Vitamine k

7/21/2019 Vitamine k

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Vitamin KVitamin K 1 (phylloquinone) -both forms of the vitamincontain a functional

naphthoquinone ring and analiphatic side chain.Phylloquinone has a phytylside chain.Vitamin K 2 (menaquinone). nmenaquinone! the side chainis composed of a varyingnumber of isoprenoidresidues. "he most commonnumber of these residues isfour! since animal en#ymesnormally produce

menaquinone-$ from plantphylloquinone.% sample of phytomenadionefor in&ection! also calledphylloquinone.Vitamin K refers to a group of structurallysimilar! fat-soluble vitamins the human bodyneeds for complete synthesis of certainproteins that are required for bloodcoagulation ! and also certain proteins that thebody uses to manipulate binding of calcium inbone and other tissues. "he vitamin K-relatedmodi'cation of the proteins allos them tobind calcium ions! hich they cannot dootherise. ithout vitamin K! bloodcoagulation is seriously impaired! anduncontrolled bleeding occurs. *o levels ofvitamin K also ea+en bones and promotecalci'cation of arteries and other soft tissues.,hemically! the vitamin K family comprises 2-methyl -1!$-naphthoquinone (-) derivatives .Vitamin K includes to natural vitamersvitamin K 1 and vitamin K 2. /10 Vitamin K 2! inturn! consists of a number of related chemicalsubtypes! ith diering lengths of carbon sidechains made of isoprenoid groups of atoms.Vitamin K 1 ! also +non as phylloquinone !phytomenadione ! or phytonadione ! issynthesi#ed by plants! and is found in highestamounts in green leafy vegetables because itis directly involved in photosynthesis. t maybe thought of as the plant form of vitamin


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K. t is active as a vitamin in animals andperforms the classic functions of vitamin K!including its activity in the production ofblood-clotting proteins. %nimals may alsoconvert it to vitamin K 2.Vitamin K 2 ! the main storage form in animals!

has several subtypes! hich dier inisoprenoid chain length. "hese vitamin K 2homologues are called menaquinones! and arecharacteri#ed by the number of isoprenoidresidues in their side chains. 3enaquinonesare abbreviated 3K-n! here 3 stands formenaquinone! the K stands for vitamin K! andthe n represents the number of isoprenoidside chain residues. 4or e5ample!menaquinone-$ (abbreviated 3K-$) has fourisoprene residues in its side chain.3enaquinone-$ (also +non as

menatetrenone from its four isopreneresidues) is the most common type of vitaminK 2 in animal products since 3K-$ is normallysynthesi#ed from vitamin K 1 in certain animaltissues (arterial alls! pancreas! and testes)by replacement of the phytyl tail ith anunsaturated geranylgeranyl tail containing fourisoprene units! thus yielding menaquinone-$.

"his homolog of vitamin K 2 may have en#ymefunctions distinct from those of vitamin K 1.6acteria in the colon (large intestine) canalso convert K 1 into vitamin K 2. n addition!

bacteria typically lengthen the isoprenoid sidechain of vitamin K 2 to produce a range ofvitamin K 2 forms! most notably the 3K-7 to3K-11 homologues of vitamin K 2. %ll forms ofK 2 other than 3K-$ can only be produced bybacteria! hich use these forms in anaerobicrespiration. "he 3K-7 and other bacteriallyderived forms of vitamin K 2 e5hibit vitamin Kactivity in animals! but 3K-78s e5tra utilityover 3K-$! if any! is unclear and is a matterof investigation.

"hree synthetic types of vitamin K are +nonvitamins K ! K $! and K 9 . %lthough the naturalK 1 and all K 2 homologues and synthetic K $and K 9 have proven nonto5ic! the syntheticform K ( menadione) has shon to5icity. /20:iscovery of vitamin K 1Vitamin K 1 as identi'ed in 1;2; by :anishscientist


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cholesterol-depleted diet. /0 %fter severalee+s! the animals developed haemorrhagesand started bleeding. "hese defects could notbe restored by adding puri'ed cholesterol tothe diet. % second compound=together iththe cholesterol=apparently had been

e5tracted from the food! and this compoundas called the coagulation vitamin. "he nevitamin received the letter K because theinitial discoveries ere reported in a >erman

&ournal! in hich it as designated asKoagulationsvitamin .,onversion of vitamin K1 tovitamin K 2 in animals

"he 3K-$ form of vitamin K 2 is produced byconversion of vitamin K 1 in the testes!pancreas! and arterial alls. /$0 hile ma&orquestions still surround the biochemical

pathay for this transformation! theconversion is not dependent on gut bacteria!as it occurs in germ-free rats /90/?0 and inparenterally-administered K 1 in rats. /70/@0 nfact! tissues that accumulate high amounts of3K-$ have a remar+able capacity to convertup to ;AB of the available K 1 into 3K-$. /;0/1A0 "here is evidence that the conversionproceeds by removal of the phytyl tail of K 1to produce menadione as an intermediate!hich is then condensed ith an activatedgeranylgeranyl moiety (see also prenylation )

to produce vitamin K 2 in the 3K-$(menatetrione) form. /110Cubtypes of vitamin K 23ain article Vitamin K2Vitamin K 2 (menaquinone) includes severalsubtypes. "he to subtypes most studied aremenaquinone-$ ( menatetrenone! 3K-$) andmenaquinone-7 (3K-7).3enaquinone-7 is dierent from 3K-$ in thatit is not produced by human tissue. 3K-7consumption has been shon to reduce theris+ of bone fractures and cardiovasculardisorders that are crucial health issuesorldide. *eading research teams from%ustralia! Dapan! and Korea are broadeningthe understanding of 3K-7 and its production.3K-7 may be converted from phylloquinone(K 1) in the colon by E. coli bacteria. /120


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overall vitamin K status. /10/1$0 3K-$ and3K-7 are both found in the Fnited Ctates indietary supplements for bone health.

"he F.C. 4ood and :rug %dministration (4:%)has not approved any form of vitamin K forthe prevention or treatment of osteoporosisG

hoever! 3K-$ has been shon to decreasethe incidence of fractures up to @7B. /1903K-$ ($9 mg daily) has been approved by the3inistry of


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carbo5ylation of certain glutamate residues inproteins to form gamma-carbo5yglutamate(>la) residues. "he modi'ed residues areoften (but not alays) situated ithin speci'cprotein domains called >la domains . >laresidues are usually involved in binding

calcium ! and are essential for the biologicalactivity of all +non >la proteins. /0%t this time! 1? human proteins ith >ladomains have been discovered! and they play+ey roles in the regulation of threephysiological processes6lood coagulation prothrombin (factor ) !factors V! I ! and I ! and proteins , ! C ! and J/$06one metabolism osteocalcin! also calledbone >la protein (6>P)! matri5 >la protein(3>P)! /90 periostin ! /?0 and the recently

discovered >la-rich protein (>P). /70/@0Vascular biology groth arrest-speci'cprotein ? (>as?) /;0Fn+non function proline-rich g-carbo5yglutamyl proteins (P>Ps) 1 and 2! andtransmembrane g-carbo5y glutamyl proteins("3>s) and $. /$A0*i+e other lipid-soluble vitamins (%! :! E)!vitamin K is stored in the fat tissue of thehuman body.%bsorption and dietary needPrevious theory held that dietary de'ciency is

e5tremely rare unless the intestine (smallboel) as heavily damaged! resulting inmalabsorption of the molecule. %nother at-ris+group for de'ciency ere those sub&ect todecreased production of K 2 by normalintestinal microbiota! as seen in broadspectrum antibiotic use. /$10 "a+ing broad-spectrum antibiotics can reduce vitamin Kproduction in the gut by nearly 7$B in peoplecompared ith those not ta+ing theseantibiotics. /$20 :iets lo in vitamin K alsodecrease the body8s vitamin K concentration./$0 "hose ith chronic +idney disease are atris+ for vitamin K de'ciency! as ell asvitamin : de'ciency ! and particularly thoseith the apoE$ genotype. /$$0 %dditionally! inthe elderly there is a reduction in vitamin K 2production. /$90ecent research results also demonstrate thatthe small intestine and large intestine (colon)


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seem to be ineLcient at absorbing vitamin Ksupplements in rat populations lo in VitaminK. /$?0/$70 "hese results are reinforced byhuman cohort studies! here a ma&ority of thesub&ects shoed inadequate vitamin Kamounts in the body. "his as revealed by

the presence of large amounts of incompletegamma-carbo5ylated proteins in the blood! anindirect test for vitamin K de'ciency. /$@0/$;0/9A0 %nd in an animal model 3K-$ as shonto prevent arterial calci'cations! pointing toits potential role in prevention of suchcalci'cation. /910 n this study vitamin K 1 asalso tested! in an attempt to ma+econnections beteen vitamin K 1 inta+e andcalci'cation reduction. Mnly vitamin K 2 (as3K-$) as found to inNuence arfarin-induced calci'cation in this study.

ecommended amounts"he F.C. :ietary eference nta+e (:) foran %dequate nta+e (%) of vitamin K for a 29-year old male is 12A micrograms (Og) per day.

"he % for adult omen is ;A OgHday! forinfants is 1A2A OgHday! and for children andadolescents 191AA OgHday. "o get ma5imumcarbo5ylation of osteocalcin! one may have tota+e up to 1AAA Og of vitamin K 1. /920%nticoagulant druginteractionsPhylloquinone (K 1 ) /90/9$0 or menaquinone

(K 2) are capable of reversing theanticoagulant activity of the anticoagulantarfarin (tradename ,oumadin ). arfarinor+s by bloc+ing recycling of vitamin K! sothat the body and tissues have loer levels ofactive vitamin K! and thus a de'ciency ofvitamin K.Cupplemental vitamin K (for hich oral dosingis often more active than in&ectable dosing inhuman adults) reverses the vitamin Kde'ciency caused by arfarin! and thereforereduces the intended anticoagulant action ofarfarin and related drugs. /990 Cometimessmall amounts of vitamin K (one milligram perday) are given orally to patients ta+ing,oumadin so that the action of the drug ismore predictable. /9?0 "he properanticoagulant action of the drug is a functionof vitamin K inta+e and drug dose! and due todiering absorption must be individuali#ed for


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each patient. /citation needed 0 "he action ofarfarin and vitamin K both require to to've days after dosing to have ma5imumeect! and neither ,oumadin or vitamin Kshos much eect in the 'rst 2$ hours afterthey are given. /970

n to separate studies in the rat model! afterlong term administration of ,oumadin toinduce calci'cation of arteries in the rodents!supplemental vitamin K as found to reverseor prevent some of the arterial calci'cationattendant on the long-term bloc+ade ofvitamin K. /9@0 % second study found that onlyvitamin K 2 as 3K-$! and not vitamin K 1 aseective at preventing arfarin-inducedarterial calci'cation in rats! suggestingdiering roles for the to forms of thevitamin in some calcium-dependent

processes. /9;0"he neer anticoagulants dabigatran andrivaro5aban have dierent mechanisms ofaction that do not interact ith vitamin K! andmay be ta+en ith supplemental vitamin K./?A0/?10Vitamin K 1 is found chieNy in leafy greenvegetables such as dandelion greens (hichcontain 77@.$ Og per 1AA g! or 7$1B of therecommended daily amount)! spinach! sisschard! lettuce and 6rassica ( e.g. cabbage !+ale ! cauliNoer! broccoli! and brussels

sprouts) and often the absorption is greaterhen accompanied by fats such as butter oroilsG some fruits ! such as avocado! +iifruitand grapes ! are also high in vitamin K. 6yay of reference! to tablespoons of parsleycontain 19B of the recommended dailyamount of vitamin K. /?$0 Come vegetable oils!notably soybean! contain vitamin K! but atlevels that ould require relatively largecalori'c consumption to meet the FC:%-recommended levels. /?90 ,olonic bacteriasynthesi#e a signi'cant portion of humans8vitamin K needsG neborns often receive avitamin K shot at birth to tide them over untiltheir colons become coloni#ed at 've toseven days of age from the consumption oftheir mother8s mil+.Phylloquinone8s tight binding to thyla+oidmembranes in chloroplasts ma+es it lessbioavailable. 4or e5ample! coo+ed spinach has


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a 9B bioavailability of phylloquinone! hoever!fat added to it increases bioavailability to 1Bdue to the increased solubility of vitamin K infat. /??0

Vitamin K 2

4ood sources of vitamin K 2 include fermentedor aged cheeses! eggs! meats such as chic+enand beef and their fat! livers! and organs! andin fermented vegetables! especially natto ! asell as sauer+raut and +e'r.Vitamin K 2 (menaquinone-$) is synthesi#ed byanimal tissues and is found in meat! eggs! anddairy products. /?@0 3enaquinone-7 issynthesi#ed by bacteria during fermentationand is found in fermented soybeans ( natto )!and in most fermented cheeses. /?;0 n natto !none of the vitamin K is from menaquinone-$!

and in cheese only 27B is. /7A0:e'ciency3ain article Vitamin K de'ciency%verage diets are usually not lac+ing invitamin K! and primary de'ciency is rare inhealthy adults. Qeborn infants are at anincreased ris+ of de'ciency. Mther populationsith an increased prevalence of vitamin Kde'ciency include those ho suer from liverdamage or disease (e.g.! alcoholics)! cystic'brosis! or inNammatory boel diseases! orhave recently had abdominal surgeries.

Cecondary vitamin K de'ciency can occur inbulimics! those on stringent diets! and thoseta+ing anticoagulants. Mther drugs associatedith vitamin K de'ciency include salicylates!barbiturates! and cefamandole! although themechanisms are still un+non. Vitamin K 1de'ciency can result in coagulopathy ! ableeding disorder. /710 Cymptoms of K 1de'ciency include anemia! bruising! andbleeding of the gums or nose in both se5es!and heavy menstrual bleeding in omen.Msteoporosis /720/70 and coronary heartdisease /7$0/790 are strongly associated ithloer levels of K 2 (menaquinone). Vitamin K 2(3K-7) de'ciency is also related to severeaortic calci'cation and all-cause mortality. /7?03enaquinone is not inhibited by salicylates ashappens ith K 1! so menaquinonesupplementation can alleviate the chronicvitamin K de'ciency caused by long-term


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aspirin use. /citation needed 0"o5icity%lthough allergic reaction fromsupplementation is possible! no +non to5icityis associated ith high doses of thephylloquinone (vitamin K 1 ) or menaquinone

(vitamin K 2) forms of vitamin K! so notolerable upper inta+e level (F*) has been set./7706lood clotting ( coagulation ) studies in humansusing $9 mg per day of vitamin K 2 (as 3K-$)/270 and even up to 19 mgHday ($9 mg threetimes daily) of K 2 (as 3K-$)! /7@0 shoed noincrease in blood clot ris+. Even doses in ratsas high as 29A mgH+g body eight did notalter the tendency for blood-clot formation tooccur. /7;0Fnli+e the safe natural forms of vitamin K 1

and vitamin K 2 and their various isomers ! asynthetic form of vitamin K! vitamin K ( menadione)! is demonstrably to5ic. "he F.C.4:% has banned this form from over-the-counter sale in the Fnited Ctates becauselarge doses have been shon to causeallergic reactions! hemolytic anemia ! andcytoto5icity in liver cells. /206iochemistryVitamin K structures. 3K-$ and 3K-7 are bothsubtypes of K 2.

"he function of vitamin K 2 in the animal cell

is to add a carbo5ylic acid functional group toa glutamate amino acid residue in a protein!to form a gamma-carbo5yglutamate (>la)residue. "his is a somehat uncommonposttranslational modi'cation of the protein!hich is then +non as a >la protein. "hepresence of to -,MM< (carbo5ylate) groupson the same carbon in the gamma-carbo5yglutamate residue allos it to chelatecalcium ion. "he binding of calcium ion in thisay very often triggers the function or bindingof >la-protein en#ymes! such as the so-calledvitamin K dependent clotting factorsdiscussed belo.ithin the cell! vitamin K undergoes electronreduction to a reduced form called vitamin Khydroquinone by the en#yme vitamin Kepo5ide reductase (VKM). /@A0 %notheren#yme then o5idi#es vitamin K hydroquinoneto allo carbo5ylation of >lu to >laG this


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en#yme is called the gamma-glutamylcarbo5ylase /@10/@20 or the vitamin K-dependent carbo5ylase. "he carbo5ylationreaction only proceeds if the carbo5ylaseen#yme is able to o5idi#e vitamin Khydroquinone to vitamin K epo5ide at the

same time. "he carbo5ylation and epo5idationreactions are said to be coupled. Vitamin Kepo5ide is then reconverted to vitamin K byVKM. "he reduction and subsequentreo5idation of vitamin K coupled ithcarbo5ylation of >lu is called the vitamin Kcycle. /@0 la protein (3>P)! the cell grothregulating groth arrest speci'c gene ?protein (>as?)! and the four transmembrane>la proteins ("3>Ps)! the function of hichis at present un+non. >as? can function asa groth factor to activate the %5l receptortyrosine +inase and stimulate cell proliferationor prevent apoptosis in some cells. n allcases in hich their function as +non! thepresence of the >la residues in these proteinsturned out to be essential for functional


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activity.>la proteins are +non to occur in a idevariety of vertebrates mammals! birds!reptiles! and 'sh. "he venom of a number of%ustralian sna+es acts by activating thehuman blood-clotting system. n some cases!

activation is accomplished by sna+e >la-containing en#ymes that bind to theendothelium of human blood vessels andcataly#e the conversion of procoagulantclotting factors into activated ones! leading tounanted and potentially deadly clotting.%nother interesting class of invertebrate >la-containing proteins is synthesi#ed by the 'sh-hunting snail ,onus geographus . /@?0 "hesesnails produce a venom containing hundredsof neuroactive peptides! or conoto5ins! hichis suLciently to5ic to +ill an adult human.

Ceveral of the conoto5ins contain to to 've>la residues. /@70Vitamin K status can be assessed by

"he prothrombin time (P") test measuresthe time required for blood to clot. % bloodsample is mi5ed ith citric acid and put in a'brometerG delayed clot formation indicates ade'ciency. "his test is insensitive to mildde'ciency! as the values do not change untilthe concentration of prothrombin in the bloodhas declined by at least 9AB. /@@0Fndercarbo5ylated prothrombin (PVK%-)!

in a study of 9 neborns! found P"(prothrombin time) is a less sensitive mar+erthan PVK% ! /@;0 and as indicated above! P"is unable to detect subclinical de'cienciesthat can be detected ith PVK%- testing.Plasma phylloquinone as found to bepositively correlated ith phylloquinone inta+ein elderly 6ritish omen! but not men! /;A0but an article by Cchurgers et al. reported nocorrelation beteen 44R and plasmaphylloquinone. /;10Frinary S-carbo5yglutamic acid responds tochanges in dietary vitamin K inta+e. Ceveraldays are required before any change can beobserved. n a study by 6ooth et al. ! increasesof phylloquinone inta+es from 1AA Og tobeteen 77 and $17 Og for five days did notinduce a signi'cant change. esponse may beage-speci'c. /;20Fndercarbo5ylated osteocalcin (FcMc)


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levels have been inversely correlated ithstores of vitamin K /;0 and bone strength indeveloping rat tibiae. %nother study folloing7@ postmenopausal Korean omen found asupplement regimen of vitamins K and :! andcalcium! but not a regimen of vitamin : and

calcium! as inversely correlated ithreduced FcMc levels. /;$03any bacteria! such as Escherichia coli foundin the large intestine ! can synthesi#e vitaminK 2 (menaquinone-7 or 3K-7! up to 3K-11)!/;90 but not vitamin K 1 (phylloquinone). nthese bacteria! menaquinone transfers toelectrons beteen to dierent smallmolecules! during o5ygen-independentmetabolic energy production processes( anaerobic respiration). /;?0 4or e5ample! asmall molecule ith an e5cess of electrons

(also called an electron donor) such aslactate ! formate ! or Q%:< ! ith the help of anen#yme! passes to electrons to amenaquinone. "he menaquinone! ith the helpof another en#yme! then transfers these toelectrons to a suitable o5idant! such fumarateor nitrate (also called an electron acceptor).%dding to electrons to fumarate or nitrateconverts the molecule to succinate or nitrite Tater! respectively.Come of these reactions generate a cellularenergy source! %"P! in a manner similar to

eu+aryotic cell aerobic respiration! e5cept the'nal electron acceptor is not molecularo5ygen! but fumarate or nitrate . n aerobicrespiration! the 'nal o5idant is molecularo5ygen (M 2)! hich accepts four electronsfrom an electron donor such as Q%:< to beconverted to ater . E. coli ! as facultativeanaerobes ! can carry out both aerobicrespiration and menaquinone-mediatedanaerobic respiration.n&ection in neborns

"he blood clotting factors of neborn babiesare roughly A to ?AB that of adult valuesGthis may be due to the reduced synthesis ofprecursor proteins and the sterility of theirguts.


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vitamin K 1. Mccurrence of vitamin Kde'ciency bleeding in the 'rst ee+ of theinfant8s life is estimated at A.29 to 1.7B! itha prevalence of to to 1A cases per 1AA!AAAbirths. /;70 Premature babies have even loerlevels of the vitamin! so they are at a higher

ris+ from this de'ciency.6leeding in infants due to vitamin Kde'ciency can be severe! leading tohospitali#ation! blood transfusions! braindamage! and death. Cupplementation canprevent most cases of vitamin K de'ciencybleeding in the neborn. ntramuscularadministration is more eective in preventinglate vitamin K de'ciency bleeding than oraladministration. /;@0/;;0%s a result of the occurrences of vitamin Kde'ciency bleeding! the ,ommittee on

Qutrition of the %merican %cademy ofPediatrics has recommended A.9 to 1.A mgvitamin K 1 be administered to all nebornsshortly after birth. /;;0n the FK vitamin K supplementation isrecommended for all neborns ithin the 'rst2$ hours. /1AA0 "his is usually given as asingle intramuscular in&ection of 1 mg shortlyafter birth but as a second-line option can begiven by three oral doses over the 'rstmonth. /1A10,ontroversy arose in the early 1;;As

regarding this practice! hen to studiessuggested a relationship beteen parenteraladministration of vitamin K and childhoodcancer! /1A20 hoever! poor methods and smallsample si#es led to the discrediting of thesestudies! and a revie of the evidencepublished in 2AAA by oss and :avies foundno lin+ beteen the to. /1A0 :octorsreported emerging concerns in 2A1! /1A$0after treating children for serious bleedingproblems. "hey cited lac+-of neborn VitaminK administration! as the reason that theproblems occurred! and recommended thatbreast-fed babies could have an increased ris+unless they receive a preventative dose.


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3inistry of P may play a role in preventing ectopiccalci'cation in the arteries. %lthough themechanism of 3>P on arterial calci'cation isnot fully understood! it is +non that 3>Pmust be in its active form to have a bene'cialeect in the blood vessel. 3>P becomesactivated by carbo5ylation! hich requiresvitamin + as a cofactor. 6ecause it is thought


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that phylloquinones e5erts its actions mainlyin the liver! it is speculated thatmenaquinones may have a more signi'cantinNuence in the e5tra-hepatic regions of thebody! such as VC3,s! here they are +nonto travel to by *:*. /1A;0 n addition!

menaquinones have been demonstrated tohave a longer half-life in circulation comparedto phylloquinone. /1A;0 3enaquinones maytherefore be important for preventing vascularcalci'cation (V,) and thus reducing ris+ for,V:.Previous research conducted on 3>P+noc+out mice demonstrated the importanceof 3>P on inhibiting V,. *uo! :ucy! 3cKee!Pinero! *oyer! 6ehringer! and Karsenty (1;;7)found that the aorta of 3>P +noc+out micebecame severely calci'ed ithin the 'rst to

months of life! leading to rupture of the arteryand 'nally death of the mice due to internalhemorrhaging. /11A0 "his study became a basisfor many future studies to further e5plore theinNuence of 3>P on V, since it ashypothesi#ed that if a human had lo levelsof 3>P they could develop V, more quic+lythan those ith optimal levels of 3>P. tbecame a question as to hether 3>P couldhelp to reduce the ris+ of ,V: development.P undergoes dierentpost-translational modi'cations! several forms

of 3>P can e5ist in the human body! sohich form of 3>P is most eective atpreventing V, Cchurgers! Cpron+! Coute!Cchiers! :e3ay! andVermeer (2AA7) foundthat the carbo5ylated form of 3>P asresponsible for reducing V, in rats. /1110 nthe study! rats ere sub&ected to a dose ofarfarin to induce V,. arfarin is acommonly prescribed drug given to humans tohelp prevent heart disease and stro+e byreducing the development of blood clots inthe blood vessels. arfarin acts to inhibit thevitamin + cycleG thereby preventing activationof essential blood clotting factors. n theaforementioned study! V, as signi'cantlydecreased in the rats inNicted ith V, viaarfarin! hen supplemented for ? ee+s itha high dose of either menaquinone orphylloquinone. /1110 6oth menaquinone andphylloquinone supplementation in


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concentrations of 1AA OgHg (supplied in therat food)! ere able to inNict a signi'cantreduction in V, in the rats. /1110 hene5amining the dierent 3>P forms in therats! it as found that the high menaquinoneand phylloquinone supplement groups had

greater levels of carbo5ylated 3>P comparedto the control! rats receiving arfarin! andrats receiving a normal phylloquinone dose./1110 4urthermore! levels of uncarbo5ylated3>P ere higher in the rats receivingarfarin and in the rats receiving a normalphylloquinone dose. /1110 "his studydemonstrated a bene't of both menaquinoneand phylloquinone on V, but did notdetermine the mechanism by hichcarbo5ylated 3>P as able to reduce V,. n2AA@! allin! Cchurgers! and a&ih set out to

help establish this mechanism. "heresearchers evaluated uncarbo5ylated 3>Pand carbo5ylated 3>P by e5perimenting iththe glutamic acid and gamma-carbo5yglutamic acid residues of 3>P. /1120 tas found that the gamma-carbo5yglutamicacid residues ere capable of inhibiting aprotein called bone morphogenic protein-2(63P-2)! that may play a role indierentiation of vascular smooth musclecells (VC3,s) into bone-li+e cells. /1120 Mnthe other hand! the glutamic acid residues

ere unable to inhibit 63P-2! hichcon'rmed that 3>P must be carbo5ylated tobe active in V, inhibition. /1120ntervention studies ith menaquinones inhumans have become more frequentlypublished in recent years. n a randomi#ed!double blind! placebo controlled human trial!menaquinone-7 supplementation as studiedin healthy adults for its inNuence oncirculating forms of 3>P. n the telve-ee+study! si5ty adults ere divided into threesupplement groups placebo! 1@A Ogmenaquinone-7Hday! and ?A Ogmenaquinone-7Hday and circulating forms of3>P ere analy#ed from blood and urinesamples that ere collected at ee+s 1! $!and 12. /110 "he researchers found that afteronly $ ee+s of menaquinone-7supplementation! the total level ofdephosphorylated-uncarbo5ylated 3>P as


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decreased compared to baseline and that theeffect as dose dependent ith ?A Ogmenaquinone-7Hday having a greater eectthan 1@A Og menaquinone-7Hday. /1104urthermore! no change in dephosphorylated-uncarbo5ylated 3>P as evident in the

placebo group. /110 n another studye5amining the relationship beteenmenaquinone-7 supplementation andcirculating dephosphorylated-uncarbo5ylated3>P levels! 1?9 patients undergoing chronichemodialysis ere divided into threemenaquinone-7 supplementation groups ?AOgHday! 72A OgHday! or 1A@A OgHday for a totalof @ ee+s. /11$0 %t baseline! it asdetermined through -day food diaries thatthere as a signi'cant inverse relationshipbeteen menaquinone inta+e and

dephosphorylated-uncarbo5ylated 3>P levels!hereas phylloquinone inta+e had noassociation. /11$0 %fter @ ee+s ofmenaquinone-7 supplementation! theresearchers found that circulatingdephosphorylated-uncarbo5ylated 3>P levelshad signi'cantly decreased! and that theeect as dose dependent. /11$0Fnfortunately! other forms of 3>P ere notmeasured. n both of these aforementionedstudies! neither e5amined the relationship ofdephosphorylated-uncarbo5ylated 3>P levels

to V, or ,V:. P levels (less than $AApmolH*) ere signi'cantly associated ithincreased ris+ of fatal and non-fatal ,V: in977 healthy men and omen aged 99 ?9years. /1190f V, can be prevented or reduced bymenaquinones then the ris+ for ,V: may alsobe reduced. 4uture strategies to reduce theris+ of ,V: may one day encourageincreasing oneWs inta+e of dietarymenaquinone.% study by >ast et al. (2AA;)! /790 reports aninverse association beteen vitamin K 2 andris+ of ,


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Vitamin K 1 inta+e as not signi'cantlyrelated to ,


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participants ith the loest levels of thevitamin. /1220Vitamin K is part of the suggested treatmentregime for poisoning by rodenticide . /120Vitamin K antagonists are substances thatreduce blood clotting by reducing the active

form of vitamin K. "hey are used as ratpoisons and as medications to preventthrombosis . E5amples include $-hydro5ycoumarins such as the pharmaceuticalarfarin ! and also anticoagulant-mechanismpoisons such as bromadiolone ! hich arecommonly found inrodenticides . /citation needed 0$-


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amounts of brain sulfatide concentrations./12$0 "his study indicates that vitamin K hasmore uses than originally thought! thusfurthering the importance of daily vitamin Kinta+e. "he same study shoed that a dietith insuLcient vitamin K levels decreased

the brain sulfatide concentrations in rats atthe (p X A.A1) signi'cance level. %notherstudy involving rats has indicated thatdierent species! strains and genders of ratsrequired dierent amounts of vitamin Kinta+e! depending on ho much as stored intheir livers. /1290 "his may indicate thatdierent humans should have dierent needsfor their vitamin K inta+e. % third study loo+edat the ay rats and chic+s are able to recycleparts of vitamin K. "he study found thatchic+s are about 1AB less eLcient in

recycling the vitamin K than their ratcounterparts. /12?0 "his evidences also helpsto con'rm that vitamin K levels are unique toeach species! and the previous study shosthat required vitamin K inta+e also variesithin species.Vitamin K may be applied topically! typicallyas a 9B cream! to diminish postoperativebruising from cosmetic surgery and in&ections!to treat bro+en capillaries (spider veins)! totreat rosacea! and to aid in the fading ofhyperpigmentation and dar+ under-eye circles.

/1270/12@0


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shared the 1;$ Qobel Pri#e for medicine fortheir or+ on vitamin K (K 1 and K 2 ) publishedin 1;;. Ceveral laboratories synthesi#ed thecompound(s) in 1;;. /1A04or several decades! the vitamin K-de'cientchic+ model as the only method of

quantifying vitamin K in various foods thechic+s ere made vitamin K-de'cient andsubsequently fed ith +non amounts ofvitamin K-containing food. "he e5tent tohich blood coagulation as restored by thediet as ta+en as a measure for its vitamin Kcontent. "hree groups of physiciansindependently found this 6iochemicalnstitute! Fniversity of ,openhagen (:am and

Dohannes >lavind)! Fniversity of oa:epartment of Pathology ( Emory arner!Kenneth 6rin+hous! and

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Vitamine k