Functional dyspepsia (FD) refers to dyspepsia without any organic cause to explain the patient’s symptoms despite upper endoscopy and other necessary tests. Refractory FD (RFD) is defined as prolonged FD more than 6 months without response to PPIs, prokinetics, or Helicobacter pylori eradication. Non-celiac gluten sensitivity (NCGS) is a spectrum of gluten related disorders that can be associated with gastrointestinal (GI) symptoms, including dyspepsia. A randomized, double-blind, placebo-controlled (DBPC), cross-over trial was performed to determine the effects gluten free diet (GFD) on symptoms of patients with RFD

: Patients with RFD whom celiac disease, wheat allergy and H.pylori infection were ruled out, were underwent six weeks GFD. Patients who had at least 30% improvement in one of their GI symptoms, according to visual analogue scale, were entered to a DBPC challenge. Patients were randomly divided to two groups and their symptoms recurrence were evaluated after gluten/placebo challenge during three weeks. Also the extra- intestinal symptoms, anti gliadin antibody (AGA-IgG) titer and stool calprotectin value in these groups were assessed. Furthermore, all responders were followed up for three months after challenge, to evaluate symptoms in the absence and presence of gluten.

out of 77 patients with RFD, 50 patients (65%) did not show an appropriate response to GFD and were excluded; but in 27 patients (35%) showed improvement. Symptoms recurred in five patients (6.5 % out of 77 patients with RFD). Adding three more months follow up, 3 more cases were diagnosed as NCGS. Serum AGA (IgG) titer was high in 20% of patients.

In addition to five patients who were initially diagnosed as NCGS, three more patients were categorized as NCGS during extra follow up (10.3% out of patients with RFD).Overall we recommend GFD in every patient with RFD.