by Jasmine Amini

Graphic design by Jeah Kim

From grabbing a snack with co-workers to enjoying dinner with friends, food is often the centrepiece of our day-to-day social interactions. As such, severe food allergies (FA) can often be a lifelong sentence of fastidious label-checking, careful food preparation, and restricted social opportunities. With self-reported FA increasing in prevalence across Canada,¹ the need for new treatment approaches is imperative. But what if a cure to debilitating allergies lies in leveraging the allergen itself? Oral immunotherapy (OIT)—the practice of ingesting micro-doses of allergens—has gained traction as a treatment for FA¹ and may offer an approach to achieving food freedom by desensitizing food allergens and reducing allergic reactions.

 To understand how OIT works, it is important to first understand what causes FA. FA are distinct from food sensitivities or intolerances as they cause an immunologic event, in which the body mistakenly responds to proteins in food as pathogens.² For example, in peanut allergies, peanut proteins (e.g., AraH1 or AraH2) are identified as a threat by immunoglobulin E cells (IgE). Typically, IgE antibodies mark invading pathogens, which mediate a large-scale immune reaction by activating inflammatory cells such as macrophages and mast cells, leading to the onset of allergic symptoms.  In OIT, the idea is to desensitize this response over time through repeated small exposures to the allergen. While the precise mechanisms by which OIT alleviates allergies remains under investigation, several lines of research corroborate a reduced immunologic response following OIT, characterized by reduced mast cell and basophil reactivity and increased activity of T-regulatory cells, which suppress the general immune response.³ OIT typically involves a regimen of dosing food allergens mixed with a safe “vehicle” food (e.g., applesauce or yogurt).⁴ Allergen doses increase incrementally over time to build tolerance and desensitize individuals to the food allergen.

In recent years, OIT has seen a rise in public awareness, in part due to its coverage on social media.  TikTok and Instagram users use the hashtag #oralimmunotherapy to document their journeys with OIT treatment. However, underlying these trends are decades of allergy and immunology research. A 2022 meta-analysis of 39 randomized-controlled trials (RCT) (n = 2126 participants, mainly children) found that oral immunotherapy was effective in increasing tolerance to peanuts, cow’s milk, and hen’s egg.⁵ While longitudinal  OIT clinical trials are scarcer, the literature is slowly growing. In a two-year follow-up study of a probiotic and peanut OIT trial, >70% of participants achieved at least desensitization (i.e., heightened threshold for allergic reaction) to allergic reactions over time across all treatment groups.⁶

In addition to clinical trial outcomes of lower immunological reactivity post-treatment, OIT has the potential to drastically and positively impact the quality of life of those afflicted with food allergies. One prospective cohort study (n= 175 participants) from 2019 demonstrated that children undergoing OIT had scores on the Food Allergy Quality of Life Questionnaire significantly improved from OIT initiation to full maintenance (i.e. up to 3 years). Quality of life scores were particularly improved on subscale items relating to food anxiety, social and dietary restrictions, and emotional impact.⁷

While anecdotal, the active OIT-based social media community also frequently echoes these benefits, crediting OIT with reducing the chronic burden of living with severe allergies, for both patients and their families. For one TikTok user, @AllergicGina, OIT has provided a sense of security for her niece Evelyn, who suffers from a severe peanut allergy, stating, “[Oral] Immunotherapy has removed that constant gripping fear of ‘if I have something that’s cross-contaminated, I will die’…”. ⁸

However, OIT does not come without its criticisms or failures. Foremost, in some cases, OIT has been shown to increase allergic and anaphylactic reactions.⁹ For example, a meta-analysis from 2019 that included 12 OIT trials (n = 1041 participants) for peanut allergy found OIT increased anaphylaxis risk and frequency of anaphylactic reactions during both the treatment and maintenance periods.¹⁰ Notably, these anaphylactic reactions occurred despite achieving immune desensitization, meaning that participants had previously tolerated similar doses of the allergen while supervised in-clinic. Other criticisms of OIT include poor clinical trial standardization and reporting: to date, there is little consensus on which outcomes should be reported, and few studies examine allergic responses longitudinally.⁹ Moreover, OIT is only a viable treatment option for a select population, and, as such, cannot be viewed as a “catch-all” therapy. Current evidence corroborates the use of OIT to treat peanut, cow’s milk, and hen’s egg allergies,^5,9 but current studies show seldom focus on other common allergens such as soy, tree nuts, or shellfish. Finally, OIT is primarily safe and effective for infants and children with FA.  One study comparing OIT effectiveness among children, adolescents, and adults found that adults were more likely to experience adverse reactions and achieve lower levels of allergen desensitization, reducing the potential clinical impact of OIT for the adult population.¹¹

 OIT offers an exciting, novel approach to the longstanding challenge of food allergies. However, further research is vital to overcoming current efficacy limitations. Identification of reliable biomarkers and treatment outcomes for OIT are critical first steps in establishing solid evidence for OIT efficacy or inefficacy. Further standardization of OIT protocols within RCTs is also necessary to compare results between trials. Finally, cautious expansion of OIT treatment into other priority allergens, like soy, and across age groups is crucial to advancing allergy treatment and supporting the greatest number of individuals. With an ever-expanding literature base, OIT has the potential to revolutionize allergy treatment, one microgram of peanut protein at a time.

References

Epstein-Rigbi N, Levy MB, Nachshon L, et al. Efficacy and safety of food allergy oral immunotherapy in adults. Allergy 2023; 78: 803–811.

Clarke AE, Elliott SJ, St Pierre Y, et al. Temporal trends in prevalence of food allergy in Canada. J Allergy Clin Immunol Pract 2020; 8: 1428-1430.e5.

Lopez CM, Yarrarapu SNS, Mendez MD. Food Allergies. In: StatPearls. Treasure Island (FL): StatPearls Publishing, http://www.ncbi.nlm.nih.gov/books/NBK482187/ (2025, accessed 21 January 2025).

Gorelik M, Narisety SD, Guerrerio AL, et al. Immunologic Suppression To Peanut During Immunotherapy Is Often Transient. J Allergy Clin Immunol 2015; 135: 1283–1292.

Wood RA. Oral Immunotherapy for Food Allergy. J Investig Allergol Clin Immunol 2017; 27: 151–159.

de Silva D, Rodríguez del Río P, de Jong NW, et al. Allergen immunotherapy and/or biologicals for IgE-mediated food allergy: A systematic review and meta-analysis. Allergy 2022; 77: 1852–1862.

Loke P, Wang X, Lloyd M, et al. Two-year post-treatment outcomes following peanut oral immunotherapy in the Probiotic and Peanut Oral Immunotherapy-003 Long-Term (PPOIT-003LT) study. Allergy 2024; 79: 2759–2774.

Epstein-Rigbi N, Goldberg MR, Levy MB, et al. Quality of Life of Food-Allergic Patients Before, During, and After Oral Immunotherapy. J Allergy Clin Immunol Pract 2019; 7: 429-436.e2.

AllergicGina on TikTok. TikTok, https://www.tiktok.com/@allergicgina/video/7299125208730848517?_t=ZM-8tOlnpVb1K1&_r=1 (accessed 26 January 2025).

Mori F, Giovannini M, Barni S, et al. Oral Immunotherapy for Food-Allergic Children: A Pro-Con Debate. Front Immunol 2021; 12: 636612.

Chu DK, Wood RA, French S, et al. Oral immunotherapy for peanut allergy (PACE): a systematic review and meta-analysis of efficacy and safety. The Lancet 2019; 393: 2222–2232.