By Mayo Clinic staff
Anaphylaxis is a severe, potentially life-threatening allergic reaction. It can occur within seconds or minutes of exposure to something you’re allergic to, such as the venom from a bee sting or a peanut.
The flood of chemicals released by your immune system during anaphylaxis can cause you to go into shock; your blood pressure drops suddenly and your airways narrow, blocking normal breathing. Signs and symptoms of anaphylaxis include a rapid, weak pulse, a skin rash, and nausea and vomiting. Common triggers of anaphylaxis include certain foods, some medications, insect venom and latex.
Anaphylaxis requires an immediate trip to the emergency department and an injection of epinephrine. If anaphylaxis isn’t treated right away, it can lead to unconsciousness or even death.
By Mayo Clinic staff
Your immune system produces antibodies that defend against foreign substances. This is good when a foreign substance is harmful (such as certain bacteria or viruses). But some people’s immune systems overreact to substances that shouldn’t cause an allergic reaction. When this occurs, the immune system sets off a chemical chain reaction, leading to allergy symptoms. Normally, allergy symptoms are not life-threatening. But some people have a severe allergic reaction that can lead to anaphylaxis. Even if you or your child have had only a mild allergic reaction in the past, there’s still a risk of future anaphylaxis.
A number of allergens can trigger anaphylaxis, depending on what you’re allergic to.
Common anaphylaxis triggers include:
* Certain medications, especially penicillin
* Foods, such as peanuts, tree nuts (walnuts, pecans), fish, shellfish, milk and eggs
* Insect stings from bees, yellow jackets, wasps, hornets and fire ants
Less common causes of anaphylaxis include:
* Muscle relaxants used during general anesthesia
Anaphylaxis triggered by exercise varies from person to person. In some people, aerobic activity, such as jogging, triggers anaphylaxis. In others, less intense physical activity, such as walking, can trigger a reaction. Eating certain foods before exercise or exercising when the weather is hot, cold or humid has also been linked to anaphylaxis in some people. Talk with your doctor about any precautions you should take when exercising.
Anaphylaxis symptoms are sometimes caused by aspirin, other nonsteroidal anti-inflammatory drugs – such as ibuprofen (Advil, Motrin, others) and naproxen sodium (Aleve, Midol Extended Relief) – and the intravenous (IV) contrast used in some X-ray imaging tests. Although similar to allergy-induced anaphylaxis, this type of reaction isn’t triggered by allergy antibodies.
If you don’t know what triggers your allergy attack, your doctor may do tests to try to identify the offending allergen. In some cases, the cause of anaphylaxis is never identified. This is known as idiopathic anaphylaxis.
By Mayo Clinic staff
Anaphylaxis symptoms usually occur within minutes of exposure to an allergen. Sometimes, however, anaphylaxis can occur a half-hour or longer after exposure. Anaphylaxis symptoms include:
* Skin reactions, including hives along with itching, flushed or pale skin (almost always present with anaphylaxis)
* A feeling of warmth
* The sensation of a lump in your throat
* Constriction of the airways and a swollen tongue or throat, which can cause wheezing and trouble breathing
* A feeling of impending doom
* A weak and rapid pulse
* Nausea, vomiting or diarrhea
* Dizziness or fainting
When to see a doctor
If you, your child or someone else you’re with has a severe allergic reaction, call 911 or seek emergency medical help. If the person having the attack carries an epinephrine autoinjector (such as an EpiPen, EpiPen Jr or Twinject), give him or her a shot right away. Even if symptoms improve after an emergency epinephrine injection, a visit to the emergency department is still necessary to make sure symptoms don’t return.
If you or your child have had a severe allergy attack or any signs and symptoms of anaphylaxis in the past, make an appointment to see your doctor. The diagnosis and long-term management of anaphylaxis are complicated, so you’ll probably need to see a doctor who specializes in allergies and immunology.
By Mayo Clinic staff
There aren’t many known risk factors for anaphylaxis, but some things that may increase your risk include:
* A personal history of anaphylaxis. If you’ve experienced anaphylaxis once, your risk of having this serious reaction is increased. Future reactions may be more severe than the first reaction.
* Allergies or asthma. People who have either condition are at increased risk of having anaphylaxis.
* A family history. If you have family members who have experienced exercised-induced anaphylaxis, your risk of developing this type of anaphylaxis is higher than it is for someone without a family history.
Tests and diagnosis
By Mayo Clinic staff
Your doctor will ask you questions about your allergies or any previous allergic reactions you’ve had. This evaluation will include questions about:
* Whether any particular foods seem to cause a reaction
* Any medications you take, and if certain medications seem linked to your symptoms
* Whether you’ve had allergy symptoms when your skin has been exposed to latex
* Whether stings from any particular type of insect seem to cause your symptoms
To help confirm the diagnosis:
* You may be tested for allergies with skin tests or blood tests
* You may also be asked to keep a detailed list of what you eat or to stop eating certain foods for a time
Your doctor will want to rule out other conditions as a possible cause of your symptoms, including:
* Fainting spells
* A condition other than allergies that causes flushing or other skin symptoms
* Mastocytosis, an immune system disorder
* Psychological issues, such as panic attacks
* Heart or lung problems
Treatments and drugs
By Mayo Clinic staff
During an anaphylactic attack, an emergency medical team may perform cardiopulmonary resuscitation (CPR) if you stop breathing or your heart stops beating. You may be given medications including:
* Epinephrine (adrenaline) to reduce your body’s allergic response
* Oxygen, to help compensate for restricted breathing
* Intravenous (IV) antihistamines and cortisone to reduce inflammation of your air passages and improve breathing
* A beta agonist (such as albuterol) to relieve breathing symptoms
What to do in an emergency
If you’re with someone who is having an allergic reaction and shows signs of shock caused by anaphylaxis, act fast. Signs and symptoms of shock caused by anaphylaxis include pale, cool and clammy skin, weak and rapid pulse, trouble breathing, confusion, and loss of consciousness. Even if you’re not sure symptoms are caused by anaphylaxis, take the following steps immediately:
* Call 911 or emergency medical help.
* Check the person’s pulse and breathing and, if necessary, administer CPR or other first-aid measures.
* Give medications to treat an allergy attack, such as an epinephrine autoinjector or antihistamines, if the person has them.
Using an autoinjector
Many people at risk of anaphylaxis carry an autoinjector. This device is a combined syringe and concealed needle that injects a single dose of medication when pressed against your thigh. Always be sure to replace epinephrine before its expiration date, or it may not work properly.
Be sure you know how to use the autoinjector. Also, make sure the people closest to you know how to administer the drug – if they’re with you in an anaphylactic emergency, they could save your life. Medical personnel called in to respond to a severe anaphylactic reaction also may give you an epinephrine injection or another medication to treat your symptoms.
If your anaphylactic reaction is triggered by insect stings, you may be able to get a series of allergy shots (immunotherapy) to reduce your body’s allergic response and prevent a severe reaction in the future.
Unfortunately, in most other cases there’s no way to treat the underlying immune system condition that can lead to anaphylaxis. But you can take steps to prevent a future attack – and be prepared in the event one does occur.
* Avoid your known allergy triggers as much as you can.
* You may need to carry self-administered epinephrine. During an anaphylactic attack, you give yourself the drug using an autoinjector (EpiPen, EpiPen Jr or Twinject).
* Your doctor may recommend taking prednisone or antihistamines.
By Mayo Clinic staff
The best way to prevent anaphylaxis is to avoid substances that you know cause this severe reaction. Follow these steps:
* Wear a medical alert necklace or bracelet to indicate if you have an allergy to specific drugs or other substances.
* Alert your doctor to your drug allergies before having any medical treatment. If you receive allergy shots, always wait at least 30 minutes before leaving the clinic so that you can receive immediate treatment if you have a severe reaction to the allergy shot.
* Keep a properly stocked emergency kit with prescribed medications available at all times. Your doctor can advise you on the appropriate contents. This may include an epinephrine autoinjector. Make sure your autoinjector has not expired. These medications generally last 18 months.
* If you’re allergic to stinging insects, exercise caution when they’re nearby. Wear long-sleeved shirts and pants. Avoid bright colors and don’t wear perfumes or colognes. Stay calm if you are near a stinging insect. Move away slowly and avoid slapping at the insect.
* Avoid wearing sandals or walking barefoot in the grass if you’re allergic to insect stings.
* If you have specific food allergies, carefully read the labelsof all the foods you buy and consume. Manufacturing processes can change, so it’s important to periodically recheck the labels of foods you commonly eat. When eating out, ask about ingredients in the food, and ask about food preparation because even small amounts of the food you’re allergic to can cause a serious reaction.
It’s important to do everything you can to prevent an anaphylactic reaction by avoiding your triggers. But even if you’re careful, at some point you’ll likely be exposed to the substance you’re allergic to. Fortunately, you can be prepared to respond quickly and effectively to an allergy emergency by knowing the signs and symptoms of an anaphylactic reaction, and having a plan to quickly treat those symptoms.
By Mayo Clinic staff
An anaphylactic reaction can be life-threatening when a severe anaphylactic attack occurs; it can stop breathing or stop your heartbeat. In this case, you’ll need cardiopulmonary resuscitation (CPR) and other emergency treatment right away.
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Approaches to Establish Thresholds for Major Food Allergens and for Gluten in Food
(Also available in PDF, 708 kB)
The Threshold Working Group
Table of Contents
B. Definitions of Thresholds
II. Food Allergy
. Adverse Reactions to Foods
A. Mechanism of Allergic Reaction
B. Range of Adverse Effects
D. Allergenic Foods of Concern
E. Measuring Thresholds
G. Collective Allergens
H. Published Challenge Studies
I. Food Treatments to Reduce Allergenicity
III. Celiac Disease
A. Mechanism of Pathogenesis
B. Range of Adverse Effects
D. Celiac Foods of Concern
E. Gluten Contamination of Grains
F. Gluten Challenge Studies
G. Measuring Gluten in Food
H. Gluten-Free Labeling
IV. Discussion and Recommendations
. General Approaches
A. General Criteria for Evaluating and Selecting Approaches to Establish Thresholds
B. Allergen Thresholds: Evaluation and Findings
C. Gluten Threshold: Evaluation and Findings
0. Appendix 1: Evaluation of Analytical Methods for Food Allergens
1. Appendix 2: Evaluation of Available Allergen Oral Challenge Studies
2. Appendix 3: Evaluation of Published Measurements of Protein Concentrations in Oils
3. Appendix 4: Evaluation of Gluten Testing Methods
4. Appendix 5: Evaluation of Gluten Oral Challenge Studies
VII. List of Tables
0. Table I-1. Summary of Various Types of Thresholds
1. Table II-1. Signs and Symptoms of Allergic Reactions
2. Table II-2. Allergy Prevalence in the United States
3. Table III-1. Estimated Daily Gluten Consumption from Combinations of Different Amounts of Food Containing Different Levels of Gluten
4. Table IV-1. Approaches to Establishing Thresholds
5. Table IV-2. General Criteria for Evaluating and Selecting Recommended Approaches to Establish Thresholds
6. Table IV-3. Specific Criteria for Evaluating Analytical Methods for Food Allergens
7. Table IV-4. Specific Criteria for Evaluating Allergen Oral Challenge Studies
8. Table IV-5. Summary of Published LOAELs for Food Allergens
9. Table IV-6. Example of Uncertainty Factors for the Safety-Assessment-Based Approach Using Peanuts
10. Table IV-7. Specific Criteria for Evaluating Protein in Oil Studies
11. Table IV-8. Specific Criteria for Evaluating Gluten Analytical Methods
12. Table IV-9. Specific Criteria for Evaluating Gluten Oral Challenge Studies
13. Table IV-10. Example of Uncertainty Factors for the Safety Assessment-Based Approach
VIII. List of Figures
0. Figure II-1. Adverse Reactions to Foods
1. Figure II-2. Mechanism of Allergic Reactions
2. Figure III-1 Mechanism of Celiac Disease
The Food Allergen Labeling and Consumer Protection Act of 2004 (P.L. 108-282) (FALCPA) amends the Federal Food, Drug, and Cosmetic Act (FFDCA) and requires that the label of a food product that is or contains an ingredient that bears or contains a “major food allergen” declare the presence of the allergen as specified by FALCPA. FALCPA defines a “major food allergen” as one of eight foods or a food ingredient that contains protein derived from one of those foods. A food ingredient may be exempt from FALCPA’s labeling requirements if it does not cause an allergic response that poses a risk to human health or if it does not contain allergenic protein. FALCPA also requires FDA to promulgate a regulation defining the term “gluten-free.”
This report summarizes the current state of scientific knowledge regarding food allergy and celiac disease, including information on dose-response relationships for major food allergens and for gluten, respectively. The report presents the biological concepts and data needed to evaluate various approaches to establish thresholds that would be scientifically sound and efficacious in relation to protection of public health. Each approach has strengths and weaknesses, and the application of each is limited by the availability of appropriate data. It is likely that there will be significant scientific advances in the near future that will address a number of the limitations identified in this report.
The Threshold Working Group expects that any decisions on approaches for establishing thresholds for food allergens or for gluten would require consideration of additional factors not covered in this report. Furthermore, one option that is implicit in the report’s discussion of potential approaches is a decision not to establish thresholds at this time.
Accurate and informative labeling is critical for allergic consumers, individuals with celiac disease, and their families because they need to rely on strict avoidance of specific foods and ingredients to prevent potentially serious reactions. The Food Allergen Labeling and Consumer Protection Act of 2004 (P.L. 108-282) (FALCPA) amends the Federal Food, Drug, and Cosmetic Act (FFDCA) and requires that the label of a food product that is or contains an ingredient that bears or contains a “major food allergen ” declare the presence of the allergen as specified by FALCPA. FALCPA defines a “major food allergen ” as one of eight foods or food groups (milk, egg, fish, crustacean shellfish, tree nuts, wheat, peanuts, and soybeans) or a food ingredient that contains protein derived from one of those foods.
An important scientific issue associated with the implementation of FALCPA is the existence of threshold levels below which it is unlikely that a food allergic individual would experience an adverse effect. FALCPA provides two processes by which an ingredient may be exempted from the FALCPA labeling requirements, a petition process [21 U.S.C. 343(w)(6)] and a notification process [21 U.S.C. 343(w)(7)]. Under the petition process, an ingredient may be exempt if the petitioner demonstrates that the ingredient “does not cause an allergic reaction that poses a risk to human health.” Under the notification process, an ingredient may be exempt if the notification contains scientific evidence that demonstrates that the ingredient “does not contain allergenic protein,” or if FDA previously has determined, under section 409 of the FFDCA, that the food ingredient does not cause an allergic response that poses a risk to human health. Thus, understanding food allergen thresholds and developing a sound scientific framework for such thresholds are likely to be centrally important to FDA’s analysis of, and response to, FALCPA petitions and notifications.
FALCPA also requires FDA to promulgate a regulation to define and permit the use of the term “gluten-free” on the labeling of foods. Such labeling is important to patients suffering from celiac disease, an immune-mediated illness. Strict avoidance of gluten at levels that will elicit an adverse effect is the only means to prevent potentially serious reactions. Thus, consumers susceptible to celiac disease need accurate, complete, and informative labels on food. Understanding thresholds for gluten will help FDA develop a definition of “gluten-free” and identify appropriate uses of the term.
Section 204 of FALCPA directs FDA to prepare and submit a report to Congress. The report is to focus principally on the issue of cross-contact of foods with food allergens, and is to describe the types, current use of, and consumer preferences with respect to advisory labeling. Cross-contact may occur as part of the food production process where residues of an allergenic food are present in the manufacturing environment and are unintentionally incorporated into a food that is not intended to contain the food allergen, and thus, the allergen is not declared as an ingredient on the food’s label. In some cases, the possible presence of the food allergen is declared by a voluntary advisory statement. Understanding food allergen thresholds and developing a sound scientific framework for such thresholds is also likely to be useful in addressing food allergen cross-contact issues, including the use of advisory labeling.
Both as part of its ongoing risk management of food allergens and in response to FALCPA, CFSAN established an ad hoc internal, interdisciplinary group (the Threshold Working Group) to evaluate the current state of scientific knowledge regarding food allergies and celiac disease, to consider various approaches to establishing thresholds for food allergens and for gluten, and to identify the biological concepts and data needed to evaluate the scientific soundness of each approach. This report is the result of the working group’s deliberations.
This report summarizes the current state of scientific knowledge regarding food allergies and celiac disease, including information on dose-response relationships for major food allergens and for gluten, respectively. The ability to establish a threshold depends on understanding the dose-response relationship between the ingestion of an allergen or gluten and the elicitation of an adverse response. Implicit in establishing such dose-response relationships is the identification of susceptible populations and characterization of any exposure levels below which all, or part, of the susceptible population does not respond. There is no consensus in the scientific literature regarding thresholds for major food allergens or gluten. Therefore, the Threshold Working Group identified the biological concepts and data needed to evaluate various approaches for establishing thresholds that would be scientifically sound and efficacious in relation to protection of public health.
B. Definitions of Thresholds
The term “threshold” has been used to refer to a variety of different concepts (Table I-1) that apply either to individuals or populations. Thresholds can be measured experimentally in animals or humans [i.e., No Observed Adverse Effect Level (NOAEL) or Lowest Observed Adverse Effect Level (LOAEL)], derived from epidemiological data, estimated by modeling (statistical or simulation), established by statute, or arising as the result of the selection of an analytical method. The ability to measure or determine a threshold may be limited by the sensitivity and specificity of the methods available to measure either the stimulus or the response. Understanding the strengths and limitations of the data underpinning the different approaches is particularly important when dealing with adverse effects that have low probabilities of occurring.
Table I-1. Summary of Various Types of Thresholds Type Description Etymological Definition “The intensity below which a mental or physical stimulus cannot be perceived and can produce no response.” (Webster’s Dictionary). Toxicological The dose at, or below which, an adverse effect is not seen in an experimental setting. Methodological The limit of detection of an analytical method. Statutory The establishment of a limit by statute, below which no regulatory action will be taken. C. FALCPA
As noted, FALCPA amends the FFDCA to prescribe the manner in which food labels must disclose that a food is, or contains an ingredient that bears or contains, a major food allergen. The law also requires the FDA to issue a regulation to define and permit use of the term “gluten-free.”
FALCPA establishes a petition process through which a food ingredient may be exempt from FALCPA’s labeling requirements if the ingredient does not cause an allergic response that poses a risk to human health. FALCPA also establishes a notification process under which a food ingredient described in section 201(qq)(2) of the FFDCA may be exempt from FALCPA’s labeling requirements if the ingredient does not contain allergenic protein, or if FDA previously has determined, under section 409 of the FFDCA, that the food ingredient does not cause an allergic response that poses a risk to human health.
From the perspective of the Working Group, implementation of the FALCPA petition and notification provisions could present several key scientific issues. First, what is an “allergic response?” Second, do all allergic responses pose a risk to human health, or do some allergic responses pose more of a risk than others? Third, can allergens occur in a food either in a form or at a level that is too low to cause harm (i.e., either the allergen does not cause a biological response or the response is too mild to be considered hazardous)?
Under FALCPA, a “highly refined oil” derived from one of eight foods or food groups and “any ingredient derived from such highly refined oil” are exempt from the definition of “major food allergen ” and from FALCPA’s labeling requirements. As discussed further below, there is evidence that consumption of highly refined oils does not appear to be associated with allergic responses despite the potential presence of low levels of protein in these oils.
Section 202 of FALCPA requires FDA to issue a proposed rule to define and permit use of the term “gluten-free” on labeling of foods. Section 203 of FALCPA recognizes that “the current recommended treatment is avoidance of glutens in foods that are associated with celiac disease.” FALCPA does not directly state how the term “gluten-free ” should be defined.
II. Food Allergy
A. Adverse Reactions to Foods
Many consumers consider a wide variety of adverse reactions associated with the ingestion of foods to be “food allergies.” While adverse reactions may occur for a variety of immunological, toxicological, or metabolic reasons only a small fraction of these are related to food allergies (figure II-1). The signs and symptoms associated with these reactions can range from oral irritation and swelling to cardiovascular collapse (Jackson, 2003). Although adverse reactions caused by microbial and toxicological agents can affect any most individual, immunological reactions only affect a small group of sensitive individuals. Reactions caused by the presence of toxic compounds such as histamine in seafood (e.g., scombroid poisoning) or from metabolic (e.g., lactose intolerance) are not true food allergies. The nomenclature used to describe these well documented reactions in sensitive individuals is not consistent in the scientific literature. Generally, reactions not involving immune responses are termed food intolerances (Johansson et al., 2001; Sampson, 2004).
Immunological responses to foods, including food allergies, occur in a sensitive population of individuals. The major immunological responses to foods, termed food hypersensitivities, can be divided into two major categories based on mechanism: (1) immunoglobulin E (IgE)-mediated hypersensitivity (e.g., oral allergy syndrome, anaphylaxis) and (2) non-IgE-mediated hypersensitivity (e.g., celiac disease, food protein-induced enterocolitis) (Johansson et al., 2001; Wershil et al., 2002, Sampson, 2004). A group of food-related disorders (e.g., allergic eosinophilic gastropathies, atopic dermatitis) may involve both IgE- and non-IgE-mediated immune mechanisms (Sampson, 2004). For the purposes of this report, the term “food allergy” will be used to describe IgE-mediated immune responses resulting from the ingestion of specific foods (Johansson et al., 2001; Jackson, 2003; Sampson, 2004). The most severe and immediately life-threatening adverse reactions to foods are associated with IgE-mediated hypersensitivity (Johansson et al., 2001; Jackson, 2003; Zarkadas et al., 1999).
Figure II-1. Adverse Reactions to Foods
B. Mechanism of Allergic Reaction
An allergic reaction stems from an abnormal, or exaggerated, immune system response to specific antigens, which in foods are proteins (Sampson, 1999). This immune response occurs in two phases, an initial “sensitization” to an allergen and the “elicitation” of an allergic reaction on subsequent exposure to the same allergen. Sensitization occurs when a susceptible individual produces IgE antibodies against specific proteins in a food. Upon re-exposure to the same food, the allergenic proteins bind to IgE molecules on immune mediator cells (basophiles and mast cells), leading to activation of these mediator cells. This elicitation causes the release of inflammatory molecules (e.g., leukotrienes and histamine). The specific effects that are seen and the severity of an allergic reaction are affected by the concentration and type of allergen, route of exposure, and the organ systems involved (e.g., skin, GI tract, respiratory tract, and blood) (Taylor and Hefle, 2001).
Figure II-2. Mechanism of Allergic Reactions
C. Range of Adverse Effects
The clinical manifestations of food allergic reactions range from mild irritation to severe, life-threatening respiratory distress and shock. Specific signs and symptoms may involve the skin (e.g., pruritis, erythema, urticaria, angiodemia, eczema), eyes (e.g., conjunctivitis, periorbital swelling), nose (e.g., rhinitis, sneezing), oral cavity (e.g., swelling and itching of lips, tongue, or palate), or gastrointestinal tract (e.g., reflux, colic, abdominal pain, nausea, vomiting, diarrhea). In more severe reactions, involvement of the respiratory tract (e.g., cough, asthma, difficulty breathing, swelling around the larynx and vocal cords) and cardiovascular system (e.g., faintness, hypotension) can lead to loss of consciousness, asphyxiation, shock, or death. The term “anaphylaxis” is used to describe multisystemic severe reactions to an allergen requiring immediate medical intervention (Jackson, 2003).
Table II-1 provides a summary of the signs and symptoms that may be experienced during an allergic reaction. Allergic reactions usually occur within a few minutes to hours after ingestion of an offending food and often progress on a continuum from mild to severe, with higher doses causing more severe reactions (Sampson et al., 2005). Once exposure occurs, individuals may experience immediate numbness or pruritis at the site of contact or experience general uneasiness. These symptoms are characterized as “subjective” since they cannot be observed by others. As the effects progress, “objective” signs such as flushed skin, hives, or swelling of the lips and face may occur. These signs are often mild and short-lived. However, in some cases, they may be associated with more severe responses involving the respiratory and/or cardiovascular systems. Such responses can lead to hospitalization or death, even with appropriate medical intervention. Not all severe, or anaphylactic, reactions are necessarily preceded by milder signs and not all reactions are immediate. In some cases, anaphylactic reactions may be delayed by a few hours after the initial response (Sampson et al., 2005).
Anaphylaxis is a poorly defined condition representing a severe or multisystemic allergic reaction (Sampson et al., 2005). Allergic reactions described by objective signs involving the respiratory or cardiovascular systems would be considered severe and managed as an anaphylactic reaction by most clinicians. In some classifications, reactions involving two or more of the categories shown in Table II-1 (e.g., cutaneous, gastrointestinal, respiratory), would also be classified as anaphylaxis, if they are relatively mild. Anaphylactic “shock” denotes a consequence of anaphylaxis where heart irregularities and leakage of blood vessels leads to extreme blood volume loss (usually greater than 25% of resting blood volume) and extreme hypotension.
Table II-1. Signs and Symptoms of Allergic Reactions to Food Subjective Symptoms Objective Signs CUTANEOUS Skin Pruritus (Itching) Skin flushing or erythema (redness)
Pilor erection (“goosebumps”)
Rash: Urticaria (hives) – acute
Eczema (usually delayed, >6 hours)
Angioedema (swelling, especially face) Oral cavity (lips, tongue, palate) Pruritus (Itching), numbness, dryness Edema (swelling, may also include the uvula) Eyes, conjunctiva Pruritus (Itching) Periorbital (around eyes) edema, redness of conjunctiva and tearing GASTROINTESTINAL Nausea, pain (except infants/young child) Vomiting, diarrhea, abdominal pain (infants) RESPIRATORY Nose Pruritus (Itching) Nasal congestion or runniness, sneezing Larynx, throat Pruritus (Itching), dryness/tightness Swelling around the larynx and vocal cord, voice hoarseness, stridor (inspiratory wheeze), cough Lungs Shortness of breath, chest pain/tightness Respiratory distress (i.e., ? breathing rate, difficulty catching breath, ? peak expiratory flow measurement), cough, wheezing HEART and CARDIOVASCULAR Chest pain/ tightness, feeling of faintness, dizziness Syncope (fainting, loss of consciousness), hypotension (low) or shock (very low blood pressure), dysrhythmia (abnormal heart rhythm) OTHER “Sense of impending doom” Uterine contractions (women) The severity of an allergic reaction is affected by several factors that include genetic predisposition (atopy), age, type of food allergen, nature of any food processing, environment, and physiological conditions (Taylor and Hefle, 2001; Sampson, 2003; Maleki, 2004). For example, exercise, medications (e.g., non-steroidal anti-inflammatories), alcohol consumption, and asthma may enhance the severity of an allergic reaction (Sampson, 2005). Most severe and fatal allergic reactions to foods have occurred in adolescents and teens whom were highly atopic and had a history of asthma (Sampson, 2003; Pumphrey, 2004).
It is generally assumed that a history of previous serious allergic reaction(s) indicates an increased risk of future severe reaction(s). However, a history of mild reactions does not preclude the possibility of a future severe reaction. For example, Sicherer et al. (1998) observed that mild reactions to peanut in childhood tend to become more severe and unpredictable in later childhood and adulthood. This may be due to the fact that these children tend to develop asthma later in life (Sampson, 2005). Also, a recent review of anaphylactic fatalities in the United Kingdom showed that in 85% of fatal food reactions the patient had previously experienced a non-severe reaction (Pumphrey, 2004). Pumphrey (2004) stated that the severity of previous reactions is not a risk factor for fatal reactions in nut allergic patients. These data imply that any individual with a clinical history of IgE-specific food allergy may be predisposed to anaphylaxis or severe reaction.
Information on the prevalence of food allergies in the U.S. suggests that up to 6% of children and 4% of the total population have IgE-mediated food allergies (Sampson, 1997; Sampson, 2004; Sicherer et al., 2003; Sicherer et al., 2004). The estimated prevalence in the U.S. population of allergies to each of the food allergens identified by the FALCPA is given in Table II-2. Severe food-related allergic reactions result in an estimated 30,000 emergency room visits, 2,000 hospitalizations, and 150 deaths per year (Sampson, 2004). Clinical data and surveys indicate that the prevalence of allergy, including food allergy, has been rising in recent years, though there are limited historical data to compare to more recent estimates (Sicherer et al., 2003; Grundy et al., 2002). Peanut allergy has received the most attention in the U.S., and data indicate an apparent doubling of peanut allergy in children under 5 years old from 1997 to 2002 (Sicherer et al., 2003). An increase in peanut allergy has also been seen in the United Kingdom (Ewan, 1996; Grundy et al., 2002). Peanuts and tree nuts are the most common cause for fatal reactions in the US, although seafood allergy is increasingly being recognized in adults (Yunginger et al., 1988; Sampson et al., 1992b; Bocket al., 2001, Sicherer et al., 2004, Ross et al., 2006).
Table II-2. Allergy Prevalence in the United States Age Group Percentage of the Population All Allergens Milk Egg Peanut Tree nuts Fish Shellfisha Wheat Soy Children 6.0 2.5 1.3 0.8 0.2 0.1 0.0 UNKb 0.2 Adults 3.7 0.3 0.2 0.6 0.5 0.4 2.0 UNKb UNKb aShellfish includes both crustaceans and mollusks. bUNK = unknown.
Sources: Cordle, 2004; Sampson, 1997; Sampson, 2004; Sampson, 2005; Sicherer et al., 2003; Sicherer et al., 2004.
E. Allergenic Foods of Concern
1. Whole foods
The FALCPA identifies eight major foods or food groups: milk, eggs, fish (e.g., bass, flounder, cod), crustacean shellfish (e.g., shrimp, crab, lobster), tree nuts (e.g., almonds, walnuts, pecans), peanuts, wheat, and soybeans. These eight foods are believed to account for 90 percent of food allergies and most serious reactions to foods (FALCPA section 202(2)(A); Bousquet et al., 1998; Hefle et al., 1996). More than 160 other foods are known to cause food allergies; however, these allergies are relatively rare with prevalence rates ranging from a few percent of the allergic population to single cases (Hefle et al., 1996). Each of the eight major food allergens contains multiple allergenic proteins, many of which have not been fully characterized (Gendel, 1998).
2. Food Ingredients
Some food ingredients such as edible oils, hydrolyzed proteins, lecithin, gelatin, starch, lactose, flavors, and incidental additives (e.g., processing aids), may be derived from major food allergens (Taylor and Hefle, 2001). The role that these ingredients play in food allergy has not been fully characterized. For example, lecithin is a common food ingredient which is often derived from soybeans. It is possible that soy lecithin, which contains residual protein, could elicit an allergic reaction in sensitive individuals (Muller et al., 1998; Gu et al., 2001). Another example is protein hydrolysate, which is often made from major food allergens such as soybeans, wheat, peanuts, or milk protein. Partially hydrolyzed protein ingredients can elicit allergic reaction. For example, hot dogs formulated with partially hydrolyzed casein have elicited allergic reactions in children allergic to cow’s milk (Gern, et al., 1991; Kocabas and Sekerel, 2003). Allergic reactions to partially hydrolyzed protein ingredients are more common than are reactions to extensively hydrolyzed protein ingredients (Bock and Atkins, 1989; Elliset al., 1991; Saylor and Bahna, 1991; Kelso and Sampson, 1993; Niggemann et al., 1999).
Gelatins are ingredients derived from animals (e.g., cows, pigs) but also from the skin of various species of fish. A study of 10 fish allergic patients and 15 atopic individuals with eczema revealed that 3 and 5 individuals respectively had specific IgE to fish gelatin, suggesting the presence of allergenic protein (Sakaguchi et al., 2000). However, in a recent double-blind placebo-controlled food challenge (DBPCFC) study, all 30 fish allergic subjects in the study showed no response to a cumulative dose of 3.61 g of fish gelatin (Hansen et al., 2004).
Edible oils can be derived from major food allergens such as soybeans and peanuts, and they may contain variable levels of protein (Taylor and Hefle, 2001). The consumption of highly refined oils derived from major food allergens by allergic individuals does not appear to be associated with allergic reactions. For example, Taylor et al. (1981) and Bush et al. (1985) did not observe any reactions to refined peanut or soy oils in 10 and 7 allergic patients, respectively. On the other hand, unrefined or cold-pressed oils that contain higher levels of protein residues (Taylor and Hefle, 2001) may cause allergic reactions. For example, Hourihane et al. (1997b) reported that 6 of 60 peanut allergic individuals reacted to crude peanut oil but none responded to refined peanut oil. Similarly, Kull et al. (1999) reported that 15 of 41 peanut allergic children responded positively to crude peanut oil in skin prick tests, but none responded to refined peanut oil. The actual protein levels reported in various edible oils varies, probably due to differences in the oil, refining process, and the protein detection analytical method used. Crevel et al. (2000) reported that crude peanut and sunflower oils contained 100 to 300 µg/ml of protein, but that the most highly refined oils contained 0.2 to 2.2 µg/ml of protein. Intermediate protein concentrations were seen for partially processed oils. Teuber et al. (1997) showed that the amount of protein in both crude and refined gourmet nut oils varied both by type of oil and degree of processing; the reported values ranged from 10 to 60 µg/ml for various unrefined oils and from 3 to 6 µg/ml for the refined oils. Other investigators reported undetectable levels of proteins in refined edible oils (Hoffman et al., 1994; Yeung and Collins, 1996; Peeters et al., 2004) using assays with detection sensitivities of <0.3 ng/ml (Peeters et al., 2004) and 0.4 mg/kg (Yeung and Collins, 1996).
Starch, which is a widely used ingredient, is often derived from corn which is not a major food allergen. However, starch can also be derived from wheat, and may contain trace levels of wheat protein. For example, Lietze (1969) reported the presence of antibodies to wheat starch in several wheat sensitive individuals. However, the allergenicity of wheat starch for sensitive individuals has not been clinically evaluated (Taylor and Hefle, 2001).
A wide variety of flavoring substances are used in foods, but only a few are derived from known allergens (Taylor and Dormedy, 1998). As such, IgE-mediated allergic reactions to flavorings are rare, although a few cases have been documented involving hydrolyzed proteins. For example, several milk allergic individuals reacted to either hot dogs or bologna containing partially hydrolyzed casein as part of the natural flavoring used in the formulation of these products (Gern et al., 1991). Two other milk-allergic individuals reacted to milk protein in the natural flavoring used in a dill pickle-flavored potato chip (St. Vincent and Watson, 1994). The presence of peanut flour in the natural flavoring of a packaged soup elicited a reaction in a peanut-allergic individual (McKenna and Klontz, 1997).
Allergens, or proteins derived from allergenic foods, may be present in foods as the result of cross-contact during processing and handling. The term “cross-contact” describes the inadvertent introduction of an allergen into a product that would not intentionally contain that allergen as an ingredient. Cross-contact may occur when a residue or other trace amount of a food allergen is present on food contact surfaces, production machinery, or is air-borne, and unintentionally becomes incorporated into a product not intended to contain, and not labeled as containing, the allergen. Cross-contact may also result when multiple foods are produced in the same facility or on the same processing line, through the misuse of rework, as the result of ineffective cleaning, or may result from customary methods of growing and harvesting crops, as well as from the use of shared storage, transportation, or production equipment. Cross-contact of foods with allergens has been shown to lead to allergic reactions in consumers on numerous occasions (Gern et al., 1991; Jones et al., 1992; Yunginger et al., 1983). Much cross-contact can be avoided by controlling the production environment.
F. Measuring Thresholds
1. Design of Food Challenge Studies
A history of clinical reaction to a food and a positive skin prick test or the presence of food-specific IgE antibodies in serum are sufficient to establish that an individual has an allergy to that food. However, none of these reliably predicts the level of patient sensitivity to low doses of the food. At present, the level of individual sensitivity can only be determined using food challenge studies (including open, single-blind, and double-blind, placebo-controlled food challenges). The double-blind, placebo-controlled food challenge (DBPCFC) is the “gold standard” diagnostic measure for determining clinical reactivity to low concentrations of an allergen. In this type of study, neither the subject nor the researcher knows which test foods contain the allergen. Open (where both the subject and the researcher know which test foods contain the allergen) and single-blinded (where only the researcher knows which foods contain the allergen) challenges are used primarily for screening foods of low allergenic importance or for determining tolerance to food allergens. Single-blinded challenges can be placebo-controlled (SBPC). However, in open and SBPC challenges, experimenter bias may play a role in interpreting patient reactions.
The typical diagnostic food challenge protocol is a dose escalation study, usually with 15 to 30 minute dose intervals, which proceeds until a clinical effect is observed or the final dose is achieved. The test substance, starting dose and successive incremental doses vary between protocols. Because reactions are assumed to be less severe at lower doses, the starting dose for most diagnostic studies is generally in the milligram range for whole foods (Bindslev-Jensen et al., 2004). In the few studies designed to determine minimal eliciting doses, the initial doses are in the low microgram range for the whole food or whole food protein (Hourihane et al. 1997; Wensing et al. 2002a; Wensing et al. 2002b). Incremental doses are usually doubled or increased logarithmically, so that a reasonable number of incremental doses (i.e., 6 to 10) separate the starting dose from the end dose. This final dose is usually chosen to be the normal amount in a food serving, usually 8 to 10 gm of dried food or 60 to 100 gm of wet food (Bock et al., 1988; Bindslev-Jensen et al., 2004). The ability to tolerate this amount, followed by a negative open challenge on a different day, is considered to be evidence that the individual is not allergic to that allergen (Taylor et al., 2004).
Most oral challenge studies are designed to establish a diagnosis of food allergy rather than to determine safety (Taylor et al., 2004). Consequently, these studies do not start at doses below a known LOAEL. Thus, individuals who react to the starting dose are not necessarily demonstrating a true LOAEL because it is not possible to know whether these individuals would have reacted to a lower dose without further testing. A NOAEL cannot be established as long as one or more study participants react to the starting dose.
Most elicited reactions occur within 3 to 15 minutes after a challenge (Bindslev-Jensen et al., 2004). Thus, an interval of 15 minutes between challenge doses may be sufficient to confirm a negative response. Most challenge studies report the dose that elicits the first objective sign. Because subjective symptoms may have preceded the first objective sign at lower doses, it is often difficult to ascertain whether the reported LOAEL truly represents the lowest dose to elicit a reaction. The measurement and interpretation of allergic reactions is discussed below.
2. Inclusion/Exclusion of Sensitive Populations
Individuals with a history of anaphylaxis to foods, infants and children are often excluded from challenge studies for ethical reasons (Taylor et al., 2002). Moreover, individuals with very high food allergen IgE serum titers are often excluded. Thus, food challenge studies may not include subpopulations of those allergic individuals who may be the most sensitive to allergen exposure.
Individuals with allergies to a specific food have different genetic backgrounds and express a wide distribution of sensitivity and reactivity. Studies have shown that there may be a range of as much as one-million-fold (106) in eliciting doses from the least sensitive to the most sensitive individuals (Leung et al., 2003; Wensing et al., 2002b; Bindslev-Jensen et al., 2002). Moreover, sensitivity and reactivity may change with age for individuals within a population. For example, unpublished challenge data described in Moneret-Vautrin and Kanny (2004) show that 83% of wheat allergic children reacted to less than 2 g of wheat flour compared to 18% of wheat allergic adults. Therefore, the inclusion or exclusion of data for highly sensitive individuals can greatly affect the NOAEL determination for the population. To add to this uncertainty, the most sensitive individuals also may have more severe reactions (Wensing et al., 2002b; Perry et al., 2004). The thresholds measured for populations that exclude these individuals may not apply to those with severe allergic disease.
3. Testing Materials
Food challenges vary in the type of testing material used (e.g., peanut flour versus ground peanut), oral challenge vehicle (e.g., whole food versus capsules), and in the efficacy of blinding. Differences in these variables could modify the distribution or concentration of allergen within the test material, affect digestibility and absorption, influence false-positive subjective reactions, and therefore, affect interpretation of the dose-response data.
The nature of the testing material is very important, as this can enhance or diminish the overall immunogenicity of the native allergen (Beyer et al., 2001; Maleki et al., 2003). The matrix used (e.g., fatty substances) can delay absorption, thus affecting the time interval to a reaction, or may affect the intrinsic allergenic properties of the food. Also, gustatory differences in the challenge doses (because of the food matrix used) may influence subjective reactions due to poor taste or fear of consuming the allergen. The use of capsules eliminates problems caused by taste, but bypasses the oral cavity. Because the oral cavity plays an important role in the initial contact and metabolism of food allergens, this may affect the subsequent severity or character of response to the challenge dose.
4. Subjective Versus Objective Reactions
There are two types of physiologic reactions or effects that can occur during a food challenge – subjective symptoms, those reported by the subject, and objective signs, those observed by the researcher. Because subjective symptoms may be the result of non-immunological mechanisms, elicitation of objective signs is believed to be the more reliable indicator of clinical reactivity to the food allergen (Taylor et al., 2004).
The signs of a severe allergic reaction are associated with life-threatening conditions, e.g., anaphylaxis. However, there is no consensus as to which of the less serious signs or symptoms should be considered adverse effects. For example, can eczema be seen as a “safer” reaction than angioedema? Unlike well-defined toxicity endpoints, reactions to allergenic food ingredients are part of a wide spectrum of severity that includes trivial injury, objective systemic reactions, anaphylaxis, and death. Further, allergic reactions may involve multiple organ systems. For example, in Scibilia et al. (2006) 62% of responses involved more than one organ system.
Subjective symptoms may be good indicators of a subsequent objective reaction, i.e., subjective symptoms may precede or signal objective signs in a dose-dependent manner (Moneret-Vautrin, 2004). However, most challenge studies base their LOAEL determinations on the first objective sign rather than a subjective symptom. For example, although the Hourihane et al. (1997a) study reported a threshold for peanut proteins in the milligram range, mild subjective reactions were noted in two individuals at doses of 100 µg of peanut protein. Other studies do not report specific types of reactions but rather characterize reactions as mild, moderate, or severe. For example, a retrospective review of 253 failed challenges at one clinic showed that the initial reaction was severe in 72 (28%) and moderate in 88 (33%) of the challenges (Perry et al., 2004). There is only one published study (Wensing et al., 2002b) that evaluated reproducible subjective symptoms.
Currently, there is no universally accepted endpoint or response that can be used to predict significant harm from an allergic reaction. Anaphylaxis, a clearly significant endpoint, is a syndrome which is poorly described and subject to variable interpretation (Sampson et al., 2005). Moreover, anaphylactic reactions are at one extreme of a continuum of severity. There are a number of additional factors (e.g., use of medicine, alcohol consumption, anxiety) that can significantly reduce or potentiate the impact of exposure to an allergen. Given this combination of factors, a particular dose could result in mild symptoms one day and life-threatening reactions the next.
5. Anecdotal Evidence
Although a great deal of attention has been focused on the use of challenge studies to determine threshold doses or reaction patterns for food allergens, anecdotal reports of individuals suffering life-threatening allergic reactions from minute exposures to food allergens suggests that there may not be a measurable allergen threshold level, especially for sensitive individuals. For example, literature reports have linked kissing (Hallett et al., 2002; Steensma, 2003; Eriksson et al., 2003) and exposure to airborne particles (Crespo et al., 1995; Casimiret al., 1997; Sackesen and Adalioglu, 2003) to allergic reactions. Although in many of these cases the amount of allergen exposure cannot be assessed, it is conceivable that the whole food exposure level needed to elicit a harmful reaction is extremely low. In this context, it should be noted that the statistical model developed by Bindslev-Jensen et al. (2002) suggested that concentrations as low as 700 ng for peanut and in the low microgram ranges for egg, soy flour, and cow’s milk may elicit a reaction in one in a million allergic individuals. Although this model also suggests that a majority of allergic individuals would likely tolerate food allergen concentrations in the milligram range, it supports the anecdotal evidence that very low concentrations of allergen may, at some low but finite probability, elicit harm in highly sensitive individuals.
1. Matrix Effects
Food allergens often occur as components of processed foods, and many allergic reactions occur following exposure to such allergens (Bock et al., 2001). Therefore, it is important to understand how the nature or composition of the food (i.e., the food matrix) affects the elicitation of a reaction.
Very little information exists on matrix effects for the majority of allergens. It has been reported that fat content can modify the reactions in a peanut DBPCFC (Grimshaw et al., 2003). Three of four subjects challenged with peanut flour in a matrix containing 31.5% fat reacted at a higher than expected dose, and had reactions that were more severe than expected, based on previous exposures to a standard recipe containing 22.9% fat. Upon rechallenge with the 22.9% recipe, their reactions returned to expected levels with respect to dose and severity. The cumulative dose of peanut protein required to elicit reactions was 12 to 31 times higher when using the higher fat recipe. The authors suggested that the peanut allergens in the higher fat recipe were not readily available to react with IgE on mast cells in the mouth. This was based on the observation that radioallergosorbent test (RAST) inhibition assays and enzyme linked immonosorbent assay (ELISA) detection tests showed that peanut allergens in the higher fat mixture were less available in vitro. In addition, these three patients all had histories of an initial oral challenge response. The lack of an oral early warning with a high-fat food may have caused these patients to consume more allergen prior to the onset of other symptoms. By the time digestion of the fat took place in the stomach and intestine, the total dose consumed was higher, resulting in a more severe reaction.
Grimshaw et al. (2003) further reported that the slopes of RAST-inhibition curves did not change for peanut allergens in high-fat versus low-fat mixtures, indicating that there was no change in antibody-binding properties. Thus, it appears that the antigenic properties of the peanut flour were not altered by the higher fat matrix, and that the changes in apparent threshold may have resulted from a combination of physiological and behavioral factors.
Kato et al. (2001) also observed a matrix effect with the major egg allergen ovomucoid. The ability of ovomucoid to bind IgE was reduced in a model pasta composed of durum wheat and egg white. This decrease was attributed to changes in antigenicity associated with formation of disulfide bonds between the ovomucoid and wheat gliadins.
2. Processing Effects
Numerous studies have described alterations in allergens as a result of processing or cooking. Various types of processing (e.g., heating, milling, fermentation) may alter the antigenic properties of allergens because these processes can affect the three-dimensional structure of proteins and thus the IgE binding epitopes. The type and extent of structural alterations may vary depending on the processing method. This is especially true for conformational epitopes because they are dependant on tertiary structure (Cooke and Sampson, 1997; Vilaet al., 2001). For many food allergens, processing effects are inherent in the data used to characterize thresholds because the test articles used in DBPCFCs are processed. For practical reasons, the test material must be concealed in some way for the study to be “blinded.” For example, the taste of peanut butter or peanut flour must be disguised in DBPCFCs for peanut allergies. Preparation of the test material typically involves cooking or processing of the allergenic food. In addition to altering existing epitopes, processing might also induce chemical or structural changes that result in the formation of new antigenic epitopes, or neoantigens (Maleki, 2004).
Altered antigenic reactivity is most commonly assessed by measuring changes in the binding of antibodies to extracts of raw and processed foods. Reduced or enhanced IgE binding in such studies would suggest that the threshold for an allergic reaction could be affected by processing. However, definitive proof of an altered threshold requires DBPCFC testing.
The effects of processing on some specific major allergens have recently been reviewed, and are discussed below (Besler et al., 2001; Poms and Anklam, 2004). Variable patient responses make it difficult to conclude that a particular processing or cooking procedure affects allergenicity in all cases.
Peanuts. Extracts of roasted peanuts have been shown to bind IgE from patients at 90-fold higher levels than do similar extracts of raw peanuts in competitive, IgE-based ELISAs (Malekiet al., 2000). Using immunoblot techniques, two of the major allergenic proteins in peanut, Ara h 1 and Ara h 2, were shown to be highly resistant to heat and gastrointestinal digestion following treatment in the Maillard Reaction (which occurs during the processing or browning of foods in the presence of heat and sugars). Earlier studies also observed increased IgE binding and altered IgE epitopes in roasted versus raw peanuts (Nordlee et al., 1981). The allergenic proteins Ara h 1, Ara h 2, and Ara h 3 from fried or boiled peanuts bound significantly less IgE than the same proteins from roasted peanuts (Beyer et al., 2001), even though there were similar amounts of the allergenic proteins in peanuts processed by each method. These studies suggest that thresholds for boiled or fried peanuts may be higher than for roasted or raw peanuts, at least for the three major peanut allergens. In practical terms, the vast majority of peanuts consumed whole or in processed foods in the U.S. are roasted. Boiled or fried peanuts are an ethnic or regional specialty and are usually eaten whole, rather than as a component of processed foods.
Milk. Pasteurization and homogenization did not reduce allergenicity in skin prick tests or DBPCFC (Host and Samuelsson, 1988). However, boiling milk for 10 minutes reduced IgE binding of the allergenic proteins alpha-lactoglobulin and casein by 50 to 66% and eliminated beta-lactoglobulin and serum albumin reactivity in skin prick tests (Besler et al., 2001; Norgaard et al., 1996). Hypoallergenic infant formulas produced from heat denatured or enzymatically hydrolyzed caseins or whey proteins showed reduced allergic reactivity by immunoblot, RAST, and DBPCFC in most milk-allergic children. However, some severe reactions have been reported (Sampson et al., 1991; Saylor and Bahna, 1991). Maillard reaction products in milk are reported to have increased allergenicity in skin tests (Maleki, 2004). Allergic reactions have also been reported involving both hard and soft cheeses (Besler et al., 2001).
Egg. Both soft and hard boiling of eggs decreased, but did not eliminate, antigen binding of rabbit antiserum to ovomucoid and ovalbumin (Besler et al., 2001). Heated egg white showed a 58% decrease in IgE binding in RAST (Anet et al., 1985). A decrease in positive reactions was seen with heated egg white in 55% of egg allergic patients using DBPCFC (Urisu et al., 1997). There are reports of allergic reaction to egg contained in cooked meatballs or hamburger (Sampson et al., 1992b; Besler et al., 2001).
Fish. Boiling ten species of fish failed to eliminate allergenicity in DBPCFC (Bernhisel-Bradbentet al., 1992b). IgE binding to fish proteins in immunoblots was reduced, but not eliminated. Canning (presumably due to the heat processing) appears to reduce allergic reactions to tuna and salmon in allergic patients tested by DBPCFC (Bernhisel-Broadbent et al., 1992b). IgE binding of allergenic proteins from canned fish was reduced by 98 to 99% compared to boiled fish. IgE binding studies indicate that fish allergens are present in surimi (Mata et al, 1994).
Shellfish. Boiling does not reduce the allergenicity of shrimp allergens (Daul et al., 1988; Naqpal et al., 1989).
Soy. Heating soybeans at 100°C for 60 minutes does not completely eliminate IgE binding to allergenic soy proteins (Burks et al., 1992). Various soybean products including sprouts, soy sauce, hydrolyzed soy protein tofu, miso, and lecithin all retained IgE-binding activity (Besleret al., 2001). IgE binding proteins have been found in soy lecithin (Gu et al., 2001; Porras et al., 1985; Paschke et al., 2001). Allergic reactions to soy lecithin have also been reported (Renaud, 1996; Palm, 1999). The protein content of soy lecithin has been reported to vary between 2.8-202 mg per 100 g (Besler et al., 2001; Paschke et al., 2001). IgE binding proteins have been consistently detected in unrefined soybean oils (Paschke et. al., 2001), but inconsistently in refined oil (Awazuhara et al., 1998; Paschke et al., Errahali et al., 2002)
Tree nuts. Protein extracts of several hazelnut-containing products demonstrated less IgE binding than raw hazelnut aqueous extracts suggesting that heating reduced allergenicity. However, some IgE binding capacity remained (Wigotzki et al., 2001). Several cases of anaphylaxis have been described for a variety of processed nut-containing products, suggesting that tree nuts in general retain allergenic activity after heating (Besler et al., 2001).Roasting, blanching, autoclaving, or microwaving did not change the ability of animal antisera to bind almond proteins (Venkatachalam et al., 2002).
Wheat. Baking of wheat flour-containing foods results in the loss of IgE binding to one group of recognized wheat allergens, the alpha-amylase inhibitors. However, baking does not affect the ability of wheat prolamins to bind IgE from wheat allergic individuals (Simonato et al. 2001). The wheat allergen omega-5 gliadin also retains allergenic activity after cooking. For example, Daengsuwan et al. (2005) found IgE to omega-5 gliadin in seven children who had anaphylactic reactions to breads, buns, noodles, macaroni and pizza.
3. Detecting and Measuring Allergens
There are several factors that make it difficult to detect and measure food allergens. These include sampling problems and difficulties in quantifying proteins, particularly allergenic proteins, in a wide variety of foods. Further, an allergen may be a minor component of a highly complex, heterogeneous food. The food matrix can sequester allergens, hindering detection, while not significantly affecting allergenicity. It is also difficult to estimate the amount of a food allergen that may be present from the result of an assay that only measures protein, particularly when there is more than one allergenic protein.
The only commercial methods that have been shown to detect food allergens reliably use immunological techniques such as ELISA (Poms et al., 2004; Krska et al., 2003), although non-commercial PCR assays have been described (e.g., Popping et al., 2004). In some cases, these methods were designed to detect representative biomarkers, not necessarily a specific allergenic protein. Many kits contain polyclonal antibodies that detect both non-allergenic and allergenic proteins (e.g., Nogueira et al., 2004). For example, the peanut ELISA assays that have completed Multiple Laboratory Performance Tested validation are designed to detect multiple proteins indicative of the presence of the food (e.g., peanuts), not to detect or quantify specific allergenic proteins (Park et al., 2005). There are no validated detection methods or commercially available kits for most food allergens or allergenic proteins.
The FDA and AOAC investigated the ability of three commercial peanut test kits [BioKits Peanut Testing Kit (Tepnel), Veratox for Peanut Allergens (Neogen Corp.), and RiDASCREEN Peanut (R-Biopharm GmbH)] to accurately measure peanuts in four food matrices (cookies, ice cream, milk chocolate, and breakfast cereal) (Park et al., 2005). The validation study, requiring 60 analyses of test samples at the target level of 5µg peanut/g of food and 60 analyses of “peanut-free” controls, was designed to ensure that the lower 95% confidence limit on the true sensitivity and specificity rates exceeded 90% (Park et al., 2005). The results from this study showed that all the test kits correctly allocated the test samples at the target level. No comparable studies have been completed for any other food allergen.
Scientific practice is to calibrate, standardize, and validate assays and commercial test kits for each food product because minor differences in the matrix change the recovery and detection of specific food proteins. Standardization requires the preparation of samples identical to the test sample and containing known amounts of a specific food allergen. Nevertheless, because different antibody-based assays recognize different protein epitopes, variable results may be obtained using different test systems. This variability was evident in results obtained in the Food Analysis Performance Assessment Scheme (FAPAS(r)) supervised proficiency studies of wheat (Central Science Laboratory, 2003a; Central Science Laboratory, 2004b), peanut (Central Science Laboratory, 2003b), egg (Central Science Laboratory, 2004a), and milk test kits (Central Science Laboratory, 2004a).
Highly variable food matrices and the nature of food production also create sampling challenges. The distribution of allergenic proteins within whole foods is not necessarily homogenous, and allergenic ingredients may not be evenly distributed throughout processed foods. In addition, cross-contact may result in a heterogeneous distribution of allergens within or on a food. For example, nuts may be introduced into chocolate on a production line where nut-containing and nut-free products are processed sequentially. In this case, cross-contact is most likely to occur at the beginning of a production run for the nut-free product. Thus, allergen testing using chocolate taken from the end of a production run might not adequately characterize the risk.
For a food product, development of a scientifically sound sampling plan that includes a statistical analysis of the probability that any allergens present are detected and measured accurately. Important sampling questions that need to be considered include whether the allergen is likely to be heterogeneously distributed within the batch; the number of samples per batch that should be tested; which batches should be tested; which portion of a run should be tested; and how to obtain a specific degree of confidence (e.g., 95% confidence) that no allergen is present.
H. Collective Allergens
Three of the major food allergens identified in the FALCPA are actually groups of foods: crustaceans, fish, and tree nuts. It is possible that proteins from two or more species within each of these “collective allergens” might be present in a food and the available analytical methods are unable to distinguish between species in a group. Therefore, it may be necessary to consider total protein levels from all species in a group rather than the level of protein from each species. In addition, an individual allergic to one species is likely to also be allergic to other species in the group.
The ability of available test methods to distinguish different species within each group of “collective allergens” varies. To date, there are no commercially available test kits for finfish proteins and only one for crustacean tropomyosin. Ben Rejeb et al. (2003) reported the development of an ELISA for shrimp that showed significant cross-reactivity with other crustaceans. There are three commercially available tree nut test kits (two for hazel nut, one for almond), but the species specificity of these kits is not clear. Hlywka et al. (2000) showed that an almond ELISA detected protein from seven other tree nuts. The hazel nut ELISA developed by Holzhauser et al. (2002) showed cross-reactivity with other nuts, and the walnut assay developed by Niemann and Hefle (2003) reacted with three other nut species. Wei et al. (2003) developed an ELISA for cashew that showed cross-reactivity with several other nuts. Ben Rejeb et al. (2003) developed a hazel nut-specific ELISA that did not cross-react with other nuts, and Clemente et al. (2004) developed a Brazil nut assay with “negligible” cross reactivity to five other nut species.
Although not likely to be useful for routine screening or testing, techniques such as liquid chromatography/mass spectrometry (LC/MS) are being used to identify specific allergenic proteins in complex food matrices (Shefcheck and Musser, 2004). These approaches may be useful either as confirmatory tests or for characterization of foods containing several allergens.
Crustacean Shellfish. Allergenic cross-reactivity among crustaceans is considered to be common. Sicherer (2001) estimated that there is a 75% probability that a shrimp-allergic individual will also react to at least one other crustacean. Waring et al. (1985) reported that 11 of 12 (92%) patients with skin prick reactions to shrimp also had positive skin prick reactions to at least one other crustacean. Similarly, Daul et al. (1987) showed that between 73 and 82% of shrimp allergic patients had positive skin prick tests to another crustacean. Chiou et al. (2003) showed that sera from 20 of 32 individuals with either shrimp- or crab-reactive IgE were reactive to both species. Further, inhibition studies with 15 of these cross-reactive sera showed relatively high affinity for both allergens. The basis for this high rate of cross-reactivity appears to be sensitivity to the highly conserved protein tropomyosin, which is considered to be a panallergen (Daul et al., 1993; Leung et al., 1999; Sicherer, 2001).
Fish. Allergenic cross-reactivity among fish species has been described in the clinical literature, but appears to be less common than among species of crustacea. Both Sicherer (2001) and Sampson (1999) estimate that there is a 50% probability that an individual allergic to one fish species will react to at least one other fish species. Helbling et al. (1999) reported that 4 of 14 (29%) fish allergic patients reacted to two or more species in DBPCFC tests. Bernhisel-Broadbent et al. (1992a) reported that 3 of 10 (30%) fish allergic patients responded to more than one fish species in oral challenges, but that skin prick tests were positive to multiple species for all of these patients. Similarly, Hansen et al. (1997) showed that eight cod allergic patients all had positive skin prick tests with two other fish species. The data presented in Pascual et al. (1992) suggest that at least 80% of a group of 79 fish allergic children had IgE antibodies to two or more fish species. In some cases, cross-reactivity has been shown to reflect the presence of one of more closely related allergenic proteins (e.g., paralbumins) in different species (Pascual, 1992; Hansen et al., 1997; Leunget al., 1999; Hamada et al., 2003).
Tree Nuts. The prevalence of cross-reactivity among tree nuts is difficult to determine accurately for several reasons: the high proportion of severe reactions among nut-allergic patients makes it dangerous to carry out oral challenge studies, many published works test for reactivity to a small number (and variable assortment) of tree nuts, and studies often combine tests for tree nuts and peanuts. Nevertheless, Sicherer (2001) estimates that a tree nut allergic patient has a 37% chance of being allergic to two or more species of tree nut, and Sampson (1999) estimates that the probability of multiple tree nut sensitivities at greater than 50%. Ewan (1996) reported that 12 of 22 (55%) of tree nut allergic patients responded to multiple tree nuts by skin prick tests. Sicherer et al. (1998) and Pumphrey et al. (1999) both used in vitro IgE testing and found multiple sensitivities in 37% and 61% of tree nut allergic patients, respectively. There are a number of studies that report cross-reactions in one or a few patients (e.g., Teuber and Peterson, 1999; Ibanez et al., 2003; de Leon et al., 2003; Asero et al., 2004). The complex pattern of cross-reactivity among the tree nuts may reflect the fact that several different panallergens (lipid transfer proteins, profilins, Bet v1-related proteins) and evolutionarily conserved proteins (seed storage proteins) occur in various tree nuts (Roux et al., 2003).
I. Published Challenge Studies
An extensive literature review was conducted from November 2004 through April 2005 that included key word, author, and “related article” searches of the PubMed database and analysis of citations found in the published literature. Seventeen publications with quantitative dose-response data from DBPCFC testing were reviewed to identify those that contained data that could be used to estimate LOAEL levels for the major food allergens. These studies are described in more detail in Appendix 2. Fourteen (82%) of these report results from testing adults; the remaining three tested infants and children. In four cases, the population being studied was not specifically chosen to be food allergic, and a large fraction of the individuals in these populations did not respond to the highest doses tested. In eight studies (47%), patients reacted to the lowest dose tested, and in three studies there was insufficient information to determine either the lowest dose used or the number of patients who responded to that dose. The most sensitive population was seen by Hourihaneet al. (1997b), who reported that 67% of the patients tested reacted to “peanut rubbed on the lip,” including one severe reaction.
Peanut. Hourihane et al. (1997b) observed the lowest measured dose of an allergen that provoked a reaction (i.e., a LOAEL), 0.1 mg of peanut protein provoked subjective reactions in two patients and 2 mg of peanut protein provoked an objective reaction in one patient. Objective reactions were observed in two other patients on exposure to 5 mg of peanut protein. Wensing et al. (2002a) also reported a LOAEL of 0.1mg for subjective reactions in two of 26 peanut allergic individuals tested. The LOAEL for the initial objective symptom was 10 mg. Several other papers reported LOAELs of 25-100 mg of peanut protein for objective reactions (May, 1976; Hourihane et al., 1997a; Bock et al., 1978).
Egg. A wide range of LOAELs have been observed for egg. Caffarelli et al. (1995) reported a LOAEL of 0.5 mg of dried whole egg (approximately 0.42 mg protein). Bock et al. (1978) reported observing an objective reaction with 25 mg of whole egg (approximately 1 mg protein), although the data are difficult to interpret as presented. In contrast, Eggesbo et al. (2001) report a LOAEL of 1 g of whole egg (approximately 260 mg of protein) for an objective reaction.
Milk. Relatively consistent LOAELs have been reported for milk. Bellioni-Businco et al. (1999) found a LOAEL of 1 ml of whole milk (approximately 362 mg of protein) with children, and Pastorello et al. (1989) found a LOAEL of 0.5 g of freeze-dried milk (approximately 187 mg of protein) with adults.
Soy. LOAELs of approximately 522 and 88 mg protein have been reported for soy (Zeiger et al., 1999; Magnolfi et al., 1996).
Tree Nut. Hazel nut is the most commonly studied tree nut. Wensing et al. (2002b) observed reactions to 1 mg of hazel nut protein in 4 of 29 patients, which was the lowest dose tested. Hansen et al. (2003) found a LOAEL of approximately 32 mg of hazel nut protein, although it is not clear whether this was the lowest dose tested.
Fish. Hebling et al. (1999) reported a LOAEL of 50 mg for catfish protein.
Wheat. Unpublished data described in Moneret-Vautrin and Kanny (2004) show that 83% of wheat allergic children reacted to less than 2 g of wheat flour while only 18% of wheat allergic adults responded at this level. Unpublished data described in Moneret-Vautrin (2004) on wheat flour challenges using 32 children and 32 adults with wheat allergy, reported a LOAEL of = 1.8 mg protein for allergic children (the lowest tested dose) and 52.8 mg protein for allergic adults. Scibilia et al. (2006) reported that 2 of 13 responders reacted to the lowest dose of wheat flour tested (100 mg of a mix of bread and durum flour, approximately 15 mg protein) in DBPCFCs. In total, 31% of the patients who reacted did so to challenge doses less than or equal to 240 mg of wheat protein.
J. Food Treatments to Reduce Allergenicity
The best example of food products that are processed to render them less allergenic are hydrolyzed infant formulas derived from cow’s milk proteins (i.e., casein and whey). Enzymatic hydrolysis of these proteins has been shown to significantly reduce the levels of both total and allergenic (e.g., b-lactoglobulin in whey) protein (Host and Halken, 2004). The degree of protein reduction depends on the method of hydrolysis. There is ample clinical evidence to suggest that both partially hydrolyzed formulas (PHF) and extensively hydrolyzed formulas (EHF) have reduced allergenicity in comparison to intact milk formulas (Amer. Acad. Ped., 2000; Host and Halken, 2004). Furthermore, there is preliminary evidence that the use of these hydrolyzed formulas may also delay or prevent the development of cow’s milk allergy (CMA) in high-risk infants (Host and Halken, 2004).
Both PHF and EHF contain varying amounts of residual protein, including allergenic proteins, which can be detected using either in vitro or in vivo methods (Giampietro et al., 2001; Docena et al., 2002), that have been shown to retain immunologic activity. Both PHF and EHF can cause allergic reactions, including anaphylaxis, in sensitive infants (Saylor and Bahna, 1991; Schwartz and Amonette, 1991; Tarim et al., 1994; Ammar et al., 1999; Giampietro et al., 2001; Host and Halken, 2004). In general, the higher the level of residual protein, the higher the risk for an allergic response. Although the level of residual protein tends to be higher in PHF, the degree of hydrolysis cannot always be used as a predictor of the degree of allergenicity. Hydrolysis methods are not standardized, and formulas undergoing similar treatments may vary considerably in their residual protein levels. Additional processing, such as heat treatment and ultrafiltration, may further reduce residual protein levels in certain products (Host and Halken, 2004).
In 1989, the American Academy of Pediatrics (AAP) concluded that a formula could be considered “hypoallergenic” if challenge studies showed, at a minimum, 95% confidence that 90% of allergic infants would not react adversely to the formula (AAP, 1989). Since this time, a number of DBPCFC studies using various infant formula preparations have been performed in infants with CMA (Sampson et al., 1991; Sampson et al., 1992b; Giampietro et al., 2001; Sicherer et al., 2001), and a substantial number of infant formulas (most EHF) have met this criterion for hypoallergenicity. Even though they note that EHF contain residual proteins and may provoke allergic reactions in infants with CMA, the AAP currently recommends these formulas as alternatives for infants with CMA stating that at least 90% of these infants will tolerate the formula (AAP, 2000).
Newer technologies, such as genetic modification, are being developed to reduce allergenicity by removing, silencing, or modifying the genes for specific allergenic proteins within foods (Tada et al., 1996; Herman et al., 2003; Dodo et al., 2005; Gilissen, 2005). To date, however, there is no example of a food allergen that has been rendered completely devoid of allergenic activity using these methods. This is due to the fact that each food contains a number of allergenic proteins, each with multiple allergenic epitopes. Unless these methods can eliminate all of these proteins, or modify all allergenic epitopes, the remaining proteins or epitopes could still elicit a reaction in sensitive individuals.
Page Last Updated: 11/25/2009
What is an allergy?
Viennese pediatrician Baron Clemens von Pirquet coined the term “allergy” (from the Greek “allos” meaning changed or altered state and “ergon” meaning reaction or reactivity) in 1906. Von Pirquet used the term to describe an altered reaction he had observed in patients, which he put down to the influence of external factors, an allergen, on the immune system.
Allergies are reactions of the immune system to specific substances called allergens (such as pollen, stings, drugs, or food) that, in most people, result in no symptoms. The most severe form of allergy is anaphylactic shock, which is a medical emergency.
What’s the difference between allergy and sensitivity, and intolerance?
Allergy: This term is used by the medical profession and allergy specialists to denote the body reactions involving the entire immune system, particularly the IgE (immuno-globulin, type E) immune reaction. These IgE antibodies can be measured by a blood or scratch test.
During an allergic process, the substance responsible for causing the allergy, or allergen, binds to allergic antibodies present on allergic cells in a person’s body, including mast cells and basophils. The mast cells and basophils then release inflammatory chemicals such as histamine and leukotrienes, resulting in allergic symptoms.
The allergic person can make allergic antibodies, or IgE antibodies, against a variety of allergens, including pollens, molds, animal danders, dust mites, foods, venoms and medications. This occurs through a process called sensitization, where a person’s immune system is exposed to enough of the allergen to make the body produce allergic antibodies to that substance. For example, food allergies are an immune system reaction in which undigested food particles are absorbed into the bloodstream and perceived as if they were foreign proteins. The body makes antibodies against the undigested food because the immune system views these proteins as unrecognizable and thus as a foreign invader. With later exposures, that same allergen binds to its corresponding IgE on allergic cells, and the body reacts with symptoms of allergies. Allergic symptoms can vary somewhat with the type of allergen and route of exposure (airborne pollen exposure may cause different symptoms than eating a food to which you are allergic).
Sensitivity: Similar to an allergy, but generally involves IgG antibodies instead of IgE antibodies. IgG antibodies are the slowly occurring variety, and do not appear in the blood until 24 to 72 hours after exposure to an offending food or substance. This will result in a delayed onset of symptoms. IgG antibodies can also be detected by a blood test.
Intolerance: Here, the problem is not with the body’s immune system, but, rather, with its metabolism.This term refers to a food intolerance, which is characterized by a missing enzyme that is needed to digest a particular food. Familiar examples include the enzyme lactase which is necessary to digest milk products, and the enzyme needed to digest beans. Both cause intestinal problems, mostly gas from the fermentation of the food instead of digestion.
NAET and BioSET view an allergy quite simply:
An allergy is anything that causes the body to react negatively. Reactions encompass a broad spectrum of symptoms, ranging from itchy eyes and a runny nose to eczema, fatigue, or digestive upset.
How do I know if I have allergies?
Allergic symptoms cover a wide range, depending on the individual and the particular allergen.
Hay fever, whether due to pollen, trees, grass, dust, weeds, or chemicals, has a detrimental effect on organs such as the throat, the nose, the larynx (voice box), the trachea, and the bronchioles. When allergens infiltrate the nose, hay fever symptoms occur. This can include symptoms such as congestion, sneezing, and nasal discharge. When allergies affects the throat, a patient can experience itching and scratchiness. When the larynx is affected by an allergy, hoarseness and voice loss can occur. Environmental allergies also affect the airways, resulting in asthma and bronchitis. Here is a partial list of allergic symptoms:
* Sneezing, often accompanied by a runny or clogged nose
* Coughing and postnasal drip
* Itching eyes, nose, and throat
* Allergic shiners (dark circles under the eyes)
* The “allergic salute”
* Watering eyes
* Post nasal drip
* Mental dullness and fatigue
* abdominal cramping, anaphylactic shock
* arthritic type symptoms, canker sores
* constipation, depression
* difficulty concentrating, difficulty sleeping
* emotional upset, eczema
* fatigue, hives
* heartburn, indigestion
* irritability, itching
* migraine headaches, nocturnal enuresis
* red rash around the mouth, reddening or swelling skin
* rhinitis, stiffness
* stomach ache, swelling of the joints
* swelling of the lips and face
* vomiting, wheezing
Meridian Energy and Allergy
According to the Chinese system of medicine, the Qi energy flows along specific pathways in the body, known as meridians. Sickness is viewed as a blockage of the energy flow along the meridians. If the energy flow can be restored to normal, good health will return. Needles inserted at specific points along the meridians can restore the energy flow to normal.
The body’s energy is not confined to the energy that flows through the meridians. Every cell in the body is a bundle of energy – ATP, electrical currents in the heart cells, and muscle fibers. Energy is involved in every process in our bodies, including the biochemical changes within our cells. In this sense, any disease or malfunction, including allergy, is really an energy disturbance. When allergy is present, it means that the flow of energy is blocked, disturbed, or unbalanced, and therefore that the biochemical processes are not proceeding properly.
NAET and BioSET are energetic procedures designed to restore balance in the body with respect to a particular allergen. By combining exposure to the allergen with a specialized balancing treatment protocol, the body’s energy is reprogrammed so that it no longer clashes with the allergen’s energy.
Imbalanced Health with Allergy Exposure
Balanced Health with Allergen Exposure
Energetic testing for allergies
The body’s meridian energy is connected to the muscles of the body. If you are exposed to the energy field of a substance to which you are allergic, it disturbs your energy flow. This energy disturbance is manifested in the form of a weakened muscle.
Muscle testing, or applied kinesiology, is one method to identify allergic substances that are interfering with the body’s energy flow. Unlike the traditional allergy testing methods, muscle testing does not require that we observe an actual allergic response. Rather, if a substance has the ability to weaken the muscle being tested, we deduce that that energy is being disturbed and that the person is sensitive to that substance. Thus, muscle testing can identify more subtle allergies and sensitivities whose effects are not directly or immediately observable.
Special computers, such as the Biomeridian, are capable of directly measuring these energy imbalances. The Biomeridian is an FDA approved device that is used to screen and desensitize allergies. The basic principle of the Biomeridian computer is the same as muscle testing, but the Biomeridian is capable of physically measuring the energetic stress or blockages associated with a sensitivity or allergic response. Computerized sensitivity screening takes muscle testing one step further, allowing the practitioner to quantitate the degree of sensitivity with a computerized readout. Computer software is used to register the conductance of an electrical charge at an acupuncture point.The process is simple and painless: an initial baseline scan is done on an acupuncture point on the surface of the skin. These acupuncture points are considered to be “information access windows”. Once baseline conductivity is established, frequencies of over 40,000 different potential foods, allergens, medications, and stressors can be output and the body’s response to each of these items can be measured. The response to different frequencies will affect the concentrations of the ions at the measurement points along the meridian. Inflammation may cause an increase ion concentration, and this increase of ions enhances the flow of electrons causing resistance to decrease while the conductance increases. Conversely, a weakened response may cause decease in ion concentration that hinders the flow of electrons, so as the resistance increases conductance decreases. A measurement of 50 is considered a balanced reading. Above 60 indicates an increased conductance of the body in response to a stressor, which is suggestive of an inflammatory process. Below 45 indicates decreased conductance, which signifies a more chronic weakness, or degeneration.
NAET: Nambudripad’s Allergy Elimination Technique
The NAET technique was developed in 1984 by Dr. Devi Nambudripad, who began teaching it to other health professionals in 1989. There are now about 5000 NAET practitioners worldwide.
Current distribution by medical specialization is roughly as follows: 15% medical doctors, 40% acupuncturists, 30% chiropractors and 15% others (homeopaths, dentists, osteopaths, physiotherapists, naturopaths, etc.).
An allergy is an adverse physical, physiological, and/or psychological response of an individual towards one or more substances also known as allergens. However, these substances may be harmless, well tolerated or even useful for most people. Dr. Nambudripad’s approach is the same for full-blown allergies involving the release of immunoglobulin type E (IgE-mediated reactions) in the body, and for intolerances, sensitivities and hypersensitivities (non-IgE mediated reactions). Her technique diagnoses and treats them all in the same way.
NAET believes that allergic reactions are determined by the way in which the brain perceives the substance in question. If the brain considers the substance a threat to the body, it will order the immune system to mobilize its defenses to fight the intruding substance. This manifests as an allergic reaction whose initial signs are aimed at chasing the intruder away. However, more often than not this perception is erroneous and our brain actually betrays us by triggering an inappropriate response, manifesting as allergic symptoms.
When a person consumes a food substance or inhales something the body believes is harmful, the immune system also mistakenly believes that the substance is harmful. In its attempt to protect the body, the immune system creates specific antibodies. The next time the individual eats that food or inhales the allergen, the immune system releases chemicals and histamines in order to protect the body. These chemicals trigger a cascade of allergic symptoms that can affect all the systems of the body such as the gastrointestinal tract, respiratory system, genitourinary system, skin, the mind, the nervous system, and the cardiovascular system. According to traditional medicine, the only way to treat allergies is to avoid the foods or substances that are triggering the reactions. NAET is a technique that reprograms the body to eliminate these allergic symptoms, effectively eliminating the need for lifelong avoidance.
Dr. Nambudripad discovered that if the roots of the sympathetic nervous system are given specific stimuli, the brain will receive messages that enable it to correct its faulty perception of the substance concerned (analogous to a computer “reset”). These new messages will be permanently imprinted in the brain after a number of other acupressure/acupuncture points have been stimulated, provided the patient follows certain precise rules for a specified time period after the treatment. This “reprogramming” constitutes the core part of the NAET methodology, and this theory has been extensively verified for more than fifteen years with highly satisfactory, long-lasting results. After the treatment, the incompatibly or clash of energies disappears completely and there is no trace of allergy, sensitivity or intolerance when the patient next comes into contact with the substance. This is because NAET treats the cause of the allergy, not the resulting symptoms.
NAET utilizes a combination of modalities to detect and desensitize patients from their allergies. NAET is an all natural and drug-free solution to eliminate allergies of all types and intensities by using a blend of testing and treatment procedures from acupuncture, allopathy, chiropractic, nutritional, and kinesiological disciplines of medicine. Applied kinesiology, or muscle response testing (MRT), is used to determine the allergic substance, or allergen, causing the allergic reaction. Computerized testing is now also available by equipped practitioners. Once the allergen has been determined, a chiropractic acupressure technique on the spine is used to desensitize the patient to the allergen. Acupuncture, acupressure, or cold laser is then given to keep the patient clear of their allergy. When NAET is done in the presence of a given allergen, an allergic reaction should not result upon future contact with that same substance. When this result is obtained, the patient is “clear”of his or her allergy to that substance.
BioSET: Bioenergetic Desensitization and Enzyme Therapy
BioSET builds upon the NAET protocol, using computerized bioresonance. Computer assisted technology has greatly improved the more permanent clearing of the sensitivities, and also quickened the process of the BioSET clearing of sensitivities.
As previously explained, each allergen or substance has a unique and specific resonant energy signal. An individual can react to that signal (via the various meridians of the human body) which is profiled on a computer with BioSET. The bioresonance device, in combination with the BioSET system, can recognize a resistance or dissonance and then reverse the resonant energy which directs or reprograms an allergen through the acupuncture meridians and nervous system which then becomes a permanent memory of the individual. This device is also thought to take the body’s own electro-magnetic signals, alter them and then feed them back into the body. Feeding this altered signal back into the body cancels out the pathological electronic information coming from viruses, bacteria, chemical toxins. food and environmental sensitivities. This causes the cells of the body to start pushing out and eliminating these disease-causing factors, and as the root causes of disease are removed from the body, healing can take place. Clinical symptoms are alleviated and tolerance to the specific allergen can be seen immediately. Re-testing on the computer or via kinesiological testing can verify this change. Many so-called permanent sensitivities can be reversed as well as many chronic health problems resolved with BioSET and the new bioresonance instrumentation.
Enzymes are easily recognized because they all end in “-ase”. There are three basic categories of enzymes: metabolic enzymes, digestive enzymes, and enzymes in raw foods. Metabolic enzymes run body processes, repair damage and decay, and heal disease, while digestive enzymes assimilate carbohydrates, proteins and fats into the body.
The human body makes approximately 22 digestive enzymes, capable of digesting protein,carbohydrates, sugars, and fats. The function of the enzyme, a specialized protein molecule, is to catalyze chemical reactions within the cells so that all physiological processes can occur.
There are four categories of plant enzymes that have uses in plant enzyme therapy: 1) protease-digests protein, 2) amylase-digests carbohydrates, 3) lipase-digests fat, 4) cellulase-digests fiber.
What is homeopathy and how does it relate to allergy elimination?
Instead of holding the actual allergen during an allergy treatment, you may be given a small homeopathic vial to hold. Homeopathics have energy too. The vial contains the energetic imprint of a particular allergen. Specialized computers may also be programmed to output homeopathic energies.
Homeopathics are made by taking a small amount of any substance, allergen, medicinal herb, or metal, and diluting it to a tiny percentage in water. A small amount of this solution is removed, and diluted again in another large batch. This process is repeated until the dilution is so small that none of the original material exists – only the frequency, like a “memory” of the herb or element, is left in the water.
BioSET therapy also incorporates the use of oral homeopathics to assist the body with detoxification.
NAET allergen vials
Practice muscle testing with a partner to detect possible allergies and sensitivities. With sufficient practice you can become quite proficient. Ask your practitioner to correlate your findings with a computerized screen.
1. Have the person being tested extend their dominant arm out at a 90 degree angle.
2. Slowly push down on the extended arm at the wrist and ask the person to “resist” against you. The object is to establish a baseline measurement, not to evaluate the absolute power of the muscle.
3. If the person is unable to exert a sufficient resistance pressure against your push, have them drink a glass of water or have them massage clockwise just below the navel and on their chest. This helps to balance them for the testing.
4. Place a vial or actual allergen in the hand of the arm not being tested. You can use anything-an apple, a peanut, an egg, a flower, etc. Repeat the muscle test, asking the person to resist. An arm that holds strong indicates no allergy. If the person is allergic to the substance, their arm will immediately and markedly weaken. Any weakness or dropping of the arm is a sign of allergy.
Computerized Medicine FAQs
Explanation of the readings
There are two types of computerized testing methods: the high/low and the dynamic testing. The high/low testing is more specific for testing inflammation. The dynamic testing is geared towards detecting imbalances in general, which may include inflammation, an allergy or sensitivity, metabolic processes, or nutritional deficiencies.
High low testing for inflammation
Computer software is used to register the conductance of an electrical charge at an acupuncture point.The process is simple and painless: an initial baseline scan is done on an acupuncture point on the surface of the skin. These acupuncture points are considered to be “information access windows”. Once baseline conductivity is established, frequencies of over 40,000 different potential foods, allergens, medications, and stressors can be output and the body’s response to each of these items can be measured. The response to different frequencies will affect the concentrations of the ions at the measurement points along the meridian. Inflammation may cause an increase ion concentration, and this increase of ions enhances the flow of electrons causing resistance to decrease while the conductance increases. Conversely, a weakened response may cause decease in ion concentration that hinders the flow of electrons, so as the resistance increases conductance decreases. A measurement of 50 is considered a balanced reading. Above 60 indicates an increased conductance of the body in response to a stressor, which is suggestive of an inflammatory process. Below 45 indicates decreased conductance, which signifies a more chronic weakness, or degeneration.
Dynamic testing for imbalances
Here we are looking at the shape of a curve, rather than the height of a line. Pressure is applied to the palm of the hand with the electrical probe, and a baseline is recorded. A small initial rise followed by a plateau, and then a subsequent rise, indicates a balanced reading. The plateau signifies the body’s ability to adapt or balance. As different frequencies are output, the body will either maintain balance, or respond to a signal with stress. A stressed or imbalanced signal will appear as a rise only; the lack of a plateau indicates inability to balance or adapt with respect to the particular signal.
Balanced BioSET Reading
Imbalanced BioSET Reading
Is it possible that my readings can change from one day to the next?
The body is a dynamic and intimately interconnected system. It is constantly on the search for homeostasis, or balance, and will utilize compensatory mechanisms to maintain equilibrium. Symptoms are merely the body’s manifestation of this quest for balance. For example, high intake of salt will trigger biochemical pathways within the body to release hormones that will signal the body to retain water, in order to balance the increased levels of salt. The blood sodium levels will therefore fluctuate over time, but maintain a general range. The same goes for blood pressure, electrolyte levels, glucose levels, cholesterol levels, etc. Blood work at a laboratory will reflect these phenomena of subtle fluxes. We’ve all seen our levels change slightly from one blood test to the next. Similarly, bioenergetic sensitivities and imbalances may be detected at certain times under various conditions, but it is the generalized readings that are of consequence and relevance. Computerized bioenergetic scans are able to detect such subtle energies that it is possible to detect minute changes, sensitivities, and imbalances that we may not even be aware of. The key take home point is that computerized screens are an excellent tool for detecting imbalances and sensitivities, but like any other testing, a range must be allowed.
Reasons why a treatment didn’t “hold”
Too many items cleared at once, underlying issue not addressed, microbial pathogen overload, adrenal imbalance, structural or emotional trauma.
Tips for maximizing treatment effects
The body requires a proper foundation upon which to build balance and strength. It is imperative to address any nutritional deficiencies through a sound dietary plan and high quality supplementation. Like a car, the body requires gas to run on. Higher quality gas increases performance, while a lack of gas prevents the car from running. Similarly, higher quality nutrition will increase the body’s ability to perform, and malnutrition will cause deficiencies. Statistics show that today’s food has a lower nutrient than ever before, due to soil depletion, fertilization methods, and lack of rotational farming. Ironically, as our stress levels increase, we have increased nutritional needs that are not being met by our current food supply. Even a healthy and organic diet is often not sufficient to provide adequate nutrients for today’s lifestyle needs. Nutrients and metabolism are so intricately linked that any shortage of enzymes, minerals, vitamins, amino acids, or fatty acids can prevent the body from conducting its optimal biochemical cellular reactions, which are vital for good health. In short, the body requires adequate substrates, or the raw building blocks of nutrition, to maintain equilibrium. These building blocks come from food, clean water, and/or supplements.
Likewise, it is important to detoxify any underlying virus, bacteria, fungus, parasite, or mycoplasma. This may be done via BioSET treatments coupled with detoxifiying herbs, homeopathic formulas, and/or enzymes.
Exercise is also essential to maintain proper metabolic rates and overall wellness. A mix of strength and cardiovascular is best, and basic forms include yoga, pilates, stretching, weight training, running, bicycling, swimming, and walking/hiking,
A daily meditation, breathing, or centering practice will promote alignment of the chakras and enhance mental and spiritual well-being.
This is an allergic reaction after having a henna tattoo
the 3 steps of the allergic reaction: the initial encounter, primed and activated. Provides visuals and definitions of allergens, Antigen Presenting Cell (APC), T-lymphocytes, cytokines, B-lymphocytes, IgE, basophils, eosinophils and mast cells.
Avoiding Allergic-Reaction Triggers
Ann Ng and David Q. Pham, PharmD, BCPS
Published Online: April 1, 2006 – 1:00:00 AM (EST)
Millions of Americans suffer from allergies. According to the National Institute of Allergy and Infectious Diseases, an allergy is defined as a specific reaction of the body’s immune system to a normally harmless substance. People who experience allergic reactions often are prone to being sensitive to more than one substance.
Allergies can be classified into several different categories, such as inhaled allergies, food allergies, medication allergies, and skin allergies. Oftentimes, it is difficult to distinguish between an allergy and a cold, because both exhibit symptoms of runny nose, sneezing, and coughing (Table 1). The only way for patients to know for sure whether they have an allergy or a cold is for them to consult a health care provider.
Types of Allergies
Most people who suffer from allergies become sensitized to proteins found in such items as latex, pollen, certain fruits, and drugs. If the reaction to these allergens involves the entire body, it is called a systemic reaction. Systemic reactions (also known as anaphylaxis) may lead to further complications such as anaphylactic shock, where the entire body shuts down.
Common sources of inhaled allergies include insects, dust mites, and pollen from plants. These types of inhaled allergens are common not only in the United States, but also worldwide.
Dust mites can be found in various places, including pillows, rugs, soft toys, upholstered furniture, clothes, mattresses, and bedsheets. In both adults and children, it is believed that 65% to 90% of all asthma cases are due to dust mites. Mites need moisture and human dander for survival and growth. In order to reduce exposure to this inhaled allergen, one must take certain preventive steps, such as putting pillows and mattresses in allergen-impermeable covers, keeping rugs out of bedrooms, washing soft toys at least once a week, limiting the number of soft toys a child may sleep with, and trying not to lie down or sleep on upholstered furniture.
Contrary to popular beliefs, these mites can be found in virtually any home, regardless of levels of cleanliness or economic status. In order to kill dust mites, it is recommended that all individuals affected by inhaled allergens wash bedsheets and pillow cases frequently with water temperatures >130?F.
Pollen from plants also is a very common source of allergens, with people experiencing symptoms more during the change of seasons (ie, fall and spring). In particular, ragweed, grass, flowers, and even common houseplants can trigger an allergic reaction.
Insects and animals may contribute to allergy symptoms. Cockroaches, which can shed their body parts and drop waste, may act as a trigger for allergies. Pets, such as dogs and cats, may shed loose hair or skin, resulting in exposure to pet dander.
Food allergies may be mild to lifethreatening. People have been found to be allergic to just about anything. Yet, some food allergies are more common than others, such as allergies to peanuts, shellfish, fish, eggs, fruits, preservatives, dyes, and spices. Symptoms can range from sore throat, numbness around the mouth, cough, and itchiness to anaphylaxis, which can be deadly. Patients should avoid the offending foods whenever possible and always carry epinephrine (eg, EpiPen Auto-Injector) if they suffer from severe food allergies. If, at any time, swelling of the lips, tongue, or difficulty in breathing is experienced, patients must visit an emergency room immediately.
Skin allergies are common with wool, dust, cosmetics, soaps, metals, and plant exposure (eg, poison ivy). A reaction may be immediate or prolonged after exposure.
Treatment of Allergies
The most important principle to remember in considering treatment is to avoid known allergens whenever possible. Unfortunately, doing so is often difficult, and patients may not realize until it is too late that they have been exposed to an allergen. Many treatments for allergies (Table 2) can be purchased without a prescription. They are packaged in the form of lotions, creams, ointments, syrups, pills, inhalers, and injectables. The pharmacist should refer a patient to a physician if the condition needs special attention and/or a prescription medication.
Several types of medications are used to treat allergies. The most common are antihistamines, corticosteroids, decongestants, mast cell stabilizers, and, in cases of anaphylaxis, epinephrine (Table 2).
Antihistamines typically are used to relieve itching of the skin, nose, or eyes. They will help reduce nasal swelling and drainage to reduce sneezing. Side effects include drowsiness, dry mouth, and possibly constipation. While taking antihistamines,patients should be sure to stay well hydrated and avoid any activity that requires full attention. Antihistamines may interact with other medications, particularly those that cause sedation.
Topical Nasal Steroids
Topical nasal steroids often are used to relieve inflammation in the nasal passages in order to help breathing. Side effects are mild and include dryness of the nasal passages, sneezing, and stinging. Prolonged use may lead to worsening of symptoms. Patients always should use these products as directed.
Certain allergic-reaction triggers (pollen, latex, certain foods, and certain drugs) have been identified as problemprone. Patients need to understand which allergens affect them and to avoid those substances when possible. When an allergic reaction takes place, however, several OTC medications are available. Pharmacists should know when it is most advantageous for patients to use an OTC medication and when they should be referred to a doctor. If the attack makes patients’ lips or tongue swell, makes breathing difficult, or makes blood pressure drop, patients should go immediately to an emergency room.
Clinical response to immediate (Type 1 Hypersensitivity) immunologic reaction between
specific antigen and antibody
Reaction results from IgE antibody
CLINICAL MAIFESTATIONS OF ANAPHYLACTIC REACTIONS
Mild Systemic Reactions
Sensation of warmth
Possible accompanied by fullness in mouth and throat
Tearing of eyes
Onset symptoms begins within first 2 hours of exposure
Moderate Systemic Reactions
Above symptoms with added:
Warmth that increases in intensity
Itching that increases in intensity
Bronchospasm and edema of airways or larynx and dyspnea, cough and
Onset same as mild
Begins within the first 2 hours of exposure
Severe Systemic Reactions
Abrupt onset with same S/S as mild and moderate
Within approx 30 min:
CV, Resp, GI, Integumentary are affected
Progress rapidly to bronchospasm, laryngeal edema, severe dyspnea, cyanosis
Dysphasia (difficulty swallowing)
Abdominal cramping due to increased GI secretions
Rarely: Cardiac arrest and coma result
Single most important aspect for client at risk for anaphylaxis
People sensitive to insect bites and stings
Those experience food or medication reaction
Those experience idiopathic or exercise induced anaphylactic reaction (EPI-PEN)
Careful History any sensitivity to suspected antigens obtained before administration ofany medications particularly parenteral form because this route associates with mostsevere anaphylaxis
Clients predisposed to anaphylaxis should wear some form of identification (Medic Alert
Bracelet: Naming allergies to meds, food, and other substances)
Epi Pen 0.3mg
Epi Pen Jr 0.15mg
Administer mid portion of thigh
Client allergic to insect venom may require venom immunotherapy
Used as a control measure and not a cure
Insulin-allergic diabetic clients and penicillin-sensitive clients may require desensitization
Desensitization based on controlled anaphylaxis with gradual release of mediators
Clients who undergo desensitization cautioned there should be no lapses in
therapy because may lead to reappearance of allergic reaction when medication is
Depends on severity of reaction
Cardiovascular and respiratory function evaluated closely
Increase O2 Concentration
Epinephrine 1:1000dilution: given SQ in upper extremity or thigh and may be followed
by continuous IV infusion – Why Given????????????
Antihistamines and Corticosteroids: May be given to prevent recurrences of reaction and
treat urticaria and angioedema
Volume Expanders and Vasopressor Agents(Dopamine): Given to maintain BP and
normal hemodynamic status (LR, Plasma)
Brings Blood Pressure Up
Aminophylline and Corticosteroids: Administer to improve airway patency and function
Episodes bronchospasm or history of bronchial asthma or COPD
Glucagon IV: Hypotension unresponsive to vasopressors; administer IV; also acute
inotropic and chronotriopic effects
Improves muscle contractility in heart
Severe reaction observed closely 12-14 hours because potential recurrence even with
mild reactions must be educated concerning risk