It was a question Dr. Gideon Lack asked often, when giving lectures to fellow allergists and pediatricians on the topic of food allergies: How many doctors in the room had a patient allergic to peanuts?
Normally, “virtually every doctor would have put up their hand,” Lack said. Peanut allergy is one of the most common food allergies, affecting more than 2% of US children, with a similar prevalence in the United Kingdom, where Lack was practicing.
But at a lecture in Tel Aviv, Israel, about 25 years ago, the audience’s response took Lack by surprise. Only two or three out of about 200 raised their hand.
“I said, ‘Wait, this doesn’t make sense,’ ” he recalled recently. “I was practicing in London, which has a big Jewish community, and I was seeing a high frequency of peanut allergy amongst Jewish children who share similar ancestral background.”
Lack and his colleagues’ investigations into why, which played out over the next 15 years, led to last month’s remarkable finding that the incidence of peanut allergies in the US – after a precipitous rise – appeared to have fallen dramatically.
It turned out that the guidance parents and pediatricians – and Lack himself – had been following, to avoid giving peanuts to babies and young children to try to prevent the development of dangerous allergies, was completely backward.
“By thinking we were protecting them, we were actually causing the problem,” Lack told CNN.
The story of how he and his colleagues proved that was the case is a primer in the scientific process.
There’s a joke in Israel that the first three words babies learn are “mother,” “father” and “Bamba,” Lack said – for the peanut puff snacks that Israeli parents give babies when they’re very young.
“They’ve sort of become a national snack,” he noted, pointing out that the joke is actually “a truism.”
As he had conversations with the doctors there, as well as parents of young children, “They all told me one very clear thing: ‘We give peanut snacks to our babies from between 4 and 6 months of age.’ ”
Bambas contain “vast amounts of peanut protein,” Lack said. And he came to suspect that, just by “happenstance … this product was developed in Israel and protected the Israeli population.”
But that was an observation, something he’d learned at a lecture, Lack emphasized. “That’s not really proof of anything.” Could there be other differences Israeli children experience – weather, sunshine, vitamin D exposure – that could have contributed?
So he and a team of colleagues set out to study it. They looked at about 5,000 schoolchildren in Israel and 5,000 Jewish schoolchildren in London who shared a similar ancestral background – to control for genetic differences – and compared their rates of peanut allergy.
“In the UK, it was tenfold higher”: almost 2% of kids, Lack said, whereas in Israel, it “virtually didn’t exist.”
Examining the children’s diets, including when peanuts were introduced in the first year of life, revealed an obvious difference: UK babies were consuming a median zero grams of peanut per week. Israeli babies were eating about 2 grams – equivalent, in Bambas form, to about 10 weekly peanuts.
“The kids were eating this with great relish,” Lack noted; it’s a “very popular snack.”
But “at the time when I suggested this hypothesis, it was virtually impossible to get funding,” he said. He and his team turned to the National Peanut Board, the group representing American peanut farmers. He said the study was criticized for who funded it but emphasized that it had no bearing on the outcome.
“The idea of eating peanuts was felt to be preposterous, that we would be putting babies at risk and causing peanut allergy based on the old thinking we had, and that it would even be an unethical thing to do,” he recalled.
The results suggested otherwise. But the work was only beginning.
What Lack and his colleagues had shown with that study, which was published in the Journal of Allergy and Clinical Immunology in 2008, was an association between eating peanuts early in infancy and a lower likelihood of developing peanut allergy.
What they wanted to prove was that early introduction of peanuts was the cause of those reduced allergy rates.
For that, they’d need to run a randomized controlled trial, in which they randomly separated participants – in this case, infants with severe eczema, egg allergy or both, putting them at higher risk of peanut allergy – into two groups. One set was directed to consume foods with peanut – such as Bambas peanut puffs – starting between 4 and 11 months of age, and the other was told to avoid them until they turned 5 years old.
This time, Lack and his colleagues received funding from the US National Institutes of Health, specifically the National Institute of Allergy and Infectious Diseases, which Lack called “patient and generous.” It was not an overnight result. It took two years to recruit the 640 infants into the trial, Lack said, and then they were followed for five years.
The results were stark. Of the 530 kids who didn’t start out with a sensitivity to peanut, 13.7% developed peanut allergy by age 5 if they avoided peanuts. In the group that consumed peanuts starting before age 1, 1.9% developed peanut allergy. Among kids who’d shown signs of sensitivity to start with, 35.3% who avoided peanuts developed the allergy, versus 10.6% of those who ate them.
“I was hoping for an effect, but I was not expecting to see a more than 80% reduction,” Lack said.
When the biostatisticians called him and colleague Dr. George Du Toit with the results, “we toasted the good news to whiskey and roasted peanuts,” Lack recalled. They published the findings from the trial, called the LEAP study, in 2015 in the New England Journal of Medicine.
It wasn’t clear, though, whether the message would resonate with parents and pediatricians – if they could change course and do the opposite of what they’d been told for so long.
Guidelines had been issued in 2000 by the American Academy of Pediatrics, and although they’re often described now without nuance, they were anything but definitive.
“Conclusive studies are not yet available to permit definitive recommendations,” the academy’s Committee on Nutrition wrote in a document about hypoallergenic infant formulas. For infants at high risk of developing allergies, the committee continued, “the following recommendations seem reasonable at this time” – including delaying introduction of dairy products until 1 year, eggs until 2 years and peanuts, nuts and fish until age 3.
Lack himself followed the avoidance guidance with his own sons, which of course, “in retrospect, was the wrong advice.”
But he emphasizes that the scientific process of proving it was the way medicine should work.
“The history of medicine is a series of zigzags,” he said. “It’s not one linear, perfect progression, and people forget that.”
In 2008, the American Academy of Pediatrics withdrew its guidance that said potential allergens should be avoided for high-risk babies, but didn’t have enough data to recommend introducing them early.
After the LEAP study was published in 2015, the guidance was updated in what researchers now refer to as a landmark move, and the recommendations were expanded in 2017 and 2021.
A study published last month in the journal Pediatrics found that rates of peanut allergies among US kids 3 and under declined 33% after the 2015 recommendation and fell 43% after 2017 – and peanut allergies slipped from being the most prevalent to the second-most, behind eggs.
Study leader Dr. David Hill of Children’s Hospital of Philadelphia notes that those reductions, extrapolated to the number of US kids under age 3, suggest that almost 40,000 children may have avoided peanut allergy diagnoses since the guidelines changed.
Lack’s work continues. He’s currently co-leading another trial funded by the NIH, called the SEAL study. It seeks to test another question that once seemed backward: Could treating eczema early in a baby’s life prevent the development of food allergies?
“For years, we used to think that food allergies cause eczema,” Lack said. “Now we know it’s the reverse.”
The idea is referred to as the dual-exposure hypothesis, and Hill noted that it’s supported by decades of research, including from the LEAP trial.
“Early exposure to food proteins through the gut promotes tolerance, teaching the immune system that these foods are safe,” he told CNN. “In contrast, exposure through inflamed or disrupted skin – as often occurs in infants with eczema – can sensitize the immune system and increase the likelihood of developing food allergy.”
Babies might encounter food proteins through their skin if they have eczema just from their parents eating those foods, Lack said.
He put the hypothesis another way: “If I were to knock on your front door and ask for directions, you’d probably greet me in a civil way. But if I were to break into one of the windows, you might greet me in a different way.”
The SEAL study aims to treat dry or red, flaky skin in the first 12 weeks of life, before babies have developed allergies, using moisturizers and topical steroids, and give babies more time to be exposed to foods by eating them. The goal: see if that helps reduce the likelihood they develop food allergies.
If they’re right, it could change medicine again.
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