False Alarm Hypothesis of Food Allergy

Food allergies are an increasing trend over the past several decades or so, uniquely in countries on a Westernized diet. These conditions are not only potentially serious in themselves but often pave the way for other chronic disorders, more specifically allergic asthma, conjunctivitis, and rhinitis.

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Mechanisms of a food allergy

There are many hypotheses that try to explain the underlying mechanism that causes an individual to develop a food allergy. Current examples include the hygiene hypothesis, the timing of food introduction, low vitamin D levels, and other factors.

However, these theories do not fully explain the increase in food allergies over the past few decades. Comparatively, the false alarm food allergy theory introduces the association of the westernized diet and increase in food allergies.

The hygiene hypothesis

Animal studies show that rearing animals from birth in highly sterile environments results in the development of allergies, characterized by Th2 domination and anaphylactic reactions.

The hygiene hypothesis puts emphasis on the influence of the type and diversity of human microbiota, with the timing of exposure to these antigens. This theory is strengthened by the observation that probiotics and prebiotics reduce the incidence of these conditions. Another piece of supporting evidence is the reduction in severe infections concomitant with the increase in allergies and autoimmune disease.

The timing of food introduction

The time when complementary foods are introduced to children also plays a role in the development of tolerance. For this reason, the introduction of peanuts in infancy is now being recommended to reduce the incidence of peanut allergies in children at high risk.

Low vitamin D levels

Infants with low levels of cholecalciferol seem to have a higher risk of allergies to some foods, especially eggs and peanuts. Thus, adequate sunlight exposure is crucial to preventing the development of allergies.

Other factors

The use of antibiotics, antacids, and the diversity of fatty acids and other food components in the diet are also important contributors to food allergies.

Innate and adaptive immunity

Overall, food allergies mediated by immunoglobulin E (IgE) may be considered a defective form of adaptation to a non-noxious, and in fact, beneficial substance, so that the body mounts a learned immunologic reaction against it in an inappropriate manner.

However, innate immunity is also closely concerned with allergies, including lymphoid cells and mucosal or epithelial barriers, to microbial penetration into the body. The innate immune system is therefore responsible for guiding the development of adaptive immunity.

The role of alarmins

Alarmins are chemicals that are released from dying cells and help warn of danger and attract immune cells to the site to fight the threat. One such important alarmin is the high mobility group box 1 (HMGB1), which is secreted by activated dendritic cells in the presence of inflammation. HMGB1 can also be released following the recognition of certain pathogen-linked molecular patterns, which leads to T cell activation and proliferation.

HMGB1, as well as other alarmins, bind to Igs called receptor for advanced glycated end-products (RAGE) and other receptors such as Toll-like receptors (TLRs) to initiate further immunologic and inflammatory reactions. TLR-4 acts as an agonist, together with HMGB1, to enhance the allergic response.

The binding-induced RAGE activation promotes inflammatory and allergic changes, including airway hypersensitivity and asthma. However, advanced glycation end-products (AGE) also activate RAGE.

Unfortunately, diabetes encourages the glycation of many proteins in the body. AGE is also contributed by the typical Western diet, which features animal fats and proteins cooked at high temperatures, enabling the glycation of exposed amino acids by breaking the peptide structure. This is the Maillard reaction, and it is important in making foods crisp or browned. AGE is also abundant in microwave-cooked foods.

Additionally, dendritic cells are critical in starting off immunologic responses. When RAGE activates these cells, the individual is prone to become sensitized to allergens that are otherwise innocuous. Thus, RAGE binding by HMGB1, S100, and other similar ligands, set off recruitment of other cytokines. When the RAGE is on a T or B cell, the resulting sequence of events usually results in generalized immunologic responses, rather than a specific response to an AGE.

AGE and the Western diet

The relation between AGE, allergies, and the Western diet is a question that awaits a definitive reply. However, it is true that fructose is metabolized to a significant amount of uric acid, which imparts sensitivity to inhaled allergens and potentiates Th2 responses during an allergic reaction. An excess of uric acid can thus facilitate food allergies through the activation of dendritic cells.

Food rich in AGE includes sugars, microwaved food, food sterilized by autoclaving, highly processed food, barbecued or roasted meat, and desserts. These are more commonly consumed in affluent families, which is consistent with the higher incidence of food allergies in these households. This pattern changes towards more healthy eating, however, in the richest families.


Further Reading

Last Updated: Apr 24, 2021

Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.


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