Causes of Food Intolerance

By Dr. Liji Thomas, MD

Food intolerance is a functional or structural intolerance to food, which is non-immunologic and non-toxic in origin, but is chemically based instead. A third type of food intolerance involves the effects produced by pharmacologically active amines and other compounds present in foods.

Thus, food intolerance describes a range of food-related symptoms that are not immunologically-mediated. These account for the majority of food reactions.

Functional intolerance

Functional food intolerance is not associated with structural abnormalities of the digestive tract, but may be due to an isolated enzyme deficiency. A prime example of functional food intolerance is lactose intolerance.

Enzymatic defects

Carbohydrate intolerances involve the inability to digest and absorb sorbitol, fructose or other simple sugars. Lactase deficiency is the best known and is the cause of intolerance to milk and other dairy products, which contain lactose, also known as milk sugar.

Other examples include the isolated or combined disaccharide malabsorption syndrome, which prevents the absorption of sucrose, lactose and other disaccharides, either one in particular or all together. In addition to this, there is isolated maltase, galactase or saccharase deficiency.

When these sugars are not absorbed properly, they reach the large intestine in increased amounts, resulting in excessive fermentation and bacterial overgrowth. The production of osmotic sugars and their fermentation products in larger quantities causes symptoms, such as meteorism (i.e. the accumulation of excess gas in the gastrointestinal tract), flatulence and diarrhea, as described below.

Diamine oxidase deficiency may cause histamine intolerance.

Transport defects

Other than enzyme deficiencies, transporter molecule defects may be present. These include defects in GLUT 5, which transports fructose, or GLUT 2 for glucose, galactose or fructose. The inability to transport these carbohydrates into the intestinal cells results in their metabolism in the large intestine where they are transported intact in large quantities. Bacterial fermentation of these sugars produces short-chain fatty acids, methane, hydrogen and carbon dioxide. These gases and decomposition products lead to abdominal pain, diarrhea, flatulence and bloating.

Bacterial overgrowth of the small bowel

Patients who are at risk for bacterial overgrowth include those who have been surgically treated by bowel resection, or are on chronic treatment with proton pump inhibitors, such as ranitidine or omeprazole. This leads to symptoms of food intolerance following ingestion of a number of foods, due to the release of excessive bacterial decomposition products in the gut.

Active compounds in foods

Many foods contain compounds with intrinsic biologic activity, such as:

  • Salicylates, as in curries, peppers and some spices, as well as fruits like raisins, sultanas, oranges and pears.
  • Biogenic amines, such as histamine, serotonin or tyramine, as in chocolates, may lead to intolerance due to enzyme deficiencies, such as diamine oxidase or histamine N-methyl transferase. Foods which are rich in histamine include fermented foods, such as sauerkraut, aged cheese and red wine.

Other foods release histamine, such as citrus fruits or nuts. Black tea and some colorants actually inhibit diamine oxidase. In addition, factors that increase histamine release may precipitate intolerance, such as sports activity, some infections or emotional upsets.

Idiosyncratic intolerances

Some substances evoke individual intolerances, such as:

  • Sulfites used in wines and some medications
  • Monosodium glutamate used as a flavor enhancer in many Oriental foods
  • Coloring and preservative agents, such as benzoates and tartrazine dye
  • Artificial sweeteners like aspartame

Infections and other causes

Some intolerance-like symptoms are due to:

  • Chronic infections of the digestive organs, such as giardiasis.
  • Carcinoid tumors and other neuroendocrine tumors, which can induce severe and acute symptoms of intolerance to small amounts of biogenic amines.
  • Some psychosomatic reactions can cause symptoms, which closely mimic those of true food intolerance  like anorexia nervosa.
  • Infections that are due to certain strains of Escherichia coli called EHEC and ETEC.
  • Chronic bowel disease due to tissue transglutaminase antibodies (anti-tTG) in celiac disease. This may in turn precipitate other intolerances due to the development of various enzyme deficiencies, such as lactase deficiency.
  • Systemic mastocytosis, which is due to an abnormality of mast cell proliferation, maturation and degranulation.

Structural intolerance

Structural intolerance is due to abnormal structure of the digestive tract; for example, this occurs with intestinal diverticula. Here food is trapped within the outpouchings with resulting bacterial overgrowth. The production of abnormal fermentation products results in secondary gastrointestinal symptoms, such as bloating and diarrhea.

Examples of structural abnormalities of one or more parts of the digestive tract include:

  • Esophageal achalasia
  • Gallbladder disease leading to fat malabsorption
  • Chronic pancreatitis
  • Intestinal diverticula or bacterial overgrowth
  • Chronic inflammatory bowel disease
  • Colonic diverticula
  • Post-inflammatory strictures or other abnormality
  • Lympho-vascular abnormalities


Reviewed by Jonas Wilson, Ing. Med.

Further Reading

Last Updated: Sep 26, 2016

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