foods
O. Fraser, S. Sumar and
N. Sumar
Adverse reaction to foods in humans is very common; in milder cases it causes discomfort and in the more severe cases it can cause anaphylaxis and even death. Avoidance of the offending food can in most cases alleviate this problem; however, accidental exposure is very common due to the unsuspected presence of the offending food component in a wide range of processed foods (e.g. peanut, soybean, milk, egg and cereal proteins). Adverse reaction to foods causes discomfort not only when the offending food is consumed, but also when an individual is exposed via physical contact or inhalation of vapour or particles of food.
Adverse reactions to foods may be classified into two fundamental groups:
(1) food aversion; and (2) food intolerance.
Food aversion is an unpleasant reaction to food, which is caused by emotions associated with the food rather than by the food itself. Food intolerance, which includes food allergy, is a general term referring to a non-psychological, reproducible, unpleasant reaction to a specific food or food ingredient. Food intolerance is then further subdivided into food allergy and non-immunologically mediated food intolerance.
Food allergy is a specific adverse reaction to food where there is evidence of an abnormal immunological reaction to the food.
Non-immunologically mediated food intolerance can also occur in some
individuals. This may be due to a number of mechanisms including:
. the lack of a particular enzyme needed for the digestion of food;
. the presence of toxic substances; . irritant effects such as those caused by
highly spiced foods;
. pharmacological effects of some food components; and
. indirect effects caused by fermentation of unabsorbed food in the digestive system.
In this review we will focus on foods which elicit allergic (immunological) and non-allergic (non-immunological) response in humans since these are of greater importance when considering the safety of the foods.
The authors
O. Fraser,S. SumarandN. Sumarare all at the Department of Surgery, St George's Hospotal Medical School, University of London, UK.
Keywords
Food, Allergies
Abstract
Outlines the prevalence of adverse reactions to food and what it means to the individual. Lists and describes the known main food allergies.
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Nutrition & Food Science
Volume 30 . Number 5 . 2000 . pp. 236±242
Prevalence
The true prevalence of adverse reaction to food particularly food allergy is unknown. Epidemiological data differ according to age categories, country, public perception, and study methods. Results of community surveys have reported the perceived incidence of food allergy to be 14 to 33 per cent. This wide disparity in statistics is probably due to a combination of improper terminology and public misconceptions, and a lack of challenge proven confirmation of symptoms (Sloan and Powers, 1986). In 1982, a Finnish study in which 866 children aged between one and six years reported the prevalence of food allergy as 19 per cent at one year of age, 27 per cent at three years, and 8 per cent at six years (Kajosaari, 1982). Results were based on history, effect of an elimination diet, and non-blinded food challenges. A more rigorous study looked prospectively at 1,749 Danish infants for the development of cow's milk allergy during their first year. About 7 per cent of the children had suggestive clinical symptoms, but only 2.2 per cent actually were proven to have cow's milk allergy by food challenges in the hospital (Host and Halken, 1990). These results were similar to an earlier study from the Isle of Wight (2.5 per cent) (Hidc and Guycr, 1983), and a more recent study from The Netherlands (2.7 per cent) (Schranderet al., 1993). In a prospective study of children followed through the first three years of life in a general paediatric practice, Bock (1981), concluded that about 8 per cent of children have adverse reactions, most of which are transient. It may be concluded from these studies that 4 to 6 per cent of children experience food
hypersensitivity in the first three years of life, but only 1 to 2 per cent of the paediatric population are still affected by their tenth birthday. Figures were similar to those for the adult population.
In the UK, studies carried out by the Wycombe Health Authority in 1986 showed that the occurrence of intolerance to food in the general population was in the range of 0.01 to 0.23 per cent (between 1 in 500 and 1 in 10,000). A later study of the same
population showed that the number of individuals actually showing a demonstrable reaction was between 1.4 and 1.9 per cent (between 1 in 50 and 1 in 70) (Younget al., 1987; 1994).
Allergic reactions to food
The concept of foods generally consumed within a population causing an allergic reaction in some individuals has existed for quite a long time and is expressed in the vocabulary of the indigenous Amerindian in South America as ``kinna''. If a person had a ``kinna'', this meant that when that person consumed a particular food (the ``kinna''), he would become ill. The first recorded
significant investigation into adverse reaction to foods was in 1912 by two scientists, Kustner and Prausnitz, who observed that an intradermal injection of fish extracts into a fish-sensitive individual, elicited an
immediate wheal and flare reaction. Of equal importance was the observation that
immediate reactivity of the fish allergen could be passively transferred to a non-atopic subject by intradermal injection of sera from fish sensitive individuals. Subsequently, the passive transfer of hypersensitivity to other allergens was also observed. The nature of these reaginic antibodies remained unknown for more than 40 years until lshizaka and lshizaka (1967) identified IgE as the carrier of reaginic activity in the serum of patients with hayfever.
The discovery of IgE antibody has provided the basis for immunochemical approaches to the study of mechanisms underlying
immediate hypersensitivity reactions. It is now well recognised that the major feature distinguishing atopic individuals from non-atopic individuals is their capacity to develop a sustained IgE response to an allergen. IgE has the unique property of binding to high-affinity receptors on basophils and mast cells. The cross-linking of specific membrane bound IgE with an allergen triggers the release of vasoactive mediators, leukocyte chemotactic factors, and cytokines
responsible for the clinical manifestation of immediate hypersensitivity reactions (Lebrer, 1986; Tayloret al., 1987).
The development of allergic reactions to food most commonly occurs in two phases: (1) sensitisation; and
(2) allergic response.
immune system by antigen presenting cells (APC), which causes T-helper cell
stimulation (via cytokine IL4) of B cells to produce antigen-specific IgE antibodies. These IgE antibodies then bind to high affinity receptors on the surface of mast cells and basophils resulting in sensitisation. The allergic reaction to the food antigen occurs on subsequent exposure, which results in the degranulation of mast cells or basophils thereby releasing mediators responsible for the manifestation of clinical symptoms (Figure 1).
The major food allergens are water-soluble glycoproteins, with molecular weights ranging front 12.5kDa to 63kDa (Tayloret al., 1987). Most of these allergens are heat and acid stable and can survive protease digestion. The antigens responsible for most of the morbidity and mortality owing to food allergy will be discussed individually. The importance of these food antigens varies in different countries, depending on dietary habit and amount consumed.
Food antigens
Cow's milk
Cow's milk is one of the most common food allergens in children, perhaps because it is usually the first foreign protein encountered by infants. Protein fractions from cow's milk are subdivided into casein and whey proteins. Although extensive heating may denature some of these proteins, it does not
significantly decrease the allergenicity of most protein fractions. Casein fractions are used extensively in processed foods as well as cheeses. The whey fraction consists of
-lactoglobulin,-lactalbumin, bovine immunoglobulin, bovine serum albumin, and small amounts of various other proteins. IgE antibodies to these whey proteins have been demonstrated in most milk-allergic patients. Cross-reactivity among milk proteins
obtained from cows, goats and sheep has been reported. Clinical reactivity to goat's milk has been estimated to occur in 50 per cent of children allergic to cow's milk (Clein, 1958).
Egg
Chicken's egg is probably the most common cause of food allergic reactions in children. The major protein allergens found in egg white are ovomucoid, ovalbumin, and ovotransferrin (Holen and Elsayed, 1990). Egg yolk contains a variety of proteins namely lipovitellin and lipovitellenin (lipo-proteins), levitin (water-soluble protein), and phosvitin (phospho-protein). Although the yolk is considered to be less allergenic than egg white, IgE antibodies to egg yolk proteins have been demonstrated (Anetet al., 1985). IgE antibodies from children allergic to chicken's egg have been shown to cross-react with eggs from other species (Langeland, 1983).
Soybean
Soybean, a legume, is another common cause of food-allergic reactions, mainly in children. It is used in many commercial foods since it is an inexpensive source of high-quality protein. Of the four major protein fractions identified, no one fraction appears to be more allergenic than the other in a study of eight children with IgE-mediated hypersensitivity to soybean (Buttset al., 1988). Soybean proteins have been identified in some soybean oils, lecithin,
and margarine, but the impact of this is yet to be determined. Immunological
cross-reactivity among legumes has been demonstrated. However, symptomatic hypersensitivity to more than one legume is rare (Bernhisel-Broadbent and Sampson, 1989).
Peanut
Allergic reactions to peanut occur quite frequently in both children and adults. Peanut allergy is probably the most common cause of anaphylaxis. Peanut proteins are classified as water-soluble albumins or non-water-soluble globulins. Sixteen allergenic protein fractions have been identified in unprocessed peanuts. Two major allergens, Ara h 1 and Ara h 11 with molecular weight 63.5kDa and 17kDa respectively, have been identified in peanuts (Burkset al., 1992a). Thermal denaturation does not alter the IgE specific binding capacity of allergenic peanut proteins (Burks
et al., 1992b). Peanuts may be included as
flavouring in variety of foods including confectioneries and condiments. Some products may also contain deflavoured, reflavoured and recoloured peanuts to resemble walnuts, pecans, or almonds. This poses a serious food safety hazard to individuals allergic to peanut. Allergenic protein fractions have also been isolated from commercially refined peanut oil (Olszewski, 1998).
Tree nuts
Tree nuts are frequently implicated in allergic reactions in both adults and children. Walnuts, pecans, Brazil nuts, cashews, hazelnuts, pine nuts and pistachios have all been implicated as food allergens. Studies have shown that allergy to individual tree nut is mostly nut-specific, while multiple tree-nut allergies, although rare, have been shown to occur (Bock and Atkins, 1989). Cross-reactivity with peanut and other legume allergens is quite uncommon; however, cross-reactivity with certain tree pollen and plant ``pan allergen'' profilin has been shown to occur in some atopic individuals (Hirschwehr
et al., 1992).
Fish
Allergic reaction to fish is particularly common in communities where fish is handled and consumed on a large scale. Several species are known to cause allergic
reactions, but only few of the offending allergens have been studied in great depth. The allergens present in codfish have been studied quite extensively. Even though there are several other allergenic proteins in codfish protein extracts, Gad c 1 is considered to be the major allergen (Doryet al., 1998; Christinaet al., 1992; Chopinet al., 1998). The major allergen in codfish, Gad c 1 (also known as allergen M), is a 12.5kDa
sarcoplasmic protein belonging to a group of proteins known as parvalbumins. Cross-reactivity of codfish allergens with those of other fish, have been shown to occur in some codfish allergic individuals (de Martinoet al., 1990; Hansenet al., 1997); however,
hypersensitivity to fish allergens are generally species specific (Kelsoet al., 1996; Nagpal, 1989).
Shellfish
Shellfish, which is made up of crustaceans and molluscs, have been shown to be allergenic. Crustaceans are by far the more frequent offenders. Two major allergens found in shrimp have been identified and characterised. SA I and SA II of molecular weight 20.5kDa and 38kDa respectively, are myofibrilliar proteins (tropomyosin) (Nagpal, 1989). SA I is heat labile while SA II is heat stable (Nagpalet al., 1989. The allergens found in shrimp (including a 36kDa heat stable protein) have been shown to be highly cross-reactive with other allergens found in snow crabs, fruit fly, lobster, squid and cockroaches (Lebrer, 1986; Leunget al., 1996).
Cereal grain
Cereal grains include wheat, rice, corn, rye, barley and oats. The most common allergic complaint with the cereal grains is
with the other major protein fractions, the gliadins and glutenins (gluten complex) (Hoffman, 1975). In rice, two major allergens have been identified and characterised (Shibasaki et al., 1975). These two major allergens belong to the glutenin and globulin protein fractions. Several antigenic wheat proteins have been shown to cross-react with rye antigens (Yunginger, 1991).
Non-immunological reactions to food
The incidence of non-immunological
reactions to food is much greater than that of allergic reactions (Young et al., 1994). The mechanisms by which foods and food additives elicit non-immunological adverse reactions are very diverse and beyond the scope of this review. Several food components and additives are known to elicit adverse reactions. Most of these reactions are normally not life threatening on their own; however, when combined with other clinical conditions such as asthma, they can then result in death.
The most common offending food components are wheat and milk. Wheat protein gluten (gliadin and glutenin) is responsible for causing Celiac disease (Kagnoff, 1992). Celiac disease is a permanent intolerance of the small bowel mucosa to gluten. The avoidance of a gluten-containing diet normally results in the disappearance of symptoms.
Intolerance to the milk sugar lactose is also the source of discomfort in individuals. This intolerance arises from the deficiency of the enzyme -galactosidase in the small intestine (Kocian, 1988). -galactosidase is necessary for the hydrolysis of milk disaccharide, lactose, into its constituent monosaccharides, glucose and galactose. While glucose and galactose can be absorbed and used for metabolic energy, lactose cannot be absorbed without prior hydrolysis. If-galactosidase activity is insufficient, incomplete hydrolysis of lactose from milk or dairy products occur. Undigested lactose passes into the colon, where the large numbers of bacteria will convert it to CO2, H2, and H2O. Symptoms associated with lactose intolerance include abdominal cramps, flatulence, and frothy diarrhoea.
Favism, which is caused by the ingestion of fava beans, is an adverse reaction resulting
from a deficiency of a metabolic enzyme, glucose-6-phosphate dehydrogenase (Mager
et al., 1980). Erythrocyte
glucose-6-phosphate dehydrogenase (G6PDH) is essential for maintaining adequate levels of the reduced form of glutathione (GSH) and nicotinamide dinucleotide phosphate (NADPH) in erythrocytes. GSH and NADPH protect the erythrocyte membrane from oxidation. Fava beans contain two potent, naturally occurring oxidants, vicine and convicine, which when consumed by G6PDH-deficient individuals can result in acute hemolytic anaemia (Mageret al., 1980). The typical symptoms include fatigue, abdominal and/or back pain, fever and chills, and in more severe cases, renal failure.
Naturally occurring constituents in foods are known to cause adverse reactions. Some of these constituents exert pharmacological effects on the sensitive individual.
Compounds such tyramine,
phenylethylamine, ethanol, caffeine and phenolic flavanoids, which are present in many foods such as cheese, chocolate and red wine have been reported to cause migraines in some individuals (Weber and Vaughan, 1991). Histamine poisoning can result from the ingestion of foods with high histamine content. Foods such as fish (tuna, mackerel, herring and sardine), wine, vegetables (spinach and eggplant), and some cheeses (Parmesan, Roquefort and blue) have a high histamine content. High histamine content in scrombroid and non-scrombroid fish occurs due to improper storage, resulting in bacterial enzymic decarboxylation of histidine to histamine. Histamine, when taken orally can stimulate degranulation of mast cells and basophils and is one of the mediators in the production of symptoms in allergic reactions (Baldwin, 1991).
of these results in vomiting, diarrhoea, abdominal cramps, and headaches and in the most severe cases even death. Puffer fish poisoning also results from the ingestion of the puffer fish neurotoxin (tetrodotoxin) (Taylor and Schantz, 1990).
Food additives used as preservatives, thickeners, colourings, flavourings and anti-oxidants have all been implicated as causative agents of adverse reaction to foods. The most common additives known to cause a wide range of clinical symptoms are sulphites, salicylates, benzoates and parabens,
tartrazine, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), nitrates, nitrites, aspartame, and monosodium glutamate (Weber et al., 1991).
Other contaminants commonly found in food such as heavy metals, agricultural chemicals and industrial waste pollutants have also been known to cause adverse reactions in human (Taylor, 1991).
Conclusion
Even though adverse reactions to food are very common and have been shown to increase two-fold over the last two decades, very few of the offending food antigens have been purified and characterised.
Furthermore, very little research has been done to investigate the effects of post-harvest handling and processing on the ability of these food-components to elicit adverse reactions in humans. With the increase in global trade in foods and ever-changing eating habits, it is conceivable that more people will come into contact with an even wider diversity of food antigens. In order to develop a more detailed understanding of the chemistry of food allergens and additives with respect to their ability to cause adverse reactions in humans, much further research is necessary.
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