Allergies and Intolerances - are they the same?

Some adverse reactions can occur in your body following food intake. These can be immunologic (known as food allergies) or non-immunologic (known as food intolerances). Given that their discrimination is sometimes confusing not only for people experiencing the food issue but also for physicians, a correct diagnostic approach of the food reaction is necessary to manage the dietary problem and to prevent potential nutritional deficiencies. 

Immune response versus non-immune response

A food allergy is defined as an adverse health effect arising from a specific immune response that occurs on exposure to a given food. It is generally caused when a specific molecule within food (usually a protein) triggers a reaction of the immune system that tries to battle the “invader”. This reaction can be mainly mediated by a specific type of antibodies known as immunoglobulins E (IgE) or by other immune responses. The IgE-mediated food allergies are characterized by its rapid onset –from few minutes to an hour– after the allergen intake. Their signs and symptoms can be mild and localized or can affect different systems in what is called systemic anaphylaxis (a serious life-threatening allergic reaction). The non-IgE-mediated food allergies are disorders caused by some proteins present in food and are characterized by an early onset (normally within the first year of life) and gastrointestinal problems. This group of allergies includes the well-known celiac disease, triggered by dietary gluten –a protein found in cereals such as wheat, rye, and barley–, and other food protein-induced gastrointestinal issues such as the food protein-induced allergic proctocolitis (FPIAP), typically induced by cow’s milk proteins.

On the other hand, a food intolerance, also known as non-immunological adverse reaction to food, is a non-immune reaction that include metabolic, toxic, pharmacologic or other unknown mechanisms. It is mostly a digestive problem that occurs when a specific molecule within food irritates the digestive system (a host-independent intolerance) or when a person cannot properly digest or break down the molecule (a host-dependent intolerance). Food intolerances  are mainly characterized by their gastrointestinal clinical manifestations and, unlike food allergies, are dose-dependent, being the amount of food molecule directly related to the severity of symptoms. Host-independent intolerances are caused by natural food chemicals such as histamine or food additives such as glutamates or sulfites. Host-dependent intolerances are mainly caused by a shortage or malfunction of the enzymes breaking down the food molecule. This is the case of the well-known lactose intolerance –when the enzyme lactase activity is lacking–, or fructose intolerance –when the enzyme aldolase B activity is lacking–. 

How frequent are food allergies and intolerances in the population?

Although there is a discrepancy between the perceived number of food-related adverse effects and their true number within the population after diagnosis, recent studies indicate an increasing trend of pediatric and adult food allergies as well food intolerances in westernized countries. The eight most common self-reported food allergies in the US are shellfish (~3% of population), cow’s milk (~2%), peanut (~2%), tree nuts (~1%), wheat (~1%), egg (~1%), fish (~1%) and soy (~0.5%). Regarding food intolerances, a recent survey in the US among adult internet users showed that 1 out of 4 participants self-reported a food intolerance.

 Cow’s milk: a paradigmatic example of a food triggering allergy and intolerance 

Humans have been extracting and consuming milk from domestic animals for thousands of years. Cow’s milk is still one the most produced nutritionally rich beverages in the world. It is composed of water (85−87%), fats –primarily triglycerides– (3.8−5.5%), proteins –such as casein, alpha-lactalbumin and beta-lactoglobulin– (2.9−3.5%) and carbohydrates –primarily lactose, glucose, and galactose– (5%), as well as several vitamins, minerals, and other metabolites. Two of these molecules are related to some of the most frequent food reactions in US population: cow’s milk protein (especially casein and alpha-lactalbumin) and lactose. Cow’s milk proteins are involved in a non-IgE-mediated food allergy characterized by hives, itching and/or swelling of mouth, vomiting, and diarrhea, among others symptoms, which can eventually worsen to anaphylaxis. Lactose is involved in a host-dependent food intolerance characterized by several gastrointestinal problems including abdominal pain and distension, bloating, flatulence, and diarrhea, usually starting from thirty minutes to a few hours after eating or drinking the lactose-containing food. Due to lack of enzyme lactase activity, the undigested lactose is accumulated in the colon and is subsequently digested by colonic bacteria, which produce several gasses including hydrogen, carbon dioxide, and methane, affecting the normal gastrointestinal function.

 What are the symptoms of food allergies and intolerances?

Food allergies generally involve a combination of gastrointestinal problems and clinical manifestations in other body parts, depending on the severity of the immune response. The main  symptoms of IgE-mediated food allergies are gastrointestinal tract hypersensitivity including itching, tingling sensation and mild edema of mouth, nausea, abdominal pain, cramps, vomiting, and/or watery/mucous diarrhea. Beyond the gastrointestinal system, cutaneous problems such as hives and respiratory problems such as asthma can also appear. In serious allergic events where anaphylaxis is present, neurological problems such as dizziness or unconsciousness and cardiovascular problems such as fast heartbeat or low blood pressure may arise. In some severely allergic patients, even a very small amount of food can cause a life-threatening reaction. In non-IgE-mediated food allergies the main gastrointestinal clinical symptoms are vomiting and diarrhea. In particular, celiac disease patients can show, in addition, bloating and gas, fatigue, anemia, weight loss and neurological problems. 

 The spectrum of symptoms of food intolerances include gastrointestinal problems such as abdominal pain, bloating, abdominal distension, flatulence, and diarrhea. In addition, some host-independent intolerances may mimic food allergies symptoms presenting with chronic hives or swelling, low blood pressure, flushing or asthma. However, there is a delay in symptom onset and a prolonged symptomatic phase compared to true food allergies.

 How can they be diagnosed and treated? 

For an accurate diagnosis of any food allergy or intolerance, a detailed medical history documenting the timing and clinical features of the reactions attributed to food is mandatory. In IgE-mediated allergies, the clinical history reported by the patient can guide for the execution of several tests that will help in the final diagnosis. These include in vivo tests such as the elimination diet or the oral food challenge, and in vitro tests such as the measurement of IgE concentration in blood. In food intolerances a “food and symptoms diary” can be useful in the diagnostic process. In lactose intolerance, for example, after clinical evaluation, the diagnosis can be confirmed by the resolution of symptoms after avoiding lactose-containing foods for 5 to 7 days.

The clinical management of all types of food allergies includes both short-term interventions for acute reactions and long-term strategies to minimize the risk of further reactions. For acute severe IgE-mediated reactions epinephrine injections are used, and antihistamines and steroids are used for milder reactions. As long-term therapies, the removal of offending foods from diet –what is known as avoidance diet– is the golden standard. Also allergen immunotherapy can be used by exposing an allergic individual to initially small, gradually increasing quantities of the specific allergen responsible for clinical presentations in order to get an immune system tolerance. This is the case of the recently FDA-approved Peanut Allergen Powder® for the treatment of peanut allergy in children. Food intolerances are generally managed by restricting food intake containing the insulting molecule, such as in histamine or lactose dietary restrictions. In lactose intolerance, a bacterial adaptation or tolerance can be induced by using prebiotics or regular consumption of lactose-containing products, or administering exogenous enzymes as capsules/tablets (such as Lactaid®) before eating. 

 Prevention and nutritional concerns

Patients suffering from food allergies are at risk of both severe acute anaphylaxis and the worsening of chronic conditions. The problems experienced by patients with food intolerances are more related to correctly identify the thousands of chemical or natural food additives in their Western diets. Hence a correct diagnosis and discrimination of a food reaction (allergy or intolerance) is essential for a fast an adequate management. Also professional support is necessary for achieving correct nutritional standards when diets need to be chronically replaced due to necessary exclusion of particular food allergens.

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 References: 

Gargano D, Appanna R, Santonicola A, De Bartolomeis F, Stellato C, Cianferoni A, Casolaro V, Iovino P. (2021). Food Allergy and Intolerance: A Narrative Review on

Nutritional Concerns. Nutrients, 13(5):1638

https://my.clevelandclinic.org/health/diseases/10009-food-problems-is-it-an-allergy-or-intolerance

https://www.mayoclinic.org/diseases-conditions/food-allergy/expert-answers/food-allergy/FAQ-20058538?p=1

https://www.mayoclinic.org/diseases-conditions/milk-allergy/symptoms-causes/syc-20375101

https://www.mayoclinic.org/diseases-conditions/celiac-disease/symptoms-causes/syc-20352220