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NC State team develops fruit-infused flour that could reduce deadly reactions to peanut allergies

By Reid Creager

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  • Allergies and the hygiene hypothesis

    Although there’s no confirmed explanation for the increase in peanut and other allergies in children, one theory has a lot of supporters.

    “The hygiene hypothesis” says that kids growing up in rural areas and around animals seem less prone to allergies than others because they have more exposure to viruses and bacteria. This helps children build up more immunities, the theory says.

    N.C. State’s Mary Ann Lila said the hypothesis could make sense: “There’s so much more of an emphasis on kids being clean now.”

    Skeptics argue that extra exposure to dirt and germs is harmful, regardless.

  • Schools’ peanut policies

    Schools and school districts throughout the country have varying policies regarding peanut products.

    Charlotte-Mecklenburg Schools was one of the first districts in the U.S. to stop selling or using products with peanuts, effective for the 2006-07 school year.

    The Wake County Public School system works individually with families to address allergy needs of children. According to the 2013-14 Wake County Public Schools Student/Parent handbook, school staff may administer medication to students if a “Parent Request and Physician Order for Medication” form is completed and present at the school.

You’ve heard the horror stories or seen them depicted on TV. Maybe you’ve even lived some yourself.

A routine meal is interrupted when someone has trouble breathing, exhibiting swelling of the face, tongue and other uncontrollable symptoms. These are often signs of an allergic reaction to peanuts or their byproducts – which can be fatal if not addressed in time.

Research scientists have been unable to solve this medical mystery. But there’s new hope via research from N.C. State University, whose team at the Plants for Human Health Institute at the North Carolina Research Campus in Kannapolis developed a fruit-infused peanut flour that could reduce deadly allergic reactions to peanuts and provide a safer ingredient for immunotherapy treatments for children.

“I think in my 25 years in academia, this has got to be the most exciting and intriguing project that I’ve worked on, with the most exciting results,” said Mary Ann Lila, the study’s lead researcher and head of the plants institute. “It relates to human health and has the potential to really impact a lot of people.”

That “a lot” is growing steadily. The nonprofit group Food Allergy Research and Education, based in McLean, Va., reports that the number of children with peanut allergies tripled between 1997 and 2008 for unknown reasons. The American College of Allergy, Asthma & Immunology said that about 400,000 school-age children in the U.S. have a peanut allergy – and only 20 percent of children with a peanut allergy outgrow it, according to

It’s all in the binding

For years, Lila has worked with health-promoting plant compounds from food crops such as cranberries and cinnamon. Her N.C. State research team discovered that these compounds make peanut flour more hypoallergenic by hiding or changing the allergy-causing proteins, meaning the body no longer recognizes peanuts as allergens. The study was recently published in the Journal of Agricultural and Food Chemistry.

She said the key to the process is polyphenol protein binding, which is well known in the scientific community. “It’s just that nobody’s put two and two together for the allergies before.

“We had our original revelation in our lab team meeting – that there might be a way to counter peanut allergy symptoms through this natural binding between polyphenols and proteins – back in late 2011 and early 2012,” Lila said. “We got this sort of ‘Aha!’ moment in the NCSU lab: What about allergenicity, and could this simple binding alter the allergenicity of the peanut protein?

“It was like, ‘Whoa, it seems too simple, too good to be true.’ But all of the experiments we did, one after the other, just turned out so beautifully to show us this reduced hypoallergenicity.”

Lila emphasizes that the research is preliminary and much more needs to be studied, such as how the polyphenol binding occurs.

“We’re not sure exactly how and we’re not sure of the nature of the binding, but there’s a specific affinity of the polyphenols for protein. … What that means is that the protein that otherwise is exposed and is provoking allergic reaction is either masked or is changed in confirmation because of the strength of the binding so that it is no longer in a form or shape that’s going to provoke the allergy. We need to do that research to figure out exactly what is changing.”

Firsthand knowledge

Lila said that after N.C. State researchers made their discovery, “we got a provisional patent finished last year, did all of the preliminary work and then invited some UNC Chapel Hill researchers a little over a year into the project so that we could have access to their peanut allergy work.”

Explained Mike Kulis, a research assistant professor at UNCand one of eight names on the study: “Her group was instrumental in producing the product and providing it for us. On our end, we do all of the allergenicity testing.”

Kulis has had a personal interest in the subject for most of his life.

“I have allergies myself to peanuts and walnuts,” he said. “That’s honestly what got me into this whole field about eight or nine years ago.”

He recalled two instances in graduate school when he unknowingly ate something with peanut content and ended up in the emergency room. “It just blew me away, like, ‘How did this happen to me? You mean, I almost died from eating half a bagel? This is crazy!’ It just really spurred my curiosity.”

Funding worries

Like Lila, Kulis’ excitement about the project is unaffected by funding questions. But both acknowledge money is a substantial hurdle.

Lila said her team’s research has never had any federal funding, just small peanut endowment grants.

“It’s expensive to do animal trials and even more expensive to do clinical trials,” she said. “That is our biggest holdup right now: funding to take this research forward, because general funding is dismal.

“We actually submitted an NIH grant on this project and came in with such glowing comments and such enthusiasm from the panel,” but it didn’t qualify for funding under the strict criteria in place.

The provisional patent centers only on oral immunotherapy, a procedure in which patients with a peanut allergy are fed small, incremental amounts of nut protein.

“We need to do more work and then take this into clinical trials,” Lila said.

Said Kulis: “Our group has kind of pioneered this oral immunotherapy with the peanut flour, but not with anything that’s modified. There still would need to be a lot of pre-clinical testing with animal models (often mice) that would go on for a while, and then going to the FDA and saying, ‘Hey, can we try this in a human experiment?’ 

With sufficient funding in place, Lila and Kulis say their research could also help others who have bad allergic reactions involving milk, soy and eggs, among other products.

“All of those are provoked by the protein in the product,” Lila said. “We can actually bind polyphenolics to other kinds of edible flours. We already know the binding works. Just like with the peanuts, why not?”

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