PMID- 21224837 OWN - NLM STAT- MEDLINE DCOM- 20110428 LR - 20220409 IS - 1572-0241 (Electronic) IS - 0002-9270 (Linking) VI - 106 IP - 3 DP - 2011 Mar TI - Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. PG - 508-14; quiz 515 LID - 10.1038/ajg.2010.487 [doi] AB - OBJECTIVES: Despite increased prescription of a gluten-free diet for gastrointestinal symptoms in individuals who do not have celiac disease, there is minimal evidence that suggests that gluten is a trigger. The aims of this study were to determine whether gluten ingestion can induce symptoms in non-celiac individuals and to examine the mechanism. METHODS: A double-blind, randomized, placebo-controlled rechallenge trial was undertaken in patients with irritable bowel syndrome in whom celiac disease was excluded and who were symptomatically controlled on a gluten-free diet. Participants received either gluten or placebo in the form of two bread slices plus one muffin per day with a gluten-free diet for up to 6 weeks. Symptoms were evaluated using a visual analog scale and markers of intestinal inflammation, injury, and immune activation were monitored. RESULTS: A total of 34 patients (aged 29-59 years, 4 men) completed the study as per protocol. Overall, 56% had human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8. Adherence to diet and supplements was very high. Of 19 patients (68%) in the gluten group, 13 reported that symptoms were not adequately controlled compared with 6 of 15 (40%) on placebo (P=0.0001; generalized estimating equation). On a visual analog scale, patients were significantly worse with gluten within 1 week for overall symptoms (P=0.047), pain (P=0.016), bloating (P=0.031), satisfaction with stool consistency (P=0.024), and tiredness (P=0.001). Anti-gliadin antibodies were not induced. There were no significant changes in fecal lactoferrin, levels of celiac antibodies, highly sensitive C-reactive protein, or intestinal permeability. There were no differences in any end point in individuals with or without DQ2/DQ8. CONCLUSIONS: "Non-celiac gluten intolerance" may exist, but no clues to the mechanism were elucidated. FAU - Biesiekierski, Jessica R AU - Biesiekierski JR AD - Monash University Department of Medicine and Gastroenterology, Box Hill Hospital, Box Hill, Victoria, Australia. FAU - Newnham, Evan D AU - Newnham ED FAU - Irving, Peter M AU - Irving PM FAU - Barrett, Jacqueline S AU - Barrett JS FAU - Haines, Melissa AU - Haines M FAU - Doecke, James D AU - Doecke JD FAU - Shepherd, Susan J AU - Shepherd SJ FAU - Muir, Jane G AU - Muir JG FAU - Gibson, Peter R AU - Gibson PR LA - eng PT - Controlled Clinical Trial PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20110111 PL - United States TA - Am J Gastroenterol JT - The American journal of gastroenterology JID - 0421030 RN - 0 (Biomarkers) RN - 8002-80-0 (Glutens) SB - IM CIN - Am J Gastroenterol. 2011 Mar;106(3):516-8. PMID: 21378766 CIN - Am J Gastroenterol. 2011 Dec;106(12):2201; author reply 2201-2. PMID: 22138947 CIN - Gastroenterology. 2012 Mar;142(3):664-6. PMID: 22281277 CIN - Med Clin (Barc). 2014 Nov 18;143(10):446-7. PMID: 25190586 MH - Adult MH - Aged MH - Biomarkers/blood MH - Celiac Disease/diagnosis MH - Colitis/chemically induced MH - *Diet, Gluten-Free MH - Double-Blind Method MH - Enteritis/chemically induced MH - Female MH - Gastrointestinal Tract/*drug effects/immunology/*physiopathology MH - Glutens/*adverse effects/*immunology MH - Humans MH - Irritable Bowel Syndrome/immunology/*physiopathology MH - Male MH - Middle Aged MH - Treatment Outcome EDAT- 2011/01/13 06:00 MHDA- 2011/04/29 06:00 CRDT- 2011/01/13 06:00 PHST- 2011/01/13 06:00 [entrez] PHST- 2011/01/13 06:00 [pubmed] PHST- 2011/04/29 06:00 [medline] AID - ajg2010487 [pii] AID - 10.1038/ajg.2010.487 [doi] PST - ppublish SO - Am J Gastroenterol. 2011 Mar;106(3):508-14; quiz 515. doi: 10.1038/ajg.2010.487. Epub 2011 Jan 11.