As the gluten-free fad presses on amongst consumers, a new study shows that only a minority of patients diagnosed with non-celiac gluten sensitivity experience adverse symptoms in response to gluten intake.

The research, spearheaded by a team of gastroenterologists based out of the University and Spedali Civili of Brescia in Italy, joins the growing ranks of studies casting doubt on the prevalence and even the existence of the condition.

Non-celiac gluten sensitivity (NCGS) is diagnosed in patients confirmed not to have celiac disease but who still experience symptoms like bloating, diarrhea, headache, and abdominal pain after eating gluten-containing foods. Wide-ranging estimates have placed its prevalence between 0.6 and six percent of the population, meaning that as few as two million to as many as twenty million Americans could be affected. The condition's existence remains in doubt, however, as no discernible biomarkers have been found. The only evidence we have is sufferers' self-reported symptoms.

In the new study, published to the journal Alimentary Pharmacology & Therapeutics, researchers placed the diagnosis of NCGS under rigorous scrutiny. Thirty-five subjects diagnosed with NCGS who maintained a strict gluten-free diet for six months prior took part in a multi-week gluten challenge. As the authors described:

The challenges comprised gluten-containing and gluten-free flours. These were dispensed in sealed sachets labelled A and B. The participants and the investigators were blind to the contents of the sachets... Each sachet contained 10 grams of flour, and instructions were given to the participants to sprinkle the contents of the sachet over pasta or soup; one sachet to be consumed each day for 10 consecutive days. This was followed by a 14-day washout period, and then by a further 10-day challenge, when participants were crossed over to receive the other flour.

Participants were instructed to rate their symptoms of pain, reflux, indigestion, diarrhea, and constipation on a scale of 1 (no discomfort) to 7 (very severe discomfort) throughout the trial and to write down any other adverse symptoms. At the end of the challenges, participants would be asked to guess, based on their symptoms, which of the flours contained gluten. If they guessed correctly, they would be classified as having NCGS.

At the conclusion of the trial, just twelve of the 35 subjects correctly identified the gluten-containing flour and reported experiencing worse symptoms during the challenge involving gluten. Of the remaining subjects, 17 identified the gluten-free flour as causing symptoms and six reported no adverse symptoms during the trial whatsoever. (Below: The figure shows the symptom scores for the patients who correctly identified the flour containing gluten.)

Also of note, most subjects tended to experience very mild symptoms throughout the trial. On average, participants rated the majority of gastrointestinal symptoms at 3 or lower on the aforementioned scale.

The study was plagued by the usual methodological limitations of nutrition research. Symptoms were self-reported, the sample size was somewhat small, and the researchers relied on subjects to carry out the challenges faithfully. It is also somewhat strange that the researchers would consider correctly identifying the gluten-containing flour to be evidence of NCGS, as it seems logical that fifty percent of subjects would guess the flour by pure chance.

Ultimately, what the study shows, in line with previous scientific research, is that the majority of people who believe they are sensitive to gluten in fact are not, and if adverse symptoms do develop they may be attributed to the nocebo effect or the presence of hard-to-digest carbohydrates called FODMAPS.

"Our study has shown that gluten challenge leads to a recurrence of symptoms in only a third of patients fulfilling the recognised diagnostic criteria for the clinical diagnosis of NCGS," the researchers concluded. "Consequently, NCGS is likely to be the correct diagnosis in only a minority of those who do not have celiac disease, but whom themselves choose to follow a gluten-free diet."

Source: Zanini, B., Baschè, R., Ferraresi, A., Ricci, C., Lanzarotto, F., Marullo, M., Villanacci, V., Hidalgo, A. and Lanzini, A. (2015), Randomised clinical study: gluten challenge induces symptom recurrence in only a minority of patients who meet clinical criteria for non-coeliac gluten sensitivity. Alimentary Pharmacology & Therapeutics. doi: 10.1111/apt.13372

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