William F. Balistreri, MD

February 04, 2016

The question of whether to adopt a gluten-free diet is especially timely, given its impressive increase in popularity over the past decade. In fact, gluten avoidance has become the most popular dietary trend in the United States, with approximately 100 million Americans consuming gluten-free products last year.

Presently, there are at least three proposed clinical syndromes related to gluten ingestion: celiac disease, an autoimmune-mediated disorder; wheat allergy, an immunoglobulin E (IgE)-mediated entity; and gluten sensitivity, in which celiac disease and wheat allergy have been ruled out. Therefore, the decision to “go gluten-free” is either mandatory or elective; a gluten-free diet is mandatory for those individuals with appropriately diagnosed celiac disease and possibly wheat allergy. However, many individuals elect to follow a gluten-free diet because of a presumed sensitivity. While approximately 1% of the population are believed to have celiac disease, it is estimated that as many as 60% of Americans believe that a gluten-free diet will improve their physical and/or mental health.[1-4] It is their choice to follow a gluten-free diet in the hopes of improving digestion and bolstering their immune system, while also enabling enhanced performance and weight loss.

This belief has been fostered by the testimony of celebrities and athletes who attribute their success and well-being to adherence to a gluten-free diet. A survey done by Lis and colleagues[5] of 910 world-class athletes and Olympic medalists found that 41% followed a gluten-free diet, the majority because of a self-diagnosis of “sensitivity to gluten” and perceived ergogenic or health benefits. The same authors investigated the effects of a gluten-free diet on exercise performance, gastrointestinal symptoms, perceived well-being, intestinal injury, and inflammatory responses in nonceliac endurance athletes.[6] The short-term gluten restriction had no overall beneficial effect on any of these outcomes. In addition, numerous books and websites cater to this gluten-free phenomenon. Claims have even been made that gluten can be harmful to all of us.

The appeal of a gluten-free diet has become big business, leading to greater gluten-free product availability and a wider variety of dietary options. The market for gluten-free foods continues to expand and is estimated to have reached over $4 billion in retail sales in the past year. However, there are barriers to going gluten-free, including the cost and long-term safety of gluten-free foods and the potential for gluten cross-contamination of products. In addition, a gluten-free diet could present social restrictions, possibly leading to nonadherence.[7-9] Continue Reading

Nonceliac Gluten Sensitivity

Nonceliac gluten sensitivity (NCGS) is the newly minted term used to describe a clinical disorder related to ingestion of gluten or gluten-containing cereals.[8-13] Lebwohl and colleagues[14] suggest that a more accurate term for this condition is simply “people who avoid gluten.”

Clinical Spectrum

NCGS has largely been characterized by a series of self-reported gastrointestinal symptoms such as abdominal pain, gastroesophageal reflux, gas/bloating, nausea, diarrhea, and/or constipation.[15] However, a wide variety of nongastrointestinal symptoms has also been reported, including headache, fatigue, “foggy mind,” anxiety, depression, muscle aches, and skin rashes. A similar spectrum of symptoms has been reported in children.[16,17] Aziz and Hadjivassiliou[9] demonstrated that in patients with NCGS, gluten is independently associated with depression, which might share pathophysiologic mechanisms with other neurologic manifestations observed in gluten-related disorders, such as ataxia and encephalopathy.

Working Definition

A recent report by Fasano and colleagues[8] reviewed the current understanding of NCGS and outlined steps to dissipate some of the confusion related to this disorder. They propose a working definition as follows: “a clinical entity induced by ingestion of gluten leading to intestinal and/or extraintestinal symptoms that resolve once gluten is eliminated.” This definition requires that celiac disease and wheat allergy have been ruled out. They further propose that NCGS is associated with prevalent gluten-induced activation of innate—rather than adaptive—immune responses in the absence of detectable changes and mucosal barrier function. Gluten sensitivity was similarly defined by an international panel as the occurrence of intestinal and extraintestinal symptoms related to the ingestion of gluten-containing food in subjects without celiac disease or wheat allergy.[18-21]


Aziz and colleagues conducted a survey in order to estimate the prevalence of self-reported NCGS in the general population and the frequency of adherence to a gluten-free diet outside of celiac disease.[1,22] They determined that 13% of the population (79% female; mean age, 39.5 years) self-reported gluten sensitivity, only 0.8% of whom had a valid diagnosis of celiac disease. During investigation of another cohort of 200 patients with presumed gluten sensitivity (84% female; mean age, 39.6 years), 7% were found to have celiac disease and 93% to have NCGS.[1,22] All patients with celiac disease were HLA (human leucocyte antigen) DQ2 or DQ8 positive compared with 53% of the subjects with NCGS. Nutritional deficiencies, autoimmune disorders (23% vs 10%), and a lower mean body mass index were significantly associated with celiac disease compared with NCGS.

In a survey of more than 1000 Australians, 7% reported adverse effects when ingesting wheat products, although the majority had not undergone formal assessment for celiac disease or wheat allergy.[23]

Biesiekierski and colleagues[15] also surveyed a series of adults who believed that they had NCGS. They learned that a gluten-free diet was most commonly self-initiated among respondents (44%) and was less often prescribed by alternative health professionals (21%), dietitians (19%), or general practitioners (16%). Initiation of a gluten-free diet without adequate exclusion of celiac disease was common; no investigations to rule out celiac disease had been performed in 15% of respondents. In 25%, symptoms are poorly controlled despite gluten avoidance.

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