Introduction
Food is necessary to provide energy and nutrients for sustaining life. Food also provides pleasure when it is tasted and ingested. However, some individuals can undergo unfavorable physiological and neurological reactions after ingestion of foods that are known to be safe for consumption by the vast majority of the population.

An adverse reaction to a food, as defined by Anderson (3), is a clinically abnormal response attributed to an exposure to a food or food additive. In some people, these undesirable reactions occur after ingestion of some foods. Table 1 lists some of the complaints of some individuals after consumption of specific foods or food containing certain chemical additions. As yet, the scientific community has not accepted many of these complaints, seemingly real to individuals experiencing the condition or response.

Food allergy and sensitivity (intolerance) have been documented for centuries. Hippocrates (460-370 B.C.) recognized and documented the fact that cow's milk could cause gastric upset and hives. Galen (131-210 A.D.) described a child who developed allergic symptoms after drinking goat's milk (6, 20). Years later in 1873, allergic rhinitis was recognized when Charles Blackley presented evidence that "seasonal symptoms" involving the nose and eyes, as well as asthma, were due to the pollen of certain plants. Also at this time in the 1870s, "food idiosyncrasy" was recognized. During the later half of the 19th century, research to develop vaccines led to the initial understanding of toxic substances and anaphylactic reactions. Since that time, much research has focused on determination of causes of adverse environmental and physiological reactions in animals and humans.

"The Asthma and Allergy Foundation estimates that between 35 and 40 million Americans suffer some form of significant allergy. These include hay fever, asthma, allergic eczema, uticaria, angioedema, and allergies to drugs, insect stings, and food. This foundation suggests that food allergies are thought to be 5% to 10% of this total or about three million people in the United States today. The United States Department of Agriculture estimates that some 15% of the population may be allergic to some food ingredients or ingredient and estimates that 34 million people in the United States have an ingredient sensitivity (26)." However, it is difficult to separate true food allergies from other adverse reactions to food. Taylor (27) estimates that the incidence of true food allergies in the overall population is less than 1%. Sampson (23) states that good studies show food allergies are present in up to 4% of children less than 3 years of age and in 1 to 2 % of adults.

Different Types of Adverse Reactions
Kniker and Rodriguez (16) suggested looking at disorders that follow the ingestion of foods in order to understand the steps that lead to any acquired disease. "A pathogenic reaction always involves the activation of host mediators or biologic amplification systems. It is the action of these activated cells and/or non cellular factors that lead to deranged (altered) function or inflammation. The process begins when a particular triggering agent activates one or more mediators by one of several pathways. If a food (or food component) serves as an antigen and specifically interacts with antibodies or lymphocytes, the triggering agent is immune-related. On the other hand, the triggering food (or food component) may activate mediators directly (non-immunologically), by a chemical or idiosyncratic reaction."
Anderson (2) classified adverse reactions to food on an immunologic versus non-immunologic basis.

 Taylor (27) discussed adverse reactions to food and classified food sensitivities into four subcategories on the basis of the nature of the disease process: food allergies; food intolerances or metabolic disorders; idiosyncratic reactions to foods; and anaphylactoid reactions.

1. Food allergy is a term that should be used to identify adverse reactions to certain foods that have an immunologic basis. These reactions are characterized by the presence of larger amounts of immunoglobulin E in individuals with allergies. Some reactions, such as anaphylactic shock, occur almost immediately following ingestion of offending foods and are of a severe life-threatening nature. Some allergic reactions occur 4 to 6 hours after ingestion of a specific food, while other reactions may take more than 6 hours for the development of any adverse reaction or condition.
     Allergic reactions are characterized by any one or a number of the following conditions: hives, red inflamed skin, difficulty in breathing, cardiac seizure or arrest, increase or decrease in blood pressure, gastrointestinal disturbances, dizziness, ringing of the ears, tearing of eyes, headaches, drowsiness, restlessness, hyperactivity, (14, 23).

2. Food Intolerances or Metabolic Disorders. Some food sensitivities are caused by genetic deficiencies. For example, lactose intolerance is caused by a deficiency of the intestinal enzyme, lactase. As a result, lactose, the predominant sugar in milk, cannot be broken into its two component sugars: glucose and galactose. Phenylketonuria is caused by an inability of some individuals to metabolize and clear the amino acid, phenylalanine. Too much phenylalanine in the blood affects the central nervous system and leads to mental retardation in infants and children. Individuals with phenylketonuria must control their intake of phenylalanine. Therefore, they must consume minimally required amounts of protein, and must avoid foods containing significant amounts of phenylalanine (e.g., foods containing aspartame).
     An example of a drug-induced metabolic disorder occurs in individuals taking monoamine oxidase inhibitors (MAOI). These drugs interfere with the metabolism and clearance of tyramine. Too much tyramine in the blood can cause severe headaches, increased heartbeat, and elevated blood pressure. In severe situations, heart failure and intercranial hemorrhages have occurred. People taking monoamine oxidase inhibitors are instructed not to consume fermented or ripened foods (e.g., ripened cheeses, olives, pickles, sauerkraut, wine, beer, salami and other fermented sausages).

3. Idiosyncratic Reactions to Foods. These are types of food sensitivity for which the biological mechanism of action is not always well understood. Examples include: celiac disease (occurs in some individuals when they ingest any food containing wheat gluten); asthma induced in some individuals as a result of ingesting sulfites or FD&C Yellow No. 5. Other idiosyncratic reactions to foods reported to occur are: hyperkinetic behavior in children as a result of the consumption of food coloring agents and sugar; migraine headaches due to consumption of chocolate or aspartame; and "Chinese restaurant syndrome" due to consumption of excessive amounts of monosodium glutamate.

4. Anaphylactoid Reactions. These reactions are often confused with true food allergies because of similar symptoms. Scromboid fish poisoning and reactions of individuals after consumption of certain types of cheeses are due to ingestion of large amounts of histamine in these foods. Immune factors and the presence of high amounts of immunoglobulin E (IgE) do not seem to be factors in this type of adverse reaction to food consumption. In other words, these same individuals can consume cheeses with low histamine content and fresh fish with no adverse reaction.

Allergic Mechanism
It is common for several members of the same family to have hay fever, asthma, or eczema. The tendency for these diseases to cluster in certain families is known as "atopy," and affected individuals are described as being "atopic." The amount of food that must be eaten in order for an atopic person to become sensitized is unknown. Atopic infants have been reported to become sensitized to minute quantities of food allergens present in their mothers' breast milk. Once a person has become sensitized, ingestion of milligram quantities of food allergens may be enough to trigger an allergic reaction (30). Being exposed to vapors from fish can be enough for some individuals.

Environmental agents such as pollens, mold spores, dust mites, and some foods are common "allergens." Following a sufficient exposure to these allergens, atopic persons may become sensitized and produce IgE antibodies (immunoglobulin E) to these or other allergens. After IgE antibodies are produced they circulate in the blood and bind to basophils (white blood cells) and to the surface of body cells called "mast cells". Mast cells and basophils contain granules packed with chemicals such as histamine. When an allergic person encounters an allergen to which he/she has previously produced IgE antibodies, the allergen combines with the IgE antibody on the surface of the mast cells and basophils. This triggers a complex series of reactions that result in the release of histamine and other mediators (prostaglandin D2, Leukotreine C4, tryptase, chymase, heparin, and chondroitin sulfate) from the granules inside the mast cells and basophils (11). The release of histamine and other mediators occurs rapidly, within 5 minutes after the interaction between the allergen and the IgE antibody on the surface of the mast cell (21). (See Figure 1.)

Histamine and other mediators are the agents responsible for producing symptoms of allergy. Once released, these compounds enter the blood stream and bind to "receptors" on other cells in the body, causing typical allergic symptoms that may include sneezing; red, itchy eyes; hives; cough and wheezing; swelling of various body parts; and in severe (anaphylactic) reactions, fall in blood pressure or shock. The severity of the allergic reaction to a food depends on how sensitized the person is and the amount of the allergenic food that is eaten. Histamine release from mast cells is usually complete within 30 minutes after the allergen-IgE antibody interaction.

The release of mediators (other than histamine) is slower and their effects are more prolonged. Allergic reactions may sometimes take place in two phases. The first stage or first symptoms go away on their own or with medication, only to recur 4 to 6 hours later. For this reason, it is important for extremely sensitized individuals to go to the nearest hospital and stay for observation for at least 4 hours. Some food-sensitive persons who have experienced more than one allergic reaction usually report the same "early warning signs" and symptoms with each reaction. However, it cannot be assumed that each reaction will take the same course and last the same period of time (30).

Anaphylactic Shock
Systemic anaphylaxis (anaphylactic shock) represents the most dramatic and potentially catastrophic manifestation of immediate hypersensitivity. Virtually every organ in the body can be affected, although reactions involving the pulmonary (lungs), circulatory (blood and lymph), cutaneous (skin), neurologic (nervous system), and gastroentestinal systems are the most common. Reactions range in severity from mild skin inflammation and hives to shock and death (more than 500 deaths in the United States, annually, which is about the same number of fatalities due to disease or illness from Listeria monocytogenes). Once anaphylaxis has occurred, it is imperative that every effort is made to identify the agent responsible so that appropriate avoidance measures can be taken. However, since exposure is often unexpected or unavoidable, the prevention or reversal of life threatening reactions by a variety of pharmacologic (medication: e.g. epinephrine) or immunologic therapies (desensitization shots for insect stings and some medications) become an essential part of the management of anaphylaxis (11).

Desensitization shots have not been shown to be effective for food allergy (23). Currently, the only way to prevent reactions is strict avoidance. Once a reaction occurs, epinephrine or antihistimines are necessary to reverse symptoms (19).

Individuals with a peanut allergy are most likely to suffer severe anaphylactic reactions and are least likely to "lose" their food hypersensitivity (9). Many women ingest substantial amount of peanuts (especially peanut butter) while they are breast feeding. The peanut allergen is often secreted in breast milk and may sensitize the infant (24). Peanut oil, sufficiently processed so that it contains no detectable protein, does not produce a reaction in peanut-sensitive individuals (9, 28). However if peanut oil is insufficiently processed, or if peanut oil and other oils are used to fry peanut-containing foods, peanut allergens may be retained in the oil(s) to cause a severe life-threatening condition (anaphylactic shock) if a peanut-sensitized individual consumes this fried food. At the present time, there is little information on the quantities of peanut allergen that pose a risk to peanut-sensitive individuals (15).

Bock and Dorion (10) reported the results of a 2-year study of people reporting severe reactions to food. Severe reactions were defined as respiratory or cardiovascular symptoms requiring emergency intervention. In the 2-year period, 25 individuals (2 to 71 years) were identified as fulfilling these criteria. One fatality was identified as being probably due to food in a woman known to have systemic mastocytosis and previous food reactions. Colorado has a population of about 3.3 million, yielding 1 severe food reaction per 264,000 per year. Reporting was incomplete and this number must be viewed as an estimate. If extrapolated to the United States population this equals approximately a minimum of 950 citizens per year having severe food reactions, with an unknown number having fatal reactions. Based on this information, a nationwide statistical research study should enlist the assistance of emergency departments throughout the nation to regularly report all severe food reactions to a data collection center for at least one year.

Foods Responsible for Allergic Reactions
Sampson (24, 25) states that the peak of hypersensitivity in people occurs about 1 year of age. It is estimated that about 3% to 4% of infants are sensitive to some foods. Most infants usually outgrow their sensitivity by about 10 years of age. However, allergy to some foods remains in about 1% of the adult population. Although virtually any food may cause a hypersensitivity reaction, eggs, peanuts, and cow's milk seem to account for 80% of allergic reactions in American children, and peanuts, nuts, and seafood are responsible for most allergic reactions in American adults. Research studies have isolated heat and acid-stable glycoproteins in these foods ranging in size from 10 to 40 kilodaltons that seem to be the allergenic fraction of these foods (1, 7). Exactly what makes these glycoproteins such potent allergens, remains unanswered.

Fatal or near-fatal anaphylactic reactions to foods in children and adolescents are rare, but such incidents do occur and are of great concern to affected individuals and their families. Sampson et al. (25) reported a study that identified 6 children and adolescents who died of anaphylactic reactions to foods and seven others who nearly died and required intubation.

"Of the 13 children and adolescents (2 to 17 years), 12 had asthma that was well controlled. All had known food allergies, but had unknowingly ingested the foods responsible for the reactions. Allergic reactions occurred when peanuts (4), nuts (6), eggs (1), and milk (2) contained in foods such as candy, cookies, and pastry were consumed. The six patients who died had symptoms within 3 to 30 minutes after ingestion of the allergen, but only two received epinephrine in the first hour. All the patients who survived had symptoms within 5 minutes of allergen ingestion, and all but one received epinephrine within 30 minutes. The failure to recognize the severity of these reactions and to administer epinephrine promptly increases the risk of a fatal outcome (25)."

Bock and Atkins (9) also reported 12 of 19 children with known peanut sensitivity had positive skin test reactions to other nuts (walnut, 11; filbert, 10; cashew, 9; almond, 6; pecan, 6; and pistachio, 6). Thirty-two subjects with known peanut sensitivity were also tested for allergy reactions to other foods (egg, milk, wheat, and corn.) Twenty-two subjects had a positive skin reaction to eggs, 12 to milk, 6 to wheat and 2 subjects reacted to corn.

Seafood is another common cause of food allergy. Allergic reactions in some individuals are reported following ingestion of seafood, by inhalation of vapors generated during cooking, and by processing workers after occupational exposure to seafood. Based on estimates, approximately 100,000 to 250,000 Americans are at risk of developing allergic reactions to seafood products. Although occupational seafood allergy is not well studied, it can be estimated that 57,000 American seafood workers are at risk of developing work-related allergic reactions (18). Table 3 provides a list of foods involved in allergic reactions.

Case Histories
Bock (8) estimates that adverse reactions to cow's milk occurs in 0.1 to 7.5 percent of children. Gern et al. (13) reported case histories of 6 children with known allergies to milk who had adverse reactions occurring minutes after they ate products presumed to be milk-free. The cases are described as follows:

Patient 1, a 9-year-old boy, ate a few bites of a frozen tofu product. He immediately complained of a burning sensation in his tongue and minutes later developed facial hives. He was given oral diphenhydramine and the symptoms resolved in 30 minutes. His parents saved the tofu product for analysis. Results indicated the presence of milk in the product. When the company producing the product was contacted, it was found that no milk products had been added to the tofu, however the company was producing the product in a dairy processing facility.

Patient 2, an 11-year-old girl ate one bite of a beef hot dog (a product she had consumed with no ill effects in the past) on a bun and noticed immediate tingling of her lips. Within minutes her lips, face, and tongue became swollen, and hives and swelling of her joints developed. She was treated with subcutaneous epinephrine and intramuscular hydroxyzine at an emergency room. The girl was fed a small portion of a hot dog from the same package a week later, with similar results.
     When contacted, the company producing the hot dogs stated that recipe formulations had been changed recently to include sodium caseinate (the sodium salt of casein), which was added to improve the texture of the processed meat. Product labels, approved by the USDA, did not indicate the change and presence of sodium caseinate.

Patient 3, a 10-year-old boy, had allergic reactions on two occasions after eating food presumed to be milk-free. Minutes after he ate a small quantity of bologna, angioedema, rhinorrhea (nasal discharge), and increased itching and inflammation of his chronic eczema developed. A few months later, a second reaction occurred after he ate a small amount of a frozen dessert which was reported to be milk free. Within 15 minutes he experienced urticarial lesions (hives) on his face and mouth, followed by rhinorrhea, wheezing, and shortness of breath. On both occasions he was given oral diphenhydramine at home and also required a shot of epinephrine at an emergency room.
     The bologna and Rice Dream dessert were both found to contain small amounts of milk protein. Investigations found that the Rice Dream dessert (a "milk-free" product) was being produced in a dairy production facility.

Patient 4, a 6-year-old boy, ate sandwiches containing either bologna or hot dog produced by the same company described previously. Each time he had a burning sensation in his mouth and throat, hives, and vomiting within 2 minutes after biting into the sandwich. He was treated successfully with oral diphenylhdramine.

Patient 5, a 5-year-old boy, ate 1 teaspoon of tuna fish, and within 5 minutes periorbital swelling, flushing of the face and bronchospasm developed. He was treated with oral hydoxyzine and nebulized albuterol at home and received further treatment in an emergency room. The tuna was sent for analysis and was found to contain milk protein.
     Prior to March 1991, it was acceptable for companies to add sodium caseinate and not list it as such, but let it fall under the heading as a "natural flavoring" for labeling purposes.

Medication and Medical Treatment
Medications such as antihistamines, epinephrine, adrenaline, bronchodilators, and steroids reverse the symptoms produced by the mediators. Epinephrine is the medication of first choice in treating reactions and it should be administered as soon as possible after "early warning" signs and symptoms appear. Many times food-sensitive people react to allergens hidden in food and therefore are unable to know how much of the allergen they consumed. Food-sensitive individuals must not wait to see how severe the reaction will become, especially if they are a distance from medical facilities. Epinephrine can be administered by the allergic person or by a family member. Emergency medical help may be required to provide other medication and treatment (e.g., oxygen, intravenous fluids, or drugs to raise blood pressure) (30, 31).

Avoidance Is Best Control
Despite development of new antiallergic therapies (prompt administration of epinephrine or other drugs offering relief of symptoms, if any anaphylactic or less severe allergic condition is suspected), avoidance continues to be the best "treatment" for allergic ingestive, inhalative, and occupational disease (18). Avoiding food that contains offending allergens is quite difficult for affected individuals. For example, milk proteins are added to many foods that are not suspected of containing milk (e.g., nondairy creamers, margarines, canned tuna, and hot dogs). Peanuts are being processed to look and taste like other nuts and may be added in ground forms to products so that it is difficult to detect their presence. People experiencing adverse reactions to food must request and receive correct information about the food they purchase and consume.

Legal Implications
The importance of giving the correct information to consumers is illustrated by the following account given by the Star Tribune, Minneapolis, Minnesota, August 8, 1992 (4):

The widow of a Farmington man who died from an allergic reaction to peanut butter will receive $450,000 in a settlement with a Twin Cities restaurant. The man died within 90 minutes after taking a few bites from an egg roll at a Chinese restaurant. Before he ate it, a waitress assured him that the roll was not fried in peanut oil. However, the waitress did not know that the egg roll recipe had been changed several years ago to include peanut butter, which was used to enhance taste. After the man developed the allergic reaction, his wife and mother summoned the manager, who disclosed that peanut butter was an ingredient in the egg roll.

The man drove himself to a near-by urgent care center where he went into shock. His throat swelled, he stopped breathing, and was subsequently pronounced dead.

The man's wife sued the restaurant. As a part of the settlement of $450,000, it was agreed that the restaurant must change the language on its menu to alert customers that it will disclose ingredients in foods if requested.

The man had a prescription for epinephrine, a form of adrenalin, but it was unclear whether he injected himself with it.

Food Labeling
Labeling is an appropriate way to enable "hyper-reactive" people to avoid intensive exposure to "triggering" compounds in food or food products (17). The FDA announced changes in nutrition and ingredient labeling in January, 1993 as a result of the Nutrition Labeling and Education Act (NLEA) (5). Listed below is a brief summary of final rules and proposed rules that will affect people with food allergies.

Final Rules
Certified color additives will be listed by name (e.g., FD&C Blue No. 1).
Foods that contain hydrolyzed protein will have to identify the source of the protein (e.g., soy protein hydrolysate).
Products labeled as "non-dairy" that contain casein will have to indicate that casein is a milk derivative.
Sulfite, when present at 10 or more parts per million will have to be declared on the label.
Ingredients will be listed on standard foods, such as yogurt, tuna, or catsup.
Fruits and vegetables that have preservative coatings will declare "coated with food-grade, animal-based wax to maintain freshness."

Proposed Rules
An amendment to the standard of identity for canned tuna would be added that claims "includes soybeans" to declare the ingredient
     vegetable broth when soybeans are used to make the broth that is sometimes used in canned tuna.
"Contains glutamates" would be added to ingredient list of products made with autolyzed yeast extracts and certain hydrolyzed proteins.

Exemptions
Food offered for sale by small businesses.
Food sold in restaurants.
Food similar to restaurant foods that is ready to eat but is not for immediate consumption or is not offered for sale outside of that location
     (e.g., airplane food).
Foods that contain insignificant amounts of all nutrients (e.g., coffee and tea).
Dietary supplements.
Infant formula.
Medical foods used for the nutritional needs of patients with certain diseases.
Custom-processed fish or game meats.
Foods shipped in bulk.
Donated foods.

Foods in packages too small to list nutrition information must provide an address or phone number to make it possible for consumers to obtain product information.

Future Food and Medical Research Is Necessary
As suggested by Taylor (27), there must be a continuing effort to determine the specific allergen components of foods known to produce allergic reactions in some individuals. Studies should also focus on the determination of tolerance levels in foods. There must be increased development of hypoallergenic foods (developed through formulation or by use of hypoallergenic processing techniques that destroy allergens). The food industry must be aware of the adverse effects (potential hazards associated with presence of allergenic residues) of food and food ingredients for a small portion of the population that includes both consumers and workers.

How a Retail Food Supplier Can Deal with This Problem
A low but significant percentage of the population does exhibit adverse reactions to the consumption of some foods. These reactions may occur because of severe allergies, metabolic abnormalities, anaphylactoid reactions, and other conditions that, at this time, are not well understood. Retail food suppliers (food producers, food retailers, restaurants, delicatessens) must be informed of this health concern and must attempt to provide necessary information to food sensitive consumers (17, 27, 22, 31). This information is necessary to prevent adverse reactions and possible fatalities, as well as litigation and loss of business as a result of this type of event. There is no mention of this in any current retail regulatory program (FDA Food Codes, vending codes, retail food store codes).

Communication and concern for food sensitive customers can be given in the following manner.

1. Potentially allergenic ingredients are disclosed on food labels. (Note: regulations for ingredient disclosure must be adequate for allergenic individuals, yet at the same time not restrictive, because most customers are not affected.)
2. Food wait personnel must be trained to know about allergic and other adverse reactions to food, and how to help food-allergic and/or food-intolerant customers with menu choices.
3. Retail food operators can provide additional information (22), by:

a. Labeling cups and wrappers with correct ingredient information.
b. Having printed pamphlets or sheets that accurately list and/or describe ingredients in their products.
c. Using menus that accurately describe entrees and all menu items.
d. Having a sign that invites customers to ask about ingredient disclosure when necessary. For example, "We will gladly provide information about our ingredients. Just ask." or "We will do our best to answer any question about the contents of our food and preparation methods."

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