Review Article

The Diagnosis and Management of Food Allergy and Food Intolerances

J. L. Turnbull; H. N. Adams; D. A. Gorard

Disclosures

Aliment Pharmacol Ther. 2015;41(1):3-25. 

In This Article

Food Intolerances

Food intolerances are adverse reaction to foods which do not involve the immune system. They are more frequently reported than food allergy. Some food intolerances involve an organic pathophysiological process, e.g. lactose and fructose intolerances. Other foods that can cause explicable reactions in susceptible individuals that would not occur in others unless taken in excess, include caffeine in beverages, and tyramine or other vasoactive amines found in cheeses. However, most intolerances are harder to explain. Symptoms may not occur until several hours after food consumption and can last for hours to days. Identifying culprit foods can be challenging as several food groups may be implicated in the same individual. Food additives such as monosodium glutamate and sulphites can cause reactions too. Respiratory symptoms, rhinitis, urticaria and angioedema arising from food intolerances are similar to those arising from food allergy. However, unlike in true food allergy, in intolerance there is a delay in symptom onset, prolonged symptomatic phase and negative sIgE serology.[9] Other varied symptoms may include gastrointestinal upset, headaches and migraine, fatigue, musculoskeletal problems and behavioural changes. These symptoms are frequently within the spectrum of common medically unexplained symptoms, often overlapping with symptoms found in IBS and fibromyalgia.

In some individuals, perceptions that food intolerance explains their symptoms may be exaggerated. Some studies of patients in secondary care with unexplained food intolerances have found an increased prevalence of psychiatric distress,[129,130] but individuals in the community describing food intolerances do not seem to have increased prevalence of psychiatric morbidity.[131,132]

There may also be an overlap of food intolerance with food aversions, which can be learnt in a Pavlovian fashion.[133] If the ingestion of a food is coincidental with significant abdominal or other symptoms, or even coincidental with a psychological perturbation such as receiving bad news, aversion to that food can be learnt. This has parallels with the anticipated nausea and vomiting that may occur in chemotherapy recipients.[134] Foods ingested prior to emetogenic chemotherapy can become so associated with the chemotherapy-induced nausea and vomiting, that the foods themselves are avoided long after chemotherapy has finished.[68]

By definition there are no immunologically based objective tests to help clarify the presence of food intolerances. However, one study of IBS patients found that testing for food-specific IgG antibodies helped to tailor an elimination diet.[135] Objective testing for food intolerance requires double-blind placebo-controlled food challenging but is rarely done. Individuals whose symptoms improve or resolve with dietary restriction simply continue to avoid those foods that are perceived to produce their symptoms. With food intolerances it is often possible to build up tolerance to culprit foods through a period of food exclusion with reintroduction at a later date without symptom reproduction. Maintaining tolerance may depend on the quantity of food ingested when it is being reintroduced in a trial-and-error fashion.

In general individuals complaining of nonspecific abdominal symptoms arising from specific foods tend to be diagnosed as having IBS or other functional gastrointestinal disorders. Lactose intolerance, fructose intolerance, gluten sensitivity and food intolerances in IBS will be discussed further:

Lactose Intolerance

Dietary lactose is hydrolysed by small intestinal mucosal lactase to glucose and galactose prior to absorption. Hereditary alactasia is a rare condition in which lactase is completely absent from birth. However, most individuals who malabsorb lactose possess normal lactase levels as a neonate, but these fall after weaning, leading to deficiency in older children and adults.

Approximately 20% of North Europeans and Americans, and the majority of the world's population malabsorb lactose, but most are asymptomatic. Lactose malabsorbers do get symptoms of lactose intolerance – abdominal cramps, bloating, flatulence and osmotic diarrhoea, if they ingest excessive amounts of lactose, such as in the lactose tolerance test. This involves ingesting the lactose load (50 g) contained in 1 L of cow's milk on an empty stomach. These symptoms arise from unabsorbed lactose reaching the colon, where it causes osmotic diarrhoea and where its bacterial fermentation releases gas responsible for flatulence and bloating. However, lactose malabsorption is rarely a clinical problem in adults, since malabsorbers usually recognise that excess dairy products cause upset and modify their diet without medical consultation. Furthermore, when lactose malabsorbers chronically ingest lactose, colonic bacterial flora adaptation occurs with increased tolerance for lactose.[136]

The abdominal symptoms of lactose intolerance resemble those of IBS.[137] However the prevalence of lactose malabsorption in IBS is the same as in the general population.[138] Many IBS sufferers either perceive themselves as lactose malabsorbers when they are not,[138] or blame their coincident true lactose malabsorption for their symptoms despite evidence showing a poor symptomatic response to dietary lactose withdrawal.[139–141] Even lactose malabsorbers who consider themselves to be very lactose intolerant can actually tolerate moderately large amounts (12–24 g) of lactose (1–2 glasses milk) daily without symptoms.[142,143]

Despite these data, some patients with IBS and coincident lactose malabsorption may make unnecessary efforts to avoid all lactose, including lactose used to make up pills. Such misapprehensions about the role of lactose in their symptom production are fuelled in some countries by a multi-million dollar industry promoting largely unnecessary lactase enzyme supplements and alternative milk products.

Fructose Intolerance

Fructose is one of the two simple monosaccharides within sucrose. It is found in fruits and often added to foods because of its sweet taste. Fructose is absorbed without enzymatic breakdown. It is transported by facilitated diffusion, primarily using the GLUT5 transporter. A glucose-dependent fructose co-transporter GLUT2, enhances absorption by solvent drag and passive diffusion.[144,145] Thus fructose absorption is stimulated by the co-ingestion of glucose in a dose dependent manner.[146] The absorption process is incomplete in some individuals, and can be overloaded if there is excess intestinal luminal fructose, particularly if there is little intestinal luminal glucose. Any unabsorbed fructose will reach the colon where colonic fermentation leads to gas production and symptoms, similar to those found in lactose malabsorption and IBS.[146]

Gluten Sensitivity

In distinction to both coeliac disease which is an immune-mediated reaction to gluten in genetically predisposed individuals, and to wheat allergy which is an IgE-mediated allergic response to gliadins, the concept of 'gluten sensitivity' has been proposed.[147–150] Gluten sensitivity in the absence of coeliac disease or wheat allergy is a somewhat controversial clinical diagnosis in which dietary exclusion of gluten may improve a multitude of various symptoms including headaches, abdominal and musculoskeletal complaints, and even behavioural disturbances. In the USA there may be as many people without coeliac disease but following a gluten-free diet as there are coeliac patients.[151] Individuals deemed to have gluten sensitivity have none of the serological or histological abnormalities found in coeliac disease. However gluten sensitivity may possibly be associated with innate rather than adaptive mucosal immune responses.[152]

Although there is much interest amongst the public and in the media about potential benefits of gluten avoidance, scientific proof for the existence of a gluten sensitive state outside of coeliac disease/wheat allergy is lacking. There is understandable sceptism to the concept of gluten sensitivity,[153] and concerns that the food industry and alternative health practitioners may be driving much of the interest in gluten exclusion in noncoeliac conditions. Despite the dearth of clinical controlled trial evidence to support a gluten sensitive state, one double-blind study did show that some IBS patients without coeliac are improved with a gluten free diet.[154] It will be only through such further controlled trials that verification and clarification of the concept of non-coeliac gluten sensitivity and its overlap with IBS will be achieved.[155]

Food Intolerances in IBS

Symptom production in IBS remains poorly understood. Abnormalities of gut motility, inflammation, microflora, visceral hypersensitivity, central processing, psychological factors and dietary factors may be relevant. Symptoms are often worse postprandially,[156] and most IBS patients think they have some form of adverse reaction to food(s).[157–160] Patients whose abdominal symptoms are only induced by eating may perceive themselves as having a food 'allergy' or intolerance, but their doctors may simply and not inappropriately diagnose these postprandial symptoms as IBS. Conversely many adults with adverse reactions to foods leading to gastrointestinal symptoms will be diagnosed as having IBS or other functional disorder without any further attempt to investigate the problem.

Typically IBS patients report that foods rich in carbohydrates, as well as fatty food, coffee, alcohol and hot spices are the most frequent culprits causing symptoms. Patients often restrict their diets according to their perceived intolerances. The development of cramping abdominal pain and an intense urge to defaecate postprandially may simply be an exaggerated gastrocolic response. A meal's calorific content, fibre content and proportion of fat vs. carbohydrate may all influence the distal colonic contractions of the gastrocolonic response.[161,162] The effects of specific foods have been little studied. However, a manometric study showed that drinking coffee precipitates rectosigmoid contractions and a defaecatory urge within minutes in some individuals.[163] The gastrocolic response to ingesting other specific foods has not been formally studied in this way.

There is no evidence for increased IgE-mediated food allergy in IBS although studies have been limited.[157,159] Although the presence of food-specific IgG antibodies merely denotes exposure to the food, one trial showed symptomatic improvement when IBS patients followed a diet restricted in foods to which they had positive food-specific IgG antibody tests.[135]

Some IBS patients may have increased sensitivity to luminal distension.[164] Luminal distension arising from the osmotic effects of, and the colonic bacterial fermentation of foods that are poorly absorbed in the small intestine, has been proposed as causative in IBS symptoms. Thus although soluble fibre helps IBS symptoms,[165] insoluble slowly fermentable fibre in the form of wheat bran is less useful,[166] and may be deleterious in worsening symptoms.[167] Such controversy over whether fibre, and in particular bran, worsens IBS symptoms is further explored by Eswaran and colleagues.[168]

Although IBS – like symptoms can be provoked in individuals who malabsorb lactose, sorbitol or fructose, the exclusion of lactose, sorbitol or fructose in established IBS sufferers has not produced any conclusive benefits.[169] However, the low FODMAP (Fermentable Oligo-Saccharides, Disaccharides, Monosaccharides And Polyols) diet builds further on the strategy of excluding poorly absorbed fermentable carbohydrates in an attempt to improve IBS symptoms.[170] The low FODMAP diet specifically limits the intake of poorly absorbed short chain carbohydrates which would induce luminal distension by promoting osmosis and colonic gas production.

FODMAPs include fructans (many vegetables, wheat, barley, rye), galactans (beans/pulses), polyols (found in many fruits) lactose, fructose and many artificial sweeteners. Increasing the dietary intake of FODMAPs worsens IBS symptoms.[171] Controlled trials have now shown that IBS symptoms can be improved by following a low FODMAP diet.[172,173] However, the diet is restrictive and supervision by a trained dietician is needed.

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