New Research on Non-Celiac Gluten Sensitivity

NCGSWordle Non-celiac gluten sensitivity (NCGS) is a poorly understood disorder in which gluten and other wheat proteins cause a variety of both intestinal and other symptoms when eaten by affected individuals. The symptoms improve, sometimes dramatically, when people with NCGS go on a gluten-free diet. However, unlike celiac disease, NCGS does not cause actual intestinal damage, so that intestinal biopsies are not useful in making the diagnosis. The diagnosis can only be made by ruling out celiac disease and wheat allergy, and seeing if the symptoms improve off gluten.

Recent studies have revealed information about NCGS. There does seem to involvement of the immune system in at least some people with the disorder, although it is different than what happens in celiac disease. Researchers have discovered that perhaps as many as 40% to 50% of people with NCGS do make antibodies to the pieces of gluten called gliadins. However, these are usually IgG antibodies. A much smaller number, estimated by some researchers as about 8%, make IgA antibodies against gliadin.

Anti-gliadin antibodies (AGA) used to be measured to screen for celiac disease, but they are not specific or sensitive enough and are no longer used for screening. This may be one reason why there were false positives using this screening – people with NCGS were actually being discovered. People with celiac disease can make both IgG and IgA antibodies to gliadin, like people with NCGS, but the presence of the antibodies does not reflect disease activity.

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To understand these tests, it is important to know a little bit about how and why antibodies, also called immunoglobulins, are made. Different types of immunoglobulins are made in different parts of the body because of different kinds of perceived threats.

“NCGS does not cause actual intestinal damage, so that intestinal biopsies are not useful in making the diagnosis”

IgG antibodies are usually made as the body responds to an infection spread through the respiratory tract, or in response to vaccines. Measuring IgG can indicate whether or not a person has had a particular illness or been vaccinated for it. For example, women are tested for IgG against rubella (German measles) to see if they are at risk for catching the disease during pregnancy, which is dangerous to the developing fetus.

In allergic individuals, the body makes antibodies called IgE in response to substances called allergens. IgE levels to allergens, including certain foods, plant pollen, and pet saliva and dander, among others, can be measured. People who are allergic to wheat make IgE. stomachPains

IgA antibodies are made by cells in the intestine in response to a threat that has been ingested, for example, a virus that is spread person-to-person by mouth and through the gastrointestinal tract. They are made by people with celiac disease in response to gliadins, but more importantly for diagnosis, to specific substances that are part of the process leading to intestinal damage. The two measured most frequently now to screen for celiac disease are IgA anti-tissue transglutaminase and IgA anti-endomysial antibodies. IgG is only measured if a person does not make IgA, which occurs in about 5% of people with celiac disease, making their diagnosis a bit more difficult.

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In a person with symptoms that occur after eating gluten-containing food, the presence of the IgG antibodies to gliadin is one piece of information that can help make the diagnosis of NCGS, although as already indicated, it is also a diagnosis of exclusion where both celiac disease and wheat allergy must be eliminated.

A recent study explored the role of IgG antibodies in NCGS. In those who have them, the levels change based on gluten exposure. They can be monitored as a way to check whether or not a person is really eating a gluten-free diet. They drop significantly in those who stay on a gluten-free diet and have significant symptomatic improvement. This can be contrasted with the reaction of people diagnosed with celiac disease. Antigliadin antibodies in CD patients do not drop with a gluten-free diet and do not correlate with symptomatic improvement.

“People with celiac disease & NCGS can make both antibodies to gliadin, but the presence of the antibodies does not reflect disease activity”

The small study which yielded this information looked at 44 patients with NCGS all of whom had IgG antigliadin antibodies. After six months, these antibodies disappeared in all 39 patients whose symptoms improved on a gluten-free diet. 3 of the 5 patients who had limited improvement on the diet continued to have the antibodies. 3 people said they did not strictly follow the diet, and 2 of these 3 still had the IgG antigliadin antibodies. On the other hand, the antibodies disappeared in 40 of the 41 who followed the diet.

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40 people with confirmed celiac disease who were otherwise similar had the same tests measured as they started on a gluten-free diet. They all had IgG AGA before starting the diet. In this group there was no correlation between IgG to gliadin and staying on the diet or symptomatic improvement. 30% to 45% of the people with celiac disease still had the IgG antibodies regardless of symptoms or how well they stayed on the gluten-free diet.

On the other hand, in celiac patients, persistence of IgA against gliadin was correlated with less improvement in symptoms and lack of adherence to the diet. There were 30 who started out with IgA AGA. 4 of these patients still had the antibodies, and they had continued symptoms as well as admitting to not staying on a strict gluten-free diet.

The two main things learned from this study were that there is evidence of an immune response to gluten in at least some people with NCGS, and that a gluten-free diet both quiets the response in this group and improves symptoms. Further research is needed to see if these results are confirmed in a larger group of people. The immune response may be one way to evaluate both NCGS and patients’ responses to a gluten-free diet.

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Caio et al. Effect of gluten free diet on immune response to gliadin in patients with non-celiac gluten sensitivity. BMC Gastroenterology 2014, 14:26.


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  1. I had IBS for years. It got worse in later years. Heard Bill O’reilly on Fox about him being Gluten free. Bought the book “Wheat Belly” and now have been IBS free for over two years. I am so grateful.

  2. I started GF diet in January this year. Now spring is over, I didn’t have seasonal asthma this year that had bothered me every year in the spring season. Thank God, gluten_free diet helps.

  3. I have never been tested for celiac, but I did test positive to week allergy years ago, thought I had developed the immunities but it’s back. Seemingly worse so I have been eliminating both wheat and gluten, I also have to avoid soy, so I like to frequent the gluten free folks because I know in the process I will be eliminating the wheat altogether and it is so nice to be dealing with days of diarrhea and cramps, and the upset stomach that feels like it would be better to throw up. Thanks for the web site and the info on NCGS.

  4. Angie: I’m so grateful to you for your posts. At times I get tricked, by myself usually. Last night looking for a place to safely eat out, I ordered falafels from a Greek restaurant & as soon as I cut into one, I KNEW! Bread crumbs were used. I’d eaten clean, thought I’d ordered clean. Avoiding gluten just takes extra thought. Mostly good cooking skills because true gluten free restaurants are just publicizing to get customers & still cross contaminate. Thank God I’m intolerant & not celiac. Still … A challenge to be sure & your providing recent reports is extremely useful. Our brains are at risk! Can you imagine how I felt when that might bulb went on? Yes! I can make a difference in my life. And I will, especially with such great people like you. Thank you so much.

  5. Thanks so much for your kind words! We try hard to provide our members with the most current up to date research and information that’s out there, and of course great tasting recipes that don’t taste ‘gluten free’!

  6. I acquired Gluten Intolerance thanks to a blood transfusion due to hemorrhaging 15 days afer a lapro-hysterectomy. Now I start to go into Anaphylaxis when exposed or ingest gluten. Some doctors are still uneducated as to this hard to believe! My allergist knew of it and has a bone marrow receipient that acquired allergies from his known donor. Being in the nursing field I am so shocked that this testing is ignored during blood donation as this can kill patienrs

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