By Umair Irfan 

Peanuts. Shellfish. Soy. Wheat. Tree nuts. Dairy. Eggs.

For millions of Americans, these ingredients are a recipe for an upset stomach, hives, swelling, or even a trip to the emergency room — all because of allergies to food.

Food allergies are becoming increasingly common, in children and in adults. Yet it’s surprisingly difficult to get a handle on even the basics. The United States Department of Agriculture estimates about 2 percent of adults and 4 to 8 percent of children suffer from food allergies, but some scientists think the number is as high as 10 percent across the board, around 33 million people in the US. Some have even described food allergies as an epidemic.

It adds up to a tremendous burden across the health system and the economy. Allergies can be dangerous but are rarely lethal. About 150 to 200 people die per year in the US from food-related allergies. However, allergies lead to 30,000 emergency room visits and 2,000 hospitalizations annually. Even for people who avoid serious reactions, their food allergies can take a toll. They may have to say no to a favorite dinner for fear of contamination, or struggle with the anxiety that they have to trust their lives to strangers at restaurants. Managing allergies can get expensive, too. Between doctor visits, hospitalizations, medicines, caregiving, lost productivity, and specialized meals, food allergies cost the US economy close to $25 billion per year.

All this adds immense urgency to perhaps the biggest mystery of food allergies: Why are they on the rise? Why are more babies and kids reacting badly to cookies, ice cream, cake, and milk? Why are more adults discovering that they can’t eat a lobster roll anymore?

“Certainly the word ‘unexplainable’ fits here,” said Alkis Togias, branch chief for allergies at the National Institute of Allergy and Infectious Diseases.

It turns out that some of the trappings of the modern world may have had some unintended consequences, and some well-intentioned guidance on how we should eat may have been completely wrong.

What makes an allergy an allergy?

Lots of things get lumped in as allergies, but scientists have a strict definition: Allergies are an overreaction of the immune system involving an antibody called immunoglobulin E (IgE). This is a protein that’s produced to help the immune system identify and counteract invaders. When IgE finds a threat, it triggers the production of a hormone called histamine, which causes blood vessels to dilate, tissues to inflame, skin to itch, and the airways to wheeze, cough, or sneeze — all in the hope of getting the threat away from the body.

This mechanism evolved to help our bodies cope with parasites and venom. But occasionally, something benign like pollen or peanut proteins can set off the alarms. The immune system might have been trained wrong, or an allergen may have a structure in common with something that is a threat.

Most often, allergies are a nuisance, but they can sometimes ramp up the immune system to dangerously high levels. Blood vessels dilate so wide that they cause a major drop in blood pressure while inflammation forces airways to swell shut, a life-threatening condition known as anaphylaxis. For people with severe allergies, this reaction can turn deadly in minutes.

Many things can cause allergies, but food allergies are particularly concerning. After all, people have to eat every day. They’re also confounding because allergies aren’t the only type of bad reactions people have to food. Being lactose intolerant is not the same thing as having a milk allergy, for example. The former involves the digestive system, while the latter is a function of the immune system, and thus they require different treatments.

So when someone feels sick after eating something, allergies aren’t the only suspect. In recent years, doctors have improved their ability to sort out these problems, which explains some of the rise in allergies.

“There is a little bit of an effect of better epidemiology and better diagnostics here, no question about that, but there’s also no question that a real increase has occurred,” Togias said.

That means there must be some other mechanism that is making increasing numbers of people unable to eat their favorite meals and snacks.

The theories behind the rise in food allergies

So why are food allergy rates going up? There are a few ideas, and they aren’t exclusive. No single theory explains everything, and there are likely several factors at work. And because we’re talking about a trend over years and decades across entire countries, it takes time to figure out exactly what’s at play.

Here are what scientists are thinking most about when it comes to food allergies:

Hygiene hypothesis

As sanitation and cleanliness have improved, food allergy rates have increased. The thinking is that with fewer germs and parasites to counteract, the immune system starts to turn against harmless things like allergens. But not every germ is equally important in this regard. There are specific benign, even helpful, microorganisms that evolved alongside humans and may play a crucial role in regulating the immune system: the so-called “old friends.” As people spend more time in highly sanitized environments, they are less likely to meet their old friends.

Circumstantial evidence for this is apparent around the world. Wealthy countries have some of the highest rates of allergies. Developing countries are seeing allergy rates rise as their standards of living improve. In China, food allergy rates rose from 5 percent in the decade between 1999 and 2008 to 8 percent between 2009 and 2018. People who emigrate from poorer countries with low allergy rates to wealthier countries see their allergy rates go up, and their children soon experience allergies as frequently as native residents. Allergy rates are higher in urban areas than in rural regions where people spend more time with nature.

But the hygiene hypothesis doesn’t explain everything we see with allergies. Sanitation has been improving for centuries, but allergies have spiked in the past couple of decades. Within wealthy countries, it’s minorities and lower-income residents who have the highest rate of food allergies.

Some researchers now object to the term “hygiene hypothesis” because it doesn’t capture all these nuances and makes it seem like being dirtier is the solution to allergies. It’s not, so keep washing your hands and don’t go out licking subway poles.

Exposure timing

Babies have malleable immune systems, and the first months of life are critical for calibrating an immune system’s response to threats. That time period is particularly important for infants who have a family history of food allergies or a risk factor for developing them, such as eczema.

“Our guidelines suggested initially that kids should avoid food allergens early in life,” said Douglas Mack, an assistant clinical professor of pediatrics at McMaster University. But this thinking may have been wrong, and it may have even backfired. It could explain why allergy rates have risen so much in the past 30 years compared to the decades prior.

A seminal 2015 study called LEAP (Learning Early About Peanut) randomized 640 infants with allergy risk factors to either consume or avoid peanut products. It found that by 5 years old, the babies who avoided peanuts had a peanut allergy rate of 13.7 percent while those that didn’t had a rate of 1.9 percent. Exposure to peanut proteins early in life actually reduced allergy rates.

Conversely, telling parents to avoid food allergens for their babies may have made things worse.

It’s not clear why, but it may relate to another idea sometimes called the dual exposure hypothesis. Food allergens can be introduced through the digestive system, but also through the skin, particularly in babies that have eczema. Allergen exposure through the skin seems to sensitize people, but through the gut, it appears to tamp down allergic responses. So even if a baby isn’t eating peanuts, soy, or eggs, the baby may still be exposed in the home through the skin, tilting the balance toward an allergy.

“I think we have to take some of the blame as clinicians,” Mack said.

Health officials in many countries now say that babies should be slowly exposed to potential allergens under the guidance of a pediatrician. According to the USDA’s updated dietary guidelines, “There is no evidence that delaying introduction of allergenic foods, beyond when other complementary foods are introduced, helps to prevent food allergy.”

Genetics

It does appear that some people are more inherently susceptible to developing allergies than others. However, the genetic roots of allergies are complicated, as nearly 100 genes are known to be involved. Among twins where at least one in the pair is allergic, 64 percent of identical twins — twins that have the same genetics — shared a peanut allergy, while just 7 percent of fraternal twins had an allergy in common.

Genetic susceptibility may also explain why the rates of some types of allergies are leveling off in wealthy countries.

“What we think is happening is that there is a plateau we’re reaching now,” Togias said. “Perhaps this plateau is a genetic limit.”

Like other explanations, genetics don’t explain everything about allergies, but they could shed more light on other ways to prevent allergies, according to Togias.

Vitamin D deficiency

The human body produces vitamin D with exposure to sunlight, though you can also get it through your diet. Vitamin D plays an important role in regulating the immune system, and as vitamin D levels have declined across populations, food allergy rates have gone up.

People in wealthy countries that spend more time indoors have higher food allergy rates than those spending more time outside. Countries that are further from the equator have higher allergy rates than those along the planet’s sunny middle.

This is a less-studied explanation than the other theories, and researchers are trying to figure out whether vitamin D supplements could play a role in reducing allergy rates.

Theories behind adult-onset allergies

Many of these other theories get at the rise of foodborne allergies in children, but say little about adult-onset allergies, which are even harder to study. Stories abound of people finding out the hard way that they can no longer eat their favorite foods, but adults often don’t bother to get an official allergy diagnosis, which means that other types of food sensitivities can get lumped in.

As for why adults can suddenly develop allergies, there are a couple of explanations. One is that the immune system itself goes through an aging process. With time, it does a poorer job of regulating itself. So an adult might become sensitized to an allergen over time.

Allergies in adults might also arise from immunological stresses like “a strong infection that somehow affected the immune system and sent a message for the immune system to start developing IgE antibodies where it did not before,” according to Togias.

People with food allergies don’t have to suffer

Even though scientists are still grappling with why food allergy rates have shot up, the good news is that it’s easier than ever to live with them. The first order is to figure out whether you actually have an allergy. The gold standard is a test known as a food challenge, where you eat the suspicious shrimp, peanut butter, or omelet under medical supervision. There are also skin tests. Figuring out the mechanism can help you suss out whether you need to avoid the food completely or if you can manage it with treatment.

In terms of preventing exposure, more foods carry allergy warnings and more restaurants are aware of allergy risks, but it can still be dicey. According to the Centers for Disease Control and Prevention, half of fatal food allergic reactions came from restaurants and food service.

For severe reactions, tools like an epinephrine injector, commonly known as an EpiPen, can stem anaphylaxis. If you see someone having a severe allergic reaction and they have an EpiPen, remember: blue to the sky, orange to the thigh. More than 3 million Americans keep these emergency injectors close by, but one manufacturer, Mylan, has in recent years jacked up the price more than 400 percent.

As for ongoing treatments, there are drugs that can mitigate mild allergy symptoms. There is also immunotherapy, where a patient is gradually exposed to increasing doses of an allergen over time under medical supervision.

Right now, there is no known way to reliably “cure” an allergy, but scientists have some leads. One hot area of research is the pool of microorganisms that live on the skin, in the lungs, and in the gut, what’s known as the microbiome. This appears to be a critical element in all allergies, not just food allergies, according to Togias. By figuring out how the microbiome interacts with allergies, scientists hope to cultivate a way to reduce food allergy severity over the long term.