Food intolerance is a detrimental reaction, often delayed, to a food, beverage, food additive, or compound found in foods that produces symptoms in one or more body organs and systems, but generally refers to reactions other than food allergy. Food hypersensitivity is used to refer broadly to both food intolerances and food allergies.
Food allergies are immune reactions, typically an IgE reaction caused by the release of histamine but also encompassing non-IgE immune responses. This mechanism causes allergies to typically give immediate reaction (a few minutes to a few hours) to foods.
Food intolerances can be classified according to their mechanism. Intolerance can result from the absence of specific chemicals or enzymes needed to digest a food substance, as in hereditary fructose intolerance. It may be a result of an abnormality in the body's ability to absorb nutrients, as occurs in fructose malabsorption. Food intolerance reactions can occur to naturally occurring chemicals in foods, as in salicylate sensitivity. Drugs sourced from plants, such as aspirin, can also cause these kinds of reactions.
Definitions Food hypersensitivity is used to refer broadly to both food intolerances and food allergies. There are a variety of earlier terms which are no longer in use such as "pseudo-allergy".
Food intolerance reactions can include pharmacologic, metabolic, and gastro-intestinal responses to foods or food compounds. Food intolerance does not include either psychological responses or foodborne illness.
A non-allergic food hypersensitivity is an abnormal physiological response. It can be difficult to determine the poorly tolerated substance as reactions can be delayed, dose-dependent, and a particular reaction-causing compound may be found in many foods.
Metabolic food reactions are due to inborn or acquired errors of metabolism of nutrients, such as in lactase deficiency, phenylketonuria and favism. Pharmacological reactions are generally due to low-molecular-weight chemicals which occur either as natural compounds, such as salicylates, amines and glutamates or to food additives, such as preservatives, colouring, emulsifiers and flavour enhancers. These chemicals are capable of causing drug-like (biochemical) side effects in susceptible individuals. Gastro-intestinal (GI) reactions can be due to malabsorption or other GI tract abnormalities. Immunological responses are mediated by non-IgE immunoglobulins, where the immune system recognises a particular food as a foreign body. Toxins may either be present naturally in food, be released by bacteria, or be due to contamination of food products. Toxic food reactions are caused by the direct action of a food or substance without immune involvement. Psychological reactions involve manifestation of clinical symptoms caused not by food but by emotions associated with food. These symptoms do not occur when the food is given in an unrecognisable form.
Elimination diets are useful to assist in the diagnosis of food intolerance. There are specific diagnostic tests for certain food intolerances.
Signs and symptoms
Food intolerance is more chronic, less acute, less obvious in its presentation, and often more difficult to diagnose than a food allergy. Symptoms of food intolerance vary greatly, and can be mistaken for the symptoms of a food allergy. While true allergies are associated with fast-acting immunoglobulin IgE responses, it can be difficult to determine the offending food causing a food intolerance because the response generally takes place over a prolonged period of time. Thus, the causative agent and the response are separated in time, and may not be obviously related. Food intolerance symptoms usually begin about half an hour after eating or drinking the food in question, but sometimes symptoms may be delayed by up to 48 hours.
Food intolerance can present with symptoms affecting the skin, respiratory tract, gastrointestinal tract (GIT) either individually or in combination. On the skin may include skin rashes, urticaria (hives), angioedema, dermatitis, and eczema. Respiratory tract symptoms can include nasal congestion, sinusitis, pharyngeal irritations, asthma and an unproductive cough. GIT symptoms include mouth ulcers, abdominal cramp, nausea, gas, intermittent diarrhea, constipation, irritable bowel syndrome (IBS), and may include anaphylaxis.
Food intolerance has been found associated with irritable bowel syndrome and inflammatory bowel disease, chronic constipation, chronic hepatitis C infection, eczema, NSAID intolerance, respiratory complaints, including asthma, rhinitis and headache, functional dyspepsia, eosinophilic esophagitis and ear, nose and throat (ENT) illnesses.
Causes
Reactions to chemical components of the diet may be more common than true food allergies, although there is no evidence to support this. They are caused by various organic chemicals occurring naturally in a wide variety of foods, animal and vegetable, more often than to food additives, preservatives, colourings and flavourings, such as sulfites or dyes. Both natural and artificial ingredients may cause adverse reactions in sensitive people if consumed in sufficient amounts, the degree of sensitivity varying between individuals.
Pharmacological responses to naturally occurring compounds in food, or chemical intolerance, can occur in individuals from both allergic and non-allergic family backgrounds. Symptoms may begin at any age, and may develop quickly or slowly. Triggers may range from a viral infection or illness to environmental chemical exposure. Chemical intolerance occurs more commonly in women, which may be because of hormone differences, as many food chemicals mimic hormones.
A deficiency in digestive enzymes can also cause some types of food intolerances. Lactose intolerance is a result of the body not producing sufficient lactase to digest the lactose in milk; dairy foods which are lower in lactose, such as cheese, are less likely to trigger a reaction in this case. Another carbohydrate intolerance caused by enzyme deficiency is hereditary fructose intolerance.
Celiac disease, an autoimmune disorder caused by an immune response to the protein gluten, results in gluten intolerance and can lead to temporary lactose intolerance.
The most widely distributed naturally occurring food chemical capable of provoking reactions is salicylate, although tartrazine and benzoic acid are well recognised in susceptible individuals. Benzoates and salicylates occur naturally in many foods, including fruits, juices, vegetables, spices, herbs, nuts, tea, wines, and coffee. Salicylate sensitivity causes reactions to aspirin and other NSAIDs, and also in foods which naturally contain salicylates, such as cherries.
Other natural chemicals which commonly cause reactions and cross reactivity include amines, nitrates, sulphites and some antioxidants. Chemicals involved in aroma and flavour are often suspect.
The classification or avoidance of foods based on botanical families bears no relationship to their chemical content and is not relevant in the management of food intolerance.
Salicylate-containing foods include apples, citrus fruits, strawberries, tomatoes, and wine, while reactions to chocolate, cheese, bananas, avocado, tomato or wine point to amines as the likely food chemical. Thus, exclusion of single foods does not necessarily identify the chemical responsible as several chemicals can be present in a food, the patient may be sensitive to multiple food chemicals and reaction more likely to occur when foods containing the triggering substance are eaten in a combined quantity that exceeds the patient's sensitivity thresholds. People with food sensitivities have different sensitivity thresholds, and so more sensitive people will react to much smaller amounts of the substance.
Pathogenesis
Food intolerance are all other adverse reactions to food. Subgroups include enzymatic (e.g. lactose intolerance due to lactase deficiency), pharmacological (e.g. reactions against biogenic amines, histamine intolerance), and undefined food intolerance (e.g. against some food additives).
Food intolerances can be caused by enzymatic defects in the digestive system, can also result from pharmacological effects of vasoactive amines present in foods (e.g. histamine), among other metabolic, pharmacological and digestive abnormalities.
Allergies and intolerances to a food group may coexist with separate pathologies; for example, cow's milk allergy (CMA) and lactose intolerance are two distinct pathologies.
Gut Microbiome Relationship
The gut microbiome includes all the microorganisms in our gut. Having a healthy and diverse gut microbiome can have many beneficial effects such as production of vitamins, help in educating the immune system and facilitate maturation of the gut, and discourage the overgrowth of pathogenic bacteria. The gut microbiome is heavily influenced by our diet, and can have health consequences when there is not sufficient diversity. This is a condition known as dysbiosis. During dysbiosis, harmful bacteria can compromise the gut barrier and allow dietary proteins to enter the bloodstream and trigger immune responses that can cause food allergies or intolerance. There are several ways to address dysbiosis including oral immunotherapy and dietary restrictions. Oral immunotherapies attempt to directly offer relief, and dietary interventions attempt to reduce balance and diversity in the gut microbiome by promoting healthy bacteria.
Bacteria can impact the health of the gut microbiome in a number of ways. A more diverse microbiome allows for stability between harmful and beneficial bacteria, each with a different function. Beneficial bacteria regulate gut health through several mechanisms, including the production of short-chain fatty acids, which enhance mucus production and strengthen tight junctions between intestinal epithelial cells.(Shen et al, 2025) On the other hand, harmful bacteria, in excess, can prevent the growth of beneficial bacteria through competitive exclusion, production of toxins, and chronic inflammation. An overgrowth of harmful bacteria can cause a breakdown of crucial intestinal barriers through the activation of pro-inflammatory pathways that increase sensitivity to harmless dietary proteins, known as food antigens. As the intestinal lining becomes more permeable, these antigens can escape into the bloodstream through gaps in the intestinal lining, triggering immune responses, such as bloating, inflammation, and abdominal pain.(Shen et al, 2025) Common food antigens that lead to allergic reactions include proteins from wheat, dairy, tree nuts, and shellfish.
Intolerances to certain foods are less severe than a food allergies. While allergies invoke an immune response, intolerances are non-immunological, often leading to dose-dependent symptoms of discomfort. Intolerances are caused by a lack of digestive enzymes needed to properly break down food compounds.(Gardner, 2026) For example, individuals who are lactose intolerant lack the enzyme lactase, causing bloating and diarrhea, due to an inability to digest dairy products. For individuals who have a dairy allergy, their immune symptom perceives milk proteins to be harmful invaders, triggering defense mechanisms that promote life-threatening allergic reactions, such as anaphylaxis and swelling of the airways.