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Elimination diet in food allergy: friend or foe?

Abstract

Objectives

To review and discuss the role of an elimination diet in food-allergic children, emphasizing nutritional aspects for a better practical approach.

Sources

Non-systematic review of the literature.

Findings

Under an elimination diet, food-allergic patients may suffer from growth impairment or obesity and compromised quality of life. Disease phenotype, age, type, number of foods excluded, comorbidities, eating difficulties, economic status, and food availability must be considered for an appropriate diet prescription. Diet quality encompasses diversity and degree of food processing, which may alter immune regulation.

Conclusions

A friendly food elimination diet prescription depends on a multidisciplinary approach beyond macro and micronutrients.

Keywords
Food hypersensitivity; Children; Adolescents; Dietary intake; Immune system; Advanced glycation end products

Introduction

After diagnosing a food allergy (FA), dietary avoidance of the involved allergen is the central pillar in managing these patients to prevent allergic symptoms. However, more active treatments such as allergen-specific immunotherapy and biologicals are emerging possibilities. A temporary elimination diet, followed by reintroduction, either for the child or the breastfeeding mother, can still be helpful as a diagnostic tool, especially for non-IgE mediated manifestations of mild severity, for which other diagnostic auxiliary tools are still lacking.

Food restriction may impose nutritional11 Meyer R. Nutritional disorders resulting from food allergy in children. Pediatr Allergy Immunol. 2018;29:689-704. and emotional burdens, not being an easy task, both for the growing and developing child, as well as for the breastfeeding mother and other family members. On the other hand, dietary diversity and quality, especially in the first year of life, is vital to prevent allergies.22 Vlieg-Boerstra B, Groetch M, Vassilopoulou E, Meyer R, Laitinen K, Swain A, et al. The immune-supportive diet in allergy management: A narrative review and proposal. Allergy. 2023;78:1441-58.

This review aims to discuss the role of an elimination diet in allergic children in its diagnostic and "therapeutic" contexts, emphasizing nutritional aspects.

Elimination diet for diagnostic purposes

In non-IgE-mediated allergies, especially in food protein-induced allergic proctocolitis (FPIAP), the elimination diet is recommended, usually for one to two months, followed by reintroduction.33 Solé D, Rodrigues Silva L, Cocco RR, Ferreira CT, Sarni RO, Oliveira LC, et al. Brazilian Consensus on Food Allergy: 2018 - Part 2 - Diagnosis, treatment and prevention. Joint position paper of the Brazilian Society of Pediatrics and the Brazilian Association of Allergy and Immunology. Arq Asma Alerg Imunol. 2018;2:39-82. An elimination diet for at least two weeks is recommended for IgE-mediated manifestations before the oral food challenge under medical supervision.22 Vlieg-Boerstra B, Groetch M, Vassilopoulou E, Meyer R, Laitinen K, Swain A, et al. The immune-supportive diet in allergy management: A narrative review and proposal. Allergy. 2023;78:1441-58.

Some food allergies outgrow naturally, so regular reassessment of the allergic status should be considered to avoid unnecessary prolonged food restriction.

More recently, low-dose oral food challenges have been proposed to establish the minimum eliciting dose of a specific protein source. This approach aims to reduce anxiety and possibly unnecessary restriction due to precautionary labeling (“may contain”).44 Hourihane JO, Allen KJ, Shreffler WG, Dunngalvin G, Nordlee JA, Zurzolo GA, et al. Peanut Allergen Threshold Study (PATS): Novel single-dose oral food challenge study to validate eliciting doses in children with peanut allergy. J Allergy Clin Immunol. 2017;139:1583-90.

Elimination diet in the care of food-allergic patients

To prevent allergic reactions, once the diagnosis of FA is confirmed, food elimination is indicated with appropriate replacement.

It is important to emphasize that, in the case of breastfeeding, this should be stimulated for its numerous benefits, and the food restriction of the maternal diet with adequate substitution is indicated in cases in which the allergic manifestation occurs through breast milk, such as, for example, FPIAP. In the context of IgE-mediated allergic reactions, it is exceedingly rare for symptoms to happen via breast milk, as evidenced by a recent systematic review.55 Gamirova A, Berbenyuk A, Levina D, Peshko D, Simpson MR, Azad MB, et al. Food Proteins in Human Breast Milk and Probability of IgE-Mediated Allergic Reaction in Children During Breastfeeding: A Systematic Review. J Allergy Clin Immunol Pract. 2022;10:1312-24.e8. When there is no reaction via breast milk, it is desirable and recommended not to eliminate the food from the maternal diet, not only because maternal dietary restriction impairs the quality of the produced milk66 Rajani PS, Martin H, Groetch M, Järvinen KM. Presentation and Management of Food Allergy in Breastfed Infants and Risks of Maternal Elimination Diets. J Allergy Clin Immunol Pract. 2020;8:52-67. but also because breastfeeding may be a route of presentation of the allergen to the child that favors the induction of tolerance,77 Yokanovich LT, Newberry RD, Knoop KA. Regulation of oral antigen delivery early in life: Implications for oral tolerance and food allergy. Clin Exp Allergy. 2021;51:518-26. especially in those with atopic dermatitis and increased risk of skin sensitization.88 Tsakok T, Marrs T, Mohsin M, Baron S, du Toit G, Till S, Flohr C. Does atopic dermatitis cause food allergy? A systematic review. J Allergy Clin Immunol. 2016;137:1071-8.

When breastfeeding is not possible in the context of Cow's Milk Allergy (CMA) under two years of age, substitute formulas are indicated:
  • -

    Soy-based formulas: for children over six months of age for IgE-mediated reactions.

  • -

    Extensively hydrolyzed formula: infants at any age for all phenotypes.

  • -

    Amino acid formula: infants with anaphylaxis due to Cow's Milk (CM) and when extensively hydrolyzed formulas are not tolerated.

Noteworthy, milk from other mammals is commonly allergenic to those children because of the high similarity among proteins, and when intestinal symptoms are not present, extensively hydrolyzed formulas containing lactose are a possibility.22 Vlieg-Boerstra B, Groetch M, Vassilopoulou E, Meyer R, Laitinen K, Swain A, et al. The immune-supportive diet in allergy management: A narrative review and proposal. Allergy. 2023;78:1441-58.

Most CM and egg allergies tolerate processed food associated with a wheat matrix and baked in high temperatures for a prolonged time (180°C for 25 to 30 minutes), which reduces the allergenicity of proteins by denaturing the conformational epitopes present in foods.99 Wright K, Feeney M, Yerlett N, Meyer R. Nutritional Management of Children with Food Allergies. Curr Treat Options Allergy. 2022;9:375-93. Once the tolerance to baked goods is confirmed through clinical history and/or oral food challenge, the allergens are allowed to be consumed in this way, respecting the conditions of preparation that guarantee their reduced allergenicity. It is noteworthy that not all processing decreases the allergenicity of food and that even some food sources, when processed, induce greater clinical reactivity.1010 Mondoulet L, Paty E, Drumare MF, Ah-Leung S, Scheinmann P, Willemot RM, et al. Influence of thermal processing on the allergenicity of peanut proteins. J Agric Food Chem. 2005;53:4547-53.

More recently, allergen-specific oral immunotherapy is sometimes a more active approach to immediate FA. It consists of administering increasing doses of allergen under medical supervision and in a controlled environment, followed by home maintenance to induce tolerance. However, to date, most achieve the status of "sustained non-responsiveness" (tolerance only when submitted to a regimen of controlled and regular dose intake) and not true tolerance (ingestion as much as wanted and when desired).1111 de Silva D, Rodríguez Del Río P, de Jong NW, Khaleva E, Singh C, Nowak-Wegrzyn A, et al. Allergen immunotherapy and/or biologicals for IgE-mediated food allergy: A systematic review and meta-analysis. Allergy. 2022;77:1852-62.

Regarding eosinophilic esophagitis (EoE) a meta-analysis including thirty-four studies with 1762 patients showed that the overall rate of histologic remission due to diet management was 53.8% (95% CI, 48.0%-59.6%), and in the individual dietary groups was 61.3% (95% CI, 53.0%-69.3%) for six-food elimination diet, 49.4% (95% CI, 32.5%-66.3%) for four-food elimination diet, 51.4% (95% CI, 42.6%-60.1%) for one-food elimination diet, and 45.7% (95% CI, 32.0%-59.7%) for a targeted elimination diet. Dietary regimen and patient age did not significantly affect rates of histologic remission. The authors concluded that dietary therapy is an effective treatment for EoE patients of any age. The current results could support a trend toward less restrictive dietary regimens as a primary treatment option.1212 Mayerhofer C, Kavallar AM, Aldrian D, Lindner AK, Müller T, Vogel GF. Efficacy of Elimination Diets in Eosinophilic Esophagitis: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2023;21:2197-210.e3.

Diet quality and immune system

As the main form of treatment for FA is the exclusion of the food involved in allergic reactions, nutrition's role in managing FA has always been central, both to avoid adverse reactions and to prevent nutritional risks.

Until recently, the focus in nutritional therapy for FA was finding a substitute/replenishing nutrients for the excluded food(s) to prevent/treat nutritional deficits. However, with the increase in the persistence and prevalence of FA and the emergence of new evidence regarding the interface between nutrition and the functioning of the immune system, there is growing concern about the quality of the diet of children and adolescents with FA.1313 Kalmpourtzidou A, Xinias I, Agakidis C, Mavroudi A, Mouselimis D, Tsarouchas A, et al. Diet Quality: A Neglected Parameter in Children With Food Allergies. A Cross-Sectional Study. Front Pediatr. 2021;9:658778.

Diet quality encompasses many aspects; among them, one can mention dietary diversity, which emerges as a promising role in the immune system and healthy intestinal microbiota1414 Venter C, Eyerich S, Sarin T, Klatt KC. Nutrition and the Immune System: A Complicated Tango. Nutrients. 2020;12:818. and the degree of industrial food processing (ultra-processed foods - UPF, substances resulting from processing, such as advanced glycation end products - AGEs and food additives).1515 Briceno Noriega D, Zenker HE, Croes CA, Ewaz A, Ruinemans-Koerts J, Savelkoul HFJ, et al. Receptor Mediated Effects of Advanced Glycation End Products (AGEs) on Innate and Adaptative Immunity: Relevance for Food Allergy. Nutrients. 2022;14:371.,1616 Celebi Sozener Z, Özbey Yücel Ü, Altiner S, Ozdel Oztürk B, Cerci P, Türk M, et al. The External Exposome and Allergies: From the Perspective of the Epithelial Barrier Hypothesis. Front Allergy. 2022;3:887672.

Food diversity and food allergies

As the name suggests, dietary diversity refers to the number of foods/groups consumed in a period but also includes the nutritional value and frequency with which these foods are consumed.1414 Venter C, Eyerich S, Sarin T, Klatt KC. Nutrition and the Immune System: A Complicated Tango. Nutrients. 2020;12:818. Food diversity in children's diets has been associated with allergy prevention, as it is related to reduced childhood allergy outcomes.1717 Venter C, Greenhawt M, Meyer RW, Agostoni C, Reese I, du Toit G, et al. EAACI position paper on diet diversity in pregnancy, infancy and childhood: Novel concepts and implications for studies in allergy and asthma. Allergy. 2020;75:497-523.

It would not be possible to discuss dietary diversity and not mention complementary feeding in infants with CMA. Some foods that are part of the dietary introduction, such as eggs and fish, are considered most allergenic. Furthermore, essential foods such as fruits and vegetables, not the most common food allergens, have been increasingly linked to allergic reactions.1818 Li SK, Liu Z, Huang CK, Wu TC, Huang CF. Prevalence, clinical presentation, and associated atopic diseases of pediatric fruit and vegetable allergy: A population-based study. Pediatr Neonatol. 2022;63:520-6. Given this, many parents and health professionals delay food introduction to infants with FA or do so very slowly. However, the variety of foods offered in the first year of a child's life appears to be associated with a reduced risk of developing FA in the first ten years.1919 Venter C, Maslin K, Holloway JW, Silveira LJ, Fleischer DM, Dean T, et al. Different Measures of Diet Diversity During Infancy and the Association with Childhood Food Allergy in a UK Birth Cohort Study. J Allergy Clin Immunol Pract. 2020;8:2017-26.

It is worth mentioning that the introduction of food to infants with FA must be done as recommended for all infants from 6 months of age (respecting the child's signs of readiness), prioritizing unprocessed and minimally processed foods, including all groups of foods (fruits, vegetables, cereals, roots and tubers, beans, nuts, and animal proteins) and offering them frequently in the infant's diet.2020 Brasil. Ministério da Saúde. Secretária de Atenção Primária à Saúde. Departamento de Promoção da Saúde. Guia alimentar para crianças brasileiras menores de 2 anos. Brasília: Ministério da Saúde; 2019. 265 p. The only caveat is that for children who have presented symptoms of FA in the first months of life, before introducing foods other than breast milk, it is best to avoid the simultaneous introduction of two or more foods that are protein sources.33 Solé D, Rodrigues Silva L, Cocco RR, Ferreira CT, Sarni RO, Oliveira LC, et al. Brazilian Consensus on Food Allergy: 2018 - Part 2 - Diagnosis, treatment and prevention. Joint position paper of the Brazilian Society of Pediatrics and the Brazilian Association of Allergy and Immunology. Arq Asma Alerg Imunol. 2018;2:39-82.

Introducing foods considered more allergenic and a varied diet should be encouraged so infants with FA do not lose the already recognized benefits of a diversified diet.

Consumption of ultra-processed foods in food allergies

UPF consumption has tripled in the last 30 years among adults, and there is much evidence in the literature, including meta-analyses, that its consumption is associated with one or more negative health outcomes.2121 Jaime P, Campello T, Monteiro C, Bortoletto AP, Yamaoka M, Bomfim M, orgs. Diálogo sobre ultraprocessados : soluções para sistemas alimentares. São Paulo: Núcleo de Pesquisas Epidemiológicas em Nutrição e Saúde (NUPENS) e Cátedra Josué de Castro da Universidade de São Paulo (USP); 2021.

In children and adolescents, the most relevant findings demonstrated an association between UPF consumption and overweight and obesity, cardiometabolic comorbidities, worsening of lipid profile, and metabolic syndrome.2222 De Amicis R, Mambrini SP, Pellizzari M, Foppiani A, Bertoli S, Battezzati A, et al. Ultra-processed foods and obesity and adiposity parameters among children and adolescents: a systematic review. Eur J Nutr. 2022;61:2297-311.

23 Petridi E, Karatzi K, Magriplis E, Charidemou E, Philippou E, Zampelas A. The impact of ultra-processed foods on obesity and cardiometabolic comorbidities in children and adolescents: a systematic review. Nutr Rev. 2023. doi: 10.1093/nutrit/nuad095. Online ahead of print.
https://doi.org/10.1093/nutrit/nuad095...

24 Beserra JB, Soares NI, Marreiros CS, Carvalho CM, Martins MD, Freitas BJ, et al. Crianças e adolescentes que consomem alimentos ultraprocessados possuem pior perfil lipídico? Uma revisão sistemática [Do children and adolescents who consume ultra-processed foods have a worse lipid profile? A systematic review]. Cien Saude Colet. 2020;25:4979-89. Portuguese.
-2525 Frías JR, Cadena LH, Villarreal AB, Piña BG, Mejía MC, Cerros LA, et al. Effect of ultra-processed food intake on metabolic syndrome components and body fat in children and adolescents: A systematic review based on cohort studies. Nutrition. 2023;111:112038. Results of a study conducted with 110 Brazilian children and adolescents with FA that evaluated the consumption of UPF2626 Kotchetkoff EC de A, Souza FI, Almeida DN, Barreto TL, Oliveira LC, Sarni RO. Is there an association between food allergy and the consumption of ultra-processed foods? Allergy. Forthcoming 2024. showed a high consumption among these individuals (average 33% contribution of UPF to the total energy consumed) when compared to individuals healthy between 10 and 18 years old (average 26% UPF contribution to the total energy consumed).2727 Instituto Brasileiro de Geografia e Estatística (IBGE). Pesquisa de Orçamentos Familiares (POF) - 2017-2018 [Internet]. Vol. 46. Rio de Janeiro: IBGE; 2003. p. 983-7. Available from: http://scholar.google.com/scholar?hl=en&btnG=Search&q=intitle:Pesquisa±de±Or?amentos±Familiares#0.
http://scholar.google.com/scholar?hl=en&...
It was emphasized that there is no safe amount of UPF intake.

UPF are industrial formulations with little fiber, water, micronutrients, and a large amount of added sugar, sodium, saturated fat, and food additives.2020 Brasil. Ministério da Saúde. Secretária de Atenção Primária à Saúde. Departamento de Promoção da Saúde. Guia alimentar para crianças brasileiras menores de 2 anos. Brasília: Ministério da Saúde; 2019. 265 p. Additionally, the composition and way UPF are produced induces the Maillard reaction (MR - a non-enzymatic reaction between carbohydrates and proteins, also known as glycation), one of the primary mechanisms for forming advanced glycation ends exogenous products (AGEs).1515 Briceno Noriega D, Zenker HE, Croes CA, Ewaz A, Ruinemans-Koerts J, Savelkoul HFJ, et al. Receptor Mediated Effects of Advanced Glycation End Products (AGEs) on Innate and Adaptative Immunity: Relevance for Food Allergy. Nutrients. 2022;14:371.

MR promotes chemical and conformational changes in food proteins, influencing digestibility, bioavailability, immunogenicity, and allergenicity.1515 Briceno Noriega D, Zenker HE, Croes CA, Ewaz A, Ruinemans-Koerts J, Savelkoul HFJ, et al. Receptor Mediated Effects of Advanced Glycation End Products (AGEs) on Innate and Adaptative Immunity: Relevance for Food Allergy. Nutrients. 2022;14:371. This MR effect may appear to be linked to the structural characteristic of the protein, ionic strength, heating time and temperature, carbohydrate type, pH, and water activity.2828 Teodorowicz M, van Neerven J, Savelkoul H. Food Processing: The Influence of the Maillard Reaction on Immunogenicity and Allergenicity of Food Proteins. Nutrients. 2017;9:835.

In recent years, it has been postulated that the accumulation of AGEs in the body could influence the persistence and increase of FA (Figure 1).

Figure 1
The accumulation of AGEs in the body has been related to the increased prevalence and worsening of FA. Among the proposed mechanisms: (A) inflammation, through the interaction of AGEs with their receptors (RAGEs), which can lead to increased production of pro-inflammatory cytokines; (B) induction of new IgE-binding epitopes; (C) Reduction in the diversity of the intestinal microbiota, which can lead to increase susceptibility to allergies, as well as a delay in acquiring tolerance. AGEs - advanced glycation end products; RAGEs - receptor advanced glycation end products.

Below, the authors list some proposed mechanisms of the interaction of AGEs with FA:
  1. Inflammation (receptors present on antigen-presenting cells): Food allergens in the presence of AGEs can trigger the RAGE receptor and cooperate to produce pro-inflammatory cytokines through antigen-presenting dendritic cells and T cell responses. And that has been associated with the development and progression of several diseases. Among them, FA causes allergic sensitization through dendritic cells, antigen-presenting cells, and T-cell responses. Furthermore, the interaction of AGEs with RAGEs appears to activate mast cells, with a possible participation in the pathogenesis of FA.2828 Teodorowicz M, van Neerven J, Savelkoul H. Food Processing: The Influence of the Maillard Reaction on Immunogenicity and Allergenicity of Food Proteins. Nutrients. 2017;9:835.

    29 Gupta RK, Gupta K, Sharma A, Das M, Ansari IA, Dwivedi PD. Maillard reaction in food allergy: Pros and cons. Crit Rev Food Sci Nutr. 2018;58:208-26.
    -3030 Toda M, Hellwig M, Henle T, Vieths S. Influence of the Maillard Reaction on the Allergenicity of Food Proteins and the Development of Allergic Inflammation. Curr Allergy Asthma Rep. 2019;19:4.

  2. Induction of new IgE binding epitopes (change in protein structure): The alteration of the function of glycated proteins occurs because MR leads to the aggregation of proteins through intermolecular or intramolecular cross-linking between lysine and arginine residues in the creation of shared AGEs. This process can alter the level of IgE and antigen-presenting cell recognition. In other words, proteins modified by AGEs can lead to immunogenic responses.3131 Yang H, Qu Y, Gao Y, Sun S, Ding R, Cang W, et al. Role of the dietary components in food allergy: A comprehensive review. Food Chem. 2022;386:132762.

  3. Reduction in the diversity of the intestinal microbiota: There is evidence that the intestinal microbiota can influence anti- and pro-inflammatory responses in the intestine.22 Vlieg-Boerstra B, Groetch M, Vassilopoulou E, Meyer R, Laitinen K, Swain A, et al. The immune-supportive diet in allergy management: A narrative review and proposal. Allergy. 2023;78:1441-58. It has been proposed that the breakdown of the integrity of the intestinal epithelial barrier may allow entry of food allergens, toxins, and other substances that can lead to inflammation.3232 Hirata SI, Kunisawa J. Gut microbiome, metabolome, and allergic diseases. Allergol Int. 2017;66:523-8.,3333 Akdis M, Aab A, Altunbulakli C, Azkur K, Costa RA, Crameri R, et al. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases. J Allergy Clin Immunol. 2016;138:984-1010.

AGEs have been associated with reduced intestinal microbiota, leading to greater susceptibility to allergies and/or a delay in the acquisition of tolerance in individuals with FA.1515 Briceno Noriega D, Zenker HE, Croes CA, Ewaz A, Ruinemans-Koerts J, Savelkoul HFJ, et al. Receptor Mediated Effects of Advanced Glycation End Products (AGEs) on Innate and Adaptative Immunity: Relevance for Food Allergy. Nutrients. 2022;14:371. Reduction of butyrate-producing bacteria has been associated with an allergic phenotype,3434 Fujimura KE, Lynch SV. Microbiota in allergy and asthma and the emerging relationship with the gut microbiome. Cell Host Microbe. 2015;17:592-602. as this stimulates the development of regulatory T cells (Treg).3535 Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013;504:446-50. Erratum in: Nature. 2014;506:254. PMID: 24226770.

On the other hand, the participation of some fatty acids in improving the function of the intestinal epithelial barrier has been proposed. It is possible that Lactobacillus derived from 10-hydroxy-cis-12 octadecenoic acid (a metabolite derived from linoleic acid), as well as short-chain fatty acids (acetate and butyrate), favor the maintenance of the intestinal epithelial barrier and, therefore, is a protective factor for FA prevention.3636 Yu LC. Intestinal epithelial barrier dysfunction in food hypersensitivity. J Allergy (Cairo). 2012;2012:596081.

Furthermore, the hypothesis has recently emerged that phosphorus, a mineral widely found in foods considered more allergenic, such as eggs, fish, milk, oilseeds, peanuts, soybeans, and wheat, when consumed in large quantities and associated with a diet rich in AGEs could harm the immune system.3737 A Cocores J. High-Temperature Cooking May Explain the Rising Pervasiveness of Food Allergies Worldwide. Int J Clin Studies Med Case Reports. 2023;32:001.

Although many mechanisms have been proposed and the adverse health effects of exogenous AGEs are known, it is still unknown whether chronic consumption of AGEs alone is to blame for their negative impact on human health.3838 Del Castillo MD, Iriondo-DeHond A, Iriondo-DeHond M, Gonzalez I, Medrano A, Filip R, et al. Healthy eating recommendations: good for reducing dietary contribution to the body's advanced glycation/lipoxidation end products pool? Nutr Res Rev. 2021;34:48-63.,3939 Uribarri J, del Castillo MD, de la Maza MP, Filip R, Gugliucci A, Luevano-Contreras C, et al. Dietary advanced glycation end products and their role in health and disease. Adv Nutr. 2015;6:461-73. Studies need to be carried out to elucidate this binomial. Furthermore, it is pertinent to mention that exogenous AGEs are more related to how the food is cooked. This covers all foods that suffer from MR, including homemade food.4040 Uribarri J, Woodruff S, Goodman S, Cai W, Chen X, Pyzik R, et al. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc. 2010;110:911-16.e12.

Another component of interest in the literature on UPF is food additives, which are substances intentionally added to UPF without nourishing but altering these foods' chemical, biological, physical, or sensory characteristics.4141 Randhawa S, Bahna SL. Hypersensitivity reactions to food additives. Curr Opin Allergy Clin Immunol. 2009;9:278-83. The variety of food additives is vast, as is their applicability. Foods such as processed bread, margarine, and even baby foods such as infant formula may contain food additives such as polysorbate (P20 and P80), carboxymethylcellulose (CMC) and carrageenan (E407). Such additives have been associated with compromised intestinal mucosa and changes in the intestinal microbiota, with consequent inflammation, increased oxidative stress, and changes in the immune system.4242 Chassaing B, Van de Wiele T, De Bodt J, Marzorati M, Gewirtz AT. Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation. Gut. 2017;66:1414-27.

43 Martino JV, Van Limbergen J, Cahill LE. The Role of Carrageenan and Carboxymethylcellulose in the Development of Intestinal Inflammation. Front Pediatr. 2017;5:96.
-4444 Lerner A, Matthias T. Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease. Autoimmun Rev. 2015;14:479-89.

Nutrition for health

Diets rich in UPF may increase the risk of developing and worsening FA. On the other hand, evidence is growing regarding the immunomodulatory functions of the nutrients (Figure 2). A diet rich in unprocessed and minimally processed foods should be the basis of a healthy diet, as they are rich in fiber, macro and micronutrients, and antioxidant substances.

Figure 2
Immunomodulatory functions of nutrients. Adapted from Vlieg-Boerstra.22 Vlieg-Boerstra B, Groetch M, Vassilopoulou E, Meyer R, Laitinen K, Swain A, et al. The immune-supportive diet in allergy management: A narrative review and proposal. Allergy. 2023;78:1441-58. Adapted from Allergy, volume 78, issue 6, Vlieg-Boerstra, B., Groetch, M., Vassilopoulou, E., Meyer, R., Laitinen, K., Swain, A., Durban, R., Benjamin, O., Bottse, R., Grimshaw, K., Netting, M., O'Mahony, L., de Jong, N., & Skypala, I. J., “The immune-supportive diet in allergy management: A narrative review and proposal”, pages 1441-1458, doi: 10.1111/all.15687, with permission from John Wiley and Sons.

A crucial topic in FA nutritional therapy is appropriate substitution based on the principles proposed by the Dietary Guides.99 Wright K, Feeney M, Yerlett N, Meyer R. Nutritional Management of Children with Food Allergies. Curr Treat Options Allergy. 2022;9:375-93. There are several publications suggesting substitute foods for the main food allergens. However, it is essential to differentiate between types of substitute foods, as they are not all the same. For better reasoning in nutritional management, the authors suggest classifying them into (i) nutritional substitute (equivalent foods or with some nutrients present in the food allergen source) and (ii) cooking substitute (an ingredient used for cooking that has technological functions like the allergenic source), for example, vegan cheeses. When comparing them with CM-based cheeses, the authors see that the primary nutrients of interest in CM-based cheese, protein and calcium, are not equivalent between these two versions (Table 1), making the vegan cheese unviable for nutritional purposes, although possible as a cooking substitute.

Table 1
Comparison between cow's milk cheese and vegan cheese (quantity in 100g of food).

Understanding that the formation of AGEs goes beyond the issue of UPF consumption and given the possible harmful effects of AGEs on human health, Uribarri et al.4040 Uribarri J, Woodruff S, Goodman S, Cai W, Chen X, Pyzik R, et al. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc. 2010;110:911-16.e12. published a practical guide to reducing dietary AGEs. The set of measures proposed by the authors ranges from the degree of food processing, including herbs and acids such as lemon and vinegar in meat preparation, to cooking methods (Figure 3). The authors emphasize that there is no safe and ideal intake recommendation to prevent diseases.

Figure 3
Measures proposed by Uribarri et al.4040 Uribarri J, Woodruff S, Goodman S, Cai W, Chen X, Pyzik R, et al. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc. 2010;110:911-16.e12. . Reprinted from Journal of the Academy of Nutrition and Dietetics, volume 110, issue 6, Uribarri, J., Woodruff, S., Goodman, S., Cai, W., Chen, X., Pyzik, R., Yong, A., Striker, G. E., & Vlassara, H, “Advanced glycation end products in foods and a practical guide to their reduction in the diet”, pages 911-16.e12, 2010, doi: 10.1016/j.jada.2010.03.018, with permission from Elsevier.

Nutritional Risks of the Elimination Diet

The strict elimination of the responsible food from the diet means removing all forms of it, such as preparations. It can compromise an adequate and balanced diet and lead to nutritional risks.

Studies point to impaired growth in children with FA, especially short stature (height-for-age z-score < -2), affecting around 10% of children.4545 Sova C, Feuling MB, Baumler M, Gleason L, Tam JS, Zafra H, et al. Systematic review of nutrient intake and growth in children with multiple IgE-mediated food allergies. Nutr Clin Pract. 2013;28:669-75. Multiple factors contribute to impaired growth and include the elimination diet itself, which impacts the intake of macro and micronutrients; coexistence with eating difficulties; the presence of comorbidities such as atopic dermatitis and asthma; persistent gastrointestinal inflammation affecting nutrient absorption4646 Berni Canani R, Leone L, D'Auria E, Riva E, Nocerino R, Ruotolo S, et al. The effects of dietary counseling on children with food allergy: a prospective, multicenter intervention study. J Acad Nutr Diet. 2014;114:1432-9. and the use of medications such as corticosteroids, which can also affect height growth, and proton pump inhibitors (PPIs).99 Wright K, Feeney M, Yerlett N, Meyer R. Nutritional Management of Children with Food Allergies. Curr Treat Options Allergy. 2022;9:375-93. PPIs, commonly used in EoE, can also affect micronutrient status. A reduction in gastric acid production potentially impacts the absorption of calcium, phosphorus, iron, and vitamin B12.4747 Yadlapati R, Kahrilas PJ. The "dangers" of chronic proton pump inhibitor use. J Allergy Clin Immunol. 2018;141:79-81. The elimination diet can also cause anxiety and stress (concern about eating, increased responsibility, caution, and fear of accidental exposure), particularly in parents and caregivers, and thus affect the child's and their family's social activities. Family with restrictions on socialization (going to restaurants and traveling), problems adapting to school.

Eating difficulties also contribute to the nutritional risk of children with FA and range from hypersensitivity and/or aversion to different textures and flavors in younger children to ARED (avoidant restrictive eating disorder) in older children, significantly reducing food consumption. The elimination diet reduces the number of food exposures and dietary variety, a traumatic event (i.e., food protein-induced enterocolitis syndrome event or anaphylaxis), and FA symptoms that can lead to abdominal discomfort and pain are all possible contributing factors.4848 Meyer R, Rommel N, Van Oudenhove L, Fleming C, Dziubak R, Shah N. Feeding difficulties in children with food protein-induced gastrointestinal allergies. J Gastroenterol Hepatol. 2014;29:1764-9.,4949 Chehade M, Meyer R, Beauregard A. Feeding difficulties in children with non-IgE-mediated food allergic gastrointestinal disorders. Ann Allergy Asthma Immunol. 2019;122:603-9.

On the other hand, other studies indicate that obesity can also occur in children with FA due to inappropriate substitutions, unbalanced diets, and poor food choices.5050 Venter C, Mazzocchi A, Maslin K, Agostoni C. Impact of elimination diets on nutrition and growth in children with multiple food allergies. Curr Opin Allergy Clin Immunol. 2017;17:220-6.

A good diet is based on a varied, balanced, and individualized diet, avoiding consuming ultra-processed industrialized foods, which may be the best model for treating food allergies. The biggest challenge for anyone working in this area is to ensure that the quality and quantity of nutrients are guaranteed, even with one or more exclusions.22 Vlieg-Boerstra B, Groetch M, Vassilopoulou E, Meyer R, Laitinen K, Swain A, et al. The immune-supportive diet in allergy management: A narrative review and proposal. Allergy. 2023;78:1441-58. Comprehensive dietary advice should consider individual nutritional needs and appropriate and locally available food alternatives and assess the family's cooking skills and economic status. Furthermore, caregivers should receive guidance on promoting dietary diversity, particularly during complementary feeding, and know the long-term impact of diet on health and disease prevention.

Concerning micronutrients, Meyer et al., analyzing the dietary surveys of 110 children with non-IgE-mediated FA, showed that the children were at risk of inadequate vitamin D, zinc, calcium, and selenium.5151 Meyer R, De Koker C, Dziubak R, Skrapac AK, Godwin H, Reeve K, et al. A practical approach to vitamin and mineral supplementation in food allergic children. Clin Transl Allergy. 2015;5:11. Low concentrations of serum biomarkers such as zinc, iron, selenium, vitamin A, vitamin D, and calcium have also been described in children with FA.99 Wright K, Feeney M, Yerlett N, Meyer R. Nutritional Management of Children with Food Allergies. Curr Treat Options Allergy. 2022;9:375-93.,5252 Boaventura RM, Mendonça RB, Fonseca FA, Mallozi M, Souza FS, Sarni RO. Nutritional status and food intake of children with cow's milk allergy. Allergol Immunopathol (Madr). 2019;47:544-50. Thomassen et al. studied urinary iodine concentrations in children with CMA and found that a third had levels compatible with iodine deficiency.5353 Thomassen RA, Kvammen JA, Eskerud MB, Júlíusson PB, Henriksen C, Rugtveit J. Iodine Status and Growth In 0-2-Year-Old Infants With Cow's Milk Protein Allergy. J Pediatr Gastroenterol Nutr. 2017;64:806-811.

It has been widely established that children with FA who receive nutritional guidance and monitoring from a specialized nutrition professional are at significantly lower risk of developing deficiencies, particularly micronutrient deficiencies.4545 Sova C, Feuling MB, Baumler M, Gleason L, Tam JS, Zafra H, et al. Systematic review of nutrient intake and growth in children with multiple IgE-mediated food allergies. Nutr Clin Pract. 2013;28:669-75. Although there are no specific guidelines for routine measurement of serum biomarkers for micronutrients in children with FA, a detailed dietary history can guide the need for measurement and eventual supplementation. The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition has developed a guideline on the accuracy of nutrition-related biomarkers for sick children that may also be useful for those with FA.5454 Gerasimidis K, Bronsky J, Catchpole A, Embleton N, Fewtrell M, Hojsak I, et al. Assessment and Interpretation of Vitamin and Trace Element Status in Sick Children: A Position Paper From the European Society for Paediatric Gastroenterology Hepatology, and Nutrition Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2020;70:873-81.

Below, the authors list some aspects that should be considered when assessing the nutritional risk of children with FA:
  1. Low age (generally children under two years): due to the intense period of growth and development that must be monitored longitudinally with appropriate curves. Food consumption should be assessed at every consultation to guide nutritional management.

  2. Disease phenotype (EoE) or associated allergic diseases (atopic dermatitis or asthma): Children with EoE present symptoms that can limit adequate nutritional intake, such as recurrent vomiting and regurgitation, abdominal pain, lack of appetite, low volume, and/or small variety of foods. Patients with chronic inflammation of the esophagus develop compensatory eating habits (i.e., drinking plenty of fluids during meals, eating slowly, chewing carefully, cutting food into small pieces, lubricating food with sauces or liquids) or avoiding certain foods (meat, crispy bread and hard or fibrous foods such as meat). Furthermore, young children fed liquid formula for a long time do not engage their masticatory muscles and are prone to delayed onset of oral motor skills. Another important aspect is the delay in diagnosis, which can culminate in the presence of esophageal rings and strictures, which further prolongs gastrointestinal symptoms and eating discomfort with the possibility of impaction. Patients with episodes of food impaction may be at high risk of developing anxiety and eating disorders, compromising adequate nutrient intake. Therefore, chronic gastrointestinal symptoms, compensatory eating habits, and eating disorders can complicate the nutritional status of EoE patients, especially if they are children. Finally, poor adherence to therapy is the main reason for therapeutic failure and persistent active inflammation.5555 Votto M, De Filippo M, Lenti MV, Rossi CM, Di Sabatino A, Marseglia GL, et al. Diet Therapy in Eosinophilic Esophagitis. Focus on a Personalized Approach. Front Pediatr. 2022;9:820192.

This emerging chronic disease's complexity and clinical heterogeneity imply a multidisciplinary approach, including an allergist, pediatrician, gastroenterologist, nutritionist, and psychologist, to manage these patients. Before starting diet therapy and during the follow-up period, the team must periodically assess the nutritional status of patients and rule out a potential deficiency. The risk of nutritional deficiency and impaired growth increases with the restrictive nature of the diet and the number of foods removed.5555 Votto M, De Filippo M, Lenti MV, Rossi CM, Di Sabatino A, Marseglia GL, et al. Diet Therapy in Eosinophilic Esophagitis. Focus on a Personalized Approach. Front Pediatr. 2022;9:820192.
  • 3)

    Type and number of foods excluded: The exclusion of allergenic foods can lead to deficiencies in macro and micronutrients, such as vitamins, minerals, and fiber, if measures are not taken to ensure appropriate substitution. For example, people allergic to milk may be at risk for calcium deficiency, while those allergic to grains may face a reduction in fiber intake. If left untreated, malnutrition and other nutritional deficiencies progress and can result in inadequate nutrient intake, malabsorption, metabolic changes, and/or increased nutritional needs.5656 Groetch M, Nowak-Wegrzyn A. Practical approach to nutrition and dietary intervention in pediatric food allergy. Pediatr Allergy Immunol. 2013;24:212-21. Christie et al. reported that children who eliminated two or more foods were shorter in height for their age than those who eliminated just one food.5757 Christie L, Hine RJ, Parker JG, Burks W. Food allergies in children affect nutrient intake and growth. J Am Diet Assoc. 2002;102:1648-51.

CM and dairy products contribute to early childhood nutrition for non-breastfed children and are responsible for most allergic reactions at this stage. Children who eliminated CM from their diet had lower protein and lipid intakes than the control group, which resulted in lower energy levels.5858 Flammarion S, Santos C, Guimber D, Jouannic L, Thumerelle C, Gottrand F, et al. Diet and nutritional status of children with food allergies. Pediatr Allergy Immunol. 2011;22:161-5.

Plant-based drinks have increased in popularity in recent years. While soy-based beverages have been on the market for more than 30 years, consumers now have the option of beverages made from almond, coconut, hazelnut, walnut, macadamia, quinoa, oat, hemp, potato, pea, and rice. Such drinks generally have low energy and protein content; some are supplemented with calcium.5959 Merritt RJ, Fleet SE, Fifi A, Jump C, Schwartz S, Sentongo T, et al. North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper: Plant-based Milks. J Pediatr Gastroenterol Nutr. 2020;71:276-81. They do not correspond to the nutritional content of any infant formula. They can only be considered a cooking substitute (food ingredient) after six months and as a drink after two years of age, subject to nutritional monitoring.99 Wright K, Feeney M, Yerlett N, Meyer R. Nutritional Management of Children with Food Allergies. Curr Treat Options Allergy. 2022;9:375-93.
  • 4)

    Consumption of processed foods: There is an ongoing effort to define limits on allergens in processed foods that would inform the need for precautionary labeling of allergens. A recent position suggested a universal limit of 0.5 mg of protein per 100g of processed food as a universal guideline for food labeling.6060 Zuberbier T, Dörr T, Aberer W, Alvaro M, Angier E, Arasi S, et al. Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food-A first step in an initiative to better inform patients and avoid fatal allergic reactions: A GA²LEN position paper. Allergy. 2022;77:1736-50. Careful reading and interpretation of labels should be part of the nutritional guidance offered to patients with FA and their families. In current Brazilian legislation, the term “may contain” sometimes confuses families with increased unnecessary consumption restrictions.

How to reduce nutritional risk:
  1. 1.Preventing malnutrition and nutritional deficiencies is fundamental in treating FA, as they can lead to sequelae in somatic and cognitive growth and development. Therefore, the importance of a nutritionist in the team who assists children with FA is highlighted.

  2. 2.Monitoring anthropometric measurements at each consultation with longitudinal monitoring on appropriate curves.

  3. 3.Assess food consumption and, when necessary, request nutritional biomarkers.

  4. 4.Encourage, whenever possible, breastfeeding with appropriate guidance on the exclusion diet for the mother.

  5. 5.Children under two years of age with CMA who are not breastfed should receive soy-based (over six months and without GI manifestations), extensively hydrolyzed (under six months), or amino acid-based infant formulas (anaphylaxis and non-IgE-mediated forms with poor response to extensively hydrolyzed) as substitutes.

  6. 6.Nutritional guidance, including dietary diversity and expanding texture and flavor from the beginning, to avoid eating difficulties.

Conclusion

The elimination diet is fundamental to avoid reactions to food allergies, but it imposes enemies as nutritional risks and emotional burdens, so a multidisciplinary effort is necessary. First, the correct diagnosis of the allergic status is essential. The quality of a friendly elimination diet must consider not only macro and micronutrients but also diversity, food processing, possible eating difficulties, and other comorbidities. Consuming unprocessed and minimally processed foods should be prioritized over UPF as it prevents the development of other chronic diseases and modulates the immune system. When appropriate, allergic status must be reassessed to avoid further unnecessary restrictions.

  • Funding
    None.

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Publication Dates

  • Publication in this collection
    13 May 2024
  • Date of issue
    Mar-Apr 2024

History

  • Received
    17 Sept 2023
  • Accepted
    20 Sept 2023
  • Published
    31 Oct 2023
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