Julia E. M. Upton, MD, MPH, from the Food Allergy and Anaphylaxis Program at The Hospital for Sick Children in Toronto

Julia E. M. Upton, MD, MPH

very low–dose oral immunotherapy (VLOIT) can both meaningfully and safely increase tolerated doses across multiple nuts

In 18 children allergic to 2 to 5 nuts, a low, slow escalation strategy to a 30 mg per nut maintenance dose led to significant gains in reaction thresholds by 18 months, with mean tolerated doses reaching 1000 mg. Most participants achieved at least a 5-fold increase over baseline, and many tolerated amounts associated with protection from accidental exposure. Adherence approached 100%.

VLOIT demonstrated safety and tolerability, with no epinephrine use, serious adverse events, or hospitalizations reported during the study. Adverse effects were generally mild, most commonly abdominal pain or transient oral discomfort during home dosing. Immunologic outcomes aligned with clinical improvements, including reductions in skin prick test wheal sizes, decreases in allergen-specific IgE, and increases in IgG4 blocking antibodies.

In the Q&A that follows, study investigator Julia E. M. Upton, MD, MPH, from the Food Allergy and Anaphylaxis Program at The Hospital for Sick Children in Toronto, explains the rationale behind selecting a 30 mg per nut maintenance dose and why this threshold may be sufficient for real-world protection against accidental exposures. She also discusses how the safety profile compares with that of higher-dose OIT, how immunologic changes are tracked with clinical outcomes, and what the findings mean for the quality of life in families managing multiple food allergies. Upton also outlines ongoing and future trials aimed at defining the minimal effective dose needed to balance efficacy, safety, and treatment burden.

 How do you determine that a 30 mg per nut maintenance dose would be sufficient for meaningful desensitization?

 We picked 30 mg of each nut protein as the amount for maintenance dosing because it is easily measurable and is 1/10 of a commonly used dose. We looked at how well it worked with food challenges. At the start of the study, we fed the nuts to the children under medical supervision. We proved they were allergic to peanuts and that they reacted to 444 mg or less. We started with tiny amounts and increased to about 30 mg protein of each nut with up doses about every 2 months. For peanut butter, this would be about 1/32 tsp of peanut butter. We then fed them again, 18 months after starting oral immunotherapy, to see how much they could safely eat.

 The study reports that most participants tolerated 5 times their baseline dose or ≥ 300 mg per nut. How significant is this increase in tolerated dose for day-to-day allergy management and accidental exposure risk?

 We know from other studies that, if a person can safely eat about 1 peanut (about 300 mg), then they have an extremely low chance of having accidental exposure reactions because most foods do not accidentally contain this amount. So being able to safely eat 300 mg provides the reassurance that an accidental exposure reaction is very unlikely. Hopefully, this gives children and families some peace of mind and helps to lessen the fear around food.

 How does the safety profile of VLOIT compare to traditional high-dose OIT protocols in children?

 In this multi-nut study, no child required [an] epinephrine autoinjector with dosing at home. This study does not compare to higher doses. In a different study, we had children randomly assigned to peanut OIT up to 30 mg maintenance, 300 mg maintenance doses, or avoidance. The safety analyses in that study found that the children assigned to 30 mg had fewer systemic allergic reactions and a trend toward fewer withdrawals (0 in the 30 mg group and 3 in the 300 mg group).

 How well did reductions in skin prick test wheal size align with clinical outcomes?

 The skin prick tests to the treated nuts also decreased over the 18 months. We also saw other immunological improvements: IgG4 went up, and the basophil activation test showed reduced degranulation. Overall, the immunological tests supported what we observed clinically: that very low dose OIT works to increase how much nut protein a child can safely ingest.

 How do improvements in social and dietary restrictions per parent-reported FAQLQs translate to practical benefits for families managing multiple food allergies?

 The main objective of this study was to see whether these low doses could increase the amount of food a child with a nut allergy could safely eat. Food allergy is so important for quality of life that we explored QOL. We performed this QOL survey at the start and at the end. Importantly, the QOL survey at the end was administered before they knew their food challenge result, which, for most, showed they could eat far more nuts safely than at the start of the study. It is reassuring that we saw some quality of life improvements just from eating the tiny amounts in the study, before they knew what they had achieved for desensitization. We want children and their families to feel safe and confident, and we are encouraged we saw some improvements in these scales even in this small study.

 How important is the ongoing trial comparing 30 mg versus 300 mg peanut OIT in determining the optimal minimal dose for efficacy?

 The ongoing trial with our group and Montreal Children's Hospital is more rigorous to examine safety and efficacy because the children are assigned to 30 mg or 300 mg in a blinded and randomized trial, and the food challenges are also performed in a rigorous, blinded, and placebo-controlled manner. This multi-nut trial shows that multi-nut allergies can be safely treated for many, even if only using a small amount of nut butters and with up-dosing visits spread out to every two months. Together, these studies may help to allow OIT to be delivered in a way that reduces the burden on the families and the health-care system with fewer visits, less taste aversion, less systemic allergic reactions, and hopefully more adherence and improvements to quality of life.

 What is next for future research on this topic?

 We will soon report our 21-month outcome experience with our randomized trial of 30 and 300 mg maintenance doses. We have also implemented 30 mg as our initial maintenance dosing in our food immunotherapy clinics, and we are in the process of collecting our real-world experience with this dosing.

Derman C. HCPLive. Very Low-Dose OIT Safely Increases Multi-Nut Tolerance in Young Children. Published on January 9, 2026. Accessed on January 16, 2026. 

https://www.hcplive.com/view/very-low-dose-oit-safely-increases-multi-nut-tolerance-young-children

Upton JEM, Li CH, Berenjy A, et al. Safety and Efficacy of Very Low-Dose Multi-Nut Oral Immunotherapy in Children. 

. 2025;15(12):e70125. doi:10.1002/clt2.70125

Articles

A recent study indicates that very low-dose oral immunotherapy (VLOIT) can significantly and safely increase tolerance to multiple nuts in children with food allergies. Involving 18 children allergic to 2-5 nuts, the study used a low, slow escalation strategy to a 30 mg per nut maintenance dose, resulting in substantial increases in reaction thresholds by 18 months. VLOIT showed a favorable safety profile, with no serious adverse events. Immunologic improvements correlated with clinical outcomes, and quality of life enhancements were reported. Ongoing trials aim to optimize dosing for efficacy and safety.

Upton discusses an open-label trial showing a 30 mg per nut very low-dose oral immunotherapy strategy increased multi-nut tolerance and remained safe in children.
