest observed adverse effect level (LOAEL) was pooled from multiple centers with a large number of reactions to the first dose (left-censored).  

Methods: Oral food challenge (OFC) results in patients with CMA were retrospectively analyzed. OFC's were performed diagnostically and/or for initiation into a milk oral immunotherapy (OIT) program. Confirmation of a no adverse effect level (NOAEL) was determined prospectively in the severest patients (n=12) with an OFC starting dose of 0.3 mg milk protein followed by a 120 minute observation interval. 

Results: OFC was performed in 746 patients (57.6% male), aged 6 months to 36.5 years (median = 7.67). 240/746 (32.2%) reacted at 30 mg of protein or less, only four of whom were left censored on OFC.  The LOAEL value was 3 mg (n=1). The NOAEL value was 0.3 mg (n=742), which was confirmed prospectively in highly-sensitive patients (n=12) reacting to low levels of protein.

Conclusions: This large cohort of CMA patients suggests a safe minimal threshold level.  Confirming these observations would avoid PAL and allow direct labeling of products with quantities of milk protein calculated per serving, that are safe for the vast majority of severe CMA patients.