Editing Vitamin K (section)

==Research==
=== Osteoporosis ===
Vitamin K is required for the gamma-carboxylation of [[osteocalcin]] in bone.<ref name=Hamidi2013>{{cite journal | vauthors = Hamidi MS, Gajic-Veljanoski O, Cheung AM | title = Vitamin K and bone health | journal = Journal of Clinical Densitometry | volume = 16 | issue = 4 | pages = 409–413 | year = 2013 | pmid = 24090644 | doi = 10.1016/j.jocd.2013.08.017 | type = Review }}</ref> The risk of [[osteoporosis]], assessed via [[bone mineral density]] and fractures, was not affected for people on warfarin therapy&nbsp;– a vitamin K antagonist.<ref name=Fiordellisi2019>{{cite journal |vauthors=Fiordellisi W, White K, Schweizer M |title=A Systematic Review and Meta-analysis of the Association Between Vitamin K Antagonist Use and Fracture |journal=J Gen Intern Med |volume=34 |issue=2 |pages=304–311 |date=February 2019 |pmid=30511289 |pmc=6374254 |doi=10.1007/s11606-018-4758-2 }}</ref> Studies investigating whether  vitamin K supplementation reduces risk of bone fractures have shown mixed results.<ref name=PKIN2020VitK /><ref name=Hamidi2013 /><ref name=Mott2019>{{cite journal |vauthors=Mott A, Bradley T, Wright K, Cockayne ES, Shearer MJ, Adamson J, Lanham-New SA, Torgerson DJ |title=Effect of vitamin K on bone mineral density and fractures in adults: an updated systematic review and meta-analysis of randomised controlled trials |journal=Osteoporos Int |volume=30 |issue=8 |pages=1543–1559 |date=August 2019 |pmid=31076817 |doi=10.1007/s00198-019-04949-0 |s2cid=149445288 |url=http://eprints.whiterose.ac.uk/145682/1/Main_text_final.docx}}</ref><ref name=Hao2017>{{cite journal |vauthors=Hao G, Zhang B, Gu M, Chen C, Zhang Q, Zhang G, Cao X |title=Vitamin K intake and the risk of fractures: A meta-analysis |journal=Medicine (Baltimore) |volume=96 |issue=17 |pages=e6725 |date=April 2017 |pmid=28445289 |pmc=5413254 |doi=10.1097/MD.0000000000006725 }}</ref>

=== Cardiovascular health ===
Matrix Gla protein is a vitamin K-dependent protein found in bone, but also in soft tissues such as arteries, where it appears to function as an anti-calcification protein. In animal studies, animals that lack the gene for MGP exhibit calcification of arteries and other soft tissues.<ref name=PKIN2020VitK /> In humans, [[Keutel syndrome]] is a rare [[recessive gene]]tic disorder associated with abnormalities in the gene coding for MGP and characterized by abnormal [[diffuse]] [[cartilage]] [[calcification]].<ref name=Munroe1999>{{cite journal |vauthors=Munroe PB, Olgunturk RO, Fryns JP, etal |s2cid=1244954 |title=Mutations in the gene encoding the human matrix Gla protein cause Keutel syndrome |journal=Nat. Genet. |volume=21 |issue=1 |pages=142–144 |year=1999 |pmid=9916809 |doi=10.1038/5102 }}</ref> These observations led to a theory that in humans, inadequately carboxylated MGP, due to low dietary intake of the vitamin, could result in increased risk of arterial calcification and coronary heart disease.<ref name=PKIN2020VitK />

In [[Meta-analysis|meta-analyses]] of population studies, low intake of vitamin K was associated with inactive MGP, [[artery|arterial]] [[calcification]]<ref name="ReferenceA">{{cite journal | vauthors = Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MH, van der Meer IM, Hofman A, Witteman JC | title = Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study | journal = The Journal of Nutrition | volume = 134 | issue = 11 | pages = 3100–3105 | date = November 2004 | pmid = 15514282 | doi = 10.1093/jn/134.11.3100 | doi-access = free | hdl = 1765/10366 | hdl-access = free }}</ref> and arterial stiffness.<ref name=Roumeliotis2019>{{cite journal |vauthors=Roumeliotis S, Dounousi E, Eleftheriadis T, Liakopoulos V |title=Association of the Inactive Circulating Matrix Gla Protein with Vitamin K Intake, Calcification, Mortality, and Cardiovascular Disease: A Review |journal=Int J Mol Sci |volume=20 |issue=3 |date=February 2019 |page=628 |pmid=30717170 |pmc=6387246 |doi=10.3390/ijms20030628 |doi-access=free }}</ref><ref name=Maresz2015>{{cite journal | vauthors = Maresz K | title = Proper Calcium Use: Vitamin K<sub>2</sub> as a Promoter of Bone and Cardiovascular Health |journal = Integrative Medicine |volume = 14 |issue = 1 |pages = 34–39 |date = February 2015 |pmid = 26770129 |pmc = 4566462 }}</ref> Lower dietary intakes of vitamin K<sub>1</sub> and vitamin K<sub>2</sub> were also associated with higher [[coronary heart disease]].<ref name=Chen2019 /><ref name="autogenerated1">{{cite journal | vauthors = Gast GC, de Roos NM, Sluijs I, Bots ML, Beulens JW, Geleijnse JM, Witteman JC, Grobbee DE, Peeters PH, van der Schouw YT | title = A high menaquinone intake reduces the incidence of coronary heart disease | journal = Nutrition, Metabolism, and Cardiovascular Diseases | volume = 19 | issue = 7 | pages = 504–510 | date = September 2009 | pmid = 19179058 | doi = 10.1016/j.numecd.2008.10.004 }}</ref> When blood concentration of circulating vitamin K<sub>1</sub> was assessed there was an increased risk in all cause mortality linked to low concentration.<ref>{{cite journal |vauthors=Zhang S, Guo L, Bu C |title=Vitamin K status and cardiovascular events or mortality: A meta-analysis |journal=Eur J Prev Cardiol |volume=26 |issue=5 |pages=549–553 |date=March 2019 |pmid=30348006 |doi=10.1177/2047487318808066 |s2cid=53037302 |doi-access=free }}</ref><ref name=Shea2020>{{cite journal |vauthors=Shea MK, Barger K, Booth SL, Matuszek G, Cushman M, Benjamin EJ, Kritchevsky SB, Weiner DE |title=Vitamin K status, cardiovascular disease, and all-cause mortality: a participant-level meta-analysis of 3 US cohorts |journal=Am J Clin Nutr |volume=111 |issue=6 |pages=1170–1177 |date=June 2020 |pmid=32359159 |doi=10.1093/ajcn/nqaa082 |pmc=7266692 }}</ref> In contrast to these population studies, a review of randomized trials using supplementation with either vitamin K<sub>1</sub> or vitamin K<sub>2</sub> reported no role in mitigating vascular calcification or reducing arterial stiffness. The trials were too short to assess any impact on coronary heart disease or mortality.<ref name=Vlasschaert2020>{{cite journal |vauthors=Vlasschaert C, Goss CJ, Pilkey NG, McKeown S, Holden RM |title=Vitamin K Supplementation for the Prevention of Cardiovascular Disease: Where Is the Evidence? A Systematic Review of Controlled Trials |journal=Nutrients |volume=12 |issue=10 |date=September 2020 |page=2909 |pmid=32977548 |doi=10.3390/nu12102909 |pmc=7598164 |doi-access=free }}</ref>

===Other===
Population studies suggest that vitamin K status may have roles in inflammation, brain function, endocrine function and an anti-cancer effect. For all of these, there is not sufficient evidence from intervention trials to draw any conclusions.<ref name=PKIN2020VitK /> From a review of observational trials, long-term use of vitamin K antagonists as anticoagulation therapy is associated with lower cancer incidence in general.<ref>{{cite journal |vauthors=Shurrab M, Quinn KL, Kitchlu A, Jackevicius CA, Ko DT |title=Long-Term Vitamin K Antagonists and Cancer Risk: A Systematic Review and Meta-Analysis |journal=Am. J. Clin. Oncol. |volume=42 |issue=9 |pages=717–724 |date=September 2019 |pmid=31313676 |doi=10.1097/COC.0000000000000571 |s2cid=197421591 }}</ref> There are conflicting reviews as to whether agonists reduce the risk of prostate cancer.<ref>{{cite journal |vauthors=Luo JD, Luo J, Lai C, Chen J, Meng HZ |title=Is use of vitamin K antagonists associated with the risk of prostate cancer?: A meta-analysis |journal=Medicine (Baltimore) |volume=97 |issue=49 |pages=e13489 |date=December 2018 |pmid=30544443 |pmc=6310569 |doi=10.1097/MD.0000000000013489 }}</ref><ref>{{cite journal |vauthors=Kristensen KB, Jensen PH, Skriver C, Friis S, Pottegård A |title=Use of vitamin K antagonists and risk of prostate cancer: Meta-analysis and nationwide case-control study |journal=Int. J. Cancer |volume=144 |issue=7 |pages=1522–1529 |date=April 2019 |pmid=30246248 |doi=10.1002/ijc.31886 |s2cid=52339455 |url=https://findresearcher.sdu.dk:8443/ws/files/154496758/SDU_kopi_kristensenetal.pdf |access-date=13 October 2020 |archive-date=17 April 2021 |archive-url=https://web.archive.org/web/20210417215749/https://findresearcher.sdu.dk:8443/ws/files/154496758/SDU_kopi_kristensenetal.pdf |url-status=dead }}</ref>