Is Gluten-Sensitivity Real? New Research Causes New Thinking

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.”

What Exactly Is Yacón Syrup?

The South American yacón plant is often cultivated for its edible root, which can be juiced and evaporated to produce a syrup. The high fructooligosaccharide content of yacón root has drawn recent attention. A type of soluble fiber, fructooligosaccharide functions as a prebiotic, feeding beneficial bacteria in the gut.

Research has found that it may improve blood lipids, prevent constipation and improve absorption of minerals, such as calcium and magnesium. Fructooligosaccharide has potential to regulate blood glucose levels, especially for individuals with diabetes.

However, few studies have examined the effects of yacón syrup on humans. One study on obese women without diabetes found that when consuming yacón syrup before meals for 120 days, participants experienced a significant reduction in body weight, BMI, waist circumference, serum insulin and LDL cholesterol, and a significant increase in frequency of defecation. Glucose levels did not change significantly. More research is needed on yacón syrup as a supplement for individuals with diabetes, and currently, there is insufficient evidence to promote its use as a weight-loss aid.

A Global Mission for Nutrition Education

From emergency relief posts to missions organized by faith-based organizations, the dietetics community is no stranger to international volunteerism — and the expertise and skill sets of registered dietitian nutritionists often make them unique assets on these initiatives. Yet RDNs and other practitioners face a major challenge working in developing nations: a lack of appropriate nutrition education aids.

"In searching through catalogues of nutrition education materials, I found they depicted foods, people and settings that these [overseas communities] have never seen," says Dixie Havlak, RD, who has worked in rural Nicaragua and Honduras. "It takes months to put together information, and that makes people think twice about going overseas and doing work."

In countries where people may not have a very sophisticated understanding of science and most local community nutrition workers have little training or poor access to education materials, health practitioners must go back to basics. Visual aids that meet the needs of minimally literate people are especially important, Havlak stresses.

"In the U.S., most people know we get nutrients from food. But some cultures may not even have a word for that," she says. "We have to go back to the very fundamentals of nutrition, health care and how the body works."

Culturally appropriate and effective education aids not only support volunteers, but also the efforts of practitioners whose careers are with government agencies, NGOs or military services. "Before and after my journeys in Central America, I often met other people going down there — dietitians, nurses and medical teams who commonly teach about nutrition and health issues — who had to throw together health education materials at the last minute," Havlak says. "That seems really inefficient."

To help close the gap and support international nutrition education, the Academy of Nutrition and Dietetics has launched a pilot project to develop a collection of free resources for health practitioners working in developing countries. Made possible through funding from the Academy Foundation through the Wimpfheimer-Guggenheim Fund for International Exchange in Nutrition, Dietetics and Management, the first phase of the collection will focus on Central America.

All RDNs, registered nurses, pediatricians, family practitioners, physician assistants and other public health workers with field experience in this region are invited to take an online survey to assess needs for materials and tools that could aid in international medical missions and humanitarian assistance efforts. Respondents also can submit examples of materials (handouts, posters, visual aids) they have developed or used in nutrition education efforts.

"When we can share materials, we improve our ability to serve the developing world and make it easier for more practitioners to volunteer," Havlak says. "Many people on the ground are desperate for material, and we can help them facilitate understanding of health issues and improve the ability to communicate that with the people they serve."

To share your ideas and experiences, visit sm.foodnutrimag.org/intsurvey or email IRproject@eatright.org. Resources will be available mid-2016 on eatrightPRO.org.

How the Latest Research May Shed Light on Serum Cholesterol

It was such a simple sound bite: Know your number and know your risk. When research emerged in the 1980s implicating dietary and serum cholesterol in the development of heart disease, cholesterol became the nutrient that everybody loved to hate.

Over time, science slowly moved the needle away from this mindset. “Good” and “bad” serum cholesterol were delineated, and more recently, studies determined that eating cholesterol-rich foods didn’t actually increase serum cholesterol like we once thought. And while some still maintain that lower total serum cholesterol is always best, more recent research challenges the validity of measuring cholesterol as a singular marker of cardiovascular health. So where does the medical community stand now on serum cholesterol?

What is Cholesterol?
First, a refresher. Manufactured by the liver, cholesterol’s functions extend well beyond the cardiovascular system. It’s the structural backbone to sex hormones, including testosterone, estrogen and progesterone (in addition to the adrenal hormone cortisol), and is crucial to brain function, both as part of myelin sheath structure and its role in nerve impulse conductivity. Because it is required to synthesize vitamin D from sun exposure, cholesterol is relevant to the immune and skeletal systems. And in cell membranes, cholesterol provides structural support and may also act as an antioxidant.

There’s even evidence that cholesterol may play a role in protecting against bacterial and parasitic infection.

Serum cholesterol travels through the blood stream within lipoproteins, of which the two most abundant are low-density lipoprotein and high-density lipoprotein. LDL carries cholesterol from the liver to peripheral tissues, while HDL carries cholesterol back to the liver for excretion or recycling. Routine cholesterol panels typically include total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides. LDL and HDL cholesterol levels measure the amount of cholesterol carried in these lipoproteins, and many health professionals rely on these figures to gauge risk for cardiovascular and coronary artery disease.

What if "Normal" Does Not Equal "Healthy"?
This is where it gets interesting. Studies have found that up to 75 percent of patients hospitalized for heart attacks had normal to optimal serum LDL levels, and in 2013, revised guidelines from the American Heart Association and American College of Cardiology removed LDL cholesterol target levels and recommended that doctors not prescribe cholesterol-lowering medication based on cholesterol levels alone — a significant departure from long-held advice.

The key to understanding LDL cholesterol’s risks and rewards may lie in the size and density of its particles, which range from large, buoyant, cholesterol-rich particles to small, dense particles low in lipids. Since everyone has a mix of different types of LDL particles at any given time, some practitioners are testing for serum cholesterol “phenotype” patterns to discern composition (see sidebar).

Pattern A describes having mostly large, more buoyant LDL particles and is linked with good cardiovascular health, while pattern B refers to having mostly smaller, more dense LDL particles that are more prone to oxidation — and therefore associated with greater risk of atherosclerosis and higher overall cardiovascular disease risk. So whereas a person with low triglycerides, high HDL cholesterol and slightly elevated total and LDL cholesterol with pattern A phenotype (big, buoyant particles) may not be at increased risk for atherosclerosis or cardiovascular disease, a person with low to normal HDL cholesterol and normal total and LDL cholesterol levels with pattern B phenotype (small, dense particles) may indeed be at increased risk.

LDL particle size and density are influenced by genetics, diet and body weight — and dietary interventions have demonstrated measurable effects. More long-term studies are needed to help shape recommendations, but some researchers are exploring the effect of diet and weight loss on LDL patterns.

While the mechanisms are not yet understood, they include:

Higher intakes of saturated fat may increase large, buoyant LDL particles.
Reducing carbohydrates may reduce small, dense LDL particles.
Reducing dietary fat may reduce total LDL cholesterol, but specifically lowers large, buoyant particles.
Weight loss has been shown to improve LDL patterns in overweight men.
A high-carbohydrate, low-fat diet has been shown to shift study participants from pattern A to pattern B.
Study participants who started out as pattern B on a high-fat diet remained pattern B on a low-fat diet.
Although the clinical value of measuring LDL patterns remains hotly debated, many agree that more research is warranted since findings potentially could change the landscape surrounding serum cholesterol. In the meantime, staying up to date on emerging research and new practices is advice that any practitioner can get behind.

Why the Low-FODMAP Diet Is a Growing Dietitian-Led Treatment for People with IBS

Irritable bowel syndrome is a complex digestive condition that interferes with the daily lives of millions of people worldwide. Typically occurring in episodes, the condition is characterized by symptoms such as moderate to intense abdominal pain, bloating and gas. This set of digestive symptoms is not unique to IBS; therefore, to accurately diagnose the condition, health care professionals must rule out other issues such as celiac disease, small intestinal bacterial overgrowth and food allergies.

While diet does not cause IBS, individualized nutrition therapy can significantly lessen symptoms Tweet this through identification and restriction of trigger foods. Fermentable oligosaccharides, disaccharides, monosaccharides and polyols, or FODMAPs, have been identified as a group of short-chain carbohydrates that are rapidly digested and poorly absorbed in the gut, thus provoking excess fluid and gas in the bowels of many people with IBS. FODMAPs are naturally occurring carbohydrates found in foods such as apples, watermelon, asparagus, broccoli, milk and beans and are sometimes added to food as sweeteners.

Although some carbohydrates under the FODMAP umbrella, such as lactose and fructose, have been targeted in IBS therapy in the past, research on diet therapy addressing all FODMAPs as a group only began within the last decade. Research started in Australia in 2006, and subsequent studies have occurred elsewhere, including the United Kingdom, New Zealand, Scandinavia and the U.S. The results have been clear: When people with IBS consumed high amounts of FODMAPs, their symptoms got worse; when they restricted FODMAPS, their symptoms improved.

Now with enough evidence to support its use, a low-FODMAP diet is recommended as a nutrition prescription for patients with IBS in the Academy of Nutrition and Dietitics' Nutrition Care Manual. Client education materials for a low-FODMAP diet will be available in the NCM later this year.

Nonetheless, doctors caution that low-FODMAP diet therapy is not a cure for patients with IBS. Individual response to the diet varies, and some people with IBS experience little relief from following a low-FODMAP diet. And while a low-

FODMAP diet produces significant results in most IBS patients, it doesn't always eliminate all symptoms. For instance, some patients may experience relief from gas and bloating, but their irregular bowel patterns remain.

FODMAP expert Patsy Catsos, MS, RDN, LD, began using low-FODMAP diet therapy in her private practice almost a decade ago. To date, she has helped thousands of patients through the diet and says that "the FODMAP elimination diet is more than just a list of foods — it's a process. To get the best outcomes, patients need a strategic plan, and that's where the dietitian comes in."

One concern about following a low-FODMAP diet is the effect it may have on a patient's gut microbiota. Evidence shows IBS patients have different gut microbiomes compared to the healthy population. Preliminary research suggests taking a probiotic supplement during low-FODMAP diet therapy can prevent the washout of beneficial gut bacteria, leading some FODMAP experts to recommend this type of supplement to people with IBS on the diet.

In addition to IBS, limited evidence shows promise of a low-FODMAP diet for people with inflammatory bowel disease, which is a separate medical condition (an autoimmune disease characterized by chronic inflammation; includes Crohn's disease and ulcerative colitis). Some researchers suspect a low-FODMAP diet may help alleviate digestive symptoms in people with non-celiac wheat sensitivity, but the diet has not been validated in this population.

Not all FODMAP-containing foods worsen IBS symptoms for all patients, which is why the diet therapy is conducted in two phases. To identify specific foods that trigger symptoms in a patient, phase 1 restricts all high-FODMAP foods and phase 2 gradually reintroduces them.

Phase 1 typically lasts up to eight weeks and is when patients feel most challenged by the restrictiveness of the diet. Elimination and reintroduction of FODMAP-containing foods is the only effective strategy to identify trigger foods in patients with IBS. Reliable assessment methods such as hydrogen breath tests are available to detect some, but not all, FODMAP malabsorption, but these tests are capable of false positives and are not perfect. Because long-term evidence is not available and there is a risk of nutritional inadequacy if the diet is poorly planned, restricting high-FODMAP foods should be temporary and reintroduction should be as quick as possible in accordance with the patient's symptoms.

Patients and physicians should work with an RDN who is trained in administering a low-FODMAP diet to ensure the success of the nutritional therapy. According to low-FODMAP diet educator Kate Scarlata, RDN, LDN, "The low-FODMAP diet has many nuances, and online resources are often outdated, making the IBS patient confused and frustrated. The role of the dietitian is to be well-prepared with the latest and most accurate low-FODMAP diet research to successfully guide the patient with this effective nutrition intervention." While research shows good patient compliance of about 75 percent following the diet, it is restrictive by nature.

Barriers include expense of low-FODMAP specialty foods, dislike for the taste, unwillingness to follow the diet and the challenge of identifying and selecting low-FODMAP foods when eating away from home. Additional challenges are the lack of defined cutoff values for high- and low-FODMAP foods and shortage of FODMAP content on food packaging.

Two voluntary certifications for low-FODMAP food products are available, one from Monash University and the other from FODMAP Friendly, both of which have access to FODMAP laboratories to conduct food testing. These seals are on few products in grocery stores today, but likely will increase as the diet gains popularity. Dietitians interested in learning more about FODMAP diet therapy are encouraged to read books by reputable FODMAP experts, seek continuing education opportunities such as workshops and trainings led by FODMAP experts and use the Monash University low-FODMAP diet app.