Food allergy

Interim update of September 2015 version, dated December 2018  

Food allergens are part of a wider problem of a variety of adverse reactions to foods, which can result from microbial and chemical food poisoning, psychological aversions and specific non-allergenic responses.

Food allergy is now recognised as an important food safety issue, hence dealing with at least the major food allergens is an essential part of Good Manufacturing Practice. Great care must be taken by food manufacturers to:

  • formulate foods to avoid inclusion of unnecessary major allergens as ingredients, wherever possible
  • organise raw material supplies, production schedules and cleaning procedures, to prevent unintended allergen presence
  • train all personnel in an understanding of necessary measures and the reasons for them
  • comply with the relevant labelling legislation, providing appropriate warnings, to potential purchasers, of the presence of a major allergen contained in a product
  • have an appropriate system in place for recall of any product found to contain a major allergen, not indicated on the label warning.

The purpose of this statement is to describe the nature and cause of food allergies, to indicate ongoing research, to outline developments in legislation that aim to help allergic consumers to live with their condition, and to emphasise the measures that manufacturers and caterers should take to minimise the problems.

Background

Adverse reactions to foods

Adverse reactions to foods include not only food allergies but may also result from microbial and chemical food poisoning, psychological aversions, and specific non-allergic responses.

What are food allergy and food intolerance and why are they a problem?

Adverse reactions to food that have an immunological basis are termed ‘food allergies’ and include those which involve immunoglobulin E (IgE) - mediated reactions. The gluten intolerance condition, Coeliac disease, is thought to have a cellular immune mechanism. The macromolecules (usually proteins) involved in sensitising and eliciting IgE mediated allergic reactions are termed ‘allergens’.  In contrast, the term ‘food intolerance’ is used to describe reactions that do not involve the immune system and includes reactions to histamines and other amines found in foods.  Lactose intolerance is where individuals lack the enzyme necessary to break down lactose in the gut. Such adverse reactions to foods, which lack an immunological mechanism, can also be referred to as non-allergic food hypersensitivity reactions.

At present there is no cure for food allergies or food intolerance conditions and, as a result, sufferers must avoid eating problem foods, or in some individuals with severe forms of these conditions, any traces of them. Some tragic instances of accidental consumption of allergenic foods, (including so-called ‘hidden’ allergens which have not been declared on food labels) have occurred causing severe, and even fatal, reactions.  Avoidance of allergenic foods can prove difficult for the allergic consumer, and their families or carers, making shopping a time-consuming process involving checking food labels.  Market stalls, where foods are sold loose, also present problems if utensils used, for example, to serve nut-containing confectionery, are then used for nut-free products.  Problems also occur in catering where dishes are presented without detailed provision of ingredients information, and where in a busy kitchen the same utensils may be used for different foods. Ordering food online via apps and websites also presents challenges in communicating the presence of allergenic ingredients and ensuring that risks are fully understood.

IgE-mediated food allergies

The immune system produces several different types of molecules, known as immunoglobulins, as part of the body’s defense mechanism against viral, microbial and fungal infections. One particular form, immunoglobulin E (IgE), is also produced in response to parasitic infections such as the malaria parasite. Sometimes the body can also mount an IgE response towards agents such as pollen, dust, and food, and it is these responses that give rise to allergy syndromes, such as hay fever and food allergy.

IgE-mediated allergies develop in two stages:

i)  the first stage is known as sensitisation and occurs when a person’s immune system encounters a particular allergen prompting the formation of allergen specific IgE which becomes bound to specific receptors on the surface of basophil or mast cells, containing inflammatory mediators, such as histamine.;  

ii) the second stage involves the elicitation of an allergic reaction. On re-exposure to the sensitising agent, the cell-bound IgE becomes cross-linked by the allergen, causing the mast cells to release the inflammatory mediators.  These mediators then trigger the physiological changes leading to symptoms of an allergic reaction.  They usually occur within minutes of exposure to an allergen and are quite varied, including respiratory (e.g. asthma), gastrointestinal (e.g. vomiting) and skin [e.g. hives (nettle rash)] reactions.

Common trigger allergens include foods, but also insect stings (e.g. from bee, wasp and hornet) as well as from medication, including beta-blockers, nonsteroidal anti-inflammatory drugs (NSAID), angiotensin converting enzyme (ACE) inhibitors, antibiotics and aspirin.  Although allergy to foods, such as peanut, tree nuts and seafood, is likely to continue throughout an individual’s life, sensitivity to most other food allergens is often lost in late childhood.   There is recent evidence to suggest that the dermal route of exposure may also be relevant to sensitisation.

Primary prevention of food allergy seems to be possible through protocols for early dietary intervention, but the longer-term allergy profile for these children is not yet known.  Initiatives are underway to reverse food allergy through immunotherapy, both through supervised consumption of everyday foods and through pharmaceutically prepared up-dosing for consumption, or via the skin.

In adults the onset of food allergy may be related to inhaled allergens such as birch, grass pollen and latex.  Because of homologies between the allergens in pollen, latex and various fruits and vegetables, for example, such individuals can develop cross-reactive allergies to fresh fruits and vegetables, known as pollen-fruit and latex-fruit syndromes.

Allergic reactions may be triggered by minute amounts of allergen and may range from relatively short-lived discomfort to anaphylactic shock and death, not only from the well-publicised peanut, but increasingly from milk and other foods.

What is the size of the food allergy problem?

Currently good quality information on the prevalence and patterns of food allergy is lacking. However, about 1-2% of adults and between 5-7% of children are thought to suffer from some type of IgE-mediated food allergy. The higher incidence of allergies in infants is due to allergy to cow’s milk, which the children generally grow out of by school age. Estimates of prevalence are complicated by the fact that individuals can develop IgE responses (i.e. be sensitised to an allergen) without that allergen causing an allergic reaction. For example, many patients allergic to peanuts have IgE that can cross-react with soya proteins, but generally they suffer no allergic reaction when they eat soya-containing foods.

This has meant that the “gold standard” for food allergy diagnosis is the double-blind placebo-controlled food challenge, where individuals are given the offending food in increasing doses until objective symptoms of an allergic reaction are observed.

Which foods are most often involved in triggering allergies?

About eight types of food are thought to be responsible for causing the majority of food allergies, including foods such as cow’s milk, egg, fish and shellfish, peanuts, tree nuts, wheat, and soya. A summary of the major allergens in these foods is given in Table 1, together with the allergen names designated by the Allergen Nomenclature sub-committee of the International Union of Immunological Societies. Allergens included in this listing must induce IgE-mediated (atopic) allergy in humans with a prevalence of IgE reactivity above 5%. An allergen is termed major if it is recognised by IgE from at least 50% of a cohort of allergic individuals but does not carry any connotation of allergenic potency; allergens are otherwise termed “minor”. The allergen designation is then based on the Latin name of the species from which it originates and is composed of the first three letters of the genus, followed by the first letter of the species finishing with an arabic number e.g. Ara h 1 relates to an allergen from Arachis hypogea (peanuts). More detailed information on allergenic foods can be found in: http://research.bmh.manchester.ac.uk/informall/allergenic-foods/

Table 1: Major Allergenic Foods

Food

Summary

Major Allergens

Examples of specific allergen proteins

Cow’s milk

Allergens are found in both the whey and casein fractions, although other IgE-reactive proteins have been identified. Cow’s milk allergy is predominantly an allergy during infancy and is generally outgrown by school age.  It can cause severe reactions and there are reports of just a drop of milk being sufficient to trigger an anaphylactic reaction. Due to the similarity of the amino acid sequences in the proteins (caseins and whey proteins), individuals with cow’s milk allergy cannot usually tolerate dairy foods based on sheep’s and goat’s milk either. The allergenicity of milk cannot be removed by simple thermal processing

 

Casein

 

b-lactoglobulin

 

a-lactalbumin

 

Bos d 8

 

Bos d 5

 

Bos d 4

Hen’s Egg

Egg allergy is more frequent in infants, many of whom outgrow their allergy by school age. Major allergens originate primarily from egg-white, and include ovomucoid and ovalbumin, which constitute 10% and 50% of egg-white proteins respectively. Both proteins are heavily glycosylated with 25% of the mass of ovomucoid comprising carbohydrate. They are also resistant to enzymatic digestion and denaturation. There are other minor allergens in egg white and yolk. In general, cooking, such as boiling to completely solidify the egg, reduces its allergenic activity. In some instances, people who keep birds as pets may develop allergies to their pets, which can sometimes result in allergies to eggs when eaten

Ovomucoid

 

Ovalbumin

Gal d 1

 

Gal d 2

Fish

The major fish allergen is parvalbumin, a protein which is conserved across fish species. This similarity is responsible for the cross-reactive nature of allergens in cod, salmon, mackerel, herring and plaice, as well as many other fish species. Like other calcium-binding proteins, it is heat-stable, with the holo form being more IgE-reactive and more heat stable than the apo form. As a consequence, individuals with fish allergy cannot even consume well cooked fish 

Parvalbumin

Gad c 1 (cod) Sal s 1 (Altlantic salmon)

 

Shellfish and seafood

Tropomyosin, a heat-stable muscle protein, is the major allergen in shell-fish and seafood, with highly homologous proteins being found in the commonly edible crustaceans. These homologies are responsible for the cross-reactive allergies observed between various types of seafood, including shrimps, lobsters, crab, squid and abalone, and inhalant insect allergens, such as those from cockroaches. In addition to being stable to cooking, the allergen leaches from shellfish and seafood into cooking water 

Tropomyosin

Pen i 1 Penaeus aztecus and similar allergens from other shrimp species including Penaeus indicus, Penaeus monodon and Metapenaeus ensis

Peanut

Peanut allergy has apparently increased in the last 20 years, particularly in Western countries, and appears to be responsible for triggering a greater proportion of severe, life-threatening reactions. Thermal processing, including roasting, does not destroy its allergenic activity, although boiling may reduce allergenicity as a consequence of allergens leaching into the cooking water. There do not appear to be significant differences in allergenic properties between different varieties of peanuts.  Research has shown that peanut oil (including ‘refined’ peanut oil as opposed to ‘highly refined’ peanut oil) can cause allergic reactions

 

 
 

7S seed storage globulin

 

11S seed storage globulins

 

2S albumin

Ara h 1

 

 

Ara h 3,4

 

 

 

 

Ara h 2, 6, 7

 

Ara h 5

Soya

Whilst allergy to soya is perceived to be a major problem, there are many fewer reports of it in the literature than exist for peanut. The allergens include the seed storage globulins and a homologue (Gly m 4) of the major birch pollen allergen, Bet v 1, and appear to be stable to processing.  It can be found in textured soya protein, although not in roasted beans, or fermented products such as soy sauce. In the USA populations with soya allergy have been reported that react to a protein related to a family of proteases, although its sequence has been modified and it has lost its enzymatic activity

7S seed storage globulin

 

11S seed storage globulins

Bet v 1 homologue

 

Inactive papain-related thiol protease

 

 

 

 

 

 

 

Gly m 4

 

 

Gly m Bd 30K

 

Tree nuts

 

Almond

 

Brazil nut

 

Cashew nut

 

Hazelnut

 

Macadamia

 

Pecan

 

Pistachio

 

Queensland

 

Walnut

Many tree nuts have been described as triggering food allergies, with the best studied being hazelnut, Brazil nut and walnut. The major allergens are the seed storage proteins, including both the 2S albumins and the 7S and 11/12S globulins. For some nuts, such as hazelnut, allergy can be associated with prior sensitisation to birch pollen, whilst in others, such as hazelnut and walnut, the non-specific lipid transfer proteins are found as allergens. Whilst hazelnut allergies are well known those to other nuts, such as Macadamia, are poorly characterized in the literature, although they are included in Annex IIIa of the EU labelling directive 

2S albumin

 

 

 

 

7S storage globulins

 

 

 

 

11S seed storage globulins

 

Non specific lipid transfer proteins

 

Bet v 1 homologue

Almond

Ber e 1 (Brazil nut) Jug r 1 (Walnut), Ana o 3 (Cashew)

 

Jug r 2, Major

Almond Protein

Ana o 1 (cashew) Cor a 11 (hazelnut),

 

 

Ber e 2 (Brazil nut)

Ana o 2 (cashew)

Cor a 9 (hazelnut)

 

Cor a 8 (hazelnut)

Jug r 3 (walnut)

 

 

Cor a 1.0401(Hazelnut)

Seeds

 

Mustard

 

 

Sesame

 

Mustard allergy has been reported amongst children, in France, whilst sesame seed allergy is especially important in countries such as Israel, where tahini, a sesame-based weaning food, is widely used. The major allergens in both sesame and mustard belong to the seed storage proteins and are remarkably stable to processing and proteolysis. Consequently, the allergenicity of the foods is unlikely to be modified by thermal processing, although there are no studies reporting the impact

2S albumin

 

 

Bra j 1 and Sin a 1 (Mustard)

 

Ses i 1, Ses i 2 (Sesame seeds)

Cereals

 

Wheat

Wheat, barley and rye contain a range of allergens, including the prolamins (alcohol-soluble storage proteins), which are responsible for triggering Coeliac diseases and food allergies such as food-dependent exercise-induced anaphylaxis and atopic dermatitis. Cereals have been found to trigger two types of allergic disease: the occupational allergy, known as Baker’s asthma (resulting from inhalation of flour particles in dusty working environments, such as bakeries), and as a consequence of ingestion of cereal containing foods. Due to the similarity of cereal storage proteins, individuals with Coeliac disease, or IgE-mediated allergies to wheat, often react to wheat, rye and barley.

Protein inhibitors of proteases, and a-amylases of cereals, have also been described as both inhalant (e.g. Baker’s asthma) and food allergens. A number of other proteins have been described as allergens in Baker’s asthma including Tri a Bd 17K, a wheat peroxidase

 

Seed storage prolamins

 

 

 

 

 

 

 

a-amylase/

trypsin inhibitors

 

 

 

 

Glycosylated peroxidase

Gliadins, glutenins (wheat gluten proteins) together with homologues from barley (hordeins) and rye (secalins)

 

 

Members of the CM (chroloform-methanol) soluble proteins including CM3

 

Tri a Bd 17K

Fresh fruits and vegetables

 

Kiwi

 

Peach

 

 

Celery

Fruit allergy is often associated with allergy to tree and grass pollen, and to latex. Thus, individuals who develop an allergy to birch pollen tend to be allergic to a major birch pollen protein called Bet v 1. Related proteins are found in other plant species, and edible tissues of fresh fruits and vegetables. Consequently, when people with a Bet v 1-type birch pollen allergy eat fruits, such as apples, they often experience a reaction to the fruit which is confined to the oral cavity. The latter reaction has been termed oral allergy syndrome (OAS). Many Rosaceae fruits are involved in this pollen-fruit allergy syndrome, together with vegetables, such as celery. In general, such types of allergens are rapidly destroyed by cooking, except for the form found in celery, which can retain its allergenic activity, even in soups.

 

Other types of fruit allergy occur where there is no association with a prior pollen or latex allergy, notably kiwi fruit allergy, which involves the cysteine proteinase actinidin. Similarly, allergies to peach and related Rosaceae fruit found in southern Europe can often be life-threatening, being more akin to peanut allergies experienced in the USA or UK. They are triggered by non-specific lipid transfer proteins which are thermostable and not destroyed by processing, with the allergens even finding their way into fermented products such as wine and beer

Homologues of the major birch pollen allergen Bet v 1

 

Cysteine protease

 

LTP

 

 

 

Act c 1 of kiwi fruit

 

Pru p 3 of peach

 

Api g 1 of celery,

 

 

Please note, the following allergens, currently included in Annex II to Regulation 1169/2011, remain to be added to the above table: lupin, molluscs and sulphites.

It has been estimated that around 95% of food allergic reactions are caused by several major groups of food allergens. However, such estimates are imprecise, and debate about which allergens should be the subject of mandatory label warnings accounts for the fact that it took until 2003 (EU) and 2004 (USA) to determine regulatory lists.

The EU Regulation 1169/2011 (EU FIC) on the provision of food information to consumers, came into mandatory force on 13 December 2014 and superseded Directive 2003/89/EC. It specifies the highlighting in the ingredients list of any of the legislated allergens (the ‘Annex II allergens’) intentionally incorporated in the food., These must be ‘emphasised through a typeset that clearly distinguishes it from the rest of the list of ingredients, for example by means of the font, style or background colour’.

Current guidance will be found here:  https://www.food.gov.uk/sites/default/files/media/document/food-allergen-labelling-technical-guidance.pdf

 

Table 2: Major Allergenic Foods listed in EU FIC

Cereals containing gluten, (i.e wheat, rye, barley, oats spelt or their hybridised strains) and products thereof

Crustaceans and products thereof

Eggs and products thereof

Fish and products thereof

Peanuts and products thereof

Soybeans and products thereof

Milk and products thereof (including lactose)

Nuts i.e.  Almond, Hazelnut, Walnut, Cashew, Pecan nut, Brazil nut, Pistachio nut, Macadamia nut and Queensland nut and products thereof

Celery and products thereof

Mustard and products thereof

Sesame seeds and products thereof

Sulphur dioxide and sulphites at concentrations of more than 10mg/kg or 10 mg/litre expressed as SO2.

Molluscs and products thereof

Lupins and products thereof.

N.B. The gluten proteins of wheat that trigger coeliac disease can also cause IgE-mediated allergies. The inclusion of wheat in the WHO and EU allergen lists covers both its allergenic properties and its coeliac toxic effects although the dose-response and management issues regarding these diseases are distinctly different.

 
The responsibilities of individuals

No form of warning about the presence of an allergen in a food can be effective for an individual unless they are aware of the foods or food substances to which they are allergic.  This information cannot be derived from any source except that individual and his/her medical adviser.  People who think that they suffer from a food allergy should undergo tests to determine if it is a true allergy, and if so, what substance is the cause.  There are two methods of determining whether a person is allergic to a food or food substance. The first, and simpler, is the skin test and the second, more elaborate, but more definitive, is the double-blind, placebo-controlled oral challenge test.

Precautionary allergen labelling (PAL) – ‘may contain’

The EU Regulation does not address the problems of allergens that enter foods accidentally from:

  • accidental inclusion of an ingredient, before or after it is received
  • accidental mis-formulation
  • contamination by an allergen from a different product.

Accidental inclusion of an ingredient or a product by an allergen from a different ingredient or product may arise in storage and handling of raw materials, or during production due to residues in shared equipment, airborne dust, or the improper incorporation of re-work material without consideration of the allergen problem.  Mis-formulation resulting in the inclusion of an allergen (or any other ingredient) not in the product formulation recipe should be prevented by proper attention to the formulation development and the operation of appropriate control provisions to ensure that the product as prepared contains only the ingredients specified.  It should be emphasised that the importance of recognising unintended allergen presence applies not only to a product nominally free from allergens, but equally to a product containing one or more declared allergens at risk of unintended presence of others.

Food manufacturers have a responsibility to minimise the risks to allergen-susceptible consumers of their products. As with any other food-related hazards, action should be based on a HACCP-style analysis of the operations in relation to allergen hazards. This should lead to adoption of appropriate measures.  In a multi-product company, the ideal would be the complete segregation in different buildings, which some companies have done. In any event appropriate measures should include:

  • formulation of foods to avoid, wherever possible, inclusion of unnecessary major allergens as ingredients
  • organising raw material supplies, storage and handling, production procedures, production schedules and cleaning procedures to prevent contamination of products by unintended allergens
  • training all personnel in an understanding of necessary measures and the reasons for them
  • compliance with the relevant labelling legislation providing appropriate warning, to potential purchasers, of the presence of a major allergen in a product
  • having in place an appropriate system for recall of any product found to contain a major allergen not indicated on the label warning
  • having in place an appropriate system to collect and collate information about complaints and possible allergic reactions to foods they sell, and to implement lessons learned

In response to the problems posed by accidental inclusion of allergens, and the lack of resources to implement appropriate control systems, many manufacturers have adopted a ‘precautionary labelling’ approach. Precautionary statements such as ‘may contain’ are expressly allowed in Australia and New Zealand and are used widely in these countries. In the UK, longstanding industry guidelines state clearly: it is emphasised that the use of advisory ‘may contain’ labelling should be the last resort of a series of assessments. It should never be used as an alternative to GMP and relevant controls. However, unless responsibly applied by the manufacturer as a last resort, following a thorough assessment of each product on a case-by-case basis, such labels do not help allergic consumers cope with their condition and may mean their food choices become ever more restricted. Such labels, if applied without the necessary risk assessment, can be viewed also as a cover for sub-optimal allergen control practices, and may run the risk of devaluing the label itself: https://www.food.gov.uk/safety-hygiene/allergy-and-intolerance  

There is anecdotal evidence that some allergic consumers ignore precautionary labels, putting themselves at a potential risk, and for these individuals provision of more meaningful information about allergens possibly present, may enable them to make better informed choices. Other types of allergic consumer prefer the manufacturers to take responsibility for deciding which products are suitable for someone with an allergy with clear negative, e.g. ‘not suitable for nut allergy sufferers’, or positive e.g. ‘This product is nut-free’, statements, though it is not clear how ‘not suitable for …’  provides greater consumer choice than ‘may contain’. There are issues regarding provision of more information on allergens on crowded food labels and conflicts with the need to make them clear and simple to read.

Allergic consumer groups, such as the European Federation of Allergy and Airways Diseases Patients' Associations (EFA) have called for the EU to regulate precautionary labelling. It may also be useful to back-up information on labels with additional background information to facilitate interpretation of labels.  However, the preferences of different end-users regarding the format that such information should take, and the type of additional information required to back-up what is provided on the label still need to be defined.

Foodservice responsibilities and problems

In general, the principles referred to for product formulation and avoidance of unintended allergen presence by manufacturers apply equally to foodservice providers; and similar warnings should be given adjacent to appropriate items on menus or self-service display notices.

In some large restaurant chains, the expertise exists to do this, and their buying power enables them to lay down specifications and monitor performance of ingredient suppliers; but many small foodservice outlets have neither that expertise nor sufficient buying power. Label warnings on bulk packs supplied by manufacturers for foodservice use may be of some help but such information must remain readily available after the packs have been opened and the contents decanted.

How much allergen does it take to cause a problem?

In order to control allergens in foods effectively, it would be important to know how much of an allergen (or allergen containing food) can trigger an allergic reaction in an individual.

While low doses of allergenic foods clearly can present some risk to allergic consumers, the imposition of a zero-tolerance level for undeclared allergens in such foods places unachievable burdens on the food industry.

Current evidence appears to enable the establishment of allergen reference doses which might be translated into action limits or population thresholds to underpin reliable food safety management plans for some foods. However, further work is required to include a wider variety of foods and to understand the impact of the food matrix as well as additional factors which affect the progression and severity of symptoms as a function of dose. There is an urgent requirement for effective communication between healthcare professionals, patient organizations, food industry representatives and regulators to develop a better approach to protecting consumers with food allergies.  Crevel and colleagues have described two approaches – ‘deterministic’ and ‘probabilistic’. In the deterministic approach action levels are derived from reference doses, food intake and contamination data by a simple arithmetical method. In the probabilistic approach modelling is used to derive action levels using food intake and minimum eliciting dose distributions, as well as a certain accepted residual risk level as a starting point. As an example of deterministic approach the Allergen Bureau Food Industry Guide to the Voluntary Incidental Trace allergen Labelling (VITAL) Programme is a standardised allergen risk assessment process for food industry; http://allergenbureau.net/about-us/). It is widely used in Australia and New Zealand but has yet to gain widespread acceptance globally. The VITAL system is free to download and should be consulted in full but operates under the following broad principles:

  • Intentionally added allergens must be declared on the product label (e.g. in the List of Ingredients according to local law).
  • Action Levels are the concentrations which define the labelling outcomes for each concentration of unintended allergen present. They are determined using the Reference Dose and the Reference Amount/Serving Size. 
  • Unintended allergen presence must be reviewed for opportunities to reduce or eliminate cross contaminant allergens from the product.
  • Where such unintended allergens cannot be eliminated, they should be labelled as specified by the appropriate Action Level:
  • Action Level 1: precautionary allergen labelling statement is not required for the relevant allergen under evaluation
  • Action Level 2: precautionary allergen labelling statement is required for the relevant allergen using the standard VITAL statement.
  • Precautionary labelling should only be used after a thorough assessment of the risk. Precautionary allergen labelling must NEVER be used as a substitute for good manufacturing practice (GMP) or as a generic disclaimer. Every attempt must be made to eliminate or minimise unintended presence by adhering to GMP
  • The ONLY precautionary statement to be used in conjunction with VITAL is: ‘May be present: name of allergen’.

In practice, the food industry may be nervous of such an approach.  ED01 is the eliciting dose in relation to an underlying risk that 1 in 100 allergic individuals will have a reaction, but the question is if this is an acceptable balance of risk.  It may be acceptable to a food business selling 1,000 units a week, but not to a food business selling 100,000 units a week. Food retailers may be tempted to, and probably do, opt for the analytical limit of detection as a default action limit, which may not bear any relation to true risk. Thus, we need to factor in sales and consumption as a measure of exposure, and the percentage of the population who have the allergy which may be better addressed by a probabilistic approach. The severity of reaction is also an issue. The UK Food Standards Agency clinical study, into how sensitivity to peanut is altered by external factors, involved a three-year TRACE study led by Dr Andrew Clark, allergy consultant at Addenbrooke’s (part of Cambridge University Hospitals), and Dr Robert Boyle and Professor Steven Durham from Imperial College, London. Adults aged 18-45 with clearly defined IgE mediated allergy to key peanut proteins underwent 'challenges' under varying conditions to find out how sensitivity to peanut is altered by external factors, including exercise and stress.

What to analyse for?

Analysis for food allergens is required for many reasons. Key industry standards emphasise greater transparency, traceability and integrity in the supply chain requiring analysis to check that food is what it is claimed to be and encourage systems to reduce exposure to fraud. Analysis supports validation and verification of factory cleaning and investigation of recalls and incidents. Surveillance and enforcement, rely heavily on analysis and provide evidence for criminal or civil action in the courts. Investigation of adverse reactions may require analysis to find out what caused the reaction, and therefore enable the individual to avoid it in the future.

Food allergens that bind to IgE are large protein molecules and many approaches have been taken to their analysis. Most routine food allergen analysis is undertaken by Enzyme Linked Immunosorbent Assay (ELISA) enabling detection and (semi-) quantification. Polymerase Chain Reaction (PCR) assays are also applied in allergen risk assessment and management. For both techniques detection is less of an issue, although not without problems but sound quantification remains elusive.  Commercially available ELISA kits exhibit variable and manufacturer specific sensitivities and cross-reactivity. In proficiency testing multimodal datasets for allergen ELISAs are common and different assigned values must be generated for the different kits used.  Structural changes in the target molecules by food processing or sample extraction may prevent detection. PCR assays are probative of the source species DNA (which may not be present e.g. egg white) rather than the allergen protein. Moreover, proteins are the hazard and thus the key measurand. PCR is essentially qualitative at present. There is a requirement for orthogonal methods that confirm molecular identity and that are capable of valid quantification. Liquid chromatography with tandem mass spectrometry, LC-MS/MS methods, e.g. multiple reaction monitoring of peptides arising from enzymatic digestion of proteins, offer such advantages, along with the possibility of multiplexed high throughput. The application of LC-MS/MS is still recent in food allergen analysis. It is possible to detect proteins and peptides with a high degree of sensitivity and resolving power, providing protein composition, structure and sequence information, and MS has the potential for a wide linear dynamic range, and absolute identification and quantification of allergens. However, the techniques require a high level of expertise and costly equipment; extraction and clean-up steps are necessary, and the methods can be laborious and time consuming. The complexity of most food matrixes represents a significant challenge even to MS although guidance is available, including on a model system that demonstrates isotope dilution mass spectrometric traceability from a set of peptides to an allergenic protein. Because ELISA is much more widely used for allergen analysis than MS or PCR there is more published evidence of its deficiencies, but similar deficiencies apply to both MS and PCR approaches. Thus, the promise of MS or PCR will be lost if underpinning work is not carried out.

In summary, current allergen analysis would be impossible without ELISA which has brought many benefits in allergen risk assessment and risk management. However, all current forms of allergen analysis present some deficiencies which may jeopardise present and future risk assessment and risk management of food allergy, a problem of high and increasing importance. The provision of reference materials, a task under way in several institutions, is essential to calibrate and validate analytical methods for allergens.

 

Allergenic potential of GM foods and novel foods

In many countries an assessment of the allergenic risks posed by a GM food or a novel food must be performed before it can be released into the market. This is now a routine feature of European assessments of GM or novel foods before authorisation is granted.  

Food allergy research

Research into food allergy spans many disciplines. It should aim to increase our understanding of the molecular basis of allergic disease. Improved information resulting from research into what makes an individual become allergic and what makes some proteins become allergens and not others will provide even more effective assessment of the allergenic potential of novel foods.

The UK Food Standards Agency has a significant food allergy and food intolerance research programme to improve the understanding of the causes and mechanisms of food allergy https://www.food.gov.uk/research/food-allergy-and-intolerance-research

EuroPrevall was an EU-funded multidisciplinary integrated project (IP) involving 24 countries, including 17 European Member States. The project came to an end in December 2009, but publications related to the project continue to appear. EuroPrevall research focused on:

  • Characterising the patterns and prevalence of food allergies across Europe in infants, children and adults
  • Developing methods to improve the quality of food allergy diagnosis, reducing the need for food challenge tests
  • Determining the impact of food allergies on the quality of life and its economic cost for food allergic people and their families, workplace and employers, and healthcare.

This project was followed by the iFAAM project http://www.eurofir.org/our-resources/past-projects/ifaam/ which finished in February 2017.

 

Further reading

Anagnostou, K., Islam, S., King, Y., Foley, L., Pasea, L., Bond, S., Palmer, C., Deighton, J., Ewan, P. and Clark, A., (2014). Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial. The Lancet, 383 (9925), pp. 1297–1304.

http://www.nature.com/news/2007/070702/full/news070702-16.html  

iFAAM (2013) allergen research project http://www.manchester.ac.uk/aboutus/news/display/?id=9743 

Prescott, S.L., Pawankar, R., Allen, K.J., Campbell, D.E., Sinn, J.K., Fiocchi, A., Ebisawa, M., Sampson, H.A., Beyer, K. and Lee, B.W., (2013). A global survey of changing patterns of food allergy burden in children. World Allergy Organization Journal, 6 (21), pp. 1-12.

Regulation (EU) No.1169/2011 of 25 October 2011 on the provision of food information to consumers. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2011:304:0018:0063:EN:PDF  

Sampson HA. Update on food allergy. J Allergy Clin Immunol. 2004 May; 113(5):805-19 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15131561

UK Food Standards Agency. Advice for caterers on allergy and intolerance. http://www.food.gov.uk/business-industry/allergy-guide   

UK Food Standards Agency. Guidance on food allergen labelling legislation http://www.food.gov.uk/science/allergy-intolerance/label   

UK Food Standards Agency. Providing allergen information for non-prepacked foods.

https://www.food.gov.uk/business-guidance/allergen-information-for-pre-packed-and-loose-foods

UK Food Standards Agency. Food Intolerance including Food Allergy Research Programme https://www.food.gov.uk/research/food-allergy-and-intolerance-research 

Michael Walker and Hazel Gowland, 2017, Food Allergy: Managing Food Allergens’, in ‘Analysis of Food Toxins and Toxicants’, Eds. Yiu-Chung Wong & Richard J. Lewis, Wiley, ISBN: 978-1-118-99272-2, pp 711 – 742, http://eu.wiley.com/WileyCDA/WileyTitle/productCd-1118992725.html

References

1. Muraro, A., Hoffmann‐Sommergruber, K., Holzhauser, T., Poulsen, L.K., Gowland, M.H., Akdis, C.A., Mills, E.N.C., Papadopoulos, N., Roberts, G., Schnadt, S. and Ree, R. (2014) EAACI Food Allergy and Anaphylaxis Guidelines. Protecting consumers with food allergies: understanding food consumption, meeting regulations and identifying unmet needs. Allergy 69, 1464–1472.

2. Crevel, R.W., Baumert, J.L., Baka, A., Houben, G.F., Knulst, A.C., Kruizinga, A.G., Luccioli, S., Taylor, S.L. and Madsen, C.B. (2014a) Development and evolution of risk assessment for food allergens. Food and Chemical Toxicology 67, 262–276

3. Taylor, S.L., Baumert, J.L., Kruizinga, A.G., Remington, B.C., Crevel, R.W., Brooke-Taylor, S., Allen, K.J., of Australia, T.A.B. and Houben, G. (2014) Establishment of reference doses for residues of allergenic foods: report of the VITAL expert panel. Food and Chemical Toxicology 63, 9–17.

4. Allen, K.J., Remington, B.C., Baumert, J.L., Crevel, R.W., Houben, G.F., Brooke-Taylor, S., Kruizinga, A.G. and Taylor, S.L., (2014). Allergen reference doses for precautionary labeling (VITAL 2.0): clinical implications. Journal of Allergy and Clinical Immunology, 133 (1), pp. 156–164.

5. For example, the British Retail Consortium (BRC) Global Standard for Food Safety, https://www.brcglobalstandards.com/

6. Forensic investigation of a sabotage incident in a factory manufacturing nut-free ready meals in the UK, Walker M J, In:  J Hoorfar, Ed. Case Studies in food safety and authenticity, Woodhead Publishing 2012, pp288 – 295

7.  M.  J.  Walker, P.  Colwell, S.  Elahi, K.  Gray and I.  Lumley, Food Allergen Detection: A Literature Review 2004 – 2007, J. Assoc. Public Analysts, 2008, 36, 1-18

8. A.  Scharf, U. Kasel, G. Wichmann, and M. Besler, Performance of ELISA and PCR methods for the determination of allergens in food: an evaluation of six years of proficiency testing for soy (Glycine max L.) and wheat gluten (Triticum aestivum L.), J. Agric. Food Chem., 2013, 61, 10261-10272

9. Török, Kitti, Lívia Hajas, Vanda Horváth, Eszter Schall, Zsuzsanna Bugyi, Sándor Kemény, and Sándor Tömösközi. "Identification of the factors affecting the analytical results of food allergen ELISA methods." European Food Research and Technology (2015): 1-10

10. P.  E. Johnson, N. M. Rigby, J. R. Dainty, A.  R. Mackie, U. U. Immer, A. Rogers, P. Titchener, M. Shoji, A. Ryan, L. Mata et al., A multi-laboratory evaluation of a clinically-validated incurred quality control material for analysis of allergens in food, Food Chem., 2014, 148, 30-36

11. M.  Sykes, D. Anderson, and B. Parmar, Normalisation of data from allergens proficiency tests, Anal. Bioanal. Chem., 2012, 403, 3069-3076

12. L. Monaci and A. Visconti, Mass spectrometry-based proteomics methods for analysis of food allergens. TrAC, ,28, 581-591

13. J. Heick, M. Fischer, S. Kerbach, U. Tamm, and B.  Popping, Application of a liquid chromatography tandem mass spectrometry method for the simultaneous detection of seven allergenic foods in flour and bread and comparison of the method with commercially available ELISA test kits, JAOAC Inter., 2010, 94, 1060-1068

14. P. E. Johnson, S. Baumgartner, T. Aldick, C. Bessant, V. Giosafatto, J. Heick, G. Mamone et al., Current perspectives and recommendations for the development of mass spectrometry methods for the determination of allergens in foods, 2011, J AOAC Int., 2011, 94, 1026-1033

15. A. Cryar, C.  Pritchard, W.  Burkitt, M.  Walker, G.  O’Connor, D. T. Burns and M.  Quaglia, 2013, Towards Absolute Quantification of Allergenic Proteins in Food—Lysozyme in Wine as a Model System for Metrologically Traceable Mass Spectrometric Methods and Certified Reference Materials, JAOAC Int., 96, 1350-1361

The Information Statement was originally prepared by Professor J. Ralph Blanchfield, MBE CSci FIFST, in cooperation with IFST’s Scientific Committee. An interim review was carried out in September 2018, by Dr. Hazel Gowland FIFST and Dr. Michael Walker FIFST. A full review of the Information Statement is expected in 2019.

 

The Institute takes every possible care in compiling, preparing and issuing the information contained in IFST Information Statements, but can accept no liability whatsoever in connection with them. Nothing in them should be construed as absolving anyone from complying with legal requirements. They are provided for general information and guidance and to express expert professional interpretation and opinion, on important food-related issues.