Editing Intrinsic factor (section)

== Insufficiency ==
In [[pernicious anemia]], which is usually an [[autoimmune disease]], [[autoantibody|autoantibodies]] directed against intrinsic factor or parietal cells themselves lead to an intrinsic factor deficiency, [[malabsorption]] of vitamin B<sub>12</sub>, and subsequent [[megaloblastic anemia]].<ref name="Osborne_2015">{{cite journal | vauthors = Osborne D, Sobczyńska-Malefora A | title = Autoimmune mechanisms in pernicious anaemia & thyroid disease | journal = Autoimmunity Reviews | volume = 14 | issue = 9 | pages = 763–768 | date = Sep 2015 | pmid = 25936607 | doi = 10.1016/j.autrev.2015.04.011 | department = (review) }}</ref> [[Atrophic gastritis]] can also cause intrinsic factor deficiency and anemia through damage to the parietal cells of the stomach wall.<ref name="Neumann_2013">{{cite journal | vauthors = Neumann WL, Coss E, Rugge M, Genta RM | title = Autoimmune atrophic gastritis--pathogenesis, pathology and management | journal = Nature Reviews. Gastroenterology & Hepatology | volume = 10 | issue = 9 | pages = 529–541 | date = Sep 2013 | pmid = 23774773 | doi = 10.1038/nrgastro.2013.101 | s2cid = 205487577 | department = (review) }}</ref> [[Exocrine pancreatic insufficiency|Pancreatic exocrine insufficiency]] can interfere with normal dissociation of vitamin B<sub>12</sub> from its binding proteins in the small intestine, preventing its absorption via the intrinsic factor complex.<ref name="Gueant_1990">{{cite journal | vauthors = Guéant JL, Champigneulle B, Gaucher P, Nicolas JP | title = Malabsorption of vitamin B12 in pancreatic insufficiency of the adult and of the child | journal = Pancreas | volume = 5 | issue = 5 | pages = 559–567 | date = Sep 1990 | pmid = 2235967 | doi = 10.1097/00006676-199009000-00011 | s2cid = 9077477 | department = (review) }}</ref> Other risk factors contributing to pernicious anemia are anything that damages or removes a portion of the stomach's parietal cells, including [[bariatric surgery]], gastric tumors, gastric ulcers, and excessive consumption of alcohol.{{citation needed|date=November 2021}}

Mutations in the ''GIF'' gene are responsible for a rare inheritable disease called ''intrinsic factor deficiency''<ref name="gard">{{cite web | title = Intrinsic factor deficiency {{!}} Genetic and Rare Diseases Information Center (GARD) – an NCATS Program|url=https://rarediseases.info.nih.gov/diseases/3024/intrinsic-factor-deficiency|website=rarediseases.info.nih.gov|access-date=2022-03-15|archive-date=2022-05-27|archive-url=https://web.archive.org/web/20220527032557/https://rarediseases.info.nih.gov/diseases/3024/intrinsic-factor-deficiency/|url-status=dead}}</ref> which results in malabsorption of vitamin B<sub>12</sub>.<ref name="Kozyraki_2013">{{cite journal | vauthors = Kozyraki R, Cases O | title = Vitamin B12 absorption: mammalian physiology and acquired and inherited disorders | journal = Biochimie | volume = 95 | issue = 5 | pages = 1002–1007 | date = May 2013 | pmid = 23178706 | doi = 10.1016/j.biochi.2012.11.004 | department = (review) }}</ref>

=== Treatment ===

In most countries, [[intramuscular injection]]s of vitamin B<sub>12</sub> are used to treat [[pernicious anemia]].<ref name="Shipton_2015" /> Orally administered vitamin B<sub>12</sub> is absorbed without intrinsic factor, but at levels of less than one percent than if intrinsic factor is present.<ref>{{cite journal | vauthors = Alpers DH | title = What is new in vitamin B(12)? | journal = Current Opinion in Gastroenterology | volume = 21 | issue = 2 | pages = 183–186 | date = Mar 2005 | pmid = 15711210 | doi = 10.1097/01.mog.0000148331.96932.44 | department = (review) }}</ref>  Despite the low amounts absorbed, oral vitamin B<sub>12</sub> therapy is effective at reducing symptoms of pernicious anemia.<ref name="Andres_2010">{{cite journal | vauthors = Andrès E, Fothergill H, Mecili M | title = Efficacy of oral cobalamin (vitamin B12) therapy | journal = Expert Opinion on Pharmacotherapy | volume = 11 | issue = 2 | pages = 249–256 | date = Feb 2010 | pmid = 20088746 | doi = 10.1517/14656560903456053 | s2cid = 37088496 | department = (review) }}</ref>

Vitamin B<sub>12</sub> can also be given [[sublingual administration|sublingually]], but there is no evidence that this route of administration is superior to the oral route,<ref name="Sharabi_2003">{{cite journal | vauthors = Sharabi A, Cohen E, Sulkes J, Garty M | title = Replacement therapy for vitamin B12 deficiency: comparison between the sublingual and oral route | journal = British Journal of Clinical Pharmacology | volume = 56 | issue = 6 | pages = 635–638 | date = Dec 2003 | pmid = 14616423 | pmc = 1884303 | doi = 10.1046/j.1365-2125.2003.01907.x | department = (primary) }}</ref> and only Canada and Sweden routinely prescribe this route of administration.<ref name="Shipton_2015">{{cite journal | vauthors = Shipton MJ, Thachil J | title = Vitamin B12 deficiency - A 21st century perspective | journal = Clinical Medicine | location = London, England | volume = 15 | issue = 2 | pages = 145–150 | date = Apr 2015 | pmid = 25824066 | pmc = 4953733 | doi = 10.7861/clinmedicine.15-2-145 | department = (review) }}</ref>

Because vitamin B<sub>12</sub> absorption is a multistep process that involves the stomach, pancreas and small intestine, and is mediated by two carriers: [[Haptocorrin]] and intrinsic factor, and because [[Haptocorrin]] ([[Transcobalamin|transcobalamin I]]) binds to vitamin B<sub>12</sub>, and  Vitamin B<sub>12</sub> is acid-sensitive, when vitamin B<sub>12</sub> binds to [[Haptocorrin]] it can safely pass through the acidic stomach to the duodenum, given time in the mouth.<ref name="Fedosov_2012" />