One of the mysteries in food allergy is why a person’s reaction to an allergen may involve only minor symptoms on one occasion. Yet another time, such exposure leads to full-blown anaphylaxis.
Now, new research from Japan sheds light on the major role cofactors often play in severe reactions, especially for food-allergic adults. A large data analysis finds a cofactor, most often exercise, implicated in about 50 percent of adult cases of anaphylaxis to foods.
In children, the role of cofactors was less common, but still significant. Twenty-one percent of anaphylaxis cases in those under age 18 involved a cofactor.
The researchers analyzed records from an anaphylaxis registry of over 1,000 children and adults seen for food-induced anaphylaxis at 40 hospitals in Japan. The records span the years 2022 through 2024.
The study found adults and children had somewhat different allergy cofactors.
Exercise was the most common cofactor, identified in 70 percent of anaphylactic reactions in kids and half of adult cases.
Among children and teens, colds or illness was the next most frequent cofactor, present in 18 percent of cases. That was followed by fatigue (10 percent), bathing (3 percent), menstruation (2 percent), and stress (2 percent). Travel and NSAID drugs such as ibuprofen were each a cofactor 1 percent of the time.
Among adults, alcohol was the second biggest cofactor, contributing to anaphylaxis in 25 percent of cases. It was followed by fatigue (19 percent) and NSAIDs (10 percent).
Other adult cofactors included bathing (5 percent), cold and illness (4 percent), menstruation (4 percent), travel (3 percent), and stress (2 percent).
“We found different cofactors between the children and adults,” notes Sakura Sato, MD, PhD, senior study author. She’s the director of the Department of Allergy at Sagamihara National Hospital in Japan.
What is a Food Allergy Cofactor?
A cofactor in a food-allergic reaction acts alongside the allergen. It can lower the threshold for the reaction to occur, or cause a more severe reaction.
New York allergist Dr. Scott Sicherer notes for example a person who “always is fine with a bowl of pasta but has an allergic reaction when exercising after eating that bowl of pasta.”
Or, that a mild reaction to a food in the past becomes a severe reaction when a cofactor is present.
Sicherer, director of the Jaffe Food Allergy Institute and chief of pediatric allergy at the Icahn School of Medicine at Mount Sinai, notes that cofactors can also team up and work together. “For example, exercise plus NSAIDs may [increase] the reaction more than either alone.”
Why More Cofactors in Adults?
Sicherer says there could be several reasons why adults are more inclined to anaphylaxis cofactors than children.
Grown-ups are likely to have more frequent interactions with certain cofactors, such as alcohol and NSAIDs, than kids. “Adults have lived longer and may have more opportunity to experience the impact of cofactors and then report them,” he says.
Adults may be more likely to continue eating a food that has caused mild reactions in the past, Sicherer notes. In contrast, parents of younger kids often remove a food from a child’s diet after a mild reaction.
Another factor could relate to the foods themselves, and what adults eat. Some allergens may be more impacted by cofactors than others, he says.
For example, it typically takes more shellfish protein to trigger an allergic reaction than some foods, such as peanut. Adults who are sensitized to shellfish but have high reaction thresholds may regularly eat small amounts of shellfish without symptoms, or with only mild symptoms.
“They may not ever know they have an allergy,” Sicherer says. “But when they are at a wedding and have a large serving of shrimp and then dance (exercise) and have wine, they experience the reaction.”
Sicherer also cites wheat as an allergy that may get missed when it only brings on mild symptoms. “But wheat is especially common as an allergen affected by cofactors, particularly exercise.” He says this may relate to how wheat proteins respond to the physical changes brought on by exercise.
Trigger Foods
The Japanese study, presented at the 2026 AAAAI allergists’ meeting, found a wide range of foods that triggered anaphylaxis alongside cofactors.
Tree nuts coupled with a cofactor caused 22 percent of the reactions. Cereals and grains triggered 14 percent, milk triggered 14 percent, and eggs, 12 percent.
Other food triggers included peanuts, soybeans, shellfish, fruits, fish, fish roe, buckwheat, citrus fruits and Rosaceae fruits, such apples, peaches and berries.
However, it should be noted that which foods trigger allergies can vary around the globe. Sicherer says similarly there can be regional differences with allergens involved in cofactor-enhanced reactions.
He notes that fruit triggers in the Japanese study, such as peaches, are more commonly an allergy issue in Japan and Mediterranean regions than in North America. There is more sensitization to those proteins that, with a cofactor added, can become anaphylaxis.
“Diet differences can also play a role,” he says. “If a culture is not eating much buckwheat or fish roe, you would have fewer episodes of allergy” to those foods.
How Do Cofactors Impact Reactions?
Researchers are still working out exactly how cofactors make allergic reactions worse. Sicherer says some evidence suggests exercise may make mast cells more easily activated, so that less allergen is needed to trigger them to release chemicals that result in allergic symptoms.
Exercise may also increase blood flow and gut permeability, resulting in a larger amount of allergenic protein absorbed into the bloodstream.
NSAIDs, which boost gut permeability and cause changes to inflammatory pathways, “may tip the scale toward allergic reactions,” he says. Stress and sleep deprivation can cause immune dysregulation.
Hot showers and baths or hot climates may increase blood vessel widening, which can worsen allergic reactions. Sicherer also notes that individuals with pollen allergies may be more reactive to foods when their pollen allergies are flaring.
Whether a reaction will happen depends not just on the cofactor and the allergen, but also on the amount consumed and the individual’s sensitivity, he says.
Lowering Cofactor-Related Risks
In the 2026 study, about 17 percent of adult patients had asthma, and 44 percent had experienced anaphylaxis previously. Prior anaphylaxis to the same allergen, asthma and the presence of cofactors were each associated with more severe anaphylaxis.
For someone known to react to a food, such as peanut, Sicherer says cofactors don’t impact the basic advice of: avoid the allergen.
However, a patient can be educated to be aware of potential cofactor effects. For example, “if this person accidentally ate peanut, they should not run two blocks to get their epinephrine. That exercise could increase the reaction – a reason to carry epinephrine at all times,” he says.
If a patient is undergoing oral immunotherapy, their allergist will be certain to caution about cofactors. They will advise rest periods after doses or potentially skipping doses when ill.
Young adults should also be reminded alcohol can fuel risky behaviors and raise cofactor concerns. “If they are drunk they might grab the wrong food,” Sicherer says. “They might not realize they are having allergic symptoms and they may have a worse reaction caused by the effects of the alcohol.”
Can the Food be Eaten Safely?
But what about the adult who tolerated small amounts of shellfish or wheat, then experienced a cofactor reaction? Sicherer definitely recommends that patient work with an allergist. There’s a lot to discuss to determine if the person can safely continue eating the food, as long as the cofactors are managed. With exercise, for instance, he says this might mean avoiding exercise for four hours after eating the food.
Sicherer says the allergist’s discussion would cover the person’s reaction history, details about amounts consumed, severity of past symptoms, and an overall food risk assessment. “There is a lot of nuance that has to be considered,” he says.
Related Reading:
Study Finds Doubling of Adult Food Allergies: 5 Takeaways
Shellfish Allergy: Symptoms, Causes and Tricks to Manage
