Chapter 5 Food allergy/intolerance
AETIOLOGY
Food reactions can be divided into toxic and non-toxic reactions.1,2 Toxic food reactions are rare and usually involve food toxins that may be naturally present in food or a consequence of food processing, contaminants or additives, such as aflatoxin found in contaminated grains and peanuts. In the modern world reactions are rare due to diet variety and food-processing standards. They are dose-dependent reactions and have the same effect on everybody. Non-toxic food reactions can be further divided into immune- and non-immune-mediated reactions. Reactions that involve immune activation are mediated by immunoglobulins, especially immunoglobulin E (IgE) but also possibly IgG, IgA and IgM.2 Non-immune-mediated food hypersensitivity reactions are often termed ‘food intolerances’ and include fructose and lactose intolerance. There is also another general category called ‘undefined’. As the name suggests there is little information about this category, which includes idiosyncratic and psychosomatic food reactions.
Food allergy
Most severe food allergies are IgE-mediated.3 IgE is associated with receptors on mast cells, fixed cells in the mucosa and skin, and basophils in the blood,2 and conjugation with an allergen leads to cell granulation and the subsequent release of inflammatory mediators. Vasodilation, exudation, smooth muscle contraction and mucus secretion (largely due to histamine) are common consequences. The greatest concern about an IgE-mediated food allergy is the chance that it will culminate in anaphylaxis. Common food culprits include fish, eggs, cow’s milk and peanuts.4 It is usually a reaction to the protein component of the food such as casein and gluten; if the patient is reacting to another food component, such as lactose, it is more likely to be food intolerance. Other less well-defined food allergies may also occur; these may be IgG-, IgM- or IgA-mediated.
Food intolerance
Food intolerances are much more insidious and often cause delayed symptoms. Food intolerances can be enzymatic, pharmacological or idiosyncratic in nature and are generally thought to be non-immune activated.2,4,5 Below is an outline of the two most common food intolerances: lactose and fructose.
Lactose intolerance
Lactose intolerance is due to the inability of the body to produce enough lactase to break down the lactose in milk. If lactose is undigested it will pass through to the large colon where it is acted on by colonic flora, causing pain, bloating and osmotic diarrhoea. Lactose is a disaccharide and is metabolised by β-galactosidase (lactase is a subclass of this) to glucose and galactose. Lactose maldigestion effects up to 20% of Caucasians,6,7 but incidence in some ethnic groups (African, Asian and those from the Baltic states and the Mediterranean) is up to 60%.6 A recent American study reported the prevalence of lactose intolerance in irritable bowel syndrome to be between 17 and 24%.8 Lactase deficiency can also be transitory (gastroenteritis) or as a result of mucosal damage (coeliac disease or gastroenteritis).
Fructose intolerance
Fructose is a six-carbon monosaccharide. It is ingested as a monosaccharide, as the disaccharide sucrose (glucose + fructose) or in polymerised forms such as oligosaccharides and polysaccharides.9 If the degree of polymerisation (DP) is < 10, they are usually referred to as fructo-oligosaccharides and if the DP is ≥ 10 they are usually called inulins.9 Another form of dietary fructose is the galacto-oligosaccharides (fructose + glucose + galactose), usually present as raffinose. Additional substances also poorly absorbed and readily fermented are:
Fructose intolerance may be a primary or secondary condition. Hereditary fructose intolerance is a rare autosomal recessive disorder that is due to a deficiency of the liver enzyme fructose-1,6-biphosphate aldolase.10,11 It is particularly dangerous and can result in vomiting, failure to thrive, hypoglycaemia and liver failure with jaundice and bleeding in children.10 Secondary fructose intolerance is quite different and much more common. It is usually due to abnormalities in the expression of GLUT5.12 Recent research suggests that it affects 30% of the population.13 If fructose is not absorbed in the small intestine it reaches the distal end of the small intestine and the colon where it is fermented by colonic flora to produce hydrogen and carbon dioxide.9 Fructose is fermented especially quickly, so there is not enough time for gas to be further metabolised or absorbed, increasing intralumen pressure and producing an osmotic effect. Abdominal distension, pain, flatulence and diarrhoea may result. Fructose malabsorption is associated with gastro-oesophageal reflux, small intestinal bacterial overgrowth and depression.12,14
RISK FACTORS
Genetics
It appears that genetic predisposition is a strong determining factor in allergic disease. There is an 11–13% risk of developing allergies if there is no parental history, a 20–30% risk if the patient has one allergic parent and 40–60% risk if both parents are allergic.5 Twin studies show that environmental factors are important in the development of atopic disease.15–18
Gastrointestinal mucosal hyperpermeability
The mucosal barrier in the small intestine is comprised of epithelial cells held together by tight junctions. Various cellular and chemical factors, including extremes of pH, mucus, bile salts, brush border enzymes, together with innate and adaptive immune responses also help to ensnare pathogens or render them harmless.3 Many factors, including gastrointestinal viral infections and stress, appear to increase intestinal permeability.17 If this intestinal barrier is compromised proteins, pathogens and antigens may pass through the intestinal wall. A recent study conducted in 20 patients with food allergies and 21 patients with food sensitivities found that they all had increased intestinal permeability as diagnosed by a lactulose/mannitol test.19 It was also found that the more significant the permeability, the more severe the allergies/intolerances were.
Maternal consumption and early consumption of allergenic foods
Consumption of allergenic foods by the mother during gestation and/or lactation may predispose the child to food allergy.5 This includes foods the mother is sensitive to or common allergenic foods if the mother has any allergic conditions herself. Similarly, consumption of common allergic foods by the child at an early age may also increase risk. A recent meta-analysis found that a hypoallergenic diet during gestation was useful for the prevention of allergic disease in high risk infants.20 The authors also found that the best dietary prevention was breastfeeding for at least 4 to 6 months, together with solid food and cow’s milk avoidance for 4 months.
Lifestyle factors
Factors such as eating habits, meal frequency, lack of exercise, poor sleep and use of analgesic medication are often thought to increase the likelihood of food sensitivities, or increase the intensity of symptoms in some individuals. A recent Norwegian study, however, found that there was no difference between these factors in a group of adults with abdominal discomfort, self-attributed to food intolerance, and a placebo group.21 Stress may be an added risk factor for the development of food sensitivities. Stress (physical, biochemical, psychological) induces the central production of corticotrophin-releasing hormone, which in turn suppresses vagal activity.22
CONVENTIONAL TREATMENT
There is no particular conventional medical treatment available for IgG-mediated food allergies or food intolerances. Patients with IgE-mediated food allergies are often prescribed epinephrine and antihistamines, and cromoglycate may also be given.5,23 Strict dietary avoidance is usually recommended for all known food intolerances or allergies and hyposensitisation may be offered.
KEY TREATMENT PROTOCOLS
Case-taking assessment
The first protocol is to assess the particulars of the suspected digestive intolerance/allergy.
A range of questions should first be asked of the patient, such as:
A food/symptom diary is often useful in identifying potential allergens or intolerances.
Identify and remove offending foods and substances
There are various ways to identify problematic foods and substances, depending on what foods are suspected. A de-challenge re-challenge diet is ideal to assess this (see Figure 5.1). Below is a summary of tests that are useful for the identification of food allergies and intolerances:
Once a food has been identified it must be removed from the diet (see Figure 5.1). In the case of IgG-triggered reactions, most of these foods need to be avoided only for a period of time until the reason for their existence is rectified. They can be due to a myriad of causes such as intestinal hyperpermeability, immune dysregulation and poor digestive function. This is also the case for secondary fructose and lactose malabsorption. Foods that provoke an IgE reaction, however, need to be thoroughly avoided.
Design an appropriate healthy diet
Maintenance of a healthy diet is crucial. Many people who have suffered from long-term food allergies or hypersensitivities have self-restricted their diet, in turn leading to various nutrient deficiencies. This is a perilous situation and one that needs addressing immediately if present. Deficiencies of protein, calcium, zinc, iron, vitamin B12 and magnesium are common, and a diet should always be designed with this in mind (see Appendix 4 for nutritional chart). Problematic foods must be avoided and the patient must also be offered as many alternatives as possible as the treatment will often fail if the patient finds compliance difficult.
For patients with lactose intolerance, the severity of symptoms depends on how much lactase is being produced by the small intestine. Many people can tolerate up to 7 g and many up to 12 g.6 This is important when designing a diet for a lactose-intolerant patient as it is not necessary to take patients off all dairy foods. It is also essential to understand hexose transport in the gastrointestinal tract in order to design a diet for fructose intolerant individuals. GLUT5 is a fructose transporter that is responsible for moving fructose across the brush border; it has a low capacity but is present along the whole length of the small intestine.12,29 It is this mechanism that is often deficient in fructose intolerance. Glucose enhances the absorption of fructose by its co-presence in the small intestine. GLUT2 (a low-affinity transporter that will carry glucose, fructose and galactose, found on the basolateral membrane) is shunted into the brush border to facilitate the diffusion of glucose.12,30 This in turn means that higher luminal concentrations of glucose are taken up by the cells via an active process, which in turn activates a system that can more efficiently take up all hexoses including fructose.12 This becomes very important when designing a diet for fructose intolerance as foods with an amount of glucose equal to or higher than the amount of fructose can be included. Hence it is only foods with higher fructose than glucose that are avoided. See Tables 5.1 and 5.2 for a list of foods to avoid if intolerant to lactose or fructose.
| Milk—cow’s, sheep’s, goat’s. More than ½ a cup at any serving. |
| Yoghurt—more than 100 g a serving (1/2 an average tub). |
| Ice-cream |
