Gluten, Revisited: The Latest Facts on a Popular Culprit

A quick look at your grocery store shelves or the menus of your favorite restaurants shows that "going gluten-free" is a defining dietary trend that is here to stay. And with over 100 million Americans consuming gluten-free products, it may just be time to revisit what we do and don't know about the gluten-free diet (GFD).

Who Really Benefits?

Two rationales are generally behind the adoption of a GFD. For those with the autoimmune-mediated disorder celiac disease or an immunoglobulin E–mediated wheat allergy, this diet isn't a choice so much as it is a mandatory prescription. However, many people elect to follow a GFD because of presumed non-celiac gluten sensitivity. They do so in hopes of relieving gastrointestinal (GI) symptoms such as abdominal pain, bloating, and gastroesophageal reflux disease, as well as a variety of non-GI ailments. They may also hope that adhering to a GFD will help them meet health goals like losing weight, attaining "stronger immune systems," or enhancing athletic or overall performance.^[1,2,3] Studies suggest, however, that any perceived post-GFD clinical improvement in this group may not be directly attributable to the removal of gluten.^[1,4] Instead, it is probably due to a placebo effect, collateral elimination of the non-gluten components of wheat, or reactivity to "modern wheat," which has been described by some as the source of the rising incidence in both celiac disease and non-celiac gluten sensitivity.^[1,2,3,4,5]

A Big Business With a Potential Downside

The sustained popularity of this diet has had a net positive effect.

The lives of individuals who need to avoid gluten have been made significantly easier by the wider availability of gluten-free products, clearer labeling identifying products with or without gluten, and a heightened awareness of celiac disease within the culture.^[6,7] There are other positive health and lifestyle effects to going "gluten free." For example, adopting this diet means reducing the intake of ultra-processed foods and ingesting more whole foods. This, in turn, can lead to an intake of more fruits and vegetables, fewer calories, and fewer fast foods. On the other hand, it may lead to nutritional inadequacies and other unintended dietary consequences.^[6,7,8] To avoid gluten, an individual must ingest foods that contain a greater density of simple carbohydrates and saturated fats, which may contribute to obesity and metabolic syndrome. It is therefore advised that those adopting a GFD seek the input of an experienced dietician to avoid nutrient deficiencies (eg, fiber, calcium, B vitamins, folate, iron).^[6,7]

But "going gluten-free" is not for everyone.

If you don't have a medical need, then there is little to indicate that you will benefit much from this diet. As Reilly wrote in an overview of the topic, "There are no data to support the theory of an intrinsically toxic property of gluten for otherwise-healthy and asymptomatic (individuals)." There is also no evidence that habitual gluten ingestion directly contributes to cardiovascular disease, type 2 diabetes, or metabolic syndrome.

Further evidence comes from a 2019 study from Croall and colleagues, who conducted a double-blind randomized trial in which healthy adults received flour sachets containing either organic gluten (14 g) or a gluten-free blend of rice, potato, and tapioca. Both groups were instructed to take their flour sachets twice a day along with a GFD. The group receiving gluten did not experience any increase in GI symptoms or fatigue compared with the placebo group. Granted, this was short-duration study (only 2 weeks) in a small sample size, but it suggests once again that a GFD is unlikely to confer benefits to otherwise healthy individuals.

What's the Problem With 'Modern' Wheat? Probably Nothing

In the early 1940s, efforts were made to substantially increase agricultural production of wheat to meet the demands of a growing population and to combat famine. By the end of the 20th century, global wheat output had expanded fivefold. These initiatives were successful thanks to the application of sophisticated hybridization techniques (notably, this did not entail genetic modification). These intensive selection and breeding methods produced new strains of a modern hybrid wheat that were superior to older varieties, growing in both optimum and harsh conditions (eg, reduced amounts of fertilizers, fungicides, and water). For example, 20th century horticultural activities in Italy improved wheat gluten quality, increasing its strength while lowering its allergenic potential.

Thus, ancient wheat disappeared from the human diet and old wheat varieties were replaced by their superior modern versions.^[9,10,11] The hardiest, highest-yielding strains became a base for human foods despite a lack of animal or human safety testing. Some have claimed that the increase in gluten-related disorders can be linked to the historical transition to modern wheat, although such an association remains purely conjectural.^[9,10]

Several studies have attempted to dispel the myth that the increased prevalence of celiac disease is due to modern breeding practices that have changed wheat protein chemistry over the years, resulting in its being more antigenic than historical wheat. Prandi and colleagues analyzed different modern and old wheat varieties and concluded that the latter group produced a higher quantity of peptides containing immunogenic and toxic sequences. Spectrophotometric analysis of gluten protein contents (gliadins and glutenins) documented that ancient wheat species (einkorn, emmer, and spelt) had higher protein and gluten contents than modern wheat. After surveying data from the 20th and 21st centuries, Kasarda concluded that the gluten content in wheat has not increased. Malalgoda and colleagues examined 30 varieties of wheat produced in North Dakota from 1910 to 2013 and determined that the amount of troublesome α-gliadin epitopes had not changed over this 103-year period.

Considering that the average consumption of gluten is rising, including gluten that is added as an isolated ingredient in many processed foods, researchers have sought to define the role of other factors responsible for the rise in "gluten sensitivity." Modern wheat has been bred to contain proteins that increase pest resistance, thereby reducing environmental exposure to pesticides. These components of wheat—amylase-trypsin inhibitors—have been postulated to be triggers of non-celiac gluten sensitivity, although this theory awaits confirmation.

The Bottom Line

Our dietary habits influence our immune system, much as our hygienic habits have been linked to an increase in allergies and autoimmune disorders. This opens the possibility that a variety of factors are contributing to the perceived rise in gluten-related disorders, from our changing microbiome to a host of environmental exposures such as antibiotics, drugs, and chemicals. Future investigations will need to clarify the actual impact of these potential contributors.

It does seem clear, though, that the "rise" in celiac disease and non-celiac gluten sensitivity is probably not due to an increase in the gluten content of new varieties of wheat generated via modern production. There seems to be little in the way of health-related differences between ancient and modern wheats to justify this concern. But given the continued popularity of going gluten-free, it also appears clear that folks will be hashing out this debate for years to come.

William F. Balistreri, MD, is the Dorothy M. M. Kersten Professor of Pediatrics; director emeritus, Pediatric Liver Care Center; medical director emeritus, Liver Transplantation; and professor, University of Cincinnati College of Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center. He has served as director of the Division of Gastroenterology, Hepatology and Nutrition at Cincinnati Children's for 25 years, and frequently covers nutrition-related topics for Medscape. Dr Balistreri has been the editor-in-chief of several journals and textbooks, and became the first pediatrician to act as president of the American Association for the Study of Liver Diseases. In his spare time, he coaches youth lacrosse.

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