Non-celiac gluten sensitivity

Non-celiac gluten intolerance, gluten sensitivity

Non-celiac gluten sensitivity


It is increasingly accepted that gluten-containing food may cause symptoms in a relatively sizeable proportion of individuals with functional gastrointestinal disorders, such as Irritable Bowel Syndrome (IBS), despite the thorough exclusion of celiac’s disease using today’s best diagnostic tools. Gluten is a storage protein in cereal, especially in wheat, barley and rye that causes celiac’s disease in genetically predisposed individuals. The underlying mechanisms by which gluten induces symptoms in non-celiac gluten sensitivity remain unclear. Several studies suggest that gut dysfunction may be due to subtle changes in mucosal immunity, permeability or neuromuscular and epithelial gastrointestinal function. However, these data remain to be confirmed in larger human studies.

A current definition of gluten sensitivity is: Intestinal and/or extra-intestinal symptoms induced by the ingestion of gluten that resolve once the gluten-containing foodstuff is eliminated from the diet, when celiac’s disease and wheat allergy have been ruled out. However, there is increasing evidence that gluten may not be the (sole) cause of gluten sensitivity.

Potential candidates are wheat amylase-trypsin inhibitors (ATI’s: proteins that protect plants against wheat parasites) and fructans (fermentable chains of fructose molecules).

Frequency in population and natural history

Given the uncertainty of the underlying cause and the absence of an exact test, the frequency of gluten sensitivity cannot be determined. It should be noted that very large numbers of individuals currently consume gluten-free products (e.g. over 100 million in USA), in many cases without substantiation of a need or clear benefit. Figures between 0.55% and 5% are quoted.


There is considerable overlap with symptoms associated with IBS, such as nausea, abdominal cramps or pain, bloating, abnormal bowel habit (diarrhea or constipation),, as well as extra-intestinal symptoms, such as concentration problems, “mental fog”, headache, fatigue, joint or muscle pain, numbness of legs or arms, dermatitis (eczema or skin rash), anemia and depression.

The symptoms resemble those of Irritable Bowel Syndrome (IBS) as well as celiac’s disease.

The association with autism, schizophrenia, allergies and autoimmune disorders is currently contentious, but in some cases a gluten-free diet has alleviated symptoms.

Testing and diagnosis

There is currently no specific clinical test for non-celiac’s gluten sensitivity. The detailed exclusion of celiac’s disease and wheat allergy is important.

Recent studies are using blinded and placebo-controlled exposition and exclusion study designs. However, the control groups are difficult to design due to confounding factors (fructans, exclusion of celiac’s disease, ATI’s and other potential proteins).


Given the uncertainty of the underlying cause and the absence of an exact test, no current guidelines exist. The potentially detrimental effect of adhering to a restrictive diet without an absolute need should be borne in mind.