Nonceliac Gluten Sensitivity (Intolerance)

Gluten is found in wheat, rye, and barley. Going gluten-free means avoiding these grains.

Gluten sensitivity is defined as a reduction in symptoms after eliminating gluten-containing products from the diet.

As with most things health-wise, the situation is complex. The first thing to understand is that the gluten sensitivity of celiac disease, a well-established disease that affects less than 1% of the population in the U.S., is due to an autoimmune process. This can be considered an allergic reaction to proteins contained in gluten typically found in several common grains, including wheat, rye, and barley.

Celiac disease is easily diagnosed by blood tests and intestinal biopsy. The only practical treatment for celiac disease is a strict, gluten-free diet. Ninety-nine percent of individuals I see who report gluten sensitivity, however, do not have celiac disease. So, why do they feel better on a gluten-free diet? There is likely to be more than one explanation.

There is another dietary intolerance that can cause gastrointestinal symptoms, the inability to digest FODMAPs (fermentable oligo-, di-, and mono-saccharides and polyols). FODMAPs are sugars or sugar-related molecules that are found in fruits and vegetables. The most common example of a FODMAP is fructose, a common, plant-derived food sweetener.

FODMAPs in some individuals are poorly digested and absorbed. They pass through the small intestine and enter the colon where bacteria specific to the colon break them down into gas and other chemicals that can give rise to gastrointestinal symptoms, just like with the lactose in milk in individuals who are lactose intolerant.

Healthcare professionals are seeing an increasing number of patients with self-diagnosed FODMAP intolerance based on the response of reduction of symptoms to the elimination of FODMAPs from their diets. FODMAP intolerance probably is a real entity made more likely by recent changes in dietary patterns which include more fruits and vegetables and dietary sweeteners. Of course, just as with gluten sensitivity, there is a likelihood of a placebo response to the elimination of dietary FODMAPs.

Bacterial overgrowth of the small intestine is a condition in which the bacteria normally found only in the colon move up into the small intestine. Looked at simply, as the bacteria move from the colon into the small intestine (where they don't normally reside), they can get to the food within the small intestine (in particular sugars and carbohydrates) before these can be fully digested and absorbed. They then produce gas and the other chemicals that they normally produce in the colon. As a result, the production of gas and chemicals is greater than normal.

Since a gluten-free diet is low in carbohydrates, a gluten-free diet may also reduce symptoms caused by bacterial overgrowth simply because it contains fewer carbohydrates. Bacterial overgrowth exists, but it is difficult to study and remains rather unclear as a cause of gastrointestinal symptoms including IBS. Theoretically, the symptoms of bacterial overgrowth could be aggravated by FODMAP intolerance. Moreover, FODMAP intolerance could be due entirely to bacterial overgrowth or the presence of specific types of bacteria in the intestine.

Finally, there are the "functional" intestinal disorders, disorders in which no anatomic, histological (microscopic), or biochemical cause for the gastrointestinal symptoms can be found, and the abnormalities are assumed to be functional, for example, due to abnormal function of the central nervous system (brain), gastrointestinal muscles and nerves, or intestinal secretions.

Irritable bowel syndrome (IBS) is one of these functional disorders. IBS was at first defined broadly, but over the years its definition has become restricted such that it is now defined as abdominal pain associated with an alteration in bowel habit. Other non-IBS functional disorders have been defined, for example, the occurrence of abdominal discomfort after meals.

Many patients who believe that they have gluten sensitivity have previously been diagnosed with a functional disorder such as IBS.

Numerous gastrointestinal diseases could be causing symptoms similar to celiac disease. The intestine has a limited repertoire of symptoms with which to respond to disease, so it is not surprising that symptoms of many intestinal diseases can mimic those of food intolerances like gluten sensitivity.

That's why individuals need to be evaluated by their physicians to exclude intestinal diseases even if they think the problem is food intolerance. A gluten-free diet not only reduces the intake of gluten but also alters the intake of other nutrients. Therefore, the alterations of these other nutrients and not the reduction in gluten may affect the symptoms of other intestinal diseases, for example, inflammatory intestinal diseases such as inflammatory bowel disease (IBD).

People with a gluten intolerance describe their symptoms as the following:

• Feeling bloated and gassy
• Experiencing abdominal pain
• Diarrhea
• Abdominal cramping

The next question to address is could the symptoms be due to an allergy to foods in the diet other than gluten. Allergic reactions to foods are caused by the proteins they contain. Some of the most common and well-documented food allergies in adults are milk protein, eggs, soy, shellfish, and nuts, particularly peanuts.

It is difficult to diagnose a food allergy. The standard tests for allergies, including skin and blood tests, are not very precise. The only way to diagnose a food allergy is by eliminating the potentially offending food from the diet and observing the response of symptoms, which could also result in the placebo effect. Since food allergy is infrequent in adults, it probably is not the explanation for symptoms among patients, even those who think they have gluten sensitivity.

There are examples of food intolerances or sensitivities other than gluten. Probably the most common is milk intolerance, with symptoms arising because of the inability to digest lactose, the sugar in milk. The undigested, unabsorbed lactose reaches the colon where colonic bacteria turn it into gas and chemicals that cause symptoms. Most people who have improved with a gluten-free diet and believe they are gluten-sensitive already have tried eliminating milk and milk-containing foods from their diet and it didn't work.

Considering all of the available information, what is a practical approach to dietary intolerances, particularly suspected gluten sensitivity?

• First, true celiac disease and other important gastrointestinal diseases need to be excluded.
• There is nothing wrong, then, with a trial of a gluten-free diet. If symptoms respond adequately and the restricted diet is not a burden, the diet can be continued.
• There is also nothing wrong with then trying a low FODMAP diet.

As with a gluten-free diet, if the symptoms improve adequately and the diet is not a burden, it can be continued.

If the symptoms don't respond or the diet is too difficult to maintain, it is reasonable to consider bacterial overgrowth of the small intestine and test for it by breath testing.

• A fructose breath test (fructose is a FODMAP) has been proposed to identify patients with FODMAP intolerance, but we don't yet have a good idea of how effective this test is at identifying patients whose symptoms respond to reduced dietary FODMAPs. Nevertheless, the test may be worth doing, even if patients say that they have had no improvement on a low FODMAP diet.
• Since a low FODMAP diet is not easy to follow, patients may have inadequately reduced their intake of FODMAPs, and this may have prevented an improvement in symptoms.

In many cases, self-diagnosing gluten sensitivity is the placebo effect. The placebo effect is much greater for subjective symptoms (such as those of patients with self-diagnosed gluten sensitivity) than is appreciated. It is seen in 20%-40% of individuals. That is, of patients who report an improvement in symptoms by eliminating gluten, 20%-40% are not improved. They think they are improved. (Purists may argue that it doesn't matter if they are improved as long as they think they are improved.) It also is possible that some of the placebo response is real and due to psychological reasons. For some patients, the placebo effect is enough, and they don't mind the dietary restrictions of a gluten-free diet.

Of patients who report that their symptoms have improved on a gluten-free diet, almost all have had their symptoms return or continue with reduced severity despite continuing the diet. There are two potential explanations for recurrent or continuing problems:

1. Either the placebo effect is wearing off
2. Something other than gluten sensitivity is going on in addition to gluten sensitivity

You might think that it's easy to study scientifically the effects of dietary changes and determine what dietary factors are responsible for symptoms. It is not. It is very difficult and expensive to do rigorous studies on diet.

After years of debating the existence of non-celiac gluten sensitivity, a scientifically rigorous study has been done that sheds light on the issue. In this study, 37 patients with self-reported gluten sensitivity, well-controlled on a gluten-free diet were studied. They were given a baseline diet that was gluten-free and low in FODMAPs. After observing symptoms on this baseline diet, the patients were divided into two groups. In addition to the base diet, one group received relatively pure gluten, and the other group a gluten placebo. Neither the group receiving gluten nor the group receiving placebo developed symptoms. In other words, the group of patients with self-reported gluten sensitivity was not gluten sensitive when tested.

Many foods high in gluten also are high in FODMAPs, so a gluten-free diet might be expected to be lower in FODMAPs. The important message to take away from this study is that people with self-diagnosed gluten sensitivity are not gluten sensitive. It would be useful now to do a study demonstrating that it is the FODMAPs that are causing the symptoms in these patients.