Genotype moderates the impact of food additives on hyperactive behavior in children

Introduction: The claim of a relationship between artificial food color and additive (AFCs) intake and behavior is highly contentious. We have shown in a previous population-based trial with 3yo children adverse effects of food additives on parentally-rated hyperactive behaviour (Bateman et al, 2004). The possible role of genetic polymorphisms in moderating this adverse effect has not been previously examined. Methods A randomised, double blind, placebo-controlled, within subject crossover food challenge was used for 144, 8 to 9 year old children and 153, 3 year old children. Following baseline assessment children were placed on a diet eliminating food additives and a benzoate preservative for 6 weeks during which time they were challenged for weekly periods with either a placebo mix or a drink containing sodium benzoate (45mg daily) and one of two mixes of AFCs.: Results: The T939C and Thr105Ile polymorphisms of the histamine N-methyltransferase gene (HNMT) moderated the adverse effect s of AFCs but the polymorphisms in catecholamine genes COMT Val108Met and ADRA2A C1291G did not. These findings point to a possible role for histamine in mediating the effects of food additives and help to explain why there has been inconsistency between previous studies. Conclusions: Genes influencing a range of neurotransmitter systems and their interplay with environmental factors, such as diet, need to be examined to understand genetic influences on hyperactivity.<br/

Is an azo-free diet nutritionally superior than one containing azo-dyes?

Background: Few data are available in the literature as to whether an additive-free diet is more nutritious when compared to one that contains azo-dyes. The aim of this study was to investigate whether there is a significant difference in the nutritional content of an azo-free diet compared to one that contains azo-dyes. This formed part of an extension of a study that looked at the effect of food additives on behaviour of children (Bateman, 2004).Methods: Azo-dyes [(E102), (E104), (E110), (E122), (E123), 4R (E124), (E127), (E128), (E129), (E131), (E132), (E133), (E142), (E151), (E154), (E155), (E180)] and a preservative [(Sodium benzoate (E211)] were eliminated from the diet of children. The study dietitian advised families on how to avoid foods that contain food colours and preservatives such as those found in certain brands of beverages, sweets, cakes, ice lollies, desserts, jam and crisps. To aid compliance to the diet, suitable alternatives were recommended. The parents of 21 children (11 females) aged 8–9 years completed a 7 day food diary (baseline) before and during week 3 of the diet period. The food diaries were collected and coded for portion sizes by the study dietitian and analysed using CompEat. Nutrient values were compared to the recommended nutrient intake. The data was analysed using SPSS 12 and paired samples t-test (significance level P £ 0.005).Results: There was no significant difference in energy, protein or fat intake between baseline diet and the azo-dye free diet. There was a reduction in the mean intake of carbohydrate (P = 0.000), sugar (P = 0.000), phosphorous (P = 0.005), magnesium (P = 0.002), potassium (P = 0.005), chloride (P = 0.003) and vitamin C (P = 0.002) when an azo-free diet was followed.Discussions: Any dietary manipulation may effect overall nutrient intake. The effect may result in a nutritionally superior diet but this is not always the case (Isolauri et al., 1998). The children in this study showed that eliminating azo-dyes from their diet resulted in their intake of two micronutrients (potassium and magnesium) and one macronutrient (carbohydrate) being below that recommended for their age (Department of Health, 1991).Conclusion: Elimination diets may have a detrimental effect on nutritional intake, even when the food that is eliminated is perceived as unhealthy. Any nutritional manipulation should be made with caution and the resultant diet should be assessed to ensure its nutritional adequacy

Presentation of allergen in different food preparations affects the nature of the allergic reaction - a case series

Background Characterization of fatal and non-fatal reactions to food indicates that the majority of reactions are due to the ingestion of prepared foods rather than the non-processed allergen. In an ongoing study that used a double-blind placebo-controlled food challenge to investigate peanut allergy and clinical symptoms, the observed reaction severity in four of the first six subjects was greater than anticipated. We hypothesized that this was due to differences in the composition of the challenge vehicle.Objective The aim was to investigate whether the severity of observed challenge reactions would be repeated on re-challenge with a lower fat challenge vehicle.Methods Peanut-allergic subjects were re-challenged with a lower fat recipe after reacting more severely than was anticipated to an initial peanut challenge. Similar challenge vehicle recipes were used, the only difference being the lower fat content (22.9% compared with 31.5%). The peanut content of the two recipes was analysed using RAST inhibition studies and ELISA tests.Results Three of four subjects reacted to much smaller doses of peanut protein on re-challenge (mean dose equivalence – 23 times less peanut) with the lower fat recipe. RAST inhibition showed that neither recipe altered epitope recognition. The higher fat recipe required twice as much peanut to cause 50% inhibition. ELISA detected far lower levels of peanut in the higher fat recipe (220 000 parts per million (p.p.m.)) than in the lower fat recipe (990 000 p.p.m.).Conclusion The fat content of a challenge vehicle has a profound effect on the reaction experienced after allergen ingestion. This is another factor to be considered in assessing the risk of certain foods to food-allergic consumers and adds another dimension to clinical, research and regulatory practice

Does severity of low-dose, double-blind, placebo-controlled food challenges reflect severity of allergic reactions to peanut in the community

Background: The severity of allergic reactions to food appears to be affected by many interacting factors. It is uncertain whether challenge-based reactions reflect the severity of past reactions or can predict future risk.Objective: To explore the relationship of a subject's clinical history of past reactions to the severity of reaction elicited by a low-dose, double-blind, placebo-controlled food challenge (DBPCFC) with peanut.Method: Cross-sectional questionnaire assessment of community-based allergic reactions and low-dose DBPCFC in self-selected peanut-allergic subjects. Reaction severity was assessed using a novel scoring system, taking account of the dose of allergen ingested.Results: Forty subjects (15 males, 23 children, 23 asthmatics by history) were studied. Only the most recent community reaction predicted the severity of reaction in the DBPCFC, but even this association was weak (r=0.37, P=0.03). Peanut-specific IgE (PsIgE) and skin prick test (SPT) weal size were not associated with community score but PsIgE level correlated well with the challenge score (r=0.6, P=0.001). Asthma did not affect the eliciting dose or challenge score directly but the association of PsIgE and challenge score was stronger in those without asthma (r=0.72, P=0.001) than in those with asthma (r=0.48, P=0.02).Conclusions: The scoring system developed appears to improve the sensitivity of assessment of reactions induced by DBPCFC. This is the first prospective study showing an association between PsIgE levels and clinical reactivity in DBPCFC, an effect that is more pronounced in non-asthmatics. This finding has important implications for the clinical care of subjects with food allergy. There is a poor correlation between the severity of reported reactions in the community and the severity of reaction elicited during low-dose DBPCFC with peanut

11Polymorphisms impairing histamine degradation moderate behavioural responses to food additive challenge

Background: the relationship between artificial food colouring and benzoate perservative (AFCP) intake and behaviour has hitherto been contentious. We have previously shown in a population based DBPCFC study, an adverse effect of AFCP on parentally-rated behaviour of 3 year olds and have now confirmed the observations in 144 8Y9 year olds and 153 3 year olds using objective measures of observed behaviours in a school setting. One potential mechanism is IgE independent histamine release fromcirculating basophils.Methods: from the second challenge study we have genotyped the children using buccal cells and related findings to the magnitude of the behavioural response to challenge.Results: polymorphisms of catecholamine genes, COMT Val108Met and ADRA2A C1291G, previously associated with ADHD, had no impact on responses but T939C and Thr105Ile polymorphisms of the histamine Nmethyltransferasegene (HNMT) significantly (p=0.02 and 0.04 respectively)adversely affected responses to AFCP challenge.Conclusion: HNMT polymorphisms impair histamine clearance and AFCP cause histamine release. The presence of Histamine 3 receptors in the brain provides a potential mechanism (and therapeutic target) to explain the effectwe observed. Many environmental factors increase histamine including infections and many foods. This would explain the frequent claim that food intolerance and infections adversely affect behaviour in some children. Thisgene by environment interaction should be investigated in relation to AFCP induced urticaria, asthma and other atopic conditions

EAACI Food Allergy and Anaphylaxis Guidelines. Primary prevention of food allergy

Food allergy can have significant effects on morbidity and quality of life and can be costly in terms of medical visits and treatments. There is therefore considerable interest in generating efficient approaches that may reduce the risk of developing food allergy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology&apos;s (EAACI) Taskforce on Prevention and is part of the EAACI Guidelines for Food Allergy and Anaphylaxis. It aims to provide evidence-based recommendations for primary prevention of food allergy. A wide range of antenatal, perinatal, neonatal, and childhood strategies were identified and their effectiveness assessed and synthesized in a systematic review. Based on this evidence, families can be provided with evidence-based advice about preventing food allergy, particularly for infants at high risk for development of allergic disease. The advice for all mothers includes a normal diet without restrictions during pregnancy and lactation. For all infants, exclusive breastfeeding is recommended for at least first 4-6 months of life. If breastfeeding is insufficient or not possible, infants at high-risk can be recommended a hypoallergenic formula with a documented preventive effect for the first 4 months. There is no need to avoid introducing complementary foods beyond 4 months, and currently, the evidence does not justify recommendations about either withholding or encouraging exposure to potentially allergenic foods after 4 months once weaning has commenced, irrespective of atopic heredity. There is no evidence to support the use of prebiotics or probiotics for food allergy prevention. © 2014 John Wiley &amp; Sons A/S. Published by John Wiley &amp; Sons Ltd

Physician&apos;s appraisal vs documented signs and symptoms in the interpretation of food challenge tests: The EuroPrevall birth cohort

Background: Blinded food challenges are considered the current gold standard for the diagnosis of food allergies. We used data from a pan-European multicenter project to assess differences between study centers, aiming to identify the impact of subjective aspects for the interpretation of oral food challenges. Methods: Nine study centers of the EuroPrevall birth cohort study about food allergy recruited 12 049 newborns and followed them for up to 30 months in regular intervals. Intensive training was conducted and every center visited to ensure similar handling of the protocols. Suspected food allergy was clinically evaluated by double-blind, placebo-controlled food challenges using a nine dose escalation protocol. The primary challenge outcomes based on physician&apos;s appraisal were compared to documented signs and symptoms. Results: Of 839 challenges conducted, study centers confirmed food allergy in 15.6% to 53.6% of locally conducted challenges. Centers reported 0 to 16 positive placebo challenges. Worsening of eczema was the most common sign when challenged with placebo. Agreement between documented objective signs and the challenge outcome assigned by the physician was heterogeneous, with Cohen&apos;s kappa spanning from 0.42 to 0.84. Conclusions: These differences suggest that the comparison of food challenge outcomes between centers is difficult despite common protocols and training. We recommend detailed symptom assessment and documentation as well as objective sign-based challenge outcome algorithms to assure accuracy and comparability of blinded food challenges. Training and supervision of staff conducting food challenges is a mandatory component of reliable outcome data. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd

Risk Factors for Hen&apos;s Egg Allergy in Europe: EuroPrevall Birth Cohort

Background: Hen&apos;s egg is one of the commonest causes of food allergy, but there are little data on its risk factors. Objective: To assess the risk factors, particularly eczema, for hen&apos;s egg allergy in the EuroPrevall birth cohort. Methods: In the pan-European EuroPrevall birth cohort, questionnaires were undertaken at 12 and 24 months or when parents reported symptoms. Children with suspected egg allergy were invited for skin prick testing, specific IgE assessment, and double-blind, placebo-controlled food challenge (DBPCFC) as indicated. Each egg allergy case (positive DBPCFC or egg-induced anaphylaxis) was allocated up to 2 age- and country-matched controls. Results: A total of 12,049 infants were recruited into the EuroPrevall birth cohort, and 9,336 (77.5%) were followed until 2 years. A total of 86 infants had egg allergy (84 by DBPCFC) and were matched with 140 controls. Independently associated with egg allergy were past/current eczema (adjusted odds ratio, 9.21; 95% CI, 2.65-32.04), Scoring Atopic Dermatitis (1.54 per 5 units; 1.28-1.86), antibiotics in the first week of life (6.17; 1.42-26.89), and current rhinitis (3.02; 1.04-8.78). Increasing eczema severity was associated with an increasing likelihood of egg allergy. Eczema was reported to have started 3.6 (SE, 0.5) months before egg allergy. Age of introduction of egg into the diet was not associated with egg allergy. Conclusions: Similar to peanut allergy, eczema was strongly associated with egg allergy development and the association increased with increasing eczema severity. The age of introduction of dietary egg was not a risk factor. The potential role of antibiotics in early life as a risk factor for egg allergy needs further examination. © 201

Incidence and natural history of hen's egg allergy in the first 2 years of life-the EuroPrevall birth cohort study

BACKGROUND: Parents and health staff perceive hen's egg allergy (HEA) as a common food allergy in early childhood, but the true incidence is unclear because population-based studies with gold-standard diagnostic criteria are lacking.OBJECTIVE: To establish the incidence and course of challenge-confirmed HEA in children, from birth until the age of 24 months, in different European regions.METHODS: In the EuroPrevall birth cohort study, children with a suspected HEA and their age-matched controls were evaluated in 9 countries, using a standardized protocol including measurement of HE-specific immunoglobulin E-antibodies in serum, skin prick tests, and double-blind, placebo-controlled food challenges (DBPCFC).RESULTS: Across Europe, 12 049 newborns were enrolled, and 9336 (77.5%) were followed up to 2 years of age. In 298 children, HEA was suspected and DBPCFC was offered. HEA by age two was confirmed in 86 of 172 challenged children (mean raw incidence 0.84%, 95% confidence interval (95% CI) 0.67-1.03). Adjusted mean incidence of HEA was 1.23% (95% CI 0.98-1.51) considering possible cases among eligible children who were not challenged. Centre-specific incidence ranged from United Kingdom (2.18%, 95% CI 1.27-3.47) to Greece (0.07%). Half of the HE-allergic children became tolerant to HE within 1 year after the initial diagnosis.CONCLUSIONS: The largest multinational European birth cohort study on food allergy with gold-standard diagnostic methods showed that the mean adjusted incidence of HEA was considerably lower than previously documented, although differences in incidence rates among countries were noted. Half of the children with documented HEA gained tolerance within 1 year postdiagnosis

Dietary habits and supplement use in relation to national pregnancy recommendations: data from the EuroPrevall birth cohort

Assessing maternal dietary habits across Europe during pregnancy in relation to their national pregnancy recommendations. A collaborative, multi-centre, birth cohort study in nine European countries was conducted as part of European Union funded EuroPrevall project. Standardised baseline questionnaire data included details of food intake, nutritional supplement use, exposure to cigarette smoke during pregnancy and socio-demographic data. Pregnancy recommendations were collected from all nine countries from the appropriate national organisations. The most commonly taken supplement in pregnancy was folic acid (55.6 % Lithuania-97.8 % Spain) and was favoured by older, well-educated mothers. Vitamin D supplementation across the cohort was very poor (0.3 % Spain-5.1 % Lithuania). There were significant differences in foods consumed in different countries during pregnancy e.g. only 2.7 % Dutch mothers avoided eating peanut, while 44.4 % of British mothers avoided it. Some countries have minimal pregnancy recommendations i.e. Lithuania, Poland and Spain while others have similar, very specific recommendations i.e. UK, the Netherlands, Iceland, Greece. Allergy specific recommendations were associated with food avoidance during pregnancy [relative rate (RR) 1.18 95 % CI 0.02-1.37]. Nutritional supplement recommendations were also associated with avoidance (RR 1.08, 1.00-1.16). Maternal dietary habits and the use of dietary supplements during pregnancy vary significantly across Europe and in some instances may be influenced by national recommendations