“Gluten intolerance” can actually be subclinical celiac disease

glutenintolerant

I think most of us have met people who have symptoms of celiac disease, but when tested, are told that their celiac antibody blood tests and biopsy results are negative (normal). Some of these people are labeled “gluten intolerant” or “gluten sensitive” by their doctors, others are told they may have “early” celiac disease, or “pre” celiac disease, and the rest are told that they have nothing wrong and are often advised to continue to eat gluten.  Many continue to eat gluten and find themselves getting sicker and sicker, with an improvement or disappearance of symptoms when they go gluten-free.  Then, when they go gluten-free, since they are “gluten intolerant” as opposed to having celiac disease, it is unclear how closely they need to be followed for vitamin deficiencies, the development of additional autoimmune disorders, and other problems that are associated with long-standing celiac disease.

Whenever I hear that a person is “gluten intolerant” I wonder whether or not the diagnosis of celiac disease was actually missed.  Celiac blood antibody testing can be unreliable in infants and toddlers, people who have a condition called serum IgA deficiency (occurs in up to 3% of celiacs), and when patients are tested after they have already started on the gluten-free diet. Likewise, endoscopies and biopsies are often done incorrectly (see link) which can lead to celiac-induced intestinal damage being missed.

I recently read, with much interest, an article called, “Intestinal-mucosa anti-transglutaminase antibody assays to test for genetic gluten intolerance,” which was published this month by a group of celiac researchers in Italy. Although it’s a bit technical, I will do my best to summarize it for you.

In this study, the gluten-intolerant subjects consisted of 78 pediatric patients who had symptoms of celiac disease but normal celiac antibodies (anti-TTG, also called TTG IgA) and normal small bowel biopsies.  None of the subjects were IgA deficient. Of the 78 gluten intolerant subjects, 12 were found to have anti-TTG antibodies present in the tissue biopsies from their intestines–to clarify, anti-TTG antibodies were found in their intestines, but not in their blood. 3 of the 12 patients in this “gluten intolerant” group, with TTG antibodies localized to the intestine only, were started on a GFD diet and they all had improvement in symptoms and anemia after 24 months on the gluten-free diet. Of the 9 patients with anti-TTG antibodies in the intestines who were continued on a gluten-containing diet, 2 of the 12 had celiac disease at 24 month follow-up. The remaining 7 “gluten intolerant” subjects who remained on gluten-containing diets appeared to have an improvement in symptoms at the 24 month mark, but it is unclear if this reflected a period of remission v. a true resolution of the intestinal antibody response, as there has been no long term follow-up, and as far as I can tell, biopsies were not repeated.

Although this study has a very small sample size, it demonstrates that there are some “gluten intolerant” patients who actually have subclinical celiac disease. In these cases, the celiac immune response is contained to the intestines only and villous atrophy (the hallmark of celiac disease) has not yet occurred. It appears that these individuals benefit from treatment with the gluten free diet.

I am curious to see if the long-term follow-up of the remaining 7 gluten intolerant subjects will be published in the future, and if some of them will also go on the develop celiac disease. I am also curious to see if celiac antibody testing of intestinal biopsy specimens will eventually become part of the standard of care in the clinical investigation of celiac disease.

Reference:

Quaglia, S, De Leo, L, Ziberna, F, et al. Intestinal-mucosa anti-transglutaminase antibody assays to test for genetic gluten intolerance. Cellular and Molecular Immunology advance online publication, 28 April 2014; doi:10.1038/cmi.2014.32.

11 thoughts on ““Gluten intolerance” can actually be subclinical celiac disease

  1. Melissa pippin

    Great article! I was positive on one antibody test and went gf immediately after testing. I did not have a biopsy so I’m not taken seriously by doctors. I decided to go back on gluten after being off of it for a year so my doctor could get a positive biopsy. I couldn’t complete the challenge and was only able to eat gluten for about 2 weeks, eating only small amounts. My biopsy was negative so my doctor gave me a diagnosis of ibs and said celiac was ruled out. I didn’t listen and went gf again, I also went grain free. After 3 months on this new diet (paleo) I’m symptom free. I’m glad I listened to my gut. My homeopath believes I’m “early celiac”. I really enjoy your blog!

    1. Jess Post author

      Hi Melissa,
      It’s great to hear that you have trusted your instincts and remained off of gluten. As I’ve gotten to know more and more people with both celiac disease and non-celiac gluten sensitivity through this page, I am amazed by how much more severe of gluten reactions that some “gluten sensitives” have than those with celiac disease.
      The final common pathway is the same…our bodies hate gluten and we need to avoid it. We are lucky that we’ve figured it out!
      I hope you continue to feel healthy and strong!
      Jess

  2. Ross

    Hi Jess,

    Truthfully, I don’t believe it is absolutely necessary having the tests or biopsies for justifying diet/lifestyle changes that improve our health. Yes, it would be nice if there was truly accurate information that explains just how tolerant or intolerant is the human body to gluten. Something tells me that gluten is a general “no no” for the general population. However, we are a “scientific” culture and we don’t trust supositions or blanket statements and it seems that most people would prefer being inflamed or obese than trust someone without well backed-up information telling them that they should stop “partying”…

    That said, Margarita and I have returned home from our intense work with our coffee bar in possibly the most important state fair in Latin America (San Marcos)… 23 days straight of working from 8am until as late as 4am. We are now 2.5 months gluten-free and basically simple carbs-free. One month without 45-60 minute run walks. And we both continued losing weight/inflamation. In two months we’ve both lost 22.5 pounds/10kgs. I must point out one thing: in the past, the horrible sleeping and the super exhaustion caused what I call “Lack of Sleep Hang-over” and I always ended up with what seems like Peripheral Neuropathy from my right shoulder to my fingers and what seems like a form of Tunnel Syndrome. This time around, although we sold the most coffee we’ve sold per day in our history, meaning that I had a ton more work with the Frappe Machines (lifting 3 liter jugs of frappe or coffee with milk for filling the frappe machines hundreds of times per day and placing up to seven 21 liter boxes filled with sweetened black coffee for cooling for the Frappe machines), I didn’t experience any neuropathy, tunnel or arthritis symptoms. Plus, I didn’t experience the typical exhaustion and sense of Sleep Hang-over, mental fogginess. Margarita claims that she also didn’t experience the typical exhaustion or mental fogginess etc… Truthfully, I attribute this to the cross the board withdrawal of simple carbs. However, Margarita mentioned that she believes that removal of gluten removed her lactose intolerance when drinking coffee with milk and she didn’t experience the strange pain (needle prick sensation) in her knees or her ankles… 4 years ago she had developed severe pain in those regions accompanied with strange blemishes and strange bumps. She visited with various doctors and had various blood tests taken. However, nothing came back positive, not for Lupus, not for Rheumatism or for Cellulite (I don’t know if that is the translation from Spanish to English)… I did a bunch of research and came to the conclusion that it was a “warning” of what may come if she isn’t more “careful”; that she would develop Rheumatism in her legs and must remove wheat, dairy and red meat from her diet. However, she didn’t take the idea serious (since it is incredibly difficult to change one’s customs, tendencies, lifestyles, especially if not accompanied with a diagnosis).

    I hope you are doing well and am glad that I can continue relying on your blog for informing myself on what is truly most important for us.

    Ross

  3. Ross

    Oh. I forgot to mention that before the fair started I was greatly concerned about how I would prepare and sell Frappuccinos I couldn’t drink. But, when we began selling, I noticed within myself a general indifference towards the frappes. At the same time I stumbled across a recent report by the American Heart Association mentioning the general upper limit for sugar consumption for children, adult men and adult women. Actually, I was looking for the amount of grams of sugar in a teaspoon… What shocked me was that the AMA said that children shouldn’t consume more than 3 grams of sugar per day, women; the maximum of 20 grams or 5 teaspoons and men; somewhere around 38grams or 9.5 teaspoons… So, I decided to ask people, “who should consume more sugar; a child, a woman or a man?” Would you believe that EVERYONE responded, “clearly the children; they need more sugar because they expend more energy.” However, we all concluded that healthy children naturally generate energy from the food they ingest and don’t need assistance. With this idea offered by the American Heart Association, I decided to calculate the sugar content of our Frappuccinos. What I named “The Supreme”, which is 16ozs comprised of Coffee Frappe, Caramel, Chocolate Syrup, Ground Nuts, whipped cream and a Maraschino Cherry gives you 90 grams of sugar! If I am correct, the typical Moka Frappuccino offers somewhere between 60 and 70grams… Fortunately I didn’t drink one cup during the 23 days. Imagine; 90 grams of sugar, how many plates of rice, how many slices of branola bread that have minimally 2.5 grams of sugar per slice… corn tortillas, flour tortillas, 1-2 regular coffees or cappuccinos with at least 3 tsps (12 grams) of sugar, an occasional celebratory pie or cake from Costco, an occasional pizza from Costco… Heinz Ketchup has 1 gram of sugar for every gram of ketchup in the bottle; 100 % sugar. Fortunately I wasn’t a soda drinker two months ago. However, in the fairs how many grams of Sugar was I placing in my body per day? Mexicans drink minimally 3 times the amount of Coca Cola/Pepsi Co products than do “Americans”… So, how many grams of sugar is that person ingesting per day who regularly bought a 16 oz Frappuccino from us and who traditionally accompanies his/her lunch and dinner with a 20.3oz bottle of Soda and follows lunch or dinner with Hostess cakes or pies or traditional Mexican pastries?

    I so badly wanted to talk about the Diabetes epidemic here in Mexico (to my customers) while observing the parade of obesity passing infront of our stand and while measuring the sugar contents of what we sell and don’t eat. But, Margarita repeatedly told me to take my ideas and conversation to another side of our world, since the sale of what people want to put in their bodies is what pays our lifestyle and ability for me to do the research and for us to eat healthier and exercise freely as we do.

    Ross

    1. Jess Post author

      Hi Ross,
      It is really nice to hear from you and that your business has been successful.
      And that you and Margarita are feeling so much better with all of your lifestyle changes.
      About 9 out 10 people who I suggest the GF diet to look at me like I am crazy. I constantly encounter people with IBS, other autoimmune sysmptoms, arthritis, unexplained anema, fatigue and headaches, etc. who have no motivation to change their diet or lifestyles.
      You are fortunate that you did and have become a great example of the power of lifestyle changes.
      As an MD I consider it my duty to continue to recommend that people get screened for celiac disease before going GF, but I can understand your point of view as well.
      Also, the information on the sugar content of the coffee drinks is both eye opening and horrifying. Wow! It makes me happy that I am unable to drink Frappacinos at all.
      I wish you and your wife continued health and peace.
      Jess

  4. Matt

    Hi Jess,

    I am also an MD and just recently came to realize that my GERD symptoms were caused by gluten and dairy (casein). I have had a long history of IBS type symptoms that I have never been evaluated for. My wife blamed my symptoms on a racoon living in my colon =]. I just brushed them off. Finally, my heartburn was so bad PPI BID dosing combined with h2 blockers wasn’t cutting it. I decided to see a GI doc and he performed an EGD on me which showed mild to moderate inflammation of the esophagus and stomach. Only mild hiatal hernia was noted. This made me think that the pathophysiology of my disease process was not quite adding up to simple GERD. I decided to try a gluten free diet and I went from 4-6 pills a day for my heartburn to only one.

    Two weeks later I asked a physician friend of mine to order me a celiac panel and it turned out normal. This prompted me to attribute my improvement to other things and I went back on gluten. My symptoms returned with a vengeance. It was at that point I knew I was either a) celiac or b) gluten intolerant. I will not seek out an official diagnosis because of how uncomfortable it is when I make even slight mistakes and ingest gluten. Hopefully, my anecdote is helpful to someone!

    Thanks,
    Matt

    1. Jess Post author

      Hi Matt,
      Thanks so much for taking the time to comment. You are the 5th or 6th MD who I’ve “met” through here who has serious gluten issues. I would personally never be able to withstand a gluten challenge at this point, as my body reacts to the tiniest traces of gluten.
      I have a dear family member with very severe acid reflux who has refused testing for celiac (despite having a 1st degree relative with the disorder). Perhaps she will see your comment and decide to finally be tested?
      I really appreciate your willingness to share your experience.
      Jess

  5. Ashton Lee

    We are getting darn close to recognizing that Dr Fine’s Entero Lab (stool testing) results are measuring the right things. He measures TTG in the stool.

    1. Jess Post author

      Hi Ashton,
      Yes, I agree with you. I am actually probably going to go this route with my daughter who just tested negative for celiac disease but still seems to have gluten issues. If she has TTG antibodies in her stool I think my husband will be more on board with making her 100% GF (right now all my kids are GF in my home but eat gluten outside of the home). I’ll probably write a future blog post about it, but if not I’ll comment back to you on here. Hope you’re doing well!
      Jess

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