Food Intolerances

1. Food Intolerances Biochemical and Physiological Reactions

2. Characteristics of Food Intolerances • Non-immunologically-mediated reactions • May be a result of: • Enzyme deficiencies • Malabsorption • Many mechanisms imperfectly understood

3. Characteristics of Food Intolerances • Dose-related: • Individual limit of tolerance • As quantity exceeds this, symptoms increase in incidence and severity

4. Carbohydrate Intolerance • Patients complain of abdominal fullness, bloating, and cramping within 5-30 minutes after ingesting carbohydrate • Watery diarrhoea occurs from 5 minutes to 5 hours after ingestion • Occasionally vomiting • Excoriation of perianal skin and buttocks due to acid (pH less than 6) stool in babies and children • Adults do not usually experience such a low stool pH

5. Carbohydrate Intolerance: Causes of Intestinal Symptoms • Non-hydrolysed carbohydrates (polysaccharides, oligosaccharides and disaccharides) pass into the large intestine causing: • Osmotic imbalance: induces a net fluid secretion into the gut lumen resulting in loose stool • Increased bacterial fermentation resulting in production of: • Organic acids (acetic, lactic, butyric, propionic) • increase osmotic imbalance • Gases such as carbon dioxide and hydrogen • cause bloating and flatulence

6. Carbohydrate Intolerance: Causes of Intestinal Symptoms • Increased bulk results in increased stool volume • Increased fluid and acid environment stimulate intestinal motility and accelerate intestinal transit time. • Increased speed of intestinal transit results in: • loose stool since fluid is not absorbed from food • secondary malabsorption of fat

7. Disaccharidase Deficiency • Carbohydrates are broken down by digestive enzymes to oligosaccharides and finally disaccharides • Disaccharides are broken down by disaccharidases produced by brush border cells in the small intestine to monosaccharides • Monosaccharides are absorbed by active transport or facilitated diffusion • Deficiency in disaccharidases results in malabsorption of disaccharide which passes into large bowel • Symptoms result from: • Changes in osmotic pressure • Fermentation by micro-organisms

8. Lactose Intolerance • Due to lactase deficiency • Lactase splits lactose into monosaccharides: • Glucose • Galactose • Monosaccharides absorbed by active transport • Undigested lactose moves into colon: • Change in osmotic pressure • Provides substrate for microbial fermentation • Results in • Excess fluid • Organic acids • Gases including hydrogen

9. Types of Lactose Intolerance Three types of lactose intolerance: • Congenital alactasia • Present from birth • Idiopathic lactase deficiency • Natural attrition after infancy • Affects about 80% of the world’s adult population • Secondary lactase deficiency • Results from damage to the lactase-producing brush border cells, often as a result of intestinal infection • Usually temporary condition that resolves once the infection of intestinal damage resolves

10. Tests for Lactose Intolerance Tests require ingestion of lactose: usually 50 gm lactose powder • Hydrogen breath test: positive >20 ppm • Blood glucose or galactose levels: increase indicates negative test • Reducing substance in stool: presence indicates positive test (Fehlings solution changes colour from blue to red) • Fecal pH: low pH indicates lactose fermentation and hence positive test

11. Management of Lactose Intolerance • Only the milk sugar, lactose, needs to be avoided • Milk proteins are tolerated • Lactose occurs in the whey (liquid) fraction of milk • Milk products free from lactose and free from whey are safe • These foods include: • Milk treated with lactase (Lactaid; Lacteeze) • Hard cheeses (whey is removed; casein remains and is fermented to form cheese) • Many people tolerate yogurt, where lactose is broken down by bacterial enzymes

12. Sucrase-Isomaltase Deficiency • Primary deficiency is rare: it is inherited as an autosomal recessive gene • Greenland and Canadian Inuit have an unusual incidence of 10% of the population • Appears when sucrose enters the child’s diet, usually when fruit juice is introduced • Severity of symptoms depends on the quantity of sucrose in the diet • Management: Avoidance of all sources of sucrose

13. Fructose Intolerance • Fructose intolerance is an inability to absorb free fructose • Intestinal fructose absorption depends on a low-affinity transporter molecule, GLUT2 that will carry the monosaccharides glucose, fructose and galactose across the small intestine epithelium. • This carrier mechanism is facilitated by glucose, which permits lower concentrations of glucose to be taken up by the cell by an active process

14. Fructose Intolerance • Glucose is preferentially absorbed • An excess of fructose will result in inefficient absorption of the fructose • The unabsorbed fructose moves into the large bowel where it causes: • An increase in osmotic pressure • Net influx or reduced outflow of water • Acts as a substrate for microbial fermentation with production of gas (especially hydrogen) and organic acids • Resulting in loose stool or frank diarrhoea

15. Fructose Intolerance:The Problem Foods • It is usually only necessary to avoid the foods that contain considerably more fructose than glucose These foods include: • Apple • Pear • Cherry • Blackcurrant • Watermelon • Honey • High fructose corn syrup • Agave syrup

16. Pharmacologic Agents in Foods • Vasoactive amines: • Histamine • Tyramine • Phenylethylamine • Octopamine • Serotonin • Methylxanthines • Caffeine • Theobromine • Theophylline

17. Pharmacologic Agents in Foods • Pharmacologic properties may be expressed in two ways: • Chemical reacts directly with body tissue in a dose-dependent fashion • Chemical reacts with a mediator system that acts on the body tissue

18. Histamine • Histamine-mediated reactions may be clinically indistinguishable from food allergy • Histamine sensitivity is becoming recognized as a disease entity quite distinct from allergy • “Idiopathic” urticaria and angioedema is an example of histamine sensitivity

19. Symptoms of Histamine Excess • Vasodilatation • Flushing • Reddening • Hypotension: • Tachycardia (Increased heart rate) • Increased vascular permeability • urticaria (hives) • angioedema (swelling) • rhinitis (stuffy nose) • rhinorrhea (runny nose) • otitis media (earache)

20. Symptoms of Histamine Excesscontinued • Pruritus (itching) • Increase in gastric secretions • Heartburn • Reflux • Headache; usually not migraine • Symptoms of anxiety; panic attack • Rarely momentary loss of consciousness • Fatigue; listlessness • Confusion

21. Other Effects of Histamine Excess • Increase in incidence and severity of anaphylactic reactions • Increase in incidence and severity of eczema

22. Mechanism of Histamine Sensitivity • Excess histamine is controlled by two enzyme systems: • Histamine N-methyltransferase (HMT) • Diamine oxidase (DAO) • Normally DAO rapidly degrades histamine to its inactive metabolites (imidazole compounds) which are excreted in urine • HMT prevents prolonged binding of histamine to its receptors • Prevents histamine-induced symptoms

23. Mechanism of Histamine Sensitivity Symptoms develop when: • Excessive amounts of histamine exceed the enzymes’ capacity to break it down • There is a lowered enzyme capacity for histamine breakdown • Drugs inhibit enzyme action (e.g. isoniazid)

24. Sites of Diamine Oxidase Production • DAO produced in various tissues, especially: • Jejunum • Ileum • Kidney • Thymus • Placenta • Many women experience relief of symptoms of allergy and histamine sensitivity during pregnancy

25. Sources of Histamine in Foods • Histidine can be decarboxylated to histamine by intestinal bacteria • May develop in fish that have been improperly processed and refrigerated, especially: • Tuna • Mackerel • Bonito • Bluefish • Mahi mahi] • In shellfish, where intestine is not removed

26. Sources of Histamine in Foods • Histamine is produced by microbial action in manufacture of foods such as: • Cheese • Fermented meats and sausages • Wine • Beers • Vinegar • Yeast extract • Sauerkraut

27. Sources of Histamine in Foods • Some foods contain high levels of histamine naturally, especially: • Spinach • Aubergine • Plant foods may produce histamine during the ripening process, for example • Tomato • Cherries

28. Sources of Histamine in Foods • Some foods may release histamine by a non-immunologically mediated mechanism which is presently unknown. Such foods include: • Egg white • Strawberry • Alcohol (ethanol) • Citrus fruits

29. Other Sources of Histamine • Compounds that release histamine: • Food additives, especially: • Benzoates • Tartrazine and other azo dyes • Sulphites

30. Other Extrinsic Sources of Histamine • Microbial flora of the large bowel includes species that synthesise histidine decarboxylase • Microbial enzymes act on food residue forming histamine • If diamine oxidase (DAO) in the gut is deficient, histamine is absorbed into circulation • When there is normal DAO activity only 1% of extrinsic histamine enters circulation

31. Tyramine sensitivity • Symptoms: • Urticaria • Migraine headaches • Sharp rise in blood pressure • Due to: • Vasoconstriction induced by dietary tyramine • Directly because of lack of tyramine breakdown in the intestine, liver, or arterial walls • Indirectly via secretion of epinephrine or norepinephrine, which is normally kept at unreactive levels by MAO-A

32. Tyramine Sensitivity: Characteristics • Mechanism of action: • Low levels of monoamine oxidase (MAO-A and MOA-B) enzymes • Causes of low MAOs: • Genetic predisposition • Monoamine oxidase inhibiting drugs (e.g. antidepressants such as Parnate; Nardil)

33. Tyramine in Foods • Formed by microbial action in food preparation, especially: • Cheese • Wine • Yeast • Vinegar

34. Tyramine in Foods • Small amounts occur naturally in some foods: • Chicken liver • Avocado • Banana • Plum • Tomato • Aubergine

35. Sensitivity to Food Additives • Characteristics common to persons sensitive to food additives: • History of asthma and rhinitis - sometimes with urticaria and angioedema • Aspirin sensitive

36. Additives Most Frequently Causing Intolerances • Tartrazine (and other artificial colors) • Sulphites • Preservatives: • Benzoates • Sorbates • Monosodium glutamate (MSG) • Nitrates and nitrites

37. Symptoms of Tartrazine Sensitivity • Asthma • Urticaria • Angioedema • Nausea • Migraine headaches • Some evidence of neurological and behavioural reactions

38. Postulated mechanisms to explain Tartrazine Sensitivity • Inhibition of the cyclo-oxygenase pathway of arachidonic acid breakdown. • Histamine release from mast cells

39. Allergic Response:Secondary Mediator Release Arachidonic acid Lipoxygenase Cyclo-oxygenase PROSTAGLANDINS (PG2) PROSTACYCLIN (PGI2) THROMBOXANE (TX) LEUKOTRIENES LTA4 LTB4 LTC4 LTD4 LTE4

40. Foods Frequently Containing Tartrazine • Soft drinks • Liqueurs and cordials • Sweets and confectionery • Ready-to-eat cereals • Jams and jellies • Ice cream, sherbet, milk shakes • Commercial gravies and soup mixes • Flavor packets • Pickles, relish, salad dressings • Prepared baked goods • Smoked fish and fish products

41. Foods Frequently Containing Tartrazine • Snack foods • Meal replacements • Any food containing “artificial color” may contain tartrazine unless it is labeled “tartrazine free” Non-food items: • Medications (prescription and OTC) • Vitamin and mineral supplements • Toiletries and cosmetics

42. Sulphite Sensitivity • Most common in asthmatics • Steroid-dependent asthmatics are most at risk • Adverse reactions to sulphites is estimated to be as high as 1% of the U.S. population • Sulphite sensitivity in non-asthmatics is considered to be quite rare • Symptoms occur in most organ systems: • Lungs • Gastrointestinal tract • Skin and mucous membranes • Life-threatening anaphylactic reactions in asthmatics have been recorded, but occur very rarely.

43. Symptoms Reported in Sulphite Sensitivity • Severe respiratory reactions: bronchospasm; wheezing; “chest tightness” • Asthma in asthmatics • Flushing; “change in body temperature” • Hypotension (drop in blood pressure) • Gastrointestinal symptoms (abdominal pain, diarrhea, nausea, vomiting) • Swallowing difficulty • Dizziness; loss of consciousness

44. Symptoms Reported in Sulphite Sensitivity • Urticaria (hives) • Angioedema (swelling, especially of the mouth and face) • Contact dermatitis • Anaphylaxis (in asthmatics) • Anaphylactoid reaction (non-asthmatics)

45. Postulated Mechanisms to Explain Sulphite Sensitivity 1.Sulphur dioxide is formed from sulphuric acid when the sulphite dissolves • Acts as a direct irritant on hypersensitive airways 2.Sulphite acts as a hapten, combines with a body protein to form a neoantigen that elicits antigen-specific IgE • Results in Type I hypersensitivity reaction 3. Enzyme deficiency: • Deficiency of sulphite oxidase system which converts sulphite to the inert sulfate

46. Forms of Sulphites Permitted in Foods in the UK • E220 Sulphur dioxide • E221 Sodium sulphite • E222 Sodium hydrogen sulphite • E223 Sodium metabisulphite • E224 Potassium metabisulphite • E226 Calcium sulphite • E227 Calcium hydrogen sulphite • E228 Potassium hydrogen sulphite • E150b Caustic sulphite caramel • E150d Sulphite ammonia caramel

47. Sulphites Permitted in Foods • EU food labelling rules require pre-packed food sold in the UK to show clearly on the label if it contains sulphur dioxide or sulphites at levels above 10mg per kg or 10mg per litre (or if one of its ingredients contains it) • Non-pre-packaged foods (e.g. 'loose' foods or foods prepared on the premises, including take-aways and restaurant food) are not covered by this labelling requirement

48. Sulphite Sensitivity • Exposure to sulphiting agents poses very little risk for individuals who are not sensitive to sulphites • There is no evidence that avoiding all sources of dietary sulphites improves asthma • Sulphates do not cause the same adverse reactions as sulphites. They are inert in the body and need not be avoided by people who are sensitive to sulphites

49. Sulphite Sensitivity • Sulphites in foods are not denatured by cooking • Sulphites avidly bind to several substances in foods, such as protein, starch, and sugars. • Sulphites cannot be removed by washing

50. Benzoate Intolerance Symptoms • Reported to induce: • Urticaria • Angioedema • Asthma • Rhinitis • Purpura (allergic vasculitis)