Understanding the differences between food sensitivities, intolerances and allergies are one of the first steps to finding a solution for troubling symptoms. But this isn’t an easy task. Despite being different, these terms are often used interchangeably, making it confusing to understand what’s really going on inside your body.
In a 2019 study that surveyed 40,443 adults in the United States, it was estimated that 10.8% of the respondents had food allergies at the time of the survey, but 19% believed that they had food allergies. (1) This discrepancy could be due to the fact that people just aren’t sure what’s behind their symptoms.
Food sensitivities, intolerances, and allergies can cause similar digestive symptoms, including abdominal pain, bloating, and loose stools, and because most meals include a variety of foods at once, it can be even more difficult to pinpoint the specific culprits behind your symptoms. Here, I’ll try to detail more about the various types of food intolerances that lead to hypersensitivity reactions, inflammation, and unwanted symptoms and conditions. Before diving in, let’s take a look at the antibodies that are responsible for some of these reactions.
- What Are Antibodies?
- The Role of Immunoglobulins
- Immunoglobulin G (IgG)
- Immunoglobulin A (IgA)
- Immunoglobulin M (IgM)
- Food Intolerance That Leads to an Inflammatory Response
- Bio-Chemical Intolerances
- Immunologic Food Intolerances
- Type I - Allergies
- Non-Allergic Hyper-Sensitivities
- Type II - The Cytotoxic Reaction
- Type III - The Immune Complex Response
- Type IV - Delayed Immune Response
- Neuro-Limbic Reactions
- Histamine Intolerance
- Sulfite Sensitivity
- Oxalate Intolerance
- Lectin Sensitivity
- How Do You Know What’s Really Going On?
What Are Antibodies?
Antibodies, also known as immunoglobulins, are glycoproteins that are produced by white blood cells, as a part of the adaptive immune system. They play a critical role in the body’s immune response, as they are coded to specifically seek out, recognize and bind to particular antigens, such as viruses or bacteria. Highly complex and specific, the antibody immune response involves immunoglobulin isotypes that differ in distribution, structure, and target specificity.
These different antibodies are classified by isotype, each one differing in antigen responses and function. Let’s take a look at four major antibody classes that have been identified, including IgG, IgA, IgM, and IgE.
The Role of Immunoglobulins
Food allergy is defined as “an immunologically conditioned, abnormal reaction to food allergens.” (2) Everyone has a normal immunological reaction to food antigens after consuming food. These reactions are mediated by specific immunoglobulins, and even though these are immune reactions and meet the first condition of a food allergy, it’s important to know that these reactions are a normal response to food exposure.
Immunoglobulin G (IgG)
When the body is healthy, the epithelium in the digestive tract is impermeable to antigens. Due to many different factors that can damage the epithelium, including a number of inflammatory processes, food antigens can pass through the epithelium and make contact with the body’s immune cells. This leads to the production of specific defensive IgG antibodies. Repeated contact of these food antigens to the body’s antibodies leads to the creation of antigen-antibody immune complexes, which can eventually lead to increased inflammation, continued damage of the gut lining, and increased permeability to food antigens.
In many people, the increase in antigen-specific IgG antibodies is associated with non-symptomatic immune tolerance of these foods. But in other people, low production or a lack of allergen-specific IgG antibodies is linked to the development of food sensitivities, including delayed onset of digestive symptoms. (2)
Immunoglobulin A (IgA)
Secretory IgA is the dominant antibody found in mucous membranes, including intestinal, respiratory, and urogenital mucous membranes, the thin tissue that separates the outside environment from the inside of the body. Along with protection and maintaining homeostasis, a primary function of Secretory IgA is considered to be immune exclusion, a process that limits or restricts a number of microorganisms and antigens from crossing the body’s vulnerable mucosal barriers. (3) IgA deficiency is also strongly associated with gut microbiota dysbiosis, which may be the reason why many people develop food reactivity. (4)
Immunoglobulin M (IgM)
The first antibody produced in an immune response to most antigens is IgM, an antigen receptor on B cells. Due to its large size, it is found primarily in intravascular space, like the bloodstream and lymph fluid. Some types of antibodies, including natural IgM antibodies, recognize self-antigens as a critical function of immunoregulatory and cellular housekeeping properties. One of the most essential tasks of the immune system is to clear dying cells, a process that is required to prevent uncontrolled inflammation and autoimmunity. Natural IgM antibodies that recognize apoptotic cells, or dying cells, have been shown to enhance the phagocytic clearance of these cells and suppress other immune signaling pathways, making IgM essential for keeping systemic inflammation in check. (5)
Immunoglobulin E (IgE)
Food allergies, on the other hand, have been linked to a disturbance in or loss of immune tolerance to foods. Immunoglobulin E (IgE)-mediated food allergy is associated with both allergen-specific IgE antibodies and a low production or lack of allergen-specific IgG antibodies.
In IgE-mediated food allergies, a specific trigger food activates the immune system, causing a T helper 2 response, that results in IgE binding to receptors on effector cells, like mast cells and basophils. These cells are then activated, releasing histamine and other mediators, and causing a rapid onset of symptoms that can involve the dermatologic, respiratory, gastrointestinal, cardiovascular, and/or neurologic systems. (6)
To help differentiate, remember that IgG, IgA, and IgM reactions are delayed response reactions, and IgE responses are immediate and are considered a true food allergy. Now, let’s take a look at these immunoglobulins with respect to food intolerance.
Food Intolerance That Leads to an Inflammatory Response
There are 3 major categories of food intolerance that can lead to an inflammatory response within the body. These include bio-chemical intolerances and immunologic intolerances which can be either food allergies or non-allergic hyper-sensitivities.
With bio-chemical intolerances, the reactions to the food occur exclusively within the digestive system and are often the result of an enzyme deficiency, where the body lacks a sufficient amount of enzyme that’s needed to break down a specific food. An example of this is lactose intolerance, where the body does not produce enough or has insufficient amounts of lactase, the enzyme needed to break down lactose, which triggers a digestive response and can lead to a wide range of gastrointestinal symptoms.
Many of these intolerances can also be caused by reactions to other natural components or additives, like preservatives or colorants, that are often found in packaged food. In many cases, a small amount of a trigger food may be well tolerated or the intolerance may be temporary. It is estimated that the prevalence of biochemical food intolerances is between 2-20% of the adult population in the United States, but it is more difficult to track this data than true food allergies. (7)
Like many food intolerances, common symptoms of bio-chemical intolerance include digestive issues, including abdominal pain, bloating, heartburn, gas and flatulence, diarrhea, or constipation.
Immunologic Food Intolerances
With immunologic food intolerances, the immune system and its various cells and immunoglobulins play a role in starting an inflammatory response in the body. There are four types of immunological hypersensitivity reactions to food.
Type I - Allergies
Allergies are the first immunologic food intolerance type that we’ll take a look at. True allergies cause an immediate and usually severe response to a particular food. This hypersensitivity involves a reaction with IgE and can bring on symptoms including hives, swelling of the throat, lips, or tongue, an itchy sensation in the mouth and throat, abdominal pain, diarrhea, and vomiting. Allergies also include reactions like asthma, hay fever, and eczema. A severe allergic reaction, known as anaphylaxis, leads to whole-body and potentially fatal symptoms.
It is estimated that 3-10% of adults and 8% of children worldwide have IgE-mediated food allergies, making it a significant public health issue (8) Food allergies can develop at any age, from infancy to adulthood, and can even happen to foods that have been eaten before without a problem.
There are 8 major food allergens, often referred to as the “Big 8”, that are thought to account for 90% of all food allergy reactions. These include:
- Crustacean shellfish
- Tree nuts, like walnuts, pecans, Brazil nuts, almonds, pistachios, etc.
- Soybeans (8)
In addition to true IgE-mediated allergies mentioned above, there are a number of non-allergic hyper-sensitivities that also cause inflammation in the body which can lead to troubling symptoms. There are three types of non-allergic immunologic food intolerances.
Type II - The Cytotoxic Reaction
A cytotoxic reaction happens when IgG and IgM antibodies that are coded to remember specific antigens end up attacking similar-looking proteins on the cell walls of your own tissue. Remember, the immune system is very complex, and science is just now beginning to understand all of its complexities. To understand the cytotoxic reaction, you need to understand the complement system. The complement system is a part of the innate immune system and plays an important role in defending the body against infection, clearing immune complexes and cellular debris, and creating a link between innate and adaptive immunity. (9)
This system consists of more than 35 plasma proteins, cell surface complement receptors, and regulatory proteins. With proteolytic activation or activation of enzymes, inactive molecules are activated and create a proteolytic cascade that brings on even more reactions, including phagocytosis, inflammation, cell lysis, and guidance of the adaptive immune response. (9)
Since the activation of complement leads to potentially destructive reactions, the immune system has several different inhibitors to tightly regulate this system in an effort to protect your own body tissues from this destruction. When this activation and inhibition equilibrium gets upset, this can lead to a number of challenging conditions, including hemolytic anemia, rheumatic heart disease, Grave's disease, and myasthenia gravis.
Proteins in various foods can lead to the activation of the complement system, and in a body that lacks adequate inhibitors, this process can start to cause problems. Hypersensitivity reactions can occur within minutes or hours of exposure. One of the known triggers of hyper-sensitivity reactions is lectins. Lectins are poisons made by plants to deter insects and animals from eating them. While people have adapted to eating lectins without problem, as our food supplies have globalized and been mono-cultured, our body’s relationship with lectins has changed. The lectin pathway is an alternative pathway into the complement system, and for many of us, lectins activate complement proteins, triggering a cascade reaction and making the body susceptible to destruction from our own immune system.
Type III - The Immune Complex Response
In this type of hypersensitivity reaction, an abnormal immune response is mediated by the formation of antigen-antibody aggregates called "immune complexes." These reactions typically occur within 3-8 hours of exposure to viral, fungal, or bacterial pathogens, and are mediated by IgG, IgM, complement proteins, and neutrophils.
When these immune complexes are not disposed of properly by the liver, they can build in the blood and can precipitate in various tissues such as skin, joints, and vessels, triggering the complement pathway. Complement activation then leads to the recruitment of inflammatory cells that release lysosomal enzymes and free radicals, causing tissue damage. (10) Food intolerances that lead to the immune complex response have been linked to conditions like lupus and rheumatoid arthritis.
Type IV - Delayed Immune Response
Type IV is a classic delayed food intolerance that typically happens within 48-72 hours of exposure to the trigger food. Unlike the other immunologic reactions, the delayed immune response is not mediated by immunoglobulins but is instead a cell-mediated response that involves immune cells, including T-cells, monocytes, and macrophages.
Many different symptoms and serious conditions have been linked to food intolerances that cause a delayed immune response, including everything from gluten sensitivities and contact dermatitis to celiac disease, Hashimoto’s thyroiditis, Crohn’s disease, multiple sclerosis, and more.
In addition to digestive and skin symptoms, food allergies and sensitivities can cause neuro-limbic reactions that lead to emotional, mood, and behavioral symptoms.
Research is finding that the molecular and cellular pathways between the immune and nervous systems are bidirectional, where either can have significant influence over the other. There are three types of interactions between the immune system and the central nervous system (CNS):
- The immune system regulates the CNS
- The CNS drives the immune response
- The CNS acts reciprocally with the immune system (11)
In studies of food allergy, specifically, it has been shown that the prevalence of anxiety, depression, and other behavioral disorders, like OCD and Tourette’s syndrome, is higher in adults with food allergies than in healthy controls and those with known food intolerances. (11)
It is believed that dietary allergies and hyper-sensitivities can trigger neuro-limbic inflammation, causing the neurotransmitters to function differently which leads to neurological symptoms. Since the limbic system in the brain is responsible for everything from fear responses and sleep to regulating the body’s hormones, the range of symptoms arising from these neuro-limbic reactions is highly variable. (11)
Though histamine intolerance likely affects a small percentage of the population, it’s easy for people to mistake it for other conditions, like food allergies or other gastrointestinal diseases. It results from a buildup of histamine in the body, due to medical or environmental conditions, pharmaceutical drugs, nutritional deficiencies, or diet.
Histamine intolerance may arise if there is an increase in histamine release through digestion, a decrease in the effectiveness of diamine oxidase, the primary enzyme that breaks down ingested histamine, or a decrease in histamine-N-methyltransferase (HNMT), an enzyme that helps to break down histamine inside cells. (12)
Used as a preservative and an antioxidant additive in food and pharmaceutical drugs, sulfites can lead to adverse reactions in sensitive individuals. It seems that the reaction varies from person to person, causing hyper-sensitivities in most, but life-threatening anaphylactic or asthmatic reactions in others. The prevalence of sulfite sensitivity is typically reported between 3-10%, with asthmatic patients being particularly susceptible. (13)
Symptoms of sulfite sensitivity range from skin reactions, like dermatitis or hives, to hypotension, diarrhea, and more serious allergic reactions. In sensitive individuals, food containing sulfites should be completely avoided.
Oxalates are naturally occurring substances in many foods, and are primarily found in cruciferous vegetables, leafy greens, beans, nuts, and berries. They are considered an antinutrient because they interfere with the absorption of nutrients. Oxalates bind to calcium during digestion in the stomach and intestines and leave the body in the stool. However, oxalate that doesn’t bind with calcium travels from the blood to the kidneys, leaving the body through urine.
Most people have no problems with oxalate-rich foods, but others will have an oxalate intolerance and develop symptoms that include burning sensations in the eyes, ears, and mouth, abdominal pain, nausea, diarrhea, and kidney stones. People who have autoimmune conditions also tend to have an intolerance to oxalates, leading to higher levels of inflammation, joint pain, muscle stiffness, and bloating. (14)
As mentioned above, lectins are another antinutrient that can cause problems for some people. Abundant in plants, lectins are proteins or glycoproteins of non-immune origin, and they have the ability to bind to carbohydrates, glycoproteins, glycolipids, and polysaccharides without modification.
Because they are so similar to the body’s own complement proteins, lectins can bypass our natural defense systems and travel around the body causing diseases, like Crohn’s disease, colitis, and Coeliac-Sprue, by breaking down the surface of the small intestine and eliciting the cascade of the complement pathway. They play a significant role in causing leaky gut syndrome by creating holes in the gut wall. Lectins can also cause cells to act like they have been stimulated by insulin, cause an insulin release from the pancreas, and act as immunologically presenting cells, which can further exacerbate autoimmune conditions. (14)
How Do You Know What’s Really Going On?
Tests can be done to identify foods that trigger allergies and sensitivities, but these tests can be expensive and aren’t always accurate.
An alternative method to test for food hyper-sensitivities and intolerances is through an elimination diet. You should remove all suspected trigger foods and follow a strict diet for between 2-4 weeks. After this period, you will go through a period of slow reintroduction, closely monitoring your symptoms and looking for any foods that cause a reaction or symptoms.
Then, any foods that you have a diagnosed or suspected allergy to, or foods that cause bad reactions that may point towards an intolerance, should be removed from your diet, or eaten in strict moderation. Uncovering what is not serving your body well and removing it is an important step to getting a handle on troubling symptoms and living your best life!
Struggling with autoimmunity or chronic illness? Check out these success stories from clients who addressed the root-cause contributors of their autoimmune disease and are now thriving!
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- Pabst O, Slack E. IgA and the intestinal microbiota: the importance of being specific. Mucosal Immunol 2020;13:12–21.
- Catanzaro JR, Strauss JD, Bielecka A, Porto AF, Lobo FM, Urban A, et al. IgA-deficient humans exhibit gut microbiota dysbiosis despite secretion of compensatory IgM. Sci Rep 2019;9:13574.
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- Anvari S, Miller J, Yeh CY, Davis CM. IgE-Mediated Food Allergy. Clin Rev Allergy Immunol. 2019;57(2):244-260.
- Harvard Health Publishing. Food allergies and food intolerances. [Internet]. [cited 1st September 2020.] Available from: https://www.health.harvard.edu/allergies/food-allergies-and-food-intolerances
- Messina M, Venter C. Recent Surveys on Food Allergy Prevalence. Nutr Today. 2020;55(1):22-29.
- Beltrame MH, Catarino SJ, Goeldner I, Winter Boldt AB, José de Messias Reason I. The lectin pathway of complement and rheumatic heart disease. Front Pediatr. 21 January 2015.
- Usman N, Annamaraju P. Type III Hypersensitivity Reaction.StatPearls [Internet]. [Updated 2020 Jul 6]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559122/
- Mirotti L, Castro J, Costa-Pinto FA, Russo M. Neural Pathways in Allergic Inflammation. J Immunol Res. 2010;2010(ID 491928)1-11.
- Sánchez-Pérez S, Veciana MT, Comas-Basté O. Review Histamine Intolerance: The Current State of the Art. biomolecules. 2020;10:1181.
- Vally H, Misso NL. Adverse reactions to the sulphite additives. Gastroenterol Hepatol Bed Bench. 2012;5(1):16-23.
- Popova A, Mihaylova D. Antinutrients in Plant-based Foods: A Review. The Open Biotechnology Journal. 2019;13:68-76.
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