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.
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.
authors: Center for the Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milano, Italy. lucelli@yahoo.com.
authors: Luca
authors: L
authors: Elli
authors: Center for the Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milano, Italy. tomba.carolina@gmail.com.|Department of Medical, Surgical and Transplant Physiopathology, University of Milan, via Francesco Sforza 35, 20122 Milan, Italy. tomba.carolina@gmail.com.
authors: Carolina
authors: C
authors: Tomba
authors: Center for the Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milano, Italy. federica.branchi@gmail.com.|Department of Medical, Surgical and Transplant Physiopathology, University of Milan, via Francesco Sforza 35, 20122 Milan, Italy. federica.branchi@gmail.com.
authors: Federica
authors: F
authors: Branchi
authors: Center for the Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milano, Italy. leda.roncoroni@tiscali.it.|Department of Medical, Surgical and Transplant Physiopathology, University of Milan, via Francesco Sforza 35, 20122 Milan, Italy. leda.roncoroni@tiscali.it.|Department of Biomedical, Surgical and Dental Sciences, University of Milan, via Festa del Perdono 7, 20122 Milan, Italy. leda.roncoroni@tiscali.it.
authors: Leda
authors: L
authors: Roncoroni
authors: Center for the Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milano, Italy. vicky.l@hotmail.com.
authors: Vincenza
authors: V
authors: Lombardo
authors: Center for the Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milano, Italy. mariateresa.bardella@yahoo.com.
authors: Maria Teresa
authors: MT
authors: Bardella
authors: Center for the Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milano, Italy. francesca.ferretti01@gmail.com.|Department of Medical, Surgical and Transplant Physiopathology, University of Milan, via Francesco Sforza 35, 20122 Milan, Italy. francesca.ferretti01@gmail.com.
authors: Francesca
authors: F
authors: Ferretti
authors: Center for the Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milano, Italy. dario.conte@unimi.it.|Department of Medical, Surgical and Transplant Physiopathology, University of Milan, via Francesco Sforza 35, 20122 Milan, Italy. dario.conte@unimi.it.
authors: Dario
authors: D
authors: Conte
authors: Gastroenterology and Digestive Endoscopy Unit, Santa Maria del Prato Hospital, via Bagnols sur Ceze 1, 32032 Feltre, Italy. flavio.valiante@gmail.com.
authors: Flavio
authors: F
authors: Valiante
authors: Department of Internal Medicine, Gastroenterology and Digestive Endoscopy Unit, Busto Arsizio Hospital, via A. Da Brescia 1, 21052 Busto Arsizio, Italy. finilucia@yahoo.it.
authors: Lucia
authors: L
authors: Fini
authors: Operative Endoscopy Unit, Niguarda Ca' Granda Hospital, Piazza Ospedale Maggiore 3, 20162 Milan, Italy. edoardo.forti@ospedaleniguarda.it.
authors: Edoardo
authors: E
authors: Forti
authors: Gastroenterology, CRO National Cancer Institute, via Franco Gallini 2, 33081 Aviano, Italy. rcannizzaro@cro.it.
authors: Renato
authors: R
authors: Cannizzaro
authors: Gastroenterology, CRO National Cancer Institute, via Franco Gallini 2, 33081 Aviano, Italy. smaiero@cro.it.
authors: Stefania
authors: S
authors: Maiero
authors: Gastroenterology and Endoscopy Unit, Crema Maggiore Hospital, Largo Dossena 2, 26013 Crema, Italy. c.londoni@hcrema.it.
authors: Claudio
authors: C
authors: Londoni
authors: Gastroenterology Unit, Ospedale Civile Santo Spirito, via Fonte Romana 8, 65100 Pescara, Italy. adriano.lauri@tin.it.
authors: Adriano
authors: A
authors: Lauri
authors: Medicine and Gastroenterology Unit, IRCCS Arcispedale S. Maria Nuova, via Risorgimento 80, 42100 Reggio Emilia, Italy. Giovanni.Fornaciari@asmn.re.it.
authors: Giovanni
authors: G
authors: Fornaciari
authors: Gastroenterology Unit, Ospedale Valduce, via Dante Alighieri 11, 22100 Como, Italy. nicolettalenoci@libero.it.
authors: Nicoletta
authors: N
authors: Lenoci
authors: Department of Experimental and Clinical Medicine, Magna Græcia University, Loc. Germaneto, 88100 Catanzaro, Italy. rocco.spagnuolo79@gmail.com.
authors: Rocco
authors: R
authors: Spagnuolo
authors: Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milano, Italy. basilisc@policlinico.mi.it.
authors: Guido
authors: G
authors: Basilisco
authors: Alphasearch, via Gianfrancesco Parravicini 40, 20900 Monza, Italy. flavio.valiante@gmail.com.
authors: Francesco
authors: F
authors: Somalvico
authors: Medicine Unit, Ospedale San Biagio, Piazza Vittime dei Lager Nazifascisti 1, 28845 Domodossola, Italy. borgattabruno@alice.it.
authors: Bruno
authors: B
authors: Borgatta
authors: Gastroenterological Department, IRCCS "De Bellis" Hospital, SP Turi 27, 70013 Castellana Grotte (BA), Italy. leandro@media.it.
authors: Gioacchino
authors: G
authors: Leandro
authors: Gastroenterology and GI Endoscopy Unit, Macchi Hospital-Varese, Viale Luigi Borri 57, 21100 Varese, Italy. sergio.segato@katamail.com.
authors: Sergio
authors: S
authors: Segato
authors: School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900 Monza, Italy. donatella.barisani@unimib.it.
authors: Donatella
authors: D
authors: Barisani
authors: Gastroenterology Unit, Policlinico of Palermo, via del Vespro 129, 90127 Palermo, Italy. gaetanocmorreale@libero.it.
authors: Gaetano
authors: G
authors: Morreale
authors: Gastroenterology and Endoscopy Unit, Crema Maggiore Hospital, Largo Dossena 2, 26013 Crema, Italy. ebuscarini@rim.it.
authors: Elisabetta
authors: E
authors: Buscarini
mesh_terms: D000328:Adult; D002446:Celiac Disease / Q000178:diet therapy; D018592:Cross-Over Studies; D055050:Diet, Gluten-Free; D004311:Double-Blind Method; D005260:Female; D005512:Food Hypersensitivity; D005767:Gastrointestinal Diseases / Q000175:diagnosis / Q000178:diet therapy / Q000209:etiology*; D005983:Glutens / Q000009:adverse effects*; D006801:Humans; D043183:Irritable Bowel Syndrome; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012720:Severity of Illness Index
chemical_list: D005983:Glutens
keywords: double-blind placebo controlled challenge; functional gastrointestinal disorders; gluten-free diet; irritable bowel syndrome; non-celiac gluten sensitivity