{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T21:20:55Z","timestamp":1789593655094,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Danone Specialized Nutrition Indonesia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Due to its very early introduction, cow\u2019s milk is one of the first foods that can cause adverse reactions in human beings. Lactose intolerance (LI) and cow\u2019s milk allergy (CMA) are the most common adverse reactions to cow\u2019s milk. While LI is due to insufficient small intestinal lactase activity and\/or a large quantity of ingested lactose, CMA is an aberrant immune reaction to cow\u2019s milk proteins, particularly casein or \u03b2-lactoglobulin. However, the clinical manifestations of LI and CMA, particularly their gastrointestinal signs and symptoms, are very similar, which might lead to misdiagnosis or delayed diagnosis as well as nutritional risks due to inappropriate dietary interventions or unnecessary dietary restriction. Formula-fed infants with LI should be treated with formula with reduced or no lactose, while those with CMA should be treated with formula containing extensive hydrolyzed cow\u2019s milk protein or amino acids. This review is therefore written to assist clinicians to better understand the pathophysiologies of LI and CMA as well as to recognize the similarities and differences between clinical manifestations of LI and CMA.<\/jats:p>","DOI":"10.3390\/nu16030414","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T09:41:59Z","timestamp":1706694119000},"page":"414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Lactose Intolerance versus Cow\u2019s Milk Allergy in Infants: A Clinical Dilemma"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5107-5895","authenticated-orcid":false,"given":"Andy","family":"Darma","sequence":"first","affiliation":[{"name":"Department of Child Health, Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia"},{"name":"Department of Child Health, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8557-2400","authenticated-orcid":false,"given":"Khadijah Rizky","family":"Sumitro","sequence":"additional","affiliation":[{"name":"Department of Child Health, Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia"},{"name":"Department of Child Health, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5366-7605","authenticated-orcid":false,"given":"Juandy","family":"Jo","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science and Technology, Universitas Pelita Harapan, Tangerang 15811, Indonesia"},{"name":"Mochtar Riady Institute for Nanotechnology, Tangerang 15811, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nova","family":"Sitorus","sequence":"additional","affiliation":[{"name":"Danone Specialized Nutrition Indonesia, Jakarta 12940, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S1081-1206(10)62124-2","article-title":"Cow\u2019s milk allergy versus cow milk intolerance","volume":"89","author":"Bahna","year":"2002","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.paed.2007.04.007","article-title":"Adverse reactions to cow\u2019s milk","volume":"17","author":"Fox","year":"2007","journal-title":"Pediatr. Child Health"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Antunes, I.C., Bexiga, R., Pinto, C., Roseiro, L.C., and Quaresma, M.A.G. (2023). Cow\u2019s milk in human nutrition and the emergence of plant-based milk alternatives. Foods, 12.","DOI":"10.3390\/foods12010099"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1159\/000493669","article-title":"Lactose intolerance: Common misunderstandings","volume":"73","year":"2018","journal-title":"Ann. Nutr. Metab."},{"key":"ref_5","first-page":"e178","article-title":"Lactose intolerance in pediatric patients and common misunderstandings about cow\u2019s milk allergy","volume":"50","author":"Biasucci","year":"2021","journal-title":"Pediatr. Ann."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0889-8561(05)70242-3","article-title":"Is it milk allergy or lactose intolerance?","volume":"16","author":"Bahna","year":"1996","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e609","DOI":"10.3399\/bjgp16X686521","article-title":"Differentiating milk allergy (IgE and non-IgE mediated) from lactose intolerance: Understanding the underlying mechanisms and presentations","volume":"66","author":"Walsh","year":"2016","journal-title":"Br. J. Gen. Pract."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1053\/j.nainr.2005.08.004","article-title":"Milk intolerance: Lactose intolerance and cow\u2019s milk protein allergy","volume":"5","author":"Wilson","year":"2005","journal-title":"Newborn Infant Nurs. Rev."},{"key":"ref_9","first-page":"1","article-title":"Cow\u2019s milk consumption and risk of disease","volume":"33","author":"Kaskous","year":"2021","journal-title":"Emir. J. Food Agric."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1136\/adc.48.5.331","article-title":"Sugar-induced diarrhoea in children","volume":"48","author":"Gracey","year":"1973","journal-title":"Arch. Dis. Child."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"263","DOI":"10.5223\/pghn.2022.25.3.263","article-title":"International cross-sectional survey among healthcare professionals on the management of cow\u2019s milk protein allergy and lactose intolerance in infants and children","volume":"25","author":"Madrazo","year":"2022","journal-title":"Pediatr. Gastroenterol. Hepatol. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s40413-017-0173-0","article-title":"Lactose intolerance and gastrointestinal cow\u2019s milk allergy in infants and children\u2014Common misconceptions revisited","volume":"10","author":"Heine","year":"2017","journal-title":"World Allergy Organ. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1097\/MPG.0000000000001052","article-title":"Cow\u2019s milk allergy prescribing is influenced by regional and national guidance","volume":"62","author":"Wauters","year":"2016","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_14","first-page":"S9","article-title":"Lactose intolerance","volume":"24","author":"Vandenplas","year":"2015","journal-title":"Asia Pac. J. Clin. Nutr."},{"key":"ref_15","first-page":"59","article-title":"Lactose intolerance: Myths and facts. An update","volume":"120","author":"Toca","year":"2022","journal-title":"Arch. Argent. Pediatr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1542\/peds.2006-1721","article-title":"Lactose intolerance in infants, children, and adolescents","volume":"118","author":"Heyman","year":"2006","journal-title":"Pediatrics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"315","DOI":"10.4103\/1110-2098.163878","article-title":"Lactose intolerance among pediatrics: Systematic review","volume":"28","author":"ElShafie","year":"2015","journal-title":"Menoufia Med. J."},{"key":"ref_18","first-page":"1","article-title":"Lactose intolerance and health","volume":"192","author":"Wilt","year":"2010","journal-title":"Evid. Rep. Technol. Assess. (Full Rep.)"},{"key":"ref_19","first-page":"29","article-title":"Prevalence, cause and diagnosis of lactose intolerance in children aged 1\u20135 years: A systematic review of 1995-2015 literature","volume":"27","author":"Harvey","year":"2018","journal-title":"Asia Pac. J. Clin. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1177\/000992280304200406","article-title":"Abdominal pain associated with lactose ingestion in children with lactose intolerance","volume":"42","author":"Gremse","year":"2003","journal-title":"Clin. Pediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/S0016-5085(77)80031-0","article-title":"Developmental pattern of small intestinal enterokinase and disaccharidase activities in the human fetus","volume":"72","author":"Antonowicz","year":"1977","journal-title":"Gastroenterology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"437","DOI":"10.5409\/wjcp.v11.i6.437","article-title":"Cow\u2019s milk-induced gastrointestinal disorders: From infancy to adulthood","volume":"11","author":"Saeed","year":"2022","journal-title":"World J. Clin. Pediatr."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Diekmann, L., Pfeiffer, K., and Naim, H.Y. (2015). Congenital lactose intolerance is triggered by severe mutations on both alleles of the lactase gene. BMC Gastroenterol., 15.","DOI":"10.1186\/s12876-015-0261-y"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wanes, D., Husein, D.M., and Naim, H.Y. (2019). Congenital lactase deficiency: Mutations, functional and biochemical implications, and future perspectives. Nutrients, 11.","DOI":"10.3390\/nu11020461"},{"key":"ref_25","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_26","doi-asserted-by":"crossref","unstructured":"Anguita-Ruiz, A., Aguilera, C.M., and Gil, \u00c1. (2020). Genetics of lactose intolerance: An updated review and online interactive world maps of phenotype and genotype frequencies. Nutrients, 12.","DOI":"10.3390\/nu12092689"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1177\/000992287701601208","article-title":"Carbohydrate intolerance associated with acute gastroenteritis: A prospective study of 90 well-nourished Indian infants","volume":"16","author":"Kumar","year":"1977","journal-title":"Clin. Pediatr."},{"key":"ref_28","first-page":"147","article-title":"The relationship of dietary lactose to refractory diarrhoea in infancy","volume":"1","author":"Burke","year":"1965","journal-title":"Aust. Paediatr. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1111\/j.1469-0691.2011.03506.x","article-title":"High prevalence of community-acquired norovirus gastroenteritis among hospitalized children: A prospective study","volume":"17","author":"Obando","year":"2011","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1111\/j.1651-2227.1997.tb09020.x","article-title":"Carbohydrate intolerance after acute gastroenteritis\u2014A disappearing problem in Polish children","volume":"86","author":"Szajewska","year":"1997","journal-title":"Acta Paediatr."},{"key":"ref_31","first-page":"189","article-title":"Admission to hospital with childhood acute gastroenteritis in Kuala Lumpur Malaysia","volume":"62","author":"Poo","year":"2007","journal-title":"Med. J. Malays."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S1081-1206(10)62120-5","article-title":"Frequency of cow\u2019s milk allergy in childhood","volume":"89","year":"2002","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1590\/1678-457X.0019","article-title":"Lactose intolerance and cow\u2019s milk protein allergy","volume":"36","author":"Rangel","year":"2016","journal-title":"Food Sci. Technol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"608372","DOI":"10.3389\/fimmu.2021.608372","article-title":"Strategies and future opportunities for the prevention, diagnosis, and management of cow milk allergy","volume":"12","author":"Goh","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"249784","DOI":"10.1155\/2014\/249784","article-title":"Role of cellular immunity in cow\u2019s milk allergy: Pathogenesis, tolerance induction, and beyond","volume":"2014","author":"Jo","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"100785","DOI":"10.1016\/j.waojou.2023.100785","article-title":"World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow\u2019s Milk Allergy (DRACMA) Guideline update\u2014VII\u2014Milk elimination and reintroduction in the diagnostic process of cow\u2019s milk allergy","volume":"16","author":"Meyer","year":"2023","journal-title":"World Allergy Organ. J."},{"key":"ref_37","unstructured":"Da Silva, P.H.F., Oliveira, V.C.D., and Perin, L.M. (2018). Raw Milk: Balance between Hazards and Benefits, Elsevier Inc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1034\/j.1398-9995.2001.t01-1-00001.x","article-title":"A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force","volume":"56","author":"Johansson","year":"2001","journal-title":"Allergy"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.jaci.2003.12.591","article-title":"Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003","volume":"113","author":"Johansson","year":"2004","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1111\/all.15889","article-title":"Nomenclature of allergic diseases and hypersensitivity reactions: Adapted to modern needs: An EAACI position paper","volume":"78","author":"Jutel","year":"2023","journal-title":"Allergy"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1136\/adc.2006.110999","article-title":"Guidelines for the diagnosis and management of cow\u2019s milk protein allergy in infants","volume":"92","author":"Vandenplas","year":"2007","journal-title":"Arch. Dis. Child."},{"key":"ref_42","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_43","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1097\/MPG.0000000000000501","article-title":"ESPGHAN position paper on management of percutaneous endoscopic gastrostomy in children and adolescents","volume":"60","author":"Heuschkel","year":"2015","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1136\/adc.48.12.963","article-title":"Transient lactose intolerance in infancy","volume":"48","author":"Hull","year":"1973","journal-title":"Arch. Dis. Child."},{"key":"ref_45","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_46","doi-asserted-by":"crossref","unstructured":"Jessen, F.B., Mortz, C.G., Eller, E., Gudichsen, J.H., Baekdal, E.A., and Bindslev-Jensen, C. (2023). A comparison of double-blind, placebo-controlled food challenge and open food challenge. Allergy Eur. J. Allergy Clin. Immunol., 3204\u20133211.","DOI":"10.1111\/all.15834"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Salvatore, S., Agosti, M., Baldassarre, M.E., D\u2019Auria, E., Pensabene, L., Nosetti, L., and Vandenplas, Y. (2021). Cow\u2019s milk allergy or gastroesophageal reflux disease\u2014Can we solve the dilemma in infants?. Nutrients, 13.","DOI":"10.3390\/nu13020297"},{"key":"ref_48","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_49","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1097\/MPG.0b013e31825c9482","article-title":"Diagnostic approach and management of cow\u2019s-milk protein allergy in infants and children: ESPGHAN GI Committee practical guidelines","volume":"55","author":"Koletzko","year":"2012","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/apa.12962","article-title":"Algorithms for managing infant constipation, colic, regurgitation and cow\u2019s milk allergy in formula-fed infants","volume":"104","author":"Vandenplas","year":"2015","journal-title":"Acta Paediatr."},{"key":"ref_51","first-page":"193.e1","article-title":"Non-IgE-mediated cow\u2019s milk allergy: Consensus document of the Spanish Society of Paediatric Gastroenterology, Hepatology, and Nutrition (SEGHNP), the Spanish Association of Paediatric Primary Care (AEPAP), the Spanish Society of Extra-hospital Paediatric","volume":"90","author":"Burriel","year":"2019","journal-title":"An. Pediatr. (Engl. Ed.)"},{"key":"ref_52","first-page":"235","article-title":"Consensus on the diagnosis and treatment of cow\u2019s milk protein allergy of the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition","volume":"87","author":"Toca","year":"2022","journal-title":"Rev. Gastroenterol. M\u00e9x. (Engl. Ed.)"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Vandenplas, Y., Broekaert, I., Domell\u00f6f, M., Indrio, F., Lapillonne, A., Pienar, C., Ribes-Koninckx, C., Shamir, R., Szajewska, H., and Thapar, N. (2023). An ESPGHAN position paper on the diagnosis, management and prevention of cow\u2019s milk allergy. J. Pediatr. Gastroenterol. Nutr.","DOI":"10.1097\/MPG.0000000000003897"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/3\/414\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:52:08Z","timestamp":1760104328000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/3\/414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,31]]},"references-count":53,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["nu16030414"],"URL":"https:\/\/doi.org\/10.3390\/nu16030414","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,31]]}}}