Source:Clues to Gluten Sensitivity
Melinda Beck, Health Journal, Wall Street Journal (15 March 2011) Links and study added.
Lisa Rayburn felt dizzy, bloated and exhausted. Wynn Avocette suffered migraines and body aches. Stephanie Meade's 4-year-old daughter had constipation and threw temper tantrums.
All three tested negative for celiac disease, a severe intolerance to gluten, a protein found in wheat and other grains. But after their doctors ruled out other causes, all three adults did their own research
and cut gluten—and saw the symptoms subside.
A new study in the journal BMC Medicine may shed some light on why. It shows gluten can set off a distinct reaction in the intestines and the immune system, even in people who don't have celiac disease.
"For the first time, we have scientific evidence that indeed, gluten sensitivity not only exists, but is very different from celiac disease," says lead author Alessio Fasano, medical director of the
University of Maryland's Center for Celiac Research.
The news will be welcome to people who have suspected a broad range of ailments may be linked to their gluten intake, but have failed to find doctors who agree.
Some people claim that eating gluten products can cause health problems like body aches and chronic fatigue -- and even some behavioral problems in children. WSJ's Melinda Beck talks with Kelsey
Hubbard about a new study that sheds light on what may be going on.
"Patients have been told if it wasn't celiac disease, it wasn't anything. It was all in their heads," says Cynthia Kupper, executive director of the nonprofit Gluten Intolerance Group of North America.
The growing market for gluten-free foods, with sales estimated at $2.6 billion last year, has made it even harder to distinguish a medical insight from a fad.
Although much remains unknown, it is clear that gluten — a staple of human diets for 10,000 years — triggers an immune response like an enemy invader in some modern humans.
The most basic negative response is an allergic reaction to wheat that quickly brings on hives, congestion, nausea or potentially fatal anaphylaxis. Less than 1% of children have the allergy and most outgrow it
by age five. A small number of adults have similar symptoms if they exercise shortly after eating wheat.
At the other extreme is celiac disease, which causes the immune system to mistakenly attack the body's own tissue. Antibodies triggered by gluten flatten the villi, the tiny fingers in the intestines needed
to soak up nutrients from food. The initial symptoms are cramping, bloating and diarrhea, similar to irritable bowel syndrome, or IBS, but celiac disease can lead to malnutrition, osteoporosis and other more
serious health problems that can result in early death. It can be diagnosed with a blood test, but an intestinal biopsy is needed to be sure.
Background:
Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of gluten. Gluten-sensitive individuals (GS) cannot tolerate gluten and may develop gastrointestinal symptoms similar to those in CD,
but the overall clinical picture is generally less severe and is not accompanied by the concurrence of tissue transglutaminase autoantibodies or autoimmune comorbidities. By studying and comparing mucosal
expression of genes associated with intestinal barrier function, as well as innate and adaptive immunity in CD compared with GS, we sought to better understand the similarities and differences between these
two gluten-associated disorders.
Methods:
CD, GS and healthy, gluten-tolerant individuals were enrolled in this study. Intestinal permeability was evaluated using a lactulose and mannitol
probe, and mucosal biopsy specimens were collected to study the expression of genes involved in barrier function and immunity.
Results:
Unlike CD, GS is not associated with increased intestinal permeability. In fact, this was significantly reduced in GS compared with controls (P = 0.0308), paralleled by significantly increased expression
of claudin (CLDN) 4 (P = 0.0286). Relative to controls, adaptive immunity markers interleukin (IL)-6 (P = 0.0124) and IL-21 (P = 0.0572) were expressed at higher levels in CD but not in GS, while expression
of the innate immunity marker Toll-like receptor (TLR) 2 was increased in GS but not in CD (P = 0.0295). Finally, expression of the T-regulatory cell marker FOXP3 was significantly reduced in GS relative
to controls (P = 0.0325) and CD patients (P = 0.0293).
Conclusions:
This study shows that the two gluten-associated disorders, CD and GS, are different clinical entities, and it contributes to the characterization of GS as a condition associated with
prevalent gluten-induced activation of innate, rather than adaptive, immune responses in the absence of detectable changes in mucosal barrier function.
[...] "We're talking about 20 million people out there," [Dr. Fasano] says. "This gives some rational reason why people come up with the symptoms they have."
People with celiac disease have specific damage to their intestines caused by an autoimmune reaction to
gluten in their diets. People with gluten sensitivity don't have this damage, although they do experience inflammation from gluten, Dr. Fasano says.
The difference between the two conditions stems from the immune system response to gluten.
In gluten sensitivity, the innate immune system — the body's first line of defense against invaders — responds to gluten ingestion by fighting the gluten directly, creating inflammation both inside and outside
the digestive system, Dr. Fasano says.
Meanwhile, in celiac disease, both the innate immune system and the adaptive immune system — a more advanced, sophisticated part of the immune system — get involved in the fight, he says. Miscommunications between
adaptive immune system cells lead those cells to fight the body's own tissues, creating the villous atrophy seen
in celiac disease.
Some people identified as gluten-sensitive in the University of Maryland study showed some intestinal damage. However, that damage has
different biomarkers than those seen in celiac disease, and it's very unlikely that those gluten sensitive people would eventually be diagnosed with celiac, Dr. Fasano says.
There's no question that people with celiac disease and gluten sensitivity experience near-identical symptoms, including diarrhea, bloating, abdominal pain, joint pain, depression, brain fog and migraines, Dr.
Fasano says.
Only those people with the adaptive immune system response unique to celiac disease are at risk for developing intestinal lymphoma and other conditions associated with celiac, such as
osteoporosis, he says. However, gluten sensitivity appears to play a role in 20% or more of patients with autism
and schizophrenia, he says. [...]
The incidence of celiac disease is rising sharply — and not just due to greater awareness. Tests comparing old blood samples to recent ones show the rate has increased four-fold in the last 50 years, to at
least 1 in 133 Americans. It's also being diagnosed in people as old as 70 who have eaten gluten safely all their lives.
"People aren't born with this. Something triggers it and with this dramatic rise in all ages, it must be something pervasive in the environment," says Joseph A. Murray, a gastroenterologist at the Mayo
Clinic in Rochester, Minn. One possible culprit: agricultural changes to wheat that have boosted its protein content.
Gluten sensitivity, also known as gluten intolerance, is much more vague.
Some experts think as many as 1 in 20 Americans may have some form of it, but there is no test or defined set of symptoms. The most common are IBS-like stomach problems, headaches, fatigue, numbness and
depression, but more than 100 symptoms have been loosely linked to gluten intake, which is why it has been so difficult to study. Peter Green, director of the Celiac Disease Center says that research into
gluten sensitivity today is roughly where celiac disease was 30 years ago.
In the new study, researchers compared blood samples and intestinal biopsies from 42 subjects with confirmed celiac disease, 26 with suspected gluten sensitivity and 39 healthy controls. Those with gluten
sensitivity didn't have the flattened villi, or the "leaky" intestinal walls seen in the subjects with celiac disease.
Their immune reactions were different, too. In the gluten-sensitive group, the response came from innate immunity, a primitive system with which the body sets up barriers to repel invaders. The subjects
with celiac disease rallied adaptive immunity, a more sophisticated system that develops specific cells to fight foreign bodies.
The findings still need to be replicated. How a reaction to gluten could cause such a wide range of symptoms also remains unproven. Dr. Fasano and other experts speculate that once immune cells are
mistakenly primed to attack gluten, they can migrate and spread inflammation, even to the brain.
Indeed, Marios Hadjivassiliou, a neurologist in Sheffield, England, says he found deposits of antibodies to gluten in autopsies and brain scans of some patients with ataxia, a condition of impaired balance. [see Primary Autoimmune Cerebellar Ataxia (PACA)]
Could such findings help explain why some parents of autistic children say their symptoms have improved — sometimes dramatically — when gluten was eliminated from their diets? To date, no scientific
studies have emerged to back up such reports.
Dr. Fasano hopes to eventually discover a biomarker specifically for gluten sensitivity. In the meantime, he and other experts recommend that anyone who thinks they have it be tested for celiac disease first.
For now, a gluten-free diet is the only treatment recommended for gluten sensitivity, though some may be able to tolerate small amounts, says Ms. Kupper.
"There's a lot more that needs to be done for people with gluten sensitivity," she says. "But at least we now recognize that it's real and that these people aren't crazy." [...]
Gluten-Free Diet: A Comprehensive Resource (Shelley Case, 2008; 2010)
Case Nutrition | 4 January 2010 | Trade Paperback Gluten-Free Diet: A Comprehensive Resource Guide
Formerly ISBN 1-897010-28-1
Revised and Expanded Edition
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About the Gluten-Free Diet
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