Food Allergy and Intolerance: Understanding the Differences

Feeding is the process by which organisms obtain and incorporate food or nutrients for their vital functions, such as growth and reproduction. It is primarily responsible for maintaining body temperature through the digestive system, as it produces enzymes that break down calorie-containing foods.

With the hustle and bustle of daily life and the preference for faster and more convenient eating, consuming food nowadays, for many, is synonymous with consuming processed products, packaged foods, semi-prepared meals, with high salt, additives, fats, 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, which can be referred to as: adverse reactions to food, food allergy, food hypersensitivity and food intolerance, is not known for certain (1).

What is Food Intolerance?

The definitions of food intolerance are numerous and vary from any adverse reaction to food of a non-immunological nature; inability to fully digest carbohydrates (primarily disaccharides), of which lactose is the most important; type III hypersensitivity reaction (delayed immune reaction mediated by IgG) or even as a response of the body 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 may be associated with various symptoms (1,2).

This occurs due to a lack of enzymes necessary for the proper digestion and absorption of a certain food, which ends up activating the immune system, that acts against these products.

It is believed that the prevalence of food intolerance in the general population is 5 to 20%; however, due to insufficient or under-diagnosed data, the true prevalence remains unknown (3).

The majority of these adverse reactions result from contamination, toxic pharmacological reactions, metabolic and/or neuropsychological reactions due to non-immunological factors. Therefore, they are treated as intolerance and not as food allergy (4-6).

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

It is suggested that increased intestinal permeability may cause IgG-mediated intolerance, allowing food substances to access circulation and trigger the production of IgG specific to food proteins (7).

A higher production of IgG specific to food is associated with decreased production of anti-inflammatory cytokines, such as IL-10 and TGFb1, implicated in irritable bowel síndrome (8).

This type of intolerance is associated with various nonspecific symptoms ranging from skin rashes, hives, asthma, abdominal cramps, diarrhea, to even neurological manifestations such as migraines (9-12).

Food intolerances can occur from various foods, but the most commonly reported ones are gluten intolerance and lactose intolerance.

Understanding Gluten Intolerance

Gluten is a mixture of prolamins (plant storage proteins with high proline content found in cereal seeds) primarily found in wheat, barley, rye, and oats.

Gluten proteins are highly resistant to breakdown (hydrolysis) by enzymes in the gastrointestinal tract. Thus, gluten intolerance is caused by the small intestine’s inability to digest these proteins (13). This leads to inflammation in the intestine, causing pain and other digestive disturbances.

Currently, there are several ways to prevent symptoms, with the most common being a gluten-free diet, which has proven effective, enzymatic therapy, and prevention programs such as replacing wheat flour with chickpea flour or corn flour products.

Additionally, checking product labels for “gluten-free” indication and always reading the composition of purchased products is important, as they may contain traces of gluten, even if it seems unlikely.

Understanding Lactose Intolerance

Lactose is the sugar found in milk. This sugar is broken down (hydrolyzed) in the intestine by the enzyme lactase into two smaller parts, galactose and glucose, which then become energy for our bodies.

Lactose may not be metabolized by the digestive system when there is a decrease in hydrolysis capacity, meaning a decrease in lactase enzyme activity in the mucosa of the small intestine, characterizing lactose intolerance (14).

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

Lactose intolerance occurs when there is an imbalance between the amount of lactase enzyme present in the intestinal mucosa and the amount of ingested lactose that reaches the digestive tract (excess undigested lactose remains in the lumen of the intestinal mucosa), causing characteristic changes in the clinical picture.

For symptom prevention, it is recommended to temporarily avoid milk and dairy products from the diet, not consume anything containing high amounts of lactose, and consume plant-based beverages such as rice, soy, or oat milk, which are good substitutes for milk.

The highest concentrations of lactose are found in milk and ice cream, while cheeses generally contain smaller amounts. Therefore, it is important to read the composition of purchased products, which may not be so easy due to the presence of foods with unidentified lactose in their composition (16).

However, total and definitive exclusion of lactose from the diet should be avoided, as it may lead to nutritional deficiencies of calcium, phosphorus, and vitamins, and be associated with decreased bone mineral density and fractures (17).

Most lactose intolerant individuals can consume 12 g/day of lactose (equivalent to one glass of milk) without experiencing adverse symptoms (18). Consumption of lactose-free dairy products helps ensure calcium intake.

How to Know If You Have Food Intolerance? What Test Detects Food Intolerance?

Diagnosing food intolerance is usually not straightforward and requires an understanding of the presentation of clinical manifestations, including the severity and timing of symptom onset.

Due to nonspecific symptoms, the inability to be detected in skin tests, and the lack of a rapid cause-and-effect response, food intolerances are even more difficult to detect.

Since there are different mechanisms of food intolerance, ranging from pharmacological to enzymatic deficiencies (e.g., lactose absorption) and nonspecific gastrointestinal function, its diagnosis can be even more complicated.

With the advancement of science and innovative tests such as the A200 test. Identifying the profile of food intolerance through these tests, which assess the main foods related to this type of reaction, has ensured better guidance in clinical management and consequently in patient treatment.

What Are the Symptoms of Food Intolerance?

Food intolerances, in general, can be associated with symptoms after the recurrent consumption of a specific food. Some common symptoms of food intolerance include:

• Diarrhea
• Constipation
• Stomach pain
• Feeling of bloating
• Gastric reflux
• Gas
• Irritable bowel
• Muscle and joint pains
• Fatigue
• Headaches
• Skin infections.

Removing the foods that cause intolerance from the diet significantly improves the symptoms (10,11,19,20).

What is Food Allergy?

Food allergy is an immune reaction triggered shortly after ingesting a particular food, even in small quantities. 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 (21). It is estimated that food allergy affects about 6 – 8% of children under three years old, with patients with other allergic diseases (22) having a higher incidence of food allergy, that can be found in 38% of children with atopic dermatitis and in 5% of children with asthma, and up to 3% of adults.

Genetic predisposition factors have been reported to be involved in the pathogenesis of food allergy. Studies indicate that 50 to 70% of patients with food allergy have a family history of allergies. It is estimated that if at least one parent has food allergy, the probability of having allergic children is 75% (22).

What are the types of food allergies?

• Non-IgE-mediated food allergies: There are also non-IgE-mediated food allergies (23), which mainly affect the respiratory tract. It is believed that specific allergen T cells are related to the etiology of syndromes induced by food proteins, such as enterocolitis, proctocolitis, and enteropathy.

These pathologies mainly affect babies and children allergic to cow’s milk and usually cease by about 1-5 years old. Due to the lack of diagnostic tests, their prevalence remains uncertain.

• IgE-mediated food allergy: Another type of food allergy known as mixed pathway-induced (25), is characterized by both IgE-dependent and independent pathways. It causes atopic manifestations resulting from IgE-independent factors such as atopic dermatites (24), which are associated with late food allergy (symptoms appear 6 – 48 hours after food ingestion), caused by the action of Th2 helper cells and eosinophilic gastrointestinal disorders, caused by eosinophil infiltration into tissues.

The symptoms of food allergy can occur shortly after ingesting a particular food and can affect different organ systems such as the skin, gastrointestinal tract, cardiovascular, and respiratory systems (21).

Symptoms include abdominal pain, nausea/vomiting, hoarseness, hives, rash, itching, swelling of the 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 of IgE-mediated food allergies include (25):

• Itching,
• Hives,
• Angioedema,
• Abdominal pain,
• Vomiting,
• Wheezing,
• Hypotension.

Cases of mixed food allergy differ depending on their association. Cases associated with atopic dermatitis may worsen. Cases of eosinophilic esophagitis allergy may present with vomiting, growth alterations, dysphagia, and heartburn, and those related to other eosinophilic gastrointestinal disorders vary according to the region and gastrointestinal involvement.

Cases of non-IgE-mediated food allergies may result in symptoms such as severe vomiting with intermittent exposure, chronic diarrhea and difficulty improving, rectal bleeding, and steatorrhea (excess fat in stools) due to malabsorption with chronic exposure.

How to Diagnose a Food Allergy?

The diagnosis of food allergy is made by analyzing symptoms, considering the patient’s description and signs presented. Some tests are commonly performed to assist in the final diagnosis (26):

Skin Tests

When performed alone, they do not confirm the diagnosis of food allergy; they only detect the presence of specific IgE antibodies to certain foods, demonstrating sensitization.

It is a widely used test for patients with IgE-mediated milk allergy. About 1/3 of patients with atopic dermatitis have cow’s milk allergy, and about 50% of milk-allergic infants have atopic dermatitis. Although it may result in false positives (up to 24% false positives) in children with atopic dermatitis, false negative results are uncommon (27).

Specific IgE Measurement

Measures specific IgE antibodies to suspected foods. The test reveals the presence/absence of IgE for certain foods. They do not necessarily indicate that ingestion results in clinical reactions.

However, negative results are valuable as they are highly sensitive and result in about 95% accuracy for excluding IgE-mediated reactions. However, a positive result is associated with true clinical reactions only 50% of the time.

RAST (Radioallergosorbent Test) and In Vitro Semiquantitative Assays

Provide evidence of IgE-mediated food allergy. The fluorescent enzyme immunoassay methodology (CAP System) is most suitable for cases of symptomatic food allergy.

The analysis of quantitative levels of specific IgE considerably increased the positive predictive value and excluded the need for oral provocation tests in approximately 50% of cases (28).

Exclusion Diet

Based on the analysis of medical history and physical examination suggestive of food allergy, exclusion of the suspected food from the diet is performed when identified. After 2-6 weeks of excluding the food, symptoms may or may not disappear.

However, a favorable clinical response to an exclusion diet does not have good reliability and may be just a coincidence. It is also used for cases of non-IgE-mediated food allergy.

Oral Provocation Tests

When signs and symptoms disappear after exclusion. If they disappear, an oral provocation test is suggested to confirm the diagnosis of the suspected food. The test involves administering the same food to the patient and is considered positive if symptoms reappear.

They are indicated for diagnostic confirmation or to ascertain whether the patient has become tolerant to the food and are contraindicated in cases of a history of severe anaphylactic reaction. Specialized medical supervision is required for test execution. It is also used for cases of non-IgE-mediated food allergy.

Esophageal/Gastrointestinal Biopsy

Used for cases of suspected mixed food allergy related to eosinophilic gastrointestinal disorders, caused by eosinophil infiltration into 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

Indicated for cases of food protein-induced enterocolitis syndrome. Seeks to detect villous atrophy and crypt hyperplasia.

How to Treat Food Allergy?

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

Adrenaline works by reversing edema, hives, bronchospasm, hypotension, and gastrointestinal symptoms within minutes. It is considered most effective in early treatment (within 6 minutes of exposure), with early response being the primary factor in preventing death from anaphylaxis (29).

It is estimated that approximately 20% of people with food allergy may experience a biphasic reaction (30), where symptoms recur a few hours after initial adrenaline treatment. A late or insufficient first dose of adrenaline is believed to increase the risk of a biphasic reaction.

Other medications, 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, available medications only treat symptoms and not the cause of food allergies.

Desensitization immunotherapy involves sublingual, oral, or dermal administration of an allergen extract (30). It represents significant progress in food allergy treatment.

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 desensitization immunotherapy in 40 individuals with peanut allergy, with a defined response to tolerate a dose of 5g of peanut powder or a 10-fold increase in the initial dose. After 44 weeks, 70% of the 20 individuals in treatment increased the tolerated dosage from 3.5 mg to 496 mg (equivalent to 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 others, patients can be desensitized not only to prevent life-threatening reactions due to accidental exposure but also to be able to consume determined quantities of allergenic foods.

Understanding the mechanisms of molecular processes involved in sensitizing individuals has led to the development of monoclonal antibodies (31) as therapeutic agents to aid in blocking sensitization.

Promising results indicate that oral immunotherapy together with monoclonal antibodies may allow the immune system to desensitize to food allergens more quickly and safely than 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 specialized physician for proper evaluation and to establish an effective treatment plan.

What are the differences between food allergy and food intolerance?

Food allergy is a hypersensitivity that we develop to certain foods, mediated by immunoglobulin E (commonly known as IgE) triggering immediate reactions (called type I hypersensitivity reactions) with possible involvement of the mucosa, skin, airways, gastrointestinal tract, and vascular system.

Primary food allergy is based on early sensitization of IgE against animal proteins (e.g., cow’s milk, chicken eggs) or plant proteins (e.g., peanut, hazelnut, or wheat).

In the case of secondary food allergies, IgE against pollen proteins (e.g., birch) reacts to structurally related food proteins (with cross-reactions to stone fruits, for example).

Food allergy occurs when the body seeks to defend itself against the entry of certain foods, even in small quantities. Upon identifying them as foreign bodies, the body produces antibodies for defense.

Food allergies typically appear when the patient is still very young. Intolerances, however, can occur at any time due to the difficulty in digesting a particular food, becoming more frequent as we age.

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