False Alarm Hypothesis of Food Allergy

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

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

Mechanisms of food allergy

Some of the most common hypotheses for food allergy include:

  • 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. It 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 also play 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 allergy 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 egg and peanut. Thus sunlight exposure needs to be adequate to prevent allergy development.

  • 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 allergy.

Innate and adaptive immunity

Overall, food allergies mediated by 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 very much 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, or by recognition of certain pathogen-linked molecular patterns, and which leads to T cell activation and proliferation.

HMGB1, as well as other alarmins, bind to immunoglobulin called receptor for advanced glycated end-products (RAGE) and other receptors such as Toll-like receptors (TLR) 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.

The important point is that dendritic cells are critical in starting off immunologic responses. When RAGE activates these cells, therefore, the individual is prone to become sensitized to allergens which are 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 and not 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 allergy. Too much uric acid can thus facilitate food allergies via 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 allergy in such households. This pattern changes towards more healthy eating, however, in the richest families.

Reviewed by Yolanda Smith, BPharm, and Chloe Barnett, BSc

References

  1. http://www.sciencedirect.com/science/article/pii/S0091674916306182
  2. https://www.ncbi.nlm.nih.gov/pubmed/26377870
  3. http://lifeinthefastlane.com/false-alarmin-missing-link-rise-food-allergies/

Further Reading

Last Updated: May 12, 2017

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