There’s a lot of controversy surrounding the idea of non-celiac gluten sensitivity (NCGS), with some people firmly on the side of it being a legitimate health issue and others insisting that gluten sensitivity doesn’t exist and people claiming to have NCGS are mistaking their symptoms for other food sensitivities or intolerances. Following the evidence, my opinion falls somewhere in the middle. Fortunately research is ongoing.

It’s easy to see why gluten is blamed for the digestive and inflammatory symptoms commonly attributed to NCGS since celiac disease results from an autoimmune reaction to gliadin, a gluten protein found in barley, rye, and wheat, that causes inflammation and extensive damage to the mucosal lining of the GI tract. Approximately 1% of the US population has celiac disease, with up to 95% of them undiagnosed. Symptoms of celiac disease may include abdominal pain, anemia, anxiety attacks, bloating, bone and joint pain, bruising, depression, dermatitis herpetiformis, diarrhea, edema, fatigue, fat malabsorption, flatulence, infertility, malnutrition, mouth sores, muscle pain and cramps, muscle wasting, nausea, neuropathy, nose bleeds, and vomiting. In comparison, reported symptoms of NCGS include anemia, acne, bloating, brain fog, depression, diarrhea, fatigue, irritability, joint inflammation, migraines, mood changes, nausea, muscle aches and pain, and vertigo. The primary question is: does gluten cause the symptoms associated with NCGS or is it something else?

Currently studies suggest that gluten is not the main factor behind the symptoms associated with NCGS in the majority of people, even though patients self-report improved health once eliminating gluten containing foods. One possible cause of the GI symptoms are amylase trypsin inhibitors (ATIs), which are tightly bound to gluten proteins and comprise up to 4% of the protein content in wheat; ATIs are resistant to enzymic breakdown in the human GI tract.1,2 Studies show that ATIs can activate innate immune responses within the GI tract as well as outside it, worsening systemic inflammation in immune-related inflammatory diseases besides inflammatory bowel diseases (IBDs) such as lupus and MS.1,2 ATIs are thought to be one of the factors responsible for the development of celiac disease along with gluten.1,2 ATIs are only found in wheat.

One small study on people with reported non-celiac wheat sensitivity (NCWS) who did not have celiac disease or an IgE mediated wheat allergy found several biomarkers associated with innate immune activation and minor intestinal cell damage that resolved once wheat was removed from participants’ diets.3 The study authors concluded that defects in the GI barrier caused the immune response to wheat, but could not conclude that wheat caused the intestinal permeability nor if resolving the intestinal permeability would eliminate the immune response to wheat.3 This study did not look at gluten or ATIs specifically, only the biomarker changes between consuming wheat and eliminating wheat.

Other possible causes of symptoms attributed to NCGS are dairy proteins like whey or casein and/or FODMAPs (fermentable short-chain sugar and sugar alcohol polymers) found in a wide variety of foods including the gluten containing grains wheat, rye, and barley. Dairy protein intolerance, which is not the same as lactose intolerance, includes symptoms such as abdominal pain, bloating, cognitive dysfunction, constipation, diarrhea, flatulance, inflammation, and nausea. FODMAP sensitivity is caused by an imbalance of GI microbes, called gut dysbiosis, which can increase the microbial fermentation of foods containing high amounts of FODMAPs in the GI tract causing symptoms which include abdominal pain, bloating, diarrhea, and flatulance. FODMAP sensitivitity is often mistaken for inflammatory bowel syndrome (IBS). Several small RCTs in people with self-reported NCGS found that gluten was the least reactive substance whereas dairy proteins and FODMAPs were the most reactive.4,5

My conclusion is that the symptoms associated with NCGS are real, but the cause is unlikely to be gluten proteins alone. It’s important to rule out other causes of food related GI distress and inflammation including ATIs, intestinal permeability, dairy protein intolerance or allergy, and FODMAPs before self-proclaiming that you have a gluten sensitivitity. This can be done with food elimination diets with reintroduction challenges, including separate challenges for wheat products and other gluten containing grains like barley and rye. Such elimination diets should be supervised by knowledgable healthcare providers or nutritionists.

1. Schuppan D, Pickert G, Ashfaq-Khan M, Zevallos V. Non-celiac wheat sensitivity: differential diagnosis, triggers and implications. Best Pract Res Clin Gastroenterol. 2015; 29(3): 469-476. doi: 10.1016/j.bpg.2015.04.002.
2. Schuppan D, Zevallos V. Wheat amylase trypsin inhibitors as nutritional activators of innate immunity. Dig Dis. 2015; 33(2): 260-263. doi: 10.1159/000371476.
3. Uhde M, Ajamian M, Caio G, De Girorgio R, Indart A, Green PH, et al. Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Gut. 2016; 65: 1930-1937. doi: 10.1136/gutjnl-2016-311964.
4. Skodje GI, Sarna VK, Minelle IH, Rolfsen KL, Muir JG, Gibson PR, et al. Fructan, Rather Than Gluten, Induces Symptoms in Patients With Self-reported Non-celiac Gluten Sensitivity. Gastroenterol. 2017; e-pub. doi: 10.1053/j.gastro.2017.10.040
5. Biesiekierski JR, Peters SL, Newnham ED, Rosella O, Muir JG, Gibson PR. No Effects of Gluten in Patients With Self-Reported Non-Celiac Gluten Sensitivity After Dietary Reduction of Fermentable, Poorly Absorbed, Short-Chain Carbohydrates. Gastroenterol. 2013; 145(2): 320-328.e3. doi: 10.1053/j.gastro.2013.04.051.

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