Wheat Toxicity: A Quick Update

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Wheat Amylase Trypsin Inhibitors (ATIs)

Although much of the research on wheat revolves around the role of gluten as a causative agent in coeliac disease, there is an important parallel branch of enquiry studying other proteins in wheat that contribute to its overall toxicity. Among these, a class of compounds called amylase trypsin inhibitors (ATIs) have been found to activate the innate immune system leading to intestinal inflammation. The first paper on this subject appeared in 2012 [ref], and had a major impact in explaining how wheat could cause disease amongst non-coeliacs. Since then there has been a steady stream of research uncovering additional effects of these noxious compounds. This research is important because ATIs have the potential to affect anyone eating wheat, rye, barley or oats, not just coeliacs.

If you want more details about ATIs then click below…

What are ATIs and what do they do? A brief overview…

Amylase Trypsin inhibitors (ATIs) can be found in all gluten containing grains (wheat, barley, rye), and represent 2–4% of the total protein. In plants, ATIs regulate the germination processes and defense mechanisms by blocking the amylase and trypsin activity of parasites. The wheat intake of an adult person is about 250 g per day, mainly as processed bread or pasta which is equivalent to 0.5–1 g ATI. Remarkably, ATIs are resistant to cooking and other food processing, as well as to digestive enzymes in the gastrointestinal tract where they stay biologically active. In the gut ATIs are able to stimulate immune cells residing in the intestinal basement membrane and lymph nodes through TLR4 binding and stimulation, and the emigration of the activated myeloid cells. [Adapted from Kira Ziegler et al, 2019]


1. Wheat ATIs increases metabolic syndrome and non-alcoholic fatty liver disease

2018.05.29 Low Carbohydrate Meetup, Washington, DC USA 438
Wheat is now implicated as a contributory agent to the increasing levels of NAFLD

In a recent mouse study it has been found that ATIs in wheat worsen obesity when mice are fed an obesogenic diet. Groups of mice were fed an obesogenic diet either with or without wheat ATIs. While both groups gained weight and became obese, the mice that had the added wheat ATIs showed increased visceral and liver fat, and a higher insulin resistance. ATI feeding promoted liver and adipose tissue inflammation, with macrophage infiltration, and enhanced liver fibrogenesis. The researchers identified that wheat gluten did not cause these changes, only the wheat ATIs.

The authors stated:

“wheat ATI ingestion in minute quantities comparable to human daily wheat consumption exacerbated features of the metabolic syndrome and non-alcoholic steatohepatitis, despite its irrelevant caloric value.”

Muhammad Ashfaq-Khan et al, 2019

2. ATIs increase allergic airway inflammation and may contribute to asthma

ATIs in wheat have been shown to increase inflammation of the airways. (Source: Wikimedia CC BY-SA 3.0)

Two studies have found that ATIs increase the inflammatory response of the airways during an allergic challenge. In one study the presence of ATIs in the diet increased multiple inflammatory markers in the airways of study mice when exposed to air-born allergens. [Victor F Zevallos et al 2019]

In another study ‘humanised’ mice sensitized to grass or birch pollen showed strongly increased allergic response (IgE reactivity) to allergens if they had been fed a diet containing wheat ATIs, but not when fed maize. [Iris Bellinghausen et al, 2019]

These studies suggest that wheat may be contributing to the prevalence and severity of asthma, hay fever and related allergic respiratory conditions.

3. ATIs increase gut permeability and inflammation; and in susceptible individuals enhances gluten toxicity

It now appears that wheat ATIs as well as gluten can increase gut permeability

A study in mice has found that ATIs increased gut inflammation and permeability in healthy mice. The researchers also found that ATIs increased the inflammatory effects of gluten in mice with the gluten-susceptibility genes (HLA-DQ8). [Alberto Caminero et al, 2019]

Although it was previously known that ATIs contribute to intestinal inflammation, this study shows that wheat ATIs increase gut permeability too, which suggests they may contribute to the development of autoimmune diseases other than coeliac disease as a leaky gut is thought to be one of the prerequisites for triggering aberrant immune responses.

In relation to autoimmune diseases and leaky gut, a recent Danish study found that patients with autoimmune diseases had a much higher rate of food intolerance, leading the author to recommend that:

a food intolerance test is a very important tool in patients with AI disease, and should be performed in each patient to tailor an individual diet program, which if properly followed, could relieve symptoms and probably stop or slow the the progression of the autoimmune disease.

Coucke, Autoimmune Review, 2018

I can confirm that this approach works in practice, as this is exactly the kind of testing I offer in my clinic, and for many of my patients the information we get back is life changing and really empowering as they can effectively treat their condition simply by avoiding the foods they react to, once we know what they are. My years of clinical experience in recognising subtle signs wmean that I am frequently able to identify culprit foods without needing private lab tests, but they can be invaluable in some cases. If you think food reactivity testing could help you, please feel free to give me a call:

Food Reactivity Lab Testing

If you suffer from an autoimmune disease or have food-related health issues, please contact me for a free 10 minute discussion about the lab tests that may help you.

call today: 01243 868108

Learn More About the Health Effects of Gluten and Grains

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