{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T04:20:24Z","timestamp":1787977224665,"version":"build-2784847793"},"reference-count":52,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background. Lactose malabsorption (LM) is a frequent clinical problem associated with several digestive and extra-digestive diseases. The aim of this manuscript was to clarify the real clinical impact of LM on these disorders. Methods. A literature search for digestive and extra-digestive disorders related to LM was carried out using PubMed, Medline and Cochrane. Results. A transient lactase deficiency is present in celiac disease (CD) on a normal diet. The persistence of symptoms in CD on a gluten-free diet may be instead, in part, attributed to a primary LM. Similar circumstances are present in inflammatory bowel diseases (IBD), in which LM can be responsible for a part of persistent symptoms in IBD on clinical remission. LM and irritable bowel syndrome (IBS) are instead independent conditions. On the other hand, a lactose-restricted diet may be useful for some IBS patients. A reduced lactose intake can lead to low bone mass and limited risk of fragility fractures. Finally, the absorption of levothyroxine could be conditioned by LM. Conclusions. LM can be responsible for persistent symptoms in CD and IBD. The association with IBS seems to be casual. Bone mass and levothyroxine absorption can be affected by LM.<\/jats:p>","DOI":"10.3390\/nu14030584","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T05:26:17Z","timestamp":1643433977000},"page":"584","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Lactose Malabsorption and Presumed Related Disorders: A Review of Current Evidence"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3344-927X","authenticated-orcid":false,"given":"Paolo","family":"Usai-Satta","sequence":"first","affiliation":[{"name":"Gastroenterology Unit, Brotzu Hospital, 09121 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariantonia","family":"Lai","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, University of Cagliari, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Oppia","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, Brotzu Hospital, 09121 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.gtc.2012.06.003","article-title":"Diarrhea caused by carbohydrate malabsorption","volume":"41","author":"Hammer","year":"2012","journal-title":"Gastroenterol. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1177\/2050640613484463","article-title":"Lactose malabsorption and intolerance: Pathogenesis, diagnosis and treatment","volume":"1","author":"Misselwitz","year":"2013","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","unstructured":"Fassio, F., Facioni, M.S., and Guagnini, F. (2018). Lactose Maldigestion, Malabsorption, and Intolerance: A Comprehensive Review with a Focus on Current Management and Future Perspectives. Nutrients, 10.","DOI":"10.3390\/nu10111599"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Usai-Satta, P., Oppia, F., Lai, M., and Cabras, F. (2021). Hydrogen Breath Tests: Are They Really Useful in the Nutritional Management of Digestive Disease?. Nutrients, 13.","DOI":"10.3390\/nu13030974"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1111\/j.1572-0241.2002.05664.x","article-title":"Using breath tests wisely in a gastroenterology practice: An evidence-based review of indications and pitfalls in interpretation","volume":"97","author":"Romagnuolo","year":"2002","journal-title":"Am. J. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1086\/500053","article-title":"Mutations in the translated region of the lactase gene (LCT) underlie congenital lactase deficiency","volume":"78","author":"Kuokkanen","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/ng826","article-title":"Identification of a variant associated with adult-type hypolactasia","volume":"30","author":"Enattah","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1097\/MPG.0b013e31805b5899","article-title":"Decline of lactase activity and c\/t-13910 variant in Sardinian childhood","volume":"45","author":"Schirru","year":"2007","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1093\/ajcn\/65.5.1502","article-title":"Tolerance to the daily ingestion of two cups of milk by individuals claiming lactose intolerance","volume":"65","author":"Suarez","year":"1997","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2036.2009.03951.x","article-title":"1st Rome H2-Breath Testing Consensus Conference Working Group. Methodology and indications of H2-breath testing in gastrointestinal diseases: The Rome Consensus Conference","volume":"29","author":"Gasbarrini","year":"2009","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/ajg.2017.46","article-title":"Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus","volume":"112","author":"Rezaie","year":"2017","journal-title":"Am. J. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Hammer, H.F., Fox, M.R., Keller, J., Salvatore, S., Basilisco, G., Hammer, J., Lopetuso, L., Benninga, M., Borrelli, O., and Dumitrascu, D. (2021). European H2-CH4-breath test group. European guideline on indications, performance, and clinical impact of hydrogen and methane breath tests in adult and pediatric patients: European Association for Gastroenterology, Endoscopy and Nutrition, European Society of Neurogastroenterology and Motility, and European Society for Paediatric Gastroenterology Hepatology and Nutrition consensus. United Eur. Gastroenterol. J.","DOI":"10.1002\/ueg2.12133"},{"key":"ref_14","first-page":"14","article-title":"H2 breath testing for carbohydrate malabsorption","volume":"29","author":"Anania","year":"2009","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_15","first-page":"137","article-title":"Genetic testing is ready to change the diagnostic scenario of lactose malabsorption","volume":"57","author":"Congia","year":"2008","journal-title":"Gut"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1038\/sj.ejcn.1602638","article-title":"Genetic testing improves the diagnosis of adult type hypolactasia in the Mediterranean population of Sardinia","volume":"61","author":"Schirru","year":"2007","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/j.1365-2036.2011.04962.x","article-title":"Meta-analysis: The diagnostic accuracy of lactose breath hydrogen or lactose tolerance tests for predicting the North European lactase polymorphism C\/T-13910","volume":"35","author":"Marton","year":"2012","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_18","first-page":"1","article-title":"Lactose intolerance and health","volume":"192","author":"Wilt","year":"2010","journal-title":"Evid. Rep. Technol. Assess."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"29","DOI":"10.4292\/wjgpt.v3.i3.29","article-title":"Lactose malabsorption and intolerance: What should be the best clinical management?","volume":"3","author":"Scarpa","year":"2012","journal-title":"World J. Gastrointest. Pharmacol. Ther."},{"key":"ref_20","first-page":"68","article-title":"Celiac disease and lactose intolerance","volume":"6","author":"Aaron","year":"2018","journal-title":"Int. J. Cel. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"33","DOI":"10.2298\/SARH0902033R","article-title":"Lactose intolerance in infants with gluten-sensitive enteropathy: Frequency and clinical characteristics","volume":"137","author":"Djurdjevid","year":"2009","journal-title":"Srp. Arh. Celok. Lek."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/j.1365-2036.2009.04018.x","article-title":"Comparison of the prevalence of fructose and lactose malabsorption across chronic intestinal disorders","volume":"30","author":"Barrett","year":"2009","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1159\/000084526","article-title":"High prevalence of celiac disease in patients with lactose intolerance","volume":"71","author":"Ojetti","year":"2005","journal-title":"Digestion"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Penny, H.A., Baggus, E.M.R., Rej, A., Snowden, J.A., and Sanders, D.S. (2020). Non-Responsive Coeliac Disease: A Comprehensive Review from the NHS England National Centre for Refractory Coeliac Disease. Nutrients, 12.","DOI":"10.3390\/nu12010216"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Schiepatti, A., Savioli, J., Vernero, M., Borrelli de Andreis, F., Perfetti, L., Meriggi, A., and Biagi, F. (2020). Pitfalls in the Diagnosis of Coeliac Disease and Gluten-Related Disorders. Nutrients, 12.","DOI":"10.3390\/nu12061711"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.cgh.2006.12.006","article-title":"Etiologies and predictors of diagnosis in nonresponsive celiac disease","volume":"5","author":"Leffler","year":"2007","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1038\/ejcn.2012.153","article-title":"Association between celiac disease and primary lactase deficiency","volume":"66","author":"Basso","year":"2012","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s12937-016-0183-8","article-title":"Systematic review and meta-analysis of lactose digestion, its impact on intolerance and nutritional effects of dairy food restriction in inflammatory bowel diseases","volume":"15","author":"Szilagyi","year":"2016","journal-title":"Nutr. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"111043","DOI":"10.1016\/j.nut.2020.111043","article-title":"Lactose intolerance in patients with inflammatory bowel diseases and dietary management in prevention of osteoporosis","volume":"82","author":"Ratajczak","year":"2021","journal-title":"Nutrition"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Nardone, O.M., Manfellotto, F., D\u2019Onofrio, C., Rocco, A., Annona, G., Sasso, F., De Luca, P., Imperatore, N., Testa, A., and de Sire, R. (2021). Lactose Intolerance Assessed by Analysis of Genetic Polymorphism, Breath Test and Symptoms in Patients with Inflammatory Bowel Disease. Nutrients, 13.","DOI":"10.3390\/nu13041290"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"185","DOI":"10.4166\/kjg.2020.76.4.185","article-title":"Association between Inflammatory Bowel Disease and Lactose Intolerance: Fact or Fiction","volume":"76","author":"Asfari","year":"2020","journal-title":"Korean J. Gastroenterol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"164","DOI":"10.2174\/1574884713666180807143606","article-title":"Therapeutic Approach for Irritable Bowel Syndrome: Old and New Strategies","volume":"13","author":"Bellini","year":"2018","journal-title":"Curr. Clin. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/j.1365-2036.2007.03557.x","article-title":"Review article: Lactose intolerance in clinical practice--myths and realities","volume":"27","author":"Lomer","year":"2008","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_34","first-page":"e6710","article-title":"Is There a Correlation Between Irritable Bowel Syndrome and Lactose Intolerance?","volume":"12","author":"Cancarevic","year":"2020","journal-title":"Cureus"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e13527","DOI":"10.1111\/nmo.13527","article-title":"Lactose intolerance but not lactose maldigestion is more frequent in patients with irritable bowel syndrome than in healthy controls: A meta-analysis","volume":"31","author":"Gede","year":"2019","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/S1590-8658(01)80713-1","article-title":"Lactose malabsorption, irritable bowel syndrome and self-reported milk intolerance","volume":"33","author":"Vernia","year":"2001","journal-title":"Dig. Liver Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1111\/apt.16597","article-title":"Review article: Diagnosis and investigation of irritable bowel syndrome","volume":"54","author":"Black","year":"2021","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1136\/gutjnl-2017-313750","article-title":"The low FODMAP diet: Recent advances in understanding its mechanisms and efficacy in IBS","volume":"66","author":"Staudacher","year":"2017","journal-title":"Gut"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Altobelli, E., Del Negro, V., Angeletti, P.M., and Latella, G. (2017). Low-FODMAP Diet Improves Irritable Bowel Syndrome Symptoms: A Meta-Analysis. Nutrients, 9.","DOI":"10.3390\/nu9090940"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Bellini, M., Tonarelli, S., Barracca, F., Morganti, R., Pancetti, A., Bertani, L., de Bortoli, N., Costa, F., Mosca, M., and Marchi, S. (2020). A Low-FODMAP Diet for Irritable Bowel Syndrome: Some Answers to the Doubts from a Long-Term Follow-Up. Nutrients, 12.","DOI":"10.3390\/nu12082360"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Buchowski, M.S. (2016). Chapter 1 Calcium in the context of dietary sources and metabolism. Calcium: Chemistry, Analysis, Function and Effects, The Royal Society of Chemistry.","DOI":"10.1039\/9781782622130-00003"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Hodges, J.K., Cao, S., Cladis, D.P., and Weaver, C.M. (2019). Lactose Intolerance and Bone Health: The Challenge of Ensuring Adequate Calcium Intake. Nutrients, 11.","DOI":"10.3390\/nu11040718"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.bone.2008.02.022","article-title":"Impact of dairy products and dietary calcium on bone-mineral content in children: Results of a meta-analysis","volume":"43","author":"Huncharek","year":"2008","journal-title":"Bone"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1080\/07315724.2003.10719294","article-title":"Bone density in axial and appendicular skeleton in patients with lactose intolerance: Influence of calcium intake and vitamin D status","volume":"22","author":"Segal","year":"2003","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/j.bone.2008.12.019","article-title":"Cardiovascular Risk in Young Finns Study Group. Associations of genetic lactase non-persistence and sex with bone loss in young adulthood","volume":"44","author":"Laaksonen","year":"2009","journal-title":"Bone"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s11657-018-0420-1","article-title":"Dairy product intake and bone properties in 70-year-old men and women","volume":"13","author":"Hallkvist","year":"2018","journal-title":"Arch. Osteoporos."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1002\/jbmr.279","article-title":"Milk intake and risk of hip fracture in men and women: A meta-analysis of prospective cohort studies","volume":"26","author":"Baron","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s00198-017-4285-8","article-title":"Milk and other dairy foods and risk of hip fracture in men and women","volume":"29","author":"Feskanich","year":"2018","journal-title":"Osteoporos. Int."},{"key":"ref_49","unstructured":"Miller, G.D., Jarvis, J.K., Council, N.D., and McBean, L.D. (2002). Handbook of Dairy Foods and Nutrition, CRC Press."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"184","DOI":"10.26444\/aaem\/112331","article-title":"The importance of nutritional factors and dietary management of Hashimoto\u2019s thyroiditis","volume":"27","author":"Ihnatowicz","year":"2020","journal-title":"Ann. Agric. Environ. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s12020-013-0065-1","article-title":"Decrease in TSH levels after lactose restriction in Hashimoto\u2019s thyroiditis patients with lactose intolerance","volume":"46","author":"Asik","year":"2014","journal-title":"Endocrine"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"E1454","DOI":"10.1210\/jc.2014-1217","article-title":"Systematic appraisal of lactose intolerance as cause of increased need for oral thyroxine","volume":"99","author":"Cellini","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/3\/584\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:10:17Z","timestamp":1760134217000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/3\/584"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,28]]},"references-count":52,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["nu14030584"],"URL":"https:\/\/doi.org\/10.3390\/nu14030584","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,28]]}}}