Just a Moment: 4 Mindful Supports to a Gluten-Free Diet

Accidentally eating gluten is like a three-alarm fire, but mindfulness can help you survive the blaze.

When it happens to Shayna Coburn, PhD, who has celiac disease, she says, “What comes to mind automatically is the worst-case scenario. ‘This is going to get so much worse. It’s going to last forever and be painful and embarrassing.’”

Coburn, a psychologist who works with celiac patients at Children’s National Hospital in Washington, D.C., compares practicing mindfulness to doing a fire drill when you are calm. “In case of a fire we want to know what to do. That’s why we practice when there’s not an emergency. That’s how we would train people to use mindfulness.”

Anxiety about the past or future is common for people with celiac disease, says Coburn. If they experienced a stressful health incident, their thoughts may linger on what went wrong.

“Being in the moment can clear that emotional baggage,” Coburn says. “It brings peace and clarity, because there’s just one thing to focus on.”

She describes four ways mindfulness can support living gluten free.

4. Adjusting to diagnosis

A diagnosis of celiac disease can overwhelm people with information. Sometimes, it brings grief or guilt about not getting help earlier. It raises worries about future health or not being able to do certain things.

“Bringing your attention back to the current moment with what you’re currently trying to do can make a big difference to move step by step through the process,” says Coburn.

The basic strategy focuses on the five senses.

“You’ll use smell, taste, touch, hearing and sight to notice everything that’s going on. This makes it more challenging for our brains to think about all the other stuff in our lives,” Coburn explains.

“For instance, for some people going to the grocery store and trying to buy food suddenly becomes a trigger for being overwhelmed. Using mindfulness to bring your attention back to your current task can help you move through it. Mindfulness, too, is accepting the thoughts and feelings that come up for you. If being in a grocery store makes you anxious and overwhelmed, it’s OK to feel that way. Give yourself permission. Try not to judge or make yourself feel a certain way. Instead, recognize this is where you are now. It will pass,” Coburn says.

Then use a strategy to help remember you are safe in the moment. It could be a quick walk around the store just noticing things instead of thinking about them, taking a few moments to focus on breathing, or inspecting the ingredient label on one package.

3. Safer food choices

Mindful eating is beneficial for many reasons, even for those who are not on a restricted diet, because the practice usually leads to people making healthier food choices while eating less.

Coburn says, “It’s easy to multitask while eating and not pay attention to the body’s cues about hunger and fullness. Mindfulness gives the perspective of what is making me want to eat, how my body feels, what this food is like, and when I feel satiated.”

Impulsive eating can cause mistakes if we neglect to look and ask questions first, such as when sharing food with a friend, Coburn adds.

“When I’m shopping, I often need to remind myself to slow down,” says Emily Souder, a social worker who coaches young moms and expectant parents in Catonsville, Maryland. She has Hashimoto’s thyroiditis, which causes thyroid damage, and is gluten sensitive. “I need to remind myself to see what I’m currently looking at rather than thinking about the next thing or five things on my list. I stop, pause and take in the product. I read the ingredients and check in with its impact on my body. If it feels that it will nourish me—yes, this includes chocolate, I’m all about intuitive eating—I can make an informed choice.”

Andrea Nazarenko, PhD, author of When Food Hurts and co-owner of a wellness clinic in Lexington, South Carolina, says she regularly uses mindfulness to prevent falling off the gluten-free wagon.

“Mindfulness helped me take control of my mind. It helped me pause and allow myself the space to say, do I really want this? What are the implications? The slight pause is the essence of willpower. It’s the ability to move beyond what you desire to what you actually need.”

Coburn says children especially may resist trying new foods. She encourages parents to provide a range of options without forcing children to try them. Whatever they choose to eat, avoid making judgments.

“Talk about the color of the food, the texture. What does it smell like? What are the flavors: not just yummy or disgusting, but is it sweet, salty, bitter, crunchy, soft, hot or cold? Mindful practices can help us accept different kinds of foods, not view them as good or bad.”

Coburn says mindfulness exercises are most effective for teenagers and into adulthood. Younger children might be ready when they talk about thoughts or worries going through their heads.

2. Managing symptoms with mindfulness

The mind connects to the whole body through the nervous system. A particularly complex link ties into the digestive system. Coburn calls this the gut-brain axis.

In some individuals, the brain may perceive any digestive discomfort as a threat. Conversely, anxiety sends stress hormones throughout the body. It can impair digestion. Regardless of whether the gut or brain drives symptoms, the two are connected. Mindfulness eases the mind and relaxes the body. Targeting both builds resilience, a sense of being able to overcome stress. The goal is to break the cycle of constant activation and the burden it causes, Coburn says.

For example, when experiencing cramps, she suggests, “Ask yourself what is coming up for you when you feel those cramps. Are you scared of them, expecting them to get worse? Or do I have cramps because I’m already stressed about something else going on in my life?”

Try to lean into the experience instead of judging or trying to make it stop, she says: “Do a scan of the body. What does this feel like? Can I visualize where it is in my body? Is it sharp, blunt, diffuse or localized to one area? Try to understand it. It’s telling us something, and we want to listen.”

1. Handling emotions

Exposure to gluten can cause embarrassment, sadness, depression and frustration. Risk of exposure may cause people to avoid difficult situations. While it is important to learn from mistakes, mindfulness helps find a balance between being safe and living life freely. Awareness of thoughts and feelings helps find new ways to face difficult situations, Coburn says.

For example, many people worry about going to restaurants or parties, making a mistake and becoming sick, or how other people will judge their diet.

Souder says, “My dietary needs seem to make other people more uncomfortable than they make me. People sometimes apologize for eating in front of me, and that feels so silly. Mindfulness has helped a great deal in social situations, though. Instead of focusing on food, I can focus on people, conversations, sights and smells.”

Souder adds, “The biggest effect Hashimoto’s currently has on my quality of life is through physical symptoms (fatigue, joint pain, etc.) rather than through feeling deprived. Mindfulness has helped me reach a place of acceptance.”

In people with celiac, the first stomach twinge can raise anxiety.

Coburn says, “The fire alarm can sound those sirens too early and send our body into survival mode. That in itself can bring on more digestive distress and physical pain. If we allow ourselves to say, ‘This is not great, but you know what? It’s going to be such a relief when it’s over,’ it helps us move through much more quickly. Similarly, as we start to recover, trying not to relive what just happened can make a big difference. Staying in that moment, things might be painful or unpleasant, but it passes. If we stick with it, we’ll experience relief.”

Learning mindfulness

Many find it difficult to stay in the here and now. However, there are many approaches to suit different lifestyles. Formal meditation can support mindfulness but is not required.

Coburn admits, “Activity is much easier for me than something more passive. You can do anything mindfully. The more mundane, the more repetitive, the better.”

Here are some ways to learn:

  • Download an app. Coburn recommends Mindfulness Coach. Souder recommends Insight Timer.
  • Many guided exercises are available online. Coburn recommends a relaxing body scan to guide you from head to toe.
  • Smart home devices offer mindfulness exercises on request.
  • Yoga promotes mindfulness.
  • Ask a doctor for a referral or look for local mindfulness-based therapists.
  • Look for local courses in mindfulness-based stress reduction or mindfulness-based cognitive therapy.

Arielle Lapiano, a mindfulness facilitator in New York, says she is a huge fan of affirmations before eating, such as, “Food fuels my health,” or, “I take a beat before I eat.” Diagnosed with celiac as a baby and later with Hashimoto’s thyroiditis, Lapiano suggests affirmations could also help after exposure to gluten. Think of a short sentence expressing acceptance and trusting in the body to heal.

Whatever activity you choose, it should promote a simple focus to clear the mind, Coburn says. The best approach varies from person to person. Some people have a hard time noticing where their attention goes. Even people who find mindfulness useful need lots of practice.

A fire drill works when there is no emergency. It takes commitment to keep practicing, accept whatever happens, and live in the moment.

Symptom Search Results Study Takes Look at Celiac Risk

A study of search engine queries shows people at risk for celiac are hard to identify based on symptoms. The analysis from Columbia University tried to identify what inquiries users made prior to being diagnosed with celiac but found no common set of terms.

The cost of screening everyone for celiac would be high, but so is the burden of undiagnosed disease. This study explores an alternative to screening: case finding, which identifies and screens only groups most at risk. While experts advise testing everyone with a family history of celiac, finding patients outside this group requires other information, such as symptoms. This study confirms that undiagnosed patients experience such variable symptoms that they are hard to distinguish from the general population.

The study extracted all queries submitted to Bing in the United States from January to October 2017. It identified 90,142 users who submitted a new celiac-related inquiry in October without any in the previous nine months. This narrowed to 6,528 who showed sustained interest by querying celiac more than once, likely indicating a new diagnosis. The study then analyzed all symptom inquiries prior to the supposed diagnosis.

This approach helped include symptoms patients might feel embarrassed to discuss. The data showed an increase in queries about celiac symptoms such as diarrhea, bloating and weight loss prior to the date of diagnosis. Searches about depression and anxiety also increased.

Defeat Deficiency: What Nutrients are Lacking in the Gluten-Free Diet?

The glow has dimmed on the gluten-free halo. The diet is no panacea, no formula for peak performance.

“A gluten-free cookie or a brownie is no more nutritious than a regular brownie or cookie or cake made with gluten,” says Shelley Case, RD, of Calgary, Canada, author of Gluten Free: The Definitive Resource Guide. “There’s nothing magical about going gluten free.”

However, for people with celiac disease, it is the only treatment available. Having removed all sources of gluten from their diet, they must also achieve good nutrition. As with any diet, convenience foods may not be the healthiest choices.

“Every time you go on a restrictive diet, there is a risk for nutritional deficiency,” says Jocelyn Silvester, MD, instructor of pediatrics at Harvard Medical School in Boston. “While treating celiac disease helps you absorb nutrients better, it might also put you at risk for not absorbing the right profile of nutrients.”

Medical literature contains little data about long-term nutrition of patients on a gluten-free diet. The Manitoba celiac cohort study is following a group two years after diagnosis to see how treatment affects their nutrition. Silvester, who completed her residency training at University of Manitoba in Winnipeg, Canada, maintains ties with this research. She hopes it will show whether patients normally achieve good nutrition or need more follow-up. So what’s lacking when it comes to nutrients in the gluten-free diet? Read on for more on missing nutrients and what steps to take when going gluten free. 

Malabsorption and the Gluten-Free Diet 

The first hurdle for new patients is avoiding gluten so they can heal. Celiac flattens the villi, small, finger-like projections lining the small intestine. Damaged villi have less surface area and absorb fewer nutrients. If children do not get enough calories, they may fail to thrive or have delayed growth. Adults can suffer unwanted weight loss.

“Oftentimes, kids will adapt to this by increasing their caloric density to try to keep their weight stable. Once the gut heals, that higher caloric diet is suddenly too much for them,” says Hilary Jericho, MD, director of pediatric clinical research at University of Chicago Celiac Disease Center.

Adopting a new mindset that they do not need to consume 3,000 calories a day can be a big adjustment along with many other changes during childhood.

Malabsorption can cause specific nutrient deficiencies. Silvester says, “Nutrients that are absorbed in the first part of the duodenum—iron and calcium—are two of the main nutrients we see difficulties with.”

Iron and the Gluten-Free Diet 

Iron maintains a healthy red blood supply and stores oxygen in the muscles. Iron-deficiency anemia is common in new patients and often alerts doctors that a patient might have celiac. Fatigue, weakness and dizziness are common symptoms.

Adopting a gluten-free diet should be the first step to address iron deficiency, says Case. When the villi heal, they should absorb nutrients normally again.

Jericho says, “If you are having ongoing iron deficiency problems, then we really need to look into this and understand why. Once the gut is fully healed, you should not run into that problem.”

Case adds that iron supplements can be hard on the stomach, often problematic for people recovering from celiac.

She advises that the human body absorbs iron most readily from meat, fish and shellfish. The form of iron occurring in plants is less easily absorbed. Plant foods rich in iron include beans, peas, lentils, tofu, quinoa, seeds and eggs. The gut absorbs iron from plants better if they are eaten alongside meats or vitamin C foods like citrus fruit, strawberries, cantaloupe, peppers, tomatoes and potatoes.

Vitamin D, calcium and the Gluten-Free Diet 

Malabsorption can affect calcium and vitamin D. Both nutrients support healthy bones. Calcium in the bones alone contributes up to 2% of body weight. Children need a lot of it to grow and lay down critical bone mass.

“Adolescence and early 20s is a peak age when bone mineral density is accrued,” says Silvester. “Then, like so many other things in life, it’s a downhill slope from there. It’s really important to get kids better and make sure they’re getting adequate calcium and vitamin D so they can start with normal stores. If they start with a lower bone mass, then they are at greater risk of developing osteoporosis later in life.”

Calcium is also necessary for functions of the muscles, nerves, heart and other systems. If the body lacks enough for these vital tasks, it extracts calcium from the bones. Calcium deficiency can cause osteopenia, a thinning of the bones, or osteoporosis, making the bones more porous and fragile.

The prevalence of bone disease in celiac is unclear. However, patients face a greater risk of bone fracture. Experts consider poor bone density one of the potentially serious effects of untreated celiac.

Adding to the problem, damaged villi produce less lactase enzyme to digest lactose. Before being diagnosed with celiac, many patients compensate for lactose intolerance by restricting their milk consumption. This could potentially increase risk for bone disease, says Silvester.

Sometimes new celiac patients need a temporary lactose-free diet, says Case. Once the villi heal, they begin producing lactase enzyme normally. Then dairy products can be reintroduced to the diet. Intestinal healing also restores normal absorption of calcium and vitamin D.

Bone mass is difficult to improve in adulthood, Silvester says, “There is some interesting recent data from people diagnosed with celiac disease in adulthood that suggests that they might be able to recover their bone mass when they start a gluten-free diet.”

Exposure to sunlight provides the most important natural source of vitamin D. However, people in the northern states and Canada don’t get enough and need more from fortified food or supplements.

Milk, cheese and yogurt are the best dietary sources of calcium. Leafy green vegetables, seafood, nuts and dried beans offer smaller amounts.

Dairy products, cereals, juices and some other foods may be fortified with vitamin D depending on the producer in the United States. In Canada, vitamin D fortification is mandatory for milk and margarine. Fortified foods can also provide vital calcium.

Fiber and the Gluten-Free Diet 

Once the body heals, it needs the right profile of macronutrients: protein, carbohydrates and fat. Here convenience foods often fall short. For example, many gluten-free breads rely heavily on starch and fat to compensate for the missing textural properties of gluten.

Fiber is often overlooked. Case says it used to be assumed everyone with celiac had diarrhea, so no one considered adding fiber to the diet. However, one-third of celiac patients now present with constipation.

“If they already were constipated and then you remove your whole grains and wheat bran and all those high-fiber foods because they’re full of gluten, now we’ve got even more problems. All the more reason why we need to focus on fiber-rich foods,” says Case.

She advises checking nutritional information to compare products and see which contain more fiber. Whole fruits, vegetables, pulses (part of the legume family), nuts and seeds are naturally good sources of fiber. With oats and pulses like dried beans, peas and lentils, it is critical to look for a gluten-free label because they are subject to cross-contamination from wheat.

“I’m delighted to see a lot more pulse-based pastas coming on the market, such as lentils and chickpeas,” Case adds. “Traditional gluten-free pastas are usually made with white rice flour, corn flour and maybe quinoa. If you look at the label, again, they’re not enriched with iron and B vitamins like wheat-based pasta, and they don’t tend to have a lot of fiber. If you can switch to a pulse-based pasta, you get a lot more fiber and protein and more satiety.”

Convenience Foods and the Gluten-Free Diet 

“Convenience foods tend to be higher in sugar and fat and have less vitamins and nutrients than if you’re eating non-processed foods,” says Silvester. “Previously, going gluten free often meant cooking a lot of food for yourself. People would often substitute in more healthy foods, more whole foods, more fruits and vegetables. Now it’s easier to follow a low-quality gluten-free diet than ever before. It’s not enough to just be gluten free. You have to make sure that they’re eating a balanced, healthy gluten-free diet.”

To investigate the effect of gluten-free products, Jericho’s research team compared patient records before and after 2011, when gluten-free products became widely available. Specifically, they looked at how quickly body weight increased after diagnosis and treatment. The new study in Journal of Pediatric Gastroenterology and Nutrition found no significant change overall due to small sample size. However, adolescents showed a tendency toward higher body mass index after 2011.

In follow-up phone surveys, her team asked the teen patients now in their 20s to recall their eating habits at the time. All respondents diagnosed after 2011 said they consumed processed gluten-free foods sometimes or all of the time. One reported never eating processed foods before 2011 but admitted to always using them after they became available in stores. Besides the products being convenient and easy to prepare, patients reported it helped them fit in with their friends.

If further research shows an impact on adolescents, Jericho suggests they would benefit from a refresher nutrition course two years after diagnosis. It will affect their health down the road.

As a consulting dietitian, Case often receives products from companies. Her responsibility is to make sure they are safe, and the gluten-free claim is valid: “But then I look at the nutrition facts and have to say, ‘Is this product really all that great, or would I be better to eat something else, like some fruit, nuts and seeds or a trail mix, rather than these gluten-free cookies?’”

Case is not against eating treats: “Remember, we all like to celebrate birthday parties and special occasions. Children like to have a treat with their friends. Just be aware that some foods can be a lot more nutritious.”

See a dietitian

Case emphasizes, “It’s critical to work with a registered dietitian with expertise in celiac to individualize the treatment. Everybody has different issues going on, likes and dislikes, their lifestyle, what their cooking ability is or access to different foods. These are all things that the dietitian will go through.”

Case encourages people on the diet to watch for and consider using brands that enrich their products. Only a few do so now.

Silvester says folate deficiency in the North American diet has been addressed with fortification of grain products. Many gluten-free products don’t have folate added, so this especially can be a problem for patients with celiac.

“Patients with CD are going back to the pre-supplementation era,” says Silvester, but adds, “One of the great things about the body is it’s very good at absorbing what it needs and can scavenge minimal amounts from the diet to have adequate amounts in the body.”

Dining Out? Some Gluten-Free Restaurant Food Isn’t

One-third of restaurant food labeled gluten-free contains detectable gluten, according to crowdsourced data1 in the United States. Contamination was even higher in pizza and pasta, occurring in half of all samples. Gluten was detected more often at dinner time (34 percent) than breakfast (27 percent).

The study from Columbia University, New York, included 5,624 tests by 804 people using Nima portable gluten detectors. The samples occurred across the country between August 2016 and January 2018.

High rates of contamination appeared across all restaurant types and regions. However, higher rates appeared in the Northeast than the West. Rates were lower at casual and fast casual restaurants than at quick service.

Nima devices are highly sensitive, detecting gluten accurately down to 20 parts per million (ppm), the level considered safe for people with celiac. They frequently detect gluten below 20 ppm, so many of the items testing positive in this study may have been safe to eat. It is unclear whether contamination levels detected in this study would be sufficient to cause intestinal damage or symptoms in people sensitive to gluten.

This crowdsourced data provided the largest study of gluten contamination in restaurant food to date. The risk of getting glutened while dining out reduces quality of life and causes anxiety for people with celiac. These findings raise concern, but more research is needed to understand how dangerous the levels of contamination are.

Van Waffle is a freelance journalist based in Waterloo, Canada, and research editor for Gluten-Free Living. He blogs at vanwaffle.com.

  1. Lerner BA, Phan Vo LT, Yates S, Rundle AG, Green PHR, Lebwohl B. Detection of gluten in gluten-free labeled restaurant food: analysis of crowd-sourced data. American Journal of Gastroenterology. 2019;114:792-797. doi:10.14309/ajg.0000000000000202.

Beating the Risk of Celiac Disease

Most children with potential celiac can continue to eat gluten and will never develop overt disease, according to research from Italy. Potential celiac is a condition in which patients develop typical blood antibodies but without damage to the small intestine. Patients may or may not have celiac-like symptoms. In this 10-year study, most cases spontaneously reverted to normal blood antibodies and remained healthy while consuming gluten.

The data came from a larger study attempting to understand how celiac develops. It is following from birth 553 children who are genetically at risk for the disease. Twenty-six individuals were diagnosed with potential celiac, all without symptoms. Biopsies showed a healthy intestinal lining. These diagnoses all occurred between age 15 months and 5 years. Parents of three children chose to start them on a gluten-free diet.

Twenty-three children continued a normal diet and were screened again for blood antibodies every year. If antibodies remained high or reappeared later, the patients underwent further biopsies. From this group, 19 children reverted to normal antibodies a year after their first biopsy and did not develop any autoimmune disease within 10 years. Three of this group (14 percent) developed celiac within three years of the first biopsy. One patient showed fluctuating antibodies, but their healthy gut persisted.

These findings will inform the debate about whether to start children with potential celiac on a gluten-free diet, especially if they lack symptoms. The authors suggest that in families with celiac history, children who test positive for blood antibodies should always undergo a biopsy to confirm a diagnosis before adopting a gluten-free diet for life. If the intestinal lining remains healthy, children can continue consuming gluten but should receive regular blood tests to make sure antibodies return to normal. Most young children with elevated antibodies will likely revert to normal and never develop celiac. However, the continued presence of antibodies indicates a high risk for developing celiac and calls for careful follow-up. The ongoing study will continue to monitor these patients.

The study notes that one of the three children who started a gluten-free diet later developed autoimmune thyroiditis. The authors suggest this contradicts the theory that a gluten-free diet protects children with potential celiac.

Lionetti E, Castellaneta S, Francavilla R, Pulvirenti A, Catassi GN, Catassi C. Long-term outcome of potential celiac disease in genetically at-risk children: the prospective CELIOREV cohort study. Journal of Clinical Medicine. 2019; 8;186. doi:10.3390/jcm8020186.

Autism Spectrum Disorder and Celiac Disease

Limited evidence exists for a link between celiac and autism spectrum disorder (ASD), according to a review from University of Calgary, Canada.

The analysis identified 15 studies made between 1946 and 2018 examining co-occurrence of the two conditions. Four studies screened celiac patients for ASD while 12 screened ASD patients for celiac. The three largest studies showed a significant link between celiac and ASD. The rest did not support a link, but these suffered from poor study design or small size.

Experts continue to debate the importance of screening people with ASD for celiac. Any patient should be tested for celiac before launching a gluten-free diet in the hope of treating ASD symptoms. This review suggests there may be a link but emphasizes a need for further research.

Quan J, Panaccione N, King JA, et al. Association between celiac disease and autism spectrum disorder: a systematic review. Journal of the Canadian Association of Gastroenterology. 2019 March. doi:10.1093/jcag/gwz006.256. 

YouTube Offers Opportunity to Spread Information on Celiac Disease

Professionals could make better use of YouTube to reach more people with information about celiac, according to analysis from William Paterson University in Wayne, New Jersey, and Columbia University in New York. The study identified 100 videos about celiac that were most viewed on YouTube between 2007 and 2010. They were viewed almost 7 million times.

Videos included 48 uploaded by health professionals, 32 by consumers and 20 by news sources. The three groups provided similar content. While 57 percent discussed gluten-containing products, these videos attracted 78 percent of views. Those providing health care information were relatively few: 56 percent did not explain how celiac is diagnosed, and they attracted only one-quarter of cumulative views. Few videos discussed age of diagnosis, who is at risk, celiac’s hereditary nature or the risk of inhibited growth in children. Only 14 percent indicated family members of people with celiac should be screened for the disease.

The investigation included only English-language videos and was the first to study YouTube as a medium for celiac education. It did not address accuracy of the information provided, so this needs further study. Medical professionals could use this avenue to reach a large audience, the authors argue.

The High Impact of Celiac Disease on Women

Claire Jansson-Knodell, MD, entered gastroenterology partly because it was a male-dominated profession. She wanted to change that. Then, during her medical residency, she researched another kind of gender discrimination—by a disease.

Celiac, like other autoimmune diseases, affects women more than men. As high as 70 percent of American patients are female. The rate of undiagnosed celiac is also higher among women.

Jansson-Knodell was the lead author of several studies from Mayo Clinic in Rochester, Minnesota, investigating how celiac affects the sexes. Using medical records and patient blood samples, she studied the gender gap in both undiagnosed and diagnosed celiac in Olmstead County, Minnesota. Local findings prompted a systematic review and meta-analysis of all medical research that detected rates of celiac in undiagnosed populations.

Among the patients referred to the celiac center, 71 percent of cases were women. In the studies of diagnosed and undiagnosed celiac in Olmstead County, the figures were 65 and 62 percent female, respectively.

“What struck me doing these research studies is that the trend persists across the different populations,” said Jansson-Knodell of the high rate of cases in women.

In the meta-analysis, 59 percent of people with undiagnosed celiac were women. The disparity appeared in data from every continent and consistently between individual studies. The overall risk for undiagnosed celiac is small: slightly under half a percent for men and slightly over half a percent for women. In comparison, however, a woman is 42 percent more likely to have undetected celiac disease.

“Overall, I think this is an important study which shows the incredibly high rate of undiagnosed celiac disease. The numbers the authors suggest is astonishing,” said Maureen Leonard, MD, clinical director of the Center for Celiac Research and Treatment, Massachusetts General Hospital for Children in Boston.

The study estimates there are 965,960 American women with undiagnosed and untreated celiac. Worldwide, the number is approximately 21.7 million. For men, the figures are 659,850 in the United States and 15.5 million worldwide.

Medical research often draws data from university hospitals. The patients who attend these centers are relatively self-motivated and can afford specialist care, possibly skewing the data. Experts call this referral bias. The Olmstead County studies took another perspective by drawing data from the community around Rochester. It found the rate of undiagnosed celiac in waste or extra blood from routine lab samples patients consented to provide for study.

Still, the findings reflect a particular community. One noted weakness is that nearly all participants were non-Hispanic whites. Other studies have consistently found the highest prevalence of celiac among white Americans.

Meta-analysis is another way to compensate for weak data such as small study size by pooling results. In the systematic review, Jansson-Knodell and colleagues narrowed 4,070 articles down to 87 that met their criteria for relevance and accuracy.

The findings have important implications for public health. The county studies found significantly higher rates of related health problems that affect women disproportionately. Among adult women with undiagnosed celiac, the prevalence of depression was 29 percent compared to a national rate of 6.7 percent. Among women over 50 with diagnosed celiac, the prevalence of osteoporosis was 35 percent compared to 16 percent nationally.

Notably, celiac also increased the rates of depression and osteoporosis among men. Most surprisingly, women and men with undiagnosed celiac had the same risk for other autoimmune diseases, 31.6 percent, though these are normally more common in women.

The reason why celiac affects more women remains unknown. A 2018 study from another team at Mayo Clinic identified differences in intestinal permeability and microbial diversity between healthy men and women. However, no research yet has connected these factors to the gender imbalance in celiac.

Potential explanations might involve environmental factors, hormones and genetics, said Jansson-Knodell: “When we wrote our first version of the systematic review and meta-analysis, we had a long discussion section about all these potential explanations for why is there this gender difference. At the end of the day, we cut out a lot of that because we simply don’t know. It was all theories. The research isn’t there yet to back up why we might see these differences.”

Leonard said, “I agree with the authors that more research into gender differences is appropriate, especially given the possibility that alternative therapies for patients with celiac disease are in the pipeline. When these therapies are successfully developed, it will be extremely important to understand these differences.”

With undiagnosed celiac so common, it is incumbent upon patients and doctors to look out for it.

Jansson-Knodell said, “I think the bottom line is to get tested, to seek medical care. If you’re having symptoms, if you’re iron deficient, if you have a family member with celiac disease, are a Type 1 diabetic or have some other risk factor, it’s important to seek medical care and to look into having your primary care doctor or your gastroenterologist consider doing some serology testing and then possibly a biopsy to confirm diagnosis.”

To emphasize the importance of pursuing a diagnosis while on a normal, gluten-containing diet, she tells of a good friend from medical school whose mother has celiac.

“My friend sees her primary care doctor once a year. Before going in for that visit, she makes sure she’s getting adequate gluten in her diet so that her testing will be accurate. She’s eating a piece of bread a day at least for the month prior to her visit. When she told me this, I was like, ‘Good for you! Staying on top of things and giving it a good shot for accurate testing.’”

After diagnosis with celiac, women should look after the key areas of bone health and mental health, said Jansson-Knodell.

Leonard said, “While more research is needed, the presentation for men and women with celiac disease and the treatment is exactly the same: a strict gluten-free diet. Women with celiac who are of child-bearing age should ensure that they are obtaining enough folic acid from their diet or a supplement to prevent neural tube defects in pregnancy. Gluten-free grains are not fortified with folic acid like their gluten-containing counterparts, so this is very important. Along the same lines, patients with unexplained infertility should talk with their doctor about getting tested for celiac disease.”

The gender divide in gastroenterology

The high impact of celiac disease on womenWe asked Claire Jansson-Knodell, MD, about her career goal to improve patient care for women in gastroenterology.

GFL: When and why did you decide to pursue a career in medicine?

CJK: In high school. I had a wonderful pediatrician growing up. I idolized him, and he provided excellent care for my sister, my brother and me.

I had rotavirus when I was a toddler before there was a vaccine. My pediatrician asked his nurse to drive my mom along with me to children’s hospital so I could be given IV fluids and supportive care right away.

Children in the developing world still have a high mortality rate related to rotavirus because the diarrhea can be so dehydrating. [My pediatrician] once told me that his gift in medicine as a pediatrician was to tell the difference between a sick kid and a not-sick kid. Because he knew I was a sick kid in his office, I was able to recover and have a healthy childhood. That practically made him a part of the family.

He helped me celebrate my high school graduation and my medical school graduation, where he joked that perhaps we could have a role reversal; I would love nothing more than to be able to care for him someday.

GFL: What drew you to study gender-based differences in celiac disease?

CJK: The interest in gender-based differences comes from a couple different angles. One is that I joined a male-dominated profession: 16.4 percent of practicing gastroenterologists in the United States are women. I was drawn to GI for that reason.

Within celiac disease, there’s this gender discrepancy within a population of people that we’re caring for. One of my goals was to provide excellent care for patients in general and in particular women with digestive issues.

Theoretically, half of the population is women. Many women prefer a female doctor. Given the male-to-female ratio of gastroenterologists right now, this isn’t always possible for our patients.

Sometimes in GI, we talk about sensitive issues such as bowel movements, patterns and habits. I want patients to feel as comfortable as possible because for most people this is not a typical topic of conversation. I can understand why some patients may prefer a doctor of the same sex, and one of many reasons why I chose GI was to help fill that gap in patient needs.

On a personal level, I would like to drive forward research in women’s health. Much of [the] research in the past, including in animal models, was done on males. This over-reliance on male cells and animals does not give us a clear understanding of sex differences in health and outcomes. Women used to be excluded from clinical trials, but the National Institutes of Health has changed that.

We need more female researchers, scientists and physicians to continue to make important contributions to their fields.

GFL: In writing for Gluten-Free Living, it seems women are equally represented among the top experts on celiac I’ve interviewed. Do you think celiac research attracts women because the disease seems biased toward them?

CJK: I am not sure. I am glad there are wonderful top experts in celiac disease who are women.  Personally, I had two male mentors in the field of celiac disease: Alberto Rubio-Tapia, MD, and Joseph Murray, MD.

You will also note that for the American College of Gastroenterology guidelines on the diagnosis and management of celiac disease, four of the five authors are men. This is one of the key references gastroenterologists use when diagnosing and caring for individuals with celiac disease.  

There are a growing number of female gastroenterologists. What is exciting right now is that all four major GI societies in the United States have female presidents.

Van Waffle is a freelance journalist based in Waterloo, Canada, and research editor for Gluten-Free Living. He blogs at vanwaffle.com.

Study Suggests Vast Majority With Celiac Remain Undiagnosed

The largest population study to date has found a lower prevalence of diagnosed celiac disease in the United States than was estimated by previous screening studies. This adds strong evidence that the vast majority of people with celiac remain undiagnosed.

Researchers at University Hospitals Cleveland Medical Center in Ohio identified 83,090 celiac cases in a commercial database of 35.9 million patients. This indicates about 0.23 percent, or 1 in 435 Americans, have been diagnosed with celiac.

Previous screening studies found celiac (both diagnosed and undiagnosed) affects up to 0.95 percent, or 1 in 105, Americans. The prevalence in some European countries is even higher. These new figures support estimates that more than three-quarters of American patients remain undiagnosed.

The data come from over 300 health centers across the country. It was aggregated to remove personal information so regional variations could not be determined. However, women, whites and adults were more than twice as likely to be diagnosed with celiac as men, non-whites and children, respectively. Age data suggests diagnoses peak during early childhood and again in women during their 30s and men during their 40s.

Celiac often occurred alongside other health complaints, especially autoimmune disorders such as lupus, inflammatory bowel diseases and Type 1 diabetes. The authors call for liberal use of celiac testing whenever unexplained symptoms could be related to celiac.

Some With Gluten Sensitivity May Regain Tolerance, Study Suggests

Research from Milan, Italy, suggests not all people with non-celiac gluten sensitivity (NCGS) must strictly avoid gluten forever. A small study of 22 patients found their responses to reintroduction of gluten varied widely. Some became sick again while others tolerated high-gluten diets.

After following a gluten-free diet for three weeks, volunteers consumed a low-gluten diet for one week. Two patients dropped out because they did not want to continue. Four others had adverse symptoms. Fourteen who reported none after the first week then switched to a mid-gluten diet. Six reported a symptom relapse. Eight who passed the second test without symptoms stepped up to a high-gluten diet for one week. All of them tolerated it without symptoms.

Those who finished the third week without problems were told to resume a normal gluten-containing diet. Others who experienced a relapse at different points were advised to continue a gluten-free diet or consume gluten at a low enough level to avoid symptoms.

While hopeful, this study has several weaknesses. The findings beg further research to see whether some NCGS patients can tolerate some gluten using a personalized approach. Long-term health effects of reintroducing gluten are unknown.

Study Finds Celiac Disease Can be Diagnosed Without Biopsy

A new study in Finland concluded celiac disease can be diagnosed accurately without a biopsy in some adults. These patients must score a triple positive on blood tests: 10 times the normal upper limit of tissue transglutaminase antibodies, positive for endomysial antibodies and a positive genetic test. In the study from University of Tampere, one-third of new celiac patients could have been diagnosed conclusively without a biopsy.

The group included 421 high-risk adults suspected of having celiac, 2,357 at moderate risk who were tested due to a family member having celiac and 2,722 low-risk individuals identified in a general population study. All participants underwent the three blood tests and a biopsy.

The tests diagnosed celiac in 274 people, with 90 meeting the triple positive criteria. In this latter group, biopsies proved blood tests diagnosis alone would have been 100 percent accurate. Triple positive diagnosis was possible in 37 percent of the high-risk, 20 percent of medium-risk and 48 percent of low-risk patients.

This large study of Finnish adults provides strong evidence for accurate diagnosis without biopsy. The authors advocate using non-invasive tests when appropriate in adults to save medical costs without sacrificing accuracy.

European gastroenterologists previously recommended the triple positive standard but only for children suspected of having celiac due to symptoms such as diarrhea. North American experts still disagree on its reliability, with some still holding biopsy as the gold standard. The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition has not yet endorsed celiac diagnosis without biopsy.

Study Supports Celiac Screening for Long-Term Health

A study from University of Bologna, Italy, supports screening for celiac disease even among adults. Earlier detection could prevent complications of the disease.

Despite high prevalence of undiagnosed celiac in Western countries, the value of screening programs remains controversial. Benefits of early diagnosis must outweigh the cost and risk of widespread testing. Critics argue patients diagnosed before they are aware of symptoms may be less motivated to stick with the gluten-free diet. This could in turn cause medical complications later on.

This study found 90 percent of patients detected through screening stuck with the diet, the same percentage found in patients diagnosed after they were suspected of having celiac. Data came from health records of 750 adult patients diagnosed from 2004 to 2013.

Researchers found an important long-term health benefit. Screened patients had a significantly lower rate of bone disease: 31.3 percent compared to 46 percent in other patients. They were also less affected by anemia.

The authors advocate screening adults to help diagnose the large hidden population of celiac patients. Improved health and reduced medical costs later on would balance costs of testing.

Following Gluten-Free Diet Essential for Bone Recovery

Celiac disease can impact bone development at a crucial stage in childhood. Compliance with a gluten-free diet is the prime contributor to bone recovery, according to a study from Virgen del Rocío University Hospital, Seville, Spain.

Intestinal damage from celiac prevents proper absorption of vitamin D and calcium for good bone health. Patients face an increased risk for osteoporosis and are twice as likely to break a bone. The gluten-free diet heals the gut lining and allows nutrients to reach the bones.

This study looked at 43 children ages 1 to 13 newly diagnosed with celiac between 2012 and 2016. A food questionnaire tracked dietary nutrition from before diagnosis to one year later. Both gluten-containing and gluten-free diets contained most of the necessary nutrients. Contrary to concerns that a gluten-free diet may be high in fat, researchers noted an improvement in the type of fat consumed. The patients consumed less saturated fats and more polyunsaturated fats.

Poor bone mineral density was found in 35.5 percent of patients at diagnosis. This improved significantly to 18.2 percent after one year on a gluten-free diet. The length of time required for full bone recovery remains unknown.

Nutrient intake was normal except for vitamin D, found to be deficient in both gluten-containing and gluten-free diets. The authors recommend supplements for children newly diagnosed with celiac but only if they have low vitamin D.

The Impacts of Celiac Disease on Mental Health

This is a common prescription for celiac disease: anxiety. Worry about every meal, every bite you take. If you happen to eat some gluten either accidentally or deliberately, it causes intestinal damage, increasing the risk for certain kinds of cancer, bone fractures and other complications.

While a gluten-free diet is the only treatment for celiac, hypervigilance can lead to mental illness.

A study from Harvard University and Columbia University recently reported people with celiac are more likely to recover from intestinal damage if they have a mood disorder. The scientific paper states prosaically, “Prior psychiatric disease was associated with mucosal healing.”

The pattern was especially strong for people who developed anxiety after being diagnosed with celiac. However, people with a prior mood disorder were also more likely to score a passing grade on their follow-up biopsy. Patients who let troubles roll off them were less likely to achieve intestinal healing. The findings came from health records of 7,648 Swedish patients collected over 40 years.

The Unseen Toll

“We see healing as a good thing. Healing is a reflection of strict adherence to the gluten-free diet,” says Benjamin Lebwohl, MD, assistant professor of medicine at Columbia University Medical Center in New York, who worked on the study. “It does appear that the treatment of celiac disease, the gluten-free diet, can exact a toll on the patients. Even if the patients are physically better off, some patients may suffer with regard to depression and anxiety.”

The impact on long-term mental health is also sobering. The study reports celiac patients who achieve complete healing of the small intestine face an almost 50 percent greater risk for future anxiety disorder and a 25 percent greater risk for depression.

“Patients who have celiac disease but have untreated depression are still patients who are suffering,” Lebwohl says. “Sometimes the presence of untreated depression can prevent a patient’s intestinal-related symptoms from improving. It comes up clinically even if a patient is strictly avoiding gluten. If they have an untreated mental illness, they will not feel better physically.”

Researchers hesitate when asked whether mood disorders are more prevalent in celiac patients than the general population.

A 2017 study of 22,000 people in the National Health and Nutrition Examination Survey found celiac patients had no increased odds for depression or sleep disorders.

Marilyn Geller, chief executive officer for the Celiac Disease Foundation (CDF) in Woodland Hills, California, points to gluten exposure itself as a frequent cause of distress: “There is a significant percentage of people with celiac disease or non-celiac gluten sensitivity (NCGS) who report anxiety, depression and brain fog from consuming gluten.”

It is often reported by patients in CDF’s online registry of 5,000, but the voluntary nature of the database prevents statistical interpretation. Geller says the percentage is significant enough that the patient advocacy group partnered with Children’s National Health System (CNHS), a children’s hospital in Washington, D.C., to develop continuing education in mental health support for celiac care providers.

Celiac and Child Psychology

In 2017, CNHS created a full-time psychologist position in its celiac program. Shayna Coburn, PhD, works directly with patients while developing a psychosocial health program to incorporate research and community outreach.

Coburn says she learned the challenges firsthand after being diagnosed with celiac while a graduate student in psychology in 2010.

“I was already interested in health psychology in children and suddenly had to face it myself,” says Coburn. “I started to notice there’s a lot of stress associated with coping with any chronic illness, especially with the challenges of the gluten-free diet. I didn’t find any resources out there. I had a lot of trouble even finding people who felt comfortable talking about the mental health struggles that come up.”

With the CNHS database in its first year, it cannot yet provide figures on how mood changes in patients over time. However, the initial baseline tells us something: “Thirty-four percent of families who come in report an existing mental health diagnosis in their child before they even walk through the doors,” says Coburn.

Anxiety disorders appear in 16 percent and attention deficit hyperactivity disorder (ADHD) also appears in 16 percent of children up to age 12 in the CNHS celiac program.

“We see large proportions of families reporting anger and overall distress in their children on an ongoing basis. That could be indicative of depression, but it is harder to diagnose that in kids. Irritability is a hallmark of depression in kids,” says Coburn.

In addition to those with a previously diagnosed psychological disorder, Coburn says she sees unrecognized cases of children who meet criteria for mental health problems. She believes 34 percent is a conservative estimate of their prevalence in children with celiac.

Parents sometimes ask if a diagnosis of anxiety disorder or ADHD could be caused by celiac itself: “We don’t fully know the answer. I usually tell them that we know there’s a link, but we don’t know if it’s going to get better. For some people it does, for some people it doesn’t, for some people it gets worse,” says Coburn, adding that CNHS’s research aims to understand the risk factors better.

Clues From Quality of Life

While not specifically a measure of mental health, quality of life has often been studied to assess the burden of chronic diseases. The questionnaire specific for celiac patients addresses problems such as social and travel barriers. In particular, patients are asked whether they feel depressed, frightened or overwhelmed by celiac.

A separate study by Columbia University in 2017 found celiac patients who were hypervigilant about their diet scored lower on quality of life. The hypervigilant group knew how to read food labels better. They cooked at home and used internet apps and sites to help stay gluten free. They chose celiac-friendly restaurants and asked questions of their servers—all things they are supposed to do.

“Eating out was particularly problematic,” the study reports.

Scoring lower on quality of life pushed hypervigilant patients into a worse category of self-rated health, stress, pain and ability to cope. The study included 50 adults and 30 teenagers enrolled at the Celiac Disease Center of Columbia University, New York. Psychological patterns were similar for both age groups.

The study notes a contrast with earlier research on quality of life in European celiac patients. However, in Europe, the gluten-free diet is more widely understood as a medical necessity for people with celiac. In North America, the gluten-free trend can lead to trivialization by food services. Some restaurants that brand themselves gluten free may not take adequate precautions. This makes celiac patients work harder to ensure their food is safe.

Both studies of hypervigilance suggest a gluten-free diet is achievable and promotes complete healing of celiac damage in the gut. However, it can restrict lifestyle and impose significant distress on many patients.

Beating Social Isolation

“It’s common that people feel socially isolated because of the combination of factors that go into trying to keep a strict gluten-free diet,” says Coburn. “In addition, when somebody experiences anxiety about potential exposure or about embarrassing or uncomfortable physical symptoms, they will cope by withdrawing from the feared situation. Social situations are scary at first. They’re overwhelming. People can accidentally reinforce avoidance and strengthen their anxiety by doing what they think keeps them safe and healthy. It’s a tough balancing act because they need to be vigilant, but it might become hypervigilant.”

For example, when attending an event where the food might not be safe, a patient can choose not to eat it. That is a reasonable coping strategy.

However, avoiding contact with friends or family out of fear of being pressured to eat something causes unreasonable social isolation.

“Shrinking into your world and only doing what you know to be safe can become a terrible feedback loop of feeling low, unmotivated and losing enjoyment in things. That makes it even harder to advocate for yourself and change the situation,” says Coburn.

A Holistic View

Lebwohl puts responsibility on doctors to become more aware of the interplay between physical and mental health, especially in celiac.

“In today’s climate, often we focus on the diagnosis at hand. We tend not to take a holistic view of the patient. If a gastroenterologist is taking care of the patient, he or she may be more likely to focus on intestinal symptoms, not impact on quality of life and mood. Because the treatment of celiac disease is a diet, too often patients report they were told by a practitioner to, ‘Google the diet, and you’ll be fine.’ This is really not enough,” says Lebwohl.

“Some patients will be very forward with regard to their psychic state and their physical state, whereas other patients may be less likely to see a connection or to raise it,” he adds. “For some, it’s not much of an issue. For others, it can really impact quality of life. For still others, there may be undiagnosed or untreated mental illness that impacts their ability to thrive.”

A holistic approach takes into account not only intricacies of the diet but also emotional challenges likely to come up, he says.

These include social challenges, impact on family life, the burden on a patient’s partner and how the diet affects work and travel. For new patients, Lebwohl says, “There’s no substitute for a session with an expert dietitian competent in the intricacies of a gluten-free diet. That competence speaks not only to what foods must be avoided but also knowing what measures might not be necessary and how to navigate a successful gluten-free diet that does not require social isolation and over-restriction.”

Van Waffle is a freelance journalist based in Waterloo, Canada, and research editor for Gluten-Free Living. He blogs at vanwaffle.com.



Shayna Coburn, MD, offers coping strategies for living with celiac disease and a gluten-free diet.

  1. Know what you want your life to look like. Identify your goals and move toward them gradually. Take your time. If you feel anxious about something you want to do, try not to do it all at once but break it down into baby steps. Keep your priorities in mind to balance being vigilant with having good quality of life.
  2. Think about how to advocate for yourself. Decide how you want to communicate with other people. How much information do you want to disclose? Create a script to explain your needs. Practice it.
  3. You do not have to tell everybody. Usually people will not even notice you avoid gluten. You can find out what you need to know from party hosts and restaurant managers without drawing attention to yourself.
  4. Parents are sometimes not careful about what they share because they are trying to advocate for their child. Some kids will not mind, but others just want to fit in and do not want people knowing all the details. Coburn encourages families to discuss what needs to be said for safety and what is optional.
  5. Reach out to people in the celiac community. Connect with people who reassure you that you are not alone.
  6. Fact check everything you hear about gluten safety, especially from online support groups, because misinformation can cause unnecessary anxiety. The best source is a dietitian knowledgeable about celiac.
  7. Parents of children with celiac are prone to feeling stressed and overwhelmed, too. They need to reach out for their own support.

Promising Drug Can Relieve Serious Celiac Disease

A drug has been found that can relieve the most rare and serious form of celiac disease. While approval for treatment will still take several years, experts hope it could also treat milder cases of the disease.

The drug AMG 714 is a form of a human antibody, anti-interleukin 15. It prevents inflammation and damage to the lining of the small intestine on exposure to small amounts of gluten.

California-based pharmaceutical company Amgen previously licensed AMG 714 to Celimmune, a smaller company focused exclusively on celiac research, to conduct early trials in people with celiac. In 2018, Celimmune reported AMG 714 relieved symptoms and stopped progress of the disease in patients with refractory celiac type II (RCDII). This is a severe, often fatal condition in which inflammation evolves into a type of cancer (see sidebar).

“While I’ve seen a reasonable number of RCDII patients in the past, they’ve all done very poorly and died,” says Peter Green, MD, director of the celiac disease center at Columbia University in New York, who worked on the study. “It is uncommon, but when one sees them, they sometimes don’t survive all that long. It is a disease that is in need of a therapy.”

The yet-unpublished study highlights how rare the condition is. Within the United States, Green says he found only two patients to enroll, one in the east and one in the west.

“I called most of the university gastrointestinal divisions in the eastern side of the country to see if they had patients,” he explains. “Either the patients are not there, or they’re not being recognized, or they’re not being looked after in university medical centers.”

However, results of the study were hopeful, says Fernando Leon, PhD, a cofounder of Celimmune.

“We showed that anti-IL 15 was able to ameliorate or reduce the effects of gluten consumption in celiac patients,” says Leon. It reduced gut inflammation and improved symptoms while being well tolerated by the patients.

Evidence in celiac monkeys

Support for the drug has come from treatment of rhesus macaque monkeys with celiac-like disease. In a recent study, six gluten-sensitive monkeys showed improvement when treated with the drug while on a normal, gluten-containing diet.

Karol Sestak, PhD, core scientist at Tulane National Primate Research Center in Covington, Louisiana, has spent 12 years describing and comparing celiac in monkeys with that in humans. Medical research has more often used mice genetically engineered to be gluten-sensitive. However, macaques are more similar to humans both genetically and physiologically, offering advantages when studying therapy for humans.

Besides, they do not need to be genetically altered. The disease naturally occurs in a small percentage of macaques as it does in people. Sestak says his team discovered this while studying digestive problems in the primate colony in 2006. Various viral infections in the monkeys had already been isolated.

“Occasionally, there would also be some disease in these nonhuman primates where you cannot trace any kind of infectious agent when they have chronic diarrhea. Back then, we were wondering what that could be,” says Sestak. “We reformulated their diet. We removed all the gluten sources from the monkey chow. It was our first gluten-free diet. Their conditions dramatically improved.”

The researchers then found the celiac monkeys had the same disease antibodies detected in humans. Those antibodies decreased when the animals were treated with a gluten-free diet. Another similarity with human patients is that gluten-sensitive macaques display a wide spectrum of disease. Some are seriously affected, some moderately and some mildly. When identified in their routine check-ups, these individuals are placed on a gluten-free diet or can be assigned to try out another promising therapy.

In AMG 714 trials, it reversed inflammation and damage in all six animals regardless of the seriousness of their disease. Their recovery was checked using biopsy for a close look at the gut lining. The treatment also improved some but not all markers for immune disease outside the intestine, such as antibodies detected by blood tests.

AMG 714 works by suppressing IL 15, which appears to be a major immune agent but not the only one active in celiac. Since the drug healed intestinal tissue but did not reduce all disease markers, this suggests it might work best alongside a gluten-free diet or other therapy.

Next step for AMG 714

After the trial in humans, Amgen acquired Celimmune. Then, later last year, Amgen offered AMG 714 for further study to Provention Bio, which focuses on autoimmune diseases. Leon is once again a cofounder and chief scientific officer of this smaller company, based in Washington, D.C.

Provention Bio will conduct the next stage of research in non-responsive celiac. This condition includes patients who have persistent disease despite a gluten-free diet, but it is not as severe as RCDII. Toxicology tests must first be performed.

“With any molecule that you block in the immune system, you’re always blocking physiological function. Then the question is, what is essential for our survival and what is not essential?” says Leon. “The goal of drug development is to identify a target which is more important in disease than it is in healthy life. That’s when you get a good benefit-risk profile.”

Amgen initially developed AMG 714 to treat rheumatoid arthritis. These large human trials already showed the drug is well tolerated by patients, says Leon. For the next round, however, more evidence is needed to support using it over a longer period of six months. This will delay starting a study in non-responsive celiac patients until 2020, Leon says. If warranted, studies of safety and effectiveness in progressively larger groups will take several more years.

“I think we’re going to see the first drugs in celiac in the next four to six years,” says Leon.

Neither AMG 714 nor any other therapy currently under study is designed to replace the gluten-free diet, says Green. Medical research prioritizes therapy for people who remain sick despite a gluten-free diet. Once such drugs are approved, further efforts could investigate a drug’s ability to restore gluten tolerance.

Leon says, “We shouldn’t leave patients on their own like we’ve been doing for decades: ‘Just avoid gluten, goodbye.’ Celiac patients need to be provided tools corresponding to the severity of this disease. They need to be provided first and foremost with a nutritional tool: How to avoid gluten. They need to be provided with diagnostics to confirm the gluten-free diet. Finally, for patients who despite best efforts do not manage to avoid gluten, they need to be provided with medicine.”

Compassionate grounds

Meanwhile, drug companies can make treatments like AMG 714 available on compassionate grounds for people with life-threatening illness like RCDII, says Green, “but I’m not sure. I don’t have any patient currently on the drug. It’s not clear how many patients with RCDII are out there, as they aren’t being seen at the few celiac centers where people are equipped to look after them.”

Patients with severe forms of celiac could play an important role in medical research, Green adds. However, they must go to university celiac centers where therapies are being developed.

Degrees of celiac disease

Are you following a gluten-free diet but still experiencing symptoms? First, give it time. Even in the absence of gluten, the gut lining can take a while to heal. If symptoms continue more than a few months, they should be investigated by a doctor. Here is what can happen with poorly controlled celiac.

Non-responsive celiac disease

Symptoms continue and the small intestine fails to heal despite adherence to a gluten-free diet. This can occur for various reasons that need thorough investigation with a doctor. The most likely cause is unknown sources of gluten. A dietitian knowledgeable about the gluten-free diet can help sort it out.

RCDI might occur if gluten exposure continues to damage the small intestine. In rare cases, the immune system produces abnormal attack cells in its ongoing defense against gluten.

This is different from non-responsive celiac. RCDI is rare even among celiac patients who continue to experience symptoms. However, people with non-responsive celiac have an increased risk of developing refractory celiac disease. Likewise, patients with RCDI have a 50 percent risk of developing the next, most serious condition.

Refractory celiac type II

RCDII occurs when one abnormal attack cell starts reproducing itself uncontrollably. This is a type of blood cancer, specifically non-Hodgkin lymphoma localized in the intestinal lining. RCDII is rare, affecting an unknown minority of adult celiac patients, probably 2 percent or less. Unfortunately, the prognosis is poor.

How AMG 714 works

Interleukin 15 (IL 15) is a small protein the immune system uses to send signals between cells. Normally it helps defend the body against viral infections. When a virus is detected, immune cells release IL 15 to stimulate production of natural killer (NK) cells and killer T-cells. They in turn destroy virus-infected cells.

However, NK cells and killer T-cells act indiscriminately. In celiac, they attack cells in the gut lining when gluten is present.

AMG 714 is a human antibody that neutralizes IL 15, breaking the signal to attack. It stops killer cells from reproducing themselves and halts damage to the small intestine.

Family Screening for Relatives of Celiac Patients

Many people at risk for celiac are not being tested according to medical guidelines. Columbia University found 30 percent of people with relevant symptoms, who had a first-degree relative with celiac disease, were not screened.

Current national guidelines do not recommend screening people without symptoms. However, experts call for a more aggressive approach to diagnose patients early and improve their outcomes. Even patients without symptoms benefit from going gluten free because they have fewer digestive problems, less intestinal damage and less anxiety about the illness.

Studies estimate the disease affects 10 percent of people who have a first-degree relative with celiac. To achieve earlier diagnosis, guidelines recommend screening parents, siblings and children of those with celiac.

Columbia University Irving Medical Center and New York-Presbyterian Hospital compiled medical data from relatives of 2,081 patients with celiac, identifying 539 relatives who later attended the center. In this group, 39.3 percent were tested for celiac. Among 165 first-degree relatives with celiac symptoms, only 71.5 percent were screened. Screening was much more likely for patients seen by a gastroenterologist (rather than another type of doctor) and those who had a family history of celiac clearly documented in their health records.

The authors speculate screening may be even less common in institutions that, unlike Columbia, do not specialize in celiac. This study calls for including family history in electronic health records and wider screening of first-degree relatives.

Faye AS, Polubriaginof F, Green PHR, Vawdrey DK, Tatonetti N and Lebwohl B, “Low rates of screening for celiac disease among family members,” Clinical Gastroenterology and Hepatology, 15 June 2018, doi:10.1016/j.cgh.2018.06.016.

Gluten-Free Diet Helps Some With Schizophrenia in Pilot Study

A gluten-free diet may help treat schizophrenia in some cases. During five weeks without gluten, patients who had elevated immunoglobulin G type antibodies (AGA IgG) improved in psychiatric and intestinal symptoms.

The treatment did not improve what are known as positive symptoms of schizophrenia, such as hallucinations. However, it significantly improved so-called negative symptoms, such as lack of motivation and inability to express emotion or experience pleasure.

“With a small population I thought we would see a mild effect. I was pleasantly surprised to see symptoms change dramatically in some of our patients,” said lead researcher Deanna Kelly, PharmD, director of treatment research at University of Maryland, Baltimore. She explained negative symptoms are arguably what hinder social functioning: “Some people can manage their voices and bizarre thoughts in a way that they can still work. But if you have no motivation and no social abilities then it becomes difficult to function.”

Kelly noted that anti-psychotic drugs target delusions but are relatively ineffective against negative symptoms.

In the blinded trial on a gluten-free diet, seven patients received 10 grams of gluten daily and seven patients received 10 grams of rice flour in a protein shake. At the beginning, no one was complaining largely about digestive problems such as abdominal pain and constipation. However, after five weeks the gluten-free group’s gastrointestinal symptom scores improved robustly. This benefit was unexpected, Kelly said.

Previous investigation suggested a link between inflammation and schizophrenia. Celiac disease, an autoimmune disorder triggered by gluten, affects about three percent of people with schizophrenia compared to one percent of the general population. However, one-third of those with schizophrenia have elevated AGA IgG. This is three times the prevalence in the healthy population. High AGA IgG is not normally found in celiac.

John Hopkins University research showed AGA IgG in schizophrenia may cross the blood-brain barrier, which normally protects the brain from antibodies. It could cause brain inflammation, which is observed in other conditions like multiple sclerosis and HIV.

Inflammation does not occur in all people with schizophrenia, suggesting it is a syndrome with various underlying causes. While a link with gluten has been discussed for decades, previous indiscriminate gluten-free trials may have obscured the benefits in the subgroup with high AGA IgG. The University of Maryland trial included only patients with elevated AGA IgG and excluded those with celiac.

“Schizophrenia is a rare but debilitating condition, and it is exciting to see any possibility for treatment,” said Shayna Coburn, PhD, psychologist at Children’s National Health System in Washington D.C., who did not work on the study. Coburn specializes in mental health for children with celiac but previously worked on schizophrenia research. “There is increasing interest on the possibility that a gluten-free diet might help certain people with mental illness, but we are still far from understanding whether this is true.

“This study is a great starting point, but it is still just a starting point,” Coburn added. “Should everyone with mental illness go on a gluten-free diet? I wouldn’t advise it just yet, given the stress and daily burden that it can create.”

Kelly said, “I’m surprised to see such a robust improvement and I’m hopeful that even in a sub-group of people this might be a potential treatment.”

Growing Gluten-Free Industry a Double-Edged Sword for Those With Celiac Disease

People with celiac experience the rising gluten-free industry as a double-edged sword with benefits and challenges. Subjective experience is hard to quantify, but a new study utilized a novel technique.

The study at University of Calgary, Canada, relied on a psychological approach called interpretive phenomenology. Instead of testing a hypothesis using numerical statistics, it analyzes unstructured interviews with a small number of volunteers to reveal recurring themes. Researchers must continually evaluate their own previous biases.

The study recruited 17 adults with celiac who followed a strict gluten-free diet. Three had been diagnosed as children and two as adolescents, the rest as adults. Time since diagnosis ranged from less than a year for four volunteers to more than 10 years for six individuals. Interviews lasted 45 to 60 minutes and addressed a proliferation of gluten-free foods. After transcribing the conversations, researchers then used phenomenology to categorize excerpts and identify connections. The process concentrated on ideas shared by many participants, while discarding those less common.

The results highlight three consequences for people with celiac: changing social climates one participant described as a “double-edged sword,” altered self-image and psychosocial perseverance. Gluten-free options allow patients to eat out but increase their risk of getting glutened, for example. This affects self-image because other people may perceive patients as rude or high maintenance. Patients may even see themselves this way. Psychosocial perseverance means they must accept the diagnosis and its consequences, developing strategies to avoid gluten while trying not to let it consume their lives.

The study provides objective insight on the complexity of living with celiac. The authors call for non-dietary therapies, allowing patients a more fulfilled social life.

Dietary Fiber May be the Real Challenge in Gluten-Free Foods

A low-gluten diet alters the human microbiome. However, this may relate to quality of dietary fiber in the food, not a reduction in gluten itself. New evidence comes from a Danish study in which healthy adults showed significant weight loss and experienced less bloating on a low-gluten diet compared to when they consumed a gluten-rich diet.

The study included 60 volunteers age 22 to 65 who were not diabetic and did not have celiac or other gastrointestinal diseases. They consumed one of two diets for eight weeks, then the other diet for another eight weeks after a washout period between. The two tests replaced all cereal foods with either a low-gluten or an enriched-gluten product of similar nutritional quality. Gluten consumption averaged 2 grams and 18 grams per day, respectively, compared with 12 grams on a normal diet.

DNA from stool samples showed the low-gluten diet consistently altered abundance of 14 bacterial species. This did not affect the health of participants over eight weeks, though long-term effects are unknown. Microbial function decreased metabolism and availability of carbs for the gut to absorb.

Other subtle changes occurred, such as availability of various micronutrients. Glucose and fat metabolism remained unchanged. However, participants lost on average 1.8 pounds during the low-gluten diet despite consuming the same amount of food energy. The cause is uncertain and requires further study.

Participants reported less bloating on the low-gluten diet. Measurements of breath hydrogen backed up these subjective experiences. Chemical analysis indicated the cause was an altered fermentation process.

These results in Danish Caucasian volunteers need further study to be generalized to a wider population.

Low Bone Density in Children With Celiac Disease

On diagnosis, children with celiac had three times the normal risk for low bone mineral density in a study at The Children’s Hospital of Philadelphia, Pennsylvania. The risk mainly concerns children with low body mass index. Patients who received a repeat X-ray showed a significant improvement, probably due to following a gluten-free diet. The study did not find any benefit to rescreening those with good bone density on the first test.

Untreated celiac can cause poor absorption of calcium, hindering bone development. However, most gastroenterologists do not screen children with celiac for low bone mineral density because there has been a lack of supportive research. Previous studies were small and did not highlight additional risk factors to help doctors know which patients were at risk.

This study considered previous medical records from 673 children with celiac who underwent X-rays between 2009 and 2016 at the hospital. Seven percent had low bone mineral density. Among children with low body mass index, the prevalence was 10 percent, almost three times higher than for those with normal body weight. This suggests body mass index could be used to indicate a need for X-rays. Further study will be necessary to clarify the prevalence of bone problems by following new patients from diagnosis through treatment and follow-up.

Webster J, Vajravelu ME, Choi C, Zemel B and Verma R, “Prevalence of and risk factors for low bone mineral density in children with celiac disease,” Clinical Gastroenterology and Hepatology, 30 Nov 2018, doi:10.1016/j.cgh.2018.10.035.

Van Waffle is a freelance journalist in Waterloo, Canada, and research editor for Gluten-Free Living. He blogs at vanwaffle.com.

Is Sourdough Bread Gluten Free?

In bread-making, sourdough cultures reduce FODMAP content, which are carbs poorly absorbed by the digestive system. European and Australian studies have found sourdough fermentation breaks down gluten too. Clinical trials indicate thorough sourdough fermentation could potentially make wheat bread safe for people with celiac.

Because they are hard to digest, a temporary low-FODMAP diet can benefit people with irritable bowel syndrome. Some studies of non-celiac gluten sensitivity blame FODMAPs in wheat products rather than gluten. Even in newly-diagnosed celiac patients with digestive problems, a temporary low-FODMAP diet might aid recovery by restoring gut function. While those with celiac must eliminate gluten, FODMAPs only need to be reduced to a safe lower level for a few weeks.

While sourdough could theoretically provide a nutritious, high-fibre addition to the gluten-free diet, such commercial products do not yet exist. Some North American artisanal bakeries falsely advertised sourdough breads as being safe. Gluten Free Watchdog tested three such products and found they contained gluten many times the level considered safe for people with celiac.

“Folks with celiac disease or another gluten-related disorder can’t eat commercially available sourdough wheat bread, including those made by artisanal bakers,” says Tricia Thompson, RD, founder of Gluten Free Watchdog. “Bakers must stop thinking that somehow their bread is special and has magical powers that somehow allow folks with celiac disease to eat it. They can’t.”

If technology could render wheat bread safe by thorough fermentation of gluten, note that it would lack the popular texture of gluten-containing sourdough.

Antibiotics in Infants Linked with Celiac Risk

Newborns exposed to antibiotics during their first year have a 26 percent higher risk for celiac disease, according to new research.

“The gut microbiota in early life is highly influenced by antibiotics,” says Stine Dydensborg Sander, PhD, of Odense University Hospital, Denmark, lead author of the study. Her findings support growing evidence that composition of the gut bacteria in early life affects the immune system and risk for celiac.

“To develop celiac disease you need to be genetically predisposed and to eat gluten. However, about 40 percent of the western population carry the genes predisposing for celiac disease, most are eating gluten, but only a few develop celiac disease. We do not know why some people develop celiac disease or what protects some people from developing celiac disease. We know that the prevalence of celiac disease has increased but we do not know why,” says Dydensborg Sander.

The research included all children born in Denmark from 1995 to 2012 and in Norway from 2004 to 2012 who had medical information available. Out of 1.7 million individuals, 3,346 were later diagnosed with celiac.

It was the largest study so far of antibiotics and celiac risk in children. Both country’s populations showed the association. Risk increased with how many antibiotic treatments a child received.

The study also compared antibiotic types and age at exposure within the first year but found no effects. The authors investigated what the paper calls, “parental health-seeking behavior,” that might influence antibiotic use and celiac diagnosis but concluded it was unlikely to skew results.

“This study does not show that antibiotics cause celiac disease in the individual child,” says Dydensborg Sander. “Use of antibiotics should always be carefully considered in consultation with your doctor; there are many important considerations to take. The risk of celiac disease is not something that needs to be addressed specifically in these considerations.”

It is too early to conclude how various risk factors affect the microbiome, she adds. However, further study may suggest opportunities for preventing celiac.

Permanent Immune Scarring Identified in Celiac Disease Patients

New research has identified permanent “immune scarring” in celiac disease which persists despite recovery on a gluten-free diet. It helps explain why patients never recover tolerance for gluten. The evidence encourages early diagnosis of celiac and has implications in the search for a cure.

The study showed, “that subsets of long-lived immune cells that reside in tissues such as the intestine and function to protect us under normal conditions can be permanently lost as a consequence of chronic inflammation,” says Toufic Mayassi, graduate student in the committee on immunology at University of Chicago, who was the primary researcher and author.

In early inflammation the healthy immune arsenal continues to operate but eventually reaches a tipping point. Then pro-inflammatory cells overtake the niche previously occupied by the protective cells. In celiac these new cells are activated by gluten.

“We were able to identify a subset of pre-celiac patients where the immune compartment was not yet fully altered suggesting interventions in these individuals may allow for the preservation of their healthy immune makeup. With the current treatment strategies this would only be accomplished by placing these individuals on a gluten-free diet prior to the full development of the disease,” says Mayassi.

“In the same vein, we observe in a subset of young children where the diagnosis was made early that they preserve various features of the healthy immune compartment suggesting again if treated early the impact of disease manifestation may be blunted. We will be able to determine whether or not these children maintain the healthy subset as we study them over time,” he adds.

Once they are supplanted, the gut does not recover the population of cells normally involved in preventing infections and tumors.

“That celiac patients permanently lose these cells leaves a functional vacancy that may predispose these patients to future infections and development of intestinal tumors,” says Mayassi. “Work towards a cure for celiac disease will need to consider that complete effectiveness of a treatment may depend on fully restoring the immune composition found in the gut in a manner that fully recapitulates the healthy gut.”

Celiac provides a good model for inflammatory disease because it can be controlled by removing gluten. Mayassi says the findings may help understand other conditions where tissue-resident immunity is profoundly altered, such as inflammatory bowel disease.

Poor Follow-Up for Children With Celiac Disease

Children with celiac receive inadequate medical follow-up, according to a study at Boston Children’s Hospital. Within three years, half of patients were lost to follow-up, despite national guidelines that all celiac patients need routine assessment. Children diagnosed at a younger age and those with private health coverage were found to continue seeing their gut specialist longer.

The data were collected and analyzed by Boston University student Bradley Blansky for a master’s thesis. He drew records of 250 randomly selected children diagnosed with celiac at the hospital between 2010 and 2014. After diagnosis, 9 percent did not attend any follow-up visits, 14 percent stopped attending within the first year and 17 percent failed to receive counseling from a dietitian. One quarter of patients gave abnormal blood tests on their last visit, indicating poor dietary adherence.

Experts advocate follow-up because children with celiac have a better quality of life when they receive medical support to change their diet and lifestyle. Adolescents need help with knowledge and skills adjusting to peer pressure and new situations. Follow-up can also prevent eating disorders, anxiety and depression, increased risks for children on restrictive diets.

Health providers may need to take more proactive measures to ensure children with celiac receive continued care.

For more information for gluten-free kids, click here.

Celiac Raises Risk for Teen Eating Disorders

Teens with celiac disease have a higher risk for eating disorders, according to new research from Tel Aviv University, Israel. The risk increases for adolescents who are overweight, female and older.

“This study could encourage families of individuals with celiac disease or their caregivers to increase their awareness to any signs of eating disturbance,” says Itay Tokatly-Latzer, MD, who worked on the research. “When there is a condition where you are preoccupied with an element of food restriction, you are predisposed to develop disordered eating behavior.”

Researchers conducted a web survey of 136 celiac patients aged 12 to 18 recruited through a national disease organization. One-third said they adhere strictly to a gluten-free diet while 11 percent reported poor adherence. The study found no link between dietary adherence and eating disorders.

Participants rated themselves on 26 questionnaire items such as, “I am preoccupied with a desire to be thinner,” and “I feel that food controls my life.” Seven percent of males and 19 percent of females recorded high scores overall for disordered eating. This compares with three and eight percent respectively among adolescents in the general Israeli population, reported by a separate study.

“Since disordered eating is even more prevalent in North America than in our region, I would say our data could not only be generalizable to North America, but the phenomenon could probably be even more prominent there,” says Tokatly-Latzer, a pediatrician at Dana-Dwek Children’s Hospital of Tel-Aviv Medical Center.

Having to follow a gluten-free diet could enhance risk for body image issues, the study suggests. Similar problems have been observed in conditions like inflammatory bowel diseases. Fear of painful symptoms, lack of alternate gluten-free foods and uncertainty about gluten contamination at parties could raise anxiety for teens with celiac.

Low FODMAP Diet Helps Heal Celiac

Italian research shows a temporary diet low in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) can help those with persistent celiac symptoms despite adherence to a gluten-free diet. Study participants showed improvements in both digestive complaints and mental health after only three weeks.

Read Getting a Grip on Gluten Sensitivity: Do FODMAPs Play a Role?

The study at a teaching hospital at University of Milan recruited 50 volunteers with celiac. Those selected still had irritable bowel syndrome or other intestinal problems after eating gluten free for at least one year.

Half the group was randomly assigned to follow a regular gluten-free diet while the other half also went on a low-FODMAP diet for 21 days. Overall symptoms improved only for the low-FODMAP group. They reported much lower abdominal pain and better fecal consistency. Both groups showed an improvement in psychological wellbeing, but it was much higher on a low-FODMAP diet. The improvement for those eating only gluten free probably resulted from increased support for dietary adherence during the study.

Click here for a list of foods with high and low FODMAPs.

This is the first study of its kind researching a low-FODMAP diet in celiac patients. In some cases, temporary elimination of FODMAPs can restore a disturbed gut to a healthier state able to tolerate most foods.

This study did not follow up to determine whether benefits impacted long-term health. More study will be needed to prove any sustained effect on celiac patients’ quality of life.

Roncoroni L, Bascuñán KA, Doneda L, et al. “A low FODMAP gluten-free diet improves functional gastrointestinal disorders and overall mental health of celiac disease patients: a randomized controlled trial.” Nutrients. 2018;10;1023. doi:10.3390/nu10081023.

Diabetes Risk from Low Gluten

Data from three large studies found that healthy American adults who eat less gluten have a higher risk for type 2 diabetes. It is already known that people who adopt a gluten-free diet sometimes miss out on dietary fiber, B vitamins, iron and calcium. This research also found they had a lower intake of folic acid and magnesium and a less-healthy diet overall. A normal, gluten-containing diet may be healthier in the long run for people without gluten sensitivity.

The data came from dietary questionnaires completed by health-care workers for their own eating habits every other year beginning as early as 1984 until 2013. It included about 202,000 healthy participants. Gluten consumption was estimated based on the foods they consumed. During follow-up, 15,947 individuals developed type 2 diabetes. The risk for diabetes was strongly and inversely proportionate to gluten consumption.

The reason for this pattern is unclear. Gluten itself probably does not protect people from diabetes. A diet low in gluten, besides lacking certain nutrients, may reduce beneficial bacteria in the intestine. It could also increase absorption of carbohydrates, straining the body’s ability to stabilize blood sugar.

Want to learn more about diabetes? Visit DiabetesSelfManagement.com.

PillCam Explores Gut for Clearer Celiac Diagnosis

A small capsule containing a camera can, when ingested by a patient, explore the small intestine for a celiac diagnosis. Combined with computer technology, it can diagnose the disease without an invasive procedure and with greater accuracy.

Gut experts normally use endoscopy to look for telltale damage from celiac. Human analysts sometimes misinterpret images and tissue samples from the gut lining. Some doctors and patients skip the endoscopy altogether, relying on even less accurate blood tests. Misdiagnosis is common in celiac patients.

Research from Singapore and Columbia University has developed an approach that could reduce the fuss and uncertainty. The patient would ingest a small capsule called a PillCam to capture images of the gut in its travels. The person would carry a data recorder for eight hours. The pill would pass out of the body after a day or two.

Video clips would be sent to a computer deep-learning system trained to detect celiac. It can distinguish diseased from healthy gut lining with 100 percent accuracy.

The technology still has some kinks. It needs a large volume of images and cannot make a diagnosis in real time. The researchers developing the system plan to fine tune it for efficiency to help doctors cut the rate of misdiagnosis.

Van Waffle is a freelance journalist in Waterloo, Canada, and research editor for Gluten-Free Living. He blogs at vanwaffle.com. 

Gluten-Free Diet Helps Kids With Celiac More Than Adults

Children treated for celiac heal faster than adults. In a study at the University of Chicago, most patients reported improved symptoms after two years on a gluten-free diet. However, gastrointestinal complaints like bloating and diarrhea resolved better than non-digestive problems like fatigue.

The study tracked 554 celiac patients—227 children and 227 adults. When first diagnosed, 78 percent of children and 91 percent of adults had at least one classic digestive complaint: abdominal pain, diarrhea, bloating, failure to thrive in children, weight loss in adults or constipation. Extra-intestinal symptoms appeared alongside or sometimes on their own: headache, fatigue, iron deficiency anemia and psychiatric disorders. Three percent of adults and 10 percent of children diagnosed through screening had no symptoms.

After two years of treatment, both groups showed high rates of gastrointestinal improvement. Bloating, diarrhea, weight loss and abdominal pain had each resolved by at least 81 percent in children and 71 percent in adults. Extra-intestinally, children recovered well from poor mood and anemia, less so from short stature and psychiatric disorders. Adult anemia resolved well, but poor mood and muscle pain improved by only 50 percent.

Hilary Jericho, MD, says a key message is patients need an appropriate expectation for the speed of recovery. She is director of pediatric clinical research at University of Chicago Celiac Disease Center, where she and colleagues collected data from patients treated between 2002 and 2015.

“Patients come to me for a second opinion because they were diagnosed with celiac disease three months ago. They went on the gluten-free diet and their symptoms have not fully resolved,” says Jericho. “Maybe the wrong expectation was set here. If you are a child, you have a very good chance of complete resolution. Sometimes it is going to take 12 to 24 months.”

Joseph Murray, MD, who runs the celiac disease research and clinical program at Mayo Clinic in Rochester, Minnesota, says this offers new insight about symptoms and recovery. Gastroenterologists know more about digestive problems but less about how manifestations like fatigue respond to a gluten-free diet. The study distinguishes how they progress and compares the response between children and adults.

Going gluten free is not easy for anyone, but newly diagnosed adults face particular challenges, Murray says. Old eating habits are hard to change. The diet presents social, psychological and practical difficulties. Adults have already been exposed to gluten for decades. Chronic inflammation may take longer to heal. These factors affect dietary adherence and recovery.

“Kids are very resilient,” says Jericho.

Maureen Leonard, MD, clinical director of the Center for Celiac Research and Treatment at Massachusetts General Hospital for Children, Boston, also welcomes the findings: “It is really helpful to tell children we see in our clinic that most kids feel better once they start a gluten-free diet.”

However, a few patients recovered poorly. Eight percent of children and 12 percent of adults did not follow a gluten-free diet. Most of these patients had ongoing symptoms.

Even among those who went gluten free, one-third of children and half of adults reported at least one persistent symptom, but that does not mean a lack of improvement, according to Murray.

“Persistence doesn’t necessarily take account of severity,” he says. “If I have headaches every single day because of celiac disease and after a year or two on a gluten-free diet I still have headaches but only once every two weeks, that is persistent but not anywhere near as bad.”

If symptoms do not improve, the patient should return to the doctor and make sure the diet is truly gluten free, says Jericho. Restaurants and processed foods can contain unrecognized contamination.

However, poor recovery often reveals different illnesses occurring alongside celiac. Doctors call these comorbidities.

A previous study of the same patient records found 28 percent of children who responded poorly to the diet had comorbidities. Genetic disorders like Turner syndrome are common in the celiac population. So are other autoimmune conditions, like thyroid disease. Jericho recommends close follow-up with a doctor to detect these in children.

Leonard agrees: “Patients need dietary reinforcement, so they should see a dietitian once a year. They should see a gastroenterologist to look for signs of ongoing celiac disease or comorbidities.”

Jericho says with patients recovering poorly, she uses follow-up blood tests to ensure celiac antibodies return to normal. She might also conduct endoscopies to inspect the gut lining. These tests normally reveal a healed gut, she says, prompting her to look for comorbidities.

The study only measured symptom recovery, not intestinal healing directly. Use of blood tests to track recovery is gaining popularity, but many experts express skepticism. Follow-up biopsies remain common practice at some referral centers. A 2016 study at Massachusetts General Hospital found blood tests poorly predicted gut healing as revealed by biopsy.

Leonard, who participated in that research, says relying on whether a patient feels better highlights a major issue in celiac research.

“What is our treatment endpoint for patients with celiac disease?” she asks, arguing the research community needs more data to answer the question. “Should we focus on symptoms, on what the serology tests show, on mucosal healing or a mixture of all three?”

“While the antibodies are very robust for diagnosis, they are not as good for monitoring [recovery] as we believed before,” says Alessio Fasano, MD, a co-author with Leonard of the 2016 study and director of the Center for Celiac Research and Treatment at Massachusetts General Hospital. “We need to see that the symptoms are gone and the intestine is healed. That gives a great level of confidence that the autoimmune process is completely under control.”

Jericho has a different view: “It would be over-reactive to re-biopsy all these patients and expose children to the risks of anesthesia and of having a second procedure, when, at the end of the day, most kids respond very well to the gluten-free diet and have good gut healing.”

What can a gluten-free diet treat?

A gluten-free diet is the only treatment for:

  • celiac disease
  • non-celiac gluten sensitivity
  • wheat allergy

Some studies support screening patients with certain genetic and autoimmune disorders for celiac. These include:

  • type 1 diabetes
  • Crohn’s disease
  • thyroid disease
  • autoimmune liver disease
  • Down syndrome
  • Turner syndrome

Some doctors might recommend a gluten-free diet to treat other conditions, but the science remains inconclusive for:

  • irritable bowel syndrome (IBS)
  • rheumatoid arthritis
  • fibromyalgia
  • autism

Patients should consult a gastroenterologist to diagnose celiac or rule it out before adopting a gluten-free diet to treat other illnesses.

Van Waffle is a freelance journalist based in Waterloo, Canada, and research editor for Gluten-Free Living.

Study Sessions: Drug Heals Celiac Monkeys, Undiagnosed CD Impacts Pregnancy

Drug heals celiac monkeys

Support has come from treatment of rhesus macaque monkeys with celiac-like disease. In a recent study, six gluten-sensitive monkeys showed improvement when treated with human anti-IL 15 while on a normal, gluten-containing diet.

Karol Sestak, PhD, core scientist at Tulane National Primate Research Center in Covington, Louisiana, has spent 12 years describing and comparing celiac in monkeys with that in humans. Medical research has more often used mice genetically engineered to be gluten-sensitive. However, macaques are more similar to humans both genetically and physiologically, offering advantages when studying therapy for humans.

Besides, they do not need to be genetically altered. The disease naturally occurs in a small percentage of macaques as it does in people. Sestak says his team discovered this while studying digestive problems in the primate colony in 2006. Various viral infections in the monkeys had already been isolated.

“Occasionally, there would also be some disease in these nonhuman primates where you cannot trace any kind of infectious agent when they have chronic diarrhea. Back then, we were wondering what that could be,” says Sestak. “We reformulated their diet. We removed all the gluten sources from the monkey chow. It was our first gluten-free diet. Their conditions dramatically improved.”

The researchers then found the celiac monkeys had the same disease antibodies detected in humans. Those antibodies decreased when the animals were treated with a gluten-free diet. Another similarity with human patients is that gluten-sensitive macaques display a wide spectrum of disease. Some are seriously affected, some moderately and some mildly. When identified in their routine check-ups, these individuals are placed on a gluten-free diet or can be assigned to try out another promising therapy.

Sestak’s team conducted trials using 04H04, another clone of human anti-IL15 not identical to AMG 714. 04H04 reversed inflammation and damage in all six animals regardless of the seriousness of their disease. Their recovery was checked using biopsy for a close look at the gut lining. The treatment also improved some but not all markers for immune disease outside the intestine, such as antibodies detected by blood tests.

Anti-IL 15 works by suppressing IL 15, which appears to be a major immune agent but not the only one active in celiac. Since the drug healed intestinal tissue but did not reduce all disease markers, this suggests it might work best alongside a gluten-free diet or other therapy.

Undiagnosed celiac disease impacts pregnancy

Women with diagnosed celiac do not see the condition impact pregnancy and childbirth, according to Danish national statistics. However, prior to diagnosis and treatment, women had an increased risk for spontaneous abortion or stillbirth.

The data came from the entire population of Danish women between 1977 and 2016. The analysis included 6,319 women diagnosed with celiac who had follow-up records in the health registry. After diagnosis, they were just as likely to become pregnant as women in the general population. They had no more problems during pregnancy and childbirth.

In contrast, women with celiac had fewer pregnancies than average during the two years prior to diagnosis. Overall, women with undiagnosed celiac had 11 more miscarriages and 1.62 more stillbirths per 1,000 live births. This supports a focus on early diagnosis in women, especially those who lose pregnancies.

Van Waffle is a freelance journalist in Waterloo, Canada, and research editor for Gluten-Free Living. He blogs at vanwaffle.com.

New Microbes Observed in Probiotic Test

A clinical study of probiotics in children with celiac has found yet-unknown microbes may participate in the disease. Several other species previously known also make an appearance either for good or ill.

Gene sequencing has revolutionized microbiology over the past 15 years. It can detect organisms that have not yet been cultured or studied in the lab. It is shedding light on unforeseen diversity in the human microbiome. Although the microbiome changes in people with celiac, it remains unclear whether virulent microbes cause the disease or gain a foothold after inflammation occurs. Bifidobacterium breve, a healthy bacterium of the infant gut, is believed by some experts to support the immune system as it matures. If so, probiotic supplements like B. breve might protect against celiac and other inflammatory diseases.

The study at University Medical Center Maribor, Slovenia, enrolled 40 children with celiac and 16 healthy children. Those with celiac were randomly assigned to receive either the B. breve probiotic or a placebo for three months. Blood and stool samples were taken from the children with celiac before and after the treatment and compared with healthy children.

Besides finding several groups of microbes that might trigger celiac, this study found little-known microbes that occur in low abundance but may help prevent disease in people at risk. In celiac patients after probiotic treatment, Firmicutes bacteria and some other unknown and lesser-known species increased as homeostasis returned. These microbes could be useful in treatment to restore a healthy microbiome.

Besides gut microbes, celiac disease relates to dietary, psychological and other environmental factors that are still poorly understood. This study provides hints about the microbiome, but there is not enough evidence yet to support treating celiac with probiotics. Meanwhile, in identifying new microbes, it sheds light on the complex world we live in and that lives in us.

Gluten-Free Consumers Make Healthy Choices, Except About Weight Loss

A new study shows people who buy gluten-free products also engage in other health-motivated behavior. That’s good news—mostly.

Consumers support a $1.6-billion gluten-free food industry, but only a fraction of them are sensitive to gluten. Researchers are trying to understand the so-called health halo that leads so many people to avoid gluten. The products are not necessarily more nutritious. They often contain less whole grain and more calories, saturated fat and salt than standard alternatives.

Researchers surveyed young adult volunteers who were initially recruited from public middle and high schools in Minneapolis-St. Paul, Minnesota, for a food study in 1998-’99. A follow-up questionnaire in 2015-’16 asked how much participants valued gluten-free products. Answers were received from 1,819 people aged 25 to 36.

Approximately 13 percent considered gluten-free an important food attribute. Those who did were also more likely to value foods that were organic, unprocessed, locally grown and not genetically modified. Compared with people who did not value gluten-free food, they practiced healthier habits, such as eating breakfast daily, using nutrition facts on package labels and meeting exercise guidelines. On average, they consumed one more daily serving of fruits and vegetables and 20 percent more fiber than others in the study. Despite the potential pitfalls of a gluten-free diet, people who valued these products appeared to achieve a healthier lifestyle overall.

On the down side, they were more likely to use unhealthy means to control their weight, such as vomiting or taking diet pills. This study from University of Minnesota suggests people who value gluten-free products want a healthier life but do not always make sound medical choices. The authors encourage clinicians to inquire about weight loss goals and consider food costs for low-income families when advising patients interested in following a gluten-free diet.

Van Waffle is a freelance journalist in Waterloo, Canada, and research editor for Gluten-Free Living. He blogs at vanwaffle.com.

Gluten, Crohn’s and Ulcerative Colitis

Diagnosed with inflammatory bowel disease (IBD) in her teens, Varda Meyers Epstein always thought fiber caused her digestive problems until she tried a ketogenic, gluten-free diet.

“I had applied through my health fund to have bariatric surgery because I felt hopelessly overweight. Then a neighbor urged me to give a low-carb, high-fat diet a chance,” says Meyers Epstein, 57, a writer in Efrat, Israel.

Adopting a ketogenic diet, she lost 60 pounds in six months — but that wasn’t the only change: “My severe flatulence left me. When I dramatically lowered carbs in my diet, fiber stopped bothering me. My stomach distress had always been about grains and sugar, apparently. I can now eat salads.”

Going gluten-free for IBD

Almost one in five IBD patients tries a gluten-free diet, according to a study from the University of North Carolina (UNC) at Chapel Hill. Of those who do, two-thirds report improved symptoms and 38 percent report fewer or less-severe flare-ups between periods of remission. This was the largest study of the gluten-free diet in patients with IBD, including a total of 1,647 participants. Among these, 314 had tried the gluten-free diet while 135 continue following it, or about 9 percent. The data were drawn from a larger internet-based study of 15,000 patients collected by the Crohn’s & Colitis Foundation. Crohn’s disease and ulcerative colitis both fall under the IBD umbrella (see below).


IBD defined

Crohn’s disease and ulcerative colitis are inflammatory bowel diseases (IBD) that cause chronic inflammation and damage in the gastrointestinal (GI) tract. IBD affects as many as 3 million Americans, according to the Crohn’s & Colitis Foundation. The national annual financial burden is estimated at $31 million.

Crohn’s disease

Crohn’s disease can affect any part of the GI tract from the mouth to the anus. It most commonly affects the end of the small intestine (the ileum) where it joins the beginning of the colon. Crohn’s disease may appear in patches affecting some areas of the GI tract while leaving other sections completely untouched. Inflammation may extend through the entire thickness of the bowel wall.

Ulcerative colitis

Ulcerative colitis is limited to the large intestine (colon) and the rectum. The inflammation occurs only in the innermost layer of the lining of the intestine. It usually begins in the rectum and lower colon but may also spread continuously to involve the entire colon.
For more information, visit crohnscolitisfoundation.org.

Animesh Jain, MD, associate professor of medicine at UNC, did not work on the study but says it is valuable because of its size. “It also reports patient-reported outcomes, which we are factoring more and more into clinical practice,” he explains.

“But that is not the end-all of treatment for IBD,” Jain says. “Both Crohn’s disease and ulcerative colitis lead to structural inflammatory damage to the bowel, which can include redness of the lining, deep ulcers and complications like blockages of the intestines. When I’m treating somebody with IBD, their symptoms are an important part of what’s going on, but the other piece of the story is: How does their bowel look?”

Bowel healing can only be assessed by clinical tests. Like celiac, IBD is an autoimmune disease with no known cure. Unlike the link between gluten and celiac, specific environmental causes of the inflammation remain unknown.

“Unfortunately, we don’t have great research for any specific diet that will either prevent the disease from starting or ameliorate the inflammatory disease once it starts,” Jain says.

Current research

A large multicenter study now underway is investigating two diets that might relieve symptoms of Crohn’s disease. It includes the Specific Carbohydrate Diet, which is low in complex carbohydrates, and the Mediterranean diet. For now, doctors typically do not prescribe dietary changes as a frontline treatment.

“Usually when we see patients in the clinic, they are quite ill,” Jain says. “They have active inflammation, which can lead to intense diarrhea, bleeding, weight loss or other complications. In that situation, we usually rely on more potent, traditional pharmacologic therapy.”

Trigger foods

Once IBD is controlled, many patients manage it by identifying trigger foods and eliminating them during flare-ups. Difficult-to-digest foods can include insoluble fiber, nuts, seeds, and raw fruits and vegetables.

Ines Pinto-Sanchez, MD, assistant professor of medicine in gastroenterology for the Michael G. DeGroote School of Medicine at McMaster University in Hamilton, Canada, says the UNC study highlights another problem: Many people attempt a gluten-free diet, experience improved symptoms and then attribute gluten as their trigger. “[But this] does not necessarily mean they will remain without symptoms or that it will lead them to remission. What is lacking is studies evaluating the real effect of a gluten-free diet in IBD.”

This can lead patients to stick with a gluten-free diet despite recurring IBD symptoms, which Pinto-Sanchez says she would not encourage.

A celiac–IBD link?

A possible overlap between celiac and IBD may be obscuring the evidence. A few studies have looked for an increased prevalence of both diseases in the same patients. Results vary widely. An Australian meta-analysis published this year pooled all the data for more conclusive results. It found a slightly higher risk for celiac among IBD patients. Conversely, the rate of IBD among celiac patients was 11 times higher than in the general population.

Pinto-Sanchez says the link isn’t surprising because both conditions involve immune reactions. “What is not very well known and clear in those studies is whether gluten-free diets will have the same effect in IBD as in celiac disease,” she says.

If an IBD patient sees improvement on a gluten-free diet, Jain says, “It would be relevant to formally test the patient for celiac disease because that would obviously be a major change in how we treat them. If we’re treating both Crohn’s disease or ulcerative colitis and celiac disease in the same patient, that adds important implications.”

Kelly Issokson, RD, of Cedars-Sinai medical center in Los Angeles, agrees. “If my patient is interested in starting a gluten-free diet, I recommend first getting tested for celiac disease before going gluten free,” she says. “Testing for celiac has many benefits, including helping the patient understand how strict they need to be on a gluten-free diet.”

The role of FODMAPS

Issokson says benefits of a gluten-free diet might not relate directly to gluten: “Gluten-containing foods are also a significant source of fructan, a type of FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols), which has been associated with functional gastrointestinal symptoms in irritable bowel syndrome and IBD.”

Recent analysis by Chinese researchers found IBD patients on a low-FODMAP diet showed significant improvement in multiple symptoms.
“Thus, a short-term, low-FODMAP diet or even a diet with a reduction in fructans may be a better choice and lead to symptom improvement without the need to follow a long-term gluten-free diet,” says Issokson.

Pinto-Sanchez says she would not advise any IBD patient who is in remission and doing well to try a restrictive diet. “The gluten-free diet is not benign. It can lead to nutritional deficiencies,” she notes.

“For symptom management, I educate patients about the importance of a balanced diet for gut healing and overall health, about foods and eating behaviors that commonly contribute to gastrointestinal symptoms, and about the role of physical activity and stress reduction in helping to manage them,” Issokson says. “Restricted diets can decrease quality of life, increase risk for malnutrition and slow the healing process. My goal is to help achieve nutritional balance through the least restrictive diet possible.”

Gluten free with colitis

Kat LefflerAfter Kat Leffler, 55, started having digestive symptoms, she was diagnosed with colitis. A freelance consultant and copywriter in Omaha, Nebraska, she questioned the diagnosis and concluded she was gluten-sensitive but could not persuade doctors to investigate.

When she first reported stomach complaints to her doctor in September 2014, she was given FODMAP and DASH diet brochures. Three months later, she landed in the emergency room (ER) with cramps, no bowel movements and vomiting. She was diagnosed with colitis and, over several ER visits, prescribed drugs to treat infection and symptoms.

“I already had suspicions about commercial food production, and this led me to the Paleo practice,” says Leffler. “It is entirely gluten and grain free. This was hard. It was almost impossible to eat out anywhere that would be compliant. In the beginning, I didn’t have many recipes or ideas, so it was also boring.”

After 90 days and again after 180 days of clean eating to reset her immune system, she would try a slice of pizza or two and end up back in the ER. She identified grains and legumes as primary irritants, while dairy affects her respiratory system. In 2016, she went to a gastroenterologist, who gave a full battery of tests. The doctor placed her on the spectrum between irritable bowel syndrome and IBD, closer to the IBD end. Again she received FODMAP and DASH diet brochures, “neither of which are gluten-free eating,” says Leffler.

When she raised her concern about gluten sensitivity, the doctor dismissed it by telling her that “everybody says they have a gluten issue these days,” Leffler recalls.

She still follows a gluten-free diet pretty strictly: “I have to if I want to function.”

Gluten free with Crohn’s disease

Heather SliwinskiHeather Sliwinski, 32, began having symptoms in 2010. The San Francisco public relations professional went through a few doctors and many different tests leading to a diagnosis of Crohn’s disease in 2013. Sliwinski says she went gluten free in 2011 after a year of symptoms, without support from any doctors.

“In the three-year gap between the onset of Crohn’s and diagnosis, I felt helpless. I wasn’t getting any answers, but I also wasn’t getting any suggestions on ways to improve my symptoms. I wanted to take my health into my own hands and do anything to relieve my gut issues,” says Sliwinski.

On the Specific Carbohydrate Diet, which removes complex carbohydrates including gluten, her symptoms continued to improve without medication. After a year on the diet and trying a new gastroenterologist, she had a second colonoscopy. Her intestines looked healthy and without inflammation compared to one a year earlier that showed indeterminate microscopic colitis.

Sliwinski says, “The new doctor supported my diet and was very interested in its effect on IBD from her own research perspective.”

She recalls, “After being gluten free and grain free, I was slowly able to add raw fruits and veggies back into my diet, which are notoriously hard for IBD patients to tolerate. Seven years later, I am still strictly gluten free, lactose free, and avoid many grains and sugars. I am not on any medication specifically to treat Crohn’s and can tolerate a much wider range of foods.”

Sliwinksi says she has no plans to ever eat gluten again: “I remember what life was like before I made these dietary changes. I would never go back to the pain, the numerous trips to the bathroom, the fatigue and the anxiety just to eat a slice of bread.”

Van Waffle is a freelance journalist in Waterloo, Canada, and research editor for Gluten-Free Living. He blogs at vanwaffle.com.

Research Brief: Global Celiac Prevalence 0.7 Percent or Higher

Large group of people walking, shown from behind

Celiac is a global disease. About 0.7 percent of people on Earth have the condition, or 1 in every 142 people. That estimate comes from a recent meta-analysis pooling data from population studies around the world. It includes studies that showed biopsy-proven diagnosis.

Scientists from the U.S., India, Norway and Italy collaborated on the study, using data from articles published between 1991 and 2016. They found 96 that screened populations using blood tests for antibodies but only 57 that followed up with adequate data on biopsy-proven celiac. Significantly lacking were studies showing prevalence of biopsy-proven celiac in North America. However, seven studies placed the prevalence of blood serology here at 1.4 percent.

Elsewhere, the prevalence of biopsy-proven celiac was 0.8 percent in Europe and Oceania, 0.6 percent in Asia, 0.5 percent in Africa and 0.4 percent in South America. Countries with the highest known biopsy-proven prevalence were Argentina, Egypt, Hungary, Finland, India, New Zealand and Sweden. Those with the highest known blood antibody prevalence were Algeria, Czech Republic, India, Israel, Mexico, Malaysia, Saudi Arabia, Sweden, Portugal and Turkey. No data were available from six of the 10 most populous countries: China, Indonesia, Pakistan, Nigeria, Bangladesh and Japan. African data came mostly from northern countries. Celiac is believed to be rarer in Sub-Saharan Africa due to lower genetic risk and less wheat consumption.

Prevalence increased from 0.6 percent in studies before 2001 to 0.8 percent in later research. Globally, celiac is 1.5 times more common in women than men and twice as common in children as in adults.

Singh P, Arora A, Strand TA, Leffler DA, Catassi C, Green PH, Kelly CP, Ahuja V and Makharia GK, “Global prevalence of celiac disease: systematic review and meta-analysis,” Clinical Gastroenterology and Hepatology, June 2018, 16;6:823-836.e2, doi.org/10.1016/j.cgh.2017.06.037.

Learn more about recent headlines and research in This Week in Gluten-Free News!

Read more briefs highlighting recent and ongoing celiac and gluten-free research here.

Research Brief: Early Celiac Diagnosis Cuts Mortality

Data from a U.K. study show the death rate for celiac patients has declined since blood tests for antibodies were introduced in the 1990s. The researchers suggest blood tests allow earlier diagnosis, facilitating better long-term health. However, after treatment, celiac patients still have higher mortality from all causes than the general population.

Celiac patients have a higher risk of dying from pneumonia. Death rates due to liver disease are also higher and have increased over time. The authors suggest both of these problems can be addressed if they are recognized and treated more promptly. The good news is the risk of death from heart disease in celiac patients has decreased significantly compared to the overall population. A rare form of cancer, non-Hodgkin’s lymphoma, remains a significantly higher risk for celiac patients after diagnosis.

The findings were drawn from 2,174 celiac patients in Southern Derbyshire diagnosed between 1978 and 2014 with at least two years of follow-up. A total of 284 died of any cause. An earlier study failed to find any change in mortality before 2006. The new study re-examined the same group and included more patients diagnosed up to 2014.

The overall decline in mortality still did not reach statistical significance. However, there is evidence that earlier diagnosis helps patients live longer. Those who died in the 1980s lived an average of 3.5 years after diagnosis. Among those who died between 2010 and 2014, survival time had increased to 10.7 years. These figures exclude patients who died within two years of diagnosis before treatment could impact long-term health.

Holmes GKT and Muirhead A, “Mortality in coeliac disease: a population-based cohort study from a single centre in Southern Derbyshire, UK,” BMJ Open Gastroenterology, 2018;5:e000201, doi.org/10.1136/bmjgast-2018-000201.

Learn more about recent headlines and research in This Week in Gluten-Free News!

Read more briefs highlighting recent and ongoing celiac and gluten-free research here.

Non-classic celiac more severe

Complementing this study on non-classic celiac symptoms delaying diagnosis, research from Finland shows most celiac children have non-intestinal symptoms upon diagnosis. Those diagnosed because of non-intestinal problems show more severe symptoms and damage to the small intestine than children presenting mainly classic symptoms (see Extraintestinal Celiac Symptoms in Kids).

The study included 511 children with biopsy-proven celiac. The main reasons for suspected celiac were classic symptoms like diarrhea and abdominal pain in 49 percent and non-intestinal conditions in 23 percent, while 29 percent were diagnosed after screening because of risk factors like family history. Researchers compared children with celiac to 180 children diagnosed with functional gastrointestinal disorders like irritable bowel syndrome without evidence of tissue damage.

The symptoms

Non-gastrointestinal complaints included skin rashes, anemia, poor growth, enamel defects, nerve problems, headaches, joint pain, mouth sores, elevated liver enzymes, eye problems and other conditions. Poor growth and anemia were most common, affecting 27 and 18 percent of children with celiac, respectively. Patients with celiac were almost twice as likely to have non-intestinal conditions as children with functional disorders: 62 compared to 33 percent.

Disease severity

On endoscopy and biopsy, children who had non-intestinal complaints showed the most severe damage to the small intestine. Symptoms were more severe in 78 percent diagnosed because of non-intestinal conditions compared to 45 percent presenting primarily classic symptoms.

These two studies highlight a need for further research to understand the prevalence of various non-classic symptoms associated with celiac. Meanwhile, doctors should consider celiac as an underlying cause.

Nurminen S, Kivela L, Huhtala H, Kaukinen K and Kurppa K, “Extraintestinal manifestations were common in children with coeliac disease and were more prevalent in patients with more severe clinical and histological presentation,” Acta Paediatrica, March 2018, doi.org/10.1111/apa.14324.

Learn more about recent headlines and research in This Week in Gluten-Free News!

Read more briefs highlighting recent and ongoing celiac and gluten-free research here.


Is a Truly Gluten-Free Diet Possible?

There is no such thing as a truly gluten-free diet, says Daniel Leffler, MD, associate professor of medicine at Harvard Medical School.

Since the 1940s, doctors have prescribed a strict lifelong gluten-free diet as the only effective treatment for celiac. The cure might be too good to be true. Leffler says 30 percent of celiac patients have ongoing symptoms that compromise daily life. New research suggests patients who believe they are following a strict gluten-free diet commonly consume unsafe amounts of gluten. Accidental exposure leads many patients to avoid eating outside the home.

Leffler says, “We really mean gluten-restricted diet, but it is way too late to rebrand that.”

The level of gluten restriction that can be achieved is effective for many patients, Leffler says. However, experts have assumed that those who don’t get better must be cheating on the diet. What really prevents recovery is the near impossibility of avoiding gluten. It is invisible, hard to detect and ubiquitous in the food supply.

The 20-ppm standard

The U.S. Food and Drug Administration (FDA) requires foods labeled gluten free to contain less than 20 parts per million (ppm) gluten. This derives from a 2007 study finding people with celiac could safely consume 50 milligrams (mg) per day. No government agency in the world recommended eliminating gluten completely. It would be nearly impossible.

A recent investigation of gluten-free oat products by PepsiCo, Inc., and General Mills suggests the distribution of contamination makes it easy to underestimate under normal test protocol. While a given sample may test safe, an occasional serving is bound to contain a harmful amount of gluten.

“In reality, people are probably getting much more than 20 ppm more frequently than they think,” says Jocelyn Silvester, MD, of Boston Children’s Hospital.

New stool and urine tests can reveal how much gluten a patient consumes. Spanish company Biomedal developed the technology GlutenDetect. Consumers can buy it online, but it is not FDA approved.

Researchers have started using it to track actual gluten consumption of patients in clinical trials for new drugs. A 2018 study from California drug company ImmunogenX, Harvard University and Biomedal was published in The American Journal of Clinical Nutrition. It concludes celiac patients consume “on average, potentially unsafe levels of gluten,” averaging at least 200 mg per day while following a gluten-free diet. At the high end, between 3 and 19 percent of patients accidentally consume more than 600 mg of gluten on a given day.

Early adopters

Children appear to adopt a gluten-free diet more readily. Stool and urine studies from Spain and Harvard suggest young children on a gluten-free diet consume the least gluten, followed by teens, with adults consuming the most.

However, even children are getting glutened. A recent study from Massachusetts General Hospital found one in five pediatric patients has persistent gut damage detected by a follow-up biopsy.

Not all experts agree with the assessment emerging from research in Boston. Hilary Jericho, MD, who treats children and teens at University of Chicago, says, “85 to 90 percent of my patients, maybe more” make full recoveries and feel great on a gluten-free diet.

A University of Chicago study comparing child and adult patients confirmed what has long been suspected:

on a gluten-free diet, children are more resilient and recover faster. Jericho says all patients need a reasonable expectation about how quickly their symptoms will resolve.

“If the gut is healed and a patient is not showing signs of inflammation or malabsorption, then we are achieving our goal. I think it is possible to be gluten free to the extent that you need to,” Jericho says. “Most of the time in kids who are not recovering, it is because they are still consuming gluten and not identifying where it comes from.”

Jericho adds GlutenDetect can reveal the problem in difficult cases.

Distinguishing symptoms

Ongoing symptoms may result from other conditions co-occurring with celiac. Silvester contributed to a study of 105 new celiac patients at University of Manitoba in Winnipeg, Canada. Gastrointestinal symptoms improved but remained common one year after treatment, with 96 percent adhering to a strict diet. They reported accidental exposure less than once per month, mostly at restaurants and other people’s houses. Celiac symptoms were difficult to distinguish from functional disorders such as irritable bowel syndrome (IBS), which cause discomfort while damaging the gut lining. Follow-up data raise further concern but are not published yet.

“We are finding higher rates of persistent mucosal damage than we necessarily expected,” says Silvester. “We did a follow-up biopsy at 24 months. In these adult patients, about 40 percent have villous atrophy.”

Celiac flattens the villi, small projections on the gut lining, but they should regrow quickly on a gluten-free diet. Although ongoing symptoms can result from functional problems after the gut heals, Silvester says a key question for follow-up is whether patients are still getting gluten: “I think the answer is definitely yes.”

Unfair judgment

Leffler says, “What we have done historically, which in retrospect was completely unfair, was put 100 percent of the onus on patients: ‘If you can’t get this right, it is your fault, you are not being strict enough.’ That was never a realistic expectation. Even when people did everything they were supposed to do, they were still getting exposed.”

Patients who are sensitive to the smallest levels of gluten need something more than a doctor berating them, he adds.

The data show what everybody knows: Some adults have more restraint than others. This is as true of celiac patients as anyone else. The Spanish study revealed 60 percent of male celiac patients were eating gluten compared to 30 percent of women.

“The number of people who claim to be on a strict diet decreases with time,” Silvester observes from the Manitoba cohort. “It is just recognizing that gluten is everywhere and striking a balance. You can be hypervigilant but that is not necessarily going to be good for your overall health. Lots of people lead happy, healthy lives on a good-enough gluten-free diet. We just do not really know what a good-enough gluten-free diet is.”

Silvester says she is concerned that ongoing damage from gluten could cause nutrient deficiency. She sees this in some patients. In small children, anemia may impair cognitive development. During adolescence, calcium malabsorption can hinder bone growth.

“The longer-term question is, if these patients have ongoing inflammation, are they at increased risk for lymphoma?” says Silvester. “We do not understand the consequences of chronic, intermittent, low-grade gluten exposure.”

Patient burden

Emma Clerx, 21 and entering her senior year at Harvard University, was diagnosed with celiac at age 12. She recalls how she adapted to a gluten-free diet: “My mom created this big binder with research from the internet, different books and whatnot to learn how to identify gluten, how to go to the grocery store and navigate the gluten-free options.”

Though satisfied with her treatment, Clerx agrees that no diet can be 100 percent gluten-free: “It is not reasonable to have to think about every single ingredient that you put into your mouth every day.”

Clerx shadows Leffler at Beth Israel Deaconess Medical Center. She sees a need for additional drug therapy: “Nonresponsive celiac disease exists. The gluten-free diet does not work for everyone. On a broader level, the gluten-free diet can be burdensome financially and socially.”

For patients who are meticulous about the diet, it can become too restrictive and make them obsessive. That leads to other unhealthy habits, Clerx says.

Quality of life

In a survey by Beth Israel Deaconess Medical Center, patients reported a heavier burden of treatment for celiac than any other chronic illness except end-stage kidney disease. Celiac patients complained of difficulty following the diet, concerns about food costs, trouble eating outside the home and time limitations in preparing their own food.

Celiac patients are drilled on the importance of a strict diet to avoid possible but uncertain health complications. For some people who generally feel well but get very sick when exposed to gluten, the experience can be traumatic, says Leffler. “They wind up leading reclusive lives and not having the social freedom or travel freedom that people without celiac disease enjoy.”

“It is not a benign treatment,” Silvester says. “Still, right now we need people to strive for as gluten free as possible.”

“We have a much better food supply for celiac disease than we have ever had before,” says Leffler, indicating expansion of the food industry. “I find it hard to believe that we are going to be able to make another leap forward in safe food availability.”

Doing their best

“People with celiac disease, we cannot spontaneously go to a restaurant and order whatever we want off a menu, even if it is labeled gluten free,” says Rachel Begun, RDN, based in Los Angeles. She is a member of the scientific and medical advisory council for Beyond Celiac, a nonprofit advocacy group. “We cannot rush to the airport without thinking ahead of time about what we will eat. I cannot show up to a weeklong business conference without having had multiple conversations with the person who plans our meals. There is a lot more planning involved.”

Begun, diagnosed with celiac in 2009, says, “As a dietitian, as a chef, as somebody who has a food- service background, I went into the gluten-free diet thinking, ‘I am leaps and bounds in front of everybody as far as education. It will be relatively easy for me to eat out.’ Now I am almost 10 years into living gluten free, and I actually eat out less than I ever have because I know that the likelihood for exposure to gluten is high.”

Back to basics

Begun recommends learning basic cooking skills so people can prepare their own meals and entertain friends at home.

“Our society’s way of socializing revolves around meeting people out for food,” adds Begun. “That’s great, but for people who need to be cognizant of what they eat, doing social things that do not require food can be the answer. Go for a walk. Go for a bike ride.”

Clerx says she had to become comfortable discussing her needs with waitstaff in restaurants. It turned out to be harder than explaining it to a friend or teacher.

“One of the most important parts of working out gluten-free living on the college campus was meeting with the dining hall manager at the beginning of the year, which I did during the first week of school to talk about what are the options, how can I eat safely in the dining hall, avoid cross-contamination and find what I need,” says Clerx. They were accommodating, and she has not experienced any egregious errors.

Jericho describes hypervigilant adolescents as “really good” patients; they choose colleges based on those with good gluten-free options in their cafeterias.

Empowered and gluten free

Jericho adds many of her patients cope well: “Though it is very daunting and scary at diagnosis, these teens come to feel empowered by it. I am always impressed by my patients. It makes them stronger people. I think it helps them with other challenges that they face in life.”

“It is better to have occasional gluten exposures and be out enjoying life, being social, than to be at home avoiding gluten and being safe,” says Silvester. “As a society, people do not see eating as an activity that involves nourishing themselves. It is seen as a task, not necessarily something that is valued or an investment. People prioritize other activities over food. Therefore, they are not willing to spend time. You get what you put into things. Often, having celiac disease forces people to shift that balance.”

Van Waffle is a freelance journalist in Waterloo, Canada, and research editor for Gluten-Free Living. He blogs at vanwaffle.com.

Looking for more gluten-free news and information? Read about the recent headlines and research in This Week in Gluten-Free News!

Research Brief: Non-classic celiac symptoms delay diagnosis

Research from three U.S. hospitals reveals patients with non-classic celiac symptoms face a much longer delay in diagnosis. In a cohort of 101 adult patients, 52 who initially saw a doctor with gastrointestinal complaints were typically diagnosed in 2.3 months. The median diagnosis time for people with non-gastrointestinal symptoms was 3.5 years. These patients showed signs including fatigue, anemia, thyroid, liver or bone density abnormalities, or dermatitis herpetiformis, a form of celiac causing skin blisters.

The study included only patients with biopsy-proven celiac. The authors say their findings show doctors should evaluate patients for celiac if they have unexplained anemia, thyroid disease or abnormal bone density.

Thyroid disease

Autoimmune thyroid disease commonly occurs alongside celiac. In this group of patients, a remarkable 43.2 percent of those lacking gastrointestinal symptoms had thyroid abnormalities compared to 15.5 percent of those with gastrointestinal symptoms. Overall one-third of patients had abnormal thyroid hormone levels, much higher than reported in any other study.

Anemia and bone density

A majority of the non-gastrointestinal group had anemia and abnormal bone scans: 69.4 percent and 68 percent, respectively. These problems were less prevalent among those with gastrointestinal symptoms: 11.5 percent and 41 percent, respectively. Few patients had dermatitis herpetiformis or liver abnormalities.

The authors note 11 percent of this study group were Hispanic and 3 percent were African American. This appears higher than expected as celiac is considered rare among U.S. ethnic minorities.

The authors say they are unaware of any previous study to compare gastrointestinal and other symptoms in biopsy-proven celiac. This fresh perspective comes from Howard College of Medicine in Washington D.C., Loyola Medical Center in Maywood, Illinois, and Medical University of South Carolina, Charleston. These are outside the group of several celiac clinics that conduct the most U.S. research. The study did not account for various other non-gastrointestinal conditions. These include peripheral neuropathy and mouth ulcers that may be associated with celiac.

Paez MA, Gramelspacher AM, Sinacore J, Winterfield L and Venu M, “Delay in diagnosis of celiac disease in patients without gastrointestinal complaints,” The American Journal of Medicine, November 2017, 130;11:1318-1323, doi.org/10.1016/j.amjmed.2017.05.027.

Learn more about recent headlines and research in This Week in Gluten-Free News!

People With Gluten Sensitivity More Skeptical

A survey of people who follow a gluten-free diet found those with non-celiac gluten sensitivity (NCGS) are more skeptical about medicine and food safety than those with celiac. A notable 41.3 percent of people with NCGS doubt vaccines are safe for people with celiac, compared to 26.4 percent of celiac patients. Significantly more people with NCGS had refused a flu shot when offered one.

The Celiac Disease Center at Columbia University emailed the questionnaire to adults on a voluntary email list and received a 27 percent response. The study included 1,291 people with biopsy-proven celiac and 217 classified as having NCGS, either self-reported or unsure of their diagnosis.

By the numbers

A majority of those with NCGS reported adverse symptoms after trying gluten-free Cheerios: 53 percent compared to 37 percent of celiac patients. They were significantly more likely to avoid genetically modified foods (47 percent), eat only organic products (29 percent), believe a gluten-free diet improves energy and concentration (40 percent), and believe gluten is unhealthy for everyone (31 percent).

This study of patients at a major referral center may not reflect the general U.S. population. Respondents with NCGS had a significantly higher level of education, 93 percent having completed a college degree compared to 82 percent of celiac patients. However, the authors believe these findings show a meaningful difference in attitudes among people who avoid eating gluten. A lack of clear information about food safety may reinforce consumer beliefs.

Rabinowitz LG, Zylberberg HM, Levinovitz A, Stockwell MS, Green PHR and Lebwohl B, “Skepticism regarding vaccine and gluten-free food safety among patients with celiac disease and non-celiac gluten sensitivity,” Digestive Diseases and Sciences, 2017 Dec 14, doi:10.1007/s10620-017-4879-1 [Epub ahead of print].

Gluten sensitivity or intolerance is a condition that causes a person to react after ingesting gluten, a protein found in wheat, barley and rye. Symptoms of gluten sensitivity are close to those associated with celiac, so it’s important to get the correct diagnosis. Check out our Gluten Sensitivity section for more information.

Research Brief: Warning about Gluten-Free Oats


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Warning about Gluten-Free Oats

Three employees of a major U.S. food manufacturer have raised alarm about the safety of gluten-free oats. In an editorial to the journal Cereal Chemistry, they warned that conventional gluten tests do not detect cross-contamination accurately on a serving-by-serving basis. Individual servings of gluten-free oats sometimes contain more than 20 parts per million (ppm) of gluten, the level considered safe for people with celiac. Their tests found both mechanically or optically cleaned oats and so-called purity protocol oats may not meet the standard.

The authors include two employees of
PepsiCo Inc. and one from its subsidiary, Quaker Foods and Snacks. Their report arose from several studies funded by PepsiCo Inc. to investigate the safety of gluten-free oats.

In 2017, the team analyzed samples of gluten-free-labeled oatmeal from two major manufacturers that rely on mechanical or optical sorting to remove wheat grains from oats. They found 1 in 57 servings did not meet the U.S. Food and Drug Administration’s 20-ppm standard. However, these tests utilized small 0.25-gram samples taken from each serving. Upon further investigation, the researchers discovered this test, which is the standard measure for food safety, underestimates the level of gluten contamination in the whole serving.

A subsequent analysis of purity protocol oats used a more rigorous approach. It measured the gluten content of entire 50-gram servings of products from three large producers. These oats are produced with strict standards to prevent contamination by wheat in the field, transportation and manufacture. However, the authors report that 5 out of 166 servings failed the test. Gluten in the contaminated samples ranged from 20.4 to 229 ppm, affecting two of the three products.

Can’t compare

The results cannot be compared scientifically with those for optically and mechanically cleaned oats because the test methods were different. However, the authors argue their findings raise unanswered questions about all gluten-free oat products. Without changes to industry and testing standards, consumers will occasionally get glutened. The health risk for this level of exposure is unknown.

However, several studies have found oats do not adversely affect people on a gluten-free diet.

Chen Y, Fritz RD and Ferrini L, “Compliance assessment of US gluten-free labeled oatmeal produced under a ‘purity protocol’ indicates ‘serving level compliance’ not attained,” Cereal Chemistry, 2018;95(1):92-93, doi:10.1002/cche.10008

Learn more about recent headlines and research in This Week in Gluten-Free News!


Altered microbiome linked to celiac in infants

Experts believe healthy gut microbes might protect children at risk for celiac. The microbiome undergoes complex changes during infancy as bacteria colonize the gut. This is an important time for the child’s immune system because it responds to both beneficial and virulent strains. A Spanish study of infants is among the first to record how the microbiome develops differently before the onset of celiac.

Previous studies noticed abnormal bacteria in celiac patients after diagnosis, but the disease itself could have caused this condition. Researchers needed to study the microbiome in healthy individuals to see how it behaved in those who remained healthy compared with those who developed the disease. The Celiac Disease Genomic Environmental Microbiome and Metabolomic (CDGEMM) study is currently recruiting participants in the U.S. to study newborns at risk.

The Spanish group identified more than 200 infants with a family history of celiac and tracked their history. They compared 10 who eventually developed celiac with 10 similar children who did not. They collected fecal samples at 4 and 6 months of age, analyzing what kinds of bacteria appeared and what antibodies the infants produced in response.

The findings

In healthy children, microbial diversity increased significantly between 4 and 6 months. In contrast, those later diagnosed with celiac showed a prematurely high microbial diversity that did not increase during that period. Bifidobacterium longum was relatively abundant in normal development, while other bacteria were associated with celiac. The two groups showed a distinct difference in immune response, suggesting microbial differences influenced how their immune systems developed.

The test matched each celiac patient with healthy children who had similar birth delivery (vaginal versus caesarean section), breastfeeding and early feeding practices. All the children were genetically susceptible to celiac. The comparison showed none of these factors caused an unhealthy microbiome.

The study was small and lacked enough data to explain what disturbed normal microbial colonization. However, these early findings encourage larger studies of the infant microbiome.

Olivares M, Walker AW, Capilla A, Benítez-Páez A, Palau F, Parkhill J, Castillejo G and Sanz Y, “Gut microbiota trajectory in early life may predict development of celiac disease,” Microbiome, 2018;6:36, doi:10.1186/s40168-018-0415-6.

Parents who are interested in enrolling their infant can visit the study’s website at www.cdgemm.org to see how their little ‘GEMM’ can help make celiac history. To enroll or inquire about enrollment, contact a participating center nearest you.

Want more information on celiac and kids? Check out our Kids section.

Research Roundup: Essential Nutrients in Gluten-Free Products

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Essential nutrients in gluten-free products

Labeling requirements from the U.S. Food and Drug Administration improve buyers’ confidence about which foods do not contain gluten. But what do they contain? A Polish study of 50 gluten-free products found low essential minerals in those based on rice, corn, potato and gluten-free wheat starch.

Non-traditional ingredients and a few traditional ones scored better. Good mineral profiles were found in foods based on oats, amaranth, teff, quinoa, chestnut, acorn, brown rice, buckwheat and millet.

Several studies have highlighted vitamin and mineral deficiencies in people following a gluten-free diet. While poor absorption by the damaged gut may be partly to blame, evidence suggests that a badly managed gluten-free diet misses essential nutrients.

This study evaluated copper, calcium, iron, magnesium and zinc. The authors urge food companies to develop more products using the ingredients that scored well. Meanwhile, consumers can enhance their mineral intake by checking ingredient lists. Less-traditional grain alternatives should appear first in the list to contribute sufficient minerals.

Gliszczyn´ska-S´wigło A, Klimczak I, Rybicka I. Chemometric analysis of minerals in gluten-free products. J Sci Food Agric, 16 Jan 2018, doi:10.1002/jsfa.8803.

Small gender divide in celiac

A Mayo Clinic study comparing characteristics of men and women with celiac found they are “more alike than unalike.” While women were diagnosed younger and more frequently than men, most differences in their symptoms and health were small.

The study used medical records to document patients living with celiac in Olmstead County, Minnesota, diagnosed between 1990 and 2015. The total 282 patients were nearly two-thirds female. The majority were non-Hispanic whites, so the findings may not apply well to diverse populations.

Women averaged four years younger than men at diagnosis. This could result from differences in the disease or because women seek diagnosis sooner.

On first diagnosis, men and women reported most symptoms with similar frequency except that women were more likely to have constipation. Women had a higher rate of low ferritin, a possible sign of iron-deficiency anemia. However, this result may not relate directly to celiac because menstruating women are prone to iron deficiency.

Mortality was no higher than in the overall Minnesota population. During follow-up, 12 men and 11 women died, cancer being the most common cause.

Other autoimmune diseases were equally common in men and women, affecting 31 percent, much higher than an estimated 3.2 percent of the general population. Men and women had a significantly increased risk for osteoporosis.

In this group, 24 percent of women and 16 percent of men were diagnosed with depression, nearly three times the national average. This finding was consistent with previous findings on depression and celiac. The authors recommend doctors assess the mood of all newly diagnosed patients.

Jansson-Knodell CL, King KS, Larson JJ, Van Dyke CT, Murray JA, Rubio-Tapia A. Gender-based differences in a population-based cohort with celiac disease: more alike than unalike. Dig Dis Sci, Jan 2018;63(1):184-92, doi:10.1007/s10620-017-4835-0.

Learn more about recent headlines and research in This Week in Gluten-Free News!


Does Breastfeeding Prevent Celiac?

Maybe not—but it can’t hurt

Ritu Verma is a pediatrician and mother of three. Two of her children have celiac and one does not. She was unable to breastfeed one of the three.

“There were a lot of people making me feel very guilty that I could not nurse,” says Verma, MBChB, director of the Center for Celiac Disease at Children’s Hospital of Philadelphia. “Being a pediatrician, I know how important it is to breastfeed, but if you are not able to do it and you have given your all, it is not fair to the mom to make her feel guilty.”

Fortunately the child she had trouble breastfeeding is the one who does not have celiac, otherwise she says she would probably feel guilty anyway. For years experts theorized that breastfeeding and timely introduction of gluten could protect children from celiac. Early research hinted that introducing gluten while still breastfeeding between 4 and 6 months of age might prime a baby’s immune system to tolerate gluten. However, the evidence was weak, often relying on past data that did not study effects of breastfeeding directly.

More recent research

Two studies published in The New England Journal of Medicine in 2014 compared different approaches to early nutrition in children at risk for celiac. They recruited infants who had a parent or sibling diagnosed with the disease. One study randomly assigned 832 newborns to be introduced to gluten at 6 months of age, the normal age for solid foods, or at 12 months. Fewer of the late group had been diagnosed with celiac by age 2 but they caught up by age 5. At age 10, one-quarter of the study group had been diagnosed with celiac. Delaying gluten introduction delayed celiac but did not reduce long-term risk.

The other study involved 944 at-risk infants randomly assigned to receive either a small dose of gluten or a placebo daily from age 4 to 6 months. Then they were introduced normally to solid foods. Introducing gluten during the 4- to 6-month window, when most children get their first taste of gluten, made no difference. This study recorded breastfeeding in more detail, comparing whether children were breastfed, whether it was exclusive and for how long. No approach to breastfeeding gave children an advantage against celiac.

This disappointed researchers trying to understand why some children genetically predisposed for celiac remain healthy while others become sick. Commenting in The American Journal of Gastroenterology in 2016, Joseph Murray, MD, of Mayo Clinic, and Benjamin Lebwohl, MD, of Columbia University Medical Center, called this a “back to the drawing board moment” for the celiac community. They wrote that these “unequivocal and disappointing” findings force researchers to refocus the search for what causes celiac.

Experts admit this leaves parents wondering how they can prevent celiac in their children at risk, but the simple answer is: nothing unusual. The American Academy of Pediatrics adopted the standpoint that a healthy child with a family history of celiac should be treated like any other healthy child.

Breastfeeding basics

Maureen Leonard, MD, clinical director of the Center for Celiac Research and Treatment at Massachusetts General Hospital for Children in Boston, says, “If breastfeeding is available, we recommend it until 4 to 6 months of age. We always recommend that an infant be exposed to as many foods as possible, again starting between 4 and 6 months of age.”

Verma says, “Breast milk has the right balance of fat and nutrition. It is the most easily digestible for the immature gut when the baby is born. Secondly, the factors in breast milk help fight infection, building immunity. Finally, bonding happens between the child and the mother with breastfeeding. Those are the three main reasons why breastfeeding is a good thing.”

As for breastfeeding preventing celiac, Verma says, “I don’t think anyone would say it is not helpful.”

Experts expect new insight from studying the microbiome, the community of bacteria that colonize the gut and interact with the infant’s immune system as it develops.

“There are many factors that will change the microbiome. Those are the factors we need to know,” says Verma. “In celiac disease, the discussion has been about breastfeeding, the timing of gluten introduction, the amount of gluten introduced, and if there is a [viral] infection.”

She adds, “Breastfeeding does make a difference. The question is two-fold. Does the microbiome change based on breastfeeding? I will say yes. Does that have an effect on at-risk patients? I think time will tell. I personally think it will be beneficial.”

Verma stresses that if a mother has difficulty nursing for any reason, there are alternatives. A mother should never feel guilty for not breastfeeding if medical or psychological factors prevent it.

Viral infections

For children at risk, she does recommend a special precaution in the case of viral gastroenteritis, which causes symptoms such as diarrhea, fever and vomiting.

In 2017, an international team of scientists reported on an innocuous reovirus that provokes immune response in people while hardly making them sick. Celiac is more common in people who have antibodies for this reovirus, proving they have been infected by it sometime in life. The study demonstrated in theory how the bug could disrupt tolerance to gluten and cause celiac. This possible cause remains unproven, but several other investigations have pointed fingers at viral infections.

Verma advises parents of children at risk: “If at 5 months you are going to introduce gluten and your baby has viral gastroenteritis, maybe hold off a little. That infection makes the gut more permeable. Time will tell, but I think it could potentially be a trigger [for celiac].”

Wait a week or two until the child has recovered, and introduce gluten when digestion is stable, she suggests. All healthy children should be introduced to gluten in time.

Celiac stress

For parents worried about avoiding celiac, Leonard says, “While children with a family history have a higher chance of developing celiac disease compared to the general public, it is still more than three times more likely that they will not develop celiac disease. If the family decision is to keep a gluten-free household, I would encourage them to allow the child [who does not have celiac] to eat gluten outside of the home so that they can participate in the many social activities that revolve around food. At this time we have no evidence to suggest that the child should refrain from eating gluten.”

Verma agrees: “I do not recommend that parents keep their children gluten free if they don’t have celiac disease. They should treat the child like any other child.”

She points out that a normal diet including whole grains can be more nutritious and less expensive than a gluten-free diet. She also warns against the psychological burden of forcing a healthy child to follow a gluten-free diet because another family member has celiac. This can lead to resentment between siblings, for example.

Genetic testing

Leonard suggests concerned parents can have their child tested for celiac genetics. Verma does not recommend doing this at birth because the child should not be treated differently regardless of risk.

She insists on having this conversation with parents who want genetic testing: “If you know that your child has the gene, is that going to make you not want to feed them gluten? As they get a little older and complain of a bellyache or a headache, are you going to be doing a celiac [test] every week? Are you going to be in constant fear the rest of the child’s life that he or she is going to end up with celiac?”

If the parent agrees not to change anything but still wants to know, Verma says, “I will give in.”

Verma and Leonard both send children for a first panel of blood tests by age 3. They then re-screen for celiac every three to five years thereafter. However, Verma points out that blood tests for celiac are invalid in children who consume lower than normal levels of gluten. This may occur, for example, in a home where others follow a gluten-free diet. She would delay screening until the child is consuming a significant amount of gluten every day.

Current study

Infants at risk can help unravel the mystery of what role the microbiome plays. The Celiac Disease Genomic Enviromental Microbiome and Metabolomic (CDGEMM) Study is enrolling children who have a first-degree relative with celiac. Leonard is one of the researchers in this study. She says it includes a questionnaire about life history, stool collection every three months and blood every six months. Infants from across the county may participate by mail free of charge. To learn more, visit https://bit.ly/2GgpFgX.

Research Roundup: Blood test detects celiac without gluten challenge


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Gluten-free diagnosis1

A new blood test offers an easier way to detect or rule out celiac in people who already avoid gluten. The HLA-DQ-gluten tetramer test identifies celiac immune cells that do not go away on a gluten-free diet.

Norwegian researchers tested 62 people with celiac on a gluten-free diet, 10 who were still consuming gluten, 19 with non-celiac gluten sensitivity (NCGS) and 52 presumed-healthy individuals for comparison. The test identified 97 percent of celiac patients on a gluten-free diet and 100 percent on a normal diet. It detected no immune cells in NCGS or healthy people.

A negative test result reliably proves the absence of celiac. However, a small minority of healthy people receive a positive result. A follow-up gluten challenge and further tests may be required to confirm diagnosis or possibly still rule out celiac.

In untreated patients on a regular diet, the test performs comparably well to those currently used for initial screening. Larger studies are needed to validate results. The authors do not recommend the test for children yet because the study took blood samples too large to be safe for children.

Many experts emphasize the need for accurate diagnosis of celiac. However, patients who suspect they have celiac sometimes go on a gluten-free diet immediately before getting diagnosed. Conventional diagnostic tools cannot detect the disease once blood antibodies have returned to normal and the intestine has healed.

Many patients in this condition are unwilling to do a gluten challenge in order to get diagnosed. With the new test, people sensitive to gluten could get closer to an answer without making themselves sick.

¹Sarna VK, Lundin KEA, Mørkrid L, Qiao SW, Sollid LM, Christophersen A. HLA-DQ-gluten tetramer blood test accurately identifies patients with and without celiac disease in absence of gluten consumption. Gastroenterology, 14 Nov 2017, doi:10.1053/j.gastro.2017.11.006 [Epub ahead of print].

Vitamin D against leaky gut2,3

Vitamin D might help treat gluten disorders by maintaining health of the small intestine. Chinese researchers showed it prevents leaky gut in gluten-sensitive mice.

Leaky gut plays a role in the onset of celiac. An early stage of inflammation opens tight junctions between cells in the gut lining. This allows gluten to cross the boundary. In underlying tissue, celiac antibodies recognize gluten as an intruder and attack it, damaging the intestine in the process.

In this study, vitamin D restored tight junctions in mice exposed to gluten. This could prevent the protein from causing further

Italian scientists commenting on the Chinese study point out that leaky gut occurs in other gluten-related disorders, notably NCGS. Although gluten does not provoke autoimmune disease in these cases, large particles may still cross the gut lining and cause inflammation. The experts theorize vitamin D could treat these conditions, too, and even make gluten consumption safe for people who do not have celiac.

Such treatments have not been tested in humans. Since vitamin D is already known to be safe and widely used to support bone health and the immune and nervous systems, the Italian group expresses hope this can quickly go to clinical trial.

²Dong S, Singh TP, Wei X, Yao H, Wang H. Protective effect of 1,25-dihydroxy vitamin D3 on pepsin-trypsin-resistant gliadin-induced tight junction injuries. Dig Dis Sci, Jan 2018;63(1):92-104, doi: 10.1007/s10620-017-4738-0.

³Scricciolo A, Roncoroni L, Lombardo V, Ferretti F, Doneda L, Elli L. Vitamin D3 versus gliadin: a battle to the last tight junction. Jan 2018;63(1):1-3, doi: 10.1007/s10620-017-4848-8.

Learn more about recent headlines and research in This Week in Gluten-Free News!


Celiac Research Needs You

According to legend, celiac research originated with Dr. Willem Dicke. He discovered the cause of celiac during the 1944-’45 Dutch famine under German occupation. He noticed children recovering on a starvation diet, then falling sick after bread was airdropped into Holland. Dicke conducted clinical trials for years, asking parents to remove one food or another from their children’s diets. The famine confirmed what he already knew: something in wheat, barley and rye was the culprit.

“That was one of the huge breakthroughs in celiac disease: identifying an environmental factor that drives the immune disease,” says Ciarán Kelly, MD, medical director of the celiac center at Beth Israel Deaconess Medical Center in Boston. “With most autoimmune diseases, we do not know what the environmental factor is.”

Celiac offers a unique tool to study autoimmunity, explains Daniel Leffler, MD, director of clinical research at the celiac center: “We can control celiac disease by adding and removing gluten in a so-called gluten challenge study, a degree of control we have in very few other diseases.”

Celiac often killed children before Dicke solved the puzzle. Now most patients live full, healthy lives on a gluten-free diet.

However, not everyone recovers well. Strict gluten avoidance affects quality of life. Inability to follow the diet or accidental gluten exposure—getting “glutened”—can cause ongoing symptoms. In refractory celiac disease, intestinal damage persists despite strict adherence.

Unraveling autoimmunity and developing alternative therapies hinge on patients willing to participate in studies. Medical experts say research could move faster if people living with celiac took a more active role. Apparently they tend to suffer in silence even more than people with other diseases. The reason may be that they have frequently been misunderstood in the past.

Silent problem

“The diagnosis of celiac disease is not taken adequately seriously by the medical community,” says Kelly. “There is a false impression that once a patient is diagnosed and told to follow a gluten-free diet, it is a straightforward treatment that almost always works.”

Recent studies uncover a different story. Patients rate their overall health better than people with other chronic diseases but consider their burden of treatment higher. Many fear getting glutened, worry about food costs, avoid eating out and become socially isolated.

In 2014, patient advocacy group Beyond Celiac met leading researchers and asked what they needed to investigate a cure. Experts concluded that the No. 1 gap was a lack of data about people living with celiac.

“We don’t have a good understanding of the burden of the disease,” says Alice Bast, chief executive officer of Beyond Celiac. “We don’t understand the long-term health consequences. At this meeting, we determined that the most important contribution Beyond Celiac could make to accelerate research was to get patients’ participation.”

Leffler says, “Something about the disease, about the treatment thus far, has made people need to be understated, to not complain, to minimize or hide the disorder and not talk about how it affects their lives. I wish I knew the roots of this in celiac disease.”

Marilyn Geller, chief executive officer of Celiac Disease Foundation, explains, “Our community has been told that this is a disease not worth investing in. Congressionally funded medical dollars go to other diseases…. We have to convince policy experts and the biopharmaceutical industry we need treatment alternatives to the gluten-free diet.”

Referral bias

Much research about celiac in North America comes from a handful of major referral centers. Peter Green, MD, director of the Celiac Disease Center at Columbia University Medical Center, New York, says eight doctors there receive 10,000 visits per year, mainly celiac patients.

“This is a very self-empowered patient population seeking specialty expertise,” says Benjamin Lebwohl, MD, a clinician and researcher at Columbia. “A referral center also attracts patients having more difficulty, whether due to recurrent symptoms or a borderline diagnosis.”

Studies of these groups provide skewed data, a problem known as referral bias. Experts know little about the lives of many patients without access to a celiac center. They might rarely even see a doctor regardless of whether they flourish on a gluten-free diet or not.

Lebwohl says, “While we are proud of our research, we are unable to answer seemingly simple questions, such as what proportion of patients with celiac disease still have symptoms despite attempting to adhere to a gluten-free diet.”

Extending the community

To go deeper, celiac advocacy groups have launched patient registries. The Celiac Disease Foundation’s iCureCeliac and Beyond Celiac’s program Go Beyond Celiac have enrolled thousands.

Geller explains, “You go online and create an account. There are a number of questions that you complete regarding your health, from diagnosis to current experiences, not just the medical data points but also your opinion on how difficult it is to exist in this world with celiac disease.”

Participants provide data anonymously. Researchers can peruse the data for clues and patterns. Columbia University used iCureCeliac to investigate whether patients with depression are more likely to have trouble staying gluten free.

Investigators testing a new drug provide a profile of patients who meet criteria such as age or location. The Celiac Disease Foundation does not release contact information but informs everyone in the registry who is eligible to participate, Geller says. Each patient may then choose whether to contact the researcher.

The case for drugs

Registry data may convince larger drug companies to help look for a cure.

Linda Deal, head of patient-centered outcomes for Pfizer, Inc., and a member of Beyond Celiac’s board of directors, says, “Folks in my discipline are interested in understanding insights from the patient’s perspective, what is their journey with their disease.”

Stating she does not speak for Pfizer or Beyond Celiac, Deal says drug companies and the FDA must balance treatment benefits against risks. They must also ensure treatment could be made affordable and available.

“The sooner patients get listed in registries and have their consequences tracked, the sooner we will understand the cost of this disease to society,” Deal says.

No trivial undertaking

“The real bottleneck is patient involvement. If I have patients willing to work with me, I can find funding or ways to partner with industry,” Leffler says. “Participating in a clinical trial, while a rigorous process, gives patients a tremendous amount of information about themselves. Often trial participation involves undergoing measurements of symptom activity and [dietary] adherence, checking in with investigators.”

Kelly says, “While an individual may have a general openness toward participating, to actually take the time and effort may not be a trivial undertaking.”

Filling out a 20-minute survey is far less demanding than a 15-week trial. Patients have an opportunity to ask any and all questions before a trial and can opt out at any time.

“Trials of medications for celiac disease require that patients be exposed to gluten,” Lebwohl warns. “These gluten challenge studies, while critical, are not for everyone. Some people get very ill when exposed even to small amounts of gluten. Those studies can be difficult to recruit for.”

Such trials rely on a small number of volunteers to minimize harm. However, a larger group provides better statistical proof of the findings.

Leffler explains, “We typically err on the side of being a little large, but overpowering a study is not the right thing to do.”

“This is a transformational time for celiac disease,” says Leffler. “Finally, after a period of being stalled, we are getting a critical mass of scientific knowledge, numbers of diagnosed patients and effective advocacy to move celiac disease to a next level where the burden is lower and treatment outcomes are better. If you are in the celiac community and want to be engaged, I see these next five years as critical.”

Van Waffle has a Bachelor of Science in biology and is research editor of Gluten-Free Living. A freelance writer based in Waterloo, Ontario, Canada, he blogs at vanwaffle.com.

Building a Case for Celiac Screening

Celiac affects an estimated 3 percent of children in the Denver area, according to University of Colorado researchers. They uncovered this startlingly high figure while evaluating screening children for celiac and type 1 diabetes. This is the highest prevalence detected anywhere. Previous data have suggested that 1 in 100 North Americans has celiac, and its prevalence is increasing. However, most people affected do not know they have it. To find the hidden patients, some experts advocate celiac screening for all people with risk factors or even the general population.

Standard heath care responds to patients who present complaints. Screening takes a more active approach, looking for signs of disease in patients who lack symptoms. This might help doctors detect celiac in people before they report painful problems such as indigestion, diarrhea and bloating. Early diagnosis could prevent long-term health problems and occasionally fatal complications.

However, these benefits remain theoretical. Medical research has yet to prove general screening programs would benefit patients in the long term. That does not even begin to address the potential public health cost of widespread screening.

Controversial recommendation

In 2017, the U.S. Preventive Services Task Force (USPSTF) issued a recommendation that research has not given enough evidence to support screening patients who lack celiac symptoms. General screening in the United States is not out of the question, but the key questions still need answers.

Still, the task force’s conclusion surprised some patients and experts.

“I agree with the overall conclusion that more evidence needs to be collected for [screening] the general population,” says Marian Rewers, Ph.D., executive director of the Barbara Davis Center for Diabetes in Aurora, Colorado. He is a principal investigator in the Denver studies. “However, the USPSTF missed a lot of published information from high-risk groups.”

Joseph Murray, MD, professor of medicine in charge of the celiac program at Mayo Clinic in Rochester, Minnesota agrees: “The task force took their charge very seriously but also took it quite narrowly.”

The USPSTF specifically asked, “What is the role for testing in patients who are asymptomatic?” Murray explains. In combing through medical research, the panel carefully excluded studies screening the general population because they might include people with symptoms who had not yet complained about them. Few studies have focused explicitly on people who lack symptoms.

Murray proposes trying to convince the USPSTF to ask a different question: “Is there evidence to support screening people who are at risk for celiac disease who may or may not have symptoms?”

Edwin Liu, MD, director of the Colorado Center for Celiac Disease and a colleague of Rewers’ at the University of Colorado, is concerned that the recommendation sends an incorrect message about the importance of celiac symptoms.

“Does it mean that if I’ve got celiac disease and I have symptoms, I only need to treat myself enough to control my symptoms? I don’t think that’s what they mean, but it might lead someone to start thinking this way,” Liu argues.

In some gastrointestinal diseases, the treatment focuses only on reducing symptoms, Liu explains.

However, that is not the case with celiac. Patients must maintain a gluten-free diet for life even after the condition is effectively controlled.

Research challenges

Public disappointment about the task force’s recommendation prompted the Celiac Disease Foundation (CDF) based in Woodland Hills, California, to post its position earlier this year on its website. The patient advocacy group supports the call for more research, but chief executive officer Marilyn Geller understands the community’s concern.

“A tremendous amount of unnecessary patient suffering occurs with undiagnosed celiac disease,” explains Geller. The average patient suffers painful symptoms for six to 10 years prior to a correct diagnosis. They may view this recommendation from the government as a step away from recognizing serious impacts of celiac.

It is a difficult but important challenge to design research to investigate screening people who have no symptoms, says Murray. Rigorous studies would be fraught with problems.

For example, he describes a theoretical study in which researchers would recruit volunteers without symptoms who agree to be tested for celiac but go untreated and not be informed of the results for five years. This would demonstrate the long-term health outcome in people who have celiac without knowing it. Not only would this be expensive, but it presents ethical problems for doctors who pledge to prevent harm.

The diabetes link

However, the ongoing Denver research that found a high celiac prevalence in children is providing an opportunity. The charitable organization JDRF, which funds research to prevent type 1 diabetes, has supported the program through the University of Colorado and Barbara Davis Center for Diabetes. The Autoimmunity Screening for Kids (ASK) study is recruiting 55,000 children ages 2 to 17 from Denver over three years to find out what happens when they are screened for type 1 diabetes and celiac.

Diabetes receives greater public awareness and funding. The two conditions share genetics and other risk factors, and patients with one appear to be predisposed for the other, so it is useful to study them together.

ASK was set up primarily to screen for type 1 diabetes, explains Rewers: “Celiac disease screening was added as a relatively easy and important secondary goal.”

Celiac disease autoimmunity

Asymptomatic children will undergo testing for what researchers call celiac disease autoimmunity (CDA). It means their immune systems have begun making antibodies against gluten but without causing any obvious symptoms. At this stage, some patients still might not show damage to the intestinal lining, the essential test for celiac.

The Denver celiac prevalence study identified 1,339 children with celiac risk factors born at St. Joseph’s Hospital between 1993 and 2004 and followed them for up to 20 years. Eventually, 66 developed CDA and also celiac, while 46 met criteria for CDA only.

The health-care community considers CDA a precursor to celiac. It remains unclear what triggers the onset of disease damage to the intestine, how long this takes and why a significant proportion of cases never appear to progress beyond producing antibodies. Some people only test positive for antibodies temporarily.

A blood test to screen newborn children for celiac might seem simple and inexpensive, but it is not enough to settle the question. People with a genetic predisposition require continual follow-up to watch for the onset of CDA or celiac at any age. Often it does not appear until adulthood.

Geller points out that infant screening would fail to detect most cases.

Some gastroenterologists recommend people with CDA adopt a gluten-free diet to prevent potential complications once the disease gets going.

Here Liu puts a positive spin on the USPSTF recommendation. In the recent past many pediatricians like himself tended to screen children at risk and treat them for CDA even if they did not have symptoms. However, it was difficult for families of children who felt fine at the outset to have their doctors impose a gluten-free diet.

Liu adds, “These official recommendations say exactly what we already know: that there’s not enough data to support this. It allows us to step back and be more thoughtful about how we approach each patient.”

This shift can also help research.

“Several years ago, I thought that we had lost our window of opportunity to study kids who are asymptomatic without treatment, because everyone was leaning toward screening them and treating them,” says Liu. “Now, with the conclusions by the USPSTF, this gives us more permission to not treat these kids but monitor them. We will be able to get some studies of the natural history of untreated, asymptomatic celiac disease.”

The ASK study should shed some light on what happens from early childhood through adolescence.

“We’re going to look at the acceptability of large-scale screening,” says Liu. “We’ll look at the potential harms that we can cause by screening, like are we going to cause kids to get a lot of unnecessary endoscopies? Are we causing a lot more anxiety and depression in families? And we are also looking at the benefits.”

He expects the study to identify about 1,000 children with celiac. An estimated one-half of them will have no symptoms.

Rather than concealing their CDA status, as in the study design Murray described, it will rely on patients’ autonomy and right to choose. Everyone is different. Some patients have more risk tolerance than others.

Liu says, “We find somebody who’s antibody-positive, and we don’t treat them, but we monitor them carefully to make sure they don’t get themselves into trouble. They come in every six months. They find out they’re still antibody-positive.

“At some point, a lot of these individuals may say, ‘You know what? These antibodies aren’t going away. Let’s just chase this and take care of it, OK?’ Or they may eventually recognize they have symptoms. I anticipate that the majority of people who continue to follow up and monitor, knowing that they’re still antibody-positive, may end up choosing to be on a gluten-free diet. There’s just no rush if you’re asymptomatic.”

Regardless of their decision, the study will continue to follow their progress. The data will allow researchers to compare people who choose early treatment with those who do not. It will indicate how earlier diagnosis and treatment through a screening program might improve long-term health outcomes.

Rewers says he believes adequate evidence will eventually prove the value of screening.

Murray says, “A lot of people who have celiac disease have no symptoms now but will get symptoms in the future. They might even get serious or fatal complications of celiac disease before they are ever diagnosed. We could prevent those if we found them and treated them early.” But, he adds, “How do we predict who is going to go on to complications and who’s not? That’s something
that’s really not understood.”

In patients with risk factors such as a first-degree family member with celiac, research has proven the benefit of screening. Murray says he tells his newly diagnosed patients their family members should undergo testing because they have a substantial risk for celiac.

In other cases, experts simply feel strongly about recommending it, for example, in children with type 1 diabetes. According to Diabetes Canada, they have a 4 to 9 percent risk of having celiac but up to 70 percent show no symptoms of it.

Murray says, “There isn’t yet enough evidence to say people with type 1 diabetes benefit from being tested, but a lot of us actively support testing in that context because we know people with atypical symptoms are often hidden from view.”

CDF works to raise awareness among doctors about who should receive testing for celiac, based on good evidence. Based on CDF’s advice, Anthem Health Insurance recently adopted guidelines to encourage testing symptomatic patients and screening their first-degree relatives.

“The real key is simply educating physicians on what to look for,” says Geller. “My son wasn’t diagnosed until he was 15. He had clear symptoms from when he was very little, but they weren’t classic symptoms. I think we’ve come a long way now in terms of realizing this broad array of symptoms.”

In the absence of screening, the broader public must rely on their doctors’ awareness of celiac risk and willingness to test for it.

Van Waffle has a Bachelor of Science degree in biology. He is research editor for Gluten-Free Living. He blogs about nature, gardening and local food at vanwaffle.com.

Study Sessions: Celiac research news roundup

Celiac hospitalization costs $7.4 million

Hospitalization for celiac in the Unite States cost $7.4 million in 2014, according to a recent analysis from the University of Rhode Island. National records revealed 805 patients were hospitalized with celiac as the primary diagnosis. Their stays typically lasted 4.9 days and cost $9,247, slightly less than the mean for all hospitalizations: $10,885. Additionally, emergency rooms saw 752 visits due to the condition.

Women accounted for 63 percent of hospital discharges, supporting previous findings that they are more prone to celiac. However, male patients typically had higher hospital costs: $10,669 compared to $8,403 for women. Some research suggests celiac affects men more severely.

Dividing celiac patients down by age group, adults from 65 to 84 had the most expensive hospital visits ($10,830), with children under 18 the second-most-costly ($10,612). Not enough data were available to allow analysis on patients 85 or older. As celiac becomes more prevalent and because it has no cure, it will require ongoing health expenditures.

Borrelli EP. “Inpatient hospital costs for celiac disease in the United States in 2014,” International Journal of Celiac Disease, 2017, 5(3), doi:10.12691/ijcd-5-3-2.

Symptoms of celiac persist after diagnosis

Many people diagnosed with celiac continue to experience abdominal pain up to a year after adopting a gluten-free diet. A study of 85 new patients in Winnipeg, Manitoba, Canada, found that 66 percent were experiencing gastrointestinal symptoms when they were diagnosed. The proportion decreased only to 47 percent after 12 months of treatment.

During in-person interviews, the participants reported the frequency of symptoms such as diarrhea, indigestion and bloating. After a year eating gluten free, there was no difference in the rate of discomfort between participants who avoided gluten completely and those who admitted consuming some either by accident or intentionally. However, dietary adherence was considered high in this group, as 93 percent reported gluten exposure less than once a month.

Despite these findings, strict gluten avoidance remains essential for celiac patients. Ongoing digestive discomfort can result from other contents of the diet, such as fiber. Even the gluten-free diet itself can be associated with bloating. Patients might blame these symptoms on accidental gluten exposure. However, only gluten in wheat, rye, barley and related grains damages the intestinal lining in people with celiac.

It is a challenge for health care workers to distinguish the true cause. New celiac patients require careful medical follow-up to check persistent symptoms and ensure dietary adherence. Many experts have been calling for a simple and reliable test to identify whether patients are being exposed to gluten. This study highlights the need for a tool that is inexpensive and noninvasive.

Sylvester JA, Graff LA, Rigaux L, Bernstein CN, Leffler DA, Kelly CP, Walker JR, Duerksen DR. “Symptoms of functional intestinal disorders are common in patients with celiac disease following transition to a gluten-free diet,” Digestive Diseases and Sciences, 2017, doi:10.1007/s10620-017-4666-z.

Safe oats for those with celiac

A survey of 896 Finns supports the safety of oats for people with celiac. Purified oats have been widely accepted and available for celiac patients in Finland for 15 years. Patients following a long-term gluten-free diet recovered equally well whether they included oats or not.

For this study, volunteers provided current blood samples along with medical histories. All had undergone follow-up biopsies about one year after diagnosis to assess intestinal healing. Typically participants had followed a gluten-free diet for 10 years, with 82 percent eating oats.

Patients diagnosed since 2000 were more likely to use oats, probably reflecting doctors’ growing awareness of the safety of oat consumption. It was also more common among patients who consulted dietitians, who are likely to focus on oats’ nutritional benefits.

Those who consumed oats were no more likely to experience ongoing symptoms than those who avoided oats. The groups performed equally well on antibody tests for inflammation related to celiac. Their follow-up biopsies were just as likely to indicate gut healing. Those who consumed oats scored slightly better on a quality-of-life questionnaire and were less likely to be smokers.

North American specialists have also been advocating pure, uncontaminated oats for the diet because they offer an important alternative source of fiber and other nutrients. Both the U.S. Food and Drug Administration and Health Canada have revised labeling requirements to make oat products more accessible for people with celiac. However, experts continue to lobby for clarification because of risks such as cross-contamination in regular commercial oats. A recent review pointed to insufficient research on oat safety for people with celiac.

This study provides compelling data on oat safety from a large study group with a long follow-up time on the gluten-free diet. However, it did not investigate whether patients had consumed pure, uncontaminated oats. These findings do not clarify the safety of oats mechanically sorted to remove contaminants such as wheat grains, a process introduced by some North American manufacturers of gluten-free products.

Aaltonen K, Laurikka P, Huhtala H, Mäki M, Kaukinnen K, Kurppa K. “The long-term consumption of oats in celiac disease patients is safe: a large cross-sectional study,” Nutrients, 2017, 9(6), doi:10.3390/nu9060611.

Safe sourdough for celiac patients

In a small clinical trial, sourdough wheat baked goods consumed for three days by 10 celiac patients caused no autoimmune response. In comparison, the same amount of a natural wheat product provoked celiac antibody production in another 10 patients.

When sourdough ferments, bacteria consume protein and break it down into smaller particles. Italian researchers used strains of Lactobacillus, bacteria extracted from traditional bread sourdough. These were chosen for having digestive enzymes highly destructive against gluten protein.

The researchers also tested gluten on samples of cultured gut tissue from celiac patients. These cell cultures reacted to gluten from natural wheat flour, but after sourdough fermentation they showed no response.

To compare the response in patients, the study took blood samples before and after the participants ate their baked goods. Those who consumed natural wheat had a spike in antibodies mirroring the effect on intestinal cells, while antibody levels remained normal in those consuming sourdough.

Other studies are investigating drug therapy for people with celiac using enzymes similar to those used by Lactibacillus to ferment gluten. Theoretically, an enzyme pill could prevent harm when eaten along with gluten-containing foods. However, normal acidity in the human gut destroys enzymes faster than they can destroy gluten. Sourdough fermentation of food may provide a better alternative by eliminating gluten before it is consumed.

European scientists have been investigating sourdough for years. Participants in earlier studies showed tolerance for sourdough products, but this research confirmed a lack of immune response. This study does not prove all sourdough is safe or that celiac patients can tolerate such products on a long-term basis. Sourdough products have not received approval from celiac experts in North America.

Mandile R, Picascia S, Parrella C, Camarca A, Gobbetti M, Greco L, Troncone R, Gianfrani C, Auricchoi R. “Lack of immunogenicity of hydrolysed wheat flour in patients with coeliac disease after a short-term oral challenge,” Alimentary Pharmacology and Therapeutics, 2017;46:440-46, doi:10.1111/apt.14175.


CD Cases Level But Gluten Avoidance On The Rise

CD cases level off[1]

Prevalence of celiac disease in the United States has stopped increasing while undiagnosed cases appear to have decreased. Meanwhile, the number of people following a gluten-free diet without a diagnosis has risen threefold since 2009 to an estimated 3.1 million Americans.

This study drew data from 22,277 participants in National Health and Nutrition Examination Surveys between 2009 and 2014. Individuals answered a questionnaire about celiac disease and the gluten-free diet and provided blood samples. Researchers at Mayo Clinic in Rochester, Minnesota, tested for elevated tissue transglutaminase (tTG) antibodies and endomysial antibodies (EMA). Celiac disease was considered confirmed in anyone who reported a clinical diagnosis or tested positive for both antibodies.

The proportion of people with celiac disease did not change significantly over the study period, holding steady at about 1 in 142 (0.7 percent), corresponding to approximately 2 million Americans. This contrasted with earlier studies showing a steady increase in the number of cases over recent decades.

During the same time period, the prevalence of undiagnosed celiac disease fell from 0.6 percent to 0.3 percent. The trend appeared particularly in non-Hispanic whites and adults. The decrease may reflect better awareness of the disease among the public and health care workers. However, popularity of the diet might also have influenced this data because antibody tests are less likely to detect celiac disease in people who avoid gluten.

The proportion of Americans who avoid gluten increased from 0.5 percent to 1.7 percent. The questionnaire did not ask participants why they made this choice. The authors note that the health and nutritional effects of the diet are unproven for people who do not have celiac disease or wheat allergy.

Persistent CD despite GF diet[2]

Nearly one in five children with celiac disease had persistent damage to the gut despite following a gluten-free diet for at least a year in a study at two Boston hospitals. Blood tests for tTG conventionally used in follow-up failed to predict damage.

The study involved 103 children who had follow-up biopsies between one and 12 years after an initial biopsy to diagnose celiac disease. Nineteen percent of the patients still had tissue damage.

Blood tests detected elevated tTG in 43 percent of those with persistent damage and 32 percent of those with healing. Only 55 percent of patients with persistent damage reported feeling any symptoms, while a majority of healed patients also complained of symptoms possibly related to celiac disease.

Experts widely endorse tTG tests to monitor gluten-free adherence and recovery in patients with celiac disease. This study raises concern that the test, while accurate for initial diagnosis, is a poor indicator of healing. The authors argue an additional biopsy is the only way to confirm recovery.

This data set was small and relied on past medical histories, which is a statistically weak approach. While the findings raise an important concern, they will need confirmation by larger studies to recommend a change in health care practice.

The study also corroborates rising concern about a significant proportion of celiac disease patients who respond poorly to the gluten-free diet. Persistent damage to the gut increases risk for complications, such as lymphoma. This adds urgency to the search for alternative treatments for patients with unresponsive celiac disease.

Bone recovery on GF diet[3]

The gluten-free diet improves impaired bone structure in women with celiac disease, according to Argentinian research.

Bone loss and fractures are common in untreated celiac disease patients. Dual-energy X-ray absorptiometry, which is typically used to detect loss of bone density, does not distinguish between the hard outer cortex and the inner spongy part of the bone. The team who performed this study had previously used an alternative, high-resolution peripheral quantitative computed tomography (HRpQCT), to look at microscopic structure of the porous tissue in premenopausal women. They detected significant deterioration in celiac disease patients.

This latest study investigated how the same bone structure changes as a result of treatment. It recruited 26 young women newly diagnosed with celiac disease. They underwent HRpQCT scans of the wrist and ankle when they were diagnosed and again after one year of treatment. Besides following a gluten-free diet, the patients took vitamin D supplements and were advised to consume adequate calcium through dairy products. The study compared the patients’ bone scores with those of a similar group of healthy women.

The microscopic structure of the spongy tissue improved significantly in all patients, especially in five women who achieved normal tTG tests after treatment. However, even after a year, the patients had not caught up with scores from the healthy control group. Researchers will continue to follow this study group and assess for recovery in the longer term. While vitamin D supplements probably accounted for some of the observed improvement, blood test scores showed an effective gluten-free diet had the most significant influence on bone recovery.

CD teens slightly smaller[4]

Teenagers with celiac disease are smaller, but the difference is generally too minimal to raise health concerns, according to Israeli researchers. They made these findings from medical records of 2 million 16- and 17-year-olds reporting to military recruitment centers between 1988 and 2015.

The records identified 10,566 teens with celiac disease. Girls averaged one-quarter inch shorter than normal but showed no difference in body mass index (BMI). On the other hand, boys with celiac disease on average were leaner but matched the height of others their age, with a BMI of 21.2 compared to 21.7. The small differences suggest celiac disease diagnosed during childhood does not severely impair height and weight at maturity.

In this set of Israeli adolescents, the prevalence of diagnosed cases increased from one-tenth of a percent in 1988 to 1.1 percent in 2013-2015. Celiac disease was also significantly more common among teens born in Western countries compared to those from the former U.S.S.R., Asia and Africa. The same pattern appeared when comparing parents’ country of origin.

Did you know?

Cosmetics and personal care products containing gluten are safe for people with celiac disease if used with caution. Gluten must be eaten to cause the autoimmune reaction in contact with the gut lining. This applies even to people with dermatitis herpetiformis, a form of celiac disease involving an intense skin rash. A study that injected gluten into the skin of people with this condition failed to produce any reaction.

Sensitive people might prefer to avoid gluten in products like lipstick, lip gloss and hand lotion that they could ingest unintentionally. However, even with such a mistake, the tiny amounts consumed would not deliver the daily 10-milligram dose of gluten considered safe for people with celiac disease.

Skin products may contain problem ingredients for people with allergies such as wheat allergy. Several case studies involving individual patients suggest that hydrolyzed wheat protein in cosmetics can cause severe allergic reactions. Skin hypersensitivities are unrelated to celiac disease.

Van Waffle has a Bachelor of Science degree in biology and lives in Waterloo, Ontario, Canada. He is research editor for Gluten-Free Living. He blogs about nature, gardening and local food at vanwaffle.com.

[1] Choung RS, Unalp-Arida A, Ruhl CE, Brantner TL, Everhart JE and Murray JA, “Less hidden celiac disease but increased gluten avoidance without a diagnosis in the United States: findings from the National Health and Nutrition Examination Surveys from 2009 to 2014,” Mayo Clinic Proceedings, Jan 2017;92(1):30-38, doi: 10.1016/j.mayocp.2016.10.012.

[2] Leonard MM, Weir DC, DeGroote M, Mitchell PD, Singh P, Silvester JA, Leichtner AM and Fasano A, “Value of IgA tTG in predicting mucosal recovery in children with celiac disease on a gluten free diet,” Journal of Pediatric Gastroenterology and Nutrition, Nov 3 2016, doi: 10.1097/MPG.0000000000001460 [Epub ahead of print].

[3] Zanchetta MB, Longobardi V, Costa F, Longarini G, Mazure RM, Moreno ML, Vásquez H, Silveira F, Niveloni S, Smecuol E, de la Paz Temprano M, Massari F, Sugai E, González A, Mauriño EC, Bogado C, Zanchetta JR and Bai JC, “Impaired bone microarchitecture improves after one year on gluten-free diet: a prospective longitudinal HRpQCR study in women with celiac disease,” Journal of Bone and Mineral Research, Jan 2017;32(1):135-142, doi:10.1002/jmbr.2922.

[4] Assa A, Frenkel-Nir Y, Leibovici-Weissman Y, Tzur D, Afek A, Katz LH, Levi Z and Shamir R, “Anthropometic measures and prevalence trends in adolescents with coeliac disease: a population based study,” Archives of Disease in Childhood, 2016(0):1-6, doi:10.1136/archdischild-2016-311376.

Research Roundup: Celiac Disease Triggers


Celiac disease triggers: Mild virus

Celiac disease can be triggered by a common virus so mild people might not even notice they have it. The immune system soon eliminates this reovirus but it leaves its mark. One event like this may not be enough, but in predisposed people the accumulation of several similar insults may provide an autoimmune response such as celiac disease.

U.S. researchers made this discovery by studying the effects of two strains of the virus with slight genetic differences. One was capable of provoking celiac in susceptible mice and the other was not. A comparison of how mice responded to both strains identified how their immune systems behaved differently as they lost tolerance to gluten. In particular, the mice with celiac produced higher levels of a protein called interferon regulatory factor 1 (IRF1).

Then researchers looked for evidence of the same activity in humans. They identified people with high levels of reovirus antibodies from previous infection. Celiac disease was unexpectedly common in this group. Further, celiac patients who had high levels of reovirus antibodies also produced more IRF1. This implicated the virus as a contributing factor in onset of their disease.

Future research might reveal a viral vaccine that can protect people at risk for celiac.

Bouziat R, Hinterleitner R, Brown JJ, Stencel-Baerenwald JE, Ikizler M, Mayassi T, Meisel M, Kim SM, Discepolo V, Pruijssers AJ, Ernest JD, Iskarpatyoti JA, Costes LMM, Lawrence I, Palanski BA, Varma M, Zurenski MA, Khomandiak S, McAllister N, Aravamudhan P, Boehme KW, Hu F, Samsom JN, Reinecker H-C, Kupfer SS, Guandalini S, Semrad CE, Abadie V, Khosla C, Barreiro LB, Xavier RJ, Ng A, Dermody TS and Jabri B, “Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease,” Science, 7 April 2017;356:44-50, doi:10.1126/science.aah5298.

Celiac disease triggers: C-section findings

Babies born by cesarean section do not have an increased risk for celiac, according to a new study from Italy.

Cesarean births do not provide babies with the same microbes as those who pass through the birth canal. Their gut microbiome matures more slowly and includes fewer of certain bacteria that assist digestion. Disturbances in the microbiome are implicated in celiac disease. For this reason, some experts believe vaginal delivery might protect babies at risk.

This study focused on 431 children born between 2003 and 2009 who had a high risk for celiac based on genetic tests. Nearly half (198) had a cesarean birth. In the study group, 71 children were diagnosed with celiac by age 10. The disease was just as likely regardless of how they were born.

This was the first study on this topic to follow a group of at-risk children from birth, providing stronger data than previous research. It did not distinguish between elective and emergency cesarean delivery.

Lionetti E, Castellaneta S, Francavilla R, Pulvirenti A and Catassi C, “Mode of delivery and risk of celiac disease: risk of celiac disease and age at gluten introduction cohort study,” Journal of Pediatrics, 10 Feb 2017;184:81-86.e2, doi:10.1016/j.jpeds.2017.01.023 [Epub ahead of print].

The Microbiome and Celiac Disease

The body depends on a balanced community of gut bacteria to support health and nutrition. Imbalance can cause illness. Some medical researchers are investigating whether such a disturbance could trigger celiac disease. Even though the human intestine on its own does not have the ability to digest gluten, gut bacteria normally help. This community, known as the microbiome, might also prevent the body from launching a needless war on gluten.

A new long-term study through Massachusetts General Hospital for Children in Boston will investigate these effects in infants at risk for celiac disease. The findings might explain why some people with the same genetic predisposition get sick while others do not. Future therapies to cure or prevent celiac disease might target the microbiome.

a sum of its parts

In 2008, the National Institutes of Health (NIH) launched the human microbiome project to describe some 100 trillion microbes that live on and in the human body. Medical science has viewed these microbes as a community for only about 10 years, according to Robert Karp, Ph.D., program director for genomic and microbiome studies at the National Institute of Diabetes and Digestive and Kidney Diseases based in Bethesda, Maryland. He specializes in genetics, the study of how all life—whether humans or microbes—inherits traits from one generation to the next.

More than 10 years ago, “Scientists tended to think in terms of what individual strains or species were doing, that they were acting on their own,” Karp explains. “People distinguished [disease-causing] pathogens from commensal bacteria that live in us but cause no harm and possibly cause benefit, but were not thinking in terms of how the whole community acts in a way that’s more than a sum of its parts.”

Dental microbiologists were first to note cooperation between bacteria, he says. Meanwhile, for decades ecologists had been studying microbial communities in nature. After these concepts spread to general medical research, the NIH’s human microbiome project began.

About 1,000 species have been associated with the human microbiome, but the average person has only about 500 or so, Karp says. Some are obscure and poorly understood even by scientists, such as archaea, which have a completely different metabolism than bacteria and are also found in deep ocean hydrothermal vents.

a revolution in research

According to Karp, “In classical microbiology, the only way to study a particular strain of microbe is to culture it in pure form in a test tube. Since we do not know how to culture the vast majority of members of the human microbiome, it is impossible to study them in this way.”

Innovative technology is providing new clues by decoding deoxyribonucleic acid (DNA), which stores the functional instructions in all life forms.

Karp says, “Fast, cheap DNA sequencing and advanced computational methods” allow scientists to sample the microbiome and disentangle the individual DNA sequences of all the microbes contained. “It is possible to deduce a great deal of information about the metabolism, physiology and general lifestyle of a previously unknown microbe from its genome sequence. Even if we can’t culture this microbe, we can clone its unfamiliar genes into a well-studied lab microbe in order to learn something about their function,” he says.

The human genome contains a mere 20,000 protein-coding genes, on par with the fruit fly. However, a 2005 review in the journal Science estimated the human microbiome collectively has at least 100 times as many genes. Its diversity empowers the human gut to extract more essential nutrients than we could manage on our own.


Karp says what fascinates him most about the microbiome is “how its members are adapted to life with us, how we have adapted to life with them. We survive better as a species than we would without them. [There are] hundreds of different ways in which they influence most aspects of our physiology. We don’t even know what most of those ways are.”

Alessio Fasano, M.D., director of the Center for Celiac Research and Treatment at Massachusetts General Hospital in Boston, leads research on the role of the microbiome in celiac disease. He says, “It’s a true symbiotic relationship. We give them hospitality, and in exchange they give us stuff that’s useful for us. For example, we can’t digest fiber, but when fiber reaches the colon, microorganisms can make products that are very good for us.”

For example, bacterial fermentation produces butyrate, which is essential for colon health.

“There’s a great deal of variability in the microbiome between different individuals,” says Karp. “Identical twins have a more similar microbiome than fraternal twins or other pairs of first-degree relatives. People who are cohabiting also tend to have microbiomes that are more similar to each other than people who are living someplace else.”

Lifestyle also affects the composition, he adds, “so someone living as a hunter-gatherer in Africa has a rather different microbiome from a Western European.”

focus on function

This variability makes it hard to draw conclusions about how the microbiome operates. Studies of individual bacterial species associated with disease often make contradictory observations. To sort them out, Karp points to the importance of meta-analysis.

This technique scans the scientific literature for all titles on a particular topic, weighs their research according to size and statistical integrity, and then combines them to see whether any significant effect can be measured overall. This combats the common error of cherry picking studies to make broad statements on health.

Research is also shifting focus from individual species to their functions. Early studies often conducted censuses of microbes, which “mask a greater functional uniformity,” according to Karp. A species that serves an important role in one person may be absent from someone else, in whom a different group serves the same purpose.

To study function, researchers can grow a microbe to identify the products of its metabolism or measure these metabolites in human blood or urine. Functional analysis is still in its infancy but may reveal more robust patterns, Karp says.

the infant microbiome

A key question is how an infant’s microbiome develops from birth. Although the fetus is exposed to a few microbes prenatally, many experts believe that passage through the birth canal provides an essential transplant of microbes. A child’s early microbiome resembles the mother’s vaginal microbiome.

“Over the first two to three years of life, the microbiome matures, so that by the time you’re 3 years old [it] looks like an adult microbiome,” says Karp. “We know something about when different strains appear. But we know very little about the mechanisms of how those changes happen.”

Fasano says, “One of the key functions for the microbiome, particularly early in life, is to teach the immune system to mature and make the right decision if and when to unleash inflammation.”

Beneficial microbes help the immune system recognize and defend itself against microbes that cause infection. A well-balanced microbiome will set the bar high for inflammation, Fasano explains. Otherwise the immune system becomes hypersensitive, reacting too easily and leading to continued injuries.

association with celiac

A nationwide Swedish study published in Gastroenterology in 2012 found children born by elective caesarean section were more likely to develop celiac disease. The authors say these findings support “the hypothesis that the bacterial flora of the newborn plays a role in the development of celiac disease.”

How this might occur remains unclear and yet to be investigated in detail, according to Yolanda Sanz, M.Sc., professor of research at the Spanish National Research Council based in Madrid, who studies the microbiome in children with celiac disease.

Sanz coauthored a 2009 paper in the Journal of Clinical Pathology that found an unbalanced microbiome in children with celiac disease. The sick microbiome included greater or lesser prevalance of certain bacterial species and, perhaps more importantly, a general reduction in species diversity. The microbiome only partially recovered after long-term treatment on a gluten-free diet.

More recently, Sanz and colleagues studied healthy infants who were genetically predisposed to celiac disease but had not developed it. Again, they found a distinctly atypical microbiome. The study, published in 2014 in Gut, suggests host genetics influence which specific microbes colonize the gut, which could in turn influence the onset of disease risk.

Further research published in 2015 in The American Journal of Pathology found certain bacteria trigger celiac disease in mice by promoting an inflammatory response to gluten in the diet. A microbiome free of disease-causing bacteria appeared to protect mice against inflammation. Notably they lost their protection after receiving a bacterium from a human celiac disease patient.

While these studies indicate bacterial associations, research has yet to prove that an altered microbiome causes celiac disease in humans.

Sanz says, “We know that exposure to microbes makes the immune system maturate, but we don’t know the type of interactions between the microbiome and gluten in the diet” and how they together might lead to celiac disease.

beyond simple genetics

The microbiome can also profoundly influence how the host interprets its own genetic code. While human DNA contains the entire library of functional tools that pass from parents to their children, many genes remain silent. Environmental factors can switch them off or on, and these switch positions may also pass from one generation to the next. Fasano says this field of study, called epigenetics, may explain why a previously rare inheritable disorder like celiac disease has become an epidemic.

“We thought that we had everything straight with celiac disease,” explains Fasano. “We knew a lot of the genetics. We know that the environmental trigger is gluten. For many years, we’ve been under the impression that there were two necessary sufficient conditions to develop celiac disease. Then, over the years, we learned that that’s not true, that there are people who eat gluten for 50 years and they stay healthy, and then at a certain point they lose the [ability] to tolerate it and develop celiac disease.”

The rapid increase in cases pointed to some environmental factor at play. Doctors speculated that changes in breastfeeding behavior and infant nutrition might be to blame, but extensive research has ruled these out.

Now Fasano is turning attention to what he calls “cross-talk between us and this parallel world [of gut microbes].” Changes in the microbiome likely alter gene expression, causing the immune system to behave differently, he says. Instead of defending the body, it begins attacking the lining of the gut, marking the onset of celiac disease.

Fasano is one of the principal investigators in the Celiac Disease Genomic, Environmental, Microbiome and Metabolomics (CDGEMM) Study through Massachusetts General Hospital for Children. It aims to follow 500 children at risk for celiac disease from birth until age 5. Participants will provide stool samples, allowing investigation of the bacteria and metabolites produced in the gut. Further, the study will explore interactions between genetics and environmental factors such as diet, infections and antibiotic use.

Fasano says a study such as CDGEMM is necessary because it follows a group of people over time, ideally from birth. It will compare the microbiome before and after onset of celiac disease, shedding light on changes when they occur. This data will help predict why an individual took the wrong turn rather than stay the course and maintain tolerance to gluten.

Eventually doctors may be able to prevent celiac disease by manipulating the microbiome to “bring it back to the right course,” Fasano says.

supporting microbiome health

While experts are still looking for evidence, they can offer advice on how to support a healthy microbiome. One of the most important practices is to avoid overuse of antibiotics.

Karp says, “There are times when antibiotics are absolutely essential, and they’ll save you from a life-threatening disease. You have to use them then.” However, in the United States, the average person receives antibiotics many times during the course of childhood. Antibiotics “totally upset the composition of your microbiome,” he says.

Research suggests that dietary fiber also supports a healthy microbiome, he adds. “Probably the best way to maintain a healthy microbiome is [through] a healthy diet, also good exercise, a good amount of sleep and try to decrease the level of stress. Laugh a lot, because that helps to boost the immune system and therefore helps the microbiota to keep us healthy.”

Van Waffle has a Bachelor of Science degree in biology and lives in Waterloo, Ontario, Canada. He is research editor for Gluten-Free Living. He blogs about nature, gardening and local food at vanwaffle.com.


Celiac Caregivers Face Emotional Burden

Celiac Diagnosis

Celiac caregivers, or family members who care for celiac disease patients, face a big emotional burden. A survey of Swedish national health records found caregivers have an 11 percent greater risk for depression and 7 percent great risk for anxiety.

The study identified 29,096 celiac patients and 41,753 first-degree relatives in the registry. It focused mainly on 27,698 high-risk caregivers: parents of diagnosed children or spouses of people diagnosed during adulthood. The high-risk group was compared with 144,293 similar caregiving parents and spouses to people in the health registry who did not have celiac.

At its worst

The increased risk for anxiety and depression appeared mostly a few years before diagnosis and four to eight years after diagnosis. The authors speculate that the first spike may coincide with onset of symptoms and initial investigation to determine the problem, followed by the relief of having a diagnosis. The second spike may reflect concerns over related long-term health complications.

Previous studies have suggested celiac disease can impair the sex life of patients and their partners, based on interviews with smaller groups of patients. The national registry study could not collect any further information on that point. Also, it could not determine whether reduced symptoms or effective treatment on a gluten-free diet influenced the burden on family members.

However, it provides stronger evidence for a general burden on caregivers because it is based on a large population with a wide range of characteristics, such as household income.

Get everyone involved

The authors advise parents and spouses to take this into account and involve the whole family in supporting those with celiac disease. Researchers from the United States, United Kingdom, Sweden and Norway contributed to this study.

Ludvigsson JF, Roy A, Lebwohl B, Green PH and Emilsson L, “Anxiety and depression in caregivers of individuals with celiac disease—a population-based study,” Digestive and Liver Disease, Nov 16 2016, doi:10.1016/j.dld.2016.11.006 [Epub ahead of print].

Van Waffle has a bachelor’s of science degree in biology and lives in Waterloo, Ontario, Canada. He is research editor for Gluten-Free Living. He blogs about nature, gardening and local food at vanwaffle.com.

Nonresponsive Celiac Disease

In patients with nonresponsive celiac disease, symptoms persist even after following a gluten-free diet for six to 12 months or return after a long period of good health. A study in the Journal of Pediatric Gastroenterology and Nutrition found that nearly one in five children with celiac disease had persistent damage to the gut despite following a gluten-free diet for at least a year. Blood tests for tTG conventionally used in follow-up failed to predict damage.

The findings

The study involved 103 children who had follow-up biopsies between one and 12 years after an initial biopsy to diagnose celiac. Nineteen percent of the patients still had tissue damage.

Blood tests detected elevated tTG in 43 percent of those with persistent damage and 32 percent of those with healing. Only 55 percent of patients with persistent damage reported feeling any symptoms. A majority of healed patients also complained of symptoms possibly related to celiac.

Experts widely endorse tTG tests to monitor gluten-free adherence and recovery in patients with celiac. This study raises concern that the test, while accurate for initial diagnosis, is a poor indicator of healing. The authors argue an additional biopsy is the only way to confirm recovery.

This data set was small and relied on past medical histories, which is a statistically weak approach. While the findings raise an important concern, they will need confirmation by larger studies to recommend a change in health care practice.

Nonresponsive celiac disease

The study also corroborates rising concern about a significant proportion of celiac patients who respond poorly to the gluten-free diet. Persistent damage to the gut increases risk for complications, such as lymphoma. This adds urgency to the search for alternative treatments for patients with nonresponsive celiac disease.

Leonard MM, Weir DC, DeGroote M, Mitchell PD, Singh P, Silvester JA, Leichtner AM and Fasano A, “Value of IgA tTG in predicting mucosal recovery in children with celiac disease on a gluten free diet,” Journal of Pediatric Gastorenterology and Nutrition, Nov 3 2016, doi: 10.1097/MPG.0000000000001460 [Epub ahead of print].

Thyroid Disease in Celiac Patients

People with celiac disease have a higher risk for thyroid disease. A new study from China Medical University, Shenyang, strengthened the evidence using a meta-analysis of all relevant research conducted prior to May 2016.

The research team surveyed medical literature for studies that addressed both celiac and thyroid disease. They set standards to exclude data having weak statistical value. Thirteen studies were included, involving 15,629 people with celiac disease and 79,342 people without celiac disease for comparison.

Those with celiac disease were three times more likely to also have thyroid disease. The reason for this association is not yet clearly understood. Shared genetic traits might contribute to both conditions.

The article recommends that people with celiac disease should be screened for thyroid disease. However, the authors urge caution in interpreting their results, as all studies so far have been subject to statistical bias.

The scientific literature lacks robust data on how a gluten-free diet affects thyroid disease in people with celiac disease. However, this analysis suggested thyroid disease was equally common in untreated patients and those following a gluten-free diet.

Sun X, Lu L, Yang R, Li Y, Shan L and Wang Y, “Increased incidence of thyroid disease in patients with celiac disease: a systematic review and meta-analysis,” PLoS ONE, Dec 28 2016, 11(12):e0168708, doi:10.1371/journal.pone.0168708.


symptoms of thyroid problems

Although several thyroid symptoms could be misinterpreted for another condition or triggered solely by celiac disease, it’s best to know potential signs of trouble:

  • Weakness
  • Fatigue or difficulty sleeping
  • Weight gain
  • Weight loss
  • Sensitivity to cold and/or heat
  • Hair loss
  • Dry skin
  • Muscle cramps
  • Irritability
  • Depression
  • Constipation or diarrhea
  • Jaundice
  • Slowed speech
  • Abnormal menstrual cycle
  • Infertility
  • Increase in tongue size
  • Mental fog
  • Difficulty focusing
  • Bloating
  • High cholesterol
  • Racing heartbeat
  • High blood pressure
  • Bulging eyes

If you notice several of these symptoms, it’s worth visiting your physician for a blood test. If you are convinced that your symptoms are not being caused by celiac disease, you must be your own advocate when it comes to asking for blood tests and having your thyroid tested. Some helpful blood tests include TSH, free T3, reverse T3, free T4, thyroid antibodies, vitamin levels, cortisol level and iron level.

—Heather Burdo

Gluten Found in Gluten-Removed Beer

So-called gluten-removed beer may not be safe for people with
celiac disease. The Gluten Intolerance Group raised this concern after testing a new method for detecting gluten.

The Brewing Process

Brewing breaks barley gluten into smaller pieces. To make gluten-removed beers, brewers add additional enzymes to break down the fragments even further. Beer companies argue the resulting protein fragments are too small to be recognized as gluten by the immune systems of people with celiac disease.

These claims are difficult to prove. Standard food safety tests measure whole gluten proteins. Once these have been broken down, no one knows absolutely what fragments remain or how toxic they may be for people with celiac disease. Although some tests can detect certain fragments, experts have not agreed on a test sensitive enough to catch all of them. For this reason, U.S. guidelines prohibit gluten-free labels on any beer made from wheat, barley
or rye.

A New Way to Detect Gluten

The Gluten Intolerance Group tried a new approach: testing reactivity of beer with antibodies from human blood. The study took blood samples from 31 people with untreated celiac disease and 29 without celiac for comparison. These were used to test samples of barley, regular commercial beer, gluten-removed beer and gluten-free beer. Gluten-free beers include those made from grains other than wheat, barley and rye.

Antibodies from 11 of 31 celiac patients reacted significantly to barley. Four of the 11 also reacted to conventional beer while three reacted to gluten-removed beer. A variable response was expected, as people with celiac disease are known to react differently to different strains of wheat and barley. Meanwhile, one of the 29 control samples reacted with barley but not with any of the beers. The results show both conventional beer and gluten-removed beer can contain protein residue potentially harmful to people with celiac disease.

None of the celiac disease patients reacted to gluten-free beer.

No Longer A European Condition: Celiac Disease Crosses Ethnic Boundaries

Once thought to afflict mostly Caucasians, celiac disease is becoming cosmopolitan. It appears with higher-than-expected frequency in parts of North Africa, the Middle East and Asia. In India, it poses a growing public health concern. Meanwhile, in North America, evidence suggests patients and doctors need to stop assuming it affects primarily white people from Western Europe.

A new study of celiac disease and ethnicity in the United States emphasizes its diversity. Researchers found that people from the Punjab region of northern India were more likely than other Americans to have celiac disease, while the prevalence is also high among people of Jewish and Middle Eastern background.

One thing is clear: Celiac disease is becoming more common almost everywhere. A 2015 review of research by German and Israeli scientists found that the worldwide incidence has increased by 9.8 percent per year over the past 60 years. Many factors may have contributed, such as increased wheat consumption, changes in microbiology of the human gut, increasing awareness by doctors and patients, and improved means of diagnosis. However, environment seems to play a bigger role than genetics in the rising problem of celiac disease, because people from diverse genetic backgrounds are getting sick.

Study sessionsCeliac disease is present in nearly 1 percent of the U.S. population,” says Benjamin Lebwohl, M.D., gastroenterologist and researcher at the Celiac Disease Center at Columbia University, New York. “Though the ‘nearly 1 percent’ figure has been cited for more than a decade in the U.S., we live in a multi-ethnic society, and to date there has been very little known about how rates of celiac disease vary between ethnic groups.”

The study, published in Clinical Gastroenterology and Hepatology, looked at 454,885 people who had biopsies of the small intestine submitted to a national laboratory between 2008 and 2015. A biopsy detects characteristic damage to the gut lining and is considered the gold standard method for diagnosing celiac disease. Researchers compared the prevalence of such damage among patients from various ethnic groups.

Lebwohl, one of the study’s authors, explains, “we used a previously developed method that categorized patients’ ethnicities based on first and last names.”

Self-identified individuals within each ethnic group checked the name classifications. Then the lists were checked with physicians in sample practices containing members of ethnic groups. “The method was found to classify ethnicity with a high degree of accuracy, well over 90 percent,” says Lebwohl.

Among all U.S. patients who had biopsies submitted, the study found a celiac disease prevalence of 1.74 percent. Celiac disease was more common in patients originating in Punjab (3.08 percent) while other North Indian (1.51 percent), Jewish (1.80 percent) and Middle Eastern (1.52 percent) ethnicities had a prevalence similar to that of other Americans. Celiac disease was rarer among Americans of South Indian (0 percent), East Asian (0.15 percent) and Hispanic (1.06 percent) origin.

“I was struck by the results regarding patients from India,” says Lebwohl. “The rate of celiac disease varies tremendously depending on the region of that country that we’re considering.”

He adds, “As we were doing this analysis, and came upon this result, we discovered that a screening study conducted in India had just come to a similar conclusion: wide variability in the rate of celiac disease depending on the region, with a northern dominance.”

The Indian study, published this year in the American Journal of Gastroenterology, screened 23,331 people across India using blood tests. Researchers found a prevalence of celiac disease antibodies of 1.23 percent in northern regions, 0.87 percent in the northeast, and 0.10 percent in the south.

Alessio Fasano, M.D., director of the Center for Celiac Research and Treatment at Massachusetts General Hospital in Boston, says the variation among ethnic groups in the United States comes as no surprise.

“I would say that this study confirms what was known already,” says Fasano. “If you have a genetic predisposition and you are exposed to gluten in the environment to trigger it—and the United States is definitely a perfect terrain in terms of exposure to gluten—the recipe [to develop celiac disease] is there.” Cultural habits also have an effect, he adds.

Different regions, different diet

Disparities of prevalence have been recognized for decades in India, where genetic variability is much more limited than the range of cultural practices. Diets are particularly variable. Southern India relies much more heavily on rice, which is gluten free, whereas wheat is more popular in the north, particularly Punjab.

Celiac disease was first described in Punjab as summer diarrhea, says Fasano. The same patients experienced this condition every year. With no apparent intestinal parasite to blame, the patients’ diet was determined to be the culprit—specifically chapatis, flatbreads eaten as a staple food.

“The bread they ate during the summer is made with wheat and during the winter it is made with maize, which is gluten-free,” says Fasano. This observation led to screening, which indicated a high prevalence of celiac disease in Punjab.

The problem followed ethnic Punjabis wherever they went. A 1993 study in Leicestershire, England, found that residents with a Punjabi background were three times more likely than Europeans and eight times more likely than East Indians to have celiac disease.

Highlighting the point that celiac disease arises from cultural practices, it has recently been documented in China. It had never been described there before, but as the Western diet becomes more popular, it opens the borders to celiac disease.

The genetics of celiac disease

In North America, few studies concerning ethnicity have been undertaken. Most concentrated on the difference between non-Hispanic whites and Hispanic people or non-Hispanic blacks. Both these minority groups appear to be less susceptible to celiac disease. However, some experts argue that celiac disease may be underdiagnosed in their communities.

A 2015 study by the Mayo Clinic in Rochester, Minnesota, drew conclusions based on the annual National Health and Nutrition Examination Survey (NHANES), which included blood tests for antibodies associated with celiac disease from 2009 to 2012. Of 14,701 participants who underwent tests, 39 percent were non-Hispanic white, 22 percent were non-Hispanic black, 28 percent were Hispanic and 11 percent belonged to other races. The study found celiac disease affecting 1 percent of non-Hispanic whites, 0.2 percent of non-Hispanic blacks and 0.3 percent of Hispanics. Only three cases of celiac disease were found among people of other races. However, the results were not confirmed by biopsy of the small intestine.

The rarity of celiac disease among the Hispanic and African-American populations presents a puzzle. The highest incidence of celiac disease ever found occurred in northwest Africa among Saharawi refugees in Algeria: 5 to 6 percent. According to several studies, Caucasian Americans and African Americans have similar genetic predisposition to the disease. Authors of the Mayo Clinic study argue that an as-yet-unidentified gene might protect non-Hispanic blacks against celiac disease.

Other contributing factors

In some parts of the world, poor economic conditions seem to protect people against celiac disease. A 2008 study focused on people from the same genetic and cultural backgrounds in Finland and Russian Karelia. Celiac disease was less common on the poverty-ridden Russian side of the border. However, other studies have refuted the theory that communities with lower socioeconomic status are less vulnerable.

Some experts suspect celiac disease may be hidden among African Americans because they are less likely to get diagnosed. Lebwohl worked on a 2012 study that found disparities in the way endoscopies are conducted. Gastroenterologists use endoscopy to look inside the small intestine. Based on what he or she observes, the specialist may decide to take tissue samples for a biopsy, which is essential for diagnosis.

“African Americans and Hispanics were less likely to have a biopsy of the small intestine during the procedure, even if it was done to investigate signs of celiac disease such as iron-deficiency anemia or diarrhea,” Lebwohl reports. “In other words, celiac disease might have been missed.”

Fasano agrees that more research needs to look at the prevalence of celiac disease in certain cultural groups: “What is totally missed in my humble opinion is a systemic survey in African Americans and Native Americans.”

“Even though our latest study found a lower rate of celiac disease in Hispanics, we should not assume that celiac disease is out of the question based on a patient’s ethnic or racial background alone,” says Lebwohl. “Symptoms that are suggestive of celiac disease should be fully evaluated.”

Results of the latest study, he adds, “underscore the notion that celiac disease is not a condition that only or predominantly affects those of European ancestry.” GF

Van Waffle is research editor for Gluten-Free Living. He blogs about nature, gardening and local food at vanwaffle.com.

Celiac disease and mental health burden

People with celiac disease are more likely to suffer from mental health problems. A study at University Hospital of Cagliari, Italy, found 30% of celiac disease patients had experienced major depression during their lives, 18% had panic disorder and 4% had bipolar disorder. In contrast, a control group showed a prevalence of 8%, 5% and 0.4%, respectively.

The study included 60 celiac disease patients and 240 randomly selected controls. The volunteers took computerized interviews and questionnaires to assess psychiatric disorders and quality of life.

Patients with celiac disease scored lower than normal on quality of life. This finding agreed with other research showing patients report impaired quality of life similar to that for serious chronic diseases such as end-stage liver disease. However, in this study celiac disease patients without psychiatric disorders did not score low on quality of life.

This indicates a key to the burden of treatment for people with celiac disease. The authors recommend screening celiac disease patients for mood and anxiety disorders, particularly if they show symptoms or have a family history. Appropriate treatment could reduce the burden of living with celiac disease.

Carta MG, Conti A, Lecca F, Sancassiani F, Cossu G, Carruxi R, Boccone A, Cadoni M, Pisanu A, Moro MF and Demelia L, “The burden of depressive and bipolar disorders in celiac disease,” Clinical Practice & Epidemiology in Mental Health, 2015, 11:180-185.

Can the Gluten-Free Diet Treat More Than Celiac Disease?

Health-care workers are prescribing the gluten-free diet for a wide range of conditions other than celiac disease. Some people claim it’s beneficial in treating other autoimmune disorders such as rheumatoid arthritis. However, not all experts agree it should be seen as a panacea. Some experts in particular point to the importance of getting tested for celiac disease before trying the diet.

Aimee Espinoza, 29, was diagnosed three years ago with rheumatoid arthritis. Like celiac disease, it’s an autoimmune disorder, but in this case the body’s immune system attacks its own joints, causing pain and swelling. There’s no cure, but Espinoza believes the gluten-free diet has helped considerably.


Painful transformation

Rheumatoid arthritis is “a life-changing body transformation,” says Espinoza. “You’re consistently tired. Your joints are always hurting. But it’s a hurt that you’ve never felt before; a very tight burning sensation. It affects all of your immune system, so you feel the flare-ups everywhere. It’s very sporadic. You never can really pinpoint when you’re going to have a good day, when you’re going to have a bad day. It’s ever-changing.”

Espinoza, a marketing specialist living in Santa Fe Springs, California, had been an active athlete since high school. During her 20s, she ran marathons. She had experienced chronic pain since her teens. But the diagnosis initially forced her to take a step back from exercise.

“My doctor told me that running wouldn’t be good for my joints and would deteriorate my knees,” she says. “It discouraged me from doing a lot of things to be active. I saw not working out as the safest thing for my joints at the time. For a good month, I didn’t do anything.”

She began taking medication to ease symptoms and slow progression of the disease. These helped for a time, but soon the pain began to return.


Why the gluten-free diet?

Searching for a better solution, she started researching online how the immune system works.

“All the foods that go through your gut actually affect your immune system,” Espinoza says. “Some people are more sensitive to gluten-containing foods, and it causes them to have inflammation.”

After consulting with her rheumatologist, she weaned herself off medication and began following an anti-inflammatory, gluten-free diet. After three months on a strict gluten-free diet, she saw benefits. She continued to have her blood tested regularly for inflammation, which has decreased.


Managing without drugs

“I have a lot of energy,” says Espinoza. “I have less swollen joints, less flares, less tiredness. I am not dependent on medication now.”

She also has resumed working out.

“I realized my body craved movement, so I started out small with a few jogs,” she says. “I started with low-impact yoga. I started running in the pool to build muscles around my joints.”

She also began doing CrossFit, an exercise program in which a different workout each day uses weights and body movement to build strength.

Espinoza has been medication-free for about three years, relying on diet and exercise. She encourages other young people with rheumatoid arthritis to “live like they’re healthy.” She recommends finding support from other people with rheumatoid arthritis through resources such as the online community Creaky Joints.

“You’re eating the best foods to make your body energetic,” she says. “You’re working out to feel good about yourself and feel good about your body. Living life healthfully and fully improves the quality of your life.”


Confusing symptoms

But some experts remain skeptical about the benefit of a gluten-free diet in the absence of celiac disease. Confusion can arise due to various factors, including the frequently hidden nature of celiac disease, the placebo effect or a general improvement in eating habits on a gluten-free diet.

“It’s common to see people with celiac disease with headaches, fatigue, joint pain, muscle problems and muscle spasms,” says Joseph Murray, M.D., a gastroenterologist at Mayo Clinic in Rochester, Minnesota. “Those are common symptoms of celiac disease and, when you treat them on a gluten-free diet, they get better.”

Then there are rare conditions such as lung problems and skin itches due to dermatitis herpetiformis, another manifestation of celiac disease.

“Because celiac disease often is covert or hidden, it may not be readily diagnosed,” he says, “but there’s a perception that if the gluten-free diet made this, that and the other symptom better, maybe it’s worth trying in people who don’t have celiac disease.”

He argues that the underlying celiac disease can be missed in these cases.

He also does not endorse the idea of prescribing a gluten-free diet casually as a “throw-away recommendation.”

The gluten-free diet “is a big deal,” Murray says. “If you’re going to do it, you have to do it right. It has major impact in terms of restriction and burden on individuals or families. As a doctor, I don’t tell a patient to go on a gluten-free diet unless I have a good rationale. You should have clear goals in mind for what it does.”

If doctors such as rheumatologists see dramatic benefits anecdotally among their patients from a gluten-free diet, he adds, they have a duty to conduct a blind study to eliminate bias, in which participants do not know what kind of treatment they’re undertaking.

Such research is scarce or non-existent. Several studies have investigated and found some benefit of a gluten-free diet for people with fibromyalgia. However, none were designed to rule out the placebo effect.

Murray says there is a significant placebo effect from a gluten-free diet, meaning people can experience a real or imagined effect even though the diet doesn’t effectively treat their condition.

For example, a 2013 Australian study treated 37 patients with self-reported non-celiac gluten sensitivity. All had been following a wash-out gluten-free diet prior to the test. When they were fed high-gluten, low-gluten or gluten-free diets, not knowing which they had been given, all reported an increase in pain and bloating.

Patients also may experience benefits if they embrace the gluten-free diet as an “entire lifestyle change,” Murray says. If they lose weight, eat less junk food, eat smaller meals and consume less fat, they will see improvements in health not specific to eliminating gluten.

“We know a 10-pound weight loss dramatically improves knee pain,” Murray adds.


Food against inflammation

Cristina Montoya, R.D., 34, who works at Northumberland Hills Hospital in Cobourg, Ontario, Canada, was diagnosed 12 years ago with rheumatoid arthritis and Sjögren’s syndrome, in which the immune system attacks the body’s moisture-producing glands, such as salivary glands, causing dry mouth and eyes.

“I used to believe that only medications and advanced biologic therapies were sufficient to treat my rheumatoid arthritis,” says Montoya. “They have been great in delaying joint damage and minimizing disease activity but have poor impact in managing digestive issues and fatigue.”

About two years ago when she experienced frequent chronic pain, she became more aware of her dietary habits and slowly began to change them. Returning to her roots of her native Colombia, she began to move away from a Western diet and eat whole foods prepared at home. She has eliminated red meat and milk, and consumes poultry only once or twice a week. She gets most of her protein from fish, eggs and legumes.

Montoya follows a gluten-free diet. She was diagnosed with non-celiac gluten sensitivity after ruling out celiac disease through small-bowel biopsies.

“I purchase local food as much as possible, as well as fruits and vegetables in season,” she adds.

Montoya says a gluten-free diet can benefit patients with a variety of autoimmune disorders if gluten sensitivity is indicated. She includes:

  • Ankylosing spondylitis
  • Crohn’s disease
  • Rheumatoid arthritis
  • Sjögren’s syndrome
  • Systemic lupus erythematosus
  • Psoriasis
  • Type 1 diabetes
  • Fibromyalgia

“I support celiac disease specialists and strongly recommend my patients get tested for celiac disease before initiating a gluten-free diet,” says Montoya.

Anyone with undiagnosed celiac disease who doesn’t eliminate gluten completely from his or her diet risks intestinal damage leading to malabsorption of essential nutrients, fatigue, malnutrition and muscle-skeletal problems, she warns.

Recent research indicates patients with untreated celiac disease or non-celiac gluten sensitivity have higher-than-normal levels of zonulin in their intestines. This protein controls the permeability of the gut lining for large molecules such as gliadin, a component of wheat gluten. Montoya holds out hope that an indicator such as zonulin may soon help identify patients with autoimmune diseases who are also gluten sensitive. However, more research is required, she says.

Murray maintains there is no data to support the argument that everyone with an autoimmune disease should avoid eating gluten.

“Thyroid disease is one of the most common autoimmune diseases,” Murray says. “It’s also the most common autoimmune disease seen in patients who also have celiac disease. They commonly overlap, probably because of some genetic predisposition. But that doesn’t mean celiac disease causes the thyroid disease.”

“I’ve seen people with celiac disease who go on to develop autoimmune thyroid disease although they’re on a gluten-free diet already. I’ve seen patients who have thyroid disease diagnosed with celiac disease and [the gluten-free diet] doesn’t change their thyroid disease.”


Listen to your body

Espinoza says she was tested for celiac disease along with rheumatoid arthritis. To her surprise, the blood tests were negative. A genetic test ruled out any possibility of celiac disease.

But on occasion, when she has cheated or accidentally eaten something with gluten, she says she immediately has felt inflammation in her body. The gluten-free diet has helped her manage rheumatoid arthritis without medication.

To people struggling with a new diagnosis, Espinoza has this advice: “Listen to your body. Each person diagnosed with a disease reacts differently to certain things. Unfortunately for me, medication didn’t work, but luckily diet has.”

Most importantly, she says, pay attention to your diet. She recommends keeping a food log to track what foods help or hurt you.

“Do whatever works for your body, whatever makes you pain free,” Espinoza advises.

But Murray argues, “We want to blame something we’re eating, because it’s something we have control over. I think it’s human nature.”

Van Waffle is a freelance journalist based in Waterloo, Ontario, Canada. He is a regular contributor to Gluten-Free Living and Edible Toronto. He blogs about local food, nature and gardening at vanwaffle.com.


Anti-inflammatory diet

Cristina Montoya, R.D., recommends the Mediterranean diet as a “useful adjunct therapy” for inflammatory conditions such as rheumatoid arthritis. It also supports cardiovascular health. A 2007 study found it decreased pain and morning stiffness in rheumatoid arthritis patients. The diet emphasizes use of:

  • Extra-virgin olive oil
  • Nuts and seeds, particularly those rich in omega-3 fatty acids, such as walnuts, hemp, flax and chia
  • Legumes: soybeans, lentils, beans and chickpeas
  • Small amounts of fermented dairy, such as yogurt, kefir and aged cheeses
  • Colorful, in-season fruits and vegetables
  • Herbs and spices: Ceylon cinnamon, garlic, turmeric and ginger
  • A variety of whole grains
  • No refined sugars, processed grains, processed meats, high trans fats or saturated fats
  • Limited red meats, fluid milk and fruit juices

Celiac Disease and Cancer: What’s the Real Risk?

It sounds like two scenes from the same science fiction thriller. With celiac disease, the body’s immune system attacks its own gut lining. With cancer, cells grow abnormally and invade other parts of the body.

But real science indicates people with celiac disease face increased risk for certain types of cancer. Fortunately they’re rare forms, and the risk declines when the gut lining heals.

“One [cancer] is called enteropathy-associated T-cell lymphoma. It’s a kind of lymphoma of the small intestine,” says Benjamin Lebwohl, M.D., assistant professor of medicine in epidemiology at the Celiac Disease Center at Columbia University in New York City. Another is small intestinal cancer, or small intestinal adenocarcinoma. These cancers are not seen very often in the general population but occur at an increased rate in people with celiac disease.

“These findings underscore the fact that celiac disease and the intestinal inflammation that is involved in this condition are a health hazard,” Lebwohl says. “The evidence is very good that healing in the intestines reduces the excess risk [for cancer], and there’s also evidence that following a gluten free-diet leads to healing of the intestines.”

It’s one more argument for why people with symptoms or risk factors should be tested for celiac disease and, if diagnosed, stick to a strict gluten-free diet.

Haunted by memory

Ken Kilgore, Ph.D., director of partnered pharmacology at Janssen Pharmaceutical Companies of Johnson & Johnson in Pennsylvania, has an especially good reason not to cheat.

“It doesn’t honor my dad,” Kilgore explains. “He was my greatest friend in the world, and that just taints the sacrifice he made if I go and cheat.”

In 2002 Kilgore’s father, Donald, had been suffering from severe weight loss when in September he was diagnosed with B-cell lymphoma. Despite chemotherapy his condition continued to decline. He could no longer pursue his passions for golfing or watching University of Michigan football with his son.

“We had season tickets for decades, and football Saturdays were a much-loved fixture of our family,” Ken Kilgore recalls. “However it became clear mid-way through the 2002 season that he was not strong enough to continue going to games. He and I had watched Michigan football together for 35 years and rarely missed a game until then.”

At the time, Ken Kilgore was an adjunct professor at University of Michigan Medical School, Ann Arbor. A gastroenterologist friend there suggested his father should get tested for celiac disease. The results came back positive.

In hindsight, Ken Kilgore believes his father’s celiac disease had been active for at least 10 years before the cancer diagnosis. Donald Kilgore had some nutritional problems, particularly low levels of vitamin B12.

Recent research shows increased cancer risk declines when celiac disease is diagnosed and treated effectively, a fact that still haunts Ken Kilgore. “We were definitely in the Dark Ages of celiac awareness,” he says.

Ken Kilgore had his father switch care to University of Michigan Medical Center because he thought physicians there were among the few who were up-to-date on celiac disease. “Unfortunately it was too late by that point,” he laments.

While getting tested for celiac disease, Donald Kilgore underwent an upper digestive tract endoscopy that revealed the cancer was actually T-cell lymphoma. For half a year his treatment had targeted the wrong form of cancer. It was too late to start over. Donald Kilgore died in September 2003, at the age of 67.

After Donald Kilgore was diagnosed, the whole family got tested for celiac disease. Ken Kilgore was the first to test positive in 2003, followed by his daughter, who also has Down syndrome, his nephew and, most surprisingly, his mother.

“We look for hidden blessings in this whole adventure,” says Ken Kilgore, now 50. “We feel in the long run that my dad did something great for all of us.”

Understanding the risk

Alice Bast, president and CEO of Beyond Celiac, a patient advocacy organization based in Pennsylvania, says people diagnosed with celiac disease are concerned about associated health problems, including cancer.

“In fact, in a recent survey that we will be submitting for publication later this year, more than 80 percent of adults in our community are specifically worried about their increased cancer risk,” she adds.

The risk came to light only recently. One of the first studies to suggest a link appeared in American Journal of Medicine (2003); it reviewed statistics from 381 celiac disease patients seen between 1981 and 2000 at New York-Presbyterian Hospital.

Researchers found a higher-than-expected incidence of non-Hodgkin lymphoma, cancer of the small bowel, esophageal cancer and melanoma in this group. B-cell lymphoma and enteropathy-associated T-cell lymphoma are two types of non-Hodgkin lymphoma. No elevated risk was found for colon, lung or breast cancer.

However, before raising alarm, Lebwohl points to weaknesses in this data.

The study was performed at a major referral center for celiac disease, he notes. There’s always concern that studies coming out of such settings don’t apply to celiac disease patients in general.

“Patients who come to our center might be different in important ways. They might be referred to our center because of particularly complex problems or difficult-to-manage disease. Their risk might be different from the typical celiac disease patient,” Lebwohl explains.

“Some of the confusion derives from the fact that cancer is often lumped into one outcome when cancer represents many different kinds of disease,” he continues. “In fact celiac disease might increase the risk of one cancer and decrease the risk of another. Studying them on the aggregate often leads to confusion. It’s important to evaluate each cancer with regard to its relationship with celiac disease.”

Early findings provoked a variety of further research. Several studies from Scandinavia have provided clarity. They’re important, Lebwohl says, because they’re population-based.

In other words they include essentially all celiac disease patients from a large population, rather than a few under special circumstances.

“In general studies coming out of population-based settings show lower risks and diminished increases of risk,” Lebwohl observes.

For example a 2014 study from University of Tampere, Finland, analyzed data on 32,439 celiac disease patients between 2002 and 2011. It is the largest study of its kind completed to date. It confirmed an increased risk for non-Hodgkin lymphoma and small intestinal cancer, though the rates were lower than in other studies.

“Patients should be aware that while the risk of these cancers is increased compared to the general population, the absolute risk is modest in size,” Lebwohl points out. For example one study found that over the course of 10 years, less than 1 percent of patients with celiac disease developed lymphoma.

That means it’s rare even for people with celiac disease.

Not all cancers ARE the same

The Finnish study didn’t support evidence for a link between other cancers and celiac disease. Overall scientific findings have been ambiguous on esophageal cancer, melanoma and colon cancer.

However the Finnish study also provided some good news. The overall risk of cancer for newly diagnosed celiac disease patients was no higher than for the general population.

“There are a couple of cancers that appear to be less common in patients with celiac disease,” explains Lebwohl. “Lung cancer and breast cancer are the two that have been studied most. For some reason celiac disease appears to be protective against these cancers.”

One possible reason is that research has shown celiac disease patients are less likely to be smokers. But even with smoking habits removed from the equation, celiac disease appears to protect against lung cancer, Lebwohl says.

Similarly celiac disease patients may have less body fat, which could reduce the risk for breast cancer. Also some studies have shown that women with celiac disease “have later onset of menstruation and earlier onset of menopause compared to the general population,” Lebwohl explains. “It could be that these hormonal factors are influencing breast cancer risk.”

While these protections remain a puzzle, Lebwohl says he is most interested in research “honing in on lymphomas,” because these cancers seem to be the ones celiac disease tracks with most closely.

“It makes a sort of logical sense that patients with celiac disease who have inflammation in their small intestine would have cancers in their small intestine,” he points out, but research has not yet proven a cause-and-effect relationship.

The link with cancer helped scientists realize celiac disease is not only an intestinal condition but rather an autoimmune disorder, he adds.

Call for prevention

Because non-Hodgkin lymphoma and cancer of the small intestine are rare even in celiac disease patients, the risk calls for vigilance more than alarm.

“With cancer, early diagnosis is key,” Bast says. “Those diagnosed with celiac disease should also be monitored annually by their physician.” The Beyond Celiac website identifies the tests patients should receive yearly.

Lebwohl says screening for preventable cancers should be the same for those with celiac disease as for the general public, including colonoscopy and mammography at the appropriate ages.

Ken Kilgore (top left) and his father Donald (top middle) with their family

“As for additional screening measures, none are routinely advised,” he says. “But patients with celiac disease should have regular medical follow ups because of the association with these cancers, including lymphoma.” This will help with early detection of any complications requiring investigation for cancer.

Given the evidence that treating celiac disease can reduce the risk of lymphoma, a follow-up biopsy might provide “important prognostic information,” he adds. A study of Swedish patients who underwent a second biopsy at an interval after starting the gluten-free diet showed the relationship between intestinal healing and risk of lymphoma.

“We compared those whose intestines had healed to those whose intestines failed to heal. Those who had healed no longer had an increased risk of lymphoma” Lebwohl says. This raises concern for celiac disease patients who do not heal despite following a strict gluten-free diet.

“These are the patients who we like to follow the closest,” Lebwohl says. “This is a substantial proportion of patients, some of whom have persistent symptoms but others [who] actually feel quite well,” despite poor healing.

Patients who have persistent intestinal damage meet with the celiac center’s dietitian more frequently than those who heal. “We try to drill down ways in which they might be exposed to gluten unintentionally,” Lebwohl explains. “This is a population that might benefit from [drug] therapy, if such therapy were to be developed in the future.”

But the absolute risk even for these patients is low.

“Those with persistent abnormalities on their intestinal biopsy have an increased risk compared to those who heal, but it’s still only about 1 percent risk of lymphoma over the course of 10 years,” Lebwohl says. “The risk should be treated the way other risk factors are generally treated, for an example having high cholesterol.”

Lurking feeling

Still Bast says cancer is a common concern for people with celiac disease, particularly those with family members who have been diagnosed with lymphoma or cancers of the gastrointestinal tract, blood, thyroid or pancreas.

“For many of us there’s always that lurking feeling that these instances may be connected to celiac disease,” she says. “My own mom died from pancreatic cancer at the age of 52. There’s no way to know for sure, but looking back, I think she had undiagnosed celiac disease. Many of us have stories like this.”

Patients with a family history of cancer are often concerned that it will increase their personal risk, Lebwohl says. In some cancers this is true; for example colon cancer. However family history doesn’t appear to increase the risk for lymphoma in celiac disease.

The lack of a genetic link only emphasizes the importance of effective, timely treatment for people with celiac disease.

“Celiac disease disrupts and devastates lives,” Bast says, but the recognition of increased cancer risk makes it “undeniable that celiac disease is serious and needs research for a cure.” She also points out an estimated 83 percent of people with celiac disease remain undiagnosed. “Their increased health risks are unrecognized and unmonitored by their healthcare professionals. It doesn’t get more serious than an increased cancer risk,” Bast says.

She encourages anyone diagnosed with celiac disease to talk to their relatives and encourage them to get tested. “We’ve found that once educated on the long-term health risks of undiagnosed and untreated celiac disease, people are more likely to get tested,” she notes.

Ken Kilgore looks back at the impact undiagnosed celiac disease had on his family.

“Celiac-associated cancer takes things, even beloved things, away long before one actually passes away. Within a few months of his diagnosis, my dad was unable to do the things he loved. [T-cell lymphoma] is a totally unforgiving and merciless disease,” he says. “It is also preventable.

“This last point is what haunts me the most. All the signs of celiac disease were there long before he got cancer, and we missed it. It is the survivors like me who have to carry that burden for the rest of our lives.”

He says he hasn’t watched a University of Michigan game since his father died. GF

Van Waffle is research editor for Gluten-Free Living. He blogs about nature, gardening and local food at vanwaffle.com.

Is the Biopsy Still the Gold Standard for Diagnosing Celiac Disease?

Maggie McCombs had been gluten free for about five years without a celiac disease diagnosis, when at age 23, with the rest of her life and big changes ahead, she needed answers.

“I realized how much work I was already putting into the diet, but I needed to know if it was for a good reason,” she says.

Traditionally, a biopsy would be key to getting an answer. For decades specialists have considered a biopsy the gold standard for diagnosing celiac disease. But debate about the absolute need for a biopsy is emerging among experts, with some saying there are times when the invasive test is not needed.

Blood tests have become more accurate in identifying antibodies associated with the autoimmune reaction. Until recently tests could only provide preliminary evidence, needing confirmation of celiac disease from a biopsy. But some celiac disease researchers say there are cases when blood tests provide enough proof.


No biopsy

McCombs had adopted the diet at 17 when her brother was diagnosed with Type 1 diabetes and celiac disease, the autoimmune disorder triggered by gluten protein in wheat, barley and rye. McCombs’ brother had undergone a biopsy to look for characteristic tissue damage in his small intestine prior to getting a final celiac disease diagnosis.

“I feel as though my brother was a guinea pig in many ways,” says McCombs, now 25 and a content marketer in Lexington, Kentucky. “He had the multiple blood tests, the follow-up visits, the endoscopy.

“After his diagnosis, my mother immediately suspected that I also had the disease due to my stomach pain complaints and itchy rashes spreading across my hands and face,” McCombs says. She started to research celiac disease and felt all her symptoms suddenly made sense.

“I’d experienced severe depression, anxiety, confusion: all hidden neurological symptoms of celiac disease. Admittedly I was both in denial of the possibility and deathly afraid of needles. So I evaded the blood tests and started adapting to the diet,” she says.

Though her health improved, she had trouble maintaining the gluten-free diet at college.

“Initially part of my problem was not knowing for sure that I had celiac disease, so I’d talk myself into sneaking some gluten-filled meals and snacks,” she admits. “Naysayers insisted that the disease was all in my head.”

After graduation she wanted to know for sure and decided to take the blood test recommended years earlier by her brother’s doctor. Celiac disease cannot be diagnosed in someone when they’re on a gluten-free diet, so McCombs had to start eating gluten again—called a gluten challenge.

“Instead of looking forward to eating anything I wanted, I actually dreaded cramming my body with my favorite foods,” she recalls. “My stomach ached. I had itchy red rashes spreading all over my hands and face. Although the doctor asked for a full month of eating as much gluten as I could tolerate, I was so sick that I had to get the test a week early.”

When McCombs’ tests came back, her doctor told her the antibody levels were the highest he had seen since her brother’s. “Any other tests would be superfluous. I had celiac disease,” she says.

Unlike her brother, McCombs received a diagnosis without undergoing an endoscopy and biopsy, a procedure in which a gastroenterologist inserts a narrow tube down the throat, through the stomach and into the small intestine, allowing a visual inspection. But more importantly, small samples taken from the lining are examined to determine if there is damage from celiac disease.

RoByn Thompson, 51, of Paterson, New Jersey, was also recently diagnosed with celiac disease after a blood test. Her doctor didn’t suggest a biopsy, but Thompson says she probably would have decided against it.

“I’m a cancer survivor and have had too much surgery already,” she explains, adding she’s confident in the diagnosis. “I’m symptom free when I avoid gluten.”


Gold standard?

A few specialists believe it’s time to move beyond the biopsy as the gold standard. Geoffrey Holmes, M.D., emeritus consultant gastroenterologist at Royal Derby Hospital in Derby, U.K., is advancing the case for blood tests.

“Endoscopic biopsy is generally safe, but it is invasive and unpleasant and often requires sedation, so why do it if it is unnecessary?” he asks.

Holmes was seeing patients with high antibody levels and started to ask the question, “What could this be other than celiac disease and why do I need to perform a biopsy which is certain to confirm it?”

Though many doctors were already making diagnoses without biopsy and putting patients on gluten-free diets, Holmes says he wanted to address the question from a scientific basis.

The most valuable blood test relies on tissue transglutaminase (TTG), an enzyme that occurs in the gut and interacts normally with gluten protein. Meanwhile the immune system produces a class of antibodies called immunoglobulin A (IgA) to fight infection. But people with celiac disease produce particular IgA antibodies that bind with their own TTG.

Holmes thought there must be a high level of IgA anti-TTG that could predict celiac disease 100 percent of the time. His research found that antibody levels at least 10 times the upper limit of normal were sufficient, so a biopsy was unnecessary to confirm diagnosis. He and his colleague published these findings in 2008.

Previous research has suggested that 20 to 30 percent of patients with celiac disease can safely be diagnosed without biopsy. However recent work by Holmes and colleagues pushes the number much higher, to 78 percent. In practice, he claims about half of celiac disease patients in Derby are diagnosed without biopsy.

In 2012 the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) published new guidelines for diagnosis, based partly on Holmes’ work. The society affirmed that in a child showing 10 times the normal anti-TTG, an additional test for IgA endomysial antibodies (EMA) could be used in follow-up. If this second test was positive, the child could be placed on a gluten-free diet. If this produced beneficial results and the child’s antibodies returned to normal, celiac disease could be considered proven.

The EMA test was discovered when researchers were studying a painful skin form of celiac disease, dermatitis herpetiformis. Certain IgA antibodies appeared in connective tissue under the skin. This led to the revelation that EMAs also occur in celiac disease without the skin manifestation. In fact almost 100 percent of people who test positive for EMA have celiac disease.

But the EMA test gives a few false negatives, not showing up in 5 to 10 percent of patients. TTG doesn’t miss as many. EMA is also more difficult and expensive to perform, demands specialized training for the pathologist, and is not widely available in North America.


Critical component

Not everyone agreed with the ESPGHAN’s protocol and movement away from biopsy.

In 2013 the American College of Gastroenterology (ACG) weighed in, recommending that an endoscopy with biopsy is a “critical component” in evaluating patients and should be used to confirm the diagnosis. While affirming the value of blood tests, the group does not recommend use of EMA. British Society of Gastroenterology guidelines published in 2014 also insist that a biopsy is always necessary.

Joseph Murray, M.D., of the Mayo Clinic in Minnesota, is a strong proponent of biopsy. He acknowledges the ESPGHAN guidelines can lead to an accurate diagnosis, but only if followed correctly.

“Unfortunately what we’re seeing is people not following the guidelines,” says Murray.

Clinical antibody tests are recommended as a starting point by physicians, but some patients don’t take that step before starting a gluten-free diet.

Jill Wirth’s daughter Kaiya is an example. At 2 years old, Kaiya was “almost at the failure-to-thrive weight,” says Wirth, 38, a technical sales professional in Cambridge, Ontario, Canada.

“As a baby she cried more often than what I would consider normal. She didn’t want to be held or fed. She had very little interest in food. She was not what I would call a happy baby by any means,” Wirth recalls. “Our general practitioner had suggested [putting] 35 percent cream in her bottle and to put sugar on her food to try to entice her to eat it.”

After dissatisfying results, Wirth took Kaiya to a holistic nutritionist who tested her for food sensitivities and celiac disease. Results from an over-the-counter test for celiac disease were positive so Wirth immediately put Kaiya on a gluten-free diet.

Murray says store-bought tests like the one used to diagnose Kaiya are available in Canada but have not been approved by the U.S. Food and Drug Administration. The tests can give accurate results, according to Murray, but that depends on the test and who does it. And patients are advised to seek further testing to confirm results before undertaking a gluten-free diet.

Kaiya’s doctor did order a blood test, which also came up slightly higher than normal. Finally Wirth asked for a referral to a gastroenterologist.

“We decided with the specialist that we would not put our daughter through having to be glutened for an extended period of time in order to go for a measurable biopsy,” she says. “Since we had seen such a positive change in weight, behavior and mental wellness, we would not put her back on a diet that included gluten.”

Kaiya, now 5, “responded incredibly,” Wirth says, “a complete transformation.” She adds that she and her husband are completely confident in the diagnosis.

“If there is any doubt about the celiac disease, there is certainly no doubt that this sweet young girl should not be consuming gluten. I guess the biopsy would only confirm the extent of the damage the gluten creates in Kaiya’s body, not whether or not she should consume gluten,” Wirth explains.

Blood tests

Blood tests for diagnosis include several alternatives suited for specific circumstances. IgA deficiency, a rare condition affecting a few people with celiac disease, causes undetectable IgA anti-TTG. This can call for an IgA deficiency test and alternate tests for celiac disease based on immunoglobulin G (IgG). However, their accuracy is less well known.

Genetic tests for celiac disease are now being commonly used. The human leukocyte antigen (HLA) gene codes for an agent in the immune system. Two forms, HLA-DQ2 and HLA-DQ8, occur in about 40 percent of the population. Only people who carry these genes can develop celiac disease: Still, the vast majority never will.

Some celiac disease experts have found the problem with HLA tests is that patients and many doctors interpret a positive result as strong evidence for a diagnosis, which it is not. It indicates only that the patient has a higher risk for celiac disease. The ESPGHAN guidelines recommend including it with other blood tests in reaching diagnosis, even though genetic testing is inconclusive and relatively expensive to perform.

A negative HLA result is helpful in ruling out celiac disease in the majority of cases. The ACG recommends this as a first step for patients who have already adopted a gluten-free diet without diagnosis. A negative result indicates the diet is unnecessary. However the genetics of celiac disease are not entirely understood, and about 1 percent of patients have none of the gene types so far identified. These rare individuals would get a negative HLA result.

The ACG strongly recommends that people with a positive HLA seek appropriate diagnosis beginning with a gluten challenge and appropriate antibody tests, instead of continuing a gluten-free diet.

Some doctors won’t understand these nuances, says Murray. He discourages the practice of sending patients for a panel of blood tests. “The problem when you combine tests is they reduce to the lowest common denominator of accuracy. I frequently have patients come to me who’ve had four tests, one out of the four was positive, and they were told they had celiac disease when it’s obvious they don’t.”

Murray says the first step after a positive anti-TTG test should always be referral to a gastroenterologist.

“One of the hardest things I do in my practice is, when someone comes to me who has been committed to being on a gluten-free diet for two or three years, I have to tell them, ‘You don’t have celiac disease.’ It is a life-long diagnosis with a life-long, life-altering treatment,” Murray says. “Many people choose to go gluten free, but that’s very different from the burden on a patient, who must go gluten free. It affects every time you eat, buy food, eat out or travel. That applies to children as well as adults, and with children it’s imposed on them, so I think there’s a higher bar for certainty.”

Ivor Hill, M.D., medical director of Nationwide Children’s Hospital Celiac Disease Center in Columbus, Ohio, says he has had cases where the symptoms were very typical, the TTG was very high, and the parents were reluctant to have their child undergo a biopsy.

“I’ve felt comfortable in those cases saying we’ll put them on the diet and monitor the response. They all had a good response and their [antibody] numbers came down, so in retrospect I’m pretty sure they have celiac disease,” Hill says. “Do we have the same level of confidence with a non-biopsy diagnosis? Hopefully we’ll get there someday but right at the moment, maybe not.”

He discusses the implications of making a positive diagnosis with the parents. “I want to be 100 percent sure that the child has celiac disease because if they’re going to go gluten free, it’s for life,” Hill explains.

Alessio Fasano, M.D., chief of the division of pediatric gastroenterology and nutrition at Massachusetts General Hospital for Children in Boston and director of the Center for Celiac Research and Treatment, says patients who have been diagnosed based on blood tests alone tend to comply poorly with the gluten-free diet over time, compared with people who have received a picture of their damaged intestine.

Previously a supporter of diagnosing without biopsy in some cases, Fasano says he now has reservations because endoscopy can reveal important information that would otherwise be missed. For example a patient may have other related conditions such as reflux.

“In a large number of people who go on the gluten-free diet, once their symptoms have gone and their antibodies go back to normal, after a year when we repeat the endoscopy, we see [a significant] number of these individuals that still have damage,” Fasano says. “So that’s another reason why we are skeptical at this point.”

Holmes argues that while biopsy remains useful, its status as the gold standard is becoming hard to defend. Celiac disease may be the correct diagnosis if the intestinal lining is typically flattened, but some cases are more uncertain.

Reading the biopsy

Biopsy has its limitations. Damage from celiac disease may be spotty, with some tissue still appearing healthy. Specialists recommend collecting at least five or six samples from different parts of the small intestine of each patient. Studies have shown gastroenterologists performing the procedure do not always take enough samples to detect celiac disease in every patient.

The tissue samples must then be correctly preserved and oriented so the damage is visible. They are sent to a lab where trained pathologists look for telltale damage. The earliest sign of damage is an increase in a certain kind of white blood cells in the tissues. However this can occur in other conditions, too.

Next comes an increase in the number of cells in depressions lining the intestine, a condition called crypt hyperplasia. This is thought to occur in response to tissue damage.

The third and most significant change is flattening of the villi, minute hair-like projections that normally line the gut, increasing its surface area. Celiac disease blunts them or flattens them completely, so the body has a hard time absorbing enough nutrients. This is the damage pathologists look for to confirm a diagnosis. It may occur in a few other conditions, but they’re very rare.

Inconsistencies in how tissue samples are collected and prepared raise concerns even among biopsy advocates. Holmes says typical flattening may provide a clear diagnosis, but with moderate damage the cause is uncertain.

“Often the villi are reported as slightly shortened or blunted. Is this celiac disease? It may or may not be, and here serology can come to the rescue,” he says.


The right diagnosis

Meanwhile, McCombs says she is confident in her celiac disease diagnosis.

“I was determined to get a definitive answer, so I definitely would have gotten a biopsy if needed,” she reflects. “Honestly I would have undergone almost any procedure to get diagnosed and end the misery of the gluten challenge.”

Two years later she is learning to cook at home, asking more questions in restaurants and looking for a follow-up with a new doctor in the area where she moved to start a career.

“I’m still so thankful to know what’s wrong with me. Most days I don’t even mind the gluten-free diet because I see it as a cure,” she says. “Changing my diet improved my health, but changing my attitude improved my entire way of life.”

Related articles

What is Celiac Disease?

Gluten-Free Recipes

Diagnosis Dilemma


Van Waffle, who has a bachelor’s degree of science in biology, is research editor for Gluten-Free Living. A resident of Ontario, Canada, he also contributes regularly to Edible Toronto and blogs about nature, gardening and local food at vanwaffle.com.



This article was originally published in our March/April 2015 issue. All information was correct at time of publication.

The New Word on Wheat Starch

A new and unlikely ingredient is making its way into a few gluten-free foods. Don’t be surprised to find wheat starch in some products in the United States.

New U.S. Food and Drug Administration (FDA) rules allow wheat starch in gluten-free foods if the wheat starch is specially processed to remove gluten. Some food companies say it can improve flavor and texture in certain products.

But gluten-free consumers who have long gone by the rule that any food that contains wheat, barley or rye in any form is forbidden may have some trouble adjusting to the idea that certain kinds of wheat starch are now allowed.

It has already appeared in a chocolate and tangerine treat in one of GoPicnic’s gluten-free packaged meals. And Dr. Schär, a European company that has made foods for special diets for 93 years, will introduce gluten-free plain and chocolate-filled croissants containing wheat starch in the United States early this year. Dr. Schär currently sells gluten-free croissants in Europe that list wheat starch as a main ingredient.

Wheat starch processed to remove gluten, called Codex wheat starch, has been allowed in gluten-free food in Europe for more than a decade based on studies that show it is not harmful to those who have celiac disease. But wheat starch was not allowed in the United States until the recent finalization of the FDA rules for gluten-free foods.

Although some food companies plan to begin using wheat starch, don’t expect many to follow quickly. Overall, use of wheat starch in gluten-free food appears to be a tough sell to both food makers and consumers.

Danger signal

For decades the word “wheat” has signaled danger to anyone on a gluten-free diet. It’s of particular concern to people with celiac disease because of the damage gluten-containing grains cause to the small intestine. There’s only one effective treatment: lifelong, complete avoidance of any food containing gluten.

Those who have gluten sensitivity do not experience intestinal damage, but they often suffer symptoms severe enough to prompt them to completely eliminate gluten-containing grains, as well.

Pam Cureton, R.D., a celiac disease specialist at the Center for Celiac Research and Treatment in Boston, teaches new patients to read ingredient labels and to avoid wheat, barley, rye, malt, brewer’s yeast and—unless the product is labeled gluten free—oats.

But she now has to make an exception for wheat starch and explain to her patients why it can be acceptable on the gluten-free diet. Whenever wheat starch is used in a food labeled “gluten free,” it must appear in the ingredients list. Wheat will also appear in the “Contains” statement if the product has one.

The label also has to say that the “wheat has been processed to allow this food to meet the Food and Drug Administration (FDA) requirements for gluten-free foods.” When an ingredient list says only “starch,” it means cornstarch, which is naturally gluten-free, Cureton notes.

“When [gluten-free consumers] see ‘Contains wheat,’ of course they’ll put [the product] back on the shelf,” Cureton observes. “They’re hesitant to purchase even a product that says it’s manufactured in a plant that contains wheat.

“Our consumers will avoid those types of products. So a lot of education is needed to explain to them that this wheat starch has been processed to remove the protein and it must meet the standards of the FDA to be less than 20 parts per million [ppm].”

The FDA in 2013 established safety standards for gluten-free foods. Products labeled gluten free have to contain less than 20 ppm of gluten and may not be made with gluten-containing grains such as wheat or any derived ingredients that have not been processed to remove gluten.

However, foods labeled gluten free may contain a derived ingredient if it has been processed to remove gluten as long as the final food product contains less than 20 ppm. Wheat starch is an example of this kind of ingredient, along with a few others, according to the FDA.

Products made with gluten-free wheat starch are absolutely safe, says Cureton, even for people with particularly high sensitivity to gluten. Wheat starch contains such a tiny amount of gluten that it doesn’t significantly add to the gluten level in the final product. But consumers have to continue to read labels, understand what they mean, and make sure anything containing wheat starch also identifies itself as gluten-free and says that the ingredient has been processed to remove gluten.

For example, the label on a chocolate snack packet in GoPicnic’s gluten-free bean dip and tortilla chip meal includes wheat starch. The snack consists of a tangerine center, a sugar shell and dark chocolate. The ingredient list identifies “starch (Codex-approved gluten-free wheat starch)” and has additional allergen information: “contains soy and wheat starch, certified gluten-free (under 10 ppm) by the Gluten-Free Certification Organization.”

This labeling might seem wordy, but Cureton says it complies with the FDA rule for gluten-free foods. The FDA does not require—but does allow—gluten-free certification by a third party, such as the Gluten-Free Certification Organization.

European record

Wheat starch in a gluten-free food may come as a surprise to U.S. consumers, but it has an established record in Europe where Dr. Schär has used it for at least 20 years, according to Anne Lee, R.D., director of nutritional services for the company’s U.S. operations in Lyndhurst, New Jersey.

Research has found no evidence that foods containing gluten-removed wheat starch harm people with celiac disease. A 2003 study at Tampere University Hospital in Finland tracked newly diagnosed patients after they adopted a gluten-free diet.

One group of 23 randomly assigned volunteers ate only naturally gluten-free foods, while 26 also ate gluten-free products that contained wheat starch. After one year both groups showed equally good recovery based on reported symptoms and quality of life, small intestine biopsies and blood tests.

In recommending wheat starch, the authors of this study argued that minute contamination of less than 20 ppm of gluten is virtually impossible to avoid in any diet. International standards have accepted this level because it’s considered safe for the vast majority of people with celiac disease.

But some experts express skepticism. “I would not expect to see gluten-free wheat starch approved in Canada in the near future, but if the experience is a positive one in the United States, there may be a review of the situation in the mid to long term,” says Sue Newell, operations manager for the Canadian Celiac Association.

While wheat glucose syrup, wheat-based caramel and wheat maltodextrin—gluten-free derivatives allowed by Canadian labeling law—occur in food only in small fractions, wheat starch could contribute a higher proportion to the final food product, Newell notes. And she worries about the cumulative effect from traces of gluten in wheat starch when added to unavoidable gluten from cross-contamination.

Tricia Thompson, R.D., founder of Gluten Free Watchdog, a food-testing company in Boston, shares Newell’s concern. If a manufacturer chooses to use wheat starch, it should thoroughly test its products with a laboratory that takes multiple samples from each lot of wheat starch and the final products, she says.

“At least some testing should be done at an independent third-party testing facility,” Thompson says. “Studies published by both the FDA and Gluten Free Watchdog found that a majority of labeled gluten-free foods are testing under 5 ppm of gluten. It will be interesting to see how wheat-starch-based products test.”

The Celiac Disease Foundation supports the legislation allowing wheat starch, however. “The FDA went through a vigorous consulting process with the national groups in celiac disease, both medical and scientific, and this was the consensus: that wheat starch that has been processed to remove gluten to the FDA standard is safe for the celiac disease population,” says Marilyn Geller, chief executive officer of the foundation.

Authors of the Tampere University Hospital study point out wheat starch’s benefits. Compliance with a gluten-free diet is more important to recovery than avoiding trace amounts of gluten, they say. Because wheat starch improves the flavor and texture of certain foods, it can mean the difference in some people’s ability to accept such a difficult diet.

Early adopters

But will gluten-free consumers buy it? Toro, a Norwegian food company, tried introducing baking mixes containing wheat starch to U.S. markets before the FDA regulations were approved. In the absence of labeling standards, the product packages went into detail to explain how wheat starch could be safe. These details only confused people, according to Cureton. They wouldn’t buy the products, and Toro’s U.S. experiment failed.

“I’ll be anxious to taste more of the products as they come out using wheat starch,” says Cureton. “I think the first outing of products is going to have a tough road. If people taste the products and they don’t get sick, I think manufacturers down the road will have an easier time. But the first few brave companies will probably have to answer a lot of questions.”

Dr. Schär will be in that group. Founded in 1922, the company introduced its first line of gluten-free products in Europe in 1981 and entered the U.S. market in 2008. The company also sells its products in Canada and some countries in Latin America and the Middle East. Focusing on new food technology and innovative products, Dr. Schär has been trying to position itself as the leading producer for specialty diets in both Europe and North America. The company makes bread for U.S. markets in a plant in Swedesboro, New Jersey, and imports all other products from Europe.

Lee emphasizes that none of the Dr. Schär products familiar to U.S. consumers will change. The company has never used wheat starch in its breads and pastas, even in Europe. The company uses processed wheat starch only when necessary to achieve a high-quality product, she says. But the new croissants will showcase the sensory benefits of wheat starch.

“Even though you’re removing the protein, wheat starch provides a certain durability to the dough, an elasticity. So you can get a croissant that’s light and flaky,” Lee says. “Everyone gets used to gluten-free pasta. We get used to breads, although they’re getting better and better all the time. But to develop a puff pastry or a croissant: That’s hard to do with most gluten-free flours and starches.”

Extracting gluten

Not all wheat starch is made the same way, and products labeled gluten free can include only the type specifically processed to remove gluten. Lee does not say where Dr. Schär’s wheat starch comes from, but several European companies manufacture the ingredient for gluten-free foods.

The main components of wheat are fiber, starch and gluten protein. Extraction involves milling the wheat into flour, making dough and washing out the starch. Starch dissolves in water but gluten does not, so the gluten-protein sediment sinks to the bottom. Then the starch solution can be drained off and dried. Traditionally, the purified gluten fraction had more value, but the gluten-free industry has placed a demand on refined starch.

Peter Koehler, Ph.D., a food chemistry specialist at Leibniz Institute in Freising, Germany, says one German company purifies starch “by excessive washing with water until the gluten concentration is below the safety threshold.”

In Europe the standard for Codex wheat starch is 200 ppm gluten or less, meaning it must be further diluted during manufacturing to give a final product that tests safely below 20 ppm. According to the FDA, this will also be acceptable for products in the United States “as long as the final food product contains less than 20 parts per million (ppm) of gluten.”

Koehler has been researching how to use peptidase, an enzyme that breaks down gluten, to produce gluten-free wheat starch. It would provide better “water-use efficiency and quality of gluten reduction,” he says. However this technology remains in the experimental stage.

Lee says Dr. Schär follows a safety protocol in all its plants in Europe and the United States, and that approach will also apply to products that contain wheat starch.

When ingredients arrive, they’re not immediately brought into production. “They’re held in red-bag isolation … until they test free of gluten,” she says. “Then they are allowed into the production facility.”

Dr. Schär tests products along the production line and at the end as well. “We hold products for sampling purpose for six months to make sure that if there are any consumer questions we can go back to that exact batch and lot and recheck,” Lee says.

Another white flour

Apart from safety, critics argue that wheat starch does not improve nutrition. Gluten Free Watchdog’s Thompson says, “Wheat starch is not a nutritious food. It contains little to no fiber, vitamins and minerals. There are so many more healthful alternatives to wheat starch that I see absolutely no need to start using it in gluten-free products.”

Canadian Celiac Association’s Newell agrees. “Do we really need yet another nutrient-light but calorie-dense white flour?” she says. “I know there would be a consumer rejection from a segment of the gluten-free market, but some would choose to eat the product and depend on their own reactions to decide whether to continue.”

Some manufacturers agree with their concerns. Consumers will ultimately make their own choices. Those skeptical about the benefits of wheat starch will still have lots of alternatives.

A matter of choice

“Both our Udi’s and Glutino products never use wheat starch simply because it is derived from wheat, and, regardless of the removal of protein, it would still be an allergen,” says Caroline Hughes, corporate communications director for Boulder Brands. This policy means that Udi’s and Glutino products are not only gluten free but also safe for people with a wheat allergy.

Meanwhile, new products from GoPicnic, Dr. Schär and other companies will increase the range of choices for people on a gluten-free diet. Lee says that innovations in the food industry can improve both nutrition and enjoyment.

“From a dietitian’s perspective I love that we’re looking at really good, healthy grains,” she says. “We’re looking at reducing the fat, reducing the salt, reducing the sugar in the products, not just making the product gluten free but also very healthy.”

“I’ve actually had wheat-starch-based products when I’ve been in Europe,” says Lee, who has celiac disease. “The texture is far superior and I didn’t react. I love that we’re becoming smarter, and that’s allowing us to enjoy food much more. My research on quality of life shows the diet can have a huge negative impact, but if we open those doors with products that are better quality and better health-wise, that’s going to make the life of an individual with celiac disease significantly better.”

Van Waffle, who has a bachelor’s degree of science in biology, is research editor for Gluten-Free Living.  A resident of Ontario, Canada, he also contributes regularly to Edible Toronto and blogs about nature, gardening and local food at vanwaffle.com.

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New Insight Into Celiac Disease

celiac diseaseSoon, when a baby is born, doctors will be able to inspect his or her genetic code and advise the parents how to avoid life-long disorders of the immune system such as celiac disease. Preventive measures might include introducing particular foods while breastfeeding or enlisting the child to help in the garden or raise chickens. So predicts Moises Velasquez-Manoff in An Epidemic of Absence: A New Way of Understanding Allergies and Autoimmune Diseases (Scribner, 2012). Velasquez-Manoff is also the author of a recent lead story in The New York Times Sunday Review that examined the role of breastfeeding and the development of celiac disease. He said he had noted the disease has been a hot topic recently in the media, but discussions seldom touched on establishing healthy microbiota in the gut.

So he chose to address it in a Feb. 23 piece, “Who Has the Guts for Gluten?” The story resonated among those who have celiac disease for its clear and reasoned description of the ways celiac disease might develop. It was the most emailed story on the paper’s website the day it appeared and as of press time it was the newspaper’s seventh-most emailed article in the past 30 days.

“Scientists are pursuing some intriguing possibilities. One is that breast-feeding may protect against the disease. Another is that we have neglected the teeming ecosystem of microbes in the gut-bacteria that may determine whether the immune system treats gluten as food or as a deadly invader,” Velasquez-Manoff wrote in the Times.

The story was based on findings in Velasquez-Manoff’s book, which highlights new ideas about the causes and rising prevalence of celiac disease. The book also details the role parasites play in combating immune disorders. Investigating the topic over two years, the author infected himself with hookworms, surveyed research and interviewed scientists from around the world.

He noticed parallel lines of research showing a rise in various diseases of the immune system, particularly in affluent countries. Some important insight turned up in obscure journals. To his knowledge, he said in an interview, some of the most surprising findings had never been reported in popular media.

“I do not know if I am able to articulate it any better than anyone else. I am just aware of a lot more science. I spent two years writing this book, so I did a lot of research,” he said. Many of the specialists he contacted for his research have expressed appreciation for the book, he said, and were happy to see it bring those “parallel lines of this science together.”

He argues that this trend in autoimmune diseases results from a declining biodiversity of germs and worms that normally live in our bodies, even the blood parasite that causes malaria.

Why the rate of celiac disease is increasing

A popular theory suggests celiac disease is becoming common because we are eating too much wheat or the wrong varieties, particularly genetically modified wheat. Velasquez-Manoff disputes this. Facts about wheat are the most essential point about celiac disease that readers should take from his book, he said.

“It is important to contextualize any autoimmune disease within the greater family of autoimmune diseases,” he said, “to recognize that sometimes at the individual level but especially at the population level, all these diseases increase together.”

People miss this pattern if they focus on just one disorder, he added. For example, he warns against jumping to the conclusion that celiac disease has arisen because of increased wheat consumption, changing molecular structure of the protein, or how we prepare it.

Wheat has increased in the American diet since the 1970s, but we actually ate more of it in the late 19th century. Despite this, celiac disease could not have been widespread then. We have no way to estimate its prevalence at the time except by noting that deaths were rare, even though celiac disease was frequently fatal in childhood cases before scientists recognized the connection to wheat and began eliminating it from their patients’ diets in the 1940s. Consumption of wheat does not seem to account for increasing incidence of celiac disease, but the argument persists, according to Velasquez- Manoff.

“You can log onto the Web and find a number of conspiracy theories in a second,” he added. “There is a lot of evidence that those are non-sequiturs. It is far more likely— at least this is the hypothesis I explore— that something has changed about us.”

The increasing prevalence of celiac disease has followed the same trajectory as other autoimmune diseases and in the same geographical locations, irrespective of how much or how little the culture relies on wheat as a staple. Velasquez-Manoff points instead to the changing ecology of our guts.

Cultivating the superorganism

author book coverAn Epidemic of Absence explores how microbes and parasites build a healthy ecosystem within our bodies, particularly the gut. The genetic diversity of our microbiota helps us digest food and has long been recognized as essential to health. However, new studies add increasing evidence that affluent lifestyles are changing the bugs that inhabit our intestines. This in turn appears to be causing the rise of allergies and autoimmune diseases, still rare in most developing countries.

One corner of the world has provided a fertile laboratory for studying this phenomenon. Karelia, historically a province of Finland, became divided during World War II. Part remains in Finland, one of the richest countries in the world. The other part in Russia is one of the poorest regions in Europe.

“You have the same population genetically, culturally and linguistically on both sides,” Velasquez-Manoff said, “and a very, very different prevalence of celiac disease.”

A 2008 study published in Annals of Medicine tested schoolchildren for celiac disease and found in Russian Karelia, “a prevalence of 1 in 496 children compared to 1 in 107 children in Finland.” Finnish children with the same heritage and living in the same climate are almost five times more likely to have celiac disease. Not only that, Finland has one of the highest incidences of autoimmune disease in the world, ranking first for autoimmune Type I diabetes.

Velasquez was quick to point out that the celiac disease epidemic cannot be attributed to wheat: “We should be focusing on what is the difference there and why the immune system seems to work differently on the Russian side. Just looking at that example you can come away and say it is not the amount of wheat we come in contact with. If anything, the Russians are consuming more wheat, the same modern varieties.”

What is the difference? The average Russian Karelian family has a lower income, lives in more crowded conditions, and often keeps farm animals. Their children encounter a diversity of microbes and are more likely to experience infections such as hepatitis A. Studies show that this exposure seems to protect Russian Karelian children from autoimmune disorders and allergies.

Germs and worms have lived in us and our ancestors for millions of years. We are their home, so they have a vested interest in keeping us well. They interact with the complex human immune system, stimulating it just enough to fight off virulent pathogens while preventing the body from launching a massive, self-destructive attack. Velasquez-Manoff considers this balanced system, including an individual with all his inhabiting life forms, a superorganism.

A healthy start: breast milk

We used to depend on nature to populate our digestive tract with the right variety of bacteria. We spend the first nine months in a sterile environment and acquire our first microbes while passing through the birth canal.

According to research surveyed in An Epidemic of Absence, breast milk contains chemical messages from a mother’s body telling her baby what bacteria to expect, which species to accept, and when to turn on the immune reaction to fend off dangerous ones. If the mother has the right balance of bacteria in the gut and a healthy immune system, it helps the baby avoid developing allergies and autoimmune diseases.

The American Academy of Pediatrics recommends gluten be introduced to babies while breast-feeding to help prevent celiac disease. But Velasquez-Manoff pointed out it’s not clear exactly when during breastfeeding this should occur. This might confuse parents. Too early may be counterproductive, he said, and possibly cause celiac disease.

However, the society’s counterpart across the Atlantic, European Society for Paediatric Gastroenterology, Hepatology and Nutrition, provides specific guidelines. They recommend introducing gluten no earlier than four months and no later than seven.

“I think some of the ambiguity in the American Academy of Pediatrics may be intentional because they are not sure,” Velasquez-Manoff said. “There are ongoing prospective studies. Once we have the results we will know better.”

He also noted, as he did in the Times article, that “there is this added layer of complexity: all breast milk is not the same.”

A study last year in Pediatric Research reported breast milk from overweight mothers contained less bifidobacterium, a bacterial group beneficial to the baby’s developing microflora.

Velasquez-Manoff refers to a study by Yolanda Sanz of the Institute of Agrochemistry and Food Technology in Valencia, Spain, which found bifidobacteria were relatively depleted in children with celiac disease, while other microbes such as E coli. were over-abundant.

In the Times article, he explained, “In a test tube, (Sanz) found that those E. coli amplified the inflammatory response of human intestinal cells to gluten. But bifidobacteria switched the response from inflammation to tolerance.” E. coli also appears to provoke the leaky gut condition implicated in celiac disease while bifidobacteria protect the intestinal barrier.

Velasquez-Manoff suggested that there should be more focus on this where prenatal healthcare is available. Meanwhile, a 2010 paper in Pediatric Allergy and Immunology found better anti-inflammatory properties in breast milk from farm mothers than from women who lived in cities.

“In some ideal future,” Velasquez-Manoff said, “doctors will proactively approach these problems.”

They will identify the genetic risk for celiac disease in a family and advise the mother, while still pregnant, to shift the microbiology of her breast milk using probiotics. This may seem to put additional pressure on mothers to do the right thing, but Velasquez-Manoff said we cannot escape the importance of a mother’s nutrition.

“The idea is not to blame women,” he said, responding to some comments after the Times story accusing his article of faulting women. “What we have to do is shift society to accommodate biology. I agree that the answer should not be, ‘Women need to leave work and go back to the kitchen.’ That is absurd. We need instead to make it possible for women to do the healthy thing without having to disrupt their lives.”

Velasquez-Manoff said his wife’s experience breast-feeding is an example of some of the difficulties women face. Her employer provided a pumping room in a converted closet. Using the space was a hassle for her, he said, but at least she had somewhere to go. Many women do not.

Hookworms and celiac disease

Velasquez-Manoff also refers to a different prospect for defense against celiac disease, intriguing but less palatable: hookworms.

As Velasquez-Manoff describes it, hookworms prevent their host from letting “loose with a higher fire power,” which might kill the parasite but also destroy the gut. Intestinal parasites are so ubiquitous that vertebrate animals now depend on them to help manage their immunity.

In people with celiac disease, the immune system recognizes gluten as an invading bacteria or virus and begins attacking the gut lining. It is theorized that hookworms can prevent this by inducing a more tightly reined response, preventing autoimmune attacks.

A clinical study, published last year in International Journal for Parasitology, infected celiac disease patients on gluten-free diets with hookworms. Although the parasites did not cure anyone, they reduced the immune reaction when subjects ate food containing gluten.

Velasquez-Manoff said, “It was not anywhere near qualifying as remission” from celiac disease. However, it was measurable and led to a less-adverse reaction. In particular it meant people with an intense sensitivity to wheat would not have to worry about encountering “a few miniscule grains of wheat flour somewhere along the way. Some patients ended up opting to keep their parasites, because they felt better,” he added.

A personal journey

As part of the research for his book, Velasquez-Manoff inoculated himself with hookworms. He wanted to see if the parasite would relieve his food allergies, asthma, eczema and alopecia areata, a condition in which the body’s own immune system attacks hair follicles, causing partial or complete hair loss.

He had put up with symptoms since childhood but became more concerned when faced with becoming a parent. Alopecia areata shares gene variants with more serious conditions such as celiac disease and Type 1 diabetes. Velasquez-Manoff was bound to pass some of those genes on to his children, and he wanted to learn all he could to ensure their health. He found some compelling evidence, from both scientists and an underground movement of patients treating themselves, that hookworms could mollify autoimmune diseases.

He decided to try it at the same time he decided to write about it. It seemed like a good way of making “a very science-rich book more accessible” to readers, he said. He was also intensely curious. The people he contacted told him parasite infections were not bad to live with, but he wanted to gauge negative side effects for himself.

Coincidentally, a certain gene is also known to be connected with curiosity and daring behaviour, but Velasquez-Manoff does not consider himself a risk-taker. “A number of scientists have self-infected with hookworm, including John Croese [an Australian gastroenterologist investigating hookworm as a treatment for celiac disease]. Once you learn that scientists, with their wealth of knowledge about the horrors of parasite infection, are willing to self-infect, well, it seems not so risky,” he said.

The results of the author’s personal experiment with hookworms were mixed. He experienced relief from hay fever and eczema. His eyebrows started to grow back and his grooved and pitted fingernails, another symptom of alopecia areata, began growing in normally. Asthma and food allergies were unaffected. However, side effects of the hookworm infection, including cramps, diarrhea and headaches, were initially intense. They eventually settled to a more acceptable level, but the cure did not justify the treatment. Velasquez-Manoff said that eventually, after writing the book, he took a deworming drug. He does not recommend using hookworms to prevent autoimmune disease or allergies in children.

“Given my symptoms,” he concludes in the book, “I would never deliberately administer them to my daughter, for example. On the other hand, if I knew with any certainty that she was destined to develop Crohn’s disease and debilitating allergies, I might think differently.”

The long view

Studies tend to focus on prevention and development of celiac disease in children. Velasquez-Manoff said he did not find much research about what triggers its onset in adults. However, celiac experts recognize it may develop after surgery, antibiotic treatment or even pregnancy, he added.

Our lives appear to be over-sanitized. Generally, the research indicates that autoimmune diseases are increasing because germs and parasites are missing, according to Velasquez-Manoff.

Specifically, with respect to celiac disease, certain bacteria may prevent it. Breast-feeding can foster the right bacteria to protect babies against the disease. Ongoing research promises new insights about how probiotics and other lifestyle choices may contribute to a healthier gut. If these studies hold, Velasquez-Manoff said, they will change the way doctors treat celiac disease.

Meanwhile, his own journey continues. His daughter is now 2 years old. At the time of the interview, he was preparing to move from New York City to California with his family the following day.

“I will continue to cover this topic and think about a next book,” he said.

Van Waffle, who has a bachelor of science in biology, is a freelance journalist based in Guelph, Ontario, Canada, and has cooked gluten free for five years. He writes frequently for Gluten-Free Living. His work has also appeared in Edible Toronto and on cottagelife.com. He blogs about urban nature, local food and environmental issues at vanwaffle.com.




Celiac disease drugs under study

Four potential drugs to treat celiac disease have currently entered clinical studies. Two have moved into phase 2 and 3 trials to test their effectiveness in patients with celiac disease, and researchers need volunteers to proceed at this level.

None of these therapies would cure celiac disease. Most would only protect patients from small amounts of gluten, such as cross-contamination in restaurants. Each of the four uses a different mechanism.

Volunteers still needed

Alvine Pharmaceuticals is testing ALV003, an enzyme that breaks down gluten celiac disease drug study before the immune system has a chance to react to it. The company is recruiting volunteers for its study in the United States, Canada, Finland and Norway. Visit CeliActionStudy.com to volunteer or for more information about the study.

Alba Therapeutics’ larazotide acetate could help close junctions between cells in the intestine, preventing leaky gut syndrome and inflammation. In February the company announced positive results from phase 2 trials for effectiveness. This drug is the closest to becoming commercially available. The company is soon expected to move forward with the last phase before approval but is not yet recruiting volunteers.

Two other drugs, BioLineRx’s BL-7010 and ImmusanT’s Nexvax2 , are in early stages of testing low doses for safety in small human study groups.

BioLineRx is testing  BL-7010, which binds the gluten protein and allows it to pass through the digestive system without causing any harm. It would only protect against small amounts of gluten. The study has been recruiting volunteers in Finland.

ImmusanT’s Nexvax2 is designed to induce immune tolerance.  Patients could stop following the gluten-free diet as long as they took the drug. It would work only for patients with a certain genetic marker for celiac disease, DQ2.  No clinical trial is open at this time.

Celiac disease and diabetes

Another clinical trial investigating a connection between celiac disease and type 1 diabetes is currently underway through the Hospital for Sick Children in Toronto, Canada. It is recruiting volunteers between ages 8 and 45 who have type 1 diabetes and have not been diagnosed with celiac disease. Initial screening will identify patients with asymptomatic celiac disease, determining eligibility for a dietary intervention study. Visit CeliacAndDiabetes.com for information.

Up-to-date information on studies needing volunteers can be found on ClinicalTrials.gov.

Van Waffle is the research editor for Gluten-Free Living. Study Sessions, his column on studies related to celiac disease and gluten sensitivity, appears in each issue.


Prognosis for Better Diagnosis

Despite a growing awareness of celiac disease, most people still don’t know they have it.

When a pediatrician phoned Marilyn Geller with test results indicating her 15-year-old son probably had celiac disease, Geller did not understand what the physician was saying.

With a master’s of science in public health and experience as a hospital administrator, Geller considered herself well educated in the health field. But she knew little about the disease.

While Geller has since learned a lot and now serves as head of a national support group, many people still know little about celiac disease. Although it is one of North America’s most common health problems, affecting close to one in 100 people, celiac disease is widely undiagnosed.

When the pediatrician mentioned celiac disease, Geller says she heard, “The animal at the zoo, you know, like S-E-A-L.”

She did not know what gluten was, either. Her husband, a trained clinician, was similarly bewildered. Their son did not have the classic symptoms he knew about: skinny limbs, swollen belly and diarrhea. In fact, he was overweight and constipated and had suffered for years with nasal problems.

Since then — now her son is healthy and attending college — Geller has become chief executive officer of the Celiac Disease Foundation in Los Angeles. Correcting the under-diagnosis of this condition is a project near to her heart.

Although the gluten-free diet and celiac disease have gained widespread attention in mainstream and social media in recent years, the rate of diagnosis has stubbornly remained nearly unchanged, with less than a paltry 20 percent aware they have the disease.

Health risks

Untreated celiac disease presents health risks. A study from Columbia University in 2013 found that the intestinal damage brings a four times greater risk of developing a type of lymphoma, or blood cancer. Celiac disease is also linked to osteoporosis, thyroid problems, type 1 diabetes and malabsorption of nutrients.

To estimate long-term health risk, a group of celiac disease experts led by Joseph Murray, M.D., of the Mayo Clinic, in 2009 analyzed blood samples collected a half century earlier, between 1948 and 1954, from more than 9,000 healthy young men at an Air Force base. Using current technology, researchers identified who had undiagnosed celiac disease. According to records traced up to 1997, these individuals faced a fourfold greater risk of death.

Early diagnosis and adoption of a gluten-free diet can eliminate or reduce health risks.

“It is a simple blood test. It is a simple biopsy,” Geller says. “There is no reason anybody should suffer.”

Silent patients

The most recent nationwide study, conducted by Murray and colleagues in 2012 and appearing in the American Journal of Gastroenterology, estimated that 1.8 million Americans have celiac disease and 83 percent remain undiagnosed.

Another study by Murray’s team a year earlier used a volunteer blood draw at a Wyoming health fair to estimate that undiagnosed celiac disease affects 1 in 126 Americans. Most participants whose blood tests indicated they likely had celiac disease reported no symptoms or atypical ones.

About 40 percent of North Americans are thought to possess the genes for celiac disease, but few of them will ever develop it. Scientists are still investigating what environmental factors cause a healthy person with these genes to develop celiac disease. A study last year from the Norwegian Institute of Public health found that introducing food grains to infants between 5 and 6 months of age while still breastfeeding may help protect against childhood onset. Stresses such as surgery and pregnancy seem to trigger the disease in adults.

Besides genetics and environmental factors, celiac disease is an autoimmune condition that also involves a reaction to gluten, a protein found in wheat, barley and rye. When a patient’s gut digests gluten, the immune system attacks the lining of the small intestine. This damages the tissues that absorb nutrients, eroding the villi, tiny finger-like projections that line the gut. This process is called villous atrophy.

However, in some people this tissue damage occurs without any obvious symptoms. Murray, a professor of medicine and consultant to the department of immunology at the Mayo Clinic in Rochester, Minn., calls people with no symptoms “silent patients.” This is the first reason he suggests why so many cases remain undiagnosed.

Confusion of symptoms

 Even if symptoms occur, Murray says patients and doctors can miss diagnosis for several reasons. Symptoms are often vague and may be attributed to other common conditions such as irritable bowel syndrome.

The classic signs of celiac disease include digestive disturbances, pain and fatigue. In children it can cause failure to thrive. Completely different sets of symptoms can manifest, such as itchy skin, anemia, osteoporosis, infertility and miscarriage. Uncharacteristic symptoms can distract patients and doctors from a connection to celiac disease.

Geller’s son had suffered for years from unexplained post-nasal drip, she says, and was undergoing an expensive battery of tests prior to sinus surgery when the pediatrician identified his celiac disease.

Murray says, “Other patients at risk — with type 1 diabetes, premature osteoporosis, or iron deficiency anemia — should be tested, but again awareness of that association is not obvious” and is unfamiliar to many doctors.

He also points out many doctors do not recognize the importance of a family history of celiac disease. “It’s not a routine question,” he says. “It should be. And if someone has a family history, they should be tested.”

Essentially, doctors lack suspicion of celiac disease. Murray says, “People just don’t think about it.”

Closer look at biopsies

Diagnosis of celiac disease involves conducting an endoscopy, which allows visual examination of the small intestine using a flexible tube, combined with biopsies, tissue samples collected from the gut. Currently this procedure provides the best way to identify villous atrophy. It remains the gold standard for diagnosis of celiac disease.

But Benjamin Lebwohl, M.D., assistant professor of clinical medicine and epidemiology at the Celiac Disease Center at Columbia University Medical Center in New York, N.Y., has found that most gastroenterologists do not collect enough tissue samples from each patient.

Diseased tissue in the small intestine can occur in patches. For this reason, in 2006 the American Gastroenterological Association issued a guideline that from four to six biopsy samples should be collected from each patient.

Based on an analysis of all procedures conducted in the United States between 2006 and 2009 on about 93,000 different patients, a research team led by Lebwohl in 2013 found that only one-third of submissions included at least four biopsies. The most common number was two. Adherence to the guidelines increased only modestly during the late 2000s, from 35 to 38 percent.

The study also found that gastroenterologists who conducted a large volume of procedures were more likely to submit fewer biopsies per procedure. However, gastroenterologists from larger endoscopy practices with multiple physicians in the group were more likely to adhere to the guidelines. This suggests that doctors who work more closely with their peers follow the rules better.

The same study found that clinics with physicians who tested a higher volume of patients were less likely to adhere to the biopsy guidelines, perhaps because of the extra time required to collect additional samples.

An endoscopy alone can often find evidence of villous atrophy. However, unless tissue samples are also taken, the procedure can miss microscopic evidence of celiac disease. Researchers including Lebwohl in 2012 found that endoscopy procedures to investigate diarrhea, anemia and weight loss often did not include biopsy, even though those symptoms are indicative of celiac disease. Patients who were male, older or black or Hispanic were less likely to have biopsies taken.

“Men are equally likely as women to show the antibodies that indicate celiac disease — most studies have shown this,” says Lebwohl. “At the same time, most studies have also shown that the majority of patients diagnosed with celiac disease are female. I believe that this discrepancy is due to a combination of factors: Women may be more likely to seek evaluation of their symptoms, and doctors may be less likely to test for celiac disease in men, due to the erroneous belief that celiac disease is uncommon in men.”

Another study headed by Lebwohl in 2011 found that following the guidelines more than doubled the probability of finding celiac disease in tested patients from 0.7 percent to 1.8 percent. Inadequate testing may be overlooking many cases of celiac disease.

Patient push

For a variety of reasons, patients themselves are prompting an unusually large proportion of celiac disease diagnoses.

“At my practice I ask all newly diagnosed patients, ‘Who thought of testing you for celiac disease first?’” Murray says. “And at least one-third of the time it was themselves or a family member.”

However, self-diagnosis without proper testing can have an unfortunate consequence: People will adopt a gluten-free diet without knowing whether they really have celiac disease.

The 2012 nation-wide survey of nearly 7,800 people, conducted by Murray’s team, found most who follow a gluten-free diet have not been diagnosed with celiac disease.

Geller’s experience talking to people echoes the research.

“They have these symptoms so they put themselves on the gluten-free diet to try it,” she says. “Then they feel better so they don’t want to do a gluten challenge to find out if they really do have celiac disease.”

On the gluten-free diet, villous atrophy and the blood levels of gluten antibodies often revert to normal, so a diagnosis is impossible unless the patient begins consuming gluten again. Most people do not want to make themselves sick through this process even if it would let them know for certain.

Some people who adopt the diet have non-celiac gluten sensitivity. Ideally, they have undergone the diagnostic procedure to rule out celiac disease, then tried a gluten-free diet under a doctor’s supervision. As yet, there is no test to diagnose non-celiac gluten sensitivity, but if the diet leads to improved health, then this confirms it as the best course of action. In other cases patients reach this conclusion on their own and adopt the diet without getting tested for celiac disease.

The danger in not knowing whether celiac disease is the culprit is in the absence of appropriate follow-up health care, Geller says.

With celiac disease, “You have the risk for the other autoimmune disorders. So if you put yourself on a gluten-free diet, who is doing your regular bloods testing to make sure that you don’t now have thyroid disease, psoriasis, lupus or type 1 diabetes?”

Some patients continue to show tissue damage from unknown sources of gluten. Symptoms may vanish, but long-term health impact is hard to assess.

Murray recommends that self-treated patients pursue diagnosis under medical supervision. This might begin with a genetic test, which can rule out the possibility of celiac disease if the required genes are missing. If a patient has the genes, Murray advises an antibody test, possibly followed by a gluten challenge and duodenal biopsy.

Better to know

Geller says diagnosis can provide a strong incentive against cheating on the diet.

It helps parents such as Margaret Steen, 43, who lives near San Francisco with her husband and two sons. Her younger son, Harrison Webster, 9, has been diagnosed with celiac disease.

“When the blood tests came back positive, we took Harrison to a pediatric gastroenterologist, who recommended that we do the endoscopy and biopsies to find out for sure whether he had celiac, disease” Steen says. “Because we knew that sticking to the diet would be difficult, we wanted to know for certain.

“It would be hard for him to refuse pizza at pizza parties, cake at birthday parties and all sorts of food offered by well-meaning people. We thought it would be easier for him (and for us, when he is asking for ‘just one bagel’) to remain firm if we had a clear medical diagnosis.”

She adds, “Since he wasn’t having painful symptoms before, I don’t think he sees much of a benefit. He has been good about sticking to the diet, though.”

The pediatrician recommended testing Harrison because he was underweight and had a family history of Crohn’s disease.

“I’m glad to know he has celiac disease so we can be sure he grows as much as he is meant to and so he doesn’t have further medical problems caused by gluten later,” Steen says.

Finding lost patients

Higher rates of diagnosis require better awareness among doctors. Lebwohl says physicians can help each other.

“In our research we found that gastroenterologists who perform endoscopy with higher numbers of colleagues in the same unit tend to have greater adherence to these [biopsy] guidelines,” he explains. “This suggests that peer education is playing a positive role in adoption of these guidelines. We learn from our colleagues.”

A 2007 study from the University of Maryland School of Medicine found that providing a checklist of symptoms at primary care clinics led to a marked increase in diagnoses.

Geller argues that change starts with the public.

“The patient community needs to support celiac disease [research] just like they would support any cancer research. Just like they would support Parkinson’s disease or lupus [research]. There need to be dollars donated to advance research, period,” she says. “That’s going to be the biggest driving factor. When the community stands up for itself and takes care of itself, that will drive diagnosis.”

Geller points out that the pharmacy industry also drives health care in North America. Doctors may have been slow to gain awareness of celiac disease because of the lack of any drug treatment for the disease. Some drugs are currently in the testing phase, so this situation may change if any of them become approved. Again, funding is required.

Meanwhile, the exploding availability of gluten-free foods may have done more than anything else to spread awareness. But while that benefits those who have celiac disease, it also has some drawbacks.

“This is the double-edged sword of the gluten-free marketplace,” Geller says, “because you have so many people adopting gluten-free and vegan and paleo diets that, from a clinician’s perspective, it falls into an alternative health lifestyle as opposed to a disease.”

The tendency for people to adopt the diet without diagnosis also casts some doubt. But overall Geller sees the outcome as beneficial.

“Because of the gluten-free marketplace, consumers are aware, and because consumers are aware and asking, physicians are doing more research.”

Van Waffle, who has a bachelor’s of science, is a freelance journalist based in Guelph, Ontario, Canada, and a regular contributor to Gluten-Free Living. His most recent feature examined the potential for gluten in yeast extract, and he is the magazine’s research editor. Waffle also blogs about nature, the environment and local food at vanwaffle.com.