The gluten-free trend keeps growing. But is it all just hype? Does gluten sensitivity really exist? Are more people being diagnosed with celiac disease? Is modern wheat the problem or could it be genetic engineering? Here we unravel the facts.

This story was produced in collaboration with the Food & Environment Reporting Network, a non-profit investigative journalism organization.

Unraveling the Gluten-Free Trend

A few years ago, when I began writing a book about grains and bread, the first question I usually got when I mentioned the project was: "Why are so many people having problems with wheat?" In many ways, the question encapsulated the current anxiety around bread and wheat, which has gyrated from a source of sustenance for humanity into a toxic pariah.

Wheat-and the main protein it contains, gluten-has been cited as a cause of weight gain, "brain fog," skin rashes, joint pain, headaches, tiredness, allergies, gas, intestinal distress, irritable bowel syndrome, depression and, in the case of celiac disease-where the immune system goes haywire and attacks the body-even death. Yet wheat, which is found not only in bread and pasta, but also in beer and numerous processed foods, makes up one-fifth of all food eaten worldwide and is the ­number-one source of protein in developing countries. Humans have been eating wheat for around 10,000 years, starting with domestication of wild grasses in the Near East, at the dawn of agriculture.

With all the illnesses and ailments associated with wheat and gluten, it leads one to wonder: Could the human race have been so wrong about this staple food for so long? Or are the health concerns a figment of over­active imagination, propelled by the gluten-free trend?

Consumer data are pretty clear: around 22 percent of adults are trying to avoid gluten, creating an estimated $8.8 billion market that grew 63 percent between 2012 and 2014, according to market research firm Mintel. As many as 20 million Americans think gluten-free diets are healthier and around 13 million are giving up gluten to lose weight. Yet "the vast majority of individuals on gluten-free diets have no business being gluten-free, because, for them, there is no medical necessity," says Alessio Fasano, M.D., director of the Center for Celiac Research and Treatment at the MassGeneral Hospital for Children and an authority on the subject. He adds, "it's simply fashion." Jimmy Kimmel even poked fun at this trend on late-night TV, asking people on the street who were going gluten-free if they actually knew what gluten was. None could answer the question. It's a protein-actually composed of about 70 different glutenin and gliadin proteins which stretch and trap gas as dough rises, creating airy bread.

Compared with this lifestyle boom, the number of people who must avoid gluten for medical reasons is considerably smaller. An estimated 1 percent of all people have celiac disease, though only a small portion have actually been diagnosed and know they must steer clear of gluten. Another smaller group, about 0.4 percent of the population, suffer from sudden allergic reactions to ingesting wheat or breathing flour dust. Then there's a third group of "gluten-sensitive" people, who appear to have symptoms when they consume gluten that can't be explained by celiac disease or wheat allergy. Like celiac disease, the symptoms of gluten sensitivity are diverse and not confined to the gut. They include joint pain, muscle cramps, leg numbness, reflux, weight loss, chronic fatigue, depression and "brain fog"-a complaint that describes an inability to focus, and which can impair work and social life. The first and still imprecise studies on gluten sensitivity estimate that 0.6 to 6 percent of people suffer from it. This rudimentary understanding of the condition may help explain why so many people think they are gluten sensitive.

Is Gluten Sensitivity Real?

For a long time, "we were adamant that gluten reactions had to be related to celiac disease and if celiac disease was ruled out you had no business going gluten-free," Fasano says. But this "dogma," as he now calls it, began to erode under the number of patients-not only in his clinic but also in many others-reporting reactions to gluten but testing negative for celiac disease. While only two studies even mentioned this disorder as recently as 2000, it has since gained much wider acceptance, especially among those who specialize in celiac disease. A definition of gluten sensitivity was only proposed in 2012 and it has yet to appear in diagnostic manuals. As an editorial in the New England Journal of Medicine pointed out last fall, "researchers are just beginning to define this entity."

Researchers think gluten sensitivity involves a mis­firing of the innate immune system, a first line of defense against a foreign substance, like carpet-bombing the enemy with general inflammation. In celiac disease, gluten triggers a more precise response in genetically susceptible people: elite squads that are part of the adaptive immune system are marshaled for attack, but they end up targeting the cells of the intestinal wall, preventing the body from absorbing nutrients. With gluten sensitivity, people may suffer from gut or joint pain, headaches or other symptoms, but not exhibit any similar intestinal damage. "We know gluten sensitivity is not celiac disease. We know it's not an autoimmune reaction, but we do know there's an immune component," says Fasano. "And that's about as much as we know."

Because the research is at such an early stage, physicians don't have the diagnostic tools to detect gluten sensitivity. "We don't have a clear blood test or biomarker for people with gluten sensitivity," says Fasano. If patients improve when gluten is removed from the diet and then worsen when challenged with gluten again, they probably have gluten sensitivity-that is, if all other explanations are ruled out.

Could Some Carbs Be to Blame, Not Gluten?

Some researchers even prefer the term "nonceliac wheat sensitivity," because gluten, which makes up about 75 percent of the proteins in wheat, may not account for the wide range of reactions. Other (nongluten) wheat proteins can stimulate an immune reaction, such as gut inflammation, in laboratory tests. Even the carbohydrates in wheat may cause the kind of intestinal discomfort that people usually attribute to gluten.

Researchers in Australia, for example, have looked at the role of a group of carbohydrates called FODMAPs-the acronym for fermentable oligosaccharides, disaccharides, monosaccharides and polyols. These poorly absorbed carbs ferment in the gut and can lead to gas, bloating, abdominal pain, diarrhea or constipation, symptoms common among people with irritable bowel syndrome (IBS)-and also associated with gluten sensitivity. About a third of those with IBS tend to improve by avoiding wheat. So the question arose: Is gluten actually the cause of the digestive ills or could it be the carbs found in wheat, rye and barley? In other words, are people actually feeling better because they are also removing some FODMAPs when they go gluten-free?

A team led by Peter Gibson, M.D., at Monash University in Australia sought to answer that question by first looking at people with IBS who had found relief on gluten-free diets. These patients were in the wider universe of gluten-sensitive people because their apparent symptoms weren't explained by celiac disease or allergy. But rather than headache, or joint pain or the myriad other symptoms attributed to gluten, these patients' problems were in the gut.

To tease out whether gluten was really the problem, the patients were split into two groups: one group ate a muffin and two slices of bread with gluten every day for six weeks while the other group were given muffins and bread that were gluten-free. The result? The gluten-eating group had more gastrointestinal symptoms and tiredness than the gluten-free group, supporting the hypothesis that gluten was the culprit. When the study was published in 2011, it was the first that appeared to confirm the existence of nonceliac gluten sensitivity.

In a second study, the Monash researchers sought to confirm the result with a more rigorous study design. They modified the test so that each person would eat both the gluten-containing and the gluten-free food. But before that dietary test, participants were placed on a low-FODMAP diet for two weeks. Then, while still on a low-FODMAP diet, they ate the gluten-­containing diet, then the gluten-free one, with a break in between-a so-called cross-over study. That way the researchers could look at each individual's reaction to gluten while eating a low-FODMAP diet.

The result differed markedly from the first study: the participants were no worse-off consuming gluten than avoiding it. Indeed, the only significant improvement came when they went on the low-FODMAP diet before the gluten challenge began. "These people were already on a gluten-free diet, but for two weeks they went on a low-FODMAP diet and all had significant improvement in their symptoms"-measured by pain, bloating, stool consistency and tiredness-said Jessica Biesiekierski, Ph.D., lead author on the study and now a postdoctoral fellow at the University of Leuven in Belgium. The study concluded that gluten had no measurable impact on these IBS patients. In other words, they were not "gluten sensitive."

Subsequently, many articles appeared pointing to FODMAPs as the culprit in the symptoms people attribute to gluten. But even Biesiekierski says she gets ticked off when she reads that. "We never ever said nonceliac gluten sensitivity does not exist," she says. What they found was that these IBS patients did not have gluten sensitivity. But the study left open the possibility that gluten may be causing reactions for other patients-perhaps those who suffer from headaches or joint pain and not IBS.

For those who find avoiding gluten reduces intestinal distress, a breath test can quickly determine whether reducing fructans-the predominant FODMAP in wheat-might be what's actually helping. If fructans are the culprit, then you'd need to reduce or eliminate the long list of fructan-rich foods, which include apples, figs, watermelon, garlic, onions, cashews, chickpeas, baked beans, as well as wheat, barley and rye. But this low-FODMAP diet isn't usually permanent. After two to six weeks, a dietitian should assess the diet and help with gradually reintroducing foods to see which ones can and can't be tolerated.

Interestingly, another paper, published in 2013, also looked at the effect of gluten on patients with IBS. Unlike the Monash study, these patients were not following a gluten-free diet at the outset of the study. One group of patients was then put on a gluten-free diet. They ended up with fewer bouts of diarrhea than the group who continued to eat gluten-containing foods, suggesting that gluten was problematic after all.

Modern Causes for Modern Diseases

When it comes to gluten, speculation is rife about the cause of the recent rise in documented celiac disease and in the anecdotal reports of widespread gluten sensitivity. Perhaps wheat has been bred to contain more gluten? Or maybe wheat itself has changed and become more toxic with the advent of modern hybrid wheat breeding? Or perhaps, people speculate, genetically modified wheat is to blame for the epidemic of gluten-related problems?

Wheat is a complex plant, the result of three different species of grasses mating together, and its genome contains five times as much DNA as that of a human. Bread wheat arose around 10,000 years ago in the Near East, when domesticated emmer wheat (itself the result of two interbred species) pollinated with a third wild plant known as goat grass and created the new species. In other words, wheat itself is a hybrid.

Plant breeders assert that these ancient hybridizations set the genetics for modern plants. "It kind of created the chassis of the car, and since then we've been tinkering with the engine and other parts, but we can't do much to change the basic structure," says Brett Carver, Ph.D., a wheat breeder and professor at Oklahoma State University. Although the technology is being tested in the field, none of the wheat we currently consume has been produced with genetic engineering because genetically modified (GMO) wheat has not been approved for sale anywhere in the world.

Some critics say modern wheat plants, which became popular in the 1960s, are to blame for rising health issues related to gluten. This line of thinking blames plant breeding, which was aimed at increasing wheat yields and boosting food supplies, especially in the developing world. The resulting less-diverse species of wheat, critics assert, had increased or altered gluten content. While diversity has narrowed as breeders focus on particular strains of wheat, one recent study found that modern varieties of wheat have similar amounts of protein to those grown in the Great Plains before World War II (and protein tracks gluten levels closely).

A 2010 study found modern wheat contains higher amounts of the specific "triggers" in gluten that can lead to celiac disease. Although this Dutch study has often been cited to argue that ancient wheat presents fewer problems for gluten­sensitive people, it only looked at celiac disease. These celiac disease triggers are located on a string of molecules that make up gluten, but those that may prompt gluten sensitivity may reside on another part of gluten entirely-it's unclear since they haven't yet been identified. Significantly, the study did not find a single variety, modern or ancient, that was free of celiac-triggering proteins.

Other theories about the rise of gluten sensitivity point toward quickly made yeast breads that took hold with industrial breadmaking. Sourdough fermentation can degrade gluten, but because this bread-baking method takes several hours or days and can be fickle, it was largely supplanted by commercial yeast until artisan bakers recently revived it. Researchers have taken the sourdough method quite far, making gluten-free sourdough wheat breads that are now being tested on celiac patients in Italy. This gluten-free bread is expected to hit the Italian market this year, says Marco Gobbetti, Ph.D., a microbiologist at the University of Bari in Italy, who has spearheaded these studies. While some people report having an easier time digesting sourdough breads, the wild yeast and bacteria in sourdough cultures are highly diverse and differ from one bakery to another and may not have the same effects on gluten. Gobbetti's specific strain was isolated and cultured in a laboratory, not on a kitchen counter.

Another theory is that we're actually consuming more gluten because vital wheat gluten is used in so many processed foods-from candy and cold cuts to soy sauce and soups. It's used to strengthen doughs, especially in whole-grain breads, and to stabilize and thicken other foods. A USDA researcher recently estimated that U.S. consumption of vital wheat gluten-which was only introduced in the mid-20th century-may have tripled in the last 40 years. More exposure to gluten might lead to a higher incidence of gluten-related diseases-a plausible explanation, but still speculative.

Then there is the "hygiene hypothesis," which posits that the modern world's desire for cleanliness has compromised the ability of the immune system to recognize true threats. Once the immune system loses the capacity to tell friend from foe, it misfires. In this way, gluten sensitivity may be part of a larger trend that the hygiene hypothesis seeks to explain: rising rates of allergies and immune-related disorders, such as celiac disease and type 1 diabetes.

How to Know if Gluten-Free Is Right for You

Because physicians don't yet have a way to test for gluten sensitivity, doctors have to rely on what patients are telling them-and if patients report feeling better by avoiding gluten, most doctors see no reason to challenge them if explanations like celiac disease and wheat allergy (which can be tested for) are ruled out. "I never try and talk people out of being on a gluten-free diet," says Peter H.R. Green, M.D., director of the Celiac Disease Center at Columbia University Medical Center, "but if they are going to be on it, we try and make sure it's a healthy one."

For a physician, this isn't an unreasonable approach. While the first account of celiac disease appeared in ancient Greece in the first century, it wasn't until after World War II that a Dutch physician proved that gluten was the cause. It took another few decades to unravel the mechanism by which gluten triggers the immune system and longer still to develop precise tools to diagnose celiac disease. In other words, the identification and treatment of the disease long preceded an understanding of the way it works, which is often the case with medicine. With nonceliac gluten sensitivity, "we're about where we were 20 years ago with celiac disease," Fasano says.

That said, the extreme of labeling gluten as a toxin for the human race only muddies the waters. Green, for one, has had patients report they are avoiding gluten at the advice of a life coach or psychiatrist-without being tested for any wheat-related illness. "So it's a bit out of control," he says. With wheat providing one-fifth of the world's calories, and even more in food-stressed regions of the world, Green thinks "you need good evidence" before you start telling people to avoid the staple altogether. And right now, that evidence doesn't exist.

Samuel Fromartz is editor-in-chief of the Food & Environment Reporting Network, an investigative journalism nonprofit, which produced this article in collaboration with EatingWell. He is also author of  "In Search of the Perfect Loaf: A Home Baker's Odyssey" (Viking).

March / April 2015