At present the only cure for food allergy is to avoid eating the food responsible for the allergy. Thus, food allergy or food hypersensitivity is a disease that is not only of concern to the individual who is affected but also to those involved directly and indirectly in supplying andpreparing food for the food-allergic individual, and its impact on society should be evaluated on this basis. It is generally assumed that questionnaire-based studies vastly overestimate the prevalence of food hypersensitivity. The reported perceived prevalence of food hypersensitivity varies from 3.24% to 34.9%, which may be explained partly by the difference in reporting lifetime prevalence compared with point prevalence. However, of more importance is the apparent inverse correlation between response rate and prevalence (the higher the response rate, the lower the perceived prevalence). The three most-recent prevalence studies on food hypersensitivity (one on perceived food hypersensitivity and two on confirmed food hypersensitivity) all report estimates for prevalence of approximately 3%, but their criteria for including subjects as being positive are not identical, although they do overlap. Furthermore, because of differences in methodology there is no definitive information to indicate whether the prevalence of food allergy is increasing. However, the high prevalence of pollen-related food allergy in younger adults in the population suggests that the increase in pollen allergy is also being accompanied by an increase in pollen-related food allergy.

Exposure assessment is one of the key parts of the risk assessment process. This task is crucial when evaluating substances for which only intake of toxicologically-important amounts can lead to adverse health effects. Ideally, dietary exposure to hazardous substances can be assessed by combining data on concentration in all food products with data on their consumption. However, it is considered to be neither cost-effective nor necessary to collect detailed data for every substance, and a stepwise procedure is commonly used to focus resources on the most important issues. Screening methods, designed to look for ‘worst case’ situations, are first used to target chemicals that might be of health concern for the general population or for certain at-risk groups. The quality of the dietary exposure assessments not only depends on the quality of the data collected, but also on the integration tools used for initial screening or for the eventual more precise estimations. A particular challenge is the evaluation of food allergens and components causing other forms of intolerances, since no reliable data seem to be currently available on the type of exposure (amounts and duration) required to induce a food allergy. A different approach from that used for dietary exposure to other hazardous substances has to be adopted. However, the methodologies (such as those used to collect food consumption data) and databases (in particular, information about food labels) developed in such a context could be useful to investigate the exposure conditions leading to the development of food allergies.

There is considerable interest in the development and evaluation of approaches for the safety assessment of novel foods, and in particular in methods for characterisation of allergenic potential. One strategy that has found favour is a tiered approach in which the potential of novel proteins to induce allergic sensitisation is assessed based on considerations of stability of the protein in a simulated gastric juice and homology with, or structural similarity to, known allergens. Linked to such an approach may be evaluation of serological identity with proteins known to cause allergic disease. With the aim of supplementing such approaches with a more direct measurement of potential allergenic activity, attempts have been made to characterise the quality of immune responses elicited in BALB/c strain mice. Such evaluations comprise measurement of IgG and IgE antibody production and (to a lesser extent) of induced cytokine expression patterns. Investigations to date suggest that in mice proteins provoke variable immune responses, those with the potential to cause allergic sensitisation stimulating IgE (and IgG) antibody production. In contrast, non-allergenic, but nevertheless immunogenic, proteins are associated with IgG antibody responses in the absence of marked IgE production. Consistent with the selective activation of selective type 2 T lymphocyte responses, exposure of mice to allergenic protein is associated with preferential expression of IL-4, -5, -10 and -13. Collectively these data suggest that characterisation of the nature of immune response induced in mice by proteins may provide a useful adjunct or alternative to current strategies for the assessment of allergenic potential.

Coeliac disease is a lifelong intolerance to the gluten found in wheat, barley and rye, and some patients are also sensitive to oats. The disease is genetically determined, with 10% of the first-degree relatives affected and 75% of monozygotic twins being concordant. Of the patients with coeliac disease 95% are human leucocyte antigen (HLA)-DQ2 or HLA-DQ8 positive. Characteristically, the jejunal mucosa becomes damaged by a T-cell-mediated autoimmune response that is thought to be initiated by a 33-mer peptide fragment in A2 gliadin, and patients with this disorder have raised levels of anti-endomysium and tissue transglutaminase antibodies in their blood. Coeliac disease is the major diagnosable food intolerance and, with the advent of a simple blood test for case finding, prevalence rates are thought to be approximately 1:100. Classically, the condition presented with malabsorption and failure to thrive in infancy, but this picture has now been overtaken by the much more common presentation in adults, usually with non-specific symptoms such as tiredness and anaemia, disturbance in bowel habit or following low-impact bone fractures. Small intestinal biopsy is necessary for diagnosis and shows a characteristically flat appearance with crypt hypoplasia and infiltration of the epithelium with lymphocytes. Diet is the key to management and a gluten-free diet effectively cures the condition. However, this commitment is lifelong and many aisles in the supermarket are effectively closed to individuals with coeliac disease. Compliance can be monitored by measuring antibodies in blood, which revert to negative after 6–9 months. Patients with minor symptoms, who are found incidentally to have coeliac disease, often ask whether it is necessary to adhere to the diet. Current advice is that dietary adherence is necessary to avoid the long-term complications, which are, principally, osteoporosis and small bowel lymphoma. However, risk of these complications diminishes very considerably in patients who are on a gluten-free diet.

The mucosal immune system fulfils the primary function of defence against potential pathogens that may enter across vulnerable surface epithelia. However, a secondary function of the intestinal immune system is to discriminate between pathogen-associated and ‘harmless’ antigens, expressing active responses against the former and tolerance to the latter. Control of immune responses appears to be an active process, involving local generation of IgA and of regulatory and/or regulated T lymphocytes. Two important periods of maximum exposure to novel antigens occur in the young animal, immediately after birth and at weaning. In both cases the antigenic composition of the intestinal contents can shift suddenly, as a result of a novel diet and of colonisation by novel strains and species of bacteria. Changes in lifestyles of man, and husbandry of animals, have resulted in weaning becoming much more abrupt than previously in evolution, increasing the number of antigens that must be simultaneously evaluated by neonates. Thus, birth and weaning are likely to represent hazard and critical control points in the development of appropriate responses to pathogens and harmless dietary and commensal antigens. Neonates are born with relatively undeveloped mucosal immune systems. At birth this factor may prevent both expression of active immune responses and development of tolerance. However, colonisation by intestinal flora expands the mucosal immune system in antigen-specific and non-specific ways. At weaning antibody to fed proteins can be detected, indicating active immune responses to fed proteins. It is proposed that under normal conditions the ability of the mucosal immune system to mount active responses to foreign antigens develops simultaneously with the ability to control and regulate such responses. Problems arise when one or other arm of the immune system develops inappropriately, resulting in inappropriate effector responses to harmless food proteins (allergy) or inadequate responses to pathogens (disease susceptibility).

IgE-mediated dietary hypersensitivity affects approximately 1% of the canine population. There are no breed associations and ≤50% of the patients are aged <1 year at presentation. The most common causative allergens are beef, chicken, milk, eggs, maize, wheat and soyabean. Affected dogs generally display cutaneous disease and 10–15% of the patients may have concurrent alimentary involvement. Diagnosis is currently based on dietary restriction followed by provocation. Procedures for the detection of serum allergen-specific IgE and IgG antibodies are widely available, but these tests correlate poorly with clinical presentation and dietary testing. Recent studies have demonstrated the allergen specificity of IgE antibodies by immunoblotting and have described blood lymphocyte proliferative responses to food allergens. In addition to investigations of spontaneously-arising dietary hypersensitivity, it has also proved possible to study this disorder experimentally. Small colonies of dogs sensitive to particular dietary proteins have been used to study clinical and serological responses to allergen challenge. Hypersensitivity has been experimentally induced in dogs of an atopic phenotype by repeated subcutaneous injection of alum-adjuvanted dietary allergen during neonatal life. These models have been used to trial a range of modified protein or hydrolysate diets. The dog provides a unique large-animal model for investigation of the immunopathogenesis of human dietary hypersensitivity. The dog is closely related genetically to man and shares environmental disease triggers with man. Spontaneously arising canine dietary hypersensitivity is a good clinical mimic of the human disease, and ability to therapeutically manipulate this adverse response in the dog might lead to benefits for human patients.

Allergy is caused by an immune reaction that is out of all proportion to the antigenic stimuli. Classical allergy is a type I hypersensitivity reaction mediated by the interaction of mast cells (and eosinophils) coated with allergen-specific IgE and a cross-linking allergen. The physiological outcome is inflammation commonly displayed by urticaria, rhinitis, vomiting and diarrhoea, depending on the route of allergen entry. In extreme reactions anaphylactic shock can result that may lead to death. Chronic allergic responses most commonly present themselves as asthma and eczema. All these symptoms are the consequence of an imbalanced immune system making an unsuitable response to an environmental or food antigen. On bacterial colonisation of the colon after birth the appropriate microbiological stimuli is essential to redress the balance of the skewed T-helper 2 immune response present in the newborn. This normal interaction between baby and microbes is thought to be compromised in the Western world, with a reduction in bifidobacteria and an increase in clostridial species, particularly in bottle-fed infants. The use of probiotic therapy to prevent allergic disease has been demonstrated in two studies using a probiotic Lactobacillus rhamnosus GG in neonates. A long-term reduction in allergy has been shown in the test group, with lactobacillus reducing the incidence of atopic eczema. Management of allergy through probiotics has also been demonstrated in infants, using lactobacilli to control atopic eczema and cow's milk allergy. Unfortunately, these positive results have not been repeated in studies with older children and young adults.

Serious attempts to estimate the impact of allergic reactions to foods on public health did not begin until the 1980s. Until about 15 years ago food allergy was considered a minor aspect of food safety. Two developments probably prompted a radical re-appraisal of that situation. The first was the apparently inexorable rise in the prevalence of atopic diseases, of which food allergy forms a part, with its possible consequences highlighted by some well-publicised severe reactions. The second was the growth of genetic modification technology, manifested by the commercialisation of transgenic crops. Each of these developments impacted on the food industry in distinct ways. On the one hand, consumers with food allergies had to be enabled to avoid specific allergens in products formulated with existing ingredients. Food manufacturers therefore had to identify those specific allergens down to trace amounts in all the ingredients forming the product and label or remove them. On the other hand, the introduction of products using ingredients from novel sources required an assessment of the allergenicity of these ingredients as an integral part of safety assurance. The approaches used by the food industry to protect existing consumers who have food allergies and those at potential risk of sensitisation from novel proteins will be illustrated, emphasising how they need to be built into every stage of the life cycle of a product.

Food allergy represents an increasingly important health problem, with prevalence in Western Europe continuing to rise. While some reactions are mild, others can include life-threatening anaphylactic shock. It is estimated that food allergies affect 1–2% of the adult population and ≤8% of children. Relatively few foods are to blame for a large majority of allergic reactions to food in the UK, with most reactions being to milk, eggs, peanuts (Arachis hypogea), nuts, fish, shellfish, soyabean, sesame (Sesamum indicum L.) and wheat. There is currently no cure for food allergy and the few available treatments are focused on relieving the specific symptoms. Consumers with food allergies and food intolerances rely on food labelling to enable them to make informed choices about the foods they eat. Whilst there have recently been important advances in the labelling of food allergens, these advances relate only to requirements for the labelling of the deliberate use of specified food allergens in foods sold pre-packed. In other areas the development of guidance for food manufacturers and retailers on how to assess the risks of possible allergen cross-contamination during food production and manufacture, and then to determine appropriate advisory labelling, is well advanced. Work to address the issue of how to provide appropriate allergen information for foods sold loose, or in catering establishments, is also in progress.

The European Food Safety Authority, following a request from the European Commission, has published a guidance document for the risk assessment of GM plants and derived food and feed to assist in the implementation of provisions of Regulation (EC) 1829/2003 of the European Parliament and Council on GM food and feed. This regulation has applied since 18 April 2004. In principle, hazard identification and characterisation of GM crops is conducted in four steps: characterisation of the parent crop and any hazards associated with it; characterisation of the transformation process and of the inserted recombinant DNA, including an assessment of the possible production of new fusion proteins or allergens; assessment of the introduced proteins (toxicity, allergenicity) and metabolites; identification of any other targetted and unexpected alterations in the GM crop, including changes in the plant metabolism resulting in compositional changes and assessment of their toxicological, allergenic or nutritional impact. In relation to allergenicity specifically, it is clear that this property of a given protein is not intrinsic and fully predictable but is a biological activity requiring an interaction with individuals with a predisposed genetic background. Allergenicity, therefore, depends on the genetic diversity and variability in atopic human subjects. Given this lack of complete predictability it is necessary to obtain, from several steps in the risk-assessment process, a cumulative body of evidence that minimises any uncertainty about the protein(s) in question.

Concerns have been expressed that the introduction of novel foods into the diet might lead to the development of new food allergies in consumers. Novel foods can be conveniently divided into GM and non-GM categories. Decision-tree approaches (e.g. International Life Sciences Institute-International Food Biotechnology Council and WHO/FAO) to assess the allergenic potential of GM foods were developed following the discovery, during product development, of the allergenic potential of GM soyabean expressing a gene encoding a storage protein from Brazil nut (Bertolletia excelsa). Within these decision trees considerations include: the source of the transgene; amino acid homology with known allergens; cross-reactivity with IgE from food-allergic individuals; resistance to proteolysis; prediction using animal models of food allergy. Such decision trees are under constant review as new knowledge and improved models emerge, but they provide a useful framework for the assessment of the allergenic potential of GM foods. For novel non-GM foods the assessment of allergenic potential is more subjective; some foods or food ingredients will need no assessment other than a robust protein assay to demonstrate the absence of protein. Where protein is present in the novel non-GM food, hazard and risk assessments need to be made in terms of the quantity of protein that might be consumed, the identity of individual protein components and their relationships to known food allergens. Where necessary, this assessment would extend to serum screening for potential cross-reactivities, skin-prick tests in previously-sensitised individuals and double-blind placebo-controlled food challenges.

Pre-eclampsia is a disorder characterised by pregnancy-induced hypertension and new-onset proteinuria occurring in the second half of pregnancy. Worldwide, approximately 2–3% of all pregnant women develop pre-eclampsia. The condition is a major cause of maternal and fetal morbidity and mortality. Abnormal placentation is an important predisposing factor for pre-eclampsia, while endothelial activation appears to be central to the pathophysiological changes, possibly indicative of a two-stage disorder characterised by reduced placental perfusion and a maternal syndrome. There is increasing evidence that pre-eclampsia is associated with both increased oxidative stress and reduced antioxidant defences, which has led to the hypothesis that oxidative stress may play an important role in the pathogenesis of pre-eclampsia, perhaps acting as the link in a two-stage model of pre-eclampsia. In support of this hypothesis a small, but important, preliminary study has shown a highly significant (P = 0.02) reduction in the incidence of pre-eclampsia in women at risk who were taking a supplement of vitamins C and E from mid-pregnancy. Furthermore, these findings support the hypothesis that oxidative stress is at least partly responsible for the endothelial dysfunction of pre-eclampsia. Several larger multicentre trials are currently underway to evaluate the efficacy, safety and cost benefits of antioxidant supplementation during pregnancy for the prevention of pre-eclampsia in both low- and high-risk women, including women with diabetes. The results of these trials are awaited with interest.

In the present paper biomarkers of micronutrient status in childhood and some of the factors influencing them, mainly dietary intake, requirements and inflammation will be examined. On a body-weight basis the micronutrient requirements of children are mostly higher than those of an adult, but most biomarkers of status are not age-related. A major factor that is often overlooked in assessing status is the influence of subclinical inflammation on micronutrient biomarkers. In younger children particularly the immune system is still developing and there is a higher frequency of sickness than in adults. The inflammatory response rapidly influences the concentration in the blood of several important micronutrients such as vitamin A, Fe and Zn, even in the first 24 h, whereas dietary deficiencies can be envisaged as having a more gradual effect on biomarkers of nutritional status. The rapid response to infection may be for protective reasons, i.e. conservation of reserves, or by placing demands on those reserves to mount an effective immune response. However, because there is a high prevalence of disease in many developing countries, an apparently-healthy child may well be at the incubation stage or convalescing when blood is taken for nutritional assessment and the concentration of certain micronutrient biomarkers will not give a true indication of status. Most biomarkers influenced by inflammation are known, but often they are used because they are convenient or cheap and the influence of subclinical inflammation is either ignored or overlooked. The objective of the present paper is to discuss: (1) some of the important micronutrient deficiencies in childhood influenced by inflammation; (2) ways of correcting the interference from inflammation.

The lungs are continually exposed to relatively-high O2 tensions, and as such, in comparison with other organs, they represent a unique tissue for the damaging effects of oxidant attack. At particular times during a lifetime this every day challenge may increase exponentially. The first oxidative insult occurs at birth, when cells are exposed to a sudden 5-fold increase in O2 concentration. Thereafter, the human lung, from infancy through to old age, can be subjected to deleterious oxidative events as a consequence of inhaling environmental pollutants or irritants, succumbing to several pulmonary diseases (including infant and adult respiratory distress syndromes, asthma, chronic obstructive pulmonary disease, cystic fibrosis and cancer) and receiving treatment for these diseases. The present paper will review the concept that consumption of a healthy diet and the consequent ability to establish and then maintain adequate micronutrient antioxidant concentrations in the lung throughout life, and following various oxidative insults, could prevent or reduce the incidence of oxidant-mediated respiratory diseases. Furthermore, the rationale, practicalities and complexities of boosting the antioxidant pool of the respiratory-tract lining fluid in diseases in which oxidative stress is actively involved, by direct application to the lung v. dietary modification, in order to achieve a therapeutic effect will be discussed.

Se is an unusual trace element in having its own codon in mRNA that specifies its insertion into selenoproteins as selenocysteine (SeCys), by means of a mechanism requiring a large SeCys-insertion complex. This exacting insertion machinery for selenoprotein production has implications for the Se requirements for cancer prevention. If Se may protect against cancer, an adequate intake of Se is desirable. However, the level of intake in Europe and some parts of the world is not adequate for full expression of protective selenoproteins. The evidence for Se as a cancer preventive agent includes that from geographic, animal, prospective and intervention studies. Newly-published prospective studies on oesophageal, gastric-cardia and lung cancer have reinforced previous evidence, which is particularly strong for prostate cancer. Interventions with Se have shown benefit in reducing the risk of cancer incidence and mortality in all cancers combined, and specifically in liver, prostate, colo-rectal and lung cancers. The effect seems to be strongest in those individuals with the lowest Se status. As the level of Se that appears to be required for optimal effect is higher than that previously understood to be required to maximise the activity of selenoenzymes, the question has been raised as to whether selenoproteins are involved in the anti-cancer process. However, recent evidence showing an association between Se, reduction of DNA damage and oxidative stress together with data showing an effect of selenoprotein genotype on cancer risk implies that selenoproteins are indeed implicated. The likelihood of simultaneous and consecutive effects at different cancer stages still allows an important role for anti-cancer Se metabolites such as methyl selenol formed from γ-glutamyl-selenomethyl-SeCys and selenomethyl-SeCys, components identified in certain plants and Se-enriched yeast that have anti-cancer effects. There is some evidence that Se may affect not only cancer risk but also progression and metastasis. Current primary and secondary prevention trials of Se are underway in the USA, including the Selenium and Vitamin E Cancer Prevention Trial (SELECT) relating to prostate cancer, although a large European trial is still desirable given the likelihood of a stronger effect in populations of lower Se status.

Whilst clinical deficiency of micronutrients is uncommon in the developed world, a suboptimal intake of certain micronutrients has been linked with an increased risk of chronic diseases such as CVD and cancer. Attention has therefore focused on increasing micronutrient status in order to theoretically reduce chronic disease risk. Increasing micronutrient status can involve a number of approaches: increasing dietary intake of micronutrient-rich foods; food fortification; use of supplements. Observational cohort studies have demonstrated an association between high intakes of micronutrients such as vitamin E, vitamin C, folic acid and β-carotene, and lower risk of CHD, stroke and cancer at various sites. However, randomised intervention trials of micronutrient supplements have, to date, largely failed to show an improvement in clinical end points. The discordance between data from cohort studies and the results so far available from clinical trials remains to be explained. One reason may be that the complex mixture of micronutrients found, for example, in a diet high in fruit and vegetables may be more effective than large doses of a small number of micronutrients, and therefore that intervention studies that use single micronutrient supplements are unlikely to produce a lowering of disease risk. Studies concentrating on whole foods (e.g. fruit and vegetables) or diet pattern (e.g. Mediterranean diet pattern) may be more effective in demonstrating an effect on clinical end points. The present review will consider the clinical trial evidence for a beneficial effect of micronutrient supplements on health, and review the alternative approaches to the study of dietary intake of micronutrients.

During the last century much evidence has accumulated to suggest that from a public health perspective the type of fat is more important than the amount of fat. Saturated and trans-fatty acids increase and both n-6 and n-3 PUFA decrease the risk of CHD. Most of the knowledge about the effects of dietary fatty acids on CHD risk is based on observational studies and controlled dietary experiments with intermediate end points (e.g. blood lipoprotein fractions). Information from high-quality randomised controlled trials on fatty acids and CHD is lacking. The Netherlands Institute for Public Health has calculated the potential health gain that can be achieved if the fatty acid composition of the current Dutch diet is replaced by the recommended fatty acid composition. The recommendations of The Netherlands Health Council are: saturated fatty acids <10% energy intake; trans-fatty acids <1% energy intake; fish consumption (an indicator of n-3 PUFA) once or twice weekly. Implementation of this recommendation could reduce the incidence of CHD in The Netherlands by about 25 000/year and the number of CHD-related deaths by about 6000/year and increase life expectancy from age 40 years onwards by 0.5 year. These projections indicate the public health potential of interventions that modify the fatty acid composition of the diet.

The current high life expectancy is overshadowed by neurodegenerative illnesses that lead to dementia and dependence. Alzheimer's disease (AD) is the most common of these conditions, and is considered to be a proteinopathy, with amyloid-β42 as a key factor, leading via a cascade of events to neurodegeneration. Major factors involved are oxidative stress, perturbed Ca homeostasis and impaired energy metabolism. Protection against oxidative stress by micronutrients (including secondary bioactive substances) has been shown in transgenic Alzheimer model systems to delay AD. Epidemiological evidence is less conclusive, but the vast majority of the evidence supports a protective effect on cognitive functions in old age and AD. Thus, a diet rich in fruits and vegetables but also containing meat and fish is the most suitable to provide adequate micronutrients. The strong link between cardiovascular risk and AD may be explained by common pathogenetic mechanisms mediated, for example, by homocysteine and thus dependant on B-vitamins (folate and vitamins B12 and B6). However, micronutrients may also be harmful. The high affinity of amyloid for metals (Fe, Al and Zn) favours the generation of reactive oxygen species and triggers an inflammatory response. Micronutrients in a balanced diet have a long-lasting, albeit low, protective impact on brain aging, hence prevention should be life long.

Diet and nutrition impact on many oral diseases, in particular dental caries. Consumption of fluoridated water coupled with a reduction in non-milk extrinsic sugar intake is an effective means of caries prevention. However, studies on the fluoride concentration of bottled waters suggest increased consumption of these waters, in preference to fluoridated tap water, would lead to a marked decrease in caries protection. Concerns have been raised about the bioavailability of fluoride from artificially-fluoridated water compared with naturally-fluoridated water. This issue has been addressed in a human experimental study that has indicated that any differences in fluoride bioavailability are small compared with the naturally-occurring variability in fluoride absorption. Research has unequivocally shown sugars to be the main aetiological factor for dental caries, and information on intakes guides health promotion. Repeat dietary surveys of English children over three decades indicate that levels of sugars intake have remained stable, while sources of sugars have changed considerably, with the contribution from soft drinks more than doubling since 1980. Dental caries eventually leads to tooth loss, which in turn impairs chewing ability causing avoidance of hard and fibrous foods including fruits, vegetables and whole grains. A very low intake (<12 g/d) of NSP and fruit and vegetables has been found in edentulous subjects. Provision of prostheses alone fails to improve diet. However, initial studies indicate that customised dietary advice at the time of denture provision results in increased consumption of fruits and vegetables, and positive movement through the stages of change. Feasible means of integrating dietary counselling into the dental setting warrants further investigation.