Recent years have seen an explosion in novel food products in international and, especially, in U.S. markets. Many novel food products seek to address consumer concerns regarding environmental impact and nutritional quality of mass-produced foods. Others look to a growing population of consumers seeking alternatives to meat products. Although no single definition of “novel food” exists, we usually consider a food to be novel if does not have a significant history of human consumption. Examples include not previously consumed plant species, algae, insects, lab-grown (cultured) foods, and fungi. We may also consider a food to be novel to a region or country, meaning that a history of consumption elsewhere may exist. An existing food that undergoes radically different processing may also be thought of as novel.
The introduction of new species to the food supply raises the possibility of new food allergens. The prevalence of food allergy in the U.S. is approximately 3 to 4 percent, though estimates vary. A common misapprehension is that only certain foods cause allergic reactions. Allergy to some foods is thought to be more prevalent, more severe, or more difficult to avoid, and these are often required to be labeled by law (e.g., wheat, milk, egg, soy, fish, crustacean shellfish, tree nuts, and peanut in the U.S.). However, almost any food can be allergenic, and predicting allergenicity of a new food has proven to be a problematic safety and regulatory issue for the novel food industry.
The Molecules that Cause Food Allergy
Almost all food allergens are proteins. All living things contain protein, meaning all foods (unless extensively processed to remove protein) also contain protein. Many novel foods on, or entering, the marketplace are designed to replace existing protein-rich foods (particularly meat) and are, therefore, rich in protein themselves. Proteins are extremely varied in structure and function, a property that enables them to perform many different roles in the human metabolism. This variability also affects allergenicity, with only some proteins having significant potential to be allergens.
The Food Allergy Research and Resource Program (FARRP) AllergenOnline database currently contains 2,129 proteins that are known or suspected allergens, including those from food, airway allergen sources (pollen and fungi), contact (latex), and venoms. Newly identified allergens are added every year. However, despite a relatively large number of known allergens, we still don’t know precisely which properties of a protein cause them to be allergens. We do, however, have some clues that help us identify types of food that may be particularly problematic.
Sensitization, Elicitation, and Cross-Reactive Allergens
Most food allergens are thought to be capable of both sensitizing (“priming” the immune system to respond later) and eliciting (causing a reaction in a “primed” or allergic individual). There are many examples of individuals who are sensitized to one allergen who then react to similar proteins in different foods. This phenomenon is known as cross-reactivity. Banana/latex allergy and birch-pollen/fruit allergy are relatively well-known examples of this. That cross-reactive allergic reactions may occur due to the consumption of a novel food by an individual who’s already allergic to a known allergen is very much a possibility. In fact, the likely susceptibility of shellfish allergic consumers to reactions resulting from the consumption of insect-based foods is already known. However, we know that different allergic individuals react to allergens in different ways, and allergens that cross-react in one may not in another.
Allergic reactions to food occur when a specific type of antibody, IgE (immunoglobulin-E) binds to food allergens. The IgE molecules that allergic individuals possess vary greatly, even among those who react to the same protein in the same food. These different IgE antibodies recognize allergens differently. Cross-reactivity can, therefore, be very different even among individuals with similar food allergy diagnoses. Because of the occurrence of cross-reactive allergy, and because the sensitization stage of food allergy is currently very poorly understood, we mostly consider elicitation when examining the possibility of food allergy from novel foods.
Predicting Allergenicity of Novel Foods
There’s no diagnostic test to determine whether a food is an allergen. When researchers refer to allergenic foods, we rely on the experience of having foods in the marketplace over years or decades and observing patterns of allergy in a population. For novel foods this often isn’t possible, as by definition there’s no well-recorded history of consumption. Additionally, animal models of food allergy are poor and do not provide accurate predictions of responses in humans.
For these reasons we look for patterns in foods that are known to be allergenic and whether or not these patterns are present in a newly introduced food. Because it’s proteins within foods that are responsible for food allergy, we are particularly interested in the proteins that are present in novel foods. Both Canada and the European Union have distinct novel food regulations that require manufacturers to examine the potential allergenicity of novel foods under intended use. Currently, the U.S. does not have a separate set of regulations for novel foods, but the questions raised are broadly similar:
How is the novel food related to known allergenic foods and commonly consumed non-allergenic foods? Organisms that are closely related to each other generally contain similar amounts of similar (by amino acid sequence) proteins. It follows that a protein type that’s an allergen in one food may also be an allergen in another food. There are numerous examples of types of proteins that are allergens in more than one type of food. Such proteins are often referred to as “pan-allergens” and include lipid transfer proteins in fruits and cereal crops, and tropomyosins in fish and shellfish. If a novel food contains a protein that’s similar to known allergenic food, this suggests the novel food may be allergenic. We can readily examine the similarity of proteins if their amino acid sequences are known. For this reason, databases of known allergenic proteins (such as www.allergenonline.org) are important when assessing allergenic risk from a new food. Proteins of similar sequence to known allergens may be further tested in the laboratory to examine the risk of cross-reactivity.
How much protein from the novel food is likely to be consumed? The higher the dose of protein consumed, the more likely it is that individuals may become sensitized or undergo an allergic reaction. The dose of protein delivered to consumers depends on how much protein is in the novel food, and how much of the novel food is likely to be consumed. For this reason, some novel protein isolates of foods that are already commonly consumed (e.g., pea protein) may pose allergen risks that weren’t previously noticed by the consumer, if they’re concentrated and consumed in a large quantity. A protein-rich novel food that’s intended to be consumed in large quantity (e.g., a meat replacer or protein-rich drink) is likely of greater concern than low-protein, low-consumption foods (e.g., an oil-based condiment).
Are the proteins in the novel food easily digested? It has long been known that proteins that are not easily digested in the human stomach, or possibly in the intestinal tract, are more likely to be allergens. Given that parts of a protein must survive for the immune system to recognize and react to it, this hypothesis is reasonable. It should be noted, however, that many poorly digested food proteins are not allergens. We can examine how digestible proteins from novel foods are in the laboratory using protein-digesting enzymes from mammals. Novel foods that contain proteins that do not break down with enzyme treatment, or that only partially break down, would be considered candidates for becoming an allergen, especially if they’re abundant in food.
Novel Foods Challenges
Novel foods are very different from one another with respect to potential allergen risk. Currently, our understanding of food allergy allows us to identify novel foods that may present a particularly high risk, but little more. Assessing the ability of a novel food to sensitize consumers is a particular problem. Ultimately, it’s regulatory agencies that decide on the safety of novel foods. Pathways to the regulatory acceptance of novel foods should be clear, rely on the best and most relevant scientific evidence, and not introduce unnecessary burden to the food manufacturer.
Informing consumers about allergen risk is the cornerstone of food allergy safety. In the absence of a food allergy cure, labeling of problematic, already known food allergens is our primary method of preventing allergic reactions. For this reason, allergen labeling regulations are tightly controlled by regulators. Communicating likely risk from novel foods, especially those that cross-react to known allergens, is therefore a problem. How should one label the presence of insects that may cause reactions in shellfish allergic consumers? By law they cannot be labeled as shellfish because they are not. A mechanism by which food manufacturers may label an allergen risk from novel foods without falling afoul of regulatory agencies is clearly needed.
Yes, novel foods will cause allergy. All, or nearly all, foods—novel or not—cause allergy. Some novel foods pose more risk than others. It’s important to note that, just as with existing foods, the presence of an allergy risk does not preclude novel foods from having a place in our diet. Wheat, egg, and milk are all recognized allergens with a crucial place in nutrition.
We don’t want to introduce extremely allergenic foods into our food supply. Equally, we must acknowledge that all foods come with an element of risk. The use of scientific risk assessment to identify the most allergenic new foods, and the use of clear labeling to communicate risk for the rest, is a sensible approach. The potential importance of novel foods in addressing nutritional challenges cannot be overstated. As the novel food market grows, sensible regulation should minimize risk while allowing benefits for all.
Dr. Johnson is an assistant professor of food science and technology at the University of Nebraska-Lincoln. Reach him at firstname.lastname@example.org. Palmer is a graduate research assistant of food science and technology at the University of Nebraska-Lincoln. Reach him at email@example.com. Dr. Goodman is a research professor of food science and technology at the University of Nebraska-Lincoln. Reach him at firstname.lastname@example.org.