{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T18:19:28Z","timestamp":1780078768730,"version":"3.54.0"},"reference-count":31,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2016,2,8]],"date-time":"2016-02-08T00:00:00Z","timestamp":1454889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione IRCCS Ca' Granda"},{"name":"Dr Schaer Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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 \u22653 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 \u00b1 11.7 years, BMI 22.4 \u00b1 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 \u00b1 11.0 years, BMI 22.3 \u00b1 4.0) reported a symptomatic improvement (VAS score 2.3 \u00b1 1.2 vs. 6.5 \u00b1 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 \u00b1 12.7 years, BMI 22.0 \u00b1 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.<\/jats:p>","DOI":"10.3390\/nu8020084","type":"journal-article","created":{"date-parts":[[2016,2,9]],"date-time":"2016-02-09T13:45:23Z","timestamp":1455025523000},"page":"84","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":168,"title":["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"],"prefix":"10.3390","volume":"8","author":[{"given":"Luca","family":"Elli","sequence":"first","affiliation":[{"name":"Center for the Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Tomba","sequence":"additional","affiliation":[{"name":"Center for the Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milano, Italy"},{"name":"Department of Medical, Surgical and Transplant Physiopathology, University of Milan, via Francesco Sforza 35, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9217-8241","authenticated-orcid":false,"given":"Federica","family":"Branchi","sequence":"additional","affiliation":[{"name":"Center for the Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milano, Italy"},{"name":"Department of Medical, Surgical and Transplant Physiopathology, University of Milan, via Francesco Sforza 35, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leda","family":"Roncoroni","sequence":"additional","affiliation":[{"name":"Center for the Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milano, Italy"},{"name":"Department of Medical, Surgical and Transplant Physiopathology, University of Milan, via Francesco Sforza 35, 20122 Milan, Italy"},{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, via Festa del Perdono 7, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenza","family":"Lombardo","sequence":"additional","affiliation":[{"name":"Center for the Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Bardella","sequence":"additional","affiliation":[{"name":"Center for the Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ferretti","sequence":"additional","affiliation":[{"name":"Center for the Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milano, Italy"},{"name":"Department of Medical, Surgical and Transplant Physiopathology, University of Milan, via Francesco Sforza 35, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Conte","sequence":"additional","affiliation":[{"name":"Center for the Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milano, Italy"},{"name":"Department of Medical, Surgical and Transplant Physiopathology, University of Milan, via Francesco Sforza 35, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio","family":"Valiante","sequence":"additional","affiliation":[{"name":"Gastroenterology and Digestive Endoscopy Unit, Santa Maria del Prato Hospital, via Bagnols sur Ceze 1, 32032 Feltre, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Fini","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gastroenterology and Digestive Endoscopy Unit, Busto Arsizio Hospital, via A. 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