Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge

Abstract

Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS.

Gluten Sensitivity Biomarkers in Menière's Disease: Is It a Gluten Related Disorder?

“…[8] Our data confirm the ethiopathogenetic role of immune response in MD, in agreement with other recent observations. [25,26,27] and our previous observation of a gluten immune reactivity in MD patients. [17,18] The association between NCGS and MD should be supported by dietary exclusions and challenges: symptoms improve or disappear upon gluten withdrawal, while they recur if gluten is reintroduced in the diet.…”

Pathophysiology of Functional Gastrointestinal Disorders: A Holistic Overview

“…Some IBS and FD patients, without evidence for celiac disease based on serological markers and histology, experience substantial improvement in symptoms upon withdrawal of gluten from their diet. In a multi-center double-blind placebo-controlled trial, 140 patients with functional GI symptoms were randomized to a strict 3-week gluten-free diet (GFD) [22]. Responders to GFD were asked to continue with the diet, but were re-challenged with gluten or placebo in a double-blind manner.…”

Dietary Triggers in Irritable Bowel Syndrome: Is There a Role for Gluten?

“…45 Although unselected IBS patients display clinical improvement after wheat withdrawal, only a proportion may truly reflect underlying gluten sensitivity (Table 1). [46][47][48][49][50][51][52][53][54][55][56] The absence of specific biomarkers and the great proportion of patients with placebo effect observed in IBS trials, are 2 barriers for identifying the specific role of wheat components in generating IBS symptoms. Therefore, double-blind-placebo-controlled-crossover (DBPCC) trials are a reliable way to establish whether wheat and its fractions are involved in IBS symptom induction.…”

“…48 In a second trial from the same group, 51 IBS patients that responded to a gluten-free diet were challenged with low dose of gluten (2 g/day), high dose of gluten (16 g 54 The results showed that pure gluten ingestion induced recurrence of a variety of symptoms including, bloating, abdominal pain, foggy mind, aphthous stomatitis, headache and depression, but not in all of NCGS patients. Two recent DBPCC trials 55,56 performed in IBS patients self-diagnosed as "gluten/wheat sensitive" strongly suggested that gluten/wheat was responsible for symptom generation in up to one-third of IBS patients. Overall the results indicated that gluten and other wheat proteins cause symptoms in the absence of celiac disease in a subset of the IBS population ( Table 2).…”