Prevalence of Non-Celiac Gluten Sensitivity in Patients with Refractory Functional Dyspepsia: a Randomized Double-blind Placebo Controlled Trial

Abstract

Refractory functional dyspepsia (RFD) is characterized by symptoms persistence in spite of medical treatment or H. pylori eradication. No study has yet investigated the presence of gluten-dependent RFD as a clinical presentation of Non-Celiac Gluten Sensitivity (NCGS). Patients with RFD, in whom celiac disease, wheat allergy and H. pylori infection had been ruled out, followed a six weeks long gluten-free diet (GFD). Symptoms were evaluated by means of visual analogue scales; patients with ≥30% improvement in at least one of the reported symptoms after GFD underwent a double-blind placebo controlled gluten challenge. Subjects were randomly divided in two groups and symptoms were evaluated after the gluten/placebo challenge. GFD responders were further followed on for 3 months to evaluate the relationship between symptoms and gluten consumption. Out of 77 patients with RFD, 50 (65%) did not respond to GFD; 27 (35%) cases showed gastrointestinal symptoms improvement while on GFD; after blind gluten ingestion, symptoms recurred in 5 cases (6.4% of patients with RFD, 18% of GFD responders) suggesting the presence of NCGS. Furthermore, such extra-intestinal symptoms as fatigue and weakness (P = 0.000), musculo-skeletal pain (P = 0.000) and headache (P = 0.002) improved in NCGS patients on GFD. Because of the high prevalence of NCGS among patients with RFD, a diagnostic/therapeutic roadmap evaluating the effect of GFD in patients with RFD seems a reasonable (and simple) approach.

Non-Celiac Gluten/Wheat Sensitivity: Clinical Characteristics and Microbiota and Mycobiota Composition by Response to the Gluten Challenge Test

“…About half of our participants were gluten responsive, in line with previous studies reporting around one-third of positive responses to the DBPC gluten challenge [ 18 , 19 , 20 , 21 , 22 ]. The various prevalences of gluten challenge responsivity may be due to the high heterogeneity in the employed methodology across the studies, including dose and vehicle of gluten, duration of wash-out and gluten administration, the employed placebo, the different dietary recommendations given to participants, and the characteristics of the enrolled participants, since other studies included patients with irritable bowel syndrome (IBS) or dyspepsia [ 18 , 29 , 40 , 41 , 42 ]. The gluten and placebo we used were in line with previous published protocols [ 20 , 21 , 22 , 29 ]; the employed gluten amount was considered as being able to induce symptoms in hypersensitive patients [ 20 ]; rice starch has low fermentable capacity due to its ready absorbability and has been frequently used as a placebo [ 20 , 21 , 29 ]; the administration of a low-FODMAPs diet in the first step of the experiment to all participants likely allowed us to exclude IBS patients who usually respond to different exclusion diets [ 18 ].…”

Recent Advances in the Definition and Management of Functional Dyspepsia

“…After blind gluten ingestion, symptoms recurred in 5 patients (6.4% of patients with refractory FD and 18% of gluten-free diet responders), suggesting the presence of NCGS. As shown by this study, 64 NCGS is highly prevalent among patients with refractory FD, and a diagnostic/therapeutic roadmap evaluating the effect of gluten-free diets in patients with FD should be included.…”

“…Among FD cases refractory to drug therapy, gluten-dependent FD as a clinical presentation of non-celiac gluten sensitivity (NCGS) should be included. Shahbazkhani et al 64 reported a randomized, double-blind, placebo-controlled trial in which, of 77 patients with refractory FD, 50 (65%) did not respond to a gluten-free diet, while 27 (35%) showed gastrointestinal symptom improvement on a gluten-free diet. After blind gluten ingestion, symptoms recurred in 5 patients (6.4% of patients with refractory FD and 18% of gluten-free diet responders), suggesting the presence of NCGS.…”

Non-Celiac Gluten Sensitivity in the Context of Functional Gastrointestinal Disorders

“…A randomized double-blind placebo-controlled trial in patients with refractory FD demonstrated that GFD was effective in improving gastrointestinal symptoms in 35% of patients; after blind gluten challenge, symptoms recurred in 18% of GFD responders. This last group of patients was considered confirmed NCGS [98].…”

“…Nutrients 2020, 11, x FOR PEER REVIEW 13 of 22 after blind gluten challenge, symptoms recurred in 18% of GFD responders. This last group of patients was considered confirmed NCGS [98].…”