Separating wheat from chaff in gluten sensitivity

Gluten-free products are proliferating like mad, and now merit whole aisles in upscale grocery stores. More and more of my friends and acquaintances are dropping gluten out of their diets and saying how much better they feel. They sleep better, feel more energetic and lose weight. They make such a compelling case for gluten-free life that I end up wondering, when I’m bloated and my pants don’t fit, whether I should consider dropping gluten myself.

There are two well-established conditions that require people to avoid gluten. Celiac disease, an immune response to gluten that produces severe inflammation of the small intestine, afflicts about 0.75 percent of the population.  A wheat allergy, sometimes called baker’s asthma, affects about 0.4 percent of the population and is usually characterized by symptoms like breathing problems and a runny nose.

But gluten sensitivity in people who don’t have celiac disease or a wheat allergy is fuzzier. Some websites suggest that 18 million people are sensitive to gluten. Most patients complain of stomach problems and gas. Some add in fatigue, brain fog and depressed mood. There are no confirmed tests for the condition. Many people who say they are gluten sensitive never receive a test for celiac disease, wheat allergy or other sensitivities. They cut out gluten and they feel better. This is often the case for people with irritable bowel syndrome, or IBS, a condition characterized by stomach pain, bloating, gas and diarrhea or constipation.

In 2011, Jessica Biesiekierski and colleagues at Monash University in Victoria, Australia, confirmed what is now known as non-celiac gluten intolerance in patients with IBS. In a study of 34 patients published in The American Journal of Gastroenterology, the authors showed that gluten, added to a previously gluten-free diet, caused gastrointestinal distress and fatigue in 68 percent of patients with irritable bowel syndrome.

But now, in results published May 6 in Gastroenterology, the same group of researchers shows that gluten had no effect in IBS patients who claimed they had non-celiac gluten sensitivity. The results seem to contradict the group’s earlier work. But the science may simply be a bit more complex than previously thought: People with irritable bowel syndrome may indeed feel better on a gluten-free diet — but gluten might not have been the culprit.

The researchers tested three different diets, controlled by handing out frozen meals to the 37 patients, all of whom had irritable bowel syndrome. The study was designed as a cross-over, so all patients got a week on each test diet (high gluten, low gluten or no gluten) with two weeks in between. The end of the study was a three-day repeat, where each patient got three days of gluten and another three days without. While there were some upset stomachs, no symptoms could be directly attributed to the gluten in the patients’ diets. Instead, the results suggested a nocebo effect: If you think your stomach will be upset, you probably will have tummy trouble, no matter what diet you’re on.

Some might say that this study’s results mean that gluten sensitivity in general is “bogus.” But the study authors propose that something else entirely is to blame for gastrointestinal distress in IBS patients. Instead of gluten, look to fermentable short chain carbohydrates, called FODMAPs. These molecules are in wheat, barley and rye, as well as other foods including apples, cabbage and beans.

FODMAPs are always going to cause some trouble. They aren’t absorbed well in the small intestine, and when they hit the large intestine, they get fermented by bacteria. That fermentation process is what gives us bean farts and cabbage gas. But while the burrito bloat will happen to everyone, study coauthor Peter Gibson, a gastroenterologist at Monash University, hypothesizes that people with IBS are more sensitive to the gastrointestinal stretching produced by FODMAPs, resulting in more pain and symptoms. Since cutting out gluten also tends to cut out some FODMAPs, he says, people with IBS may well assume that gluten was the culprit.

In the new study, the test diet was also carefully designed to be low in FODMAPs. Gibson’s laboratory also reported in the Sept. 26 Gastroenterology that 30 IBS patients cut their gastrointestinal symptoms in half when they spent 21 days on a diet low in FODMAPs.

Gibson has written a book promoting a low FODMAP diet, but more research is needed before the next diet craze takes hold. Other studies have shown positive effects of gluten-free diets in IBS patients.  Some patients who self-identify as gluten-sensitive could well have other diagnoses that have not been ruled out, including FODMAP sensitivity, sensitivity to fructose or sensitivity to other proteins in wheat.

Maureen Leonard, a pediatric gastroenterologist at Massachusetts General Hospital in Boston, is particularly concerned that a gluten-free diet may not, in fact, be any lower in FODMAPs. “Many foods that are naturally gluten free such as fruits, vegetables and beans are quite high in FODMAPS,” she says. “In patients we see with true gluten sensitivity, gluten or wheat is the culprit causing the gastrointestinal distress.” She also has worries about the patient selection for the new study and the group’s earlier work. The patients were all self-selected as being sensitive to gluten. “Non-celiac gluten sensitivity can be defined as follows:  individuals without celiac disease whose symptoms improve on a gluten-free diet after ruling out other conditions,” Leonard says. Because the patients’ symptoms were not necessarily controlled on a gluten-free diet at the start of the study, “the subjects in these studies do not meet these criteria.”

But Reiner Ullrich, an immunologist at Charite University Medicine in Berlin, Germany, says that Gibson lab studies are useful “as pilot studies in need of confirmation. We should consider FODMAP content when examining the gluten-free diet.” But he is also concerned that the studies tested the diets for only a few weeks (at most) at a time. Ullrich would like to see the diets tested for at least eight weeks. “I fear there is no shortcut to establish dietary or drug effect in IBS,” he notes.

And targeting FODMAPs doesn’t mean that gluten sensitivity is off the table. “The story is ongoing,” Gibson says, “we produced a piece of evidence to say that gluten is being overly blamed, but we have patients who we still believe have non-celiac gluten sensitivity.” It’s also important to remember that the study was in people with IBS. Many of the people who give up gluten have never been diagnosed with IBS, and whether they are gluten sensitive or not remains up in the air.

And of course, wheat is made of much more than gluten. Peter Green, a gastroenterologist at Columbia University Medical Center in New York, N.Y., says that while FODMAPs and gluten may indeed play a role, there could be other proteins in wheat that cause discomfort in some patients. “People with IBS are a very heterogeneous population,” he explains. “It’s a complex issue, and this study adds to the confusion.” But Green also notes the most important thing is that patient symptoms are not being ignored. “People are doing research on it,” he says. “We are trying to work it out.”