Food authorities apply similar evaluation criteria and safety considerations for food allergens and natural toxins. No-observed adverse effect levels (NOAELs) and lowest-observed adverse effect levels (LOAELs) have been determined for the main regulated food allergens, and reference doses have been derived, setting guidance levels that protect the vast majority of the food-allergic population. The development and introduction of new dietary protein sources has the potential to improve food supply sustainability but may also result in de-novo sensitization, with or without clinical allergy, or clinical reactions through cross-reactivity. Thus, it is important to elucidate their potential allergenicity using current methodologies and new, advanced approaches such as “omics” analytics as well as in silico, in vitro and in vivo technologies.
Background
Food allergy is considered to be the fourth most important global public health problem by the World Health Organization. About 75% of allergic reactions among children are due to egg, peanut, cow’s milk, fish and various nuts. About 50% of allergic reactions among adults are due to fruits of the latex group and of the Rosaceae family, vegetables of the Apiaceae family, and various nuts and peanuts. Food allergy has implications for the general health status, economy and legislation of a country if a considerable percentage of its population suffers food-triggered allergic reactions ranging from rather mild symptoms to life-threatening events, which can only be avoided by dietary restrictions. In consequence, not only the allergic consumer has to adapt his whole life style to his condition, but also dependent persons like family and friends as well as caterers, restaurants and the food industry are required to react appropriately. In this respect, national and supranational food labelling directives have been enacted requiring food manufacturers, restaurants, street kitchens and caterers to declare ingredients with known allergenic potential. Additionally, possible allergenicity has to be considered when introducing novel foods (e.g. genetically engineered products).
Definition of food allergy
Adverse reactions to food, i.e. food hypersensitivity, are divided into immune-mediated and non-immune mediated reactions. Immune-mediated reactions to food are mediated either by IgE antibodies or other immunological pathways. Food intolerances comprise non-immune-mediated responses that are dependent on enzyme deficiencies, pharmacological reactions, or, as true in the majority of cases, arise by unknown mechanisms.
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Figurtekst: Our activities are focused on IgE-mediated food allergy.
Risk assessment in food allergy
There is high variability in sensitivity between different sensitised individuals with respect to the dose of allergens required to trigger an adverse effect. Individual NOAELs and LOAELs have been obtained from a large number of clinical challenge studies of food allergic subjects by statistical dose-distribution models, and reference doses (RD) for the major, EU-regulated food allergens milk, egg, wheat, soybean, cashew, shrimp, sesame seed, mustard, hazelnut and lupine were derived from the respective 99 % or 95 % confidence intervals, depending on data quality. The RD range from 0.03 mg for egg protein to 10 mg for shrimp protein, and protect the majority of the allergic consumers, while the most sensitive 1 to 5 % would only experience mild symptoms.
It is important to understand the mechanisms of food allergy in order to assess risk, to prevent and treat food allergy. Through cooperation with clinical physicians in Norway and Spain we have the possibility to align our analytical research on food allergens with patient data. Additionally, we have a successful long-term cooperation with the Norwegian Institute of Public Health and the Norwegian Food Authority, and participate in international food allergen focus groups such as the CEN Technical Committee 275 Working Group 12 Food Allergens, the AOAC Food Allergen Community, the International Life Sciences Institute, Europe, Expert Group for Food Allergen Analytical Methodology and the COST Action Improving Allergy Risk Assessment Strategy for New Food Proteins. The European Food Safety Authority is currently calling for proposals regarding the detection and quantification of allergens in foods and minimum eliciting doses in food allergic individuals.
Food allergens characteristics
Food contains an enormous variety of proteins, but only a small fraction are allergenic, and these can be either abundant or minor ingredients. The known allergens belong predominantly to a limited number of protein families with biological functions such as storage, hydrolysis, metal- and lipid-binding, as well as cytoskeleton association. Molecular masses range generally from 10 to 70 kDa. Many allergens occur in multiple isoallergenic forms showing 67% or more identity in amino acid sequence. Post-translational modifications and glycosylations contribute further to allergen diversity.
The allergenic potential of specific foods can originate either from a variety of different proteins with comparable allergenic capacity or from one dominating allergen. Leguminous plants like peanut, soybean and lupin are typical examples for foods containing a considerable number of potent allergenic proteins. In contrast, crustacean, fish, and molluscan allergy are predominantly caused by allergic reactions against one prevailing muscle protein of the respective animal.
Food allergens are characterized by their high stability towards heat, low pH and enzyme digestion, and the ability to usually survive food processing. Many detection methods are therefore based on the determination of one or several of the allergenic proteins in food.
Analytical methods for food allergens
The implementation and control of product labelling guidelines depends on the availability of reliable and sensitive analytical methods that specifically identify allergenic proteins in complex mixtures. Various techniques have been developed detecting qualitatively or quantitatively either the allergenic protein itself or a typical marker that signifies its presence.
Immunochemical methods detect proteins either with IgE from patient sera, or polyclonal and monoclonal IgG-antibodies generated by animal immunisation. Polymerase chain reaction (PCR) is a commonly used indirect technique that detects DNA as a representative for the allergen. Analysis by mass spectrometry (LCMSMS) for the identification, characterisation and determination of food allergens has become more important in the last years and allows the specific and simultaneous of different food allergens in a matrix.
Important food allergens
Among the identified allergens, only a few can be considered as major allergens, occurring in common foods and affecting a large portion of the allergenic population. Different dietary habits of the consumers have resulted in national distinctions in the prevalence of specific food allergies.
In the U.S., eight foods including crustaceans, egg, fish, milk, nuts, peanut, soybean, and wheat have been found to cause the majority of food allergenic reactions. Additionally, sesame is of importance in Australia, New Zealand, Canada, and the European Union (EU). Furthermore, Canada and the EU consider mustard as important allergen, and finally, the EU has extended the list with celery, lupin and molluscs to in total 13 foodstuffs and products thereof. In Japan and Korea, allergy to buckwheat is of considerable importance aside from the eight major allergens.
