Why Don’t I Feel Great on a Gluten-Free Diet: Sensitivity or Cross-Reactivity?

Celiac.com 02/15/2019 - Answer this question honestly for yourself. Not for me, or for anyone else, answer this question honestly for yourself.

On a scale from 1 to 10, if 10 is the amount of energy you should have in life, and 5 is half as much… now, hold on a minute, one more thing, take your will power out of the equation… what’s your body energy? If you weren’t pushing yourself, motivating yourself to continue on, what is the level of energy your body is operating on? On a 1-10 scale?

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Most of us have a number we come up with right away as the first part of the question is being asked: “Oh, I’m an eight or a nine”. But when I ask patients to take their will power out of the equation, many will have a look come across their face, almost like a balloon being deflated a little, and they’ll say “three” or “five”. Rarely do I have someone who answers eight or above. Where is this fatigue coming from? Many clinicians will tell you one of the most common symptoms of food allergies and food sensitivities is fatigue.

Although the majority of individuals with gluten sensitivity and/or celiac disease experience substantial improvement within the first few weeks of gluten withdrawal, between 7% and 30% continue to have symptoms or clinical manifestations suggestive of celiac disease despite being on a gluten-free diet(1). That’s called non-responsive celiac disease--the body is not responding the way it should.

Why is that?  And why is it that so many of us do not experience the amount of energy we should feel given that we’re being so careful to avoid exposure to gluten, a food that is toxic to us? We’ll look, in this article, at a common, hidden source of this lack of vitality and lack of response to a gluten-free diet.

Non-responsive celiac disease (NRCD) has been defined as: 
referral to a clinician specializing in celiac disease for the evaluation of a lack of response to a gluten-free diet, 
failure of clinical symptoms or laboratory abnormalities typical of celiac disease to improve within six months of gluten withdrawal, recurrence of symptoms and/or laboratory abnormalities typical of CD while on a gluten-free diet. 

In one study, 12 identified causes of NRCD, the most common cause was (inadvertent) gluten exposure, accounting for 36% of patients(2). OK, that’s understandable.

But what about the other 64% who did not have an inadvertent exposure to wheat or similar grains? What is the cause of their NRCD?  An all-too-common contributor to NRCD is sensitivity to other foods commonly consumed on a gluten-free diet causing a very similar inflammatory cascade in the intestines. Another contributor is cross-reactivity of antibodies against gluten with exposure to other foods. 

On a gluten-free diet, we may substitute other grains in much larger amounts than we may have eaten when we were on a gluten-containing diet. In some cases, this may initiate an immune response very similar to that caused by eating gluten.

Cross-reactivity is the ability of an antibody to bind to similar-looking parts on different proteins called epitopes. This phenomenon is also known as molecular mimicry. In such a case the immune system confuses one food for another. Therefore, certain foods appear, to the immune system, sufficiently similar to a reactive food to initiate an immune response.  

Patients with gluten sensitivity and celiac disease may be sensitized to a broad range of dietary proteins from different foods due to cross-reactivity.

Below is a drawing of what happens when the gliadin protein molecule from wheat (labeled #1) fits into the ‘docking station’ of a wheat antibody. It fits into all three locks of the docking station. This is termed a reactive antibody. And in gluten sensitive individuals, the immune system is activated to make more antibodies to fight this invader. As we all know, that is not a problem unless we eat the offending food so often that it overwhelms the body and begins causing a great deal of damage to the intestines and other tissues (pancakes for breakfast, sandwich for lunch, pasta for dinner, toast for breakfast, sandwich for lunch, croutons on the salad at a dinner, and maybe a cookie or piece of cake,..).

Next we see how some foods (such as casein from dairy) can bind to a gliadin antibody. It fits into two of the three ‘docking stations’ and that is enough to trigger an immune response as if this person was eating gluten. This will still trigger an immune response. That food is called a ‘cross-reactive’ food.

In the third drawing we see how other foods (such as rice) may bump into a gliadin antibody, but it only fits into one docking station, or no docking station and thus will not bind to it. This is similar to putting a round peg in a square hole - can’t do it. It is ignored by the gliadin antibody.

With wheat the estimated prevalence of a cross-reactivity with rye and barley is one out of five (20%) (3). Cross reaction with dairy in different studies varies from 50 to 91%(4,5).

Up to 82% of patients with celiac disease have antibodies to other foods including rice flour, milk, beef, sheep and egg(6). Other studies have identified cross-reactivity with chocolate(7),          sesame(8,9,10,11,12), hemp(13), rye(14), kamut(15,16), buckwheat (17,18,19,20,21,22,23,24,25), sorghum(26,27,28,29,30), millet(31,32,33,34), spelt(35,36,37,38), amaranth(39,40,41), quinoa(42,43,44), yeast(45,46,47,48,49), tapiocal(50,51,52,53), oats(54,55,56,57,58,59), coffee(60,61,62,63,64), corn(65,66,67), ricel(68,69,70,71,72), potato(73,74,75).

The response to some of these food allergens parallels the response to the gluten protein in wheat with increased IgA antibodies and might be relevant to the ongoing immune response of gluten sensitivity and celiac disease without eating gluten(76). Perhaps this is why as many as 40% of children on a well-managed gluten-free diet for at least 1 year still have elevated antibodies to gluten(77).

From the diagnostic and therapeutic point of view, it makes sense to define allergen clusters (cross-reactivity)(78). Determination of serum IgA and IgG antibody activities to dietary proteins appears to be a valuable adjunct in the diagnosis and follow-up of celiac disease, both in children and adults. Increased IgA activities to other dietary antigens are likewise relatively characteristic of untreated celiac disease; monitoring of such antibodies may be particularly helpful in evaluating the response of patients on a gluten free diet(79).
Foods that may create cross-reactivity with gluten include cow’s milk, casein, casomorphin, American cheese, chocolate, rye, barley, kamut, spelt, yeast, oats, and coffee. Common foods often included on a gluten-free diet that one may be sensitive to that could cause continued inflammation include  sesame, rice, corn, potato, hemp, buckwheat, sorghum, millet, amarath, quinoa, and tapioca.

This array of 24 different foods (some are possible sensitivities while others are possible cross-reactive foods) is available from CyrexLabs.com. Ask your Health Care Practitioner to look into this array.  You might want to consider that, when a gluten-free diet is not producing the results that you had hoped for, the cause may be another common food. If you are working so hard to be in control of the quality and the selection of the foods you eat, this concept of cross-reactivity may be a missing-link that will help you get closer to feeling great and answering that initial question “On a 1-10...” with a passing grade of 7 or higher.

Dr. Thomas O’Bryan is a nationally recognized speaker and workshop leader specializing in Gluten Sensitivity and Celiac Disease. He is the Sherlock Holmes for chronic disease and metabolic disorders.  He is a clinician par excellence in treating chronic disease and metabolic disorders from a Functional Medicine Perspective.  He holds teaching Faculty positions with the Institute for Functional Medicine and The National University of Life Sciences.  Dr. O’Bryan is always one of the most respected, highly-appreciated Speakers.  Dr. O’Bryan’s passion is in teaching the many manifestations of Gluten Sensitivity and Celiac Disease as they occur inside and outside of the intestines.  Dr. O’Bryan welcomes your questions about gluten sensitivity and/or functional medicine. Please send your questions and requests by email to www.theDr.com.

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