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Is Gluten-Sensitivity Real? New Research Causes New Thinking



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Gluten-free diets have become one of the hottest approaches to a long list of health ailments and weight loss. An ongoing debate asks whether gluten sensitivity truly exists or if it is a media-driven fad, pandering to hypochondriacs and dieters, and boosting sales of gluten-free products.

The answers may not be so clear-cut. Historically, gluten was thought to pose problems only for the 1 percent to 2 percent of the population who suffer from autoimmune celiac disease, for which the cornerstone of treatment is a strict gluten-free diet. But emerging research suggests there is a spectrum of non-celiac gluten-related disorders that improve when gluten is removed from the diet.

"Celiac-Lite"

For years, gastroenterologists and researchers have been trying to understand the role of gluten in non-celiac conditions. In 2012, celiac researchers coined the term "non-celiac gluten sensitivity," or NCGS, for individuals who present with symptoms similar to celiac disease and say they feel better on a gluten-free diet. "Roughly 6 percent of the population suffers from NCGS, which pre NCGS, which presents as a trigger to gluten with a possible presence of gluten immune-reaction," says Alessio Fassano, MD, director of the Center for Celiac Research at MassGeneral Hospital for Children in Boston.

Sometimes referred to as "celiac-lite," NCGS is a form of gluten intolerance that does not meet diagnostic criteria for celiac disease or other related conditions, such as wheat allergy, and does not cause inflammation or damage to the small intestine. NCGS is a rapidly growing diagnosis, despite not having an established definition and being a controversial topic that is not well-understood.

"Gluten sensitivity is an understudied area that appears to be a gluten-induced activation of an innate, rather than adaptive, immune-mediated reaction to gluten that does not always occur in the same way when eating gluten," Fassano says.

Variability among patients, the lack of definitive biomarkers and inconclusive studies have hindered progress in identifying NCGS. However, a few studies have offered some insight into the condition. A small Australian study published in 2011 was among the first to show gluten could induce symptoms in non-celiac patients. A well-conducted study using a double-blind, placebo-controlled design found NCGS exists in specific clinical conditions, including 5 percent to 20 percent due to irritable bowel syndrome.

Researchers at the National Institutes of Health recently published a study corroborating these findings. The study population consisted of a group of 59 participants who believed they suffered from NCGS. They were given less than 5 grams of gluten or a placebo in pill form for one week. Participants taking the gluten pills reported a significant difference in symptoms compared to those taking placebo pills after just one week.

However, research published in 2013 suggests that gluten alone may not be responsible for the symptoms. The same Australian researchers conducted a follow-up study that challenged the findings of their earlier study. Only 8 percent of the participants improved on gluten-free diets, yet all of the participants had significant improvements on a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols, or FODMAP, diet. These results indicate the possibility that the positive effect was due to removing FODMAPs — not gluten.

Detecting Gluten Sensitivity

Sensitivity to gluten appears to occur at any age and to people who have previously tolerated gluten. "Gluten triggers a biological response in everyone, yet not everyone gets sick when eating gluten," Fassano says. Without biomarkers to confirm NCGS, it is considered a diagnosis of exclusion. The only way to identify NCGS is to rule out other related conditions and demonstrate both improvement when gluten is removed and recurrence of symptoms when gluten is reintroduced.

Celiac disease is a serious condition that must be ruled out first, after which other potential causes within the spectrum of gluten-related disorders should be considered. A diagnosis of NCGS can only be made when celiac disease and other related conditions are adequately excluded. Testing for celiac disease requires a celiac blood test and biopsy samples from multiple areas of the intestine, including the duodenal bulb. Consumption of gluten is essential for accurate results. Going on a gluten-free diet beforehand can mask the results of the tests and result in an inaccurate diagnosis, which many experts suspect is why celiac disease is dramatically underdiagnosed.

NCGS is a condition typically characterized by gastrointestinal symptoms (diarrhea, abdominal discomfort, pain, bloating and flatulence) or extraintestinal symptoms (fatigue, headache, brain fog and lethargy) that occur after gluten ingestion and improve after gluten is removed from the diet. Undigested gluten can act like a foreign invader, irritating the gut and the microvilli within the intestine, leading to decreased absorption of nutrients.

“Celiac disease can be a challenge to diagnose, with up to 50 percent of people presenting without any gastroenterology symptoms,” says Shelley Case, RD, author of Gluten-Free Diet: A Comprehensive Resource Guide (9th edition due in fall 2015, self-published). Many patients present with anemia due to reduced iron absorption.”

Non-Celiac Gluten-Related Disorders

Only a fraction of the patients who report NCGS have a gluten-related condition. When it is not celiac disease or NCGS, experts consider FODMAP intolerance. Fermentable sugars may be poorly digested in some people, causing discomfort, gas and bloating — symptoms similar to those of NCGS and other gastrointestinal conditions. Food intolerance occurs either when the body lacks a particular enzyme needed to digest nutrients, nutrients are too abundant to be completely digested or a particular nutrient cannot be properly digested.

Following a low-FODMAP diet can be more challenging than a gluten-free diet and requires the guidance of a registered dietitian nutritionist. The elimination diet limits fructose (fruits and vegetables), lactose (dairy), fructans (wheat, rye barley, onions, garlic and leeks, for example), galactans (some legumes, broccoli and cabbage) and polyols (types of sugars). Most people with a FODMAP intolerance are able to identify which foods are problematic and gradually add back the ones that are well-tolerated.

Since fructans include the gluten-containing grains wheat, rye and barley, people intolerant to FODMAPs show some signs of improvement on a gluten-free diet, but it may only be temporary. A hydrogen breath test is an effective diagnostic tool used to help distinguish food intolerances from NCGS.

A wheat allergy, which affects less than 1 percent of adults in the U.S., is another cause of these problematic symptoms. Food allergies are very specific immune system responses involving either the immunoglobulin E, or IgE, antibody or T-cells reacting to a particular food protein. Wheat allergy differs from celiac disease and NCGS, and therefore the body reacts differently.

An allergic immune response to wheat can lead to a variety of symptoms, including swelling, itching, skin rash, nasal congestion and tingling or burning of the mouth. People with wheat allergies are allergic to a wheat protein, not necessarily gluten, and can tolerate gluten-containing barley and rye.

Many people feel better when they remove gluten, but it may not be due to a specific food allergy or intolerance. "The number of people going gluten-free vastly outnumbers the number of people who truly have a biological problem tolerating gluten,” says Mayo Clinic gastroenterologist Joseph Murray, MD. “Some people feel better when gluten is eliminated for many reasons — including the placebo effect, they eat less, their diet is healthier, they believe it is better for them — and when they return to their old diets, they start feeling bad.”

Potential Causes for Gluten Sensitivity

There is no evidence indicating an increase in gluten sensitivity over the last 35 years, but rather a lot of media attention, Murray says. The prevalence of NCGS in the general population is unknown, largely because many people are self-diagnosing and adopting a gluten-free diet without medical advice or consultation. NCGS does not appear to be genetically based, unlike celiac disease, which has a fairly well-established pathogenesis. The cause of NCGS is not well-understood and may be different for individual patients. It has been hypothesized that symptoms may be a result of impaired intestinal mucosa barrier function or related to an innate immune response to gluten. Whether it is actually the gluten or a component in the grain that is responsible for the symptoms remains under scrutiny.

“New varieties of wheat, wheat hybridization and quality of grains that have been introduced over the past 40 years have been ruled out as causing an increase in the condition,” Fassano says. “Individuals may be predisposed to NCGS. It does not appear to be related to the timing of introduction of grains, nor does breastfeeding appear to be protective.”

In an attempt to unscramble the gluten puzzle, emerging research takes a closer look at how the microbiome may be affected by genetics, the environment and the immune system. The microbiome, a community of microorganisms in the human digestive tract housing good and bad bacteria, has been of particular interest in recent research. (Even Hippocrates believed that all diseases begin in the gut.) The microbiome is inherited from the mother, is extremely dynamic, varies among individuals and changes in the same individual over time.

Beyond genetics, nutrition is one of the most influential factors in the microbiome that may offer protection. “Babies born vaginally, consuming balanced diets and with minimal infections and antibiotics in the first few years of life establish a healthy gut and microbiome that is protective and likely lowers risk for developing diseases,” Fassano says. “On the other hand, when the microbiome is trained inappropriately, the risk for disease is greater and may be a secondary factor explaining NCGS.”

Why RDNs Are Fundamental to Success

NCGS is a growing problem encountered in clinical practice, yet is difficult to diagnosis and a challenge to manage in the absence of diagnostic markers. Whether gluten removal, wheat exclusion or a low-FODMAP diet, a carefully executed process of trial and error is required with elimination diet plans. Food diaries, in which clients record everything they eat and drink and any symptoms that follow, are especially helpful.

However, relying on what people report or anecdotal observations are subjective and open to misinterpretation. “Double-blind food challenges are the most accurate way to determine NCGS,” Murray says. No evidence-based guidelines exist for reintroduction of gluten-containing foods; it is dependent upon the level of sensitivity. Reintroducing gluten is best done when the patient feels better and with simple foods, such as matzo or soda crackers, which are pure wheat.

Gluten reintroduction is a risk-versus-benefit decision and should be highly individualized to the patient. “Unlike celiac disease, there is no damage to the small intestine, so consuming small amounts of gluten goes without incident,” Murray says. When removing gluten is effective, there could be a threshold of tolerance that allows some gluten in the diet. When it is ineffective, Case recommends trying a low-FODMAP diet.

RDNs may have been skeptical about NCGS initially, but it has proven to be an excellent opportunity to assume a leadership role in the diagnosis and care of patients. “Asking the right questions, doing a detailed diet history and overseeing gluten elimination and challenges are where dietitians can play an essential role,” Case says. “Dietitians are having great success treating NCGS patients, and unless we embrace and treat these conditions, patients will seek alternative practitioners.”


Kathleen Zelman, MPH, RD, is the director of nutrition at WebMD.
 

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