Food Intolerance

Food intolerance is a non-immune-mediated adverse reaction to a food or food component that is reproducible, that occurs at doses normally tolerated by most people, and is related to the amount ingested. It differs from food allergy, which is an immune mediated (usually IgE-mediated) reaction that can occur at trace doses and can cause anaphylaxis.

• Prevalence: self-reported food intolerance affects about 15 to 20% of adults, but the objectively confirmed rate is much lower (about 1 to 10%), because many patients misattribute symptoms to foods.
• Mechanisms and common types:
  • Enzyme deficiency: lactase deficiency (lactose intolerance), sucrase isomaltase deficiency, and alcohol and aldehyde dehydrogenase variants (flushing with alcohol, common in East Asian populations).
  • Carbohydrate malabsorption: fructose malabsorption, sorbitol and other polyols, and fermentable oligosaccharides, disaccharides, monosaccharides and polyols, which cause bloating, gas, and altered bowel habit in people with irritable bowel syndrome and visceral hypersensitivity.
  • Pharmacological reactions to food chemicals: caffeine (palpitations, tremor, anxiety, reflux), tyramine (headache and hypertensive reactions with monoamine oxidase inhibitors), histamine in fermented and aged foods (cheese, wine, fish, cured meats, with flushing, headache, diarrhoea in histamine intolerance from reduced diamine oxidase activity), phenylethylamine, and capsaicin.
  • Food additives: sulphites (wheeze and flushing, especially in asthma), monosodium glutamate (transient headache, flushing, sweating and palpitations in a minority), colourings (tartrazine), benzoate preservatives, nitrates, and artificial sweeteners (aspartame, sorbitol).
  • Non-coeliac gluten sensitivity (non-coeliac wheat sensitivity): symptoms after gluten or wheat products in people without coeliac disease or wheat allergy, probably due to fermentable carbohydrates (fructans) and other wheat components.
  • Salicylates and natural amines in fruit and vegetables, with limited evidence.
  • Other: gallbladder disease after fatty meals, and reflux triggered by fatty food, chocolate, alcohol and coffee.
• Associations: irritable bowel syndrome, functional dyspepsia, anxiety, depression, a history of eating disorders, and tendency to exclusion diets. Risk groups: women, young adults, and those with other functional conditions.
• Complications: restrictive diets that cause nutritional deficiency (calcium, iron, vitamin D, B12, fibre), disordered eating, social impairment, delayed diagnosis of organic disease (coeliac disease, inflammatory bowel disease), and unnecessary cost.

• Symptoms vary with the mechanism, and usually appear from 30 minutes up to 24 to 48 hours after the food (slower and less predictable than allergy), and depend on the dose:
  • Gastrointestinal: bloating, abdominal pain, flatulence, diarrhoea, nausea, reflux, and alteration in bowel habit.
  • Systemic and neurological: headache, migraine, flushing, palpitations, fatigue, difficulty concentrating, muscle and joint aches, and skin symptoms (itch, eczema flares, rash).
  • Respiratory: wheeze or rhinitis from sulphites in some people with asthma.
• Features favouring intolerance over allergy: delayed or variable onset, dose dependence, predominantly gastrointestinal symptoms, no urticaria, angioedema, or anaphylaxis, and tolerance of small amounts.
• Features of allergy needing urgent attention: onset within minutes to 2 hours, urticaria, angioedema, wheeze, stridor, vomiting, hypotension, collapse, and reactions to trace amounts or to a small number of foods (peanut, tree nuts, milk, egg, fish, shellfish, wheat, soya, sesame).
• Examination is usually normal. Record the weight, body mass index, nutritional state, signs of deficiency, and skin findings.
• Differential diagnosis: food allergy (IgE-mediated, and non-IgE conditions such as food protein induced enterocolitis, eosinophilic oesophagitis), coeliac disease, inflammatory bowel disease, irritable bowel syndrome, functional dyspepsia, gastro oesophageal reflux, gallbladder disease, pancreatic insufficiency, small intestinal bacterial overgrowth, bile acid diarrhoea, carcinoid syndrome, mastocytosis, scombroid poisoning (histamine from spoiled fish, with acute flushing, headache and diarrhoea within an hour), anxiety, and eating disorders (including avoidant restrictive food intake disorder).
• Red flags: weight loss, anaemia, rectal bleeding, nocturnal symptoms, persistent vomiting, dysphagia, fever, an anaphylactic reaction, failure to thrive in children, steatorrhoea, a strong family history of coeliac disease, inflammatory bowel disease or cancer, age above 50 years with new symptoms, and an extremely restrictive diet.

• Careful history: which foods, how much, the time between the food and symptoms, reproducibility, symptom type, other triggers (stress, menstruation, alcohol, medicines, exercise), and past investigations and diets. Ask about allergy features separately.
• A food and symptom diary for 2 to 4 weeks, with notes on timing, portion size, symptoms, bowel habit, stress and menstruation, helps to find patterns.
• Exclude organic disease with targeted tests when symptoms persist or alarm features exist: full blood count, ferritin, C-reactive protein, coeliac serology (tissue transglutaminase IgA with total IgA, performed while eating gluten, 6 weeks of normal gluten intake), thyroid function tests, faecal calprotectin, liver tests, and stool tests for infection. Upper endoscopy and colonoscopy for red flags.
• Allergy testing when features suggest allergy (skin prick tests or specific IgE to the suspected foods), interpreted in the context of the history, since positive tests without symptoms are common and do not diagnose allergy. Supervised oral food challenge in an allergy centre confirms or excludes allergy.
• Breath tests (hydrogen and methane): lactose (25 g), fructose (25 g) and sorbitol (5 g) malabsorption, and glucose or lactulose tests for small intestinal bacterial overgrowth, with attention to their limits.
• Genetic testing for lactase persistence in selected patients, and serum diamine oxidase or histamine tests are not reliable for histamine intolerance.
• Do not use unvalidated tests: IgG food antibody panels, hair analysis, applied kinesiology, electrodermal tests, cytotoxic tests, and pulse tests have no diagnostic value and lead to unnecessary restrictions.
• Structured elimination and reintroduction (the best method):
  • Eliminate the suspected food or group (for example, lactose, fructose, a low fermentable carbohydrate diet, or gluten after coeliac disease is excluded) for 2 to 6 weeks.
  • If symptoms improve, reintroduce one food at a time at increasing doses over 3 days, with a symptom diary, and a gap of 2 to 3 days between foods, to identify triggers and thresholds. Blinded challenge is the reference method when possible.
  • Return to a normal diet with the least restriction, because chronic exclusion is not needed for most.

• Explain the diagnosis, that food intolerance does not cause lasting harm, and that most people tolerate a small amount of the offending food. Avoid blaming single foods without evidence, and avoid over restriction.
• Dietitian led management is best, to ensure adequate nutrition and a structured approach:
  • Identify and reduce confirmed triggers to the personal threshold (not full exclusion), with attention to hidden sources and cross contamination.
  • Lactose intolerance: reduce lactose to the tolerated amount (often 12 g per day, in divided doses), use lactose free products, and lactase enzyme 3000 to 9000 FCC units with dairy meals.
  • Fructose and polyol malabsorption, and irritable bowel syndrome: a low fermentable carbohydrate diet for 4 to 6 weeks, then structured reintroduction to find tolerated foods and then a long term, least restrictive diet. Fructose intolerance may respond to the co-ingestion of glucose, and xylose isomerase supplements are used by some patients.
  • Non-coeliac gluten sensitivity: reduce wheat and gluten, after exclusion of coeliac disease and wheat allergy. Reassess at 6 to 12 months to check whether the diet can be relaxed, and consider fermentable carbohydrate reduction, which often has the same effect.
  • Histamine intolerance: a low histamine diet for 2 to 4 weeks (avoiding aged cheeses, fermented foods, cured meats, wine, beer, tinned and smoked fish, spinach, tomato, and leftovers), with reintroduction. Diamine oxidase supplements and non-sedating antihistamines (cetirizine 10 mg once daily) have limited evidence. Avoid drugs that inhibit diamine oxidase when possible.
  • Sulphite sensitivity (particularly in asthma): avoid wine, dried fruit, processed foods with sulphite preservatives, and discuss with the physician and dietitian.
  • Monosodium glutamate, caffeine and tyramine: reduce intake to a tolerated level, and avoid tyramine rich foods with monoamine oxidase inhibitors.
  • Alcohol flushing due to aldehyde dehydrogenase variants: avoid alcohol, which is linked to a higher risk of oesophageal cancer if drinking continues.
  • Reflux triggers: avoid fatty meals, large portions, late meals, chocolate, coffee, alcohol, peppermint, and spicy foods when they provoke symptoms.
• Symptom directed drug treatment (short term, as needed):
  • Bloating and gas: simethicone 40 to 125 mg after meals, peppermint oil 0.2 mL enteric coated 3 times daily before meals, and activated charcoal has little evidence.
  • Diarrhoea: loperamide 2 mg orally after each loose stool (maximum 8 mg per day without prescription, 16 mg per day with), for short term use.
  • Abdominal cramps: hyoscine butylbromide 10 to 20 mg orally 3 to 4 times daily, or mebeverine 135 mg 3 times daily before meals.
  • Constipation: increase fluids, and add macrogol 1 sachet daily, or ispaghula husk 3.5 g once to twice daily.
  • Persistent functional symptoms: amitriptyline 10 mg orally at night, increased to 25 to 50 mg, and psychological therapies (cognitive behavioural therapy, gut directed hypnotherapy).
  • Flushing, headache and itching from histamine or additives: cetirizine 10 mg once daily or loratadine 10 mg once daily as needed.
• Food allergy (when confirmed or suspected): avoid the specific allergen, refer to an allergist, and prescribe emergency treatment for those at risk of anaphylaxis: adrenaline auto injector 0.3 mg intramuscularly into the anterolateral thigh for weight over 30 kg (0.15 mg for 15 to 30 kg, and 0.5 mg in adults over 60 kg when available), with a written action plan, and a second auto injector. Do not manage suspected allergy with an elimination diet without specialist assessment.
• Nutrition: protect adequate intake (energy, protein, calcium 1000 mg per day, vitamin D 800 to 1000 international units daily, iron, B vitamins, and fibre), and monitor weight. Supplement when diet is restricted (calcium carbonate 500 mg twice daily with meals, vitamin D3 800 to 1000 units daily, and a multivitamin as needed).
• Psychological aspects: screen for anxiety, depression and eating disorders, avoid reinforcing food fears, and refer for cognitive behavioural therapy when food avoidance is extreme (avoidant restrictive food intake disorder).
• Special groups:
  • Children: take a careful history to separate allergy from intolerance, avoid unsupervised exclusion diets, monitor growth, and involve a paediatric dietitian. Fructose and sorbitol in fruit juices commonly cause toddler diarrhoea, and reducing juice resolves it. Refer for failure to thrive, bloody stools, vomiting, or allergic features.
  • Pregnancy and breastfeeding: continue a balanced diet with adequate calcium (1000 mg), iron, folic acid (400 micrograms daily before and during the first 12 weeks), and avoid unnecessary elimination. Limit caffeine to 200 mg per day (about 2 cups of coffee).
  • Elderly: preserve nutrition and protein, avoid unnecessary elimination, and check for malabsorption, medicines, and cancer in new symptoms.
  • Irritable bowel syndrome and functional disorders: use the diet as part of broader management, with time limits on restriction.
  • Coeliac disease: confirm by serology and biopsy before the start of a gluten free diet, since a gluten free diet before testing invalidates the results. If the diet has been started, perform a gluten challenge (at least 3 slices of wheat bread daily for 6 weeks) before testing.
  • Renal impairment and diabetes: adapt exclusion diets to the nutritional needs (potassium, phosphate, carbohydrate and glycaemic control).
• Follow up: review at 4 to 8 weeks after dietary changes, assess symptom control, nutrition, weight and mood, and re-evaluate the diagnosis when no response occurs. Refer to a dietitian for structured diets, an allergist for suspected allergy, and a gastroenterologist for persistent symptoms, abnormal tests, or red flags.