A reader writes: “Anne mentions Enterolab helping her confirm her gluten sensitivity. Can you please comment on the different gluten sensitivity related tests (e.g. stool test) that are offered by Enterolab (www.enterolab.com)? How much more accurate are they compared to the saliva test and the modified elimination diet that your clinic uses? Why does your clinic not use any of these tests to determine gluten sensitivity?”
Actually, here at HealthNOW we utilize many different testing methods to help a patient determine if they are sensitive to gluten. Please see below for further data:
Common Tests to Diagnose Gluten Sensitivity
Genetic Blood Tests - Genetic blood studies assess an individual’s capacity to carry one of the HLA genes that is associated with gluten sensitivity. Studies support that 90 percent of patients with gluten sensitivity carry the HLA DQ2 gene, and others may carry the HLA DQ8 gene commonly.
These tests are not performed as commonly now as other antibody tests which are more accurate and have thus replaced them. However, genetic screens can be helpful in individuals who are at risk of having gluten sensitivity. For example, in relatives and children of gluten sensitive individuals with negative blood antibody tests, HLA patterns can indicate future risk. If both HLA DQ2 and HLA DQ8 are absent, the risk of being gluten intolerant is minimal and it would negate the need for future testing for the individual. If positive, continued periodic screening and a gluten-free diet would be indicated.
The other area of benefit in genetic testing is for children. The ease of testing by simply swabbing the inside of the mouth makes this less invasive for a small child. This may be a reasonable screening test in children at risk for gluten sensitivity.
Anti-Gliadin Antibodies - Gliadin is the protein component of gluten that triggers the immune reactions in sensitive people, and therefore many people with gluten sensitivity have antibodies to this protein. Testing for anti-gliadin antibodies (AGA) is a simple blood test, but studies have shown that it is less sensitive for detecting Celiac disease compared to other antibodies which will be discussed later. The confusion, as stated earlier, is that the ability of AGA to detect gluten intolerance has been defined in conjunction with a positive intestinal biopsy. While this may be a standard for Celiac disease, we now know that this is an inaccurate standard for gluten sensitivity. In fact, AGA may be the best current diagnostic test when considering all gluten related disorders.
In testing for AGA, antibodies of both the IgG and IgA classes are checked since low total levels of IgA may be present. If a person has low total IgA levels, antibody tests for IgA may be falsely negative.
Anti-Endomysial Antibodies - Unlike Anti-Gliadin Antibodies, Anti-Endomysial Antibodies (EM antibodies) are auto-antibodies. What do we mean by this? Gliadin is a gluten protein so therefore when the immune system attacks it, is not attacking “self” tissues but instead a foreign food protein. In contrast, as gliadin is absorbed through the intestinal lining, it attaches to the smooth muscle cells of the intestinal wall. EM antibodies are directed against proteins of these smooth muscle cells, and therefore EM antibodies are directed against “self” tissue. This defines them as auto-antibodies.
Because EM antibodies attack the smooth muscle of the small intestine, these antibodies correlate better with damage to the intestine wall. Studies have supported an accuracy rate of approximately 90 percent for Celiac disease. Actually in one study, EM antibodies were present in 100 percent of individuals when total villous atrophy was present. However, EM antibodies are ineffective in detecting individuals with silent or subclinical gluten sensitivity. If minor involvement of the intestinal lining occurs or if no intestinal involvement is present, EM antibodies are much less accurate.
As with Anti-Gliadin Antibodies, EM antibody testing should evaluate IgG and IgA forms of antibodies for the same reason as described above. If a gluten sensitive patient is IgA deficient, IgA EM antibodies may be falsely negative even for Celiac disease.
Anti-tissue Transglutaminase Antibodies - Similar to Anti-Endomysial Antibodies, Anti-tissue Transglutaminase Antibodies (tTG antibodies) are also auto-antibodies directed against “self” tissue. After gliadin crosses the intestinal lining, a special enzyme called tissue transglutaminase binds to gliadin and takes off a portion of the protein. This portion is called glutamine. tTG antibodies are antibodies that are directed against the complex of gliadin attached to tissue transglutaminase. Because tissue transglutaminase is a “self” enzyme, tTG antibodies are also auto-antibodies.
Also like Anti-Endomysial Antibodies, tTG antibodies are 90 percent accurate in Celiac disease 5 because they represent immune system attack at the level of the intestinal lining. Gluten sensitivity that involves minor intestinal injury or no villous atrophy will be less likely detected by tTG antibodies. Therefore, tTG antibodies correlate best with villous atrophy as several studies have supported, and a negative tTG antibody test (or EM antibody test for that matter) does not rule out gluten sensitivity when intestinal involvement is minimal or absent.
While some researchers support tTG antibodies as being a sensitive test for identifying Celiac disease, it is less sensitive for gluten sensitivity in a broader sense. This makes logical sense given the location of where this enzyme acts on gliadin. Disorders related to gluten sensitivity that do not involve the intestinal tract would be unlikely to trigger tTG antibody response from the immune system.
Deaminated Gliadin Antibodies - After tissue transglutaminase detaches the glutamine protein from gliadin, the remaining gliadin protein is termed a “deaminated” gliadin. The immune system can make specific antibodies against several different parts of the gliadin protein, and a deaminated gliadin can provoke different antibodies to be produced compared to an intact gliadin protein. As a result, newer antibody tests detect antibodies made against deaminated gliadin selectively. In studies looking again at Celiac disease patients only, deaminated gliadin antibodies had an accuracy rate of approximately 85 percent making it comparable to EMA and tTG antibody tests.
The ability of deaminated gliadin antibodies to detect gluten sensitivity outside of Celiac disease is not known. In Celiac disease patients with IgA deficiency, the IgG test for deaminated gliadin antibodies was as effective as tTG tests. Because testing for deaminated gliadin antibodies offers little advantage over tTG and EMA antibody tests, it is usually not commonly ordered. It may be an effective tool in screening for gluten sensitivity but to date these studies have not been performed.
Total Serum IgA Level - Low total levels of IgA antibodies are rarely found in the normal population with one out of every six hundred people having this condition, but in gluten sensitivity, low IgA levels are more common. This reflects the increased IgA antibody production in the intestine to fight off gluten as it attempts to enter our bodies. If a low level of IgA is present, then certainly IgG varieties of the antibody tests described above will be more accurate in diagnosing gluten related conditions. In general, total IgA levels are not ordered often since IgG antibody tests are usually ordered concurrently. Therefore, defining a low IgA level adds little information in making a diagnosis. There is a general theory however that a lower IgA level suggests greater inflammation of the intestinal lining and greater chronicity of disease. A low IgA level may provide some insight into duration of disease.
Saliva Antibody Testing - While serum antibody testing has been shown in some studies to be more accurate than saliva testing in gluten sensitive patients, IgM and IgA antibodies are also made in the saliva allowing a less invasive way of screening for gluten sensitivity. The difficulty is that these saliva tests have yet to be tested against patient’s response to a gluten free diet in large populations. The saliva tests are therefore not as widely accepted in the medical community. However, our clinical experience shows the tests to be very accurate when correlated with clinical changes that occur with a gluten-free diet. There are research projects currently underway to show the validity of saliva testing, and it is our belief that saliva testing in the future may become one of the best screening tests because of its ease and low cost.
Fecal Anti-Gliadin Antibodies - As you may recall, the immune system begins its line of defense against gluten in sensitive individuals at the intestinal lining by producing IgA antibodies. In keeping with this information, it is predicted that IgA levels against gliadin in the stool may be a more sensitive reflection of gluten intolerance compared to blood testing. One researcher has conducted extensive research in this area and reports statistics that 100 percent of Celiac disease patients have fecal Anti-Gliadin Antibodies (fAGA) and over 70 percent of those with gluten sensitivity have fAGA. This research has yet to be independently duplicated by other research studies but if the current research holds true, then someday fecal testing may prove to be one of the best and most reliable methods for testing for gluten sensitivity.
Scopes and Biopsies
Upper Esophagogastroduodenoscopy (EGD) - Despite the advent of less invasive blood, saliva and fecal tests, there are several clinicians that feel a small intestinal biopsy is required before instituting a gluten free diet. These clinicians may not have distinguished between Celiac disease and the bigger category of disease that falls under gluten sensitivity, or they may not be aware of the broad effects that gluten can have on our health. As research supports, Celiac disease represents a fraction of all gluten related health disorders. Additionally, there exists a misconception by a few that a gluten free diet is a major inconvenience as a treatment. This lends some clinicians to support biopsies for “proof” before committing one to what they feel is a very restrictive diet. In actuality, being gluten free is quite easy and very healthy. Better understanding of this among clinicians may also change an insistence on small intestinal biopsies.
EGD is administered to a person while they are in a lightly sedated state. A flexible tube with a light and a tiny camera at the end of the scope is slowly inserted through the mouth and navigated through the esophagus, the stomach, and into the upper portion of the small intestine. The small intestine is vast, and EGD only assesses the first five feet or so of the small intestine. This causes some significant limitation in terms of finding pathology in many cases.
In addition to directly visualizing the intestinal lining, EGD can biopsy portions of the intestinal wall for evaluation. Small “pinchers” take little pieces of tissue that can be examined later under a microscope. Specifically in gluten disorders, findings sought include villous atrophy and inflammation of the intestinal wall. Unfortunately, contrary to some people’s beliefs, a negative biopsy does not rule out gluten sensitivity. In fact, it does not even rule out Celiac disease 100 percent of the time. Because EGD samples only a portion of the small intestine, and because the area of intestinal lining chosen for biopsy may not be involved with inflammation, a biopsy can be falsely negative even when Celiac disease is present. The small intestine is 21 feet long with the surface area the size of a tennis court. With that picture in mind one can appreciate that a biopsy even in Celiac disease may fail to make an accurate diagnosis.
We do want to stress that having gluten sensitivity for a prolonged time can cause secondary health problems. Chronic stimulation and attack of the immune system makes the body vulnerable to other infections which we see commonly. Evaluating for the presence of parasites, amoebas, bacteria, etc is critical for not only regaining one’s health but for the successful healing of a damaged small intestine. Also nutritional deficiencies as a result of intestinal inflammation are significant problems for many with gluten sensitivity. Calcium, magnesium, Vitamin B12 and Iron are just a few of these commonly seen. Concurrent food allergies, such as lactose intolerance, can also develop secondary to being sensitive to gluten. Lastly, adrenal exhaustion must be considered in many patients with longstanding gluten related disorders as we discussed in the chapter on adrenal disorders.
The most common scenario we see involves a patient suffering many years with gluten sensitivity. We are able to make the diagnosis and proceed to eliminate gluten from the diet. Improvements occur, but all symptoms are not completely resolved. Secondary testing then reveals one or more of these other health problems that require further attention until complete restoration of health can be achieved.
Our Approach is to Identify the Root Cause
We have helped numerous people who have suffered for years with gluten sensitivity but had not been accurately diagnosed previously. Many of our success stories utilizing the HealthNOW Method are included in our upcoming book. The bottom line is that there is no perfect blood test or biopsy protocol to define 100 percent of those with gluten sensitivity. At least not yet. Therefore, you have to consider the limitations of these tests as you undergo evaluation.
Our approach to a person in poor health is first to identify the symptoms and to which bodily system these symptoms are related. The next step is to find what stressor may be affecting this bodily system and remove it. Stressors can include toxins, foods, infections, malnutrition, physical stress, emotional stress, and others. Because our bodies are so resilient, once we eliminate the stressor our bodies have an amazing ability to heal over time.
Our algorithm for diagnostic testing in gluten sensitivity is to screen everyone. It is our belief that gluten sensitivity testing should be part of an annual health examination. Given the impact this dietary substance can have on multiple areas of the body, why shouldn’t we screen for gluten sensitivity? As a means of prevention of further illnesses and a lower quality of life, the benefits in costs alone would outweigh the costs of screening.
How do we test everyone? Generally, everyone is tested with a saliva and blood evaluation of Anti-Gliadin Antibodies (IgG and IgA) as well as Anti-tissue Transglutaminase Antibodies (IgG and IgA). In small children we will consider an oral swab for genetic screening for HLA patterns. At the same time, we place all patients on a Modified Elimination Diet (MED) for 10 days that eliminates gluten and other common food allergies such as cow’s milk, corn and soy products, while invoking a good balance of healthy foods such as lean protein, vegetables and fruits. By assessing the response to the MED and the results of the diagnostic tests, we will receive a highly accurate assessment of gluten intolerance.
For us, the gold standard for diagnosing gluten sensitivity is not an intestinal biopsy or a blood test. It is a beneficial response to elimination of gluten in the diet. We have hundreds of patients that have benefited from this diagnostic approach of getting to the root cause.
To Your Good Health,
Dr Vikki Petersen