Food Intolerance: What Causes It?

Food Intolerance: What Causes It?


Food intolerance is a reduced ability of the body to digest certain types of food or food components. While less dangerous than food allergy, it lowers the quality of life of many people around the world. Find out about its causes and management.

What Is Food Intolerance?

Food intolerance is a problem with digestion of certain foods, usually accompanied by an unpleasant physical reaction. [1] This may include abdominal pain, rash, vomiting, bloating, or diarrhea. The onset of such symptoms is usually within hours after eating the food, but could be up to days. 

Studies show that approximately 3.6% of people have adverse reactions to food in their medical records. [2] This includes both food allergy and food intolerance, two commonly confused conditions. Here’s how to discern them:

Not mediated by immune system 

Food intolerance, unlike food allergy, is not mediated by a hypersensitive reaction of the immune system. [3] Usually, the culprit is an insufficient enzyme that cannot effectively degrade a specific food molecule. 

Longer onset of symptoms

With food intolerance, the symptoms occur gradually (in hours), while food allergy symptoms present almost immediately. This is also why the diagnosis of food intolerance is often so elusive - when symptoms occur hours (or days!) after eating, it is hard to link them with a specific food.

Not a life threat 

Food intolerance is not life-threatening - as opposed to food allergy, which may result in anaphylaxis. The anaphylactic reaction is a medical emergency with rapid onset of symptoms such as rash, serious shortness of breath, vomiting and low blood pressure. In people with food allergy, this reaction can be triggered by trace amounts of food, while in food intolerance, this is virtually never the case. [4]


The most common way to diagnose food intolerance is by elimination diet. First, you create a food diary, noting what food you ate at what time. Then, you link the symptoms with a particular food. The suspect food is excluded from the diet for 2-6 weeks [1] to see whether symptoms disappear or not. If they do, the food is reintroduced little by little. Often, people find that there is a certain amount of the food they can tolerate without any symptoms.

As for laboratory testing, measuring antibody levels is the standard for differential diagnostics of some conditions. To name a few, anti-gliadin antibodies are measured when suspecting celiac disease, and anti-lactalbumin antibodies are tested for in non-IgE mediated cow-milk allergy  (both in IgG and IgA class). [3]

Another option is FOX (Food Xplorer), a testing kit for IgG antibodies against 286 food antigens. The results, however, are not diagnostic in themselves and must be carefully interpreted by your doctor. This is because increased levels of IgG antibodies may represent normal immunological response to food antigens. [5] In fact, increased IgG4 denote tolerance rather than hypersensitivity. [4]

The 8 Most Common Food Intolerances

1. Dairy

People whose symptoms occur after eating dairy products are very often lactose intolerant. In fact, the current estimates [6] suggest that 68% of people globally have some form of this condition. 

Lactose is a sugar contained in milk. It is digested by the enzyme lactase in the gut, which enables its absorption into the blood. Lactose intolerant people produce insufficient amounts of this enzyme. Undigested lactose then draws a lot of water into the gut, causing diarrhea. As lactose passes further into the colon, it is fermented by the microbiome in a process producing gas. This is why people also experience bloating and flatulence. [4] All of these lactose intolerance symptoms are commonly accompanied by nausea.

As of now, there is no cure for lactose intolerance. However, symptoms can be controlled by a lactose-free diet. Patients are advised to avoid yogurt, milk, ice creams or soft cheeses. 

2. Gluten 

Gluten is an umbrella term for some proteins contained in wheat, barley and rye. [4] In some people, eating gluten-rich foods induces unpleasant symptoms, such as bloating, diarrhea or abdominal pain. These are, however, not always attributable to gluten intolerance itself. This is because there are three different gluten-related health conditions: gluten intolerance, wheat allergy and celiac disease. Since their symptoms and associated health risks differ, it is useful to be able to distinguish them.

Celiac disease

Celiac disease is an autoimmune condition. This means that one’s own immune system attacks the body's own cells. In untreated cases, celiac disease can cause serious damage to the intestinal mucous membrane.

This condition is based on the immune system’s hypersensitive reaction to gliadin, a protein found in gluten. [7] In other words, when gluten enters the gut, inflammation occurs. In the short term, this presents as bloating, diarrhea and nausea. In the long term, however, severe damage to the intestinal cells occurs. That’s why it is so important for these patients to avoid eating gluten altogether.

At the level of genetics, there are two alleles that predispose for celiac disease: HLA-DQ2, HLA-DQ8. [4] Both of these are looked for when diagnosing celiac disease. 

Another important diagnostic test for celiac disease is the measuring of various antibody levels. Specifically, these include anti-TG (transglutaminase), anti-DGP (gliadin fragments), as well as anti-EMA (endomysium) in classes IgG and IgA. [7]

Wheat allergy

Wheat allergy is also mediated by the immune system. In this case, however, antibodies (IgE class) are produced against some of the proteins in wheat, but not necessarily gluten. [4]

Wheat allergy is characterized by a rapid onset of nausea, hives or rash after eating food containing wheat. Swelling and itching of the mouth and throat are other very common symptoms. In severe cases, wheat allergy can be life-threatening in the form of an anaphylactic reaction (with symptoms such as breathing difficulties or fainting). This requires immediate medical attention.

Wheat allergy can be diagnosed just like any other food allergy, by skin-prick tests and elimination diets.

Gluten intolerance

There are also people who experience unpleasant symptoms, but show no signs of celiac disease or wheat allergy in their laboratory and clinical tests. These are often, by exclusion, diagnosed with gluten intolerance (a.k.a. non-celiac gluten sensitivity). [8]

Gluten sensitivity symptoms include: [9]

  • bloating
  • diarrhea
  • abdominal pain
  • rash
  • headaches and fatigue
  • depression 


The management of gluten intolerance, wheat allergy, as well as celiac disease is a gluten-free diet. [1] Patients need to avoid gluten-containing food, such as bread, pasta, beer, cereals or soy sauce.

3. Caffeine 

Caffeine is a molecule found in coffee, tea, cola, and energy drinks. It increases alertness and attention, while decreasing drowsiness. For this reason, it is referred to as a stimulant.

Caffeine acts by blocking adenosine receptors, which are found in the central nervous system, heart, or the colon. In our brains, adenosine is a sleep-inducing molecule. That’s why caffeine decreases drowsiness by blocking its effects. [10] Adenosine also lowers heart frequency. [11] Drinking caffeine-rich beverages, therefore, has the inverse effect of increasing the heart frequency. Interestingly, adenosine also regulates the motor activity of the colon. [12] This may also explain why many people report that even just a sip of coffee makes them want to go to the toilet immediately.

In sensitive people, all of these effects may be amplified to the point when they become very unpleasant. Alertness turns to anxiety or insomnia, increased heart frequency becomes dangerously rapid heartbeat, and the urge to defecate reaches the level of diarrhea. Many also complain of heartburn. [12]

The basis of caffeine hypersensitivity is genetic, to an extent (a variation in adenosine receptors). [10] Another important factor is the variation in the enzymes that metabolize caffeine.

People with caffeine hypersensitivity should avoid drinking caffeine-rich beverages such as coffee, tea, cola, or energy drinks.

4. Salicylates

Salicylates are naturally occurring chemicals in plants, which serve as protection against  insects and pathogens. [13] These molecules can be found in almost every food, as well as some medications and perfumes. Salicylates generally have anti-inflammatory properties. Take aspirin, for instance - it is nothing else than acetyl-salicylic acid.

In people with salicylate intolerance, unpleasant reactions occur in place of anti-inflammatory effects. The symptoms are often respiratory in nature [13], and include:

  • stuffy nose
  • asthma
  • nasal polyps
  • intestinal inflammation
  • hives

Salicylate elimination diets tend to be very restrictive, as salicylates occur in a vast array of foods. That said, avoiding “salicylate-bombs” such as spices, oranges and berries may have some positive effect. [13] Salicylate containing medications and those acting on COX-1 enzyme (e.g. aspirin and ibuprofen) should also be avoided. [13] In patients with severe symptoms, topical or systemic corticosteroid therapy is used. 

5. Histamine

Histamine is a molecule involved in immune reactions, neurotransmission and regulation of digestive functions. It is one of the mediators responsible for itching and swelling. The role of histamine is to make capillaries more permeable for white blood cells to enter into the infection site. [4]

Histamine is present to various degrees in foods we eat on a daily basis. There is a natural balance between its degradation, intake and production. In our bodies, the degradation is enabled by the enzyme diamine oxidase (DAO). [14] It is precisely this enzyme that is dysfunctional in people with histamine intolerance.

When histamine cannot be degraded properly, it accumulates in the body. Since it is a regulatory molecule, its buildup causes a variety of symptoms: [14]

  • hives, itching
  • headache, dizziness
  • difficulty breathing
  • bloating, diarrhea or nausea

People with histamine intolerance are advised to adhere to a low histamine diet. This consist mainly of avoiding high histamine foods, such as:

  • fish (esp. canned)
  • meat (esp. cured)
  • matured cheeses
  • beer, wine & other fermented beverages
  • beans, soy, mushrooms, tomatoes
  • citrus fruits, raisins, strawberries
  • chocolate  


The abbreviation FODMAPs stands for fermentable oligo-, di-, mono-saccharides and polyols. [15] It is a group of short-chain sugars found in various foods. In sensitive people, FODMAPs can be responsible for intestinal distress.

FODMAPs are not absorbed in the small intestine to any significant degree, and so they travel to the large intestine. [15] There, they are fermented by gut bacteria. In sensitive people, this process produces excess gas, and draws water into the gut.

The symptoms include: [15]

  • cramps
  • diarrhea
  • constipation
  • bloating and flatulence

FODMAP intolerance is prevalent especially in people with irritable bowel syndrome (IBS). Emerging data suggests that a low FODMAP diet brings symptom relief in these patients. [16] With low FODMAP diet, people must avoid: [16]

  • wheat, barley, rye
  • beans, beetroot, lentils
  • apples, avocados, peaches

7. Sulfites

Sulfites are chemicals used as preservatives in foods and medications. While most tolerate them well, sulfites can cause adverse reactions in sensitive individuals. Sulfite sensitivity is most prevalent in asthmatics. [17] The most common symptoms are: [17]

  • hives
  • abdominal pain and diarrhea
  • hypotension
  • coughing and wheezing
  • severe asthmatic reaction

When a food or medication contains sulfite additives, it must be declared so on the packaging. Usually, products like wine, dried fruit, chips, pickled goods are relatively high in sulfite content. [17]

8. Fructose

Fructose is a simple carbohydrate (sugar) found in fruit, vegetables and sweeteners. High fructose foods include apples, grapes, peas, zucchini, honey, and syrups. Another significant source of fructose are soft beverages containing high amounts of fructose corn syrup. This, incidentally, is one of the reasons why the consumption of fructose is on a steady rise. [18]

Absorption of fructose in the small intestine is not dependent on any digestive enzymes. Rather, it relies on GLUT transporters. [18] These have a different capacity in different people, so once the capacity is overwhelmed by high intake of fructose, symptoms of malabsorption occur. Then, fructose travels to the colon, where it is fermented by gut bacteria, producing gas and drawing water to the colon. The symptoms of fructose intolerance are: [18]

  • bloating and gas
  • diarrhea
  • abdominal pain
  • nausea and vomiting

Fructose intolerance can be inborn, or acquired by intestinal damage, diabetes, celiac disease or Crohn disease. [18] Avoiding high fructose foods and beverages is necessary to control the symptoms. 

Note: fructose intolerance (a.k.a. fructose malabsorption) is not to be confused with hereditary fructose intolerance: a much more serious condition characterized by a deficiency in a liver enzyme.

Other Common Food Intolerances 

Egg intolerance

In sensitive people, egg whites can cause abdominal discomfort or diarrhea. [19] This is different from egg allergy, which can be life-threatening.

Food colorings

Some food colorings (e.g. Red 40) can cause mild adverse reactions, mostly of the skin. [20]


There are many other molecules that have been linked with intolerance, such as aspartame or MSG. However, the research on their adverse effects is largely inconclusive, and they are considered safe by the FDA. [21] While some studies do show that these substances can cause some symptoms, it is usually at dosages that far exceed those normally consumed. [21]

The takeaway

Food intolerances are, unlike food allergies, not life-threatening and not mediated by the immune system.

If you are experiencing adverse reactions to food, intolerance can be established by elimination diets and laboratory tests. 

While more unpleasant than dangerous, diagnosing and managing your food intolerance can significantly improve your life quality.