The internet has been ablaze with testimonials and dire warnings regarding what many see as a psychological and physical assault on the well being of mind and body by what could be for some as seemingly inconsequential a thing as a crust of bread. This "new" condition has been termed "nonceliac gluten sensitivity."

Unfortunately, the management of patients who experience wheat- or gluten-dependent symptoms in the absence of biopsy-proven celiac disease is a major challenge to health care providers of many different specialties, as this gluten sensitivity has protean manifestations:
• Intestinal symptoms such as bloating and diarrhea.
• Neurological symptoms such as headache and gait abnormalities.
• Psychological disorders such as depression, and an increase in suicide attempts.

These manifestations improve or disappear after gluten withdrawal.

But the concept of nonceliac gluten sensitivity is not new: A double-blind, crossover trial reported over 30 years ago demonstrated that 6 of 8 adult patients who experienced abdominal pain and chronic diarrhea were gluten-sensitive in the absence of celiac disease. Alas, further systematic research has not been very robust; one can imagine the researcher's nightmare of trying to objectively demonstrate nonceliac gluten sensitivity. What would they be looking for? However, that being said, a 2011 study published in the "American Journal of Gastroenterology" did show that gluten worsened functional symptoms in patients who did not have celiac disease.

Perhaps in the tradition of seeking the reason for (abdominal) pain that cannot otherwise be explained, the world wide web has served to resurrect the gluten sensitivity issue-even as science has tried to avoid it. The result has been a huge increase in the number of patients, organizations, physicians, and manufacturers of food products advocating a gluten-free diet. One does not have to only frequent a health food store to appreciate the big business gluten-free goodies have become. Likewise, one does not have to be a computer geek to become educated about gluten sensitivity: A 2008 article in USA Today estimated that "15% to 25% of consumers want gluten-free foods." And a Washington Post article in 2011 declared that "17 million Americans are gluten-sensitive."

Gluten sensitivity has gone mainstream.

Gluten is a component of the complex protein mixture contained in wheat flour. Because of this, many experts believe that gluten cannot be considered the only culprit responsible for the abdominal pain, diarrhea and other neurological and psychological complaints seen in individuals who eat bread and pasta. In fact, other proteins such as certain enzyme inhibitors, or even yeast, may be involved with allergic reactions to wheat flour. Interestingly, carbohydrates may play a role, as some of those contained in bread and pasta have been shown to escape absorption in the intestine, resulting in abdominal pain and diarrhea. Thus, starch absorption defects may represent part or all of the gastrointestinal distress experienced by otherwise healthy people who eat wheat flour.

This brings us to a consideration of the "nocebo effect." In medicine, a nocebo (Latin for "I will harm", versus the Latin for placebo-"I will please") reaction or response refers to harmful, unpleasant, or undesirable effects a subject manifests after receiving an inert dummy drug or substance. Nocebo responses are not chemically generated and are due only to the subject's pessimistic belief and expectation that the inert substance will produce negative consequences.

In other words, nonceliac gluten sensitivity may be the result of the nocebo effect of wheat or gluten ingestion. A study of self-reported lactose intolerance published in the "New England Journal of Medicine" in 1995 found this phenomenon to be a powerful force in patients who believe themselves to be food-sensitive.

Taking mind and body into consideration, and in the interest of forestalling the possibly unjustified transformation of gluten preoccupation to an urban dogma that gluten is toxic for most living beings, more clinical research is needed---research that addresses the psychological and the physical ramifications of gluten sensitivity, and the "belief' in gluten sensitivity.

The last thing society needs is a possible health problem becoming a social problem, resulting in a mental health problem.

In the meantime, probably the best diagnostic approach to the individual patient would be to use an unblinded oral gluten challenge test for those individuals who manifest objective gluten-dependent symptoms such as rash or episodes of vomiting or diarrhea; and for those who only experience subjective gluten-dependent symptoms such as headache or abdominal pain, a single-blind crossover "study" should be performed, whereby patients but not physicians are blinded as to whether the patient is receiving the respective placebo and gluten-containing substance.

Death and taxes may be certain, but the jury is still out on nonceliac gluten sensitivity, no matter what the internet may say.

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