{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T19:15:38Z","timestamp":1789499738183,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,9,21]],"date-time":"2018-09-21T00:00:00Z","timestamp":1537488000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK56338"],"award-info":[{"award-number":["DK56338"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Digest Diseases"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:p>Post\u2010prandial gastrointestinal symptoms such as diarrhea, abdominal distension, flatulence, bloating and a feeling of fullness are common complaints of often unknown etiology and pathogenesis. There is a long history of trials reporting the successful use of products containing a variety of combinations of digestive enzymes including a number of randomized placebo\u2010controlled trials. We provide a narrative review of studies describing the use of multi\u2010digestive enzymes for symptoms consistent with irritable bowel syndrome. We describe clinical trials reported over the past 60\u2009years including double\u2010blinded randomized, placebo\u2010controlled studies and recent trials that focused on post\u2010prandial diarrhea consistent with diarrhea\u2010predominant irritable bowel syndrome. Disaccharidase deficiencies or deficiencies of other carbohydrate digesting enzymes were excluded. Worldwide studies have generally reported success with multi\u2010enzyme preparations although none used a factorial design to identify subgroups or attempted to link specific symptom responses to specific components of therapy. Although there is a long history of the successful use of multi\u2010enzyme preparations for post\u2010prandial symptoms consistent with irritable bowel syndrome, long\u2010term studies using validated scoring systems and factorial designs are needed to confirm the results for specific symptoms and the components of the combination drugs received.<\/jats:p>","DOI":"10.1111\/1751-2980.12655","type":"journal-article","created":{"date-parts":[[2018,8,13]],"date-time":"2018-08-13T07:02:45Z","timestamp":1534143765000},"page":"650-656","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Enzyme therapy for functional bowel disease\u2010like post\u2010prandial distress"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6908-8317","authenticated-orcid":false,"given":"David Y.","family":"Graham","sequence":"first","affiliation":[{"name":"Department of Medicine Michael E. DeBakey VA Medical Center  Houston Texas"},{"name":"Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyanprakash A.","family":"Ketwaroo","sequence":"additional","affiliation":[{"name":"Department of Medicine Michael E. DeBakey VA Medical Center  Houston Texas"},{"name":"Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Money","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Maryland School of Medicine  Baltimore Maryland"},{"name":"Department of Internal Medicine Meritus Medical Center  Hagerstown Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antone R.","family":"Opekun","sequence":"additional","affiliation":[{"name":"Department of Medicine Michael E. DeBakey VA Medical Center  Houston Texas"},{"name":"Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.09.046"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v23.i39.7059"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2010.115"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2009.09.032"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0b013e31817c1b36"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/7952891"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-312456"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.02.032"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2012.02.029"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02924544"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-017-4493-2"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2016.48"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2016.144"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.7453\/gahmj.2013.100"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/flgastro-2015-100651"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-017-0783-y"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13791"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2018.01.027"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.56.8193"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006676-199711000-00011"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.24906"},{"key":"e_1_2_7_23_1","first-page":"734","article-title":"The use of bile acids and pancreatic enzyme substitutes in the treatment of \u2018functional indigestion\u2019","volume":"33","author":"Rider JA","year":"1960","journal-title":"Am J Gastroenterol"},{"key":"e_1_2_7_24_1","first-page":"331","volume-title":"Enzymes as Drugs","author":"Graham DY","year":"1981"},{"key":"e_1_2_7_25_1","first-page":"181","article-title":"Post\u2010marketing surveillance study to assess the efficacy and tolerability of Al5zyme \u2014 a multienzyme preparation in patients with functional dyspepsia","author":"Khandke DA","year":"2013","journal-title":"Ind Med Gaz"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-2980.2008.00361.x"},{"key":"e_1_2_7_27_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1742-1241.1969.tb04968.x","article-title":"A clinical double\u2010blind trial with a broad spectrum digestive enzyme product (\u2018Combizym\u2019) in geriatric practice","volume":"23","author":"Kataria MS","year":"1969","journal-title":"Br J Clin Pract"},{"key":"e_1_2_7_28_1","first-page":"1815","article-title":"High\u2010dose enzyme\u2010substitution therapy in digestive disorders","volume":"94","author":"Moosauer M","year":"1976","journal-title":"Fortschr Med"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2011.11.006"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40348-015-0028-0"},{"key":"e_1_2_7_31_1","first-page":"0410","article-title":"Irritable bowel syndrome: dietary interventions","volume":"2015","author":"Ford AC","year":"2015","journal-title":"BMJ Clin Evid"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mpg.0000421407.88128.5c"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-6915(02)00011-X"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1159\/000176576"},{"key":"e_1_2_7_35_1","volume-title":"Fat Land","author":"Crister G","year":"2003"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1121"},{"key":"e_1_2_7_37_1","doi-asserted-by":"crossref","first-page":"iii32","DOI":"10.1093\/rheumatology\/keg496","article-title":"Measuring dyspepsia\u2010related health in randomized trials: the severity of dyspepsia assessment (SODA) and its use in treatment with NSAIDs and COX\u20102\u2010specific inhibitors","volume":"42","author":"Rabeneck L","year":"2003","journal-title":"Rheumatology (Oxford)"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/00042737-199610000-00006"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005558204440"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1746.2002.02713.x"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2004.07.010"}],"container-title":["Journal of Digestive Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2F1751-2980.12655","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1751-2980.12655","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1751-2980.12655","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1751-2980.12655","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T19:58:00Z","timestamp":1694807880000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1751-2980.12655"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,21]]},"references-count":40,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1111\/1751-2980.12655"],"URL":"https:\/\/doi.org\/10.1111\/1751-2980.12655","archive":["Portico"],"relation":{},"ISSN":["1751-2972","1751-2980"],"issn-type":[{"value":"1751-2972","type":"print"},{"value":"1751-2980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,21]]},"assertion":[{"value":"2018-08-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}