{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T23:20:24Z","timestamp":1781738424739,"version":"3.54.5"},"reference-count":27,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T00:00:00Z","timestamp":1635292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["PE-2016-02363692"],"award-info":[{"award-number":["PE-2016-02363692"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Lactose intolerance is the most frequent food intolerance, but many subjects with self-reported milk intolerance (SRMI) are asymptomatic at lactose hydrogen breath test (LHBT). The aim of this study was to evaluate the frequency of lactose intolerance in SRMI patients and their clinical characteristics. Methods: In a retrospective study, the clinical records of 314 SRMI patients (259 females, mean age: 39.1 \u00b1 13.5 years) were reviewed; 102 patients with irritable bowel syndrome (IBS) served as controls. In a prospective study, 42 SRMI patients, negatives at the LHBT, underwent a double-blind, placebo-controlled (DBPC) whole cow\u2019s milk challenge. Results: In the retrospective study, only 178 patients (56%) were lactose maldigesters and intolerant at LHBT; 68% of the subjects with SRMI were suffering from IBS; 74% reported dyspepsia (p = 0.0001 vs. IBS controls); and weight loss was recorded in 62 SRMI patients (20%) (p = 0.01 vs. IBS controls). Duodenal histology showed intra-epithelial lymphocytosis in about 60% of cases. In the prospective study, 36 patients (86%) experienced symptoms during the DBPC cow\u2019s milk challenge, and only 4 patients (9%) reacted to placebo (p = 0.0001). Conclusions: A percentage of SRMI patients were not suffering from lactose intolerance. DBPC revealed that SRMI patients had clinical reactions when exposed to whole cow\u2019s milk.<\/jats:p>","DOI":"10.3390\/nu13113833","type":"journal-article","created":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T23:24:42Z","timestamp":1635377082000},"page":"3833","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Whole Cow\u2019s Milk but Not Lactose Can Induce Symptoms in Patients with Self-Reported Milk Intolerance: Evidence of Cow\u2019s Milk Sensitivity in Adults"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8913-7916","authenticated-orcid":false,"given":"Antonio","family":"Carroccio","sequence":"first","affiliation":[{"name":"Unit of Internal Medicine, \u201cV. Cervello\u201d Hospital, Ospedali Riuniti \u201cVilla Sofia-Cervello\u201d, 90146 Palermo, Italy"},{"name":"Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7850-555X","authenticated-orcid":false,"given":"Maurizio","family":"Soresi","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Mantia","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Fayer","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"La Blasca","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelio","family":"Seidita","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"D\u2019Alcamo","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ada","family":"Florena","sequence":"additional","affiliation":[{"name":"Unit of Pathology, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Tin\u00e8","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Garlisi","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0406-0583","authenticated-orcid":false,"given":"Pasquale","family":"Mansueto","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1038\/ajg.2013.105","article-title":"Self-reported food-related gastrointestinal symptoms in IBS are common and associated with more severe symptoms and reduced quality of life","volume":"108","author":"Bengtsson","year":"2013","journal-title":"Off. J. Am. Coll. Gastroenterol. ACG"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3810\/pgm.1998.09.577","article-title":"When to suspect lactose intolerance. Symptomatic, ethnic, and laboratory clues","volume":"104","author":"Srinivasan","year":"1998","journal-title":"Postgrad. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3748\/wjg.v12.i2.187","article-title":"Management and treatment of lactose malabsorption","volume":"12","author":"Montalto","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1136\/gutjnl-2019-318404","article-title":"Update on lactose malabsorption and intolerance: Pathogenesis, diagnosis and clinical management","volume":"68","author":"Misselwitz","year":"2019","journal-title":"Gut"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1136\/pgmj.2004.025551","article-title":"Systemic lactose intolerance: A new perspective on an old problem","volume":"81","author":"Matthews","year":"2005","journal-title":"Postgrad. Med. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1038\/ajg.2012.236","article-title":"Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: Exploring a new clinical entity","volume":"107","author":"Carroccio","year":"2012","journal-title":"Off. J. Am. Coll. Gastroenterol. ACG"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1053\/j.gastro.2015.05.040","article-title":"High Proportions of People With Nonceliac Wheat Sensitivity Have Autoimmune Disease or Antinuclear Antibodies","volume":"149","author":"Carroccio","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/S2468-1253(17)30154-1","article-title":"Country, regional, and global estimates for lactose malabsorption in adults: A systematic review and meta-analysis","volume":"2","author":"Storhaug","year":"2017","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/BF01535754","article-title":"Prediction of lactose malabsorption in referral patients","volume":"33","author":"DiPalma","year":"1988","journal-title":"Dig. Dis. Sci."},{"key":"ref_10","first-page":"254","article-title":"Lactose intolerance in adults with chronic unspecific abdominal complaints","volume":"30","author":"Parente","year":"1983","journal-title":"Hepatogastroenterology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1007\/BF01299809","article-title":"Lactose malabsorption and intolerance in Italians. Clinical implications","volume":"31","author":"Bozzani","year":"1986","journal-title":"Dig. Dis. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1080\/00365520410005405","article-title":"Lactose malabsorption in a population with irritable bowel syndrome: Prevalence and symptoms. A case-control study","volume":"39","author":"Farup","year":"2004","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1111\/j.1440-1746.2007.04986.x","article-title":"Lactose intolerance in patients with irritable bowel syndrome from northern India: A case-control study","volume":"22","author":"Gupta","year":"2007","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1007\/BF01317083","article-title":"Hydrogen breath test quantification and clinical correlation of lactose malabsorption in adult irritable bowel syndrome and ulcerative colitis","volume":"29","author":"Sciarretta","year":"1984","journal-title":"Dig. Dis. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1111\/nmo.12602","article-title":"Self-reported lactose intolerance in clinic patients with functional gastrointestinal symptoms: Prevalence, risk factors, and impact on food choices","volume":"27","author":"Zheng","year":"2015","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1093\/qjmed\/hcq082","article-title":"Lactose malabsorption and intolerance: A systematic review on the diagnostic value of gastrointestinal symptoms and self-reported milk intolerance","volume":"103","author":"Jellema","year":"2010","journal-title":"QJM Int. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1056\/NEJM199810153391602","article-title":"Intolerance of cow\u2019s milk and chronic constipation in children","volume":"339","author":"Iacono","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/S0022-3476(95)70496-5","article-title":"Chronic constipation as a symptom of cow milk allergy","volume":"126","author":"Iacono","year":"1995","journal-title":"J. Pediatr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1136\/bmj.287.6405.1593","article-title":"Allergy to cows\u2019 milk presenting as chronic constipation","volume":"287","author":"Chin","year":"1983","journal-title":"Br. Med. J. (Clin. Res. Ed.)"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1056\/NEJM199903183401114","article-title":"Cow\u2019s milk and chronic constipation in children","volume":"340","author":"Shah","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1111\/j.1365-2036.2006.03125.x","article-title":"Review article: Chronic constipation and food hypersensitivity--an intriguing relationship","volume":"24","author":"Carroccio","year":"2006","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1080\/00365520500367400","article-title":"Multiple food hypersensitivity as a cause of refractory chronic constipation in adults","volume":"41","author":"Carroccio","year":"2006","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1038\/ajg.2013.353","article-title":"Non-celiac wheat sensitivity as an allergic condition: Personal experience and narrative review","volume":"108","author":"Carroccio","year":"2013","journal-title":"Off. J. Am. Coll. Gastroenterol. ACG"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Catassi, C., Alaedini, A., Bojarski, C., Bonaz, B., Bouma, G., Carroccio, A., Castillejo, G., De Magistris, L., Dieterich, W., and Di Liberto, D. (2017). The Overlapping Area of Non-Celiac Gluten Sensitivity (NCGS) and Wheat-Sensitive Irritable Bowel Syndrome (IBS): An Update. Nutrients, 9.","DOI":"10.3390\/nu9111268"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1053\/j.gastro.2014.07.046","article-title":"Confocal endomicroscopy shows food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome","volume":"147","author":"Schuppan","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1053\/j.gastro.2019.03.046","article-title":"Many Patients With Irritable Bowel Syndrome Have Atypical Food Allergies Not Associated With Immunoglobulin E","volume":"157","author":"Pflaum","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.cgh.2009.11.010","article-title":"A cytologic assay for diagnosis of food hypersensitivity in patients with irritable bowel syndrome","volume":"8","author":"Carroccio","year":"2010","journal-title":"Clin. Gastroenterol. Hepatol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/11\/3833\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:21:32Z","timestamp":1760167292000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/11\/3833"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,27]]},"references-count":27,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["nu13113833"],"URL":"https:\/\/doi.org\/10.3390\/nu13113833","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,27]]}}}