Food Allergy

Food hypersensitivity is a term used to describe a sub-category of adverse reactions to food. Where reproducible symptoms follow contact with or (more usually) consumption of a particular food, which can be sub-classified as follows:

• immune-mediated food allergy – the focus of this IFST Information Statement
• coeliac disease – an auto-immune condition involving hypersensitivity to gluten
• food intolerance – symptoms elicited by the pharmacological effects of food components such as histamine, non-coeliac gluten sensitivity, enzyme and transport defects, such as lactose intolerance and some food additives e.g. tartrazine, annatto, sulphites, benzoic acid, and short chain fermentable carbohydrates e.g. fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs).

What is an immune-mediated food allergy?

It is estimated that approximately 1-2% of adults and 5-8% of children in the United Kingdom (UK) live with immune-mediated food allergy. This is classified according to whether the onset of symptoms is immediate (from a few minutes to about two hours from exposure or consumption of the food allergen) or delayed (from a few hours to days, or even longer after exposure or consumption). Immediate-onset food allergy involves an Immunoglobin E (IgE) antibody response, whilst delayed-onset food allergy involves different immune mechanisms. Some delayed-onset food allergy was previously described as food intolerance but is becoming increasingly better understood.

IgE mediated food allergies

The IgE mediated response is a two-step process:

1. sensitisation
2. elicitation.

Sensitisation can begin with the person being exposed to a food allergen by consumption, by inhalation or via the skin (particularly broken skin such as eczema). If predisposed to do so their body may respond by treating the allergen as a threat and make specific IgE antibodies against particular proteins (allergens) in the food. A similar mechanism is triggered for other allergens e.g. insect stings, animal dander, saliva or house dust mite.

Elicitation is the immune system trying to protect the body from a perceived attack. If a pre-sensitised person is exposed to the same allergen again e.g. by eating the food, it may bind with the specific IgE antibodies, and set off (or ‘elicit’) an allergic response. The binding event causes a release of histamine and other mediators that give rise to the symptoms of a systemic allergic response.

Further information about allergy is available at the British Society for Immunology website https://www.immunology.org/public-information/bitesized-immunology/immune-dysfunction/allergy

A useful database of food allergens can be found here: http://research.bmh.manchester.ac.uk/informAll/allergenic-foods

Allergic response symptoms

Most food allergic reactions are mild. Fluid released from blood vessels can cause swelling (angioedema), particularly of the face, mouth and throat. Localised swelling of the mouth and face, itching, rash/hives, (urticaria) runny eyes or nose, flushing, or clamminess of the skin are usually mild and may resolve with minimal or no medical treatment. Gastro-intestinal system symptoms e.g. nausea, pain, and vomiting may occur. With mild symptoms, it is prudent to bear in mind the possibility of progression to more serious illness.

Reactions which progress may often involve difficulty breathing due to swelling in the throat (larynx), or asthma. Cardio-vascular symptoms, faintness and dizziness due to compromised circulation, may lead to more severe cyanosis (not getting enough oxygen to the lungs) or cardiac arrest (inadequate circulation causing the heart to stop). Anaphylaxis is a term used to describe a more severe allergic reaction involving multiple organs, with the potential to become severe or life-threatening. 124 fatalities were assessed as being highly likely to be caused by ingestion of a food allergen, between 1992 and 2012, although misclassification might make the total somewhat higher. Hospitalisations for anaphylaxis increased between 1992 and 2012, but the incidence of fatal anaphylaxis did not. The age distribution of fatal anaphylaxis varies significantly according to the nature of the eliciting agent, which suggests a specific vulnerability to severe outcomes from food-induced allergic reactions in the second and third decades of life.[1]

Further information about anaphylaxis is available from the Anaphylaxis Campaign: https://www.anaphylaxis.org.uk/hcp/what-is-anaphylaxis/signs-and-symptoms/ 

Diagnosis and treatment

The diagnosis of IgE mediated allergy usually depends significantly on taking a careful history of reactions and symptoms, supported by skin prick testing using allergens in solution or ‘prick to prick’ using the real food. In some cases, IgE blood tests may be helpful. Some clinicians may arrange a food challenge, i.e. supervised consumption of the food allergen, to confirm the diagnosis.

Most mild allergic reactions to foods will resolve without treatment. In some cases, symptoms progress and have the potential to become severe or even life-threatening. Those known to be at risk may be prescribed adrenaline (epinephrine) auto-injectors. These provide a single measured dose of adrenaline injected into the thigh. Adrenaline acts quickly to constrict blood vessels, relax smooth muscles in the lungs to improve breathing, stimulate the heartbeat and reduce swelling around the face and lips. Repeat doses may be needed, so those known to be at risk are advised to carry two auto-injectors and to be ready to call emergency paramedics. Additional treatment may involve more adrenaline, replenishing circulatory fluids, oxygen, the use of asthma reliever medication, antihistamine and corticosteroids. 

The mechanisms of food allergy are increasingly well understood. It is now easier for clinicians to work out exactly which food proteins somebody is allergic to, leading to more targeted advice about possible symptoms and treatment. There is, however, no cure for allergy, as yet.

Causes and prevention

There are still major knowledge gaps about why some children and adults become allergic to foods, but some aspects are increasingly understood. Atopic (allergic) disease can be inherited, and related manifestations (asthma, eczema, allergic rhinitis) are common in individuals with food allergy and their family members. Mutations in the filaggrin gene[2] are associated with dry skin, atopic eczema and an impaired skin barrier, which allows access to the immune system by food allergens and may be one of the sensitisation steps.

There is currently no evidence that maternal diet in pregnancy impacts whether a baby develops food allergy.  Deliberate and regular consumption of common food allergens in early life (from 4 months of age) has been found to be protective in atopic babies. The immune system is less likely to be sensitised if the allergenic foods are regularly consumed, than from allergen exposure in the home/environment via an impaired skin barrier. There is more information about early dietary intervention to prevent allergy at:

• LEAP (Learning Early About Peanut): http://www.leapstudy.co.uk/  
• EAT (Enquiring About Tolerance): https://www.food.gov.uk/research/food-allergy-and-intolerance-research/eat-study-early-introduction-of-allergenic-foods-to-induce-tolerance

Further guidance about weaning is available from Allergy UK:

https://www.allergyuk.org/assets/000/002/342/Weaning_%E2%80%93_Introducing_your_baby_to_solids_original.pdf?1547805087

https://www.allergyuk.org/assets/000/003/032/DesignConcept_A5_Info_Book_v1.5_original.pdf?1589795676

Can food allergy be treated?

Some food allergies are naturally outgrown in early life. Others may resolve by the introduction of individual food allergens (particularly milk and egg) to the diet in forms where some of the proteins have been broken down (denatured) by baking or cooking. Immunotherapy, a desensitisation process carried out under clinical supervision, may be helpful. Over weeks or months, the baby or child will be given foods in which the allergen proteins are increasingly intact e.g. by being less heat treated. Milk, for example, may be given first in a highly baked malted milk biscuit, gradually followed by different products and dishes leading to the introduction of fromage frais and fresh milk. Egg may be introduced in a muffin, then in baked or fried batter, and eventually scrambled or lightly boiled. Peanut has been introduced in measured and increasing amounts of peanut flour added to everyday foods. With appropriate clinical guidance, peanuts, tree nuts and other foods may be given in safe incremental doses in a pharmaceutical dosage form, such as capsules.[3]

Cross-reactive allergens

Cross-reactivity may exist between proteins which are similar in size or shape from different foods. Symptoms may be elicited when consuming a new food even if there has been no previous exposure to it. It is important to recognise the possibility of cross-reactivity when determining the cause of an allergic reaction. It may not have been caused by a particular allergen, through previous exposure, but by something with a structurally similar protein, which was able to elicit a similar adverse reaction.

Pollen-Food Syndrome (Oral Allergy Syndrome) is a common example of cross-reactivity. Individuals who are sensitised to tree or grass pollen may experience seasonal allergic rhinitis or hay fever. They may also have symptoms when eating foods which have proteins which are similar to these tree or grass pollen proteins. One of the most common cross-reactive pollens comes from birch trees and the most common trigger food allergens are: raw apple, kiwi, some nuts and other fruits. In most cases, symptoms involve immediate itching and swelling of the lips, mouth and soft palate, which are rarely life-threatening, and may resolve with a drink of water and/or an antihistamine tablet. Some reactions may become more severe, requiring the use of an adrenaline auto-injector. People with asthma may be advised to keep it well-controlled using preventer medication to mitigate symptoms

https://www.bda.uk.com/resource/food-facts-pollen-food-syndrome.html

Non-IgE mediated food allergies

A range of allergic conditions not associated with IgE mechanisms are briefly described in Appendix 1.

The need for consumers with food hypersensitivity to be able to avoid exposure to eliciting foods, by accessing information, has been recognised since the 1980s. Food labelling is thus of vital importance to anyone with a food allergy.

Regulation of food allergens used as ingredients in prepacked foods

The labelling of prepacked food must carry a list of ingredients. This is where information must be found about the allergens intentionally included in the food as ingredients. To avoid possible omission of crucial allergen information through derogations (such as certain compound ingredients or flavourings) food labelling legislation has been amended and updated to require all ingredients, additives, flavourings and processing aids containing major food allergens to be declared.

As mentioned, international agreement was reached, at Codex Alimentarius, on a list of 8 allergen food groups that must always be declared. Currently[1] (as of September 2021) these are:

• ‘Cereals containing gluten; i.e., wheat, rye, barley, oats, spelt or their hybridized strains and products of these;
• Crustacea and products of these;
• Eggs and egg products;
• Fish and fish products;
• Peanuts, soybeans and products of these;
• Milk and milk products (lactose included);
• Tree nuts and nut products; and
• Sulphite in concentrations of 10 mg/kg or more’.

This list was based on estimates that about 95% of food allergic populations may react to a limited number of food groups. However, consumption and sensitisation patterns around the world must also be considered. Gendel 2012 has compared international allergen regulation[2], and as previously mentioned, FARRP’s regularly updated list of international food allergen labelling requirements is useful.

The EU prioritises 14 food groups (see Appendix 2 for more details) and moreover requires that their presence must be emphasised in the list of ingredients, e.g. by a different typeface or in bold. Allergen labelling requirements for the UK and EU are laid out in Regulation (EU) 1169/2011 which has been implemented in UK law. The list of priority food groups is in Annex II[3].  This list also recognises labelling exemptions for named particular allergenic derivatives, for example if a processing method has been assessed as removing or denaturing allergenic proteins, making the derivative no longer allergenic.

FSA has produced guidance on allergen labelling for prepacked foods[4]. More recently declarations are also required for prepacked for direct sale (PPDS) foods. Allergens present as cross contaminants from cross contact in the supply chain (including harvesting, transporting, handling, processing, storage and distribution) are dealt with differently (see below).

It is important to bear in mind that allergic reactions can occur to foods not currently prioritised in labelling legislation. For example, UK Anaphylaxis Campaign collects information from its members about what allergens they are avoiding. Their members reported a need to avoid such foods as: kiwi, banana, and a range of legumes (e.g. peas, beans, chickpeas) and many others which are more common than some of those on the EU/UK regulated list of 14.  

Regulation of food allergens used as ingredients in non-prepacked and catered foods

Allergen information must also be provided for non-prepacked and catered foods in the UK and EU [Regulation (EU) 1169/2011]. Since 2014, individual member state jurisdictions of the EU and the UK require or permit declaration of allergens for non-prepacked foods via different communication routes.

In the UK, a food business selling catered, ready-to-eat or otherwise non-prepacked food must display signage inviting customers to ask for allergen information directly from staff, whether face to face or by telephone. Such information has to be retained and made available on request for all foods, products and dishes throughout the business. In other jurisdictions, the information must be made available in written or printed form. It is vital that information is consistent across all sources: printed and online, displayed on tables and other signage within the business.  It must be accessible at the point of choice and at the point of delivery or service, and should be accurate, consistent and verifiable.

Regulated allergens, and other allergenic foods used as ingredients, have to be labelled and the appropriate information communicated throughout the supply chain to the final consumer. However, there are circumstances, such as shared primary production, transport, storage, manufacturing, preparation, presentation and service environments, that may introduce the risk of the presence of a food allergen which is not an intended ingredient.

Measures intended to reduce this risk have been endorsed by a Codex Alimentarius Code of Practice[1] and include:

• correctly labelling all food ingredients in any form throughout the supply chain
• managing food packaging and labelling materials to remove the risk of incorrectly labelled products entering the market
• consistent adherence to the recipe/product specification
• identifying any possibility of a non-ingredient allergen getting into other food or dishes
• preventing allergen cross-contamination by segregation
• communicating the possibility of any remaining unintended allergen presence using Precautionary Allergen Labelling (PAL).

Effective allergen segregation may be achieved by:

• physical separation - by production area or kitchen workspace
• separation by time - producing one product or dish at a time
• covering, wrapping, or packing and labelling part-prepared or finished foods and products
• effective allergen removal through washing and cleaning
• timely control of spillages
• validation and verification of all cleaning processes.

Policies and procedures to support allergen segregation need to be implemented, embedded in staff training, assessed, reviewed and updated to ensure that they are effective. These principles apply throughout the food supply chain, from primary production to the final consumer. They also include the need to implement alerts in case of accidental mis-formulation or cross-contamination and the ability to recall products from distribution and sale and inform relevant consumers.

Unintended allergen presence may be particulate (pieces, grains, powder) or possibly homogenised, i.e. more evenly distributed throughout the material. Bakery products, for example, may carry the risk of grains and seeds transferred in ovens and via work overalls or equipment.

Clean-in-place (CIP) equipment for wet products may be designed and processes validated and verified to demonstrate allergen removal. Chocolate production is generally ill-suited to wet cleaning, due to microbiological risks and damage to the product, so cleaning may involve passing fat or waste chocolate down the production line. This may not be sufficient to remove particles of nut, grains, or milk, in liquid or powder form.

Precautionary allergen labelling was first used in the UK in the mid-1990s on prepacked branded and ‘own brand’ products made for supermarkets. Initially, these covered the unintended presence of peanuts and different tree nuts, and then sesame, egg, milk and eventually cereals such as wheat. In 2001 the FSA commissioned research examining shopping for everyday prepacked foods with a nut or peanut allergy. https://allergyaction.org/wp-content/uploads/2017/09/AC-May-contain-report-maycontainreport.pdf

Consumer behaviour and PAL

One in ten of the warnings on products carrying precautionary allergen labelling was missed by consumers. It was recognised that such precautionary labelling needs to be adjacent to the ingredients list, legible, and conspicuous. Further research has also indicated that there are many styles and forms of wording for declaring unintended allergen presence, and different meanings and weightings are attributed to them by consumers.

Leading food manufacturers and retailers started to appreciate that the use of these warning labels was limiting food choices for a significant proportion of consumers, and those sharing their food, and continue to work to improve allergen controls to reduce the need for them and improve product choice. At the same time, consumers (and those health professionals advising them) had (and still have) very variable attitudes - in some cases following them and rigorously avoiding PAL labelled products, but in other cases paying little attention to them. Heeding, or failing to heed, such labelling is stressful, and choosing safe food has a significant impact on quality of life, and in some cases on food costs for consumers at risk and those buying their food.

There are significant gaps in consumer and health professional understanding, of the controls implemented in food businesses, and how and why such advisory labelling is used. Similarly, food industry scientists and technologists are keen to understand the challenges facing food allergic consumers, which foods they need to avoid, and the impact of living with this condition. The British Society of Allergy and Clinical Immunology (a professional body for allergy health professionals) has engaged with the food industry to improve dialogue and understanding and has invited food industry experts in allergen management to speak at recent conferences. Researchers involved in consumer and patient research also contribute to the work of the IFST Scientific Committee and Food Regulatory Special Interest Group (SIG).

Current regulation of PAL

Precautionary allergen labelling is currently voluntary, though it could be argued that not alerting food allergic consumers to the potential unintended presence of a non-ingredient allergen might render that food unsafe and breach other regulations. UK and EU food law requires food business operators to undertake risk assessments [Article 5 of Regulation (EC) 852/2004)] and to sell safe food [Article 14 of Regulation (EC) 178/2002].

PAL is expressly allowed and widely used in Australia and New Zealand. In the UK, best practice guidance from the FSA and leading trade bodies indicates that the use of advisory ‘may contain’ labelling should be the last resort of a series of risk assessments. It should never be used as an alternative to effective allergen management (as part of GMP), as this may devalue the impact of such warnings, making consumers sceptical and endangering their health.  

A standardised approach, whether voluntary or mandatory, which could be applied to any food or drink on the market, would provide consistency in food allergen risk communication. Many questions arise which would need to be addressed: which allergens would be included (all those on Annex II or others)?; would this regulation be achievable across jurisdictions, and from every manufacturer, retailer or wholesaler?; what would it cost?; how would it be communicated?; would a logo or symbol be practical or understood?; would it be effective in protecting all consumers at risk?; would it be adequate to prevent all symptoms?; how could such regulation be enforced and what analytical support would be required to do so? 

There is pressure from consumers, and others, to implement the regulation of unintended allergen presence and PAL. This will require the above questions to be addressed. It will also increase demand for appropriate, accessible and affordable analytical methods, which can be applied with some consistency across different forms of food (matrices), as well as consensus about the proportion of consumers who may be protected.

How much is too much? Setting limits of allergen presence in foods in which it is unintended as an ingredient

Risk assessment in food allergy is multi-layered. Its sole purpose is to prevent consumers at risk from exposure to a food allergen which may cause them harm. This raises many questions about: which consumers; what kind of exposure; what kind of harm. The most challenging question which has preoccupied food scientists and technologists, clinicians, analysts, regulators and consumers for decades is ‘how much is too much?’

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 may not be practical or achievable. Identifying allergen levels in foods which may be protective involves a number of approaches.

The application of principles used in toxicology has been considered in assessing the risk of unintended allergen presence in food which may be a hazard for a minority of consumers at risk but not for the general population. Similar examples where toxicology principles apply in food production include food additives, and contaminants such as metals, pesticides, veterinary residues as well as naturally occurring toxins such as mycotoxins (Walker and Wong, 2014). 

Characterising the amount of allergenic foods which would present a risk to public health requires understanding of both the severity of any allergic reactions to that food and of the ‘dose-response’ pattern for the ‘at risk’ population. If a group of food allergic individuals (under clinical supervision) all consume a specific food allergen in the same form and in measured amounts, it is possible to plot the amounts of allergen which are known to have triggered symptoms to produce a ‘dose-response’ curve. These dose-response curves for individuals can then be combined into a population dataset and calculate a ‘minimum eliciting dose (ED), the minimum dose that elicits an effect in a defined proportion of the allergic population. For example, ED50 is the dose of an allergen that will cause a reaction in 50% of the population known to be at risk. ED05 and ED01 are the eliciting doses that would be expected to be protective of 95 % and 99 % of the allergic population respectively.

A minimum eliciting dose can be translated into a ’threshold’ or ‘action level’ - the concentration of an allergen in a product, above which risk management actions must be carried out to protect the at-risk population. In the case of food allergens, the risk management actions could be to apply PAL as a risk communication warning to at-risk consumers to avoid eating that product. Below this action level, PAL for example. may be considered unnecessary.

The Allergen Bureau Food Industry Guide to the Voluntary Incidental Trace Allergen Labelling (VITAL^®) Programme Food_Industry_Guide_VITAL_Program_Version_April_2021_VF1.pdf (allergenbureau.net) is a standardised allergen risk assessment process for the food industry. It is widely used in Australia and New Zealand but has yet to gain widespread acceptance globally. The system is free to download (Version 3) and should be consulted in full, but important aspects include:

• 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 2020 and 2021, FSA undertook research prioritisation exercises on food hypersensitivity research priorities. A UK-wide public consultation identified unanswered research questions and a series of stakeholder workshops resulted in 10 priority uncertainties in evidence, from which 16 research questions were developed. These were summarised under the following five themes[1],[2]:

1. communication of allergens, both within the food supply chain and then to the end-consumer (ensuring trust in allergen communication)
2. impact of socioeconomic factors on consumers with food hypersensitivity 
3. drivers of severe reactions
4. mechanism(s) underlying loss of food hypersensitivity tolerance
5. risks posed by novel allergens/processing.

Studies are already underway looking into early life dietary intervention (following the EAT Study outlined above) and food allergy in older children and adults, collecting National Health Service (NHS) and other data about severe and fatal reactions to foods in the UK - trigger foods, treatment and management, quality of life and additional costs associated with food hypersensitivity and allergy recalls https://www.food.gov.uk/research/food-allergy-and-intolerance-research.

Further research is underway to improve allergen analysis and reporting, to understand the role of regulation in protecting individuals with food hypersensitivity and to identify routes towards standardised and even regulated PAL.