A Clinical Update

Nonceliac Gluten Sensitivity—Is it Really the Gluten?

Bernadette Capili, PhD, NP-C; Michelle Chang, MS; Joyce K. Anastasi, PhD, DrNP


Journal for Nurse Practitioners. 2014;10(9):666-673. 

In This Article

Nonceliac Gluten or Wheat Sensitivity: Is it the Gluten or the Wheat?

For individuals with NCGS, it is not entirely clear whether gluten is the sole responsible agent, as wheat contains other components that may induce symptoms.[21] Gluten is the main storage protein contained within the germ of wheat grains, which provides the elasticity in dough. Gluten is a complex mixture of proteins, mainly gliadin and glutenin. Proteins similar to gliadin found in wheat exist as secalin in rye and hordein in barley, and are collectively referred to as "gluten."[22] Gliadin binds to CXCR3 (a chemoreceptor) and leads to MyD88-dependent zonulin (protein that modulates intestinal permeability) release and increased intestinal permeability.[23] One recent study showed that gliadin did not induce any mucosal inflammation in patients with NCGS.[24]

Gluten is found mainly in foods, yet it can also be found in many commercially available food products (used as a protein filler). It may also be hidden in modified food starch, preservatives, and stabilizers made with wheat (Table 2). Gluten may also be found in everyday and unexpected products, such as medicines, vitamins, and lip balms.[6] Even products specifically targeted to dietary treatment of CD may contain small amounts of gluten proteins, either because of cross-contamination or because of the presence of wheat starch as a major ingredient.[25]

Although the term "nonceliac gluten sensitivity" is used in the current literature, it may be possible that nongluten proteins of wheat are partially, or wholly, responsible for the associated symptoms.[21,26] Nongluten proteins, such as wheat amylase trypsin inhibitors, which are enriched in wheat and other related cereals, may trigger the innate immune response and induce intestinal inflammation.[27] The lectin, wheat germ agglutinin, may also have pro-inflammatory effects and increase intestinal permeability.[28] Hence, the term "nonceliac wheat sensitivity" has also been suggested and some researchers hypothesized that patients may actually have a non–IgE-mediated food allergy.[26,29] The lay press has focused on possible theories of modern wheat strains and hybrids, although scientific evidence is lacking, and this remains a controversial topic.[30] Currently, there is no genetically modified wheat commercially grown or approved in the US.

Another possibility is a family of poorly absorbed dietary short-chain carbohydrates known as FODMAPs (fermentable oligo-, di-, and monosaccharides and polyols). FODMAPs are found in a variety of foods, including those containing lactose, fructose, fructans, galactans, and polyols (sorbitol, mannitol, and xylitol). Wheat and rye are common foods high in FODMAPs, as are milk, some fruits (eg, apples and watermelons), vegetables (eg, onions, garlic, and asparagus), and legumes (eg, lentils and chickpeas). FODMAPs are osmotic and, with their rapid fermentability, can lead to excessive fluid and gas accumulation and cause distention of the intestine, leading to functional GI symptoms.[31] Examples of low FODMAP food choices include almond and rice milk (instead of high FODMAP cow, sheep, and goat milk) or rice, oats, and quinoa (instead of wheat or rye). A low FODMAP diet is strict to follow and not intended to be a prolonged diet plan. It is best done with the help of an experienced dietitian as there is no data on nutritional adequacy or long-term consequences. The concept that FODMAPS may alter the intestinal microbiota composition has been suggested, but this remains to be determined.[32,33]

Low FODMAP diets for patients with irritable bowel syndrome have been associated with improvements in abdominal pain, bloating, gas, and diarrhea.[34,35,36] Reduced intake of foods with high FODMAPs may hold potential for those with similar GI symptoms, including NCGS. A recent study in patients with self-reported NCGS showed that GI symptoms consistently and significantly improved during reduced FODMAP intake, and there was no evidence of effects of gluten in patients with NCGS on a low FODMAP diet.[37]