Low-Dose Multi-Nut Oral Immunotherapy Shows Promise for Children with Allergies

February 24, 2026

Children with multiple nut allergies experienced significant increases in the amount of allergens they could tolerate with oral immunotherapy (OIT) using very low doses, according to a study published in Clinical and Translational Allergy. The approach, which involves administering tiny amounts of mixed nut butters over an extended period, also appears to reduce the burden on families and healthcare providers.

Addressing Barriers to Traditional OIT

Oral immunotherapy is an established method for increasing the amount of food a child with a food allergy can safely consume. Although, traditional OIT protocols can be challenging due to factors like unpleasant taste, allergic reactions to doses, the time commitment required for frequent visits, and the need for precise food weighing or pharmacy compounding. Researchers sought to address these barriers with a simplified, low-dose approach.

“We wondered if aiming for just a low dose of a mix of all the nuts a child is allergic to, with visits months apart, dosed with tiny spoons of a mix of nut butter, might be effective,” explained Dr. Julia E.M. Upton, head of the division of immunology and allergy at The Hospital for Sick Children in Toronto. “Low-dose OIT requires fewer visits and may provoke fewer allergic reactions, and children who dislike the taste of nuts may better accept it.”

Study Design and Results

The study enrolled 18 children aged 6 months to 15 years with allergies to one or more of the following nuts: walnut, pistachio, cashew, hazelnut, peanut, and macadamia. Treatment began with approximately 4 mg of each allergenic nut protein, with doses escalated during office visits every 2 months. Oral food challenges were administered at 18 months, with a cumulative maximum of 2,040 mg of protein per allergen.

Key findings included:

• The median time to reach a maintenance dose of 30 mg of protein per nut was 304.5 days.
• Median tolerated doses increased from 10 mg of protein per nut at baseline to 1,000 mg of protein per nut at the oral food challenge (P < .0001).
• 10 children tolerated the 1,000 mg dose and the cumulative maximum dose of 2,040 mg of protein per nut at the oral food challenge.
• 14 children reached the 30 mg maintenance dose.
• Significant decreases were observed in skin prick test diameters for walnut (P < .05), pistachio (P < .01), cashew (P < .01), and peanut (P < .05).
• Significant increases were observed in allergen-specific IgG4 blocking antibodies to 2S albumins of all the allergens except for hazelnut.

Notably, even a child who only increased to half the target dose (approximately 15-16 mg) still demonstrated a 100-fold increase in tolerated nut protein compared to baseline.

Improvements in Quality of Life

The Food Allergy Quality of Life Questionnaire, administered to 13 parents, two teenagers, and one child, revealed significant improvements in emotional impact, food-related anxiety, and social and dietary restrictions among parental responses. Teenagers also showed trends toward improved emotional impact and reduced allergen avoidance.

Safety Profile

The study reported a favorable safety profile, with no treatment-related severe adverse events, hospitalizations, or deaths. Epinephrine was not required for any reactions at home or during escalation visits. The most common symptom was abdominal pain, reported in seven children, but largely attributed to pre-existing gastrointestinal discomfort in one child.

Future Directions

Dr. Upton suggests that this low-dose, unhurried-escalation approach may be a viable option for protecting children with multiple nut allergies against accidental exposure, inducing immunoregulatory mechanisms, and reducing the healthcare burden. She also notes that further research is needed to compare this approach with higher-dose protocols and to determine the optimal maintenance dose.

“The lowest effective dose of OIT has not been found, so there is also the opportunity to explore even lower maintenance dosing,” Dr. Upton stated. “It will also be valuable to consider if an application of this work may be to acquire started with very low doses, stay on that dose for 1 to 2 years and then move to a much larger dose if desired, thereby removing many up-dosing visits.”

Source: Upton JEM, et al. Clin Transl Allergy. 2025; doi:10.1002/clt2.70125