Editing Lactose intolerance (section)

== 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}}