Examination of food intolerance and allergy: Understand the difference between them.

Feeding is the process by which organisms obtain and incorporate food or nutrients for their vital functions, such as growth and reproduction. It is also the main factor responsible for maintaining body temperature, through the digestive system, as it produces enzymes that work to break down caloric foods.

With the hustle and bustle of everyday life, the preference for a faster and more practical diet is increasingly frequent and for many, eating is synonymous with consuming industrialized products, packaged and semi-ready foods with a lot of salt, additives, fat and sugar. Consequently, the presence of these additives and contaminants of chemical or bacteriological origin and the large number of food antigens can easily explain the high frequency of adverse reactions to food. The true incidence of these reactions is unknown, which may be called: adverse reaction to food, food allergy, hypersensitivity to food and food intolerance (Bricks, 1994).


What is food intolerance?

The definitions of food intolerance are many and vary from any non-immunological adverse reaction to foods; inability to fully digest carbohydrates (mainly disaccharides), of which lactose is the most important; type III hypersensitivity reaction (delayed IgG-mediated immune reaction) or a body response to the ingestion of certain foods, in which the body has difficulty digesting, metabolizing or is unable to absorb some nutrients, resulting in extreme discomfort , which can be associated with several symptoms (Bricks, 1994; Dreborg, 2015). This occurs due to the lack of enzymes necessary for the proper digestion and absorption of a certain food, which ends up activating the immune system, which acts against these products.

The prevalence of food intolerance in the general population is believed to be 5-20%, however, the true prevalence remains unknown due to insufficient or underdiagnosed data (Priedite et al, 2014).

Most of these adverse reactions are due to contamination, pharmacological, toxic, metabolic, and neuropsychological reactions due to non-immunological factors, so they are treated as intolerance and not as food allergy (Ferguson, 1992; Burks; Sampson, 1992; Walker, 1992). 

There are different factors that can alter intestinal permeability or the functionality of the immune system (such as stress, infections, antibiotics or excessive use of anti-inflammatory drugs), resulting in an increased likelihood of presenting food intolerance reactions. 

It is suggested that the increased intestinal permeability may cause IgG-mediated intolerance, which allows food substances to access the circulation and trigger the production of specific IgG for food proteins (Beyer; Teuber, 2005). Greater production of food-specific IgG is associated with decreased production of anti-inflammatory cytokine antibodies, such as IL-10 and TGFb1, implicated in irritable bowel syndrome (Sentsova et al, 2014). This type of intolerance is associated with several nonspecific symptoms including skin rashes, hives, asthma, abdominal cramps, diarrhea and even neurological manifestations such as migraines (Collard, 2010; Guo et al, 2012; Kumar et al, 2013; Gaus; Kumar, 2013).  

Food intolerances can occur from different foods, but the most frequently reported are: gluten intolerance and lactose intolerance.


Understanding Gluten Intolerance

Gluten is a mixture of prolamin proteins (storage protein found in cereal seeds with a high amount of proline ) present mainly in wheat grain, barley, rye and oats. Gluten proteins are highly resistant to breakdown (hydrolysis) mediated by enzymes from the gastrointestinal tract. As a result, intolerance is caused by the inability of the small intestine to digest these proteins (Balakireva; Zamyatnin, 2016). This causes the intestines to become inflamed, causing pain and other digestive disorders.

Currently, there are several ways to prevent symptoms, the most common being the gluten-free diet, which has proven its effectiveness, enzyme therapy and prevention programs such as replacing wheat flour with chickpea flour or products containing corn flour. In addition, product labels must be checked for the indication: “gluten free” and the composition of the products purchased must always be read, as they may contain traces of gluten, even if it seems impossible. 


Understanding Lactose Intolerance

Lactose is the sugar found in milk. This sugar is broken down (hydrolyzed) in the intestine by the lactase enzyme into two smaller parts: galactose and glucose, causing these molecules to turn into energy for our bodies.

Lactose may fail to be metabolized by the digestive system when there is a decrease in the hydrolysis capacity, i.e., a decrease in lactase enzyme activity in the mucosa of the small intestine, characterizing lactose intolerance (Sahi, 1994).

Milk and dairy products are the only source of lactose in the diet. Lactose from dairy products must be digested for use by intestinal cells. Without this hydrolysis or digestion process, the lactose produces a clinical scenario characterized by abdominal pain, nausea, flatulence, and diarrhea, all of which occur due to the ingestion of foods containing lactose. The intensity of the symptoms varies, depending on the amount of lactose ingested, and increases with age.

One can consider talking about lactose intolerance when the imbalance between the amount of lactase enzyme present in the intestinal mucosa and the amount of lactose ingested that reaches the digestive tract (the excess of undigested lactose remains in the lumen of the intestinal mucosa) causes the characteristic changes in the clinical scenario (Rosado, 2016).

In order to prevent the symptoms, it is recommended to temporarily avoid milk and dairy products and refrain from eating anything containing high amounts of lactose. Ingestion of vegetable drinks based on rice, soy or oats are a good substitute for milk. The highest concentrations of lactose are found in milk and ice cream, while cheeses generally contain smaller amounts. Always read the composition of the products purchased, which may not be so easy due to the presence of foods with lactose not identified in its composition (Matthews et al, 2005).  

However, the total and definitive exclusion of lactose from the diet should be avoided, as it can cause nutritional damage regarding calcium, phosphorus and vitamins and is associated with decreased bone mineral density and fractures (Di Stefano et al, 2002). Most lactose intolerant people can ingest 12 g/day of lactose (equivalent to a glass of milk) without experiencing adverse symptoms (Vonk et al, 2003). The consumption of lactose-free dairy products helps ensure calcium intake.

With the advancement of science and innovation tests, we can analyze the main foods that trigger some type of adverse reaction, such as the A200 exam. The identification of the food intolerance profile using these tests, which evaluate the main foods related to this type of reaction, has ensured better targeting in the clinical practice and consequently in patient treatment.

What are the symptoms of food intolerance?

In general, food intolerance can be associated with symptoms following the recurrent consumption of a specific food. Some common symptoms of food intolerance include: 

  • diarrhea
  • constipation
  • stomach pain
  • bloated feeling in the belly
  • gastric reflux
  • gases 
  • irritable bowel
  • muscle and joint pain
  • fatigue
  • headache
  • skin infections. 

Removing foods that cause intolerance from the diet significantly improves symptoms (Arroyave et al, 2007; Wilders et al, 2008; Guo et al, 2012; Kumar et al, 2013).    


What is food allergy?

Food allergy is an immune reaction triggered right after eating a certain food, even in small amounts. The main cause is due to the production of immunoglobulin E (IgE) antibodies and is known as a type I hypersensitivity reaction. Food allergy occurs when the immune system overreacts to a normally harmless substance, called allergens or triggers.  

Cases of food intolerance (such as lactose and gluten intolerance) are common, however cases of food allergy are rarer. It is estimated that food allergy affects about 6-8% of children under the age of three, whereas patients with allergic diseases have a higher incidence of food allergy, which can be found in 38% of children with atopic dermatitis, 5% of children with asthma, and up to 3% of adults.

Factors such as genetic predisposition involved in the pathogenesis of food allergy have been reported. Studies indicate that 50-70% of patients with food allergy have a family history of allergy. It is estimated that if at least one parent has food allergies, the probability of having children with allergies is about 75%. 


What are the types of food allergies?

– Food allergies not mediated by IgE: There are also food allergies not mediated by IgE, which mainly affect the respiratory tract. Allergen-specific T cells are believed to be related to the etiology of food protein-induced syndromes, such as enterocolitis, proctocolitis and enteropathy. These pathologies mainly affect babies and children allergic to cow’s milk and usually cease at around 1-5 years of age. Due to the lack of diagnostic tests, its prevalence remains uncertain. 

– IgE-mediated food allergies: Another type of food allergy is known to be caused by a mixed pathway, characterized by IgE-dependent and independent pathways. It causes atopic manifestations due to IgE-independent factors such as atopic dermatitis, which are associated with delayed food allergy (symptoms appear 6-48 hours after food intake), being driven by the action of T helper 2 cells (TH2) and eosinophilic gastrointestinal disorders, caused by the infiltration of eosinophils in the tissues.  

Food allergy symptoms may occur immediately after eating a certain food and can affect different systems of the body such as skin, gastrointestinal tract, cardiovascular and respiratory system.  Symptoms include abdominal pain, nausea/vomiting, hoarseness, hives, skin rashes, itching, swollen mouth, lips, eyes, tongue and throat, difficulty swallowing, congested nose, shortness of breath and even more severe symptoms such as anaphylaxis and cardiovascular collapse. 

The most common symptoms for IgE-mediated food allergies include itching, hives, angioedema, abdominal pain, vomiting, wheezing and hypotension. However, cases of mixed food allergies differ according to their association. Cases associated with atopic dermatitis present a worsening of the dermatitis, while cases of eosinophilic esophagitis allergy may present vomiting, growth disorders, dysphagia and heartburn and related to other eosinophilic gastrointestinal disorders, vary according to the region and gastrointestinal involvement. Cases of food allergies not mediated by IgE may present symptoms such as severe vomiting, in case of intermittent exposure, diarrhea and difficulty in improving, in case of chronic exposure, rectal bleeding and steatorrhea due to malabsorption. 


How is a food allergy diagnosed?

Food allergy are diagnosed by analyzing the symptoms, considering the description of the patient and the signs presented. Some tests are commonly conducted to assist in the final diagnosis:

  • Skin tests: When performed alone, they do not confirm a food allergy diagnosis. They only detect the presence of IgE antibodies specific to certain foods, demonstrating sensitization. It is a test that is widely used for patients with IgE-mediated milk allergy. About 1/3 of patients with atopic dermatitis are allergic to cow’s milk and about 50% of infants allergic to milk have atopic dermatitis. Although it can result in false positives (up to 24% false positives) in children with atopic dermatitis, false negative results are uncommon. 


  • Measurement of specific IgE: Measure the specific IgE antibodies for suspicious foods. The test reveals the presence/absence of IgE for certain foods. They do not necessarily indicate that ingestion will result in clinical reactions. However, the results are quite valuable when they are negative, since due to its high sensitivity, it results in approximately 95% accuracy to exclude IgE-mediated reactions. However, a positive result is associated with true clinical reactions only 50% of the time.


  • Radioallergosorbent test (RAST) and semi-quantitative in vitro trials: Provide evidence of IgE-mediated food allergy. The CAP-System Fluorescent Enzyme Immunoassay methodology is the most suitable for cases of symptomatic food allergy. The results from analyzing the quantitative levels of specific IgE considerably increased the positive predictive value and excluded the need to conduct oral provocation tests in approximately 50% of the cases. 


  • Exclusion diet: Based on a medical history analysis and physical examination suggestive of food allergy, the suspected food is excluded from the diet, when identified. After 2-6 weeks of food exclusion, symptoms may or may not go away. However, a favorable clinical response to an exclusion diet is not very reliable, and it may just be a coincidence. It is also used for cases of food allergy not mediated by IgE. 


  • Oral provocation tests: When signs and symptoms disappear after exclusion. If they disappear, an oral provocation test is required to confirm the diagnosis of the suspected food. The test consists of administering the same food to the patient, being considered positive if the symptoms reappear. They are indicated for diagnostic confirmation or to verify if the patient has already become tolerant to the food and are contraindicated in case of history of severe anaphylactic reaction. Specialized medical monitoring is required to conduct the test. It is also used for cases of food allergy not mediated by IgE.


  • Esophageal/gastrointestinal biopsy: Used for cases of suspected mixed food allergy related to eosinophilic gastrointestinal disorders, caused by the infiltration of eosinophils into the tissues. It is performed after a period of 2-3 months of proton pump inhibitors to exclude gastroesophageal reflux as a possible cause. 


  • Jejunal biopsy: Used for cases of enterocolitis syndrome induced by food proteins. It seeks to detect villous atrophy and crypt hyperplasia. 


How is a food allergy treated?

As of now, there is no definitive treatment for food allergy, the standard of care being the exclusion of allergens and the treatment of systemic reactions with adrenaline. 

Adrenaline works by reversing edema, hives, bronchospasm, hypotension and gastrointestinal symptoms in minutes, being more effective in early treatment (after 6 minutes of exposure), wherein early response is the main factor in preventing death from anaphylaxis. It is estimated that 1-20% of people who have food allergy may experience a biphasic reaction, where symptoms recur within a few hours after the initial adrenaline treatment. It is believed that a late or insufficient first dose of adrenaline may increase the risk of a biphasic reaction. 

Other drugs, such as antihistamines or specific H1 receptor blockers, are used to treat localized symptoms of food allergy. Gastrointestinal symptoms can be treated with H2 receptor blockers. However, the medications available only address the symptoms and not the cause of food allergies. 

 Desensitizing immunotherapy consists of sublingual, oral or dermal administration of an allergen extract. It represents major progress in the treatment of food allergy. 

Daily doses of the allergen start in the milligram range and gradually increase over a period of days or weeks. A multicenter, randomized, double-blind study evaluated sublingual desensitizing immunotherapy in 40 subjects with peanut allergy, with a defined response to tolerate a 5g dose of peanut powder or an increase of 10 times the initial dose. After 44 weeks, 70% of the 20 subjects being treated increased the tolerated dosage from 3.5 mg to 496 mg (the equivalent of about two peanuts). 

Oral immunotherapy is a promising treatment that allows most children with food allergies to be desensitized to considerable amounts of allergenic foods. Due to the higher doses of allergens used in oral immunotherapy, compared to the others, patients can be desensitized not only to avoid a life-threatening reactions due to accidental exposure, but also to be able to consume certain amounts of allergenic foods. 

Understanding the mechanism of the molecular processes involved in sensitizing individuals has led to the development of monoclonal antibodies as therapeutic agents to help block sensitization. Promising results indicate that oral immunotherapy in conjunction with monoclonal antibodies may allow the immune system to be desensitized to food allergens more quickly and safely than with oral immunotherapy alone. However, additional clinical trials are being conducted to confirm the safety and efficacy of monoclonal antibodies, optimize maintenance doses and assess the sustainability of desensitization or the establishment of tolerance.

In the event of any suspicion of food intolerance or food allergy, seek a medical specialist so that the clinical scenario can be properly evaluated and thus make it possible to design an effective treatment plan. 


What are the differences between food allergy and intolerance:

Food allergy is a hypersensitivity that we develop to some foods, which is mediated by class E immunoglobulins (better known as IgE) that trigger immediate reactions (called type I hypersensitivity reactions) with possible involvement of the mucosa, skin, airways, intestinal tract and vascular system. Primary food allergy is based on the (early) sensitization of IgE to animal proteins (e.g., cow’s milk, chicken eggs) or vegetable proteins (e.g., peanuts, hazelnuts or wheat). In the case of secondary food allergies, the IgE against pollen proteins (e.g. birch) reacts to structurally related food proteins (with cross reactions to stone fruits, for example). 

Food allergies occur when the body seeks to defend itself against the entry of certain foods, even in small quantities. By identifying them as a foreign body, the organism produces antibodies for its defense. 

Food allergies usually appear when the patient is very young. Intolerances, however, can appear at any time from difficulty in digesting certain foods, becoming more frequent as we age.


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