The false alarm hypothesis: Food allergy is associated with high dietary advanced glycation end-products and proglycating dietary sugars that mimic alarmins

Abstract

The incidence of food allergy has increased dramatically in the last few decades in westernized developed countries. We propose that the Western lifestyle and diet promote innate danger signals and immune responses through production of "alarmins." Alarmins are endogenous molecules secreted from cells undergoing nonprogrammed cell death that signal tissue and cell damage. High molecular group S (HMGB1) is a major alarmin that binds to the receptor for advanced glycation end-products (RAGE). Advanced glycation end-products (AGEs) are also present in foods. We propose the "false alarm" hypothesis, in which AGEs that are present in or formed from the food in our diet are predisposing to food allergy. The Western diet is high in AGEs, which are derived from cooked meat, oils, and cheese. AGEs are also formed in the presence of a high concentration of sugars. We propose that a diet high in AGEs and AGE-forming sugars results in misinterpretation of a threat from dietary allergens, promoting the development of food allergy. AGEs and other alarmins inadvertently prime innate signaling through multiple mechanisms, resulting in the development of allergic phenotypes. Current hypotheses and models of food allergy do not adequately explain the dramatic increase in food allergy in Western countries. Dietary AGEs and AGE-forming sugars might be the missing link, a hypothesis supported by a number of convincing epidemiologic and experimental observations, as discussed in this article.

Glycation of the Major Milk Allergen β‐Lactoglobulin Changes Its Allergenicity by Alterations in Cellular Uptake and Degradation

“…The immunomodulatory effects of AGEs structures have been described in literature (reviewed in refs. ). For instance, the effects of MR on immunogenicity and allergenicity of food allergen OVA have also been studied and have shown an elevated risk of food allergy .…”

“…Similarly, AGE‐BSA induced maturation of DCs and augmented their capacity to stimulate T‐cell proliferation and cytokine secretion . It has even been speculated that AGEs of food allergens interact with DCs, promote immune responses, and contribute to the development of food allergy by mimicking endogenous danger signals …”

EAACI position paper on diet diversity in pregnancy, infancy and childhood: Novel concepts and implications for studies in allergy and asthma

“…44 Microbial diversity of food: Studying foods with a high biodiversity of microbial content such as unpasteurized milk (atopic dermatitis and atopy) 130 and fermented foods such as cheese or yoghurt (food allergy and atopic dermatitis) 131 as an indicator of intake of microbial diversity, and a source of short chain fatty acids, gives an indication that these foods may be associated with allergy prevention. Studies focusing on Westernized diets 116,117,132 (also high in advanced glycation end products, soda, fruit juice, 133,134 cured meats 135 and fast food 136 ) suggest that increased intake of advanced glycation end products(AGEs) is associated with reduced diet diversity and increased allergy outcomes. A number of studies have indicated that certain nutrients (eg antioxidants) of foods (fruit and vegetables or fish) may have a beneficial effect on prevention particularly of infant wheeze [137][138][139][140] or eczema in the infant 77,139 Portion size It is unclear if portion size should be included when measuring diet diversity and it will depend on the outcome being studied.…”

Maillard Reactions – An Important Factor of the Safety and Quality of Infant Formula

“…У мла-денцев, получавших с молочным питанием повы-шенные уровни КМЛ, регистрировали повышенные уровни этого соединения в образцах плазмы и мочи [68,87]. Продукты реакции Майара могут изменять аллергенный потенциал пищевых белков [88], а связь ПРМ с повышенным риском возникновения аллер-гии у детей раннего возраста была постулирована [89]. Непродолжительное воздействие КМЛ не оказывало негативного влияния на чувствительность к инсулину или биомаркеры окислительного стресса и воспале-ния у здоровых детей в возрасте от 3 до 14 мес.…”