Gluten Sensitivity

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.

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.

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."