What Happens When Patients With ‘Gluten Sensitivity’ Are Challenged with Gluten?

A recent review of double-blind, placebo-controlled trials (n=10) (J Molina-Infante, A Carroccio. Clin Gastroenterol Hepatol 2017; 15: 339-48) showed that most individuals who consider themselves to have nonceliac gluten sensitivity (NCGS) do not show gluten-specific symptoms.  Only 16% (38 of 231) showed symptoms specific to gluten ingestion.  In addition, the authors describe a 40% nocebo response (similar or increased symptoms in response to placebo).

My take: Due to the absence of a reliable test for NCGS, there are a lot of people who avoid gluten when gluten is not the main culprit for their symptoms.

On a related topic –NPR reports on colleges developing a New Niche -Gluten-free Dining Rooms.  An excerpt:

An estimated 5 to 10 percent of college students have celiac disease or other gluten-related disorders, according to Dr. Alessio Fasano, director of the Center for Celiac Research and Treatment in Boston…

There’s also a marketing angle in responding to the rising rate of gluten-related diagnoses. “Families tell us that Kent has become a top contender because this option exists

Also from NPR –For People With Celiac Disease -Could a Viral Infection Be a Trigger?

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Is a Gluten-Free Diet a Healthy Diet for Those without Celiac Disease?

A helpful commentary (NR Reilly. J Pediatr 2016; 175: 206-10) on the gluten-free diet (GFD) tries to separate fact from fiction.  A few key points:

  1. There are some health problems that can occur with a GFD, particularly when the diet is started without the support of an experienced dietician. GFD foods frequently contain a greater density of fat and sugar and can contribute to obesity and metabolic syndrome.  A GFD may lead to nutrient deficiencies in B vitamins, folate, and iron.  GFD without sufficient dietary diversity may contain increase in toxin exposures (eg. arsenic, and mercury).
  2. Gluten is not toxic. “There are no data to support the theory of an intrinsically toxic property of gluten for otherwise-healthy and asymptomatic adults and children, and certain studies have specifically demonstrated a lack of toxic effects.
  3. Most individuals with NonCeliac Gluten Sensitivity (NCGS) do not have NCGS!  First of all, many receive a GFD without proper testing to exclude celiac disease.  Secondly, most will tolerate gluten reintroduction.  In an Italian study, “only 6.6% of consecutive patients with presumed gluten sensitivity…actually had NCGS. 86% did not experience symptoms when gluten was reintroduced.”
  4. Timing of gluten introduction: “The most current understanding…in at-risk infants is that neither delaying gluten introduction from the recommended 6 months of age to 1 year, nor introducing at 4 months of age alters long-term CD risk estimates.”

My take: This is an excellent commentary.  While many people (without celiac disease) perceive benefit from a GFD, only a minority are likely  to derive better health or improved quality of life.  Those who stick with a GFD should seek the help of a well-qualified dietician.

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Glacier Nat'l Park

Glacier Nat’l Park

PPIs and Associated Heart Risk

A NY Times review PPIs and Heart Attacks of PLos One study showing an association between PPI usage (eg. prilosec, prevacid, and nexium) and heart attacks -this study does not prove any causality, but is likely to spark some questions. Excerpt:

The widely used drugs known as proton pump inhibitors, or P.P.I.’s — gastric reflux preventives like Prilosec and Prevacid — may increase the risk for heart attack, according to analysis of data involving almost three million people.

A significant limitation of the study, in PLOS One, is that P.P.I. usage may be a marker of a sicker patient population, more subject to heart disease in any case.

Here’s NPR’s take on the same study: Data Dive -Possible Link Between PPIs and Heart Attacks

“The increase in risk is about 16 to 20 percent, depending on the particular drug involved”…

Someone with a low risk of heart attack doesn’t have much to worry about. “If your risk of a cardiovascular event or a heart attack is one in a million, now it is 1.2 in a million,” [Nigham] Shah [one of the authors] says.

“The problem is, it’s very easy to do studies of this sort that lead to conclusions that can be misleading,” says Dr. David Juurlink, a drug-safety researcher at the University of Toronto…

“Having a bad diet, drinking too much alcohol, smoking and all sorts of other things … might lead people to be on a PPI,” Juurlink says. One would expect those people to be at higher risk of heart attack, which leads Juurlink to think the medicine is likely not to blame.”


Also noted:

Low-FODMAPs with or without Gluten-Free Diet in IBS

In a small study with 60 patients with irritable bowel syndrome (DDW abstract 374), the response rate to a Low-FODMAPs/Normal gluten diet was as effective as a Low-FODMAPs/Gluten-free diet.  Both diets were more effective in reducing abdominal symptoms than a normal diet.  A summary of this abstract from Gastroenterology & Endoscopy News: Nixing Gluten Offers No Added Benefit To Low-FODMAPs Diet for IBS

According to Lin Chang, MD: “The beneficial effect of low FODMAPs does not appear to be predominantly due to gluten avoidance.”

Related blog post: An Unexpected Twist for “Gluten Sensitivity” | gutsandgrowth


AJG Celiac Practice Guidelines 2013 -Useful Link

This full-text link to AJG Practice Guidelines for Celiac Disease 2013 (Am J Gastroenterol 2013; 108:656–676; doi:10.1038/ajg.2013.79) provides 45 evidence-based recommendations for diagnosis and management of celiac disease along with 264 references.  

Table of Contents for Article

Table of Contents for Article

Topics of particular interest

  • Whether to test first-degree relatives.  The article recommends testing in symptomatic individuals and consideration of testing in asymptomatic individuals
  • When to perform genetic testing
  • When to use tests besides tissue transglutaminase antibody (TTG IgA) (mainly in children less than 2 years)
  • Recommends against use of stool or salivary testing
  • How to approach refractory celiac disease
  • The limited circumstances which justify followup endoscopy

Potential Reasons for Genetic Testing:

Potential Reasons for Genetic Testing

Celiac vs. Gluten Sensitivity:

Celiac vs. Gluten Sensitivity

Bottomline: This practice guideline covers most of the issues dealing with celiac and gluten sensitivity –it is a useful reference.

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Gluten-free diet “has legs”

From NY Times: http://t.co/5cQijw7do9

An excerpt:

The Girl Scouts recently introduced a gluten-free chocolate chip shortbread cookie to their annually anticipated line of sweet treats…And Trader Joe’s recently joked in an advertising flier promoting gluten-free foods that it was selling “Gluten Free Greeting Cards 99 Cents Each! Every Day!” — even though it then went on to say the cards were not edible.

Makers of products that have always been gluten-free, including popcorn, potato chips, nuts and rice crackers, are busy hawking that quality in ads and on their packaging.

And consumers are responding with gusto. The portion of households reporting purchases of gluten-free food products to Nielsen hit 11 percent last year, rising from 5 percent in 2010.

In dollars and cents, sales of gluten-free products were expected to total $10.5 billion last year, according to Mintel, a market research company, which estimates the category will produce more than $15 billion in annual sales in 2016…

“About 30 percent of the public says it would like to cut back on the amount of gluten it’s eating, and if you find 30 percent of the public doing anything, you’ll find a lot of marketers right there, too.”

Never mind that a Mayo Clinic survey in 2012 concluded that only 1.8 million Americans have celiac disease, an autoimmune disorder that causes the body to attack the small intestine when gluten is ingested and can lead to other debilitating medical problems if not diagnosed.

An additional 18 million people, or about 6 percent of the population, is believed to have gluten sensitivity, a less severe problem with the protein in wheat, barley and rye and their relatives that gives elasticity to dough and stability to the shape of baked goods.

“There are truly people out there who need gluten-free foods for health reasons, but they are not the majority of consumers who are driving this market,” said Virginia Morris, vice president for consumer strategy and insights at Daymon Worldwide, a private brand and consumer interactions company…

“The reason I do believe this has legs is that it ties into this whole naked and ‘free from’ trend,” she said. “I think we as a country and as a globe will continue to be concerned about what’s going into our food supply.”

Rebecca Thompson, a marketing manager at General Mills, said ..“When you think about the dynamics in a household, where there are likely to be three other people eating at the same time as one person with celiac or gluten sensitivity, it’s much easier to prepare one meal for everyone.”…

General Mills, whose brands include Bisquick, Pillsbury and Betty Crocker, might seem like the least likely company to embrace gluten-free. But in the mid-2000s, more and more customers began seeking alternatives to its traditional products.

So in 2008, it began reformulating its Chex cereals, underscoring the first change, to Rice Chex, with a major marketing effort. It was relatively easy to tweak Chex by switching a few minor ingredients. But the next year, Betty Crocker introduced gluten-free brownies, cookies and cakes in a far more complicated process…

Gluten-free customers are valuable, ringing up roughly $100 in sales with their average grocery basket compared with $33 for the overall average basket, according to Catalina Marketing…

Last August, the Food and Drug Administration, which oversees food labeling, ruled that products labeled gluten free were permitted to contain no more than 20 parts of gluten per million, which made it more difficult for large food companies to get into the business. “You really need to have a captive facility because wheat floats,” Mr. Hughes said.

Sales of Udi’s and Glutino were up 50 percent last year, and Boulder Brands is finding more demand from regional food service businesses and institutions. Udi’s hot dog buns are available now in most major baseball parks, and Dunkin’ Donuts and others are turning to the company for individually wrapped gluten-free bagels and muffins…

Mr. Hughes said. “We think this is a trend with long legs because there is some insulation from the big players — it’s hard to produce gluten-free — and because so much of the category is represented by $10- and $15-million mom-and-pop businesses.”

Interest in gluten-free products also has been a boon for fruits and vegetables and other foods that are inherently gluten-free. Popcorn Indiana, for example, has labeled its ready-to-eat popcorn gluten-free since before the fad began, in part because the chief executive, Hitesh Hajarnavis, has children who have food allergies. “I had become an avid reader of labels, and so when I came over to Popcorn Indiana, I knew the value of having a clear gluten-free label for what was then a very small number of people with gluten allergies,” Mr. Hajarnavis said… “But there is a growing population of people who have somehow heard that gluten-free is healthier or think of it as fashionable, and when they remove gluten from their diet, they’re inadvertently taking out a lot of processed foods and are really feeling the benefits of eating healthier foods.”

Celiac Update: Quinoa –probably OK for gluten-free diet based on small study.  Here’s the link: nature.com/ajg/journal/vaop/ncurrent/full/ajg2013431a.html … (from KT Park twitter feed)

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Most Popular Posts

Most popular posts: In the past year, the most popular posts from this blog were the following:

I want to thank all of you who provide feedback and wish you all a good year ahead.  As always, feel free to comment on posts or to send an email with suggestions.


I had a few free minutes so I decided to take a look at a bunch of upcoming lectures from the 2013 NASPGHAN upcoming meeting.  With electronic media, it is easy to take a quick glance.  Here’s the master link to all of the following talks:

Annual Meeting page.

Some of the power point lectures that I’ve seen so far:

  • Is my PPI dangerous for me? Eric Hassall MBChB, University of British Columbia One point in his slides that I had not seen much about was a hypothesis that PPI use may predispose to the development of eosinophilic esophagitis by allowing food proteins to be more intact ( attributed to Merwat, Spechler. Am J Gastro ’09).  He explains that “acid reflux” is a clever marketing term and has a slide with Madmen actors.  If there is “acid,” one must need acid suppression.
  • My child doesn’t go to school Lynne Walker MD, Vanderbilt University.  Lynne shows an interesting fax from a parent that asks if the problem is physical, how will she help? And, if it is psychological, how can this be remedied?  She outlines a lot of pain theory and indicates that parents need to become health coaches, avoid catastrophizing (?spelling), and encourages mental health evaluation.  Use the parents words ‘I’m going to refer xxx for relaxation and stress management.’
  • My child’s H. pylori will not go away – (the resistant bug) Benjamin Gold MD, Children’s Center for Digestive Healthcare. Ben manages to stuff so much information into his talk.  His talk is like one of those clown cars where more and more people keep coming out.  He has slides with worldwide resistance maps, slides with treatment regimens and algorithms, and the reasons for treatment failure. Perhaps I can convince him to give a live preview.
  • Administrative/executive functioning Richard Colletti MD, Fletcher Allen Healthcare. Offers personal and pragmatic advice for career advancement.  His slides indicate that he started his GI fellowship at age 40.  One of his quotes, “80% of success is showing up” (Woody Allen) is definitely true.  It’s pretty much akin to what I learned about success in medical school.  You need the three As: availability, affability, and ability.  My mentor said the first was what people needed most.
  • The changing face of intestinal transplantation
    Simon Horslen MD, Seattle Children’s Hospital.  Lecture notes that number of intestinal transplants have decreased dramatically, particularly in children. In 2012, only about 100 intestinal transplants were performed whereas it had peaked at nearly 200.  Much of the credit is due to intestinal rehabilitation work and adjustments in parenteral nutrition (eg. lipid minimization, line care).  Two most common reasons for intestinal transplantation at this time are gastroschisis and volvulus.
  •  Gluten sensitivity: Fact or fiction Alessio Fasano MD, MassGeneral Hospital for Children. This blog has covered a lot of the same material, but Alessio’s slides are pretty impressive.  Also, I was not aware that Lady Gaga consumes a gluten-free diet
  • Controversies in parenteral nutrition Christopher Duggan MD, Boston Children’s Hospital.  This lecture provides a timely update on nutrient deficiencies due to component shortages and discusses lipid minimization compared with fish oil-based lipid emulsions.
  • Vitamin D and immunity James Heubi MD, Cincinnati Children’s Hospital and Medical Center.  In the beginning of the slides, Jim provides a very user-friendly definition of an expert and a suitable picture.  He indicates that in 2011 there were 3746 vitamin D publications but inexplicably only chooses to review a tiny fraction.

At the time of this posting, I haven’t had a chance to look through these talks:



An Unexpected Twist for “Gluten Sensitivity”

While the concept of gluten sensitivity without celiac disease has been recognized since 1980 (Gastroenterol 1980; 79: 801-06), a recent study indicates that gluten may not be the main culprit in inducing these symptoms (Gastroenterol 2013; 145: 320-28; editorial 276-79).

The authors of this double-blind crossover study were the same investigators who popularized the concept of nonceliac gluten sensitivity (NCGS) two years ago (Am J Gastroenterol 2011; 106: 508-14).  In this current study, they demonstrate that in NCGS patients consuming a low FODMAPs diet (see previous post links below) gluten reintroduction did not cause specific or reproducible symptoms.

Methods: In this study, they enrolled 37 subjects with NCGS who fulfilled Rome III criteria for IBS and improved on a gluten-free diet (GFD).  All participants continued their GFD and after a 1-week baseline, started on a low FODMAP diet for a 2-week run in period.  Subsequently, patients were randomly assigned to 3 study arms: high gluten (16 g gluten/day), low gluten (2 g gluten & 14 g whey per day) or control (16 g whey/day).  Each participant took this diet for 1 week, had a 2-week washout, then crossed over to each arm.  In addition, at least 8 months, 22 subjects underwent another brief crossover study (high-gluten, whey only, or control with no additional protein).  As part of the study, clinical, serological, and immunologic parameters were monitored during all aspects of the rechallenges.

Results: “Gastrointestinal symptoms consistently and significantly improved during reduced FODMAP intake, but significantly worsened to a similar degree when their diets included gluten or whey protein.” There were no changes in any serological or immunologic parameters between the dietary challenges.

There were several limitations to this study of this highly-selected cohort which are well-described in their discussion.

Bottom-line: Gluten might not be a specific trigger once dietary FODMAPs are reduced.

Related blog posts:

Why Eliminating Gluten May Help Irritable Bowel Syndrome

As noted in previous posts, gluten-free diets (GFDs) have become commonplace for individuals without celiac disease.  Clinically, subgroups of patients with irritable bowel syndrome (IBS) were noted to have gluten sensitivity.  But, these subgroups were difficult to define and the mechanisms of improvement with a GFD were purely speculative.  A new study identifies changes in the frequency of bowel habits and mucosal permeability associated with a GFD among diarrhea-predominant IBS patients (Gastroenterol 2013; 144: 903-11).

While the investigators conducted a trial of short duration (4 weeks) and only enrolled 45 patients, they completed a number of sophisticated studies.

Design: 45 patients were randomized into either a gluten-containing diet (GCD, n=22) or GFD (n=23).  In each group, there were 11 patients who were HLA-DQ2/8 positive.


  • Daily bowel frequency
  • Small bowel and colonic transit
  • Mucosal permeability using lactulose/mannitol excretion.  Lactulose is normally not absorbed except with increased permeability. Mannitol is passively absorbed throughout intestine.  Higher lactulose:mannitol ratio in urine reflects intestinal permeability.
  • Cytokine production
  • Rectosigmoid biopsies (from 28 patients) to analyze messenger RNA for tight junction proteins and immunohistochemical staining

Key Results:

  • Fewer bowel habits were noted in patients receiving GFD.  In this group, bowel habits decreased from ~2.6/day to 2/day.  This was significant compared with GCD group.  Furthermore, this effect was more pronounced among patients positive for HLA-DQ2 or HLA-DQ8.
  • There was no significant change in stool form or ease of passage between GFD and GCD groups.
  • GCD had increased small bowel permeability as shown by mannitol excretion and lactulose-to-mannitol ratio (specific #s Table 1). Again, this effect was more pronounced among patients positive for HLA-DQ2 or HLA-DQ8.
  • GCD group had a reduced mRNA expression of mucosal tight junction proteins.
  • GCD was not associated with significant effects on colonic transit, immunocyte activation, or altered histology (eg. increased intraepithelial lymphocytes, change in crypt:villus ratio).

The increased changes in HLA-DQ2/HLA-DQ8 suggest a role for adaptive immune response in mediating GCD effects on barrier function.

Conclusion: “our data provide mechanistic explanations for the observation that gluten withdrawal may improve patient symptoms in IBS.”

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