An article by William F. Balistreri
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. 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 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. 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.
Nonceliac gluten sensitivity (NCGS) is the newly minted term used to describe a clinical disorder related to ingestion of gluten or gluten-containing cereals. Lebwohl and colleagues suggest that a more accurate term for this condition is simply “people who avoid gluten.”
The postulated entity of NCGS has raised considerable interest and debate in both the medical and nonmedical literature.
A report by Fasano and colleagues emphasized that although there is clearly a “fad component” to NCGS, there is increasing evidence for its existence as a true clinical entity. However, much of the published information on NCGS was obtained from patients self-reported to be gluten-sensitive, calling into question data regarding the high prevalence, activation of the innate immunity as the presumed pathogenic mechanism, specific mucosal cytokine profile, and the clinical spectrum.
Fasano and colleagues emphasized a need for better understanding of the role of gluten and wheat in irritable bowel syndrome (IBS), chronic fatigue syndrome, and autoimmunity, with precise nomenclature and definitions. In the absence of intestinal injury, specific antibodies, or any other biomarker, there is a clear need for an optimal diagnostic algorithm and consensus-based diagnostic criteria.
Differentiating between celiac disease, NCGS, and other wheat-related disorders can be challenging, but it is important for appropriate management. As stated in a recent editorial, it is counterproductive to debate whether NCGS is “real”; the patients are real and are seeking care.
The current clinical approach involves ruling out celiac disease and wheat allergy, testing for additional food intolerances or gastrointestinal conditions, and providing the latest data on the benefit/unintended consequences of gluten avoidance and these evolving entities. It is also important to inform patients and their families about what is not known. It may also be effective to individualize the recommended dietary strategy by eliminating certain components of the FODMAP class, wheat products, and/or gluten sequentially.
Because there is no specific biomarker for NCGS, the diagnosis is “confirmed” by dietary elimination, followed by double-blind, placebo-controlled gluten-based re-challenges. This is a cumbersome, time-consuming, and difficult-to-access clinical approach. Even with this information at hand, the diagnosis of NCGS may remain unclear, raising the question of whether the salutary effects of gluten withdrawal are specifically attributed to the gluten-protein per se or to nongluten components such as fermentable carbohydrates and amylase-trypsin inhibitors.
Khabbani and colleagues reviewed records from 238 patients who presented for the evaluation of symptoms responsive to gluten restriction without prior exclusion of celiac disease. Of these study subjects, 42% had celiac disease and 52% had NCGS; the remainder had an indeterminate diagnosis. The majority (67%) of subjects with celiac disease presented with symptoms of malabsorption, compared with 25% of the NCGS subjects. In addition, those with celiac disease were significantly more likely to have a family history of celiac disease, personal history of autoimmune diseases, or nutrient deficiencies.
On the basis of these findings, the authors proposed a diagnostic algorithm to differentiate celiac disease from NCGS. They state that subjects with negative celiac serologies (IgA tTG or IgA/IgG DGP) ingesting a gluten-containing diet are unlikely to have celiac disease. Those with negative serology who also lack clinical evidence of malabsorption and risk factors for celiac disease are highly likely to have NCGS and may not require further testing. Those with equivocal serology should undergo HLA typing to determine the need for biopsy.
Guandalini and colleagues proposed assessment of the levels of gamma delta T-cell receptors in intraepithelial lymphocytes (which are specific for celiac disease) or detection of IgA anti-tissue transglutaminase antibody deposits in intestinal mucosa in order to more clearly exclude celiac disease in problematic cases.