Raw Nut Protocol Induces Allergy Tolerance in Infants by Age 4

PHILADELPHIA — A novel approach involving the introduction of raw, then roasted nuts, has shown promise in reversing peanut and cashew allergies in three infants, according to research presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting. The findings suggest a potential pathway toward sustained tolerance, offering a significant shift from traditional avoidance strategies for young children at high risk of anaphylaxis.

A Different Path to Tolerance

The protocol, dubbed KIC-IT (Keep Introducing Consistently to Induce Tolerance), centers on the idea that the form in which a nut is first introduced can significantly impact the development of an allergy. Researchers found that raw peanuts and cashews appear to be less allergenic than their roasted counterparts. This observation led to a staged introduction process, beginning with raw nuts and progressing to roasted forms, aiming to build tolerance over time. “These are kids who showed anaphylaxis at 6 months, and instead of just saying ‘You get an EpiPen’ or ‘You have to avoid it,’ we found a way to allow a sustained tolerance so that we could change the rest of their life,” explained Rachel Kado, MD, allergist and immunologist at Kado Clinic, in a statement to Healio.

The initial cases involved three infants: one with a peanut allergy and significant atopic dermatitis (eczema), another with peanut and egg allergies, and a third with a cashew allergy and a history of proctocolitis and food protein-induced enterocolitis syndrome. Notably, none of these infants initially qualified for the LEAP (Learning Early About Peanut Allergy) study, a landmark trial that demonstrated the benefits of early peanut introduction in high-risk infants. The LEAP study, published in the New England Journal of Medicine in 2015, showed that introducing peanuts early in life could reduce the risk of developing peanut allergy, but the KIC-IT protocol offers a potential alternative for those who may not be suitable candidates for LEAP or for whom early introduction wasn’t successful.

Addressing the Inflammatory Load

A crucial component of the KIC-IT protocol is addressing underlying atopic dermatitis. Researchers emphasize that controlling eczema is paramount before initiating any allergy immunotherapy. This is achieved through a proprietary non-steroidal cream designed to improve skin integrity and calm the immune system. “The eczema had to be 100% clear before we started any of the immune therapy,” stated Morgan Schmidt, clinical research fellow at Kado Clinic. The rationale behind this approach is that a heightened inflammatory state, as seen in uncontrolled eczema, can lower the threshold for allergic reactions.

The process begins with a carefully monitored introduction of the raw nut in a clinical setting. Doses are gradually increased, with close observation for any adverse reactions. Once a tolerable dose is established, caregivers continue administering the allergen at home. If three days pass without any symptoms, the dose is escalated in the clinic. This cycle continues until the infant can tolerate three whole raw nuts. The process is then repeated with roasted nuts, followed by three years of daily ingestion, with unrestricted consumption beginning at age four.

Why Raw First?

The researchers hypothesize that roasting nuts increases their allergenicity. They suggest that proteins in raw nuts may be less likely to trigger an immediate IgE-mediated response, while the changes that occur during roasting could promote the development of regulatory pathways that foster tolerance, particularly during the critical window of immune system development in infancy. This concept aligns with broader research into the impact of food processing on allergenicity, which suggests that altering protein structures can influence their ability to trigger allergic reactions.

In the reported cases, all three infants achieved sustained tolerance at the three-year follow-up. The first infant, who initially reacted to peanut with hives, spitting up, and sneezing, was able to consume three roasted African runner peanuts daily by age 8 months and exhibited full tolerance by age three. The second infant, with peanut and egg allergies, followed a similar trajectory, achieving tolerance to all forms of peanut by age four. The third infant, with a cashew allergy, experienced minimal reactions during the process and achieved full tolerance to cashew by age four.

Implications and Next Steps

The KIC-IT protocol represents a potentially significant advancement in the management of food allergies, particularly for infants who may not respond to conventional approaches. The fact that none of the infants required medications during the protocol is noteworthy, suggesting a medication-free path to tolerance. However, it’s important to emphasize that these findings are based on a small number of cases and require further validation through larger, prospective trials.

Researchers at Kado Clinic are actively encouraging other allergy clinics to adopt and study the KIC-IT protocol. “This protocol is available,” Schmidt stated. “We will be happy to share the white papers of the study and be able to share our protocol.” The team believes that the plasticity of the immune system between 6 and 11 months of age is key to the protocol’s success and are eager to explore its potential in a broader population.

Looking ahead, the researchers plan to investigate the protocol’s safety, efficacy, and generalizability through rigorous clinical trials. They also aim to understand the underlying mechanisms by which the raw-then-roasted approach promotes tolerance, potentially paving the way for even more targeted and effective allergy treatments. This research is part of a broader “renaissance” in food allergy research, as Kado described, with ongoing studies exploring immune modulators, early allergen introduction strategies, and novel therapeutic approaches.

Morgan Schmidt can be reached at [email protected]. Rachel Kado, MD, can be reached at [email protected].