What You Need to Know: Gluten Intolerance

Celiac Disease vs. Gluten Sensitivity

Do you know the difference between celiac disease and gluten intolerance or its unofficial name – non-celiac gluten sensitivity (NCGS)?

Celiac disease exists in 1% of the population and is an autoimmune disease that causes an inflammatory immune response to the proteins in gluten (specifically the protein gliaden and the transglutiminase-2 enzyme in the gut). Celiac disease sufferers produce exaggerated levels of a protein called zonulin in response to gluten. Zonulin controls the tight junctions between enterocytes in the gut. 98% of all individuals diagnosed with celiac disease have one or two variants of the HLA gene DQ2 or DQ8. They also test positive for the blood marker transglutiminase 2 (TG2) autoantibody. Celiac disease means you’ve met strict medical criteria, and you have damage to your intestinal villi caused by an autoimmune reaction.

NCGS is a term that refers to individuals who experience symptoms to gluten products when ingested but lack most or all the markers for celiac disease. These are people who have GI problems, fatigue, joint pain, headaches, bloating, depression or other issues and notice a marked improvement when they remove gluten from their diet. Remember, proteins found in wheat, rye, barley, and triticale all fall under the gluten category. They are present in a variety of foods, primarily breads, cereals and pasta. Like most food sensitivities, symptoms can be wide-ranging and sometimes delayed. This makes it very difficult to pinpoint exactly what is causing the overall complaints. If you don’t get a stomachache right after eating but are constipated a few days later or feel fatigued, how can you know what caused it? These factors are one of they many reasons there is so much controversy over gluten intolerance.

This sensitivity has confused scientists who have been unable to draw conclusions on the underlying mechanisms of the disorder. In fact, the media and some doctors refuse to acknowledge that it is an actual problem, telling patients that it is “all in your head.” In a recent study published in the Journal Gut last year (1), scientists appear to have found a possible biological explanation for NCGS. The study involved 80 subjects with self-diagnosed NCGS, 40 subjects with celiac disease and 40 healthy individuals. The final conclusion? The NCGS individuals had increased intestinal permeability or leaky gut! They also had systemic immune activation, meaning they found higher levels of things in the blood that had “leaked” out of the gut into the bloodstream, which caused an inflammatory response.

NCGS subjects had higher lipopolysaccharide-binding protein (LBP) and sCD14 (a gene that encodes a protein in our innate immune system) levels than both control and celiac subjects. Lipopolysaccharide (LPS) is a bacterial endotoxin that can cause endotoxemia and lead to septic shock if the immune system is severely weakened. Our bodies send out LBP and sCD14 to regulate LPS toxicity, prevent systemic dispersal, and maintain a healthy inflammatory response. High levels of LBP and sCD14 indicate elevated systemic inflammation. NCGS subjects also had elevated bacterial endotoxin (LPS) antibodies. This suggests that LPS was making it into circulation, most likely through a compromised intestinal lining, which causes an inflammatory response.

NCGS subjects also had elevated flagellin antibodies. Flagellin is the main protein in Gram-negative and Gram-positive bacteria. Flagellin antibodies are most often elevated during infections involving those bacteria. Since NCGS subjects were not infected, a rise in flagellin antibodies could mean there was translocation of bacterial products from the gut into circulation, most likely from the increased intestinal permeability. This was not present in the celiac or healthy groups. These same individuals were reanalyzed after adhering to a gluten free diet; the analysis found that inflammation markers had improved significantly after six months of gluten avoidance.

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Wheat: It’s Not Just Gliaden

Did you know there are other proteins in wheat besides gliaden? These proteins can also cause an immune reaction. Just because someone tests negative for celiac disease does not mean they are not reacting to some of these other proteins. Here’s a quick biochemistry lesson (don’t worry, it will be quick!).

Wheat contains different classes of proteins. Gliadens and glutenins are the two main components of the wheat seed. Gliaden has four epitopes (an antigen that is recognized by the immune system). There are also other proteins, like glutenin. Wheat germ agglutinin (WGA), gluteomorphin and deamidated gliaden are other proteins that have to be broken down in the digestive tract by enzymes, and this digestion produces even more proteins, some of which may behave like morphine and other soporific opiates. These molecules may explain the lethargy exhibited after eating wheat by some people who do not have celiac disease.

Celiac disease is an immune reaction to just one of the gliadin epitopes (the alpha-gliaden) and a reaction to the transglutiminase-2 enzyme. But some people react to the other proteins, and there are also two other transglutiminase enzymes besides 2 (the celiac marker), called 3 and 6. Transglutiminase-2 is mostly expressed in the gut, and most celiac patients have GI issues. But transglutiminase-3 is found primarily in the skin and transglutiminase-6 in the brain and nervous system. Might people with eczema or depression be expressing their gluten intolerance in another way?

Testing Options for Gluten Sensitivity

Unfortunately, there is not a definitive diagnostic test for NCGS. While there are many tests on the market, none of these tests have been validated and they are therefore not accepted by the scientific community. Currently, biomarkers (a specific indicator of disease) for gluten sensitivity have not been identified, which means that gluten sensitivity remains a diagnosis of exclusion. That doesn’t mean you can’t get tested.

There are many skilled integrative doctors who use tests like an Array 3 panel from Cyrex laboratories. This tests for the antibodies against all the proteins mentioned above and can be used as a guide. Testing for the genes HLA-DQ2 and HLA-DQ8 may also be helpful, as 98% of celiacs have one or both of these genes; but around 55% of the general population who don’t have celiac disease still have a variant of one or both of these genes, which can cause higher zonulin production (the protein that responds to gluten and may increase intestinal permeability if exaggerated). (2)

Currently, though, the only way to confirm gluten sensitivity is through a process of elimination – by testing negative for celiac disease and an IgG wheat allergy, and then eliminating gluten under the supervision of a physician or nutritionist.

What can I do?

If you have had ongoing symptoms, you may want to get tested for celiac disease before you attempt a gluten free diet. It’s good to rule this out first, as long-term avoidance of gluten can affect serologic markers for celiac disease once a gluten free diet is started. Therefore, some patients who appear to have NCGS may actually have celiac disease that remains undetected, because testing was performed after the gluten free diet was already started.

An elimination diet, where all gluten is removed from the diet for 60 days and then reintroduced, is still considered the most accurate method of assessing gluten intolerance.

Because many people with gluten intolerance are also intolerant of other food proteins, removing these common foods on the elimination diet can also be helpful. Gluten cross-reactivity can be of particular concern for people whose bodies are producing an antibody against gluten. Depending on what antibodies your body forms against gluten, you may or may not cross-react with other foods. An elimination diet is the only way to find this out. This can happen to people with NCGS and celiac disease. These antibodies may recognize similar proteins in other foods. A recent paper looked at the potential cross-reactivity of 24 food antigens (3) Based on this study, the foods to be wary of if you have celiac disease or NCGS are:

Dairy
Oats
Yeast (brewer’s, baker’s, nutritional)
Instant coffee
Milk chocolate
Millet
Soy
Corn
Rice
Potato

In addition to adding these foods to your elimination diet, be wary of processed gluten-free foods, as a lot of them include rice, corn, soy and potato flours. If you have tried a gluten-free diet and still experience symptoms, avoiding these foods for 60 days then re-introducing may be helpful.

Healing the gut by taking digestive enzymes, specifically ones like GlutenEase which may help with digesting gluten and casein proteins, or taking gut healing nutrients, such as glutamine, DGL licorice or aloe vera may be helpful in the healing process. Adding probiotics, fermented foods and managing stress can all help heal the gut lining. Unlike celiac disease, where gluten must be avoided for a lifetime, there is a possibility with a healthy gut that people with gluten intolerance may at some point be able to add gluten back into their diets. Avoidance of the offending foods for an extended period will help the gut heal, and usually if the underlying GI issue is resolved, the food(s) can be added back in.