Introduction

The percentage of people with food allergies or sensitivities is unknown because many people do not attribute their symptoms to the food they eat. In 2004, it was estimated that 6% of children and 4% of adults in America had immunoglobulin-E (IgE) mediated food allergies¹ and that 20% of the population altered their diet due to adverse reactions to foods.^2,3 It is clear that food reactions are common and the prevalence of food allergies specifically is rising.¹ There are a variety of reactions a person can have to food including:

This chapter focuses on the immune-mediated reactions to food, also referred to as food allergies.

The specific nomenclature used for food allergies has been defined in position statements written by the European Academy of Allergy and Clinical Immunology (EAACI) nomenclature review committee. Allergy reactions are defined as a “hypersensitivity reaction initiated by immunologic mechanisms.”⁴ This includes food reactions mediated by any antibody (IgE, IgG, IgA, or IgM), as well as cell-mediated reactions (as seen in contact dermatitis).⁵ Although this is the strict definition of food allergy, the same article also stated that, “Food-specific IgG antibodies in serum are not of clinical importance but merely indicate previous exposure to the food. If IgE is involved in the reaction, the term IgE-mediated food allergy is appropriate. All other reactions should be referred to as nonallergic food hypersensitivity.”⁵ Hypersensitivity is defined as a way to “describe objectively reproducible symptoms or signs initiated by exposure to a defined stimulus at a dose tolerated by normal persons.”⁵ These definitions stated that food reactions mediated through IgG or IgA antibodies would strictly be defined as a “food sensitivity.” The clinical significance of IgG and IgA antibodies is still being debated in the scientific and medical communities.⁶ Most natural medicine practitioners call IgG- and IgA-mediated reactions “food allergies” because the reaction is associated with an antibody response. Food allergies will be defined here as any response to food that is immune mediated, including antibody responses (IgE, IgG, IgA, and IgM), as well as cell-mediated food reactions.

The discussion of definitions also extends into food allergy symptoms. The scientific community typically defines food allergy symptoms as IgE antibody mediated (type I or II hypersensitivity reactions). IgE associated disorders include immediate-type gastrointestinal hypersensitivity, oral allergy syndrome, acute urticaria and angioedema, allergic rhinitis, acute bronchospasm, and anaphylaxis. Symptoms include reddening of the skin; hives; pruritus of skin, mouth, or throat; swollen lips or eyelids; tightness of the throat; wheezing; difficulty breathing; coughing; vomiting; or diarrhea.^7,8 Most of these symptoms happen right after eating the offending food. Mixed IgE- and cell-mediated food reactions cited in the literature include atopic dermatitis,^9–12 asthma,^13,14 eosinophilic esophagitis,^15–17 and eosinophilic gastroenteritis.¹⁸ Food reactions mediated by cellular (non-IgE mechanisms) include contact dermatitis,¹⁹ food-induced pulmonary hemosiderosis,^20,21 celiac disease,²² and food protein-induced enterocolitis syndrome.^23,24 Many natural medicine practitioners recognize a wider array of food-related disorders and symptoms that can affect almost any system in the body. Symptoms may include diarrhea, constipation, abdominal bloating, gas, urinary irritation, rashes (including eczema and psoriasis), tinnitus, nasal congestion, chronic sinus or ear infections, joint pain, headaches, foggy thinking, fatigue, and mood disturbances.^25–28 Many of these symptoms are delayed, sometimes taking a few days to appear. Because of the variety of symptoms and the time it takes people to show a reaction to some foods, food allergy testing can be useful.

Various types of food allergy testing methods are used as tools to identify a person’s reactive foods. Different tests are appropriate depending on the immunologic reaction a person is trying to discover. Food allergy or sensitivity testing can be a great motivational tool to encourage dietary changes, showing people in full color their specific reactive foods. People are often more willing to change their diet after a test provides “proof” that a particular food is reactive. Food allergy tests can also be useful when patients are unable or unwilling to do a full elimination diet, or when they are not aware of the food-related physical symptoms present in their body. Although an elimination diet is still the gold standard for food sensitivity testing, the time and diligence it takes to do a proper elimination diet is often overwhelming. An accurate and reproducible food allergy test allows nutritious foods to remain in a patient’s diet while eliminating reactive foods. This chapter provides a review of the immunology of food allergies and then specifically examines the different food allergy testing methods.

Immunology of Food Allergies

Healthy individuals do not have food allergies or sensitivities. Instead they eat foods, digest them well, absorb what they need, and their immune system develops “oral tolerance” to the food. Oral tolerance describes how the body learns not to react to an antigen (food) when it is delivered through the oral route.^29–31 The factors that influence tolerance include the person’s genetics, digestive function, and the nature and form of the food when it is consumed. Proteins induce tolerance more than lipids and carbohydrates,³² and proteins given in a soluble form induce tolerance more than those that are aggregated.²⁹ Low doses of antigen activate regulatory/suppressor T cells, generally described as T_H3 cells (which can be both CD4 and CD8 T cells).^33,34 The mucosal immune system consists of regulatory and suppressor T cells (T_H3 cells) in Peyer’s patches and mesenteric lymph nodes that produce transforming growth factor-β (TGF-β). The role of TGF-β in the body is to promote B-cell class switching to IgA and to act as a general immunosuppressant for both T- and B-cell responses.^35,36 In this way, we can accept food into the body while still fighting pathogens (bacteria, viruses, parasites, or toxins).

Increased intestinal permeability is related to increased aggressive inflammation and lack of tolerance. It appears that increased permeability throughout the intestine allows food antigens to pass through the disrupted tight junctions and, in animal models, induces anaphylaxis^37–39 (see Chapter 20, Intestinal Permeability Assessment). When antigens are absorbed through the paracellular spaces, the mucosa-associated lymphoid tissue does not get the proper stimulation to induce a tolerance response. Data are conflicting regarding the integrity of the mucosal barrier in children with various gastrointestinal diseases.^40–42 The role of intestinal permeability is critical for our understanding of food allergies and may play a role in a variety of types of immune-mediated food reactions. Natural medicine practitioners often talk about healing the intestines, leaky gut, and decreasing inflammation. These types of treatments are most likely aimed at increasing the tolerance response in the intestines.

Food allergies may develop when the regulatory system falters due to defects in TGF-β or when the intestinal epithelial barrier is breached. Both of these may contribute to a reactive individual developing an antibody-mediated food reaction. When a food is taken up by Peyer’s patches in a reactive individual, CD4 T cells specific for the food make T_H2 cytokines, including IL-4 and IL-13. These cytokines cause B cells specific for the protein in the food to make IgE and induce mast cell activation and growth (IL-4 and IL-9).^43,44 IgG is also produced in response to food antigens, although the mechanisms leading to the production of total IgG and its subclasses are not fully elucidated at this time. Allergic sensitization to allergens was originally attributed to a dysregulation of the Th1/Th2 balance. New subsets of T cells have been shown to induce allergies or have an effect on the immune regulatory balance. These cells include Th17 cells⁴³ and nonclassical T cells such as natural killer T cells,⁴⁵ γδ T cells, and subsets of CD8 T cells (Tc1 and Tc2 cells).^43,44

For type I hypersensitivity reactions, antigen-specific IgE is produced by B cells. Elevated levels of antigen-specific IgE allergies are found in allergic people even with antigen avoidance for several years.^46,47 Once IgE antibodies are made to a particular food, they attach to Fc receptors on mast cells and eosinophils. When the antibody binds to its triggering food, the cells degranulate, causing traditional allergy symptoms, including hives, diarrhea, and gastric distress.⁴⁸

Food Allergy Testing Methods

The immune system has a variety of possible ways it can react that could induce a food allergy reaction. Different testing methods are best for specific food allergy reactions. There are variables within a testing method that may make its reliability and clinical relevance questionable. All of these factors need to be taken into consideration when selecting a food allergy testing method.

There are a variety of ways to test for food sensitivities, including elimination/challenge, skin testing, patch testing, enzyme-linked immunosorbent assay (ELISA) antibody tests for IgE, IgG, IgG4, and IgA antibodies, biochip technology, and energetic testing methods. As immunologic methods become more sophisticated, more specific and accurate tests are likely in the future. All methods look at a particular aspect of food reactions and have specific advantages and disadvantages. Clinical interpretation is required regardless of the type of testing used.