View source for Lactose intolerance

{{Short description|Inability to digest lactose}}
{{distinguish|Milk allergy}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox medical condition (new)
| name            = Lactose intolerance
| synonyms        = Lactase deficiency, hypolactasia, alactasia
| image           = Lactose Haworth.svg
| caption         = Lactose is made up of [[disaccharide|two simple sugars]]
| field           = [[Gastroenterology]]
| symptoms        = Abdominal pain, [[bloating]], [[diarrhea]], [[flatulence]], [[nausea]]<ref name=NIH2014Dig/>
| complications   = Does not cause damage to the GI tract<ref name=Heyman2006/>
| onset           = 30–120 minutes after consuming dairy products<ref name=NIH2014Dig/>
| causes          = Non-increased ability to digest [[lactose]] (genetic, small intestine injury)<ref name=NIH2014Dig/>
| differential    = [[Irritable bowel syndrome]], [[celiac disease]], [[inflammatory bowel disease]], [[milk allergy]]<ref name=NIH2014Dig/>
| treatment       = Decreasing lactose in the diet, [[lactase supplements]], treat the underlying cause<ref name=NIH2014Dig/>
| medication      = Lactase
| frequency       = ~65% of people worldwide (less common in Northern Europeans and East Africans)<ref name=Stat2020/>
}}
<!-- Definition and symptoms -->

'''Lactose intolerance''' is caused by a lessened ability or a complete inability to digest [[lactose]], a sugar found in [[dairy product]]s.<ref name=NIH2014Dig/> Humans vary in the amount of lactose they can tolerate before symptoms develop.<ref name=NIH2014Dig/> Symptoms may include [[abdominal pain]], [[bloating]], [[diarrhea]], [[flatulence]], and [[nausea]].<ref name=NIH2014Dig/> These symptoms typically start thirty minutes to two hours after eating or drinking something containing lactose,<ref name=NIH2014Dig/> with the severity typically depending on the amount consumed.<ref name=NIH2014Dig>{{cite web|title=Lactose Intolerance|url=https://www.niddk.nih.gov/health-information/health-topics/digestive-diseases/lactose-intolerance/Pages/facts.aspx|website=NIDDK|access-date=25 October 2016|date=June 2014|url-status=live|archive-url=https://web.archive.org/web/20161025111752/https://www.niddk.nih.gov/health-information/health-topics/digestive-diseases/lactose-intolerance/Pages/facts.aspx|archive-date=25 October 2016}}</ref> Lactose intolerance does not cause damage to the [[gastrointestinal tract]].<ref name=Heyman2006>{{cite journal | vauthors = Heyman MB | s2cid = 2996092 | title = Lactose intolerance in infants, children, and adolescents | journal = Pediatrics | volume = 118 | issue = 3 | pages = 1279–86 | date = September 2006 | pmid = 16951027 | doi = 10.1542/peds.2006-1721 | doi-access = free }}</ref>

<!-- Cause -->
Lactose intolerance is due to the lack of the [[enzyme]] [[lactase]] in the [[small intestines]] to break lactose down into [[glucose]] and [[galactose]].<ref name=Stat2020>{{cite book |last1=Malik |first1=TF |last2=Panuganti |first2=KK |chapter=Lactose Intolerance |title=(StatPearls [Internet]) |publisher=StatPearls |date=January 2020 |pmid=30335318 |id=NBK532285 }}</ref> There are four types: primary, secondary, developmental, and congenital.<ref name=NIH2014Dig/> Primary lactose intolerance occurs as the amount of lactase declines as people grow up.<ref name=NIH2014Dig/> Secondary lactose intolerance is due to injury to the small intestine. Such injury could be the result of infection, [[celiac disease]], [[inflammatory bowel disease]], or other diseases.<ref name=NIH2014Dig/><ref name=BerniCananiPezzella2016>{{cite journal | vauthors = Berni Canani R, Pezzella V, Amoroso A, Cozzolino T, Di Scala C, Passariello A | title = Diagnosing and Treating Intolerance to Carbohydrates in Children | journal = Nutrients | volume = 8 | issue = 3 | pages = 157 | date = March 2016 | pmid = 26978392 | pmc = 4808885 | doi = 10.3390/nu8030157 | doi-access = free }}</ref> Developmental lactose intolerance may occur in [[premature babies]] and usually improves over a short period of time.<ref name=NIH2014Dig/> Congenital lactose intolerance is an extremely rare [[genetic disorder]] in which little or no lactase is made from birth.<ref name=NIH2014Dig/> The reduction of lactase production starts typically in late childhood or early adulthood,<ref name=NIH2014Dig/> but prevalence increases with age.

Non-digestion is not a disease ''by itself'', which even reduces total caloric intake if the microbiota do not convert it into absorbable nutrients. The symptoms are an effect of the fermentation sponsored by unabsorbed nutrients.  

<!-- Diagnosis and treatment -->
Diagnosis may be confirmed if symptoms resolve following eliminating lactose from the diet.<ref name=NIH2014Dig/> Other supporting tests include a [[hydrogen breath test]] and a [[stool acidity test]].<ref name=NIH2014Dig/> Other conditions that may produce similar symptoms include [[irritable bowel syndrome]], [[celiac disease]], and [[inflammatory bowel disease]].<ref name=NIH2014Dig/> Lactose intolerance is different from a [[milk allergy]].<ref name=NIH2014Dig/> Management is typically by decreasing the amount of lactose in the diet, taking [[lactase supplements]], or treating the underlying disease.<ref name=NIH2014Dig/><ref name=Vandenplas2015 /> People are typically able to drink at least one cup of milk without developing symptoms, with greater amounts tolerated if drunk with a meal or throughout the day.<ref name=NIH2014Dig/><ref name=SuchyBrannon2010>{{cite journal | vauthors = Suchy FJ, Brannon PM, Carpenter TO, Fernandez JR, Gilsanz V, Gould JB, Hall K, Hui SL, Lupton J, Mennella J, Miller NJ, Osganian SK, Sellmeyer DE, Wolf MA | title = NIH consensus development conference statement: Lactose intolerance and health | journal = NIH Consensus and State-Of-The-Science Statements | volume = 27 | issue = 2 | pages = 1–27 | date = February 2010 | pmid = 20186234 | url = https://consensus.nih.gov/2010/lactosestatement.htm | type = Consensus Development Conference, NIH. Review | archive-url = https://web.archive.org/web/20161218125118/https://consensus.nih.gov/2010/lactosestatement.htm | url-status = live | archive-date = 2016-12-18 }}</ref>

<!-- Epidemiology & History -->
Worldwide, around 65% of adults are affected by lactose malabsorption.<ref name=Bayless2017>{{cite journal | vauthors = Bayless TM, Brown E, Paige DM | s2cid = 2941077 | title = Lactase Non-persistence and Lactose Intolerance | journal = Current Gastroenterology Reports | volume = 19 | issue = 5 | pages = 23 | date = May 2017 | pmid = 28421381 | doi = 10.1007/s11894-017-0558-9 }}</ref> Other [[mammals]] usually lose the ability to digest lactose after [[weaning]]. Lactose intolerance is the [[ancestral state]] of all humans before the [[Recent human evolution|recent evolution]] of [[lactase persistence]] in some cultures, which extends lactose tolerance into adulthood.<ref name="Genetics of lactase persistence and"/> Lactase persistence evolved in several populations independently, probably as an adaptation to the [[domestication]] of [[dairy animals]] around 10,000 years ago.<ref>{{cite journal | vauthors = Ségurel L, Bon C | title = On the Evolution of Lactase Persistence in Humans | journal = Annual Review of Genomics and Human Genetics | volume = 18 | issue = 1 | pages = 297–319 | date = August 2017 | pmid = 28426286 | doi = 10.1146/annurev-genom-091416-035340 }}</ref><ref name="Lactose digestion and the evolution">{{cite journal | vauthors = Ingram CJ, Mulcare CA, Itan Y, Thomas MG, Swallow DM | s2cid = 3329285 | title = Lactose digestion and the evolutionary genetics of lactase persistence | journal = Human Genetics | volume = 124 | issue = 6 | pages = 579–91 | date = January 2009 | pmid = 19034520 | doi = 10.1007/s00439-008-0593-6 }}</ref> Today the prevalence of lactose tolerance varies widely between regions and ethnic groups. The ability to digest lactose is most common in people of Northern European descent, and to a lesser extent in some parts of [[Central Asia]], the [[Middle East]] and [[Africa]].<ref name=Bayless2017/> 

Lactose intolerance is most common among people of East Asian descent, with 90% lactose intolerance, people of Jewish descent, in many [[African countries]] and [[Arab countries]], and among people of Southern European descent (notably amongst Greeks and Italians). [[Traditional food]] cultures reflect local variations in tolerance and historically many societies have adapted to low levels of tolerance by making [[dairy product]]s that contain less lactose than fresh milk.<ref name="SilanikoveLeitner2015" /> One ethnographic example of this is ''[[kumis]]'', a fermented milk product that contains little to no lactose, which is the main source of dairy nutrition in [[Mongolia]].<ref>{{cite web |last1=Abdel-Salam |first1=Ahmed M. |last2=Al-Dekheil |first2=Ali |last3=Babkr |first3=Ali |last4=Farahna |first4=Mohammed |last5=Mousa |first5=Hassan M. |title=High fiber probiotic fermented mare's milk reduces the toxic effects of mercury in rats |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC3338224/ |website=North American Journal of Medical Sciences |pages=569–575 |doi=10.4297/najms.2010.2569 |date=December 2010 |quote="Fermentation destroys lactose in milk, converting it into lactic acid, ethanol, and carbon dioxide. This makes kumis acceptable for lactose intolerant people. Traditional kumis is prepared by mixing fermented milk with fresh raw mares’ milk."}}</ref>

The [[medicalization]] of lactose intolerance as a disorder has been attributed to biases in research history, since most early studies were conducted amongst populations which are normally tolerant,<ref name="Genetics of lactase persistence and"/> as well as the cultural and economic importance and impact of milk in countries such as the United States.<ref>{{cite journal |last1=Wiley |first1=Andrea S. |title="Drink Milk for Fitness": The Cultural Politics of Human Biological Variation and Milk Consumption in the United States |journal=American Anthropologist |date=2004 |volume=106 |issue=3 |pages=506–517 |doi=10.1525/aa.2004.106.3.506 |jstor=3567615 |doi-access=free }}</ref>

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== Terminology ==
''Lactose intolerance'' primarily refers to a syndrome with one or more symptoms upon the consumption of food substances containing [[Lactose|lactose sugar]]. Individuals may be lactose intolerant to varying degrees, depending on the severity of these symptoms.

''Hypolactasia'' is the term specifically for the [[small intestine]] producing little or no [[lactase enzyme]].<ref>{{cite journal | vauthors = Lember M | title = Hypolactasia: a common enzymes deficiency leading to lactose malabsorption and intolerance | journal = Polskie Archiwum Medycyny Wewnetrznej | volume = 122 | pages = 60–4 | year = 2012 | issue = Suppl 1 | pmid = 23222197 | doi=10.20452/pamw.1519}}</ref> If a person with hypolactasia consumes lactose sugar, it results in ''lactose malabsorption''.<ref name="Heyman2006" /> The digestive system is unable to process the lactose sugar, and the unprocessed sugars in the gut produce the symptoms of ''lactose intolerance''.

Lactose intolerance is not an [[Food allergy|allergy]], because it is not an immune response, but rather a sensitivity to dairy caused by a deficiency of lactase enzyme. [[Milk allergy]], occurring in about 2% of the population, is a separate condition, with distinct symptoms that occur when the presence of milk proteins trigger an immune reaction.<ref name="Bahna2002">{{cite journal | vauthors = Bahna SL | title = Cow's milk allergy versus cow milk intolerance | journal = Annals of Allergy, Asthma & Immunology | volume = 89 | issue = 6 Suppl 1 | pages = 56–60 | date = December 2002 | pmid = 12487206 | doi = 10.1016/S1081-1206(10)62124-2 | type = Review. Comparative Study. }}</ref>

==Signs and symptoms==
The principal manifestation of lactose intolerance is an adverse reaction to products containing lactose (primarily milk), including abdominal [[bloating]] and [[cramps]], [[flatulence]], [[diarrhea]], [[nausea]], [[borborygmi]], and [[vomiting]] (particularly in [[adolescents]]). These appear one-half to two hours after consumption.<ref name=NIH2014Dig/> The severity of these signs and symptoms typically increases with the amount of lactose consumed; most lactose-intolerant people can tolerate a certain level of lactose in their diets without ill effects.<ref name="Savaiano and Levitt 1987" /><ref name="Madry et al 2011">{{cite journal | vauthors = Mądry E, Krasińska B, Woźniewicz MG, Drzymała-Czyż SA, Bobkowski W, Torlińska T, Walkowiak JA | title = Tolerance of different dairy products in subjects with symptomatic lactose malabsorption due to adult type hypolactasia | journal = Gastroenterology Review | volume = 5 | pages = 310–315 | year = 2011 | doi = 10.5114/pg.2011.25381 | doi-access = free }}</ref>

Because lactose intolerance is not an allergy, it does not produce [[Allergy#Signs and symptoms|allergy symptoms]] (such as itching, [[hives]], or [[anaphylaxis]]).

==Causes==
Lactose intolerance is a consequence of [[lactase]] deficiency, which may be genetic ([[#Primary hypolactasia|primary hypolactasia]] and [[#Primary congenital alactasia|primary congenital alactasia]]) or environmentally induced ([[#Secondary hypolactasia|secondary or acquired hypolactasia]]). In either case, symptoms are caused by insufficient levels of lactase in the lining of the [[duodenum]]. Lactose, a [[disaccharide]] molecule found in milk and dairy products, cannot be directly absorbed through the wall of the small intestine into the bloodstream, so, in the absence of lactase, passes intact into the [[Colon (anatomy)|colon]].{{Citation needed|reason=nutrients take 7-9 hours to reach colon but symptoms appear after 2 hours|date=January 2019}} [[Gut flora|Bacteria]] in the colon can metabolise lactose, and the resulting [[fermentation (biochemistry)|fermentation]] produces copious amounts of gas (a mixture of [[hydrogen]], [[carbon dioxide]], and [[methane]]) that causes the various abdominal symptoms. The unabsorbed sugars and fermentation products also raise the [[osmotic pressure]] of the colon, causing an increased flow of water into the bowels (diarrhea).<ref name="eMedicine overview">{{EMedicine|article|187249|Lactose intolerance|overview}}</ref><ref name="Genetics of lactase persistence and">{{cite journal | vauthors = Swallow DM | title = Genetics of lactase persistence and lactose intolerance | journal = Annual Review of Genetics | volume = 37 | pages = 197–219 | year = 2003 | pmid = 14616060 | doi = 10.1146/annurev.genet.37.110801.143820 }}</ref>

Lactose intolerance in infants (congenital lactase deficiency) is caused by mutations in the ''LCT'' gene. The ''LCT'' gene provides the instructions for making lactase. Mutations are believed to interfere with the function of lactase, causing affected infants to have a severely impaired ability to digest lactose in breast milk or formula.<ref name="medlineplus.gov">{{Cite web |title=Lactose intolerance: MedlinePlus Genetics |url=https://medlineplus.gov/genetics/condition/lactose-intolerance/ |access-date=2022-03-22 |website=medlineplus.gov |language=en}}</ref> Lactose intolerance in adulthood is a result of gradually decreasing activity (expression) of the ''LCT'' gene after infancy, which occurs in most humans. The specific DNA sequence in the ''[[MCM6]]'' gene helps control whether the ''LCT'' gene is turned on or off.<ref>{{cite web|url=http://ghr.nlm.nih.gov/gene/MCM6|title=MCM6|author=Genetics Home Reference|website=Genetics Home Reference|url-status=live|archive-url=https://web.archive.org/web/20131004212751/http://ghr.nlm.nih.gov/gene/MCM6|archive-date=2013-10-04}}</ref> At least several thousand years ago, some humans developed a mutation in the ''MCM6'' gene that keeps the ''LCT'' gene turned on even after breast feeding is stopped.<ref name="slate.com">{{cite web|url=http://www.slate.com/articles/health_and_science/human_evolution/2012/10/evolution_of_lactose_tolerance_why_do_humans_keep_drinking_milk.html|title=Evolution of lactose tolerance: Why do humans keep drinking milk?|author=Benjamin Phelan|date=23 October 2012|website=Slate Magazine|url-status=live|archive-url=https://web.archive.org/web/20130831021427/http://www.slate.com/articles/health_and_science/human_evolution/2012/10/evolution_of_lactose_tolerance_why_do_humans_keep_drinking_milk.html|archive-date=31 August 2013}}</ref> Populations that are lactose intolerant lack this mutation.  The ''LCT'' and ''MCM6'' genes are both located on the long arm (q) of chromosome 2 in region 21. The locus can be expressed as 2q21.<ref name="slate.com"/> The lactase deficiency also could be linked to certain heritages and varies widely. A 2016 study of over 60,000 participants from 89 countries found regional prevalence of lactose malabsorption was "64% (54–74) in Asia (except Middle East), 47% (33–61) in eastern Europe, Russia, and former Soviet Republics, 38% (CI 18–57) in Latin America, 70% (57–83) in the Middle East, 66% (45–88) in northern Africa, 42% (13–71) in northern America, 45% (19–71) in Oceania, 63% (54–72) in sub-Saharan Africa, and 28% (19–37) in northern, southern and western Europe." According to Johns Hopkins Medicine, lactose intolerance is more common in Asian Americans, African Americans, Mexican Americans, and Native Americans.<ref>{{cite web|title=Lactose Intolerance|url=http://www.hopkinsmedicine.org/healthlibrary/conditions/digestive_disorders/lactose_intolerance_85,P00388/|publisher=Johns Hopkins Health Library|access-date=2014-02-18|url-status=live|archive-url=https://web.archive.org/web/20140226235255/http://www.hopkinsmedicine.org/healthlibrary/conditions/digestive_disorders/lactose_intolerance_85,P00388/|archive-date=2014-02-26}}</ref> Analysis of the DNA of 94 ancient skeletons in Europe and Russia concluded that the mutation for lactose tolerance appeared about 4,300 years ago and spread throughout the European population.<ref>{{cite journal |first=Ann |last=Gibbons |title=How Europeans evolved white skin |date=2 April 2015 |journal=Science |url=https://www.science.org/content/article/how-europeans-evolved-white-skin |doi=10.1126/science.aab2435}}</ref>

Some human populations have developed [[lactase persistence]], in which lactase production continues into adulthood probably as a response to the benefits of being able to digest milk from farm animals. Some have argued that this links intolerance to [[natural selection]] favoring lactase-persistent individuals, but it is also consistent with a physiological response to decrease lactase production when it is not needed in cultures in which dairy products are not an available food source.<ref>{{cite journal | vauthors = Beja-Pereira A, Luikart G, England PR, Bradley DG, Jann OC, Bertorelle G, Chamberlain AT, Nunes TP, Metodiev S, Ferrand N, Erhardt G | s2cid = 20415396 | title = Gene-culture coevolution between cattle milk protein genes and human lactase genes | journal = Nature Genetics | volume = 35 | issue = 4 | pages = 311–3 | date = December 2003 | pmid = 14634648 | doi = 10.1038/ng1263 }}</ref> Although populations in Europe, India, Arabia, and Africa were first thought to have high rates of lactase persistence because of a single mutation, lactase persistence has been traced to a number of mutations that occurred independently.<ref name="Lactose digestion and the evolution"/> Different alleles for lactase persistence have developed at least three times in East African populations, with persistence extending from 26% in [[Tanzania]] to 88% in the [[Beja people|Beja]] pastoralist population in [[Sudan]].<ref name=Tishkoff07/>

The accumulation of [[Epigenetics|epigenetic]] factors, primarily [[DNA methylation]], in the extended LCT region, including the gene [[Enhancer (genetics)|enhancer]] located in the ''MCM6'' gene near C/T-13910 SNP, may also contribute to the onset of lactose intolerance in adults.<ref>{{cite journal | vauthors = Labrie V, Buske OJ, Oh E, Jeremian R, Ptak C, Gasiūnas G, Maleckas A, Petereit R, Žvirbliene A, Adamonis K, Kriukienė E, Koncevičius K, Gordevičius J, Nair A, Zhang A, Ebrahimi S, Oh G, Šikšnys V, Kupčinskas L, Brudno M, Petronis A | title = Lactase nonpersistence is directed by DNA-variation-dependent epigenetic aging | journal = Nature Structural & Molecular Biology | volume = 23 | issue = 6 | pages = 566–73 | date = June 2016 | pmid = 27159559 | pmc = 4899171 | doi = 10.1038/nsmb.3227 }}</ref><ref name=Oh17>{{Cite journal|last1=Oh|first1=Edward|last2=Jeremian|first2=Richie|last3=Oh|first3=Gabriel|last4=Groot|first4=Daniel|last5=Susic|first5=Miki|last6=Lee|first6=KwangHo|last7=Foy|first7=Kelly|last8=Laird|first8=Peter W.|last9=Petronis|first9=Arturas|last10=Labrie|first10=Viviane|date=2017-01-31|title=Transcriptional heterogeneity in the lactase gene within cell-type is linked to the epigenome|journal=Scientific Reports|volume=7|issue=1|page=41843|doi=10.1038/srep41843|pmid=28139744|pmc=5282553|bibcode=2017NatSR...741843O |doi-access=free}}</ref> Age-dependent expression of ''LCT'' in mice intestinal epithelium has been linked to DNA methylation in the gene enhancer.<ref name=Oh17 />

Lactose intolerance is classified according to its causes as:

; Primary hypolactasia
: Primary hypolactasia, or primary lactase deficiency, is genetic, develops in childhood at various ages, and is caused by the absence of a lactase persistence allele. In individuals without the lactase persistence allele, less lactase is produced by the body over time, leading to hypolactasia in adulthood.<ref name="Heyman2006" /><ref name=variant>{{cite journal | vauthors = Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Järvelä I | s2cid = 21430931 | title = Identification of a variant associated with adult-type hypolactasia | journal = Nature Genetics | volume = 30 | issue = 2 | pages = 233–7 | date = February 2002 | pmid = 11788828 | doi = 10.1038/ng826 }}</ref> The frequency of lactase persistence, which allows lactose tolerance, varies enormously worldwide, with the highest prevalence in Northwestern Europe, declines across southern Europe and the Middle East and is low in Asia and most of Africa, although it is common in [[Pastoralism|pastoralist]] populations from Africa.<ref name="Genetics of lactase persistence and"/>
; Secondary hypolactasia
: Secondary hypolactasia or secondary lactase deficiency, also called acquired hypolactasia or acquired lactase deficiency, is caused by an injury to the [[small intestine]]. This form of lactose intolerance can occur in both infants and lactase persistent adults and is generally reversible.<ref>{{cite web|title=Lactose intolerance|url=http://www.milk.co.uk/page.aspx?intPageID=59|url-status=dead|archive-url=https://web.archive.org/web/20160309024816/http://www.milk.co.uk/page.aspx?intPageID=59|archive-date=9 March 2016|website=The Dairy Council UK}}</ref> It may be caused by acute [[gastroenteritis]], [[coeliac disease]], [[Crohn's disease]], [[ulcerative colitis]],<ref>[http://www.nhs.uk/Conditions/lactose-intolerance/Pages/Causes.aspx Secondary lactase deficiency causes] {{webarchive|url=https://web.archive.org/web/20160731180402/http://www.nhs.uk/Conditions/lactose-intolerance/Pages/Causes.aspx |date=2016-07-31 }}</ref> [[chemotherapy]], [[intestinal parasites]] (such as [[giardia]]), or other environmental causes.<ref name="Heyman2006" /><ref>{{cite book |last1=Lawson |first1=Margaret |last2=Bentley |first2=Donald |last3=Lifschitz |first3=Carlos | title=Pediatric gastroenterology and clinical nutrition |year=2002 |publisher=Remedica |location=London |isbn=978-1-901346-43-5 |url=https://books.google.com/books?id=dLLgzcMsbo0C&pg=PA109 |page=109 |url-status=live |archive-url=https://web.archive.org/web/20161219183419/https://books.google.com/books?id=dLLgzcMsbo0C&pg=PA109 |archive-date=2016-12-19}}</ref><ref name="eMedicine pediatric">{{Emedicine|emerg|930971|Pediatric Lactose Intolerance}}</ref><ref name=SwagertyWalling2002>{{cite journal | vauthors = Swagerty DL, Walling AD, Klein RM | title = Lactose intolerance | journal = American Family Physician | volume = 65 | issue = 9 | pages = 1845–50 | date = May 2002 | pmid = 12018807 | url = http://www.aafp.org/link_out?pmid=12018807 }}</ref>
; Primary congenital alactasia
: Primary congenital alactasia, also called congenital lactase deficiency, is an extremely rare, [[autosomal recessive]] enzyme defect that prevents lactase expression from birth.<ref name="Heyman2006" /> People with congenital lactase deficiency cannot digest lactose from birth, so cannot digest breast milk. This genetic defect is characterized by a complete lack of lactase (alactasia). About 40 cases have been reported worldwide, mainly limited to [[Finland]]. Before the 20th century, babies born with congenital lactase deficiency often did not survive,<ref name="Heyman2006" /> but death rates decreased with [[soybean]]-derived [[infant formula]]s and manufactured lactose-free dairy products.<ref name="Sinden_1991">{{cite journal | vauthors = Sinden AA, Sutphen JL | title = Dietary treatment of lactose intolerance in infants and children | journal = Journal of the American Dietetic Association | volume = 91 | issue = 12 | pages = 1567–71 | date = December 1991 | doi = 10.1016/S0002-8223(21)01435-8 | pmid = 1960350 | s2cid = 32296893 }}</ref>

== Diagnosis ==

In order to assess lactose intolerance, intestinal function is challenged by ingesting more dairy products than can be readily digested.  Clinical symptoms typically appear within 30 minutes, but may take up to two hours, depending on other foods and activities.<ref>{{cite web |author=R. Bowen |title=Lactose Intolerance (Lactase Non-Persistence) |url=http://www.vivo.colostate.edu/hbooks/pathphys/digestion/smallgut/lactose_intol.html |date=December 28, 2006 |publisher=Colorado State University |website=Pathophysiology of the Digestive System |url-status=live |archive-url=https://web.archive.org/web/20100623213029/http://www.vivo.colostate.edu/hbooks/pathphys/digestion/smallgut/lactose_intol.html |archive-date=June 23, 2010 }}</ref>  Substantial variability in response (symptoms of nausea, cramping, bloating, diarrhea, and flatulence) is to be expected, as the extent and severity of lactose intolerance varies among individuals.<ref>{{Cite journal | url=https://www.ncbi.nlm.nih.gov/books/NBK532285/ | title=Lactose Intolerance | date=2023-04-17 | access-date=2024-05-27 | website=www.ncbi.nlm.nih.gov | first1=Talia F. | last1=Malik | first2=Kiran K. | last2=Panuganti| pmid=30335318 }}</ref>

The next step is to determine whether it is due to primary lactase deficiency or an underlying disease that causes secondary lactase deficiency.<ref name="Heyman2006" /> Physicians should investigate the presence of undiagnosed [[coeliac disease]], [[Crohn's disease]], or other [[enteropathy|enteropathies]] when secondary lactase deficiency is suspected and infectious gastroenteritis has been ruled out.<ref name="Heyman2006" />

Lactose intolerance is distinct from [[milk allergy]], an immune response to cow's milk proteins. They may be distinguished in diagnosis by giving lactose-free milk, producing no symptoms in the case of lactose intolerance, but the same reaction as to normal milk in the presence of a milk allergy. A person can have both conditions. If positive confirmation is necessary, four tests are available.<ref>{{cite journal | vauthors = Olivier CE, Lorena SL, Pavan CR, dos Santos RA, dos Santos Lima RP, Pinto DG, da Silva MD, de Lima Zollner R | title = Is it just lactose intolerance? | journal = Allergy and Asthma Proceedings | volume = 33 | issue = 5 | pages = 432–6 | year = 2012 | pmid = 23026186 | doi = 10.2500/aap.2012.33.3584 }}</ref>

=== Hydrogen breath test ===
In a [[hydrogen breath test]], the most accurate lactose intolerance test, after an overnight fast, 25 grams of lactose (in a solution with water) are swallowed. If the lactose cannot be digested, enteric bacteria metabolize it and produce hydrogen, which, along with methane, if produced, can be detected on the patient's breath by a clinical gas chromatograph or compact solid-state detector. The test takes about 2.5 hours to complete. If the hydrogen levels in the patient's breath are high, they may have lactose intolerance. This test is not usually done on babies and very young children, because it can cause severe diarrhea.<ref>{{cite web|url=http://www.webmd.com/digestive-disorders/tc/lactose-intolerance-exams-and-tests|title=Lactose Intolerance Tests and Results|website=WebMD|url-status=live|archive-url=https://web.archive.org/web/20140202180831/http://www.webmd.com/digestive-disorders/tc/lactose-intolerance-exams-and-tests|archive-date=2014-02-02}}</ref>

=== Lactose tolerance test ===
In conjunction, measuring blood glucose level every 10 to 15 minutes after ingestion will show a "flat curve" in individuals with lactose malabsorption, while the lactase persistent will have a significant "top", with a typical elevation of 50% to 100%, within one to two hours. However, due to the need for frequent blood sampling, this approach has been largely replaced by breath testing.<ref>{{cite web | url=http://www.webmd.com/digestive-disorders/hydrogen-breath-test | publisher=WebMD | title=Hydrogen Breath Test and Lactose Intolerance | access-date=2017-08-19 | url-status=live | archive-url=https://web.archive.org/web/20170816012411/http://www.webmd.com/digestive-disorders/hydrogen-breath-test | archive-date=2017-08-16 }}</ref>

After an overnight fast, blood is drawn and then 50 grams of lactose (in aqueous solution) are swallowed. Blood is then drawn again at the 30-minute, 1-hour, 2-hour, and 3-hour marks.  If the lactose cannot be digested, blood glucose levels will rise by less than 20&nbsp;mg/dl.<ref>{{cite web|url=https://www.nlm.nih.gov/medlineplus/ency/article/003500.htm|date=3 May 2011|title=Lactose tolerance tests|url-status=live|archive-url=https://web.archive.org/web/20160527051702/https://www.nlm.nih.gov/medlineplus/ency/article/003500.htm|archive-date=27 May 2016}}</ref>

=== Stool acidity test ===
This test can be used to diagnose lactose intolerance in infants, for whom other forms of testing are risky or impractical.<ref>{{cite web |author=National Digestive Diseases Information Clearinghouse |title=Lactose Intolerance&nbsp;— How is lactose intolerance diagnosed? |url=http://digestive.niddk.nih.gov/ddiseases/pubs/lactoseintolerance/#diagnosed |date=March 2006 |publisher=National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health |url-status=dead |archive-url=https://web.archive.org/web/20111125192619/http://digestive.niddk.nih.gov/ddiseases/pubs/lactoseintolerance/#diagnosed |archive-date=2011-11-25 |access-date=2004-11-19 }}</ref> The infant is given lactose to drink. If the individual is tolerant, the lactose is digested and absorbed in the small intestine; otherwise, it is not digested and absorbed, and it reaches the colon. The bacteria in the colon, mixed with the lactose, cause acidity in stools. Stools passed after the ingestion of the lactose are tested for level of acidity. If the stools are acidic, the infant is intolerant to lactose.<ref>{{cite web|title=Stool Acidity Test|url=http://www.medicinenet.com/stool_acidity_test/article.htm#stool|publisher=Jay W. Marks, M.D.|access-date=2011-05-20|url-status=live|archive-url=https://web.archive.org/web/20110516210041/http://www.medicinenet.com/stool_acidity_test/article.htm#stool|archive-date=2011-05-16}}</ref>
Stool pH in lactose intolerance is less than 5.5.

=== Intestinal biopsy ===
An intestinal biopsy must confirm lactase deficiency following discovery of elevated hydrogen in the hydrogen breath test.<ref name="Berdanier">{{cite book | last1 = Hargrove | first1 = James L. | last2 = Berdanier | first2 = Carolyn D. |title=Nutrition and gene expression |publisher=CRC Press |location=Boca Raton |year=1993 |isbn=978-0-8493-6961-2 }}{{page needed|date=June 2018}}</ref>  Modern techniques have enabled a bedside test, identifying presence of lactase enzyme on upper gastrointestinal endoscopy instruments.<ref>{{cite journal | vauthors = Kuokkanen M, Myllyniemi M, Vauhkonen M, Helske T, Kääriäinen I, Karesvuori S, Linnala A, Härkönen M, Järvelä I, Sipponen P | title = A biopsy-based quick test in the diagnosis of duodenal hypolactasia in upper gastrointestinal endoscopy | journal = Endoscopy | volume = 38 | issue = 7 | pages = 708–12 | date = July 2006 | pmid = 16761211 | doi = 10.1055/s-2006-925354 | s2cid = 260130448 }}</ref>  However, for research applications such as [[mRNA]] measurements, a specialist laboratory is required.

=== Stool sugar chromatography ===
Chromatography can be used to separate and identify undigested sugars present in faeces. Although lactose may be detected in the faeces of people with lactose intolerance, this test is not considered reliable enough to conclusively diagnose or exclude lactose intolerance.{{Citation needed|date=July 2014}}

=== Genetic diagnostic ===
Genetic tests may be useful in assessing whether a person has primary lactose intolerance. Lactase activity persistence in adults is associated with two [[polymorphism (biology)|polymorphisms]]: C/T 13910 and G/A 22018 located in the ''MCM6'' gene.<ref name="variant"/> These polymorphisms may be detected by [[molecular biology]] techniques at the [[DNA]] extracted from blood or saliva samples; genetic kits specific for this diagnosis are available. The procedure consists of extracting and amplifying DNA from the sample, following with a hybridation protocol in a strip. Colored bands are obtained as result, and depending on the different combinations, it would be possible to determine whether the patient is lactose intolerant. This test allows a noninvasive definitive diagnostic.{{citation needed|date=May 2022}}

== Management ==
When lactose intolerance is due to secondary lactase deficiency, treatment of the underlying disease may allow lactase activity to return to normal levels.<ref name=Vandenplas2015>{{cite journal | vauthors = Vandenplas Y | title = Lactose intolerance | journal = Asia Pacific Journal of Clinical Nutrition | volume = 24  | issue =  Suppl 1| pages = S9–13 | year = 2015 | pmid = 26715083 | doi = 10.6133/apjcn.2015.24.s1.02 }}</ref> In people with celiac disease, lactose intolerance normally reverts or improves several months after starting a [[gluten-free diet]], but temporary dietary restriction of lactose may be needed.<ref name=BerniCananiPezzella2016 /><ref name=LevyBernstein2014>{{cite journal | vauthors = Levy J, Bernstein L, Silber N | title = Celiac disease: an immune dysregulation syndrome | journal = Current Problems in Pediatric and Adolescent Health Care | volume = 44 | issue = 11 | pages = 324–7 | date = December 2014 | pmid = 25499458 | doi = 10.1016/j.cppeds.2014.10.002 | type = Review | quote = Initially, reduced levels of lactase and sucrase activities might necessitate further dietary restrictions until the villi have healed and those sugars are better tolerated. }}</ref>

People with primary lactase deficiency cannot modify their body's ability to produce lactase.<ref name=NIH2014Dig /> In societies where lactose intolerance is the norm, it is not considered a condition that requires treatment. However, where dairy is a larger component of the normal diet, a number of efforts may be useful. There are four general principles in dealing with lactose intolerance: avoidance of dietary lactose, substitution to maintain nutrient intake, regulation of calcium intake, and use of enzyme substitute.<ref name="Berdanier" /> Regular consumption of dairy food by lactase deficient individuals may also reduce symptoms of intolerance by promoting colonic bacteria adaptation.<ref name="SilanikoveLeitner2015" />

=== Dietary avoidance ===
The primary way of managing the symptoms of lactose intolerance is to limit the intake of lactose to a level that can be tolerated.<ref name="NHS2016">{{cite web|url=http://www.nhs.uk/Conditions/lactose-intolerance/Pages/Treatment.aspx|title=Lactose intolerance - Treatment|website=NHS UK|access-date=11 August 2017|url-status=live|archive-url=https://web.archive.org/web/20170718135858/http://www.nhs.uk/Conditions/lactose-intolerance/Pages/Treatment.aspx|archive-date=18 July 2017}}</ref> Lactase deficient individuals vary in the amount of lactose they can tolerate,<ref name=NIH2014Dig/> and some report that their tolerance varies over time, depending on health status and pregnancy.<ref>{{Emedicine|med|3429|Lactose Intolerance}} Roy, Barakat, Nwakakwa, Shojamanesh, Khurana, July 5, 2006</ref><ref name="Szilagyi2015">{{cite journal | vauthors = Szilagyi A | title = Adaptation to Lactose in Lactase Non Persistent People: Effects on Intolerance and the Relationship between Dairy Food Consumption and {{sic|Evalu|tion|nolink=y}} of Diseases | journal = Nutrients | volume = 7 | issue = 8 | pages = 6751–79 | date = August 2015 | pmid = 26287234 | pmc = 4555148 | doi = 10.3390/nu7085309 | type = Review | doi-access = free }}</ref> However, as a rule of thumb, people with primary lactase deficiency and no small intestine injury are usually able to consume at least 12 grams of lactose per sitting without symptoms, or with only mild symptoms, with greater amounts tolerated if consumed with a meal or throughout the day.<ref name="NIH2014Dig" /><ref name="Szilagyi2015" /><ref name="SilanikoveLeitner2015">{{cite journal | vauthors = Silanikove N, Leitner G, Merin U | title = The Interrelationships between Lactose Intolerance and the Modern Dairy Industry: Global Perspectives in Evolutional and Historical Backgrounds | journal = Nutrients | volume = 7 | issue = 9 | pages = 7312–31 | date = August 2015 | pmid = 26404364 | pmc = 4586535 | doi = 10.3390/nu7095340 | type = Review | doi-access = free }}</ref>

{| class="wikitable floatright sortable" style="text-align:right"
|+'''Typical lactose levels in dairy products<ref name=gastroau>{{cite web|url=http://www.gastro.net.au/diets/lactose.html|title=Diet for Lactose Intolerance|url-status=live|archive-url=https://web.archive.org/web/20051224060911/http://www.gastro.net.au/diets/lactose.html|archive-date=2005-12-24}}</ref>'''
! Dairy product !! Serving<br /> size !! Lactose<br /> content !! Fraction
|-
|{{left}} Milk, regular
| 250 ml(g)
| 12 g
| 4.8%{{0}}
|-
|{{left}} Milk, reduced fat
| 250 ml(g)
| 13 g
| 5.2%{{0}}
|-
|{{left}} Yogurt, plain, regular
| 200 g
| 9 g
| 4.5%{{0}}
|-
|{{left}} Yogurt, plain, low-fat
| 200 g
| 12 g
| 6.0%{{0}}
|-
|{{left}} Cheddar cheese
| 30 g
| 0.02 g
| 0.07%
|-
|{{left}} Cottage cheese
| 30 g
| 0.1 g
| 0.33%
|-
|{{left}} Butter
| 5 g
| 0.03 g
| 0.6%{{0}}
|-
|{{left}} Ice cream
| 50 g
| 3 g
| 6.0%{{0}}
|}

Lactose is found primarily in [[dairy product]]s, which vary in the amount of lactose they contain:
* '''Milk''' – unprocessed cow's milk is about 4.7% lactose; [[goat milk|goat's milk]] 4.7%;<ref>{{cite web|url=http://www.goatworld.com/articles/goatmilk/colostrum.shtml|title=Composition of Human, Cow, and Goat Milks|work=GoatWorld.com|first=Harold|last=Eddleman|date=25 December 2003|url-status=live|archive-url=https://web.archive.org/web/20070928192428/http://www.goatworld.com/articles/goatmilk/colostrum.shtml|archive-date=28 September 2007}}</ref> [[Sheep milk|sheep's milk]] 4.7%;<ref>{{cite web|url= https://www.food-intolerance-network.com/food-intolerances/lactose-intolerance/tables-of-lactose-content.html|title= Amount of Lactose in Milk Products|date= 21 November 2013|website= food-intolerance-network.com|publisher= Food Intolerance Network|access-date= 7 September 2017|url-status= live|archive-url= https://web.archive.org/web/20170907213920/https://www.food-intolerance-network.com/food-intolerances/lactose-intolerance/tables-of-lactose-content.html|archive-date= 7 September 2017}}</ref> [[buffalo milk]] 4.86%;<ref name="Peeva">{{cite journal|author=Peeva|year=2001|title=Composition of buffalo milk. Sources of specific effects on the separate components|url=http://bjas.hit.bg/07/693A.htm|journal=Bulgarian Journal of Agricultural Science|volume=7|pages=329–35|url-status=dead|archive-url=https://web.archive.org/web/20070829232522/http://bjas.hit.bg/07/693A.htm|archive-date=2007-08-29}}</ref> and [[Domestic yak|yak milk]] 4.93%.<ref>{{cite journal|vauthors=Jiang XP, Liu GQ, Wang C, Mao YJ, Xiong YZ|title=Milk trait heritability and correlation with heterozygosity in yak|journal=Journal of Applied Genetics|volume=45|issue=2|date=2004|pmid=15131352|pages=215–24|url=http://jag.igr.poznan.pl/2004-Volume-45/2/pdf/2004_Volume_45_2-215-224.pdf|archive-url=https://web.archive.org/web/20080307083908/http://jag.igr.poznan.pl/2004-Volume-45/2/pdf/2004_Volume_45_2-215-224.pdf|archive-date=2008-03-07|url-status=live}}</ref>
* '''Sour cream''' and '''buttermilk''' – if made in the traditional way, this may be tolerable, but most modern brands add milk solids.<ref>{{cite journal|vauthors=Reger JV, Combs WB, Coulter ST, Koch RB |date=February 1, 1951|title=A Comparison of Dry Sweet Cream Buttermilk and Non-Fat Dry Milk Solids in Breadmaking|url=https://www.journalofdairyscience.org/article/S0022-0302(51)91682-7/abstract|journal=Journal of Dairy Science|volume=34|issue=2|pages=136–44|doi=10.3168/jds.S0022-0302(51)91682-7|doi-access=free}}</ref>
* '''Yogurt''' – [[Lactobacillus acidophilus|lactobacilli]] used in the production of [[yogurt]] metabolize lactose to varying degrees, depending on the type of yogurt.<ref>{{cite web |first=Sharon |last=Perkins |date=19 November 2018  |publisher=SFGATE |url=http://healthyeating.sfgate.com/can-lactose-intolerant-eat-yogurt-aged-cheese-6130.html|title=Can a Lactose Intolerant Eat Some Yogurt & Aged Cheese?|url-status=live|archive-url=https://web.archive.org/web/20150428164624/http://healthyeating.sfgate.com/can-lactose-intolerant-eat-yogurt-aged-cheese-6130.html|archive-date=2015-04-28}}</ref> Some bacteria found in yogurt also produce their own [[lactase]], which facilitates digestion in the intestines of lactose intolerant individuals.<ref name="SilanikoveLeitner2015" />
* '''Cheese''' – The [[curdling]] of cheese concentrates most of the lactose from milk into the [[whey]]: fresh [[cottage cheese]] contains 7% of the lactose found in an equivalent mass of milk.<ref name=gastroau/> Further fermentation and [[Cheese ripening|aging]] converts the remaining lactose into [[lactic acid]]; traditionally made [[hard cheese]]s, which have a long ripening period, contain virtually no lactose:<ref name=ilovecheese>{{cite web|url=http://www.ilovecheese.com/lactose_intolerant_faqs.asp|title=Dairy Good: Home|url-status=live|archive-url=https://web.archive.org/web/20130730190352/http://www.ilovecheese.com/lactose_intolerant_faqs.asp|archive-date=2013-07-30}}</ref> cheddar contains less than 1.5% of the lactose found in an equivalent mass of milk.<ref name=gastroau/> However, manufactured cheeses may be produced using processes that do not have the same lactose-reducing properties.<ref>{{cite journal |last1=Muthukummarappan |first1=K |last2=Biswas |first2=A.C. |last3=Metzger |first3=L.E. |last4=Kapoor |first4=R |title=Effect of Natural Cheese Characteristics on Process Cheese Properties |url=https://www.journalofdairyscience.org/article/S0022-0302(07)71648-X/fulltext |journal=Journal of Dairy Science |year=2007 |volume=90 |issue=4 |pages=1625–1634 |publisher=Plum X Metrics |doi=10.3168/jds.2006-746 |pmid=17369202 |s2cid=32630538 |access-date=April 19, 2022|doi-access=free }}</ref>

There used to be<ref name=Portnoy>{{cite journal |last1=Portnoy |first1=Matilde |last2=Barbano |first2=David M. |title=Lactose: Use, measurement, and expression of results |journal=Journal of Dairy Science |date=July 2021 |volume=104 |issue=7 |pages=8314–8325 |doi=10.3168/jds.2020-18706|pmid=33814136 |doi-access=free }}</ref> a lack of standardization on how lactose is measured and reported in food. The different molecular weights of anhydrous lactose or lactose monohydrate result in up to 5% difference.<ref>{{cite web|url=http://drinc.ucdavis.edu/goat1.htm|title=Goat Dairy Foods|url-status=dead|archive-url=https://web.archive.org/web/20071111141237/http://drinc.ucdavis.edu/goat1.htm|archive-date=2007-11-11|access-date=2007-10-11}}</ref> One source recommends using the "carbohydrates" or "sugars" part of the nutritional label as surrogate for lactose content,<ref name=ilovecheese/> but such "lactose by difference" values are not assured to correspond to real lactose content.<ref name=Portnoy/> The stated dairy content of a product also varies according to manufacturing processes and labelling practices, and commercial terminology varies between languages and regions.<ref name="Berdanier" /> As a result, absolute figures for the amount of lactose consumed (by weight) may not be very reliable.

[[Kosher]] products labeled ''[[pareve]]'' or ''[[fleishig]]'' are free of milk. However, if a "D" (for "dairy") is present next to the circled "K", "U", or other ''[[hechsher]]'', the food product likely contains milk solids,<ref name="OHSU">{{cite web|url=http://www.ohsu.edu/xd/health/health-information/topic-by-id.cfm?ContentTypeId=90&ContentId=P01696|title=General guidelines for milk allergy|publisher=Oregon Health & Science University|url-status=dead|archive-url=https://archive.today/20121212035247/http://www.ohsu.edu/xd/health/health-information/topic-by-id.cfm?ContentTypeId=90&ContentId=P01696|archive-date=2012-12-12}}</ref> although it may also simply indicate the product was produced on equipment shared with other products containing milk derivatives.

Lactose is also a commercial [[food additive]] used for its texture, flavor, and adhesive qualities. It is found in additives labelled as [[casein]], [[Caseinase|caseinate]], [[whey]], [[lactoserum]], [[milk solids]], [[modified milk ingredients]], etc.{{Citation needed|date=August 2017}} As such, lactose is found in foods such as processed meats ([[sausage]]s/[[hot dog]]s, sliced meats, [[pâté]]s),<ref name="OHSU" /> gravy stock powder, [[margarine]]s,<ref>{{cite web |title=Margarine Regulations |url=http://www.gov.ns.ca/JUST/REGULATIONS/regs/marge.htm |url-status=live |archive-url=https://web.archive.org/web/20071011202241/http://gov.ns.ca/JUST/REGULATIONS/regs/marge.htm |archive-date=2007-10-11 }}</ref> sliced [[bread]]s,<ref>{{cite web |title=Enriched White Bread in Canada |url=http://www.celiac.ca/Articles/PAB%20Enriching%20GF%20Foods.html |publisher=The Canadian Celiac Association |url-status=dead |archive-url=https://web.archive.org/web/20071203005124/http://www.celiac.ca/Articles/PAB%20Enriching%20GF%20Foods.html |archive-date=2007-12-03 |access-date=2007-10-11 }}</ref><ref>{{cite journal |title=Influence of Nonfat Dry Milk Solids on the Nutritive Value of Bread |journal=Journal of Dairy Science |date=December 1946 |volume=29 |issue=12 |pages=821–9 | last1 = Riggs | first1 = Lloyd K | last2 = Beaty | first2 = Annabel | last3 = Johnson | first3 = Arnold H |doi=10.3168/jds.S0022-0302(46)92546-5 |doi-access=free}}</ref> breakfast cereals, [[potato chip]]s,<ref name="Bartek">{{cite web |title=Bartek, food additive company |url=http://www.bartek.ca/pdfs/Applications/SavouryProducts/SavourySnackFoods/Savoury%20Snack%20Foods%20Alphabetical%20List%20of%20Product%20Names.pdf |url-status=dead |archive-url=https://web.archive.org/web/20081217083729/http://www.bartek.ca/pdfs/Applications/SavouryProducts/SavourySnackFoods/Savoury%20Snack%20Foods%20Alphabetical%20List%20of%20Product%20Names.pdf |archive-date=2008-12-17 |access-date=2007-10-11 }}</ref> [[Food processing|processed foods]], [[medication]]s, prepared meals, meal replacements (powders and bars), protein supplements (powders and bars), and even [[beer]]s in the [[milk stout]] style. Some barbecue sauces and liquid cheeses used in fast-food restaurants may also contain lactose. When dining out, carrying lactose intolerance cards that explain dietary restrictions in the local language can help communicate needs to restaurant staff.<ref name="AllergyFacts2">{{cite web |title=Allergen Card - Milk/Dairy |url=https://allergyfacts.org.au/shop/food-preparation-tools/allergen-cards/allergen-card-milk-dairy |access-date=16 July 2024 |website=Allergy & Anaphylaxis Australia}}</ref> Lactose is often used as the primary filler (main ingredient) in most prescription and non-prescription solid pill form medications, though product labeling seldom mentions the presence of 'lactose' or 'milk', and neither do product monograms provided to pharmacists, and most pharmacists are unaware of the very wide scale yet common use of lactose in such medications until they contact the supplier or manufacturer for verification.{{Citation needed|date=April 2015}}

=== Milk substitutes ===
{{further|Milk#Reduction or elimination of lactose|Milk substitute}}

[[Plant milk|Plant-based milks]] and derivatives such as [[soy milk]], [[rice milk]], [[almond milk]], [[coconut milk]], [[hazelnut]] milk, [[oat milk]], [[hemp milk]], macadamia nut milk, and [[peanut milk]] are inherently lactose-free.  Low-lactose and lactose-free versions of foods are often available to replace dairy-based foods for those with lactose intolerance.<ref>{{cite book |doi=10.1002/9781118906460.ch2f |chapter=Dairy Products and Their Role in Human Health |chapter-url={{Google books|z100DwAAQBAJ|page=248|plainurl=yes}} |title=Advances in Dairy Products |pages=248–61 |year=2017 |last1=Trotta |first1=Teresa |last2=Posa |first2=Francesca |last3=Mori |first3=Giorgio |last4=Porro |first4=Chiara |isbn=978-1-118-90646-0 }}</ref>

=== Lactase supplements ===
When lactose avoidance is not possible, or on occasions when a person chooses to consume such items, then enzymatic lactase supplements may be used.<ref name="Montalto">{{cite journal | vauthors = Montalto M, Curigliano V, Santoro L, Vastola M, Cammarota G, Manna R, Gasbarrini A, Gasbarrini G | title = Management and treatment of lactose malabsorption | journal = World Journal of Gastroenterology | volume = 12 | issue = 2 | pages = 187–91 | date = January 2006 | pmid = 16482616 | pmc = 4066025 | doi=10.3748/wjg.v12.i2.187 | doi-access = free }}</ref><ref>{{cite journal | vauthors = He M, Yang Y, Bian L, Cui H | title = [Effect of exogenous lactase on the absorption of lactose and its intolerance symptoms] | language = zh | journal = Wei Sheng Yan Jiu = Journal of Hygiene Research | volume = 28 | issue = 5 | pages = 309–11 | date = September 1999 | pmid = 12712706 }}</ref>

Lactase enzymes similar to those produced in the small intestines of humans are produced industrially by [[fungi]] of the [[genus]] ''[[Aspergillus]]''. The enzyme, [[Beta-galactosidase|β-galactosidase]], is available in tablet form in a variety of doses, in many countries without a prescription. It functions well only in high-acid environments, such as that found in the human gut due to the addition of gastric juices from the stomach. Unfortunately, too much acid can denature it,<ref>{{cite journal | vauthors = O'Connell S, Walsh G | s2cid = 22205720 | title = Physicochemical characteristics of commercial lactases relevant to their application in the alleviation of lactose intolerance | journal = Applied Biochemistry and Biotechnology | volume = 134 | issue = 2 | pages = 179–91 | date = August 2006 | pmid = 16943638 | doi = 10.1385/ABAB:134:2:179 }}</ref> so it should not be taken on an empty stomach. Also, the enzyme is ineffective if it does not reach the small intestine by the time the problematic food does. Lactose-sensitive individuals can experiment with both timing and dosage to fit their particular needs.

While essentially the same process as normal intestinal lactose digestion, direct treatment of milk employs a different variety of industrially produced lactase. This enzyme, produced by [[yeast]] from the genus ''[[Kluyveromyces]]'', takes much longer to act, must be thoroughly mixed throughout the product, and is destroyed by even mildly acidic environments. Its main use is in producing the lactose-free or lactose-reduced dairy products sold in supermarkets.<ref>{{Citation|last1=Belloch|first1=C.|title=Yeasts and Molds {{!}} Kluyveromyces spp.|date=2011-01-01|url=https://www.sciencedirect.com/science/article/pii/B9780123744074004994|encyclopedia=Encyclopedia of Dairy Sciences |edition=2nd |pages=754–764|editor-last=Fuquay|editor-first=John W.|place=San Diego|publisher=Academic Press|isbn=978-0-12-374407-4|access-date=2022-01-14|last2=Querol|first2=A.|last3=Barrio|first3=E.}}</ref>

=== Rehabituation to dairy products ===
Regular consumption of dairy foods containing lactose can promote a colonic bacteria adaptation, enhancing a favorable microbiome, which allows people with primary lactase deficiency to diminish their intolerance and to consume more dairy foods.<ref name="SilanikoveLeitner2015" /><ref name="Szilagyi2015" /><ref>{{cite magazine|url=http://www.agriculture.purdue.edu/agricultures/past/Spring1998/1998-Spring-Spotlights.pdf|title=Lactose intolerant? Drink more milk |first=Steve|last=Tally |magazine=Agricultures Magazine |page=2 |volume=1 |number=2 |date=1998 |archive-url=https://web.archive.org/web/20060904071717/http://www.agriculture.purdue.edu/agricultures/past/Spring1998/1998-Spring-Spotlights.pdf |archive-date=2006-09-04 |url-status=live}} Steve Tally</ref> The way to induce tolerance is based on progressive exposure, consuming smaller amounts frequently, distributed throughout the day.<ref name=GrenovBriend2016>{{cite journal | vauthors = Grenov B, Briend A, Sangild PT, Thymann T, Rytter MH, Hother AL, Mølgaard C, Michaelsen KF | s2cid = 39762161 | title = Undernourished Children and Milk Lactose | journal = Food and Nutrition Bulletin | volume = 37 | issue = 1 | pages = 85–99 | date = March 2016 | pmid = 26893059 | doi = 10.1177/0379572116629024 | doi-access = free }}</ref> Lactose intolerance can also be managed by ingesting live yogurt cultures containing [[Lactobacillus acidophilus|lactobacilli]] that are able to digest the lactose in other dairy products.<ref>{{cite journal |doi=10.2903/j.efsa.2010.1763 |title=Scientific Opinion on the substantiation of health claims related to live yoghurt cultures and improved lactose digestion (ID 1143, 2976) pursuant to Article 13(1) of Regulation (EC) No 1924/2006 |journal=EFSA Journal |volume=8 |issue=10 |year=2010 |doi-access=free }}</ref>

== Epidemiology ==
[[File:Lactose tolerance in the Old World.svg|thumb|upright=1.4|An estimate of the percentage of adults that can digest lactose in the indigenous population of the Old World<ref name="Itan et al. 2010"/>]]
Worldwide, about 65% of people experience some form of lactose intolerance as they age past infancy, but there are significant differences between populations and regions. As few as 5% of northern Europeans are lactose intolerant, while as many as 90% of adults in parts of Asia are lactose intolerant.<ref name=GHR2016>{{cite web|title=Lactose intolerance|url=https://ghr.nlm.nih.gov/condition/lactose-intolerance|website=Genetics Home Reference|access-date=18 November 2016|url-status=live|archive-url=https://web.archive.org/web/20161119060547/https://ghr.nlm.nih.gov/condition/lactose-intolerance|archive-date=19 November 2016}}</ref>

In northern European countries, early adoption of dairy farming conferred a selective evolutionary advantage to individuals that could tolerate lactose. This led to higher frequencies of lactose tolerance in these countries. For example, almost 100% of [[Irish people]] are predicted to be lactose tolerant.<ref name="Itan et al. 2010"/> Conversely, regions of the south, such as Africa, did not adopt dairy farming as early and tolerance from milk consumption did not occur the same way as in northern Europe.<ref name="SilanikoveLeitner2015" /> Lactose intolerance is common among people of Jewish descent, as well as from West Africa, the Arab countries, Greece, and Italy.<ref name=GHR2016/> Different populations will present certain gene constructs depending on the evolutionary and cultural pre-settings of the geographical region.<ref name="SilanikoveLeitner2015" />

==History==
{{main|Lactase persistence}}
Greater lactose tolerance has come about in two ways.<ref name=Schnorr2016/> Some populations have developed genetic changes to allow the digestion of lactose: [[lactase persistence]].<ref name=Schnorr2016/> Other populations developed cooking methods like milk fermentation.<ref name=Schnorr2016>{{cite journal | vauthors = Schnorr SL, Sankaranarayanan K, Lewis CM, Warinner C | title = Insights into human evolution from ancient and contemporary microbiome studies | journal = Current Opinion in Genetics & Development | volume = 41 | pages = 14–26 | date = December 2016 | pmid = 27507098 | pmc = 5534492 | doi = 10.1016/j.gde.2016.07.003 }}</ref>

Lactase persistence in humans evolved relatively recently (in the last 10,000 years) among some populations. Around 8,000 years ago in modern-day Turkey, humans became reliant on newly-domesticated animals that could be milked; such as cows, sheep, and goats. This resulted in higher frequency of lactase persistence.<ref>{{Cite web|url=https://www.npr.org/sections/thesalt/2012/12/27/168144785/an-evolutionary-whodunit-how-did-humans-develop-lactose-tolerance|title=An Evolutionary Whodunit: How Did Humans Develop Lactose Tolerance?|website=NPR.org|date=28 December 2012|access-date=2019-11-14|last1=Thompson|first1=Helen}}</ref> Lactase persistence became high in regions such as Europe, Scandinavia, the Middle East and Northwestern India. However, most people worldwide remain lactase {{em|non}}-persistent.<ref name="Genetics of lactase persistence and"/> Populations that raised animals not used for milk tend to have 90–100 percent of a lactose intolerant rate.<ref>{{Cite journal|last=Pray|first=W. Steven|date=2000|title=Lactose Intolerance: The Norm Among the World's Peoples|journal=American Journal of Pharmaceutical Education|volume=64|number=2|pages=205–207|url=http://archive.ajpe.org/legacy/pdfs/aj640216.pdf|id={{ProQuest|211177586}}|access-date=2019-11-20|archive-date=2021-04-30|archive-url=https://web.archive.org/web/20210430050702/http://archive.ajpe.org/legacy/pdfs/aj640216.pdf|url-status=dead}}</ref> For this reason, lactase persistence is of some interest to the fields of [[anthropology]], [[human genetics]], and [[archaeology]], which typically use the genetically derived persistence/non-persistence terminology.<ref>{{cite journal | vauthors = Curry A | s2cid = 4315860 | title = Archaeology: The milk revolution | journal = Nature | volume = 500 | issue = 7460 | pages = 20–2 | date = August 2013 | pmid = 23903732 | doi = 10.1038/500020a | bibcode = 2013Natur.500...20C | doi-access = free }}</ref>

The rise of dairy and producing dairy related products from cow milk alone, varies across different regions of the world, aside from genetic predisposition.<ref name="SilanikoveLeitner2015" /> The process of turning milk into cheese dates back earlier than 5200 BC.<ref>{{cite journal | vauthors = McClure SB, Magill C, Podrug E, Moore AM, Harper TK, Culleton BJ, Kennett DJ, Freeman KH | title = Fatty acid specific δ13C values reveal earliest Mediterranean cheese production 7,200 years ago | journal = PLOS ONE | volume = 13 | issue = 9 | pages = e0202807 | year = 2018 | pmid = 30183735 | pmc = 6124750 | doi = 10.1371/journal.pone.0202807 | bibcode = 2018PLoSO..1302807M | doi-access = free }}</ref>

DNA analysis in February 2012 revealed that [[Ötzi]] was lactose intolerant, supporting the theory that lactose intolerance was still common at that time, despite the increasing spread of agriculture and dairying.<ref>{{cite journal |vauthors=Keller A, Graefen A, Ball M, Matzas M, Boisguerin V, Maixner F, Leidinger P, Backes C, Khairat R, Forster M, Stade B, Franke A, Mayer J, Spangler J, McLaughlin S, Shah M, Lee C, Harkins TT, Sartori A, Moreno-Estrada A, Henn B, Sikora M, Semino O, Chiaroni J, Rootsi S, Myres NM, Cabrera VM, Underhill PA, Bustamante CD, Vigl EE, Samadelli M, Cipollini G, Haas J, Katus H, O'Connor BD, Carlson MR, Meder B, Blin N, Meese E, Pusch CM, Zink A |title=New insights into the Tyrolean Iceman's origin and phenotype as inferred by whole-genome sequencing |journal=Nat Commun |volume=3 |pages=698 |date=2012 |doi=10.1038/ncomms1701 |pmid=22426219|bibcode=2012NatCo...3..698K |s2cid=29041624 |doi-access=free }}</ref>

Genetic analysis shows lactase persistence has developed several times in different places independently in an example of [[convergent evolution]].<ref name=Tishkoff07>{{cite journal | vauthors = Tishkoff SA, Reed FA, Ranciaro A, Voight BF, Babbitt CC, Silverman JS, Powell K, Mortensen HM, Hirbo JB, Osman M, Ibrahim M, Omar SA, Lema G, Nyambo TB, Ghori J, Bumpstead S, Pritchard JK, Wray GA, Deloukas P | title = Convergent adaptation of human lactase persistence in Africa and Europe | journal = Nature Genetics | volume = 39 | issue = 1 | pages = 31–40 | date = January 2007 | pmid = 17159977 | pmc = 2672153 | doi = 10.1038/ng1946 }}</ref>

=== History of research ===
It was not until relatively recently that [[medicine]] recognised the worldwide prevalence of lactose intolerance and its genetic causes. Its symptoms were described as early as [[Hippocrates]] (460–370 BC),<ref>{{cite journal |author=Wilson J |title=Milk Intolerance: Lactose Intolerance and Cow's Milk Protein Allergy |journal=Newborn and Infant Nursing Reviews |date=December 2005 |volume=5 |issue=4 |pages=203–7 |doi=10.1053/j.nainr.2005.08.004}}</ref> but until the 1960s, the prevailing assumption was that tolerance was the norm. Intolerance was explained as the result of a milk allergy, intestinal pathogens, or as being [[psychosomatic]] – it being recognised that some cultures did not practice dairying, and people from those cultures often reacted badly to consuming milk.<ref name="pmid14044269">{{cite journal | vauthors = Auricchio S, Rubino A, Landolt M, Semenza G, Prader A | journal = Lancet | volume = 2 | issue = 7303 | pages = 324–6 | date = August 1963 | pmid = 14044269 | doi = 10.1016/s0140-6736(63)92991-x | title = Isolated Intestinal Lactase Deficiency in the Adult }}</ref><ref name="Simoons_1969">{{cite journal | vauthors = Simoons FJ | title = Primary adult lactose intolerance and the milking habit: a problem in biological and cultural interrelations. I. Review of the medical research | journal = The American Journal of Digestive Diseases | volume = 14 | issue = 12 | pages = 819–36 | date = December 1969 | pmid = 4902756 | doi = 10.1007/bf02233204 | s2cid = 22597839 }}</ref> Two reasons have been given for this misconception. One was that early research was conducted solely on European-descended populations, which have an unusually low incidence of lactose intolerance<ref name="Itan et al. 2010">{{cite journal | vauthors = Itan Y, Jones BL, Ingram CJ, Swallow DM, Thomas MG | title = A worldwide correlation of lactase persistence phenotype and genotypes | journal = BMC Evolutionary Biology | volume = 10 | pages = 36 | date = February 2010 | issue = 1 | pmid = 20144208 | pmc = 2834688 | doi = 10.1186/1471-2148-10-36 | doi-access = free | bibcode = 2010BMCEE..10...36I }}</ref> and an extensive cultural history of dairying. As a result, researchers wrongly concluded that tolerance was the global norm. Another reason is that lactose intolerance tends to be under-reported: lactose intolerant individuals can tolerate at least some lactose before they show symptoms, and their symptoms differ in severity. The large majority of people are able to digest some quantity of milk, for example in tea or coffee, without developing any adverse effects.<ref name="Savaiano and Levitt 1987">{{cite journal | vauthors = Savaiano DA, Levitt MD | title = Milk intolerance and microbe-containing dairy foods | journal = Journal of Dairy Science | volume = 70 | issue = 2 | pages = 397–406 | date = February 1987 | pmid = 3553256 | doi = 10.3168/jds.S0022-0302(87)80023-1 | doi-access=free | url=https://www.journalofdairyscience.org/article/S0022-0302(87)80023-1/abstract }}</ref> [[Fermented milk products|Fermented dairy products]], such as cheese, also contain significantly less lactose than plain milk. Therefore, in societies where tolerance is the norm, many lactose intolerant people who consume only small amounts of dairy, or have only mild symptoms, may be unaware that they cannot digest lactose.

Eventually, in the 1960s, it was recognised that lactose intolerance was correlated with [[race (classification of humans)|race]] in the United States.<ref name="pmid5953213">{{cite journal | vauthors = Bayless TM, Rosensweig NS | title = A racial difference in incidence of lactase deficiency. A survey of milk intolerance and lactase deficiency in healthy adult males | journal = JAMA | volume = 197 | issue = 12 | pages = 968–72 | date = September 1966 | pmid = 5953213 | doi = 10.1001/jama.1966.03110120074017 }}</ref><ref>{{cite journal |vauthors=Welsh JD, Rohrer V, Knudsen KB, Paustian FF | year = 1967 | title = Isolated Lactase Deficiency: Correlation of Laboratory Studies and Clinical Data | journal = Archives of Internal Medicine | volume = 120 | issue = 3 | pages = 261–269 | doi=10.1001/archinte.1967.00300030003003}}</ref><ref name="pmid5694356">{{cite journal | vauthors = Huang SS, Bayless TM | s2cid = 33249040 | title = Milk and lactose intolerance in healthy Orientals | journal = Science | volume = 160 | issue = 3823 | pages = 83–4 | date = April 1968 | pmid = 5694356 | doi = 10.1126/science.160.3823.83-a | bibcode = 1968Sci...160...83H }}</ref> Subsequent research revealed that lactose intolerance was more common globally than tolerance,<ref name="pmid4159716">{{cite journal | vauthors = Cook GC, Kajubi SK | title = Tribal incidence of lactase deficiency in Uganda | journal = Lancet | volume = 1 | issue = 7440 | pages = 725–9 | date = April 1966 | pmid = 4159716 | doi = 10.1016/s0140-6736(66)90888-9 }}</ref><ref>{{cite journal |vauthors=Jersky J, Kinsley RH | year = 1967 | title = Lactase Deficiency in the South African Bantu | journal = South African Medical Journal | volume = 41 | issue = 46 | pages = 1194–6 |pmid=6080167}}</ref><ref name="pmid5701921">{{cite journal | vauthors = Bolin TD, Crane GG, Davis AE | title = Lactose intolerance in various ethnic groups in South-East Asia | journal = Australasian Annals of Medicine | volume = 17 | issue = 4 | pages = 300–6 | date = November 1968 | pmid = 5701921 | doi =  10.1111/imj.1968.17.4.300}}</ref><ref name="pmid5818369">{{cite journal | vauthors = Flatz G, Saengudom C, Sanguanbhokhai T | s2cid = 4201371 | title = Lactose intolerance in Thailand | journal = Nature | volume = 221 | issue = 5182 | pages = 758–9 | date = February 1969 | pmid = 5818369 | doi = 10.1038/221758b0 | bibcode = 1969Natur.221..758F }}</ref><ref name="pmid6016903">{{cite journal | vauthors = Elliott RB, Maxwell GM, Vawser N | title = Lactose maldigestion in Australian Aboriginal children | journal = The Medical Journal of Australia | volume = 1 | issue = 2 | pages = 46–9 | date = January 1967 | pmid = 6016903 | doi =  10.5694/j.1326-5377.1967.tb21011.x| s2cid = 44475025 }}</ref> and that the variation was due to genetic differences, not an adaptation to cultural practices.<ref name="Simoons_1969" /><ref name="pmid5114667">{{cite journal | vauthors = Flatz G, Rotthauwe HW | title = Evidence against nutritional adaption of tolerance to lactose | journal = Humangenetik | volume = 13 | issue = 2 | pages = 118–25 | year = 1971 | pmid = 5114667 | doi = 10.1007/bf00295793 | s2cid = 33253438 }}</ref>

==Other animals==
Most [[mammal]]s normally cease to produce lactase and become lactose intolerant after [[weaning]].<ref name="Genetics of lactase persistence and"/> The downregulation of lactase expression in [[House mouse|mice]] could be attributed to the accumulation of [[DNA methylation]] in the ''[[Lactase|Lct]]'' gene and the adjacent ''[[MCM6|Mcm6]]'' gene.<ref name=Oh17 />

== See also ==
{{Portal|Food|Drink}}
{{columns-list|colwidth=30em|
* [[Food intolerance]]
* [[Gastroenterology]]
* [[Glucose-galactose malabsorption]]
* [[Gluten intolerance]]
* [[Lactase persistence]]
* [[Lactagen]]
* [[Recent human evolution]]
* [[Soy cheese]]
* [[Soy milk]] and [[plant milk]]
* [[Sucrose intolerance]]
}}

== References ==
{{Reflist}}

== External links ==
{{Medical resources
|  oMIM_mult       = {{OMIM2|150220}}
|  DiseasesDB     = 7238
|  ICD10          = {{ICD10|E|73||e|70}}
|  ICD9           = {{ICD9|271.3}}
|  ICDO           =
|  OMIM           = 223100
|  MedlinePlus    = 000276
|  eMedicineSubj  = med
|  eMedicineTopic = 3429
|  eMedicine_mult = {{eMedicine2|ped|1270}}
|  MeshID         = D007787
}}
* {{cite news |first=Nicholas |last=Wade |title=Human Culture, an Evolutionary Force |newspaper=New York Times |date=1 March 2010 |url=https://www.nytimes.com/2010/03/02/science/02evo.html }}

{{Gastroenterology}}
{{Carbohydrate metabolic pathology}}

{{Authority control}}

{{DEFAULTSORT:Lactose intolerance}}
[[Category:Digestive system]]
[[Category:Milk]]
[[Category:Conditions diagnosed by stool test]]
[[Category:Food sensitivity]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Wikipedia neurology articles ready to translate]]
[[Category:Ötzi]]
[[Category:Lactose]]